Articles of Incorporation for a Reability Center

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					                              SECOND SCIENTIFIC CONFERENCE
                               “RESTAURACIÓN NEUROLÓGICA
                                    Havana City, February 24-27, 2004


   International Brain
 Research Organization

  International Society for

And the cooperation of:
     Federation of Clinical
     Neurological Society
          American Society
     for Neurochemistry
     Iberoamericana de
     Informacion Cientifica
         ACNR Magazine
     (Advances in Clinical
     Neuroscience &
Tuesday 24 february 2004

Precongress Course: Neurogenesis and brain repair

Restorative Neurology. Hopes and perspectives

Jorge A. Bergado
                         International Center for Restorative Neurology (CIREN) Havana, Cuba
Restorative neurology is a new developing branch of Neurology, aiming to the recovery of nervous
functions affected by disease or trauma. The concept and accumulated knowledge of neural
plasticity have provided a conceptual frame to explain recovery and for the planning of new
therapeutic strategies. Developments in basic Neurosciences have lead to new concepts and
potential tools intended to improve efficacy of therapy. Neural transplantations have been tested
with excellent results in animal models for Parkinson´s Disease. Results in humans have been
limited by several factors, particularly the low survival rate of transplanted cells. Trophic factors
with actions on nerve cells have been under intensive study during the last decades. Several factors
have hindered its clinical application and new strategies are searched to open the ways to clinical
practice of this powerful molecules. The most recent development in Neural Sciences have ended
with the old dogma of no new neurons in the adult brain. Research on stem cell of neural or non-
neural origin represents one of the more promising efforts for the future of Restorative Neurology.

Stem cells for brain repair

Mendez Ivar
  Brain Repair Centre, Dalhousie University and Department of Neurosurgery, Queen Elizabeth II Health Science Center,
                                              Halifax, Nova Scotia, Canada
Brain repair, using restorative approaches such as stem cell neural transplantation holds the greatest
promise for the treatment of neurodegenerative disorders and other incurable neurological
conditions such as stroke and spinal cord injury. Stem cells are pluripotent and have the capacity to
differentiate into neurons and provide us with unlimited neuronal populations of specific
phenotypes such as dopaminergic neurons for the treatment of Parkinson‟s disease. This
presentation will explore the concepts of brain repair using stem cell transplantation and intrinsic
repair by resident adult stem cells. The potential applications of embryonic, adult and skin-derived
stem cells in brain repair strategies for Parkinson‟s disease, stroke and spinal cord injury will be
reviewed. Bioreactor technology for the standardized production of stem cells in large quantities
will be discussed. Particular emphasis will be given to neural transplantation techniques and
histological analysis of stem cell grafts in the mammalian brain. Behavioral tests used in assessing
the ability of stem cells to restore function in animal models of Parkinson‟s disease, stroke and
spinal cord injury will also be reviewed. Finally, the challenges of stem cell research and the
potential of translating brain repair strategies using stem cells from the laboratory bench to the
clinical setting will be discussed.

Programmed cell death of adult-generated hippocampal neurons is mediated by the pro-
apoptotic gene Bax

Ronald W. Oppenheim and Woong Sun
      Wake Forest University School of Medicine, Department of Neurobiology and Anatomy, Winston-Salem, USA
In the dentate gyrus (DG) of the adult mouse hippocampus, several thousand new cells are
generated daily, but only a small subset of these survive and differentiate into mature neurons,
whereas the majority of the newly generated cells undergo programmed cell death (PCD).
However, neither the intracellular machinery required for adult stem cell-derived neuronal death,
nor the biological implications of the significant loss of these newly generated cells have been
examined. Several markers for apoptosis failed to reveal cell death in Bax-deficient mice, and this
together with a progressive increase in neurons number in the DG of the Bax-KO, indicates that
Bax is critical for the PCD of adult-generated hippocampal neurons. In Bax-KO mice, doublecortin
(DCX)-labeled early migrating neurons were ectopically localized in the hilus, and the majority of
the DG neurons failed to express the mature DG neuronal marker, calbindin. Furthermore, in the
absence of PCD in the DG, there were age-dependent perturbations of spontaneous locomotor
activity in the Bax-KO mice. These results suggest that PCD in the adult brain plays a significant
role in the regulation of adult neurogenesis and in its absence some aspects of hippocampal-
mediated behavior are affected.

Neuronal differentiation potential of neural stem cells versus embryonic stem cells

José-Manuel Baizabal, Mayra Furlán-Magaril, Yuri Ximello, Jesús Santa-Olalla, and Luis
Departamento de Génética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma
                       de México, Avenida Universidad 2001, Cuernavaca, Mor. 62210, México
Recently, enormous interest in neural stem cells (NSCs) has arisen from both basic and medical
points of view. Different NSC populations have been identified, which emerge in time and tissue
specific manner during development. On the other hand, distinct diseases associated with reduction
in specific neuronal populations affecting humans are urgently requiring of therapeutic procedures
that use NSCs. The discovery of neurogenesis in the adult brain opens the possibility to induce
specific neuronal regeneration from endogenous NSCs. In this regard, characterization of
neurogenesis during development will play a fundamental role for the rational design of those
therapeutic procedures. In order to study the in vivo differentiation potential of different NSC
populations and the influence of the surrounding environment on NSC-specific differentiation, we
have designed a system based on the implantation of NSCs in explant cultures of different
developing nervous system regions. Our data indicate that NSCs in culture modify its original
differentiation potential and that local factors influence their fate. Particularly, we found that
neurosphere-derived cells in natural developing environments do not differentiate markedly into
neurons, whereas NSCs derived from embryonic stem cells do. Finding the right NSC population
and/or the factors guiding its specific differentiation will be the first step for the development of
therapeutic procedures based on activation of NSC differentiation. This work is supported by

Precongress course: Assesment and rehabilitation of memory disorders

Assessment and rehabilitation of memory disorders

Hans J. Markowitsch
                           Physiological Psychology, University of Bielefeld, Bielefeld, Germany
Assessment of memory will be described as a theory-guided process which has to rely on
knowledge of brain circuits engaged in time-based (short-term/working memory, long-term
memory, anterograde/retrograde amnesia, encoding, storage, retrieval) and contents-based
information processing (procedural memory, priming, perceptual, semantic, episodic memory,
verbal/non-verbal memory). Furthermore, it will be emphasized that memory should never be
assessed in isolation, but has to be embedded in a broad range of additional tests covering
personality dimensions, attention and concentration abilities, intelligence, sensory and motor
(including language) abilities, etc. The resulting intellectual profile will show preserved abilities
and dysfunctions and provides a prerequisite for successful rehabilitation. Concerning
rehabilitation, it is again necessary to base this on current theories of memory functioning, for
example, on distinctions between implicit and explicit memory training programs (e.g., errorless
learning, method of vanishing cues, method of loci, imagery, association learning procedures,
internal and external memory strategies in general). Of special importance is that training is
generalized to everyday situations and that a proper level of motivation has to accompany the
patients' training program.

Precongress course: Speech and reading mechanisms

Localisation of    syntactic             and      semantic       sentence        processing       using
magnetoencephalography (MEG)

Elisabet Service ab , Paivi Heleniusc , Sini Mauryb and Riitta Salmelinc
  Cognitive/Clinical Neuroscience Unit, Department of Psychology, Dalhousie University, Halifax,
Nova Scotia, Canada, b Department of Psychology, University of Helsinki, Helsinki, Finland, cBrain
Research Unit, Low Temperature Laboratory, Helsinki University of Technolo gy, Helsinki, Finland
Finnish is a morphologically rich language in which nouns can occur in 15 different cases. Case
inflections are used both to signal syntactic (e.g., subject vs. object) relations and semantic (e.g.,
location in vs. movement from within something) relations. Participants were presented with written
sentences that ended in normally inflected nouns, nouns in the wrong case, verbs instead of nouns,
or nouns that were correctly inflected but made no sense in the sentence context. The data were
analysed in three ways: 1) MEG raw data from nearby channels were averaged to area activations,
2) equivalent current dipoles were modelled, 3) minimum current estimates were modelled. The
three methods of analysis supported each other, revealing two major sources of activation correlated
with incongruent sentence-ending words. In a time window from 350 to 450 ms, semantically
anomalous last words gave rise to the highest activation in the left temporal lobe with clear
activation of the same sources also for incorrect word class words and morphological errors.
Weaker activation was seen in homologous areas in the right hemisphere. In a later time window,
600–700 ms after word onset, the largest activation was seen to words of incorrect word class and
morphological errors at the ends of sentences. Semantically anomalous words did not deviate from
correct words in this time window. This activation was localised to more posterior bilateral sources
in the temporal lobe.

Dynamic visual processes in normal reading: implications for developmental dyslexia?

Piers Cornelissena, Kristen Pammera, Ruth Lavisa and Peter Hansenb
  School of Biology, University of Newcastle, Newcastle, UK, b Centre for Cognitive Neuroscience,
FMRIB Centre, Oxford University, Oxford, UK
Data from two studies relating visual task performance to contextual reading are presented. The first
study investigated the relationship between contextual reading and, a) relative spatial encoding for
symbol arrays, and b) central versus peripheral sensitivity to the frequency doubling illusion. In the
first study, thirty school children were measured on their ability to solve a foveally-presented spatial
encoding task, as well as their sensitivity to the frequency doubling illusion across the retina. Their
performance in the frequency doubling and spatial encoding tasks was uncorrelated, suggesting that
these tasks tap independent visual processes. Peripheral (but not central) sensitivity to frequency
doubling, and spatial encoding, predicted statistically significant, independent proportions of
variance in contextual reading (Neale Analysis of Reading). These effects persisted even when
variance due to age, IQ, phonological skill and short-term memory was statistically accounted for.
The data suggest that successful reading requires not only information about letter identity, but also
at least two additional sources of information, probably related to spatial processing of words. The
first is a central mechanism that may define the relative spatial location of letters within words, and
the second is a peripheral mechanism that we speculate may be related to the attentional processes
involved in coarse-scale localisation within a body of text. Consistent with this speculation, we
found in the second study, that reading accuracy for dyslexic readers was most impaired relative to
chronological- and age-matched controls when contextual material was presented in whole
paragraphs, rather than line-at-a-time or word-at-a-time reading conditions.

Dissociated semantic access for spoken words and environmental sounds

Guillaume Thierrya, Anne-Lise Giraudb and Cathy Price c
  School of Psychology, University of Wales, Bangor, UK, b Cognitive Neurology Unit, J.W. Goethe
University, Frankfurt am Main, Germany, cWellcome Department of Imaging Neuroscience,
Institute of Neurology, London, UK
Left hemispheric dominance for language processing has long been established. Recently, in an
attempt to tease apart the neural substrates involved in manipulating verbal and nonverbal
information using Positron Emission Tomography, we have found signs of functional dissociation
between the left and the right superior temporal cortices for accessing the meaning of spoken words
(Words) and environmental sounds (Sounds), respectively (Thierry, Giraud and Price, 2003,
Neuron, 38:499-506). We have then sought converging evidence for the dissociation from Event-
Related Potentials (ERPs). In a context of dichotic listening, acoustic signals from the left ear are
better received by the right auditory cortex and signals from the right ear are better received by the
left auditory cortex. Therefore, when a Word is presented to the right ear while a Sound is presented
simultaneously to the left ear (Optimal condition according to the previous P ET study), semantic
integration should be easier than when the sides of presentation are permuted (Crossed). Fifteen
participants were asked to perform semantic congruency judgement on dichotic pairs of Words and
Sounds which had the same meaning or not and which were presented as Optimal or Crossed pairs.
We expected to find a classical N400 ERP modulation induced by semantic incongruence and a
further N400 modulation for Crossed versus Optimal presentation. We found that N400 peak
latencies were delayed by approximately 60 ms for Crossed pairs as compared to Optimal pairs,
irrespective of semantic congruency. This is consistent with a functional lateralisation of semantic
access depending on stimulus symbolism.

Lexical stress and sublexical phonology influence spoken word recognition mechanisms:
an ERP study

John F. Connollya and Jing Tian Wanga,b
  Cognitive/Clinical Neuroscience Unit, Department of Psychology, Dalhousie University
Halifax, NS, Canada, b Cognitive Electrophysiology Laboratory, NY Psychiatric Institute - Unit 6,
NewYork, NY, USA
Theories of spoken word recognition can be divided into two major themes: “sequential” and
“goodness of fit.” A third class of model proposes that prosodic or stress features of speech are
critical for word identification. This study describes research that used ERP to hypothesis test
between theories that do or do not account for stress. ERP were recorded to the terminal words of
sentences in five conditions: Congruent (“Three people were injured in a highway accident”); Non-
initial stress & prime (“She told the lost tourist to turn right at the traffic polite (light)”; Initial stress
& prime (“Eight minus seven equals wonder (one)”; Non-initial stress/initial prime (“The pirate
wore a patch over his idea (eye)”; Incongruent (“The spider sat in its web awaiting a closet (fly).”
Also, 120 fillers were used (“The girl had long brown hair.”). Two components, the phonological
mismatch negativity (PMN) and the N400, were differentially affected by these manipulations. The
PMN to both the Incongruent and Eye/Idea conditions differed from each other and were both
larger than the PMN seen in the other three conditions. The N400 proved to be sensitive to both
stress and sub-lexical phonology with larger amplitudes seen in the Incongruent condition compared
to the Eye/Idea and One/Wonder conditions which, in turn, were larger than those seen in the
Light/Polite and Congruent conditions. Both the PMN and N400 findings support the importance of
word stress in spoken word recognition and its relevance to any theory of spoken word recognition
(e.g., the MERGE model).

Precongress course: Face to face with MCI

Clinical Markers to Predict Progression from Mild Cognitive Impairment to Alzheimer

M.Borrieab , M. Smithb , J. Wellsab , J. Mowatb
  Division of Geriatric Medicine, University of Western Ontario. b Aging Brain Clinic, Parkwood
Hospital 801 Commissioners Road East, London, Ontario, Canada N6C 5J1
Mild Cognitive Impairment (MCI) is an evolving concept in the field of dementia. To date, there is
no way to predict which patients with this diagnosis are more likely to progress to Alzheimer
disease. The purpose of this retrospective analysis was to examine whether measures of daily
function could predict who would progress to Alzheimer disease following a diagnosis of MCI.
Methods. Analysis of longitudinal data from patients with the diagnosis of Mild Cognitive
Impairment was examined. Variables related to cognitive and functional measures were assessed
and, based on conversion status at 2 years, predictor variables were analyzed. Mini-Mental Status
Examination total score and Lawton-Brody Instrumental Activities of Daily Living (IADL) and
Physical Self-Maintenance Scale (PSMS) subscale and total scores were analyzed.Results. Eight of
the patients (40%) progressed to Alzheimer disease over the following 2 years. Subscale analysis
revealed that there was a significant difference between groups with respect to their ability to plan
and prepare meals (p<0.05). This difference was independent of gender. There was no significant
difference in age (p>0.05), gender (p>0.05), or baseline MMSE scores (Conversion = 27.0 vs Non-
Conversion = 27.3, p>0.05). Total IADL and PSMS scores did not predict conversion. Discussion.
Subscale IADL items are more sensitive to change than cognitive screens or total IADL scores. The
relative impact of particular IADL‟s may be lost in Total ADL scores. Outcome scales such as Goal
Attainment Scaling of individualized activities may be a more sensitive measurement technique to
predict conversion of people with MCI to dementia.

Mild cognitive impairment – fact or fiction?

Anna Marriot, Roger Bullock
                           Kingshill Research Centre, Victoria Hospital, Sw indon, UK
MCI is a clinically significant syndrome, but remains poorly characterised and unlinked to patient
perceptions of the impact of the condition. It is generally considered a pre dementia syndrome, but
the objective of this paper is to argue that within the current accepted MCI spectrum more than one
area of cognition can be demonstrated, functional decline can be measured reliably and patient and
carer aspects of life are altered. The methods used are analysis of cognitive testing in controls, MCI
patients and AD patients from the memory clinic database, a correlation of the Bayer-ADL scale
with a staging instrument and focus groups of patients and informants with both MCI and AD.
Results show a spectrum of cognitive impairments, not just memory, increasing in severity even
before research criteria standards for dementia are met; significant changes in all items on the
Bayer-ADL scale between Global Deterioration Scale 2 and 3 and focus group informants showing
under reporting of problems by the patients with MCI – in a manor very similar to that previously
described in dementia studies, plus a patient perspective of MCI that mirrors a lot of difficulties
faced by those with very mild AD. These results thus suggest that the current definitions of MCI do
meet most diagnostic criteria for dementia, and pose the question as to why the “diagnosis” is
needed. Several possible explanations will conclude the presentation.

Self-Administered Mild Cognitive Impairment Touch Screen Tests: The CANS-MCI Study

Emory Hill.
                                               Seattle, WA, USA
This presentation examines the validity of a fully self-administered instrument, the Computer-
Administered Neuropsychological Screen for Mild Cognitive Impairment (CANS-MCI), with
respect to its ability to provide useful screening information about the need for full diagnostic
evaluations of dementia. The CANS-MCI can generate automated graphical reports of longitudinal
findings in languages other than those used for test administration and using images that are
country-specific. 310 elderly community-dwelling volunteers enrolled in a 3-year longitudinal
NIA-funded study in the US. Baseline, and 6-month data are presented. Analyses include
confirmatory factor analysis of baseline data on CANS-MCI tests along with concurrent Weschler
Memory Scale, WAIS Digit Symbol and Mattis DRS scores. ANCOVAs examined changes at 6-
months a, controlling for baseline scores. Results: The validity of the CANS-MCI as a screening
instrument for MCI was supported. Confirmatory factor analyses supporting a 3-factor model
(Memory, Language/Spatial Fluency and Executive Functioning) provided the basis for testing
change scores within cognitive domain factors. Normal and MCI groups for each factor were
determined by standardized test scores. Significant group differences over 6 months time were
found within each factor for CANS-MCI tests (p<.05). Conclusion: The CANS-MCI is an easily
administered screening tool measuring all cognitive dimensions that predict the need for treatment.
Analyses indicate respectable levels of validity, three primary factors predictive of Alzheimer‟s, and
the ability to distinguish between MCI and normal functioning over time. The CANS-MCI provides
change scores that signal the need for full neuropsychological evaluations early enough in the pre-
clinical phase of the disease to enhance the timing of treatment decisions.

Homocysteine: a new risk factor for cognitive decline, vascular and Alzheimer’s dementia

Angeles Garcia
                   Associate Professor, Medicine Queen’s University, Kingston, Ontario, Canada
In recent years, the impact of serum tHcy on cognitive function in the older population has started
to emerge. Several studies have shown a relationship between tHcy and dementia and between tHcy
and cognitive decline associated with aging. Homocysteine is a B-vitamin dependent aminoacid
produced during the metabolism of methionine. Elevated tHcy results form low levels or function of
folic acid, cobalamin (Clb) or B6, therefore it might be possible to reduce tHcy levels with vitamin
therapy, raising the hope for possible preventive treatments. Elevated serum tHcy has been found to
be an independent risk factor for the development of Alzheimer‟s disease. In a recent 8-year follow-
up study from the Framingham Study cohort, the authors found that elevated tHcy was an
independent risk factor for the development of Alzheimer‟s disease 8 years after baseline, and that
the risk increased with higher levels of tHcy. Similarly, an association between elevated tHcy and
dementia has been described in other populations. Results from the UK have shown that serum
tHcy levels are significantly higher among patients with Alzheimer‟s disease (AD) than in the
normal elderly population. In a recent study elevated tHcy was found to be more common among
patients with vascular dementia than in patients with AD. Cross-sectional studies in the healthy
elderly have yielded conflicting results. Some authors have found significant associations between
tHcy levels and cognitive function while others did not. Early studies in a small sample of an Italian
healthy elderly population showed no significant correlations between the Mini-Mental State Exam
(MMSE) scores and tHcy levels. However, the same authors later found, in a much larger
population group, that the risk of lower MMSE scores increased with increasing levels of plasma
tHcy, and that tHcy had an independent graded association with cognitive impairment. Cohort
studies on the relationship between tHcy levels and scores of cognitive function tests have yielded
more consistent results. An early study by McCaddon et al., showed that elevated tHcy at baseline
could predict lower verbal and visuospatial deficits at 5-year follow-up. Although initial results
from a nested case-control study from the Rotterdam cohort showed no relation between tHcy levels
at baseline and decline in scores of the Mini-Mental State Exam (MMSE) (by more than 1
point/year) 2.7 years after baseline, in a population that included younger adults (age >55), follow-
up studies from the same Rotterdam cohort showed significant associations between elevated levels
of tHcy and scores in a battery of psychometric tests, including the Stroop test, among subjects
whose baseline MMSE was lower than 26/30. Recently, in a large cohort study (the Maastricht
Aging Study, or MAAS) that included normal subjects 30 to 80 years of age, Teunissen et al found
significant correlations between tHcy levels at baseline and scores of tests of cognitive
performance, including the Stroop and the Word Learning Test, at baseline and at follow-up. In
our cohort study of community living, cognitively normal older adults (with a mean MMSE of 28.4
at baseline and follow-up), we found that tHcy levels at baseline and increases of tHcy levels from
baseline to follow-up 2.3 years after, were significantly related to lower scores in the Stroop test at
follow-up, independently of other variables, and that the rate of change of tHcy from baseline to
follow-up was inversely and negatively correlated with the rate of change in the Stroop scores.
Interestingly, declines in the Stroop score were even seen in subjects whose tHcy levels were in the
upper range of the normal limit, suggesting that what is considered as “within normal” tHcy levels
might already contribute to cognitive deterioration. In conclusion, serum levels of tHcy have been
associated with cognitive function in older adults. High levels of tHcy and increases of tHcy over
time confer a significant risk of worsening of cognitive function and dementia. There are no
published treatment trials aimed at decreasing levels of tHcy, and therefore, it is not known if
supplements of B-vitamins can prevent or revert cognitive damage in this population. Given the
magnitude of the disease, such studies are warranted.
Wednesday 25 february 2004

Plenary lecture

                          Growth Factor Gene Therapy in the Central Nervous System

Mark Tuszynski, Armin Blesch, James Conner, Mary Pay
University of California-San Diego, La Jolla, California. USA
Growth factors influence nervous system development, functional plasticity, and responses to
injury. The neurotrophin family of growth factors (NGF, BDNF, NT-3 and NT-4/5) is the most
extensively characterized of nervous system growth factors. NGF prevents injury-induced and age-
related degeneration of basal forebrain cholinergic neurons in rodents and primates, ameliorates
spatial memory decline in rodents, and reverses declines in cholinergic systems in a mutant mouse
model of amyloid over-expression. Satisfactory means of delivering neurotrophins to focal brain
regions, without exposing non-targeted neurons to growth factors, is required for the practical
implementation of growth factor delivery in the clinic. Gene delivery is one means of potentially
meeting growth factor delivery requirements to the brain. Based upon extensive efficacy and safety
data in primates, we have begun a clinical trial of growth factor gene delivery in Alzheimer's
disease (AD) to test the hypotheses that 1) NGF delivery will prevent cholinergic neuronal decline
in AD, and 2) that reducing the extent of cholinergic neuronal degeneration will ameliorate
cognitive decline in AD.

Neuroplasticity and brain repair

                                Extensive cortical rew ir ing follow ing brain injury

Numa Dancause a, Scott Barbaya, Shawn B. Frosta, Erik J. Plautza , Daofen Chenc and Randolph J.
  University of Kansas Medical Center, Department of Molecular and Integrative Physiology,
  Kansas University Medical Center, Center on Aging, cNational Institute of Neurological Disorders
and Stroke, USA
In a previous publication, we showed that the ventral premotor cortex (PMV) underwent
neurophysiological remodeling when examined a few months after injury to the primary motor
cortex (M1). In the present study, we examined cortical connections of the reorganized PMV. We
provide evidence that PMV substantially increased its connections with the primary somatosensory
cortex (S1). These results support the hypothesis that following a cortical injury, as might occur in
stroke, cortical areas distant from the injury undergo major neuronatomical reorganization,
involving sprouting of corticocortical axons over long distances. Cortical rewiring over such
distances has not been demonstrated previously in adult subjects, and is likely to contribute to
behavioral recovery after stroke.

Motivational consolidation of LTP. Mechanisms and effects of aging.

William Almaguer-Meliana , Jorge A. Bergadoa, Sabine Freyb and Julietta U. Freyb
  International Centre for Neurological Restoration (CIREN), La Habana, Cuba. b Leibniz Institute
for Neurobiology, Magdeburg, Germany
Long-term potentiation (LTP) is a form of synaptic plasticity expressed in excitatory synapses in
form of an activity-dependent increase in synaptic efficacy, which might be involved in learning,
and rehabilitation. It has been shown that LTP can be modulated in its duration by
emotional/motivational factors (motivational consolidation, MC). However, the mechanisms
involved in such interaction are not known. We have studied this issue, and the consequences of
aging on motivational reinforcement of LTP in the dentate gyrus, combining behavioral,
electrophysiological, pharmacological, and biochemical methods. Results show that the amygdala is
a key structure in MC. Its stimulation mimics the effect of behavioral reinforcers and its temporal or
permanent inactivation blocks MC. This effect seemed to require the mediation of septal afferents.
Lesioning the fimbria-fornix abolishes MC while stimulating the septum mimics the effect of
behavioral reinforcers. The pharmacological studies indicate a role for noradrenergic systems.
Antagonists (propranolol) block MC, while agonists (norepinephrine) cause a similar reinforcing
effect. A role for cholinergic systems have also been shown, but resulted controversial in
pharmacological experiments using antagonists (atropine) or agonists (oxotremorine). MC requires
protein synthesis as is completely blocked by anisomycin. Microdialysis-biochemical studies have
shown an increase in acetyl choline and a reduction in norepinephrine and serotonine release at the
dentate gyrus after amygdala stimulation; while behavioral reinforcing paradigms showed changes
in glutamate and glycine, suggesting that different sub-systems might mediate different forms of
reinforcement. Finally we have shown that aging, associated with cognit ive impairments have a
profound effect impairing mechanisms of motivational consolidation, induced both by a behavioral
reinforce or the stimulation of the amygdala

The contribution of the basal forebrain cholinergic system to cortical plastic ity ass ociated with normal learning and functional
                                                recovery follow ing brain injury

James M. Conner and Mark H. Tuszynski
Department of Neurosciences, University of California San Diego, La Jolla, CA., USA
Cortical plasticity, and the reorganization of cortical sensorimotor representations, has been
proposed as a substrate for normal learning and recovery of function following brain injury. The
physiological and cellular mechanisms responsible for cortical reorganization have not been fully
elucidated. In our recent studies, we investigated the contribution of the basal forebrain cholinergic
system in modulating plasticity associated with cortical motor representations. We first
investigated the effects of specific basal forebrain cholinergic lesions upon cortical reorganization
associated with learning a skilled motor task and addressed the functional/behavioral consequences
of blocking cortical map reorganization. Results from this study demonstrate that disrupting basal
forebrain cholinergic function significantly impairs, but does not abolish, acquisition of a new
motor skill. Electrophysiological mapping techniques indicated that skilled motor learning was
associated with a significant 30.3 ± 7.7% expansion of the caudal forelimb representation in the
cortex controlling the trained limb. In animals with selective lesions of the basal forebrain
cholinergic system, the expected expansion is completely blocked. Additional experiments
demonstrated that the basal forebrain cholinergic lesions did not lead to deficits in i) global
attention associated with performing the reaching task, ii) other forms of learning such as
associative fear conditioning or iii) general sensorimotor function. Taken together, these results
support the hypothesis that the basal forebrain cholinergic system may be specifically implicated in
forms of learning requiring plasticity of cortical representations.

The development and function of mammalian motoneurons following their rescue from programmed cell death by deletion of
                                            the pro-apoptotic gene Bax

Ronald Oppenheim, David Prevette, Sharon Vinsant and Thomas Gould
Department of Neurobiology and Anatomy, Wake Forest University Medical Center, Winston-
Salem, North Carolina, USA
Genetic deletion of the pro-apoptotic gene Bax (Bax KO), a member of the Bcl-2 family,
permanently rescues many populations of developing neurons, including motoneurons (MNs) from
apoptotic programmed cell death (PCD). Because normally 50-60% of all post-mitotic embryonic
MNs undergo PCD, Bax deletion results in the survival of thousands of excess neurons into
postnatal and adult stages. Although this sub-population of “undead” MNs initially differentiate
normally and innervate peripheral muscle targets, by perinatal/early postnatal stages, two
populations of MNs can be identified: approximately one-half of all MNs appear cytologically
normal and maintain innervation of target muscles, whereas the remaining sub-population
(“undead” cells) have small atrophied cell bodies and peripheral axons that appear to reach no
further than the ventral root or proximal sciatic nerve. We reasoned that the failure of the sub-
population of “undead” MNs to grow normally and sustain muscle innervation may be due to
limiting amounts of target-derived neurotrophic factors (NTFs). To test this idea, we have provided
Bax KO mice with excess amounts of one potent NTF, GDNF, during either embryonic, postnatal
or adult stages. GDNF but not BDNF treatment was able to prevent the atrophy and loss of
innervation in Bax KO mice when available to the embryo and reversed the atrophy and denervation
of the “undead” MNs when GDNF treatment occurred postnatally or in the adult. Preliminary
studies suggest that following postnatal treatment with GDNF, the rescued “undead” MNs in the
Bax KO mice may contribute to motor behavior. Studies are in progress to examine disease
progression in a mouse model of ALS (the SOD1 mutant) when crossed with the Bax KO (i.e. will
Bax deletion or Bax deletion plus GDNF rescue the disease phenotype).

Involvement of DNA damage and repair systems in neurodegenerative process

Daniela Uberti, Giulia Ferrari-Toninelli, Maurizio Memo
Department of Biomedical Sciences and Biotechnologies. University of Brescia Medical
School, Brescia, Italy
Preservation of genomic stability is an essential biological function. Cells engage very efficiently
mechanisms involving DNA surveillance/repair proteins that work to maintaining inherited
nucleotide sequence of genomic DNA over time. After DNA damage, that can arise during
duplication or after genotoxic stimuli, cells activate intracellular pathways which are able to
recognize the damage, to arrest cell cycle, to recruit DNA repair factors, to repair the damage or
induce apoptosis. This definitely relevant process is finalized to prevent the generation and the
persistence of impaired cells which may ultimately be detrimental to the organism. Very little is
known about the role of DNA damage sensors and repair factors in terminally differentiated, not
proliferating cells, like neurons. It is well recognized that mutation of genes related with DNA
damage repair are associated with specific cancer-prone syndromes. Interestingly, many human
pathological conditions with genetic defects in DNA damage responses are also characterized by
neurological deficits. These neurological deficits can manifest themselves during many stages of
development, suggesting an important role for DNA repair during the development and
maintenance of the brain. Here I will present recent data from my group underlining the
contribution to neurodegeneration of at least two transcription factors known to be involved in DNA
damage sensing and repairing: the tumour suppressor gene p53 and the component of the DNA
repair system MSH2. Both proteins participate in the cancer prevention machinery for the body as
well as in the neurodegenerative process. Moreover, they interact with each others to orchestrate
DNA repair functions.

    The injection of the fraction 25-35 of amyloid-ß into hippocampus of neonatal rats produces changes on cognitive,
                                            morphological and biochemical tests
E-M Cuevasa, J-F Guevarab , L-J Solisa , A-E Osorioa, F-A Diaza , I-M Garcíaa, and I-D Limóna.
  Instituto Nacional de Neurología y Neurocirugía México D.F. and a Laboratorio de
Neurofarmacología FCQ-BUAP. Puebla, México
In Alzheimer‟s disease (AD), the neuropathologycal hallmarks includes extracellular deposits of b-
amyloid in senile plaques, reactive astrocytes and intracellular deposits formation of neurofibrillary
tangles, the loss of neuronal cells and synapses. Histopathological, behavioral and biochemical
research suggest that the amyloid-ß protein produce a toxic effect and start the injuries. It‟s unclear
how or when this protein is aggregated into hippocampus and cortex.The aim of this work were
evaluated the effect of 25-35 fraction Aß injected into neonatal hippocampus and cortex, on
learning, memory, histopathological and biochemical test. The animals used, were PD7 male and
female Wistar rats pups. The pups were treated uni and bilateral with 1 µL of 25-35Aß (100µM)
into hippocampus by stereotaxic surgery (AP=+1.5, L=±2.3, P=-2.0). After twelve and fourteen
weeks were evaluated spatial learning and memory in the radial maze, respectively. The program
was (number trial /number opportunities. 1st day 3/8, 3/7 y 3/6, 2nd day 1/6, 3/5, ¾ y 2/3,
3/5, ¾, 3/3, and for memory test 8/3. We found in female rats deficits 18% and 32% uni-bilatral
lesion on spatial memory, respectively. In the hye, PASS and Bielschowsky stained we found a
decrease 40% in the neuron number in CA1 region. We found until 25% reactivity antibodies to
GFAP. Moreover, we found a 23% of increase for NO levels at four hours after deposit the 25-35
fraction Aß. However, we didn‟t found amyloid deposits using the antibody to Aß. Those results
suggest that 25-35 Aß fraction produce neurotoxicity in CA1 neuron of hippocampus and decrease
the spatial memory since neonatal stage, maybe NO way.

                    Cerebellar and pontine norepinephrine contents after motor recovery in rats

Rigoberto González-Piñaa , Antonio Bueno-Navaa, Carmen Escalante-Membrillob , Sergio Montesb ,
Angélica González-Macielc, Fructuoso Ayala-Guerrerod
  Laboratorio de Plasticidad Cerebral y Proliferación Celular, InCH-CNR, SSA México, b Instituto
Nacional de Neurología y Neurocirugía MVS, SSA México, cLaboratorio de Microscopia
Electrónica, INP SSA México, d Laboratorio de Neurociencias, Fac. de Psicología, UNAM, México
Motor cortex ablation induce motor deficits such as hemiplegia in rats. A spontaneous recovery that
can be enhanced by either cerebellar infusion of norepinephrine (NE) or administration of NE
agonists has been reported. These suggest that cerebellum (C) and pons (P), that contains the
NEergic locus coeruleus, can play an important role in the recovery after motor brain injury.
However, there are not data that relate directly the cerebellar and pontine NE contents with motor
recovery. In order to assess the status of the NE contents in P and C after functional recovery, we
trained 21 male wistar rats (280-320 g) to obtain their basal gait prints. Then animals were allocated
into two groups: sham operated (n=10) and injured by right motor cortex ablation (n=11). After 6
hours post-surgery, gait prints were recorded every 6 hours during 48 hours. Subsequently, animals
were decapitated and the left and right hemispheres of P and C were processed for NE extraction
and HPLC analysis. The remained brain was fixed in formalin-buffer 10% in order to be stained
with Nissl's method to verify the extension of the lesion. Length, width and angle were measured in
the gait prints. Results showed that gait parameters were fully recovered 48 hours after performance
of the lesion, while NE contents were increased in left and right P and decreased in left and right C.
We conclude that recovery observed could be a result of a reorganization in the NE pathways,
which also could involve to other cerebral structures.

                      Proechimys guyannensis rat: an animal model of resistance to epilepsy

Esper Cavalheiro
Neurologia Experimental-Escola Paulista de Medicina- São Paulo - Brazil
The potential interest of Proechimys Guyannensis (PG), a spiny rat living in the Amazonian region,
as an animal model of anti-convulsant mechanisms prompted the investigation of the susceptibility
of PG to different epileptogenic paradigms. The findings pointed out a remarkable resistance of
these animals to different models of experimental epilepsy: 1) Amygdala kindling development –
Proechimys animals demonstrated a striking resistance to reach the stage 5 of kindling. From 43
Proechimys rats submitted to the kindling process only 3 animals reached the stage 5. From 40
animals that did not reach the kindled state, 16 did not extended beyond stage 1, 15 from stage 2, 7
from stage 3 and 3 from stage 4. Amygdala electrical stimulations were followed by very long after-
discharges, mainly in stages 1-4. 2) Intrahippocampal kainic acid (KA) – A remarkable sensibility
to intrahippocampal KA was noticed in PG. One-tenth of the KA dose usually used in Wistar rats
elicited self-sustained electrographic status epileptus in PG animals which lasted for more than 48h
with increased mortality rate. On the other hand, none of the surviving animals presented
spontaneous seizures in the long-term observation period (up to 120 days). Neuropathological
examinations of the hippocampus of Proechimys animals after KA injection showed a complete
neuronal destruction at the injected hippocampal formation, more pronounced in CA1/CA3 areas,
and with less marked changes in the contralateral hippocampus. 3) Pilocarpine – Pilocarpine (350-
380 mg/kg – doses regularly used in Wistar rats), when administered to PG induced severe tonic
seizures followed by death of all animals. Dose slightly lower (300 mg/kg) than those previous ly
mentioned was able to induce repetitive electrographic and behavioural seizures that culminated in
status epilepticus 20-30 min following pilocarpine. However, pilocarpine-induced SE in PG had a
shorter duration, rarely exceeding 2 hours, clearly in contrast to the 8-12 h long SE in the Wistar
rat.From 60 animals injected with pilocarpine, 48 presented SE and only 2 presented some
spontaneous seizures (approximately 1/week for 8 weeks) after silent periods of 60 and 66 days.The
histological analysis of the brain of these 2 animals revealed neuronal loss in the CA3 area, in the
hilus of the dentate gyrus (DG) and mossy fibers sprouting in the supragranular layer of DG and in
the stratum radiatum of CA3. Altogether these data indicate that PG, although extremely sensitive
to chemical convulsants (ie, KA and pilocarpine) and presented longer afterdischarge following
electrical stimulation of the amygadala, is unable to establish a circuitry appropriated to the
elaboration of spontaneous seizures, ie, epilepsy. In other terms, it seems probable that limbic
circuitries, such as those found in the amygdala or the hippocampus, is highly affected by excitatory
stimulation. However some “external factors” such as inputs originating in extra-limbic areas seem
to prevent or inhibit the formation of a true epileptic focus. Some behavioural aspects observed in
PG during the 3 experimental situations described above could give some hints to justify this
hypothesis. During amygdala kindling stimulation and also during the seizures observed after
systemic pilocarpine or intrahippocampal KA, a cataleptic behaviour was clearly observed in PG
animals characterized by opistotonus and S tail suggesting the participation of the opiate system in
this process.These findings indicate that PG rats may have natural endogenous antiepiletic
mechanisms and further investigations (anatomical, biochemical, etc) need to be carried out to
clarify this phenomenon.

      Subacute electrical stimulation of parahippocampus and gaba system of patients with temporal lobe epilepsy

Luisa Rocha
Depto. Farmacobiología. Centro de Investigación y de Estudios Avanzados. México, D.F.
We previously reported that subacute electrical stimulation of the parahippocampal cortex (PHC)
reduces electrographic and clinical seizures in patients with intractable mesial temporal lobe
epilepsy (MTLE). The present study was carried out to evaluate the GABA system and neuronal
loss in PHC of patients with MTLE who received subacute electrical stimulation and presented
antiepileptic effects. GABA tissue content, GABAA and benzodiazepine (BDZ) receptor levels as
well as cell density were determined in PHC of patients with MTLE who received subacute
electrical stimulation (130 Hz, 450 µs, 200-400 µA, continuously during 16-20 days) in this brain
area and demonstrated a significant decrease of interictal spikes and seizures (ESAE group, n=5).
Values were compared with those obtained from patients with MTLE plus electrical stimulation but
without antiepileptic effects (ESWAE group, n=4) and those with MTLE in whom no electrical
stimulation was applied (MTLE group, n=4). Autopsy material acquired from subjects without
history of epilepsy was considered control PHC (C group, n=4 obtained from 3 subjects). ESAE
group demonstrated high GABA tissue levels (219%), as well as a significantly higher cell count
(58.5%) when compared with the MTLE group. Both the MTLE and ESAE groups demonstrated
decreased GABAA receptor values compared to controls with no significant differences in BDZ
receptor values. The present results suggest that subacute electrical stimulation of PHC electrical
stimulation is more effective in patients with less severe epilepsy, and effect associated with a high
GABA tissue content and a low rate of cell loss.

   Localization of the epileptogenic zone in temporal lobe epilepsy by ictal V -EEG compressed spectral arrays analysis.

L. Morales Chacon, Carlos S Catasus, Rolando Palmero, J Bosch Bayard , L. Lorigados, M.E.
Garcia, J. Bender, A. Sanchez.
International Center for Neurological Restoration. Havana Cuba
Objective: Localizing the seizure onset and temporal evolution of ictally dominant frequencies in
patients with temporal lobe epilepsy submitted to successful Standard Anterior Lobectomy and
evaluate the role of this methodology in lateralization diagnosis when Resonance Magnetic Imaging
shows normal or bilateral abnormalities. Methods: The onset of the ictally dominant frequency and
its temporal evolution was studied in eight patients using Compressed Spectral Arrays Analysis.
Five clinically and electroencephalographic representative seizures were selected, the time period
chosen was 20 s before and 16s after the electroencephalographic seizure onset. Sources of EEG
activity were determined with an inverse solution method called Variable Resolution Electrical
Tomography (VARETA), which provided a spline-distributed solution. We also compared the
lateralization diagnosis provided by this methodology with the information showed by
neurofunctional techniques. Results: In all patient an ictally dominant and consistent frequency of
5.90± 1.31 Hz could be determined, however in 6 of 8 patients a second dominant frequency peak
between 4.24-8 Hz was found. The use of linear inverse solution will allow to control that the
analyzed frequency is generated approximately within the brain region whose resection rendered all
patients seizure free. The lateralization and localization of the main dominant frequency during the
evaluated period around the ictal EEG onset corresponds well with the lateralization proposed by
other neuroimaging techniques such a interictal/ictal SPECT, and Cho/Cr ratio measured by MRS
(x2 (18)=42.5 p=0.009. Conclusions: Our data suggest, that the ictally dominant frequency
analysis and inverse solutions can be reliably used to detect ictal seizures onset arising in mesial
temporal lobe epilepsy. Combination of ictal EEG using spectral analysis, SPECT and ERM
improved the reliability of the localization and lateralization diagnosis in Temporal Lobe Epilepsy
patients much more important when the Resonance Magnetic Imaging shows normal or bilateral

                             Excitatory Amino Acid Transporter Activity and Oxidative Stress

J. G. Ortiz and N. Berríos-Cartagena
Dept. of Pharmacology & Toxicology, Univ. of Puerto Rico School of Medicine, San Juan,
Puerto Rico
The activity of high-affinity, sodium-dependent, glutamate transporters (EAAT 1-5) terminates
synaptic transmission, prevents extracellular glutamate (Glu) from reaching excitotoxic levels, and
controls synaptic spillover. EAAT regulation is rather complex involving
phosphorylation/dephosphorylation states, internalization/surface expression and redox status. The
possible reversal of EAAT activity has been the focus of the last decade. However such approach is
impractical as it would require precise knowledge of EAAT status in orde to be of theapeutic use.
In addition to excessive Glu receptors activation, elevated [Glu] levels are likely to interfere with
the cystine
amyolateral sclerosis (ALS) directly increases EAAT activity and partially prevents veratridine-
induced EAAT inhibition.. Moreover, chlorpheg, a cystine-glutamate exchange inhibitor,
significantly increases EAAT activity in rat hippocampal slices in the presence of 50 µM Glu and
partially prevents the inhibitory effects of veratridine on EAAT activity. These results suggest that
modulation of EAAT activity may be accomplished by separate mechanisms; directly as with
riluzole and indirectly via cystine

                                                 Post-traumatic epilepsy

Pierre Jallon
Epilepsy Unit, Geneva University Hospital, CH.1211 Geneva.14, Switzerland
Objectives: to evaluate the frequency, the clinical presentations and the therapeutic management of
post traumatic seizures and post traumatic epilepsy . Methods: we analysed and compared the recent
studies concerning early post traumatic seizures and late post traumatic epilepsy in children and
adults. Results: Early seizures were more prevalent among subjects 0-15 years of age with severe
head trauma than among individuals over 15 years of age. A majority of early seizures are focal and
of those 75 % are partial motor seizures. The fits may be single or repetitive. Status epilepticus or
acute repetitive seizures are more common in children than in adults. The occurrence of early
seizures is an indication for repeating imaging even in case of mild head injury. EEG plays only a
limited role in the evaluation of early seizures. The incidence of late post traumatic seizures differs
largely with age, type of trauma, neurological or neuroradiological signs attesting the severity of the
trauma. Incidence varies from 7 % in civilian injuries to 35 % in military injuries. Conversely to
early seizures, late seizures are less common and more delayed in children than in adults. The
spectrum of all types of partial seizures as well as generalised seizures can be observed except
bilateral myoclonias and absences. The issue of using antiepileptic drugs (AEDs) to prevent post
traumatic seizures remains very controversial. Phenytoin remains the drug of choice for preventing
and treating early post traumatic seizures because its efficacy and the possibility to use intravenous
administration. All other AEDs can be used in treating late seizures.

 Preliminar study of the anticonvulsant and anxiolytic like effects of GABA-amides derivated from n-GABA-3-(R-fenil)-2-E-
                                                   propenamide in mice

Ma.Eva González-Trujano a, Teresa Zapateroa, Magadalena Briones Velascoa, Lino Joel Reyes
Trejob , Andrés Navarrete Castrob .
  Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñíz”, Av. México-Xochimilco No. 101.
Col. San Lorenzo Huipulco. C.P. 14370, México, D.F. b Facultad de Química de la Universidad
Nacional Autónoma de México. Ciudad Universitaria Coyoacán. C.P. 04510, México, D.F.México.
Both etiology and treatment of anxiety and epilepsy have been associated with the GABAergic
system. It is well known that GABA can not cross the blood-brain barrier. A direct substitution
therapy in neurological diseases attendant on GABA deficiency is therefore not possible. This
report concerns the relationship between ten GABA-AMIDES synthesized from GABA and R-
propenamide group in order to get major liposolubility as a fundamental strategy to develop
therapeutic alternatives as anticonvulsant and anxiolytic drugs. Taconic mice maintained at standard
conditions were used. GABA-AMIDES were obtained by synthesis and diacepam was tested as
positive drug. Mice were injected with pentylenetetrazol, strychnine and 4-aminopyridine to record
occurrence of the first episode of clonic or tonic seizures and mortality. Anxiolytic like effect was
carry out on a exploration model. Effects on the coordination motor and miorelaxation were also
assayed. The R-propenamide group increased liposolubility of GABA, important factor to produce
effect on the central nervous system, but not a determinant factor to produce anxiolytic like effect,
because it was not observed a direct relation between pharmacological effect and log P data.
Number and position of constituents appears to play an interesting roll in these pharmacological
properties. It is because, two GABA-AMIDES with the chemical group metoxi on positions 2,4 or
3,4 were the most active. Agree with LD50 data, all active GABA-AMIDES were no toxic. One of
them showed anticonvulsant activity. These results suggest that GABA-AMIDES have anxiolytic
like effects without adverse effects, it is an advantage over drugs clinically used. Differential effect
of these GABA-AMIDES could involve different mechanism of action to the GABAergic system.

            CaM kinase II- Mediated Modulation of GABAA Receptor Phosphorylation in Status Epilepticus

A. Rana a, P.D. Franksa, J.T. Parsonsa, A. de Blase e, S.B. Churna,b,c,d
Departments of a Neurology, b Anatomy and Neurobiology, cPharmacology and Toxicology, and
  Physiology, Virginia Commonwealth University, Richmond, VA USA. e Physiology and
Neurobiology, University of Conneticut, Storrs, CT USA
Calmodulin-dependent kinase II (CaM kinase II) activation has been shown to positively modulate
both agonist and allosteric modulator binding, and agonist-induced anion currents. Prolonged status
epilepticus (SE) has been shown to result in both inhibition of CaM kinase II activity and loss of γ-
amino butyric acid (GABA) receptor function. This study was designed to determine if the SE-
induced inhibition of CaM kinase II activity also resulted in loss of GABAA receptor
phosphorylation. The pilocarpine rat model of SE was utilized, and SE level was determined both
behaviorally and by EEG measurements by surface electrodes. Following SE or sham treatments,
animals were decapitated, and crude synaptic membrane fractions isolated by differential
centrifugation. Standard CaM kinase II assays were performed, GABAA receptor subunits isolated
away from synaptic proteins by detergent solublization, immunoprecipitation and resolution onto
SDS-PAGE. Phosphate incorporation into GABAA receptor subunits was quantified by direct
counting of resolved protein bands on either SDS-PAGE or western blots (Instant Imager, Packard
Instruments).There was poor correlation between behavioral seizures and loss of kinase activity.
However, all animals that progressed into continuous seizure activity measured by EEG recordings,
displayed a significant loss of kinase activity in brain fraction homogenates. In crude synaptic
membrane fractions SE resulted in an approximate 41% inhibition of CaM kinase II activity
towards exogenously added substrates (Autocamtide 3, Calbiochem). In parallel reactions, SE
resulted in approximately 40% inhibition of CaM kinase II-mediated phosphorylation of GABAA
receptor α1 subunit (27.8 vs. 16.6 amol/mm2/min). Furthermore, SE resulted in approximately
37% inhibition of GABAA receptor β 2/3 subunits that co-precipitated with α1 subunit protein.
Since CaM kinase II activation has been shown augment both GABAA receptor agonist and
allosteric modulator binding and agonist-induced current, the data suggest a mechanism whereby
SE results in loss of GABAA receptor operation. RO1-NS39970, P50-NS25630

        The hyperthermia induced seizures produce transient gabaergic cell death in the hippocampus of the rat

Sandra A. Orozcoa, Misael Gonzáleza , Sebastián Castillob and Alfredo Feria c.
 Unidad de Investigación Medica en Enfermedades Neurológicas, Hospital de Especialidades,
 Unidad de Investigación Medica en Enfermedades Oncológicas, Hospital de Oncología, CMN,
Siglo XXI, IMSS, México D.F. y cUnidad de morfología de Alta Resolución,CUCBA, Universidad
de Guadalajara, Guadalajara, Jal. México.
The febrile seizure is the most prevalent age-specific seizures in infant and young children. Whether
they result in long term sequels such neuronal lost and lobe epilepsy, it is controversial. Some
studies of human febrile seizure have found no adverse effects on the developing brain. However,
adults with temporal lobe epilepsy have a history of prolonged febrile seizures in early life. This
study is aimed to know if hyperthermia-induced seizures produced neuronal death in infant and
developing brain. Infant rats were subject to hyperthermic seizures (a model of prolonged febrile
seizure). Neuronal death was assessed in sections of forebrain, stained by DAPI nuclear stain, in
situ terminal deoxynucleotidyl tranferase dTUP nick-end labeling (TUNEL stain), annexin V
antibody and electronic microscopy. We used two neuron marker, NeuN antibody by neurons and
GAD65/67 antibody by GABAergic cells. The studies were carried at 24 hrs after the seizure and 5,
15, 20 and 30 days after seizures. The results showed TUNEL and annexin positive cells in
hippocampal formation mainly in the CA1, CA3, and dentate gyrus, 24 hrs after seizures and few
TUNEL and annexin positive cells at 5, 15 and 20 days after seizures. The 100% tunnel positive
cells, 30% co-localized with GAD65/67 positive cells and 20% co-localized with NeuN positive
cells. The electronic pictures showed some apoptotic neurons with dispersed chromatin and some
neurons with necrotic characteristics. These results showed the prolonged febrile seizures resulted
in transient neuronal death in immature hippocampus involved death of GABAergic neurons. The
loss of these neurons could be enhanced susceptibility to further limbic seizures.

                      Anticonvulsant valproic acid induces differentiation in human neuroblastoma cells

A.M. Ferreri, P. Rocchi
Department of Experimental Pathology ,University of Bologna, Bologna, Italy
Valproic acid ( vpa,2-propylpentanoic acid ) is an established drug in the long-term therapy of
epilepsy During the past years ,it has become evident that vPA is also associated with anti-cancer
activity .the present study was aimed at evaluating the effect of sodium valproate on differentiation
and proliferation in the human neuroblastoma cell lines AF8 and TS12.Neuronal differentiation was
assessed by means of morphological and cytochemical parameters,i.e. neurite outgrouth and
acetylcholinesterase specific activity Growth curves and colony-forming assay were performed in
order to determine cell growth inhibition Sodium valproate induced inhibition off cell growth
(demonstrated by growth curves) and reduced the colony forming ability in a dose dependent
manner in both cell lines. Inhibition of cell proliferation was accompanied by morphological
features of neuronal differentiation: on both cell lines valproate induced neuritogenesis in a dose
dependent fashion. Biochemical differentiation was demonstrated by the increase in the
acetylcholinesterase specific activity,an enzime widely used as biochemical marker for neuronal
differentiation in neuroblastoma cells.these results underline the role of HDACs inhibitors as new
cancer drugs and suggest the evaluation of sodium valproate for cytodifferentiation therapy in the
treatment of neuroblastoma.


Subacute electrical stimulation w ith antiepileptic effects modifies GABAergic system in patients w ith intractable temporal lobe

Manola Cuéllara, Marcos Velascob , Francisco Velascob , Ana Luisa Velascob , Sandra Orozcoc and
Luisa Rocha a
 Farmacobiologia,CINVESTAV-IPN. b Hospital General de México. cHospital de Especialidades,
México, D.F, Mexico.
Experimental studies demonstrated that high frequency stimulation (HFS) of cerebral regions
reduces seizures in patients with refractory temporal lobe epilepsy (TLE). We suggest that HFS in
these patients induces the activation of Gabaergic system. Methods: Tissue cerebral were obtained
from 3 groups: control (C, n=3), TLE (n=6) and TLE with HFS (HFS, n=6). HFS consisted of
continuous stimulation with biphasic pulses (duration: 0.45 sec; frequency: 130 Hz; amplitude: 0.2-
0.4 mA). Ammon´s horn (AH) in hippocampus and parahippocampal cortex (PC) GABAA and
BZD receptors system were evaluated using autoradiographic technique. GABA and Glu content
were determinated by high performance liquid chromatographic analysis. Neuronal population
count was performed using Nissl staining technique. Results : Concerning hippocampus TLE
showed a decrease for GABAA and BZD receptor binding, tissue content of amino acids and
neuronal count were similar to previous reports. HFS exhibited increased for GABAA receptor
levels in AH (1086%) compared with TLE, BZD receptor binding was increased in AH compared
with C (339%) and TLE (207%). GABAA receptor binding in PC (85%) exhibited decreased values
compared with C, whereas BZD receptor binding did not show changes in this region. The regions
AH (46%) and PC (44%) exhibited increased neuronal population count compared to TLE. There
was a direct correlation between increased levels of the GABA and Glu in PC with decreased
percentage of interictal spikes from the HFS. Conclusions: These results suggest that the
antiepileptic effects of HFS involve increase GABAA and BZD receptors in AH, enhanced GABA
and Glu amino acid levels and less neuronal loss in PC.

                       Inhibitory effect of 5-HT1A receptors on experimental limbic seizures in rats

María-Leonor López-Meraza,b , Leticia Neri-Bazána, María Eva González Trujanob & Luisa Rocha a
  Centro de Investigación y de Estudios Avanzados del I.P.N., México D.F., b Instituto Nacional de
Psiquiatría “Ramón de la Fuente”, México, D.F.
The purpose of this investigation was to evaluate the participation of 5-HT1A receptors on
pentylenetetrazol (PTZ, 60 mg/Kg i.p.), kainic acid (KA, 10 mg/Kg i.p.) and amygdala kindling
(daily 1s train of 1ms pulses at 60 Hz and 400 mA)- induced seizures in male Wistar rats,
employing two agonists (8-OH-DPAT 0.01, 0.1, 1 mg/Kg and indorenate 1, 3, 10 mg/Kg) and an
antagonist (WAY100635 1 mg/Kg) of these receptors. Neither of these 5-HT1A ligands modified
the latency to the PTZ- induced clonic-tonic seizures. However, 8-OH-DPAT enhanced twice the
number of clonus induced by PTZ, effect associated with decreased mortality. On the other hand, 8-
OH-DPAT and indorenate augmented the latency to the first wet dog shake (WDS) (44-58% and
67%, respectively) induced by KA, effect that was blocked with the antagonist. Additionally, 8-OH-
DPAT diminished the frequency of WDS (44-59%) and generalized seizures (GS) (78-84%) during
the KA- induced status epilepticus (SE). Similarly, Indorenate decreased in 69-75% the number of
GS. Interestingly, WAY100635 decreased non significantly the number of WDS and GS. In
addition, 8-OH-DPAT and indorenate diminished the percentage of animals with SE (63-83%). In
contrast, the evaluated drugs did not alter the kindled seizure expression. Nevertheless, indorenate
decreased the seizure susceptibility during the postictal depression (34%), effect reverted by
WAY100635. These results suggest that 5-HT1A receptors induce inhibitory effects on the KA-
induced SE and during the postictal depression associated with the amygdala kindled seizures.
Supported by CONACyT (scholarship 153240).

    Increase P-glycoprotein expression in several limbic brain regions in the phenytoin resistant amygdala-kindled rats

Graciela Jiménez-Rubioa , Sandra Orozco-Suárezb , M. Eva González-Trujanoa , Luisa Rocha c
 Instituto Nacional de Psiquiatría "Ramón de la Fuente" and Centro de Investigación y Estudios
Avanzados, Sede Sur, Farmacobiología, Instituto Politécnico Nacional. México, D.F., bUnidad de
Inv. Médica en Enfermedades Neurológicas, H de Especialidades, CMN, Siglo-XXI, IMSS. México,
D.F., cCentro de Investigación y Estudios Avanzados, Sede Sur, Farmacobiología, Instituto
Politécnico Nacional. México, D.F.
Studies have shown that multidrug transporter P-glycoprotein (PGP-1) is overexpressed in
endothelial cells (EC) from brain blood vessels of patients with refractory temporal lobe epilepsy
(TLE), suggesting the role of PGP-1 in pharmacoresistance to antiepileptic drugs (AEDs). In this
study we used the amygdala-kindled rats, a refractory model to AEDs, to evaluate the PGP-1
expression in limbic brain regions thought to be involved in TLE. Male Wistar rats (250-350 g)
were kindled by basolateral amygdala stimulation. After kindling acquisition, four independent
acute phenytoin (75 mg/kg i.p.) trials were done. Response to phenytoin was determined using a
threshold after-discharge; the response was sensitive (KSEN), variable (KVAR) or resistant kindled
rats (KRES). PGP-1-expression was analysed 24 h after the last kindled seizure by
immunohistochemistry. Cerebral cortex, hippocampus and amygdala were examined by confocal
and fluorescence microscopy. In kindled rats PGP-1 staining was observed in EC, astrocytes in
hippocampus and cortex, and neurons in amygdala. In KSEN rats PGP-1 staining was observed in
EC and astrocytes, whereas in KVAR rats it was found in EC, glia and neurons both in all testing
areas. The KRES rats showed an increased PGP-1 expression in EC and astrocytes in cortex and
hippocampus; neurons and glia in amygdala. The data indicate that PGP-1 over-expression in
KVAR and KRES rats mainly in capillary endothelial and glial cells of the blood brain barrier is
likely to reduce the penetration of AEDs into brain parenchyma, which could explain the variability
of the response and the phenytoin resistant in this epilepsy model.

               Febrile seizures modify the benzodiazepine receptor binding in the developing rat brain

González Ramírez Ma, Orozco Suárez Sa, Salgado Ceballos Ha,Briones Velasco Mb , Rocha Arrieta
  Unidad de Investigación Médica en Enfermedades Neurológicas H. Especialidades CMN SXXI
IMSS. bDivisión de Neurociencias, INP “Ramón de la Fuente” y cDepto. De Farmacobiología,
It has been described that immature brain is more susceptible to seizures than the mature one and
that febrile seizures early in life may lead to epilepsy. The present study was carried out to evaluate
the benzodiazepine (BDZ) receptor binding in specific brain areas of immature rats at different
times. So, pups of 10 days old were placed on the floor of a 3 l glass container and an air stream
was directed ~50 cm above them. Hyperthermia was maintained for 30 min, aiming for a core
temperature of 41°C. Thereafter, rats were placed on a cool surface, monitored for 15 min, and then
returned to their home cages for rehydratation by the mothers. The control group was normothermic
temperature. Animals were sacrificed by decapitation 30 min, 24 h and 20 days after seizures and
their brains were used for autoradiography assay with the purpose to determine BDZ receptor
binding in different brain areas. Animals sacrificed at 24 h increased BDZ receptor levels in
cingulated cortex (79.55%), frontal cortex (70.51%), parietal cortex (70.53%), striatum (23.94%),
basolateral amygdaloid nuclei (51.29%), central amygdaloid nuclei (32.16%), medial amygdaloid
nuclei (49.88%), entorhinal cortex (35.09%) and substantia nigra, compact part (33.41%). In
contrast, the groups sacrificed at 30 min and 20 days after febrile seizures did not present significant
changes as compared to the control ones. The results indicate that the febrile seizures do not induce
permanent BDZ changes in the immature rat brain. Moreover, it is possible that the enhanced BDZ
receptor levels 24 h after febrile seizures may play a protective effect in the immature brain.

                      In vivo study of transgene expresión of pgfa2-GAD67 into rat hippocampus

Cecilia Zavala a, Paula Vergara b , José Segovia b and Luisa Rocha a
  Farmacobiología. b Fisiología, Biofísica y Neurociencias, CINVESTAV-IPN, México, D.F.,
Decreased GABAergic inhibition has been suggested to induce hyperexcitability. The present study
evaluates the potential for preventing seizure generalization by increasing local GABAergic
inhibitory activity by applying of a new technique: to express the GABA-synthesizing enzyme
GAD67 in the host‟s own astrocytes. Using a transgene in which the activity of GAD67 is under the
control of a glial fibrillary acidic protein (GFAP) promoter, it confers astrocyte-specific expression.
The rats were transfected with 1,2 and 4 µg of gfa2-GAD67 (GAD) or pgfa2-Lac-Z (LZ) into
hippocampus. Sham control rats (CSh) were not transfected. Three days following microinjection of
the transgene, the rats received a single administration of pentylenetetrazol (PTZ, 70 mg/kg i.p.).
The latency and duration of the seizures were evaluated. The hippocampal tissue samples were
obtained 24 hours after of administration of PTZ and expression of transgene was detected by RT-
PCR. In the GAD group the latency to the first clonic seizure was decrease in 76% compared to
CSh. Nevertheless, an increase of duration of postictal period was observed in the GAD groups. The
duration of mioclonic seizures was significantly decreased in the GAD group (2 µg) (4.8 ± 0.6 sec)
compared to CSh (16.14 ± 5.2 sec). The duration of tonic seizures was decreased in the GAD group
(1µg) compared to CSh (28.67 ± 16.29 sec and 52.67 ±18.8 sec, no significant). Increased
expression of GAD67 was found in animals transfected with pGfa2-GAD67 transgene. The present
results suggest that transfection with pGfa2-GAD67 have inhibitory effects on the PTZ-induced

           Immunological disorders in epileptic patients are associated to the epilptogenic focus localization

Lourdes Lorigados, Lilia Morales, Nancy Pavón, Teresa Serrano, María de los Angeles Robinson,
María Eugenia García, Juan Bender
Centro Internacional de Restauración Neurológica (CIREN), Havana, Cuba
Clinical and experimental data support the role of immune mechanisms in the pathogenia of
epilepsy. The purpose of this work is to study the immunologic aspects in 30 epileptic patients with
complex partial crisis resistant to antiepileptic drugs. The patients were evaluated by EEG-Video
and they were grouped attending to epileptogenic focus localization in: temporal (n=16), lateralized
(n=6) and extratemporal (n=4). We also studied a group with psychogenic epilepsy (n=4); this
group was diagnosed after EEG-Video evaluation. The following immunologic evaluations have
been carried out: levels of serum immunoglobulins (IgG, IgM e IgA) by radial immuno-diffusion
test and lymphocyte subpopulations using immuno-cytochemical methods. We measured the
percent of lymphocytes T and B (CD3 and CD20), lymphocyte T helper/inductor (CD4),
suppresor/cytotoxic (CD8), interleukine-2 receptor (CD25) and human leukocyte antigen (HLA-
DR). The results show a significant increase of CD8+ lymphocytes (p<0.05) and in the activation
markers (CD25+ and HLA-DR+ cells). The evaluation of immunologic parameters applied to
different group of epileptogenic focus localization showed that the increase of CD8+ lymphocytes
is limited to temporal and lateralized patients (P<0.01). The patients with extratemporal localization
of focus and the psychogenic cases showed normal values for the evaluated immunologic
lymphocytes markers. We did not find a deficit in the humoral immunologic aspects. Taking into
account that patients diagnosed as psychogenic received an antiepileptic drug treatment identical to
that of the other group, the observed immunologic changes might be related with the pathogenia of
certain epilepsy variants associated with the focus localization and not with the medication.

                    Biochemical and morphological parameters in temporal lobectomised patients
Lourdes Lorigadosa, Lilia Moralesa, Sandra Orozcob , Leticia Neryc, Ivan García a, Barbara
Estupiñana , Barbara Paula f, Luisa Rocha c
  Centro Internacional de Restauración Neurológica, Havana, Cuba, bCentro Médico, DF, México,
  CINVESTAV, SedeSur, DF, México, f Hosp. Carlos J Finlay, Cuba
Temporal lobe epilepsy (TLE) is one of the most frequent types of human focal epilepsy. The main
goal of the present work was to examine some biochemical markers in cerebrospinal fluid (CSF)
and tissue from 8 lobectomized patients (TLE) and to determine the contribution of apoptotic
mechanism to epileptic process in these patients. Patients and methods: levels of amino acids were
measured by HPLC method in tissue and CSF. We studied the evolutive levels of amino acids in
CSF; the samples were taken before and after (1 and 6 months) surgical treatment. The CSF control
group (n=10) was obtained from surgical patients who did not present neurological diseases and the
tissue control group (n=4) was obtained from death not-neurological patients. The immune-
histochemical evaluation was carried up using the following cellular markers: enolase, Neun,
GABA and GAD 67/65. The apoptosis study was carried out for the occurrence of terminal
deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) and Anexin-V markers.
The final evaluation of cerebral tissue was done by confocal microscopy. The results showed
increased levels of glutamate in cerebral tissue. There are significant decreased of glutamate levels
between pre-treatment and before (6 months) treatment. Numerous TUNEL-positive cells were
observed whereas Anexin V-positive cells were not significant. We found a decrease of enolase,
Neun, GABA and GAD 67/65 positive cells. The results evidence there is death but not only by
apoptotic phenomena but also by necrosis. The surgery process can restore the amino acids levels.

       Effect of carbamazepine on convulsive activiv ity and brain damage induced by administration of kainic Acid

Fructuoso Ayala-Guerrero, Alfonso Alfaro, Rosa María Romero, Graciela Mexicano-Medina and
Angélica González-Maciel.
Facultad de Psicología, Universidad Nacional Autónoma de México; Instituto de la
Comunicación Humana-CNR and Instituto Nacional de Pediatría, México.
Several animal models of epilepsy have been used in order to evaluate drugs with anticonvulsant
efficacy. Since administration of Kainic Acid (KA) causes physiological and anatomical
disturbances similar to those in temporal lobe epilepsy of humans, the kainate treated rat has been
considered as an experimental model of temporal lobe epilepsy. Carbamazepine, an antiepileptic
drug, has been utilized in clinical for controlling certain types of epileptic attacks. The objective of
this work was to analize the action of carbamazepine on convulsive crisis and brain damage induced
by KA administration. Experiments were carried out on chronically implanted wistar white rats.
One group of five rats was treated with KA (10 mg/kg ) alone, while other similar group was
pretreated with carbamazepine (25 mg/kg) 30 minutes before administration of KA. Ten hour
polygraphic recordings were continuously obtained under the two mentioned conditions. Under
general anesthesia,, brain were removed from the skull for histological analysis ten days after
administration of drugs. Animals receiving administration of KA alone presented convulsive
activity and brain damage. Carbamazepine pretreatment induced a slight decrement of convulsive
activity but brain damage was still present.

                                         Epilepsy surgery. A preliminary Study

Iván García Maeso, Juan E. Bender, Lilia Morales Chacon, Margarita Báez, Lourdes Lorigados
Pedre, Bárbara Estupiñán, Maria Eugenia García, Carlos Sánchez Catasús, Rolando Palmero.
Group of Epilepsy Surgery Project. International Center of Neurological Restoration,
Havana, Cuba.
Epilepsy surgery dates back to more than two millennia and the first intervention was cranial
trepanation. This pathology occurs in 0.1% of the population. Its initial medical treatment only
achieves control of crisis in a 50% to 80%; the remaining 20% is considered medically untreatable
and surgically remediable. Method and Material: 8 patients with refractory temporal lobe epilepsy,
of 23 candidates for surgical treatment were operated in the second semester of last year. The
surgical technique used was the adjusted temporal lobectomy. Transoperatory Electrocorticographic
recordings before and after resection were performed. A follow-up of the cases took place at one,
three and six months for a posterior evaluation in a year time. Results: 88 % of operated patients are
free of crisis and only one has suffered an occasional crisis. The complications were as follows:
three patients with hemosiderotic meningitis, one with a transitory dysfunction of the type III
cranial pair; one a diminishing of the verbal memory whereas another patient presented an
inadequate syndrome of the antidiuretic hormone. Conclusions: Resective surgery of temporal lobe
is the technique that we had selected for the treatment of refractory temporal epilepsy and the
patient had a satisfactory evolution.

 Antiepileptic effect of an extract of Ambrosia paniculata (Willd.) O. E. Schultz (mug-w ort) in several models of experimental

María T. Buznego, Héctor Pérez-Saad
Department of Experimental Epilepsy, Institute of Neurology and Neurosurgery, Cuba.
The acute effect of Ambrosia paniculata in several animal models of epilepsy was studied.
Intraperitoneal injections (0.01 mL x g of body weight) of a decoction of the dry leaves
significantly enhanced the latency of the first convulsion and the survival time in mice injected with
picrotoxin (7mg/kg) or isoniazid (210 mg/kg). Epileptic spikes were induced by topical application
of penicillin -a glass electrode filled with penicillin-agar-saline mixture- and recorded in
sensorimotor and occipital cortices. The plant decoction reduced significantly the spike amplitude
in both sites. The same decoction was not effective against the electroshock-induced convulsions in
mice. Since convulsions induced by isoniazid, picrotoxin and penicillin -differing from
electroshock- implicate a disruption of the GABAergic neurotransmission, these results suggest that
Ambrosia paniculata, like several conventional antiepileptic drugs, has a selective effect on this
neurotransmitter system, that explain the traditional use of the plant in epilepsy.

        Therapeutic effect of ozone in the brain ischemia: mechanism of action seems to involv e hydrogen peroxide

JD García-Salman, M García, A Cuba, RM Coro, H Perez-Saad
Department of Experimental Neurology, Institute of Neurology and Neurosurgery, 29st and
D, Vedado, Havana 10400, Cuba.
Brain can be considered as a main target organ for active oxygen species. It is the highest oxygen-
demanding organ, has a high content of unsaturated fatty acids, a poor antioxidant defense and a
high ferrum ion content. During brain ischemia, free radical reactions increase. There are some
evidences suggesting that SOD activity reduces edema, mortality and infarct volumes. Other
findings found links between hydrogen peroxide and selective gene expression, differentiation and
neuronal plasticity. On the other hand, therapy with ozone is based in the generation of ozonids,
including hydrogen peroxide. Then, ozonids could be carried by body fluids to the target tissue and
exert therapeutic effects. It has been suggested that maximal effects be obtained after a period of
preconditioning. In that sense, we treated Mongolian gerbils with intrarectal ozone (1 mg/Kg) for
three weeks before ligation of the right carotid artery. Treatment prevents impairment of
spontaneous exploratory activity, observed 7 days after ligation in oxygen-treated gerbils. In these
animals a significant damage in CA1 pyramidal neurons of the right hippocampus was found,
compared with the contralateral hemisphere. In another experiment, the spontaneous exploratory
activity before and 7 days after 5 min bilateral carotid occlusion was tested. Ozone was
administered in the six subsequent days of reperfusion. The results show that ozone treatment also
prevents impairments of the spontaneous exploratory activity. These findings suggest that ozonids -
particularly hydrogen peroxide - are protecting memory and learning-related synapses through
improving survival of brain cells.

  Three-synaptic hippocampal response during repeated electric al stimulation of entorhinal cortex in the Mongolian gerbil.
                                                 Effect of clonidine

Héctor Pérez-Saad, Margarita Bu Wong and Nora Sánchez Rodríguez.
Department of Experimental Neurology, Institute of Neurology and Neurosurgery, 29 and D st.
Vedado, Havana 10400, Cuba.
The Mongolian gerbil (Meriones unguiculatus) has been considered as a model of temporal lobe
epilepsy, which involves the hipocampal formation. In the present work the effect of clonidine and
fenitoin on the electrophysiological response of dentate gyrus to electrical stimulation of entorrinal
cortex was studied in anaesthetized gerbils (20 % urethane, 0,01 mL x g of body weight).
Intracerebral electrodes -following the stereotaxic atlas of Loskota- were used.
The amplitude of the population spike was obtained after averaging 20 stimuli (500 µA, 1 Hz and
100 µs). Clonidine (100 µg/kg ip.) and fenitoin (10 mg/kg ip.) reduced significantly the spike
amplitude 1 h after injection. In a group of animals the entorrinal cortex was stimulated with a 7 Hz
frequency: a second and third population spikes appeared about 20 seconds after the starting the
stimulation. These two spikes immediately disappear after coming back to the initial 1 Hz
frequency and reappear again with 7 Hz stimulation; this process can be repeated several times with
similar results. These spikes also disappear if the 7 Hz stimulation persists for the next 30 to 60
seconds. Fifteen minutes after clonidine injection (100 µg/kg ip.) the primary spike was not
modified, but the second spike was retarded to about 20 seconds, with an increased latency and
decreased amplitude; the third spike –with very low voltage- completely disappeared. These results
show a particular hipocampal hyper excitability of the seizure-sensitive gerbils and new data about
the mode of action of coniine in epilepsy.

Memory and language

                                       Functional neuroimaging of amnesic disorders

Hans J. Markowitsch
Physiological Psychology, University of Bielefeld, Bielefeld, Germany
Memory disorders constitute the most frequent accompanies of brain damage as well as of
psychiatric disorders such as posttraumatic stress disorder or schizophrenia. In fact the neural
mechanisms leading to problems in encoding, consolidation, storage, and retrieval of memory may
be similar in patients with psychiatric and neurological disorders. Studying a number of patients
with either organic brain damage or with memory disorders due to psychic stress or trauma
conditions were studied in order to elucidate brain circuits and brain mechanisms leading to
memory problems. Extensive neuropsychological testing static and dynamic neuroimaging was
used; in addition, data on the social and personal background were collected. Results indicate that
there are a number of so-called bottleneck structures, embedded in certain neural circuits, which are
crucially involved in either the formation or retrieval of information. Dysfunction of these
bottleneck structures can occur as a consequence of focal brain damage or as a result of changes in
the release of stress of hormones (glucocorticoids). As a consequence, especially recent results from
functional neuroimaging suggest strong similarities between neuronal and psychiatric patients with
respect to the neural networks needed for appropriate memory processing and thereby provides
important implications for the therapy of memory disorders.

                                Brain activity related the emotional valence of familiar faces

Bobes, M.A.a, Perez H., Ja, Lopera, Fb ., Perez, Aa., Acosta, Y.a, Valdes-Sosa, M.a
  Centro de Neurociencias de Cuba , La Habana, Cuba. b Grupo de Neurociencias, Universidad de
Antioquia, Medellín, Colombia
Familiar faces possibly activate two different routes, related to semantic information and affective
valence respectively. Evidence for these two routes (obtained from normal subjects and a
prosopagnosic patient) is presented here. Two oddball paradigms using frequent unfamiliar faces as
standard stimuli were used to obtain P300 in normals. The two paradigms used different infrequent
targets: newly learned faces (devoid of emotional associations) in one case, and faces of close
relatives in the other. Despite similar target-detection in both tasks, they elicited different P300. The
P300 evoked by newly-learned faces was later in time and showed a centro-parietal distribution,
whereas that obtained for faces of relatives exhibited two sub-components, an early one located at
left frontopolar sites, and the same centroparietal P300 as above. These sub-components could be
activated by affective and semantic knowledge respectively. This idea was supported by studies of
covert face recognition in the prosopagnosic patient FE, for whom the P300 elicited by faces of
(unrecognized) close relatives resembled the early frontal sub-component found in normal subjects
for faces of close relatives but not for new-learning faces. An fMRI study with FE and controls
showed larger brain activation for familiar then for unfamiliar faces in ventromedial cortex. This
suggests that the emotional valence of faces activates ventromedial cortex and generates the frontal
P3, which possibly mediates covert recognition in FE.

Massed practice in neurorehabilitation: Intensive short-term intervention in patients w ith chronic aphasia leads to improved
                          language functions and correspondent changes in brain physiology

Marcus Meinzer, Gabriela Barthel, Daniela Djundja, Rockstroh Brigitte
Department of clinical psychology, University of Konstanz, PO-Box 25, 78457 Konstanz,
The aim of the present study was to collect evidence for the effectiveness of 3 different types of
intensive language therapy for patients with chronic aphasia after vascular stroke (> 12 months after
stroke). Evaluation criteria included neurolinguistic testing (Aachen Aphasia Test Battery) as well
as questionnaires on the quality and the amount of everyday communication. Functional brain
imaging was performed using magnetoencephalography (MEG), coregistered with structural
magnetic resonance scans (MRI). 35 patients of three intervention groups [1. Constrained-Induced
Aphasia Therapy (Pulvermüller et. al. 2001), 2. a modified version of CIAT, adding a written
language module and additional training, with relatives, 3. Model-based aphasia therapy] were
investigated and received 30 hours of language therapy over a period of 2 weeks.
Neuropsychological testing and MEG assessment were performed before and after therapy as well
as 6 months after therapy. All intervention groups improved on average. Single case analysis
revealed significant improvements in about 90% of the patients. The amount of day-to-day
communication was enhanced, furthermore relatives rated communicative abilities as improved.
There was no difference between intervention groups concerning improvements in language
performance which emphasises the importance of massed practice irrespective of treatment specific
factors. Perilesional dysfunctional slow wave activity decreased in about 60% of patients that
improved in the AAT, which might be an indicator of re-recruitment of these areas. An increase of
perilesional activity in 9 patients with improved language functions might be explained by further
segregation of dysfunctional components from the speech network with correspondent slow wave

                                          Aphasia: Characterization and Treatment

M. González Murgado and N. Armenteros Herreras
International Center for Neurological Restoration (CIREN), Cuba.
The patients who developed encephalic static lesions are liable to suffer neurolinguistic alterations
like aphasia. This language impairment is determinant for the individual ´s quality of life, from this,
the importance of the rehabilitation. Due to the complexity of this disorder and the manifestation of
its clinical status, it is necessary to perform a solid and efficient approach. The objective of our
investigation was to characterize a sample and to emphasize a strategy for intervention. For this
reason 30 aphasic subjects were studied as sample, which were therapeutically approached and
characterized using Svietkova´s modified method. This method was used as assessment scale before
and after the therapeutic approach. 70% were men, 60% of them, intellectuals who had lost their
work link, 67% were bearers of mixed aphasia predominantly motor impairment; and 100%
willingly accepted the applied therapy. A 40% of them overcame the impressive deficit. In a 100%
of patients with total lack of expressive language, functional verbal emissions appeared.
A regression analysis showed no relationship between the improvement of language skills and
variables like age, professional and education level. Only the type of aphasia was relevant to the
treatment, obtaining mixed aphasia patients significant scores in the final evaluation (p: 0.02).
A significant correlation (-0.37) between time from onset and the impressive and expressive final
evaluation support the importance of starting the aphasia therapy early. Time from onset could be a
prognostic factor for the clinical recovery.

                   Efficacy of the Neurological Restoration Program in the treatment of aphasic patients

Fernandez E., Alvarez E., Bringas M.L., Salazar S.
International Center for Neurological Restoration, Havana, Cuba
Recovery of language is one of the most complex aspects within neuropsychological practice. A
reason why for a long period of time, multiple rehabilitation techniques have been emphasized. The
objective of this work was to evaluate the evolution of verbal communication, performed on a
sample of 14 patients with aphasic syndrome as a result of ischaemic vascular lesions of the left
side. These patients were submitted to the Neurological Restoration Program at CIREN´s
department of Logopedics. Patients were classified as to the type of diagnosed aphasia. The sample
was conformed of 3 anomic, 1 global and 10 motor ones. The analysis of renderings was performed
through the adaptation into Spanish of the Boston‟s Neuropsychological test for the evaluation of
aphasias which was applied before and after treatment. Wilcoxon test was used for the comparison
of treatment effectiveness between two evaluative situations in this group of patients. Results show
that language abilities of chronic aphasic patients can be thus improved in a short period of time by
using rehabilitation methods that have significant differences as to their comprehension capacity.
The level of severity in aphasias was evaluated through Boston‟s severity scale which evidenced
qualitative changes in patients within the same level, but not sufficient enough to pass to another
range. There were no significant differences in the patient‟s communicative capacity in his/her daily

  Interferon alpha2B recombinant improved the cognitive dysfunction in patients w ith relapsing remitting multiple sclerosis
J.A. Cabrera-Gómez, N. Echazábal-Santana, P. Porrero-Martín, C. Valenzuela-Silva, C.A.
Rodríguez, I. Fuentes-Suárez, L. Pérez-Ruiz, A.M. Ramos-Cedeño, J.A. Cabrera-Núñez.
Center for Biological Research, La Habana, Cuba
Introduction. Some experimental, Phase II clinical trials and the preliminary reports of the Cuban
Phase III clinical trial indicate that alphaIFN (IFN) may be useful in relapsing-remitting (RR)
multiple sclerosis (MS). The reports in Cuba showed that 70% of the MS patients have cognitive
dysfunction. Objective. To assess the efficacy of IFN alpha 2b recombinant in the cognitive
dysfunction of RRMS. Patients and methods. 57 RRMS clinical definite (Poser et al) patients from
the randomized, double blind, placebo controlled study of 225 patients with RRMS and brain MRI
confirmed. Patients were randomly assigned to receive intramuscularly IFN alpha2b (HeberonR ®)
10 million IU (high dose), 3 million IU (low dose) or placebo twice week for 2 years. Outcome
results were blinding evaluated considering changes in the following tests: Luria, WAIS, Benton
and PASAT3. Adverse events and side effects were not evaluated to maintain physician blinding.
Results. The initial comparison of the groups did not show any differences among the placebo (n=
20), low dose (n= 18) and high dose (n= 19) considering age (p= 0.234), gender, ethnic group (p=
0.012), years ill (p= 0.787), EDSS (p=0.203) and rate of relapses (p= 0.432). The Luria‟s Test
showed an improved in the low dose group from 2.50±1.34 to 1.39±1.85 (p= 0.029) and in the high
dose group from 3.22±1.89 to 2.17±1.50 (p= 0.006) vs. placebo 2.85±1.66 to 2.90±1.97 (p=0.723).
The results of the Benton‟s test demonstrated that the low dose group had an improved from
5.50±1.10 to 6.22±1.31 (p= 0.047), in the high dose group from 4.87±1.85 to 5.78±1.35 (p= 0.005)
where as in the placebo group worse from 5.15±1.76 to 5.05±2.11 (p= 0.893). The WAIS test
showed the same results, the low dose group increased from 5.17±1.34 to 6.06±1.21 (p= 0.022), the
high dose group from 4.56±1.38 to 5.39±1.29 (p= 0.007) and the placebo group worse from
5.25±1.25 to 5.05±1.57 (p=0.354). Finally, the PASAT3 test increased in the IFNs groups: from
45.72±10.61 to 49.94±11.68 (p= 0.015) in the low dose group, from 42.67±11.04 to 48.72±8.84
(p= 0.03) in the high dose group, but in the placebo group worse from 44.55±10.86 to 41.95±13.74
(p= 0.655). Conclusion. IFN alpha improved the cognitive dysfunction in RRMS patients. The
higher dose is more beneficial.

Neuroimaging studies of reading and speech processing in dyslexia

           Neuropsychological assessment of neurological patients using cognitive event-related potentials

John F. Connolly
Cognitive/Clinical Neuroscience Unit, Department of Psychology, Dalhousie University
Halifax, NS, Canada
Assessment of neuropsychological function in brain injured, non communicative populations
represents a major health care problem. Difficulties with assessment often lead to reduced/refused
rehabilitative interventions because apparent incapacity is assumed to reflect genuine incapacity. It
was within this context that the Innovative Methods of Assessment Program (IMAP) was
developed. IMAP uses cognitive event-related potentials (ERP) in lieu of verbal/motor output as the
patient‟s response to neuropsychological tests. In IMAP, neuropsychological tests are adapted for
computer presentation and simultaneous ERP recording. Its application has been to provide
neuropsychological assessment in non communicative patients who are impossible to assess
traditionally and to monitor progress during rehabilitation. In effect, the ERP measures obtained in
these standardized tests have proven to be a valid and reliable substitute for verbal/motor behaviour.
Even in patients able to be assessed traditionally, IMAP has proven to be a valuable ancillary
measure. Traumatic brain injury (TBI) and stroke data will be presented to demonstrate the
applications and utility of IMAP. These methods have also been used to differentiate good from
poor readers and in revealing the mechanisms by which a phonologically-based reading remediation
program improves the reading skills of problem readers. A particularly interesting feature of these
ERP changes to remediation is that they precede behavioural signs of reading improvement. The
ability of cognitive ERP to monitor non communicative patients and neuroplastic changes to
behavioural interventions demonstrates the value of this neuroimaging modality and its rightful
place in the armamentarium of the cognitive or clinical neuroscientist.

         Differences in between readers w ith developmental dyslexia and normal readers as revealed by MEG

Elisabet Service
Cognitive/Clinical Neuroscience Unit, Department of Psychology, Dalhousie University,
Halifax, Nova Scotia, Canada, and Department of Psychology, University of Helsinki,
Helsinki, Finland
A series of studies used magnetoencephalography (MEG) to explore brain activation in adult
competent readers with a history of reading problems and readers who had not experienced such
problems. A study of single-word reading revealed an early abnormality in the dyslexic readers with
impaired activation in the left inferior temporo-parietal area at 150 ms after stimulus presentation.
Dyslexic readers also lacked activation in the middle and superior parts of the left temporal lobe
between 200 and 400 ms, showing instead activation in left frontal inferior areas (Broca‟s area). A
second study focussed on sentence reading revealed similar responses to anomalous sentence-
ending words in both dyslexic and normal readers, these N400m activations being 100 ms delayed
in the dyslexic group. When sentences were presented aurally, the same pattern was seen, now with
a 50 ms delay in the dyslexic group. Later experiments explored the early posterior abnormality in
brain activation seen in single word processing in dyslexic readers. The area in question was found
to specifically respond to letter strings. When other visual stimuli were used that gave rise to
activation in partly overlapping areas, responses were found to be similar for dyslexic and normal
readers, suggesting that the abnormal lack of response was functionally and not physiologically

                Dynamic visual processes in normal reading: implications for developmental dyslexia?

Piers Cornelissena, Kristen Pammera, Ruth Lavisa and Peter Hansenb
  School of Biology, University of Newcastle, Newcastle, UK, b Centre for Cognitive Neuroscience,
FMRIB Centre, Oxford University, Oxford, UK
Data from two studies relating visual task performance to contextual reading are presented. The first
study investigated the relationship between contextual reading and, a) relative spatial encoding for
symbol arrays, and b) central versus peripheral sensitivity to the frequency doubling illusion. In the
first study, thirty school children were measured on their ability to solve a foveally-presented spatial
encoding task, as well as their sensitivity to the frequency doubling illusion across the retina. Their
performance in the frequency doubling and spatial encoding tasks was uncorrelated, suggesting that
these tasks tap independent visual processes. Peripheral (but not central) sensitivity to frequency
doubling, and spatial encoding, predicted statistically significant, independent proportions of
variance in contextual reading (Neale Analysis of Reading). These effects persisted even when
variance due to age, IQ, phonological skill and short-term memory was statistically accounted for.
The data suggest that successful reading requires not only information about letter identity, but also
at least two additional sources of information, probably related to spatial processing of words. The
first is a central mechanism that may define the relative spatial location of letters within words, and
the second is a peripheral mechanism that we speculate may be related to the attentional processes
involved in coarse-scale localisation within a body of text. Consistent with this speculation, we
found in the second study, that reading accuracy for dyslexic readers was most impaired relative to
chronological- and age-matched controls when contextual material was presented in whole
paragraphs, rather than line-at-a-time or word-at-a-time reading conditions.

             Electrophysiological investigation of implicit and explicit phonological processing in dyslexia

Guillaume Thierry, Tim Fosker and Claire Williams
School of Psychology, University of Wales, Bangor, UK
In a series of experiments we attempted to characterize phonological impairments of dyslexic adults
as indexed by auditory Event-Related Potentials (ERPs). First, we addressed the question of implicit
phoneme awareness by looking at ERP correlates of phoneme expectancy during a lexical decision
task involving alliterated stimuli. The P300 elicited by non-alliterated deviants in controls was not
found in dyslexic adults, suggesting deficient phonological awareness in the latter. Furthermore,
P300 peak amplitudes correlated significantly with individual reading scores obtained in a pre-test.
Second, we used a phoneme deletion task to characterise phonological awareness when attentio n is
devoted to phonological manipulation. The P300 observed in dyslexic adults was not significantly
different from that seen in adult controls. We concluded that well-compensated dyslexic adults
display normal phonological awareness when their attention in focussed on phonological
manipulations. Third, we used a 2x2 paradigm developed by Connolly and Philips (1994) to
compare implicit phonological processing and semantic integration stages. We presented 12
dyslexic adults and 12 matched controls with sentences ending with words of different Cloze
probability regarding their meaning and their first phoneme. Preliminary results indicate that the
N400 ERP modulation induced by semantic mismatch is virtually identical in dyslexic adults and
controls whereas the N200 modulation induced by phonological mismatch (Phonological Mismatch
Negativity) is delayed in dyslexic adults. Overall, these results suggest that well-compensated
dyslexic individuals are impaired both at the level of implicit and explicit phonological processing,
although the time-course of semantic processing appears to be normal.

                  Measuring phonological awareness and remediation in dyslexic children with ERP

John F. Connollya, Randy Lynn Newmana, Marianne Hellmanna,b and Elisabet Service a,c
  Cognitive/Clinical Neuroscience Unit, Department of Psychology, Dalhousie University
Halifax, NS, Canada, b Faculty of Psychology, University of Maastricht, Maastricht, The
Netherlands, cDepartment of Psychology, University of Helsink, Helsinki, Finland
We have discovered an ERP component called the PMN (phonological mismatch negativity) that is
associated with phonological processing of spoken words. Our early studies elicited both a PMN
and a N400 often making it difficult to see the PMN clearly. Two paradigms have been developed
that elicit the PMN in the absence of the N400; one task involves cross modal priming while the
other has adapted a clinical test (the Rosner test) involving phoneme deletion. The new paradigms
not only isolate the PMN but address issues related to the nature of this response – in particular,
whether the response is pre- or postlexical. Data demonstrating the PMN‟s prelexical nature will be
presented. Also, the phoneme deletion task has been used to examine the PMN in poor readers. In
this experimental protocol, participants were asked to select the correct aural representation of
“Clap /klæp/ – without the /k/ sound.” Good readers showed clear PMNs to incorrect choices (e.g.,
/kæp/, /æp/) while problem readers either failed to show PMNs or showed small and significantly
delayed PMNs to the incorrect choices – a result that supports clinical findings that phonological
awareness is deficient in problem readers. Recent experiments have tracked problem readers
through a reading remediation program and found changes in phonological processing mechanisms
as reflected by the PMN and behavioural measures. The PMN appeared during the remediation
process in previous non-responders while problem readers who showed small and delayed PMNs
also responded positively to remediation with increased PMN amplitude and a normalization of its


        Generalized dystonia is sensitive to bilateral palidotomy: preliminary report on Neuropsychological concerns

Dora Ma. Chongo Almerall, Carlos Maragoto
International Center for Neurological Restoration.Havana, Cuba
Dystonia is a severe motor disease, which imposes a substantial burden on individuals and society
as a whole. The majority of previous movement disorders research has been found on clinical and
psychological evolution after conventional or surgical therapies in Parkinson‟s disease. Considering
recent evidences of usefulness of pallidotomy for treatment of dystonia, we have proposed a
Neuropsychological battery (NPB) to be include in the protocol which will evaluate the efficacy and
safety of this surgical approach to dystonia treatment taking into account results from the first 5
patients with generalized dystonia submitted to bilateral pallidotomy. We performed a
Neuropsychological Battery (Short Neuropsychological Test in Spanish. NEUROPSI, Auditory
Verbal Learning Test, and Intelligence test of Progressive Matrix for Adults. Raven) and the
Hamilton Scale for Depression, before and 6, 12 months after bilateral pallidotomy. The reduced
sample permits us only to report a descriptive characterization of effects, if any, of the surgical
procedure on different domains of cognition and emotion. Attention and memory functions showed
a positive outcome at 6 and 12 month‟s post-surgery (60% of patients). Additionally, depressive
symptoms exhibit a marked decrement, (4/5 patients). We suggest that the observed changes were
related to the improvement of patient‟s quality of life as well as the improvement of particular
disease symptoms. It will be important include those tests that permit us subtle distinctions within
different levels of health perceptions, physical / mental health, physical /mental role in social daily
activities in patients.

                               Neuropsychological evaluation of epileptic operated patients

Ma. Eugenia García,Lilia Morales, Ivan García, J. Bender, I. Sarduy, Sonia Salazar
International Center for Neurological Restoration, Havana, Cuba
The description of the patient‟s cognitive status is among the objectives of the neuropsychological
evaluations to the epileptic population resistant to pharmacological treatment, to determine the
patient‟s profile allowing to evaluate the risk or benefits of surgical intervention; and thus to
evaluate the success in post surgical neuropsychological evolution. The objective of the present
paper is to show the neuropsychological evolution related with general cognition and memory
process, in a sample of 8 patients diagnosed with temporal epilepsy, which had been operated, in a
post-operative period ranging from six months to a year. Results. We observed a tendency to an
increase in rendering in general cognition, so much at six months as a year after surgery. In mnesic
tasks, in those cases that present a diminishing in rendering, this cognition is presented in oral
modality when it is ipsilateral to the lesion. In the visual modality the tendency is to increase
rendering independently of the side of surgery. Conclusions. In a general way, the findings coincide
with reports in the literature. The evolutive explorations in these patients allow us to appreciate the
effects of surgery as to the quality of life and therefore, to determine the evolutive profile of
epileptic patients and in this way to offer information in relation to epileptic patients candidates to
surgical treatment.

                                        Verbal Fluency in Parkinson`s Disease(PD)
Casabona E; Bringas ML, Álvarez L, Salazar S.
Neuropsychology Department and Mov.Disod.Clinic.CIREN, Havana, Cuba
Disturbances in cognitive functions in PD has been reported and defined as a frontal ´like´
syndrome, including working memory dysfunction, visuospatial disorientation and a disexecutive
syndrome .One of the main component of the last one is the alteration of verbal fluency. This
impairment appears as a very good marker of frontal dysfunction and is easy to explore. Frontal
dysfunction could promote or amplified motor behavior disturbances. We have conducted a study to
define both verbal and semantic fluency in early and advanced stages of PD and to define the
correlations of the degree of impairment of the verbal fluency with sociodemographics, motor
performance and cognitive state. Study design includes an extense neuropsychological battery and
the UPDRS score¨ Hundred eighteen patients were enrolled and studied between Jan 2001 to Sept
2003 and all of them complete the evaluation. Patients were stratified according age, school level,
stage and severity of the disease. Phonological verbal fluency was more affected than semantic in
all groups and both categories were significant altered when compared with health controls. There is
a high correlation (p 0.005) between age, evolution time, educational level and severity and verbal
fluency. We observe a high correlation with MMSE and the Frontal Assessment Battery scores. It is
very significant that verbal fluency is affected in the very early stages of the disease. Our
preliminary results have some implications in the explanation of the motor behavioral d speech
disturbances and in the design of rehab programs in PD.

                  Speech training and verbal fluency in patients with neurodegenerativ e diseases

A. Aguiar Rodríguez, S. Salazar, E. Casabona
International Center for Neurological Restoration, Havana, Cuba
The phonologic and semantic verbal fluency tests are used to evaluate the semantic storage
capacity, the information retrieval capacity and the indemnity of the executing functions. Such
skills deteriorate with age according to studies carried out by others. Objective: To evaluate the
impact of the therapy to improve the verbal fluency in patient with neurodegenerative diseases.
Sample: 29 patients, (age between 50 and 60 years) 5 of them with cognitive impairments, 4 of
them with Supranuclear palsy (PSP) and 20 with Parkinson disease. We applied the Mattis Scale
(DRS), semantic and phonologic verbal fluency subtests from the FAB (frontal assessment battery)
as the starting and ending control test. We applied a logopedic strategy to stimulate the verbal
fluency in a cycle of 28 days of therapy. In order to analyze the verbal fluency behavior according
to the different neurological diseases, we used T-Test for dependent samples and Wilcoxon
Matched Pair Test. Results: In the general analysis, there is more deterioration for the phonological
fluency than the semantics. The patients with Parkinson‟s disease presented a better evolution than
the other patients, in the semantic (p:0. 000089) and the phonological fluency (p:0. 000356).
Patients with cognitive impairments showed an improvement (p:0. 043) only in the semantic
fluency test after the treatment. PSP patients didn‟t reach statistical significance comparing their
performance before and after treatment. We conclude that it‟s possible to improve verbal fluency in
short periods of time, which favors the communication capabilities and quality of life of patients
with neurodegenerative diseases.

                                Visuo-spatial memory and its relationship w ith age

Maria L. Bringas, Enrique Casabona, Sonia Salazar
International Center for Neurological Restoration, Havana, Cuba
We tried to determine the relation of visuo-spatial memory to age by means of a computerized task.
Fifteen pairs of figures are distributed randomly on the screen and are initially all face down. The
subject can flip up only two figures at a time and must try to identify and remember where each pair
is located. When a pair is flipped consecutively it disappears, the test ending when no figures are
left. Dependent measures were TIME needed to complete the test as well as the NUMBER OF
FLIPS used. Independent variables were AGE, search STYLE (random or systematic) and the level
of training (on a scale of 1 to 5). The sample studied comprised 33 normal subjects with an
educational level higher than 12th grade, with an age range from 18 to 81. The NUMBER OF
FLIPS was modeled by a generalized linear model with a Poisson link function which showed that
AGE was not a significant covariate, while the amount of TRAINING, search STYLE and their
interactions were. Log transformed response TIME was modeled by a linear model in which AGE,
TRAINING and STYLE were all significant. For both outcome measures the systematic search
STYLE, was most efficient. Thus elderly people take more time because they processed information
more slowly but they can be just as efficient at this task as younger subjects using an appropriate
search strategy. Consequentially this aspect of visuo-spatial memory might be trained,
independently of the age of the subject.

Technologies for Restorative Neurology and Neurosurgery

                                 Multi-modality approaches to brain imaging

Frederic H. Fahey
Children's Hospital Boston, Boston, Massachusetts, USA
A variety of approaches to brain imaging have been developed. Some are generally anatomic such
as computed tomography (CT) and magnetic resonance imaging (MRI). Others provide images of
physiology and function, such as single photon emission computed tomography (SPECT), positron
emission tomography (PET) and functional magnetic resonance imaging (fMRI). Typically, these
functional modalities do not provide the same anatomical detail as CT and MRI. Thus, approaches
that combine the functional capability of SPECT, PET and fMRI with the anatomical information of
CT and MRI are of great utility in brain imaging. Both hardware and software approaches have
been derived to provide such multi-modality presentations. Hybrid PET-CT and SPECT-CT
scanners are commercially available in the USA that provide good correlation between modalities.
For clinics without such technology, software approaches are more appropriate. These involve
three steps: converting both image sets to a common computer platform, registering one of the
images sets to the other and displaying the results. The registration can be performed either
manually or automatically. In turn, there are three approaches used for automatic image registration:
fiducial or point-based, surface-based or voxel-based methods. Once the image sets have been
registered to each other, an appropriate interface must be used for the display and analysis of these
multi-modality image sets. In this presentation, we will review both hardware and software
approaches to image fusion as well as the optimal ways to display and analyze these data sets.

                        EEG/MEG Tomography and beyond: Multimodality Image Fusion

Pedro A. Valdes-Sosa
Cuban Neuroscience Center, Havana, Cuba
During the past decade our group has contributed to the establishment of an EEG/MEG
tomography. The inherent non-uniqueness of the electrophysiological Inverse Problem has been
overcome by the use of anatomical information obtained by the structural MRI, as well as by
imposing variable smoothness constraints (VARETA). The resulting neuroimaging modality has a
spatial resolution in the order of several mm. and an unlimited temporal resolution. It does suffer,
however, from a depth bias that emphasizes sources nearer the sensors. This bias can be overcome
to a certain degree by the use of Statistical Parametric Mapping techniques for electrophysiological
tomography, also developed at the Cuban Neuroscience Center. In particular a frequency domain
application of these methods has lead to the development of Tomographic qEEG (qEEG). Several
examples show the potential clinical usefulness of this method in the evaluation of stroke patients
and in looking for early signs of Alzheimer‟s disease. It is documented in both examples that
significant increases of specificity and sensitivity of Tomographic over Topographic analysis can be
obtained. Further improvements in EEG/MEG tomography will come from two directions:
inclusion of anatomical connectivity information obtained from Diffusion Tensor MRI and of
functional information obtained by fMRI. The direct and inverse problems for these new sources of
information are discussed. Image Fusion is achievable by Bayesian statistical methods that are
outlined. A particularly favorable situation occurs when joint EEG/fMRI recordings are available.
In this case a dynamic image fusion method is possible. The applications of this method are shown
for an analysis of the alpha rhythm. It is discussed that multimodality image fusion will provide a
new generation of Neuroimages with higher temporal and spatial resolution than any current

                           Control of EMG signals for computer-based communication systems

Eric Fimbela, Martin Arguinb
  Institut universitaire de gériatrie de Montréal AND Laboratoire d'environnements de synthèse et
interfaces avancées, École de technologie supérieure de Montréal; b Institut universitaire de
gériatrie de Montréal AND Groupe de recherche en neuropsychologie et cognition, Département de
psychologie, Université de Montréal
Computer-based communication systems greatly improve the quality of life of persons with severe
motor impairments, like locked-in or quadriplegic patients. In EMG-based interfaces, the user
controls the computer by means of myoelectric signals. This non-invasive technique is applicable in
any patient with some preserved motor function, e.g., eye movements. However, the efficiency
(throughput) of the communication system directly depends on the controllability of the EMG
signals. We studied the controllability of EMG signals in face and hand muscles with 40 young
healthy volunteers. A visual feedback indicated the amplitude of the EMG signal in real time. The
subject had to reach a target (i.e., an interval of amplitude) in either of two modalities: impulsion or
sustained, i.e., the subject had to stabilize the signal within the target interval of amplitudes for a
duration of 1 s. Two levels of precision were used by dividing the range of amplitudes in 4 intervals
(low precision) or 8 intervals (high precision). No significant difference of speed or accuracy was
found between facial and distal muscles. However, accuracy was significantly lower for
intermediate amplitudes relative to the smallest or highest amplitudes. Finally, a clear tradeoff
between speed and accuracy was observed across response modalities: the sustained modality was
associated with slow but highly accurate responses whereas the impulsion modality allowed faster
but less precise responses. The average speed and error rate allow calculating a theoretical upper
bound for text entry with EMG interfaces of 2.5 bit/s, i.e., above 15 words/minute.

 Automatic system for three-dimensional anatomic-physiological correlation during stereotactic and functional neurosurgery

Juan Teijeiro Amador, Raúl J. Macías González, Juan M. Morales Oliva, Gerardo López Flores,
Lázaro M. Alvarez González, Carlos Maragoto Rizo, Eduardo Alvarez González, Iván García
International Center for Neurological Restoration.Havana, Cuba.
This paper describes the automatic 3D-graphic possibilities that are offered by a PC-based software
to facilitate the anatomic-physiological targeting during stereotactic and functional neurosurgery,
using deep brain recording. This software has been developed to substitute complex electronic
equipment with a PC for deep brain electrical activity recording, display and processing. It also
allows greater possibilities for on-line graphic analysis, automatic management of the recorded
information and flexibility to implement different forms of signal analysis. This software has been
made using a combination of two programming languages. A low level one (Assembler) was used
for the on-line working modules. For the rest of the system a high level language (Pascal) and its
compiler were used. The system uses an analog-digital converter card and allows to record, show,
process and store up to two simultaneous signals with 12 bits accuracy. The software can also
automatically show a 2D- and/or 3D-representation of the electrode track with the superimposed
electrophysiological findings, and the corresponding sagittal, coronal and axial view of a brain
anatomic atlas, after its automatic scaling for each patient. It allows graphic analysis of the recorded
information and its correlation with the anatomy, even during the surgical procedure. This software
has already been successfully used in Spain, Chile and Cuba in more than 400 neurosurgeries,
allowing to increase the targeting accuracy and safety.

                  A method for accurate determination of the first target in functional neurosurgery

Maylen Carballoa , Rafael Rodrígueza, Gerardo Lópezb .
  Brain Images Processing Group, bDepartment of Neurosurgery. International Center for
Neurological Restoration (CIREN), Havana, Cuba
Accuracy in target determination is one of the fundamental requirements of any surgical planning
systems. We developed a system for intraoperative planning of frame-based stereotactic
neurosurgery that integrates, in one complete module, all of the basic facilities that are present in
other advanced programs. All of the techniques used for our system were optimized in order to
increase the performance and precision of the system, especially facilities involved in functional
neurosurgery. Based on the vector approach used for calculation of stereotactic coordinates we
developed an algorithm for correction of first target in functional neurosurgery. A vector method
can be used to determine a frame-independent coordinated system from the coordinates of anterior
commissure (AC), the posterior commissure (PC) and another point located on the
interhemispherical line, considering the intercommissural middle point as origin. For any point in
the images we have AC/PC-based coordinates independently of its frame-based coordinates.
Likewise this correction can be used for calculations of target‟s trajectory. Due to its generality this
corrective procedure can be used with any stereotactic frame included in our planning system and
overcomes geometrical errors that are introduced when the intercommisural line and
interhemisphere plane are not parallel and orthogonal to transaxial images respectively.

Nuclear Neuroscience Symposium

                                    Mild cognitive impair ment and brain SPECT

Carlos A. Sánchez Catasús
Department of Nuclear Medicine, CIREN, Havana, Cuba.
There is an imperative need to develop sensitive biomarkers as adjuncts to current clinical and
neuropsychological tests to improve detection of early brain changes suggestive of Alzheimer's
disease (AD), particularly as new agents to delay the onset of dementia become available. The
subtle onset of AD suggests that most of the patients pass through a prodromal phase of mild
cognitive impairment (MCI) before dementia is diagnosed. Previous neuroimaging studies have
revealed that structural and functional changes are already present in this stage of the disease. Based
on basal SPECT data, longitudinal studies have shown acceptable percent of correctly identified
MCI subjects who progressed to AD. An ongoing research project of our group is presented in this
conference. This project is intended to address if the acetazolamide test by SPECT can improve
preclinical prediction of AD. The hypothesis is based on: 1) previous data strongly support that
sporadic AD is first provoked by premorbid vascular-related events; and 2) other reports show
preserved vascular reserve, but not normal, in patients with probable AD. The first results of the
project are presented.

                        Tow ard clinical application of neuroactivation probes with SPECT

Ingeborg Goethals
Nuclear Medicine Division, University Hospital Gent, Gent, Belgium
The review presents neuroimaging studies which explored the functional anatomy of a variety of
cognitive processes represented by the prefrontal cortex (PFC). Overall, these studies demonstrated
that standard prefrontal neuroactivation tasks recruit a widely distributed network within the brain
of which the PFC consistently forms a part. As such, these results are in keeping with the notion
that executive functions within the PFC rely not only on anterior (mainly prefrontal) brain areas, but
also depend on posterior (mainly parietal) brain regions. Moreover, intervention of similar brain
regions in a large number of different executive tasks suggests that higher-level cognitive functions
may best be understood in terms of an interactive network of specialized anterior as well as
posterior brain regions.

                                       Radionuclides in nuclear neurology

José Morín Zorrilla
Isotope Center, Havana, Cuba
This conference is a review of the sources of the most commonly used radionuclides in Nuclear
Neurology, the state and evolution of the market in this field and the possibilities of the local supply
of these products. It is also considered the installation and operation of a cyclotron as the most
promising and feasible source of radionuclides in this area. A comparison of the existing imaging
technologies is given in the framework of the available radionuclides, including a brief summary of
the most commonly used radiopharmaceuticals for diagnostic and therapeutics in this particular
field. The presentation shows the view of the Cuban national producer of radiopharmaceuticals and
its necessary interaction with the final user.

                                        Analysis of brain SPECT studies

Filip Jacobs
Nuclear Medicine Division, University Hospital Ghent, Belgium
Nowadays, with the most powerful computers and software packages available, the analysis of
brain images is not the most difficult part of a brain SPECT study. The most difficult questions are
encountered before the actual analysis, namely while choosing the study design, the tracer, the
acquisition protocol, the collimators, the reconstruction algorithms, the physical processes to correct
for, the existence of confounding factors, the inclusion criteria, etc. Many problems during the
analysis of brain images may be avoided by carefully designed study. Therefore, we first give an
overview of the most important issues to be solved before the data acquisit ion. Once the data have
been acquired and the images are reconstructed, one can start analysing the images. In order to
focus our attention, only two important and well known software packages are discussed, being
"Statistical Parametric Mapping" (SPM, Wellcome Department of Imaging Neuroscience, UCL,
London, UK) and "Brain Registration and Analysis of SPECT Studies" (BRASS, Nuclear
Diagnostics Ltd, Northfleet, UK). The former is designed to address most research questions
concerning brain studies, while the latter has been optimised for use in a routine clinical setting.
Both the idea behind each package and their use will be covered.


                 Topographic evaluation of bilateral subthalamothomy using an MRI-based analysis

Rafael Rodriguez Rojasa, Maylen Carballoa, Rolando Palmerob , Gerardo Lopezc , Lazaro Alvarezd ,
Raul Macíasd
  Brain Images Processing Group, b Static Lesions Clinic, c Department of Neurosurgery, dMotor
Disorders Clinic, CIREN, Cuba
The result of stereotactic ablative surgery is critically dependent of the exactitude of the lesion
localization. The aim of this work was to develop a methodology to obtain a precise anatomic
localization of stereotactic lesions and perform an accurate audit of the precision of our stereotactic
target placement. METHODS: Postoperative MRI studies of 15 parkinsonian patients submitted to
bilateral subthalamotomy were examined. Each MRI study was transformed into Talairach space
using an automatic algorithm to determine non-linear transformation between the individual
volumes and a model brain. Individual and average X, Y and Z coordinates of center of gravity
(COG) of the lesions were determined for each hemisphere, and used as input into the software
Talairach Daemon (TD), which shows the anatomical region labels corresponding to the calculated
x-y-z coordinates. RESULTS: According to TD, average coordinates in Tailarach space correspond
with subthalamic nucleus. Differences in lesion location between hemispheres did not achieve
statistical significance. CONCLUSIONS: This study has proved that surgical methodology applied
at CIREN is accurate enough for determining optimal lesion localization. This type of analysis may
also be used to examine the results of other types of stereotactic procedures in the subcortical
nuclei. As well, careful anatomic analysis can be useful in demonstrating the characteristics of
lesion resulting in known complications of this surgery.

                               Subthalamic nucleus targeting and spatial variability

G. López-Flores, R. Fernández-Melo, L. Álvarez-González, J. M. Morales, R. Macías González, J.
Tejeiro-Amador, E. Palmero, C. Maragoto Rizo, E. Álvarez-González, J. Guridi J, J. Obeso.
International Center for Neurological Restoration, Habana, Cuba
The goal of this study was to assess the effectiveness of anatomic localization (EAL) of the
subthalamic nucleus (STN) and to analyze the contralateral symmetry (SCN). The authors
conducted a retrospective analysis of 11 consecutive patients submitted to bilateral subthalamotomy
with ablative lesioning. To assess EAL - the percentage so much of first trajectory (p1) as to the
total of trajectories (pt) that hit the target - the rest of subthalamic nucleus average distance (d) was
calculated. The anatomic localization error (e) is determined as a difference between first trajectory
coordinates with those of medial determined nucleus point, through electrophysiological data as to
the statistical significance of this error. SCN is analyzed by contrasting equality hypothesis at the
nucleus maximum height along both sides of a trajectory, average electrophysiological position
center and spatial distribution of all intranuclear recordings found in each hemisphere in all patients.
The pi, pt and d obtained values were 86.36%, 86.13% and 1.41±1.01 mm respectively. The e value
was greater in anteroposterior direction of 1.11±0.83mm without statistical significance. The
average number of recorded trajectories for the first procedure was 6.45 and 6 for the second. The
asymmetry of contralateral nucleus was not significant. An indirect method with CT brain images
and a new electrophysiological mapping method with a multiunit recording for first and second
nucleus is safe enough and it yields a high effectiveness in anatomic and functional nucleus
localization. The nuclei of a same patient are symmetrical. There is little space variability among
patients non-related to the differences in the intercommisural distance.

                   Dynamics of digital EEG pattern in operated patients with Moyamoya disease

Pushkina E.A., Svadovsky, A.I.
Neuroaesculap Clinic, Moscow, Russia
Purpose of study. Our goals were investigate a different parameters in 12 patients with Moyamoya
disease. The treatment of Moyamoya disease (nonatherosclerotic obstructive vascular disease)
remains difficult problem in neurology and neurosurgery. Material and methods. The clinical
picture demonstrated transient ischemic attacks (TIA; 6 cases), transient optical complications (2
cases) and epileptiform paroxysms (4 patients). All patients (male 7, female – 5) were underwent
surgical treatment. Mean age 34 years. We performed our method of surgical revascularisation of
brain – arterioencephaloanastomosis (unilateral 8 cases and 4 bilateral). All operations were
performed after long unsuccessful medical treatment for reduce cerebral ischemia. Diagnostic
methods till and after surgery included transcranial Doppler (TCD), magnetic resonance
angiography (MRA), and digital EEG examinations with standard functional tests (fotostimulation,
hyperventilation). We performed EEG at the time 3-6-12 months after surgical tretment. Results. In
preoperative period EEG registrated seizure pattern, slow activity, three Hz spike-slow waves and
photo-paroxismal response. After surgery all patients showed in EEG alpha rhythm and alpha
variant rhytms; paroxysmal activity absent. Therefore, in follow-up period the results of surgery
were beneficial. Conclusion. We support surgical treatment lead to reduce cerebral
hypoxia/ischemia and neurological deficit. It can explain better of brain. Dinamic EEG data might
indicate that arterioencaphaloanastomosis is effective treatment of Moyamoya disease.

                      Diffusion Tensor in Magnetic Resonance Imaging and its applications

Pedro Antonio Valdés Hernández.
Neurophysics Department, Cuban Neuroscience Center, Havana, Cuba
It is presented a review of methods based on Diffusion Tensor Magnetic Resonance Imaging for the
estimation of neural fiber mean directions in each voxel of the brain. Two indexes calculated from
diffusion tensor are mentioned briefly which help in tissue segmentation and disease detection.
Also, it is made a review of the algorithms used in calculating neural fibers and probabilistic paths
taking into account anisotropical tensor geometrical shape. Those algorithms are based on the
methods mentioned before. Finally, a brief discussion of the potential application of such fiber
pathways in the inference of anatomic connectivity measures between different zones in the brain is

                            Transcraneal doppler sonography in brain death diagnosis

Anselmo A. Abdo, Roberto Castellanos, Francisco Gómez, Javier Figueredo, Aldo Alvarez, Jorge
Centro de Investigaciones Medico Quirúrgicas, Ciudad Habana, Cuba
The Transcraneal Doppler (TCD) is a useful technique to confirm cerebral blood flow alterations.
Objective: To evaluated the TCD usefulness in the brain death diagnosis. Method: A prospective
study was made in 21 neurocritical patients admitted in the Intensive Care Unit of the Centro de
Investigaciones Medico Quirurgicas, in the year 2002. TCD pattern were collected and if clinical
brain death was present. Sensibility, specificity, and Kappa index was calculated. Results: Clinical
brain death was present in 10 cases. The TCD patterns most frequently in these cases were
oscillating blood flow (reverberating flow) in 5 cases, and short systolic spikes in 4 cases. The
relationship between this TCD pattern and clinical brain death were 100% in sensibility and
specificity. Conclusions: The TCD method is useful and reliable to determine the absent cerebral
blood flow.

              Model for calc ulation of temperature distribution in resistiv e magnetic resonance scanner

Aylin Martínez Bermello
                 Centro de Biofísica Médica, Universidad de Oriente, Santiago de Cuba, Cuba
The magnetic resonance (MR) scanners are medical equipment for imaging diagnostic of central
nervous system illnesses mainly: cerebral infarcts, cortical and cerebral atrophies, skull
traumatisms, some degenerative illnesses. These equipment works due to the action of magnetic
field on the tissues. When a resistive magnet is used for generation of magnetic field the intensity,
homogeneity and temporary stability of the magnetic field define the clinical images quality. The
thermal behavior of winding and therefore, the characteristics of the magnet and of their cooling
system exercises decisive influence on these magnetic field parameters. In this paper a physical-
mathematical model for the thermal process description of resistive MR scanners is presented. The
model was applied to Cuban equipment, and the analysis of the temperature distribution in winding
facilitated a valuation of constructive parameters and design of the cooling system heat exchangers.
The model was developed according to the laws of the thermodynamic and the heat transfer. Their
effectiveness was proven for a level of significance of 0.05. The temperature maps of the magnet
were obtained. The maximum temperatures to nominal electric current are around the 146°C. These
temperatures are not dangerous for the materials of winding. The heat transfer in radial sense is
significantly bigger that in axial one. This aspect should consider as design approach for future
equipments. The winding is compact and the heat exchangers were assembling appropriately.

                         Age-related perfusion changes by brain SPECT in healthy subjects

M. Cisneros Cué a, C. Sánchez Catasúsb , N. Pérez Lache a, R. Rodríguezb , A. F. Aguila a
  Department of Neurology, ISMM; Havana, Cuba. bDepartment of Nuclear Medicine, CIREN,
Havana, Cuba.
This study characterizes the effects of aging on brain perfusion using HMPAO – SPECT in healthy
subjects. The study population consisted of 10 women and 19 men with age range of 20 - 79 y.
Their past medical histories, physical examinations, and laboratory screening tests were normal.
The sample was divided in three age groups (GI: 20 – 39 y; GII: 40 – 59 y; GIII 60 – 79 y).
HMPAO – SPECT scans of the brain were performed with a standardized acquisition and
processing protocol on a single -head camera equipped with high-resolution collimator. A
Butterworth filter and a correction for uniform attenuation were applied after back projection
reconstruction. Brain perfusion evaluation was performed both visually and by a relative
quantification method using the cerebellum as the reference region. To that end, cortical bilateral
and regular regions of interest (ROIs) were drawn on adjacent SPECT slices. Group comparison
were performed using ANOVA. Brain perfusion decreased significantly with age in frontal and
parietal regions (groups GII and GIII less than GI, p < 0.01). These results are in agreement with
previous reports. As a conclusion, aging significantly affects brain perfusion in healthy subjects. It
decreases in parietal and frontal region and it seem to occur after thirties. The brain perfusion
appears to remain relatively stable throughout middle age.
          Contribution of brain SPECT to the presurgical evaluation of temporal lobe epilepsy: CIREN experience

Morales Chacón L, Sánchez Catasús C , Aguila A, Bender J, García I.
Epilepsy Surgery Program, CIREN, Havana, Cuba
The aim of this study is to show the contribution of interictal and ictal brain SPECT to localize the
epileptogenic zone in patients with Temporal Lobe epilepsy (TLE) submitted to surgery at CIREN.
As part of presurgical evaluation, interictal and ictal SPECT scans were performed to assess
cerebral perfusion in 18 patients with pharmacoresistant TLE. A double –head gamma camera was
used (SMV DST Xli, SMV International) connected to a workstation IBM RISC System 6000,
provided with a processing system Vision 5.0 (SMV America, Inc). After visual analysis,
cerebellar perfusion ratios were calculated on irregular regions of interest (ROI), drawn on lateral
and mesial lobe and basal ganglia. Also, asymmetry indexes were calculated between homologous
ROIs (including the cerebellum). Visual analysis detected focal hypoperfusion involving the whole
temporal lobe in 100% of the patients. The hypoperfusion was extended into the frontal lobe in 50%
of them. Quantitative analysis using the ROIs method showed that the changes in lateral temporal
perfusion were the most suitable lateralizing indicator of the seizure. It was ipsilateral to the
epileptogenic zone defined by surgery in 87.4 % (p< 0.0001). Interhemispheric asymmetry indexes
of 13 % and 28 % were found in left and right TLE, respectively. Ictal SPECT showed mesiolateral
temporal lobe hyperperfusion ipsilateral to the epileptogenic zone in all patients and also
demonstrated contralateral cerebellar activation in 25 % of them . In addition ipsilateral basal
ganglia activation was observed in 75 % .Interictal SPECT defined an extensive functional deficit
zone in TLE patients. Ictal and interictal SPECT changes are a reliable lateralizing indicator of
epileptogenic zone in TLE.

 Epider mal Growth Factor receptor hr-3 monoclonal antibodies radiolabelled w ith rhenium-188 in the adjuvant treatment of
                                               high grade astrocytomas

Gerardo López, Ramses Fernández Melo, Angel Casaco, Leonel Díaz, Juan Batista, Alejandro
Pereira, Rene Leiva, Yamilé Peña, Marco Coca, Olga Torres, Tania Crombet, Mayelín Martines,
Leslie Ramos, Zaida Amador.
International Center for Neurological Restoration, Habana, Cuba
Intralesional radioimnmunetherapy (RAIT) may improve the management of malignant gliomas
whose prognosis is, at present, very poor. Current treatment modalities cannot prevent tumor
recurrence. This study was performed to evaluate toxicity, dosimetry, biodistribution and clinical
efficacy of the h-R3 monoclonal antibodies labeled with Re-188 after intralesional RAIT in cases of
malignant gliomas. Following surgical operations, radiotherapy and chemotherapy, 4 patients with
recurrent malignant gliomas, 2 with anaplastic astrocytomas and 2 with glioblastoma underwent
RAIT with h-R3 antibodies raised against epidermal growth factor receptor (EGFr) labeled with
rhenium-188 in different escalating doses. The dosimetry and biodistribution had been performed
using Single Photon Emission Computerized Tomography (SPECT), whole body and quantification
studies. In these patients the follow-up study period ranged from 6 to 12 months. No significant life-
threatening toxicities were observed. Acute side effects following treatment were seizures and
worsening of pre-existing neurological symptoms. Late side effects were radio necrosis in 1 case.
Objective response consisted in one patient with tumor stabilizations during 6 months and two with
complete remissions. RAIT is safe and an effective procedure, mainly in cases with peripheral and
reduced tumor border. Further investigations should focus on optimizing the dose delivery to the
surrounding tissue and should be set up to confirm these findings.

                        Brain perfusion SPECT in schizophrenic patients with negativ e symptoms
N. Pérez Gonzáleza, C.Sánchez Catasúsb , J.Pérez Milána,R. Rodríguezb , A. Aguila Ruizb
  Hospital Psiquiátrico de La Habana; b Department of Nuclear Medicine, CIREN, Havana, Cuba.

One of the polemic aspects in schizophrenia deals with the Cerebral Blood Flow (CBF) in patients
with negative symptoms. The most frequent finding is frontal hypoperfusion. In the present study
we intended to evaluate CBF by SPECT in a relatively homogenous sample of schizophrenic
patients with negative symptoms and compare them to a control group of healthy subjects, using a
semiquantitative methodology for CBF quantification. Ten male healthy volunteers and 15 male
patients with a clinical diagnosis of residual schizophrenia (295.60 points according to the DSM-IV
criteria) and without inability for communication were studied. Their ages ranged between 32 and
50 years (mean 44.6 years), and the evolution time, between 10 and 24 years (mean 16 years). All
patients were being treated with Haloperidol and Fluofenazine. The positive and negative symptom
scale (PANSS) was used for the evaluation of these symptoms. In each patient or healthy subject an
evaluation of the CBF by 99mTc-HMPAO SPECT was performed both visually and by a relative
quantification method using the cerebellum as the reference region. Cortical bilateral and regular
regions of interest (ROIs) were drawn on SPECT slices. An index of asymmetry was also calculated
(IA) for every pair of homologous ROIs. The results showed significant differences (less CBF in
the group of patients) bilaterally in the frontal and temporal regions (p< 0.05). In the group of
patients, the asymmetries found were not different from those observed in the normal group. As a
conclusion, a symmetrical bilateral decrease in the frontal and temporal lobes seems to characterize
schizophrenic patients with negative symptoms.

    Dose assessment and individual monitoring of workers and public during the first phase of the clinical study for the
                                   radioimmunotherapy of cerebral tumors in Cuba

Amador Balbona, Z.H., Pardo Ayra, F.E., Torres Berdeguez, M.B.
Isotope Center,Havana, Cuba.
Taking into account the international experience and the approval of the regulatory authorities, last
year it began in the Republic of Cuba the first phase of the clinical research of the humanized
monoclonal antibody h-R3 labeled with 188Re, for radio-immune therapy (RIT) of cerebral tumors
This monoclonal antibody was obtained in the country and it is required to evaluate its toxicity,
biodistribution and interna l radiation dosimetry. Five groups of three patients of each one with an
administered activity from 0.37 GBq to 1.1 GBq are considered. The aim of this work is to assess
workers and public doses for this research and to compare projected doses with the first results
related to the individual monitoring. The contribution to the total effective dose and equivalent dose
in extremities are calculated with the code Micro shield Version 4.0 by each activity level, operation
and total quantity of patients, considering the results of the radioactive decay calculation for 188Re.
It is demonstrated that individual doses are acceptable and lower than world average effective
annual dose of natural radiation background (2.4 mSv), because for the operations of more risk are
considered the use of individual protection means. Nevertheless, it is identified that nurses are the
most exposed. The projected maximum equivalent dose to hands is 3 mSv and it belongs to the
neurosurgeon. Five workers and public (four individuals) are monitoring with direct reading
dosimeters DOSICARD and TLD for extremities. The conservative assumptions in the assessment
and the compliance with established safety procedures determine that the registered doses are lower
than those were projected.

 Relative indexes of brain perfusion by 99 mtc HMPAO SPECT utilizing a mean value of the visual cortex to the cerebellum
                                             ratio derived from normal subjects
C. Sánchez Catasús, R. Rodríguez, M. Cisnero, R. Palmero, O. Díaz, A. Aguila.
Department of Nuclear Medicine, CIREN, Havana, Cuba.
Previous results show the cerebellum (CER) is the best reference to calculate relative indexes of
brain perfusion (IP) by HMPAO SPECT. It cannot be used on patients with CER perfusion deficit.
In such cases the visual cortex (VC) or others reference values are recommended. The use of
different references makes the comparison of SPECT scans almost impossible. We developed a
method for calculating IP using a reference value, which acts as a model of "normal CER counts".
This value was designated as CER* and it was calculated using the mean value of the VC/CER ratio
derived from a normal database. We tested statistically the VC/CER ratio on a group of 60 scans
from individuals without involvement of VC and CER. To demonstrate that IPCER* » IPCER, we
calculated the mean value of the absolute differences <|IPCER - IPCER*|> on two groups of scans:
10 normal subjects (GI) and 40 patients without involvement of VC and CER (GII). Using an
indirect procedure the method was tested on a third group of scans of 30 patients with CER
perfusion deficit (GIII). The VC/CER ratio was constant at a 95% confidence level; <|IPCER -
IPCER* |> for GI and GII was less than the replicability of the HMPAO SPECT studies; and it was
proved in GIII that CER* is comparable to CER as reference value with the only condition being
that perfusion in subject‟s VC must be unaffected. The method allows generalizing CER as a
reference value, inapplicable only in those cases with concurrent hypoperfusion on VC and CER.

                              Absolute quantific ation of cerebral blood flow by SPECT

Rogelio Díaz Moreno, Carlos A. Sánchez Catasús, Angel F. Aguila Ruiz.
Department of Nuclear Medicine. CIREN, Havana, Cuba
Quantification of cerebral blood flow (CBF) is useful in pat ients with neurological diseases because
of the diagnostic and therapeutic implications of such quantification. CBF quantification by SPECT
can be achieved in relative or absolute units. Relative quantification is more used due to it is less
time consuming and because most of the absolute quantification methods require a more expensive
instrumentation or blood sampling of the patient, which makes absolute quantification an invasive
procedure. In 1992, a new method was developed by the Japanese investigator H. Matsuda without
those previous handicaps. This method substitutes the blood sampling by a graphical procedure,
which is applied to a first-pass dynamic study. Mean CBF (mCBF) can be calculated by this way
for both brain hemispheres. Regional CBF values (rCBF) can then be calculated using the Lassen
correction for the distribution of the radiotracer estimated with a standard SPECT study. We
implemented Matsuda‟s method in ten healthy individuals using 99mTc - ECD. Values of mCBF
were between 44 ml/min/100g and 50 ml/min/100g for all individuals. Values of rCBF in gray
matter were around 70 ml/min/100g. Values of rCBF in white matter were around 20 ml/min/100g.
These values are similar to those reported by Matsuda. We concluded that Matsuda‟s method is
simple, not invasive and can be implemented with the technology of our country. This method can
become a valuable tool to enhance clinical diagnosis and research in other important neurological

                    A way to reduce radius of rotation in brain SPECT w ith a single-head system

C. A. Sánchez Catasúsa, M. Rodríguez Castillob , R. Rodrígueza , N. Rodríguez a.
  Department of Nuclear Medicine, CIREN, bDepartment of Nuclear Medicine, INOR, Havana,
To optimize spatial resolution in SPECT it is essential to minimize the radius of rotation (rrot). In
brain studies, different solutions have been employed in order to avoid the shoulder interference
when rrot is minimized: rectangular fields of view, modifications to the shielding around circular
detectors and fan or cone beam collimators. However, few single-head systems can utilize these
developments, particularly old cameras. A non-standard image acquisition method to reduce rrot in
brain SPECT with a single-head gamma camera is presented. The method applies a defined
transformation to the original acquired images, keeping all the brain inside the field of view without

possible to reduce rrot to 16 cm and to obtain a transaxial spatial resolution of 15.98 mm, 3.5 mm
less than standard method used in our laboratory. This procedure was implemented for a gamma
camera Siemens Gammasonics ZLC 3700 and has been validated through single-slice brain
phantom studies. The method has the advantage of not introducing any complex or costly hardware

                                          Quality assurance in brain SPECT

Angel F. Aguila Ruiz, Carlos A. Sánchez Catasús, Rogelio M. Díaz Moreno
Department of Nuclear Medicine, CIREN, Havana, Cuba
SPECT is a highly sophisticated technology, which needs a strict quality assurance, if one wishes
the data generated by this procedure to be reliable. The objective of this paper was to evaluate
different functioning parameters of the gamma camera at our department, in order to establish
which parameters most affect the quality of brain SPECT images and to find out with which
periodicity they are to be evaluated. This study was performed for a year by making periodic
evaluations. A double –head gamma camera was used (SMV DST Xli, SMV International)
connected to a workstation IBM RISC System 6000, provided with a processing system Vision 5.0
(SMV America, Inc). Sources of 99m Tc were used to perform different tests, as well as a SPECT
phantom, props for radioactive source, ruler, syringes, disposable vials, lead containers and other
materials to perform the tests were also utilized. The obtained results show an annual mean value of
2. 69 % for tomographic uniformity; and an annual mean value of 1.2 mm for the displacement of
the center of rotation. As a conclusion, we can assert that such parameters that most affect the
quality of SPECT brain images are: the displacement of the center of rotation and tomographic
uniformity. Tomographic uniformity and the displacement of the center of rotation should be
evaluated weekly and monthly, respectively, in order to assure the optimum quality of brain SPECT

         Stroke due to vasculitis associated to Systemic Erythematosic Lupus in children. A case presentation

Carmen Rosa Alvarez Gonzalez, Erduy J Infante Velásquez, Gilda Martinez Aching, Carlos
Sánchez Villar
International Center for Neurologic Restoration (CIREN). Havana, Cuba
Colagenosis is a multisystemic disease with a great evolutive variability. In the case of Systemic
Erythematose Lupus, the neurological commitment is present in almost half of all cases and it
provokes vasculitis by convulsions caused by stroke or brain hemorrhage. Diagnosis is established
with the aid of Computer Tomography. The objective of our work is the presentation of a clinical
case. Material and Method. A case under pediatric age with an autoimmune disease of the vascular-
type is presented. The disease provoked a motor sequel of the left-hemiparesia. We applied the
evaluation of motor function (at the beginning and end of neurorestorative treatment). Discussion of
results and conclusions. Keeping in mind the patients peculiarities, we evidenced that with an
adequate structured application and by giving special attention to different developmental areas
with the use of the Intensive Multifactorial Neurorestorative Program at the Children‟s Clinic of
Neurology progress can be obtained. From a quantitative viewpoint the Gross Motor Scale was
applied to the patient at the beginning and end of treatment. The results showed that in the initial
evaluation, the patient reached a 22,2% and 37,5% in the final one, for an improvement of 15,3%.
This made possible to conclude, that it is possible to improve the patient‟s quality of life.

                    New scale for the classif ication of paraplegic patients after a spinal cord lesion

Edgar N. Galarraga Triana and Carlos. Sánchez Villar
Neuropediatric Clinic, International Center of Neurological Restoration, Havana, Cuba
Medullar lesions constitute one of the more frequent causes of disability in the world. This is
produced by the rupture of nervous pathways. These axons, once broken, are unable to regenerate
causing loss of sensitiveness, and permanent and irreversible paralysis below the lesion level. In our
work we tried to validate a test we made to demonstrate that it is reliable to quantify and classify the
restoration in the physical sphere of paraplegic patients due to a medullar lesion. The test we present
here is a variant to the Barthel index where we included only physical items. This investigation was
carried out at CIREN‟s Neurology Clinic for Children and the Clinic of Spinal Lesions. The sample
was composed of 33 patients with ages between the 3 and 40 years old, all diagnosed with spinal
lesion, either congenital or acquired. They were subjected to a period of rehabilitation of 28 days,
and were evaluated with the test mentioned before, during and after treatment. To establish the
validity of the test, we used the statistical technique of product moment of Braves Pearson, and for
reliability, we used variance analysis. The results demonstrate the validity and reliability of the test
proposed to evaluate the recovery of a paraplegic patient.

         Influence of physic al exercis es on patients bearers of muscular dystrophy of Duchenne and Baker type

Elia Aguero Pacheco, Rebeca Gutiérrez de los Santos., Alexis Rodríguez Aldama, Gabriel
Rodríguez García.
International Center for Neurológical Restauration (CIREN), Havana, Cuba
Until recently, dystrophies have not been considered for rehabilitation treatment due to the course of
the disease, the role of fatigue on affected muscles and the absence of therapeutic effects of
muscular exercises. Today, it can be asserted that considering dystrophies as a kind of paralysis is
wrong. The total absence of the muscular activity will hinder patients from the stimuli that provoke
energetic reactions, which are necessary to keep the functional value in the patient. Immobilization
is said to be harmful as it disturbs deep circulation. From this, the role of rehabilitation is important
to keep functional possibilities to a maximum. Purpose: To demonstrate the influence of an integral
rehabilitation treatment to patients bearers of muscular dystrophy of the Duchenne and Baker type.
Material and method: We performed a retrospective study to selected sample of patients diagnosed
with Duchenne \ Becker muscular dystrophy for children. Each child was submitted to a
rehabilitation treatment approximately between four and eight weeks with 6 weekly frequencies.
We performed basic motor tests at the psychomotor integral evaluation lab (LEIS) at the beginning
and the end of treatment. Patients were evaluated in their gross motor function (GMF) and muscular
test or Daniel„s test of each body segment in order to determine the level of improvement reached
during treatment. Results: A significant improvement was obtained in treated patients.

                                   Chiropractic treatment for lumbar disc herniations

Raul Carrillo Rodriguez Eduardo Ahumada
Northwestern Health Sciences University, USA
A total of 100 patients between 25-35 years of age. with proven disc herniations on MRI, with
grade II classifications were treated with chiropractic specific adjustments to the lumbar spine
where the segments involved were mainly l4 and l5, with pain at site of palpation, muscle spasm,
radicular pain into legs and feet, paresthesias, some loss of strenght on leg muscles and 15%
presented with neurovascular reflexes with ankle and foot swelling. A series of 15 chiropractic
adjustments were performed with 50% of symptoms resolved within the first 5 visits, other patients
improved gradually up to 90-98% recovery on the 12th visit. The most common symptom to prevail
was the numbness at distal portion of the involved extremity. Only 10 patients needed to have a
epidural steroid spinal block and only 3 of them discontinued conservative management to undergo
selective endoscopic discectomy. This patients were treated with 5 adjustments first week, 3
adjustments per week the following two weeks and once a week the following four weeks, no
medications were prescribed only i.m. vit. B12 and icing the involved area of pain 20 mins every
hour the first 2 days then 3 times a day for 5 days. No adverse effects were presented with the
adjustments and only 2 patients had adverse allergic reaction to the vit. B12. The patients were all
evaluated with a full spine view 14x 36 and lls, flexion-extension views of lumbar spine in order to
identify vertebral misalignment and pelvic instability that influences the pressure vectors over the
disc and facet joints of the motor unit involved, as well as MRI with gadolinium contrast where all
patients had grade ii disc herniations with symptoms related to disc compression all th is imaging
performed preceded by chiro/ortho/neuro examination to determine ivdh classification and the site
of vertebral subluxation complex. Three had questionable symptoms and a bone scan (gamagram)
performed to rule out sacroilitis 2 were negative and 1 positive for sacroilitis, this patient was
removed and replaced from the treatment group for ivdh. Conclusions were made upon taking
chiropractic treatment as a primary conservative approach to treat ivdh. of the lumbar spine with
radicular ssx with excellent results to avoid spinal surgeries.

     Effect of cellular metabolism increase and decrease on lipoperoxidation process after traumatic spinal cord injury

Sergio Torresc, Hermelinda Salgado-Ceballosa ,b , Gabriel Guízar-Sahagúna,b , José Luis Torrese,
Martha E. Vázqueze, Araceli Díazd , y Camilo Ríos-Castañedac,d.
  Research Medical Unit in Neurological Diseases, CMN, S. XXI, IMSS, b Proyecto Camina A.C.,
  Metropolitan Autonomous University, Iztapalapa, dNational Institute of Neurology and
Neurosurgery, eResearch Unit in Oncology Diseases, CMN, S. XXI, IMSS, Mexico city, Mexico
Traumatic spinal cord injury (TSCI) often results in permanent paralysis. The final lesion results not
only from the physical trauma to the tissue, but also from the progressive cellular damage that
expands the injury to caudal and rostral levels of the spinal cord. This secondary injury includes
ischemia where mitochondrial function fails and ATP concentration drops within minutes, and
reperfusion process which promotes autodestructive phenomenons like tisular damage by reactive
oxygen species (ROS) and lipoperoxidation process (LP). With the aim to evaluated the effect on
LP process, metabolism activity was increased and decreased using the cocarboxilase non
degradable (CND) enzyme and 5 mitochondrial inhibitors respectively in 48 Long Evans, female,
adult rats divided into 8 groups: Group 1, laminectomy without TSCI; Group 2, TSCI plus
physiologic solution; Group 3, TSCI plus CND; Groups 4, 5, 6, 7, and 8 plus rotenone, 3-
nitropropionic acid, antimycin A, sodium azide, and cyanide respectively. Animals were subjected,
under anestesic conditions, to a moderate TSCI (T-9) using the NYU impactor system. Treatments
were injected intraperitonealy 5 minutes after TSCI. The effects of CND and mitochondrial
inhibitors on NADH dehydrogenase, succinate dehydrogenase, cytochrome oxidase and LP process
were evaluated 24 hr after treatment. CND treatment increased LP processes (p<0.05), while all
mitochondrial inhibitors, except cyanide, decreased the LP process, specially rotenone and sodium
azide (p<0.05). Our results suggest that the decrease in metabolism activity, early after a TSCI
could be an autoprotective response instead a secondary mechanism of damage since it could reduce
LP process.

                      Treatment w ith laser on ischemic ulcers for patients with medullar lesions

Carlos Rafael Leyva Barrientos.
M. H.” Dr Luis Días Soto”, Habana, Cuba
A clinical trial was made based on controlled, descriptive and prospective analysis of patients
admitted at the military hospital Dr. “Luis Diaz Soto” between February 2002 to February 2003
suffering from medullar lesions and other neurological dysfunctions with ischemic ulcers. It‟s a ten-
patient sampling. Subjects were selected at random and equally grouped into two sections with 5
cases each. The first group of patients was treated with 1% Cetavlón in order to wash ulcers, later
rinsed with 0.9% serum following the lesion necrotic tissue debridement, careful wiping and an
application of infrared Hene laser by means of a Fisser-III-brand equipment made in Cuba at 7
Joule/cm2 and 25 watts (MW) of power which optic fiber device is placed perpendicular to the
lesion ridge for 60 second/point. The second group was treated with washing and debridements
process the same as in the previous case. This time, however, a light coat of skin growth ointment
applies. In each case, sterilized dressings were placed on the ulcers until the last day of the
treatment in order to evaluate the action of laser rays in the cicatrisation process. The subgroup
composed of 15-19 year-of-age patients (60%) prevailed male individuals (80%) who had car
accidents (50%) resulting in paraplegia; major sequel found in 8 patients.

                           Bladder education with nurse neurological restoration strategies

J. Ignacio Escalante, Jaqueline Garriga, M.Angeles Peña, Marlen Savigñon, Mirna Alvaro-Diaz
Spinal Cord Injury Clinic, International Center for Neurologic Restoration, Havana, Cuba
The study and follow up of neurogenic bladder in spinal cord injuries are of vital importance for the
multidisciplinary team that cares for this patients. We presented a prospective and retrospective
study of 601 patients admitted in Spinal Cord Injury Clinic of International Center for Neurological
Restoration during the period between January 2000 and September 2003. The main goal was to
obtain bladder reeducation. We used the urological scale and the nurse evaluation during reception
in 100% of the patients being able to conclude that 95% of the patients came without bladder
education and with history of urinary infection in 97%, as principal consequences of bladder
neurogenic dysfunction. We obtained, with our intervention, the reduction of complications related
with this disease.

                            Neurological restoration in paraplegy: The CIREN experience

Juan E. Bender del Busto.
International Center for Neurologic Restoration (CIREN), Havana, Cuba
We will perform a review of principal aspects related to multifactorial management in paraplegic
patients at the Spinal Cord Injury Clinic of the International Center of Neurological Restoration,
Havana, Cuba. The results will be shown too. All patients were studied using haematologic,
imagenologic and neurophysiologic tests before the beginning of neurological restoration. The
Barthel index, spasm, motor and Asworth scales were applied too. Physical rehabilitation,
occupational and speech treatment were performed. A good evolution was found in our casuistic
and life quality was significantly increased in 25 evaluated patients.

              The w ritten language, an actual alternative for patients bearers of cervical medullar lesion

Mercedes Caridad Crespo Moinelo, Oscar Oliden Torres Carro, Tania Francia González, Ana María
International Center for Neurologic Restoration (CIREN), Havana, Cuba
Spinal cord lesions can produce different motor disorders according to the level of alteration
suffered by the spinal cord. When segments between C4-C8 are lesioned, superior limbs are most
frequently affected, and as a consequence, skilled hand activities. With the aim of evaluating the
influence of the system of therapeutic activities, developed for the correction of the functional
disorders of the superior limbs, the Oligraf quantitative scale for writing (created by CIRENS Clinic
of Movement Disorders and Neurodegenerations) was applied. We applied this scale to 20 patients
with high spinal cord lesions (C4-C7) divided into three groups according to the level of lesion,
before and after therapeutic intervention. The patients were evaluated using the LEIS Standard
Scale (CIREN. Alterations in writing were found in the majority of the sample, where
macrographia, agglutination and expansion of writing predominated in patients with C6-C7 lesion.
Upward, downward and agglutinated writing was found in patients with C5-C6. Writing on top of
the other letter was found in patients with C4-C5 lesions. OLIGRAF quantitative scale influenced in
a positive way the identification of alterations in writing in almost the totality of the sample.

    Effect of a physic al rehabilitation program on gait and Independence level in paraplegic patient w ith spinal cord injury

Yosvani Acea Cruz, Ernesto Cossío García, Alexander Echemendía del Valle.
International Center for Neurological Restoration (CIREN), Havana, Cuba
Introduction: Spinal cord injury is one of the most common causes of disability in adults. Trauma
over the spine can develop a fracture, luxation or ligament damage. Objective: to evaluate the effect
of a rehabilitation program on the gait and the independence level in paraplegic patients. Methods:
we selected 10 patients with dorso-lumbar spinal cord injury. We evaluate patients with the Barthel
index and the preparatory activities for the gait (mattress work and stand work) before and weeks
after an intensive rehabilitation program. Results: nine patients increased the ability in mattress
work, according to repetition of the exercise (15 repetitions over baseline in hip‟s flexion). Barthel
index increased in all patients (mean of 20 points). Conclusions: an intensive rehabilitation program
seems to be effective for training the gait an increase the independence level of paraplegic patients

                                      Post-paralitic sinkinesis in peripheral facial palsies

Marta Brown, Aymee Hdez, Judith Cañizares, Ana E. Fdez.
Dpto. de Neurofisiología Clínica, Hospital Carlos J. Finlay, Ciudad de la Habana, Cuba
In the facial neuropathies with an axonal lesion very predominant or exclusive axonal, takes place
in a systematic way, an aberrant regeneration that produces a clinical phenomenon named facial
cross-innervation, so called post-paralytic hemifacial spasm. In these cases, the answers R1 and R2
of the Blink Reflex are obtained in other facial muscles outside of the muscle Orbicularis oculi, as
the Frontal, Orbicular oris or Cutaneous of the neck. The physiological explanation commonly
accepted is the arrival of the nervous fibers belonging to the muscle Orbicularis oculi to other facial
muscles in the regeneration process. In such a sense, we gave ourselves to the task to explore the
existence of this phenomenon, also called post-paralytic sinkinesis, in patients with peripheral facial
palsies in different moments of the illness's evolution. In this study we present the Blink Reflex
obtained in the Orbicularis oris muscle bilaterally of 4 cases with an important facial palsies in
which was obtained electrophysiological confirmation of aberrant regeneration of the facial nerve,
in some cases even before the clinics signs appear. This study could be used as a therapeutic guide
in the treatment of the post-paralytics syndromes of the peripheral facial palsies.

A comprehensible program for the rehabilitation and restoration of the neurological dysfunction for Multiple Sclerosis patients
                                                and their caregivers in Cuba
Padilla Ma, Cabrera-Gómez JAb , Real González Yb , Luna Rodríguez-Gallo Ja, Gómez AOa, Brunet
Gómez Da, Cid Ja , González Acosta Da
  Multiple Sclerosis Rehabilitation Hospital,¨ Dr Faustino Pérez ¨, Sancti Spíritus, Cuba. b Multiple
Sclerosis Society of Cuba, Havana, Cuba
INTRODUCTION: The recent disease-modifying drugs have not eliminated the need of
rehabilitation strategies in the management of MS. Even if there were that could fully prevent
progression of the disease, hundreds of thousands of patients worldwide would still be left with
residual neurological damage and the associated impairment and disability. OBJECTIVE: To
introduce a comprehensive rehabilitation and restoration program for MS patients and their
caregivers in a natural rehabilitation hospita l in Cuba. DESIGN-METHODS: The
multidisciplinary team of rehabilitation and restoration has developed and integrated,
comprehensive and intensive rehabilitation program for MS patients. This multidisciplinary team is
composed by: neurologists (with training in MS), physiatrist, psychologists, neuropsychologists,
social workers, occupational therapist, natural medicine specialists and nurses. The program is an
intense short term rehab in 6 weeks 2 sessions for each patient and will have a single
physiotherapist (one to one) and a neuropsychologist. The evaluation of the rehabilitation and
restoration include the physical and cognitive disability and the clinical evaluation by means of
international disability scales (EDSS, Guy Scale), quality of life scales (MSQLI), psychological and
neuropsychological tests (Luria, WAIS, Benton, PASAT-3) to evaluate the efficacy of the program.
Finally, we will teach to the MS patient and her/his caregiver to learn, at their own home, the
exercises for the physical and cognitive dysfunction when the patient left the rehabilitation MS
hospital. RESULTS: The results will be presented at the meeting. CONCLUSIONS: This is one of
the most extensively program for physical and cognitive rehabilitation / restoration for MS patients
and their caregivers in a Latin-American country.

Multiple Sclerosis in the Cuban women. An update

Real González Y, Cabrera-Gómez, JA, Romero García Karina
Multiple Sclerosis Society of Cuba. Havana, Cuba
Objective: To evaluate the clinical and social-economical status of the Cuban women with MS.
Introduction: Multiple sclerosis (MS) is the cause of greater disability in the young woman in Cuba.
Design and Method: Epidemiological study: We carried out a case-control study, in 57 women with
MS clinical definite (Poser et al) and their relatives. The evaluation was gotten by means of the
questionnaire of Boiko et al. Clinical, disability and social-economical studies: 271 women with
clinical definite MS. The clinical, demographic and social-economical data were taken from the
Cuban Computerized Register of MS. Results: Epidemiological study: The risks factors were: High
educational level (OR= 2.293; 95% CI= 0.9-5.4), 2 or more children (OR= 2.84; 95% CI= 1.22 -
6.59), 4 or more pregnancies (OR= 3.60; 95% CI= 0.69-18.7), 3 or more deliveries (OR= 1.939,
95% CI= 0.44-8.4), measles infection (OR= 2.042; 95% CI= 0.76-5.47), migraine (OR= 2.538;
95% CI= 0.81-7.94), stress (OR= 3.768; 95% CI= 1.64-8.62), and insomnia (OR= 2.95; 95% CI=
1.14-7.14). Clinical, disability and social-economical studies: MS was observed, in women of 30 to
51 years, relapsing-remitting form with family history of autoimmune and psychiatric disorders and
8% with one or more relatives affected. The disability met, 62.57% of the women with moderate or
severe impairment of the ambulation and 20% of them are in wheelchair or on bed. The Cuban
women with MS have a high educational level, but 50% are divorced/single, received low or not
annual salaries or are vacated. Conclusions: It is mandatory to carry out a program in Cuba in order
to improve the medical attention, the disability and the social-economical level of the women with
                         Neurological restoration in Multiple Sclerosis: the CIREN experience

E. Hernández, JE Bender, F Zamora, F Araujo, E Infante
International Center for Neurological Restoration (CIREN) Havana, Cuba
Multifactorial therapeutic was used in patients with Multiple Sclerosis at the International Center
for Neurological Restoration, Havana, Cuba. Our proposal was the evaluation of this therapy in
Multiple Sclerosis patients. We studied 20 patients that were admitted at CIREN during 2000-2002
with different clinical manifestations. They were evaluated within the first week and after 4, 8 and
12 weeks. The Kurztke, Hauser, Cronic fatigue and Asworth scales were applied. Sympthomatic
and specific treatment, biophysical stimulation, phsysical therapy, occupational and speech
treatment were performed. The best results were observed and life quality was increased in all
patients. Our conclusions show that Neurological Restoration is an important aspect in order to
improve the life quality in patients with Multiple Sclerosis.

            Results of LEIS evaluation on patients with multiple sclerosis after a neurorestorative treatment

Gilda T. Martínez Aching, Juan Enrique Bender, Alexander del Valle Echemendía, Carmen Rosa
Alvarez González
International Center of Neurologic Restoration (CIREN) Havana, Cuba
Multiple sclerosis (ME) is a demyelinizing disease affecting the brain and the spinal cord. The
fundamental objective of this investigation was to show the improvement reached by 17 patients
with multiple sclerosis, after a 28-day rehabilitation cycle, through initial and final evaluations of
tests applied to measure strength, breathing capacity and gait. All studies were performed at the
Psychomotor Integral Evaluation Lab (LEIS) in CIREN. The tests applied at LEIS have the required
reliability and sensitiveness to detect changes undergone by the patients during their rehabilitation.
Statistical tests applied (Wilcoxon matched pair test) showed results under the significant levels.
Results. After having analyzed and compared the results of both evaluations, we verified that the
patients obtained positive results in the evaluated items after a treatment cycle. Conclusions. Of the
17 evaluated patients, 7 increased their strength (41,17%); 16 changed their gait possibility
(94,11%) and 14 increased their breathing capacity (82,35%). The positive changes observed in the
treated patients confirm the efficacy of the rehabilitation program applied.
Thursday 26 february 2004

Plenary lecture

CIREN’s strategy and results for Neurological Restoration and Stereotactic Neurosurgery
during its first fifteen years

Raul Macias Gonzalez
International Center for Neurological Restoration (CIREN) Havana, Cuba
During this last fifteen years, the International Center for Neurological Restoration have been
developing novel focus in the way to treat neurodegenerative diseases and sequels of neurological
disorders. These are based on a program to treat sequels call Neurological Restoration Program and
the necessary technology to perform stereotactic neurosurgery. The Neurological Restoration
Program is carried out by a multidisciplinary team guided by neurologists. It comprises: the correct
diagnosis of disease, incapacity quantification and objective definitions for pharmacological
treatment and multidisplinary intensive -personalized rehabilitation. Treatment cycles are organized
for periods of 28 days. Functional recovery in the patient neurological conditions is based in
neuroplastic changes in the central nervous system organization and processing. These mechanisms
had been evaluated in animal models and human being with different tools, like: long-term
potentiation, transcranial magnetic stimulation, fRMI, etc. Synaptic changes in learning and
memory process, amplification and reorganization of the motor cortical maps and function
redistribution between hemispheric cortices are documented. On the other hand, Stereotactic
Neurosurgery technology are composed by: a stereotactic frame (Estereoflex), a general
computerized planning system for neurosurgery (STASSIS), an electrical deep brain structure
recording system (NDRS) and a general team training system. Main characteristics of those
components and the accumulated experience transferring these technologies to more than 11
hospitals will be described.

Neurorestorative Treatments

Chromaffin cells exposed to ELF EMF can be used as transplant material in Parkinson’s disease and induce expression of
                                        TH positive cells in lateral ventric les.

Leticia Verdugo-Díaza , Oscar Arias-Carriónb , Arturo Hernándezb and René Drucker-Colínb .
  Depto. De Fisiología, Fac. de Medicina, b Depto. de Neurociencias, Instituto de Fisiología
Celular, UNAM, México.
Cultures of neonatal rat chromaffin cells in presence of Extremely Low Frequency Electromagnetic
Fields (ELF EMF) show morphological and ultrastructural changes (Drucker-Colín et al, 1994;
Feria-Velasco et al, 1998), different rates of catecholamine release (Verdugo-Díaz et al, 1998),
biochemical and electrophysiological modifications (Morgado-Valle et al, 1997). The efficacy of
ELF EMF differentiated chromaffin cells transplanted into a Parkinson‟s disease (PD) patient was
tested and neurological, motor and pharmacological changes were determined. A PET-scan study
was also done prior to transplant and 7 months after (Drucker-Colin et al,1999). We investigated
the effects to applying ELF EMF in vivo into an animal model of PD. Male Wistar rats were
subjected to the unilateral destruction of the substantia nigra by applying 6-OHDA and transplanted
with neonatal chromaffin cells. The application of ELF EMF (60Hz, 0.7mT) was daily 2 hours in
the morning and 2 hours in the afternoon for a period of 2 months. ELF EMF were produced by a
pair of Heltzmohtz coils. Chromaffin cells were stained prior to implant with FluoroGold or 5-
bromo-2‟-deoxyuridine (2 fold daily). The main results obtained in vivo application of ELF EMF
were: 1) Improvement in motor deficits and an over expression of Tyrosine Hydroxilase (TH)
positive cells in both lateral ventricles of the nigro-striatal lesioned rats with chromaffin cell
transplant; 2) No migration of implanted cells and differentiation of progenitor cells of both
subventricular zone. In sum, it seems that ELF EMF, can be used as therapy for patients having PD.

Roles of D1 and D2 receptor subtypes in levodopa-induced dyskinesias in a mouse model of
Parkinson disease.

N. Pavóna, Martín ABb , Alberti Ib , Grandy Db and Moratalla Rb .
  Centro Internacional de Restauración Neurológica, Ciudad de la Habana, Cuba. b Instituto Cajal,
CSIC, Madrid, Spain
Treatment with L-DOPA is today the most efficacious, non-invasive therapy for Parkinson‟s
Disease. However, chronic treatment with L-DOPA induces in most of the patients the appearance
of abnormal involuntary movements known as dyskinesias. The molecular mechanisms underlying
these abnormal movements are unknown, although the implication of dopamine receptors as well as
other neurotransmitter receptors interacting with the - system is suspected. In the present work, we
have studied the contribution of D1 and D2 receptor subtypes in levodopa-induced dyskinesia. In
this experiment dyskinesias were induced with intermittent doses of L-DOPA in unilateral 6-
OHDA-lesioned mice. Rotational tests were carried out in a rotometer system that counted
completed turns (360º) only and the abnormal involuntary movements we have divided in four
different types: orofacial, forelimb, locomotive and dystonia, and evaluated. In wild-type animals
chronic treatment with L-DOPA induced abnormal involuntary movements that including
horizontal or vertical abnormal jaw movements, ballistic movements of the contralateral forelimb
and axial dystonia. We have found that inactivation of D1 dopamine receptors completely abolished
orofacial dyskinesia, did not affect axial distonia and slightly reduced forelimb dyskinesia. By
contrast, knock out mice lacking D2 receptors showed an increase in orofacial dyskinesia after L-
DOPA treatment but axial dystonia and forelimb dyskinesia were not present. In summary, our
result demonstrate that D1 and D2 receptors play a differential and complementary a role in L-
DOPA-induced dyskinesia and that the integrity of the D1 and D2 receptors is critical for different
aspects of levodopa-induced dyskinesias.

Ex vivo VEGF gene transfer does not increase grafted dopamine neuron survival

C.E. Sortwella, W.J. Bowersb , H.J. Federoffb , M.F. Fleminga , D.M. Marchioninia , N.M Kanaana, B.
Terpstraa, K. A. Steece-Colliera and T.J. Colliera,
  Neurology, Rush-Presbyterian, Chicago, IL, USA; b Neurology., Univ. Rochester, Rochester, NY,
Specific conditions associated with the post-transplantation interval render grafted mesencephalic
dopamine (DA) neurons susceptible to apoptotic and necrotic forms of cell death. Immediately
following transplantation, grafted cells are dependent upon diffusion of oxygen and blood-borne
materials from the host vasculature until they establish circulation with the host brain. Vascular
endothelial growth factor (VEGF) is the primary endogenous endothelial cell mitogen involved in
both vasculogenesis and angiogenesis. The present study investigates the ability of ex vivo
transduction of mesencephalic reaggregates with a helper virus-free Herpes simplex virus (HSV)
amplicon vector encoding VEGF to increase DA neuron survival after transplantation.
Mesencephalic reaggregates were generated from E14 F344 rat pups and transduced immediately
with either helper virus-free HSV-vegf, HSV-lac (MOI = 1.0 or 2.0) or no vector. Four days post-
transduction (PTD4) reaggregates were analyzed for VEGF release to the culture media and levels
of VEGF within the aggregates themselves using immunoassay and grafted to the denervated
striatum of Fisher 344 rats. On PTD4 HSV-vegf-transduced reaggregates released at least 250 fold
more VEGF protein into the culture media and contained at least 130 fold more VEGF protein than
HSV-lac or non-transduced control reaggregate cultures. Although these in vitro assays yielded
promising results, results of HSV-vegf ex vivo transduction of grafted mesencephalic reaggregates
on behavioral and morphological outcome measures were not posit ive. The present results
demonstrate that ex vivo gene transfer of VEGF is not successful in augmenting the survival of
mesencephalic grafts. Supported by: AG21546, AG000844, Rochester Nathan Shock Center.

Administration of different doses of methylprednisolone in adult rats with traumatic spinal cord injury of different intensity and
                                                at different spinal cord levels .

H. Salgado-Ceballosa,b, S. Torres-Castilloa ,c, J.L. Torres-Verae, D. Zabaleta a, A. Zavala a, S.
Orozco-Suáreza, R. Capine, A. Feria-Velascod
  Research Medical Unit in Neurological Diseases, CMN, S. XXI, IMSS, b Proyecto Camina A.C.,
  Metropolitan Autonomous University, Iztapalapa, dCIATEJ SEP-CONACYT,eResearch Unit in
Oncologyc Diseases, CMN, S. XXI, IMSS, Mexico city, Mexico.
After series of preclinical and clinical works, methylprednisolone (MP) became the standard of care
in traumatic spinal cord injury (TSCI). However, in some studies MP failed to demonstrate
consistent and significant effect on functional outcome. With the aim to test if the injury intensity or
the injured level could affect the response to the MP treatment, adult rats were subjected to mild (30
g/cm), moderate (75 g/cm) or severe (150 g/cm) TSCI at cervical (C6), thoracic (T9) or lumbar (L2)
level using a standardized weight-drop contusion model. Groups were divided into subgroups that
received vehicle or MP at 15, 30 or 45 mg/kg of body weight. Using the thiobarbituric acid reaction,
malondialdehyde (MDA) levels, resulting from lipid peroxidation were obtained. Morphometric
studies were done by light and electron microscopy and motor function using the BBB scale. Mild
thoracic and mild and moderate lumbar injuries showed motor recovery with MP at 15mg/kg, while
30 and 45 mg/kg were as deleterious as in cervical and lumbar severe injuries. Non motor recovery
was observed in moderate cervical and thoracic injuries, where the mortality was increased. In
severe thoracic injuries motor recovery was observed with all doses of MP, specially with 30 mg/kg
(p<0.03). However, in all groups where MP produced motor recovery by protecting axons and
myelin sheaths from the secondary injury, it inhibited axonal collateral emission. MDA levels
correlated with morphometric parameters and motor recovery. Response to MP treatment after
TSCI seams to depend of the intensity and the injury level.

The administration of tw o new derivates of xanthines (A15ET and A15BU) reversed the locomotor impairments in rats with
                                                    dopaminergic lesion

Carmen Parra a, Miriam Alonsoa, Rogelio Maxila , Alejandro Muñozb , Jesús Sandovalb , Daniel
  Laboratorio de Neurofarmacologia, Facultad de Ciencias Químicas-BUAP, bCentro de
Investigaciones FCQ-Benemérita Universidad Antónima de Puebla. Puebla, México.
In Parkinson‟s disease therapy is symptomatic. The L-dopa like is alternative in this pathology
when is administrated by long time. Because of it is necessary to research new drugs about this
pathology. One of them are the A2A antagonists that improve some Parkinson motor behavior in
patient. In our University new derivates of xanthines like A15Et and A15Bu have been synthesized.
The aim of this work was to evaluate the effect of new A2A antagonist (Al5Et and A15Bu) on
motor behavior in rats with dopaminergic lesion. One group the rats were injected with 2 ml of 6-
OHDA(8mg/ml) in SNc. The lesioned groups were evaluated in the drug induced turning behavior
model, and in this condition were administrated A15Et or A15Bu (1mg/kg). The A15Bu was also
evaluated in the star case test. Others groups of intact rats were evaluated in locomotors activity in
and cataleptic behavior. We found that new A2A antagonist A15Et and A15Bu decreased 50% and
25% the turning behavior 70 and 80 minutes after administration. In the staircase the ability of
reach pellets improved in 98%, the catalepsy behavior was reversed by injection of A15Bu 50%
and did not modify the locomotor activity in intact rats. These data suggests that A15Et and A15Bu
improve the motor function of rats with dopaminergic lesion.

                                   Calpain inhibitor prevents axonal degeneration

 Hokoç, J.N.; bCouto, L.A.; b Narciso, M.S. and b Martinez, A.M.B.
 Instituto de Biofísica Carlos Chagas Filho and bDepartamento de Embriologia e Histologia, ICB,
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
The ultrastructural change that characterizes the onset of Wallerian degeneration is the
disintegration of axoplasmic microtubules and neurofilaments, followed by myelin breakdown. The
mechanism underlying such processes is an increase in the amount of intracellular calcium, leading
to activation of proteases called calpains. The aim of this study is to evaluate whether nerve fibers
can be preserved by the use of calpain inhibitor, after optic nerve crush. The left optic nerve of eight
opossums (Didelphis aurita) was crushed (Group A) and four of them received the calpain inhibitor-
2 that remained in the crushed area (Group B). Right optic nerves were used as control. After 96 hrs
the nerves were dissected and processed for electron microscopy. Group A presented degenerating
fibers, besides disorganization of the optic nerve structure. Group B maintained the structure of the
optic nerve, which was organized in fascicles, thus preventing the dispersion of the fibers. The
quantitative analysis showed that the Group B presented more normal fibers (25.36 ± 7.83) than
Group A (21.47 ± 7.27), p<0.05, and less degenerating fibers (7.65 ± 2.80) compared to group A
(10.22 ± 4.33), p<0.001). We also calculated the G ratio (axonal area/fiber area), which showed that
the Group B presented G ratio (0.45 ± 0.29), close to normal values (0.44 ± 0.19). However Group
A presented the largest G ratio (0.85 ± 13.57), when compared to the other two groups (p<0.01). In
conclusion, our findings suggest that calpain inhibitor is capable to provide neuroprotection after a
crush lesion.

             Striatal trophic factor pleiotrophin augments dopamine neuron survival and neurite outgrowth

Deanna M. Marchioninia, Elin Lehrmannb , William J. Freedb and Timothy J. Colliera
  Rush University Medical Center, Dept. Neurological Sciences, Chicago, Illinois, USA, b National
Institute on Drug Abuse, Baltimore, Maryland, USA
Transplantation of embryonic ventral mesencephalic (VM) tissue is an experimental therapy for
Parkinson‟s disease. Both survival of grafted neurons and reinnervation of the striatum are essential
for functional recovery. Our aim was to identify genes/factors that are upregulated during time
points critical to nigrostriatal development and synaptogenesis. We utilized a microarray to profile
gene expression in the rat E15 lateral ganglionic eminence, P1 and adult striatum. We identified
genes that are upregulated during development, and tested their ability to promote dopamine neuron
survival and neurite outgrowth in culture. Microisland cultures of E14 rat VM were exposed to
pleiotrophin. On day 4 in vitro, cells were processed for tyrosine hydroxylase immunoreactivity
(THir). Cell counts of THir neurons yielded 114.7 ± 8.0, 113.9 ± 11.0 and 134.3 ± 4.5% of control
for cells treated with 10, 50 and 100 ng/ml pleiotrophin, respectively. Furthermore, neurite
outgrowth was significantly increased in pleiotrophin treated cultures, 158.5 ± 21.3, 150.2 ± 18.1,
180.2 ± 20.1% of control for cells treated with 10, 50 and 100 ng/ml, respectively (p<0.05).
Pleiotrophin may be an important cue in the establishment of nigrostriatal circuitry. Grafting of
embryonic dopamine neurons in conjunction with pleiotrophin may promote reinnervation and
functional recovery in Parkinson‟s disease.
Molecular mechanisms of neurodegeneration

                                  Parkin and Ariadne share redundant functions

Sangram Parelkara, Kim Chula, Tanja Godenschwege b , Zhouwei Wanga, Rachel Sugala , Rodney K.
Murpheya,b and Lawrence M. Schwartza,b
 Molecular and Cellular Biology Program and bDepartment of Biology, Morrill Science
Center, University of Massachusetts, Amherst, MA. 01003 USA
Parkinson‟s Disease is characterized by the presence of Lewy Bodies and the loss of dopaminergic
neurons. Long thought to be a causative factor in neurodegeneration, Lewy bodies may in fact serve
a protective role. Patients with Autosomal Recessive Juvenile Parkinsonism (AR
early onset of symptoms and the absence of LB formation. Many of these individuals carry
germline mutations in the ubiquitin E3 ligase Parkin. We have found that Ariadne, the closest
structural homolog to Parkin, can substitute for Parkin in many cellular functions. Both Parkin and
Ariadne bind to the same substrates in vitro, and both can support the formation of Lewy body-like
aggresomes in cultured cells. The aggresomes they produce are indistinguishable and are
synuclein sequestration, and a dependence on intact microtubules. In parallel studies, we are
examining the role of Parkin and Ariadne in neuropathology using the fruit fly Drosophila as a
model. Working with wild-type and Parkin null flies, we are assessing the ability of wild-type and
mutant human Parkin and Ariadne to rescue cellular defects. Ultimately, we hope to understand
why dopaminergic neurons are selectively compromised in AR-JP.

        Effects of 6-hydroxydopamine lesion on glutamate and GABA release in the pedunculopontine nucleus

Lisette Blanco Lezcanoa, Lisis Martínez Martíb , Lázaro Alvarez Gonzálezc , Nancy Pavón Fuentesd ,
Ma. Elena González Fraguela e, Teresa Serrano Sánchezd , Raúl Macías González f Yovani Bouzà
Calderíne, Yovani Coroa , Juan C. Rosillo Martíb , Luisa L. Rocha Arrieta g ,, Magdalena Briones
Velascog , Leticia Nerig .
  Experimental Neurophysiology Department CIREN, Cuba, bNeuromorphology Laboratory CIREN,
Cuba, cMovement Disorders Clinic CIREN, Cuba, d Neuroinmunology Laboratory CIREN, Cuba,
  Neubiochemistry Laboratory CIREN, Cuba, f Basic División CIREN, Cuba g CINVESTAV sur,
Mexico DF, Mexico.
The pedunculopontine nucleus (PPN), co-localized with the mesencephalic locomotor region, has
been proposed as a key structure in the physiopathology of Parkinson‟s Disease (PD). The goal of
the present study was to assess if the amino acid neurotransmitter release in the PPN is modified by
the degeneration of dopaminergic cells, from substantia nigra pars compacta (SNc) in 6-
hydroxidopamine (6-OHDA)-lesioned rats. Simultaneously it was studied the amino acid
neurotransmitter release in the PPN of rats with lesion of the subthalamic nucleus by quinolinic acid
(100nM) intracerebral injection. The extracellular concentrations of glutamic acid (GLU) and
gamma-aminobutyric acid (GABA) were determined by brain microdialysis and high performance
liquid chromatography (HPLC). Rats were assigned to five groups: SNc lesioned (n=11), Sham-
operated (n=7), STN lesioned (n=7), Double lesion SNc+STN (n=9), and untreated rats (n=13).
The extracellular concentration of GLU in 6-OHDA lesioned rats, was significantly increased in
comparison with the others groups (F(4, 42) =16.35 p<0.001). Extracellular GABA levels exhibited
a significantly increase in all lesioned groups (SNc, STN, SNc+STN) in comparison with untreated
and Sham operated rats (F(4, 40) = 12.81 p<0.001). The infusion of artificial cerebrospinal fluid
with higher potassium (10mM) induced an increase in the GLU and GABA concentrations in all
groups, which confirm the neuronal origin of the extracellular content. These results are in
agreement with the current model of basal ganglia functioning and suggest the role of STN-PPN
projection in the physiopathology of PD.

            An animal model of ALS-PDC based on consumption of cycad toxins mimics the Human Disorder

CA Shawa, JMB Wilsonb , J Schulzb , E Hawkesb , C Meldera, M Petrika
  University of British Columbia, Department of Ophthalmology, bUniversity of British Columbia,
Graduate program in Neuroscience, Canada
ALS-parkinsonism dementia complex is a complex neurodegenerative disorder of the island of
guam which can express as classical ALS, as a form of Alzheimer's dementia with strong
parkinsonism features, or as some combination. Epidemiological data of Kurland and colleagues
linked the disorder to the consumption of neurotoxins contained in the flour of seeds of the local
cycad palm, a traditional food source. We have duplicated the disease in an animal model by
feeding male laboratory CD-1 mice a diet containing cycad flour. Exposed mice show both
behavioural abnormalities of motor, cognitive, and olfactory function, in addition to
neurodegeneration in corresponding neural subsets, including cortex, hippocampus, substantia
nigra, and olfactory bulb. Biochemically, the same areas show profound decreases in EAAT2
glutamate transporter expression, elevated protein kinase C, CDK5, and other protein kinases, and a
loss of tyrosine hydroxylase in striatum. Affected regions show the presence of activated astrocytes.
MRI analysis shows volume changes in these areas. These features of abnormal neural function and
morphology are found in various other mouse strains, but can be attenuated or potentiated by
various genetic alterations. Apo E wild type mice are as profoundly affected by cycad feeding as
CD-1 mice, but knockout Apo E mice appear to be largely neuroprotected. In contrast, mSOD1
G93A mice show enhanced neural degeneration following cycad exposure. These results support
the notion that cycad is a key factor of ALS-PDC. The isolation of the putative toxin, a sterol
glucoside, suggests that similar molecules may contribute to related age-dependent neurological
disorders elsewhere.

     Protective actions of S-allylc ysteine on quinolinate- and b-amyloid peptide-induced oxidative neurotoxic ity in rats

Francisca Pérez-Severianoa, Mayra Rodríguez-Péreza, Raquel Salvatierra-Sánchezb , José Pedraza-
Chaverríc, Jorge Guevara d and Abel Santamaría b
  Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, México D.F.,
México, b Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y
Neurocirugía, México D.F., México, cDepartamento de Biología, Facultad de Química,
Universidad Nacional Autónoma de México, México D.F., México, d Laboratorio de Enfermedades
Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, México D.F., México
We investigated the effects of S-allylcysteine (SAC), an aged garlic extract compound with well-
known antioxidant properties, on the in vivo oxidative neurotoxicities produced by the intrastriatal
injection of quinolinate (QUIN) and the intrahippocampal injection of amyloid-( peptide 25-35
(Abeta(25-35)) in rats, as experimental models of Huntington's (HD) and Alzheimer's diseases,
respectively. QUIN is an excitotoxin acting at the N-methyl-D-aspartate receptors, whereas
Abeta(25-35) is the toxic fragment of the amyloid-( peptide accumulated in Alzheimer's brains.
Reactive oxygen species (ROS), lipid peroxidation (LP) and activities of the antioxidant enzymes
superoxide dismutase (SOD) and glutathione peroxidase, were evaluated in striatum and
hippocampus 120 min after QUIN (240 nmol/µl) and Abeta(25-35) (100 µM) injections. Both
QUIN and Abeta(25-35) significantly increased ROS and LP, whereas pretreatment with SAC (300
mg/kg, i.p.) decreased these markers in both models when administered 30 min before the lesions
were done. Except for the significant recovery of the QUIN-induced decrease in Cu,Zn-SOD
activity after SAC treatment, all other enzyme activities were found unchanged in both models after
SAC or toxins administrations. In addition, SAC significantly reduced the QUIN-induced circling
behavior in rats, an specific marker of striatal neurotoxicity. In summary, SAC ameliorated the in
vivo QUIN- and Abeta(25-35)-induced oxidative toxicities by mechanisms related to its ability to
scavenge free radicals, decreasing oxidative stress and preventing cell damage in striatum and
hippocampus, respectively. For the HD model, the preservation of the striatal activity of Cu/Zn-
SOD also seems to account for neuronal protection. SAC is likely to be a promising therapeutic

   Effects of the chronic administration of L-dopa on learning, spatial memory and malonyldialdehide levels in rat with
                                                    dopaminergic lesion

Evangelina G. Quiroga, Liliana M. Mendieta , Rogelio Maxil and Daniel Limón.
Benemérita Universidad Autónoma de Puebla, Facultad de Ciencias Químicas, Laboratorio de
Neurofarmacología, Puebla, Pue. México.
L-3-4-dihydroxyphenylalanine (L-Dopa) has been administered for long periods of time in
Parkinson disease (PD) to alleviates the symptom such as motor functions. Unfortunately, many
problems such as dyskinesias, wearing-off and on- phenomenon arise over the years. This chronic
administration can be associated with cognitive deficits, and the L-Dopa metabolism to contribute
to disease progression through free radicals (FR) generates. Another markers of stress oxidative
such as malonyldialdehide are present too. In this work we evaluate, the effect of chronic
administration of L-Dopa on spatial learning and memory in water maze were studied. After that
we measured malonyldialdehide levels in rats with 6-hydroxydopamine (6-OHDA) lesion into
sustantia nigra pars compacta (SNpc) was studied. The control group was administered SSI and the
experimental group received L-Dopa/Carbidopa (200 mg/kg) for 60 days. Under these conditions,
the spatial learning and memory was evaluated in both groups. After that malonyldialdehide levels
were also measured from striatum and cortex by tiobarbituric method. We found that learning and
spatial memory decreased 50% and 20% respectively. The malonyldialdehide levels decrease 93%,
65% and 90% in the striatum, frontal and temporoparietal cortex of the rat with L-Dopa. This facts
suggest that there are relation between stress oxidative and deficits on learning and memory by
chronic administration of L-Dopa.

                  Glutathione depletion by buthionine sulfoximine potentiates cerebral oxidativ e stress

ME González Fraguela and JY Bauza Calderin
Neuroinmunochemistry Dpto. International Center for Neurological Restoration, Havana
City, Cuba
Oxidative damage to biomolecules has been postulated as a common molecular mechanism
underlying brain aging and neurodegeneration. A marked brain glutathione deficiency by
buthionine sulfoximine (BSO), an irreversible inhibitor of glutathione synthesis, provoke an
imbalance in the cellular redox state towards the pro-oxidant status causing lipid peroxidation,
protein oxidation and DNA damage. The toxicity of BSO to the brain has not been extensively
studied, but appears to be chiefly related to its effect on cerebral oxidative metabolism.
The activities of the enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione
and malondialdehyde content were studied in several rat brain areas following the
intracerebroventricularly (icv) BSO lesion. The animals were assigned to both experimental
groups: icv BSO lesioned 24 and 48 hours, control groups: icv saline lesioned 24 and 48 hours and
intact groups. The SOD and CAT activity levels in the BSO lesioned group were higher than the
values detected in saline lesioned and intact animals in 24 and 48 hours. Concerning CAT activity
showed an increase, non-significant, with regard to the saline lesioned group in 24 hours. We found
both, SOD and CAT activity, the saline lesioned group exhibited higher levels than the intact
animals in 24 hours, in contrast, the saline lesioned group showed a slight increase, non-significant,
with regard to the intact group in 48 hours. In addition the increment of SOD activity in the BSO
lesioned groups in 24 hours with regard 48 hours was statistical significant but in the CAT activity
only showed a non-significant tendency.

                          Mechanism of ethanol-induced glial apoptosis. Site of trophic protection

S. Nahuel Villegas, Fernando A. Polleta, Mirta Reynaldo and Néstor G. Carri
IMBICE(CONICET-CIC), CC 403, 1900 La Plata, Argentina.
We have previously shown that GDNF protects glial cells in culture from ethanol induced
apoptosis. The aim of the present work is to investigate the mechanisms involved in ethanol-
induced glial cell death and in trophic mediated glioprotection. Briefly, B92 glial cells were plated
over glass coverslips with 100 ml D-MEM at 30,000 cells/cm2. After 24 h medium was replaced by
treatment medium with 86, 172 mM EtOH, during 1 or 2 h, alone or supplemented with GDNF (30
ng/ml). After fixation, cells were prepared for immunochemistry, cytosqueleton kit detection, and
for DAPI nuclear staining to identify apoptotic nuclei. We observed that active JNK (pJNK), a
MAP kinase involved in apoptotic signal transduction, is unusually placed as stress fibers, and co-
localized with actin filaments. After ethanol exposure cells lose their stellated form and acquire
circular morphology. They exhibit a significantly higher amount of ring-formed actin cells, and a
more diffuse organization of actin filaments. In the meantime, pJNK can be observed in the nucleus
and perinuclearly. This data suggest that cytosqueleton may play a protective role abducting pJNK
and thus, ethanol noxious effects may be drived by the disorganization of actin cytosqueleton
through the release of pro-apoptotic actin associated pJNK. In turn, GDNF protective treatment fails
to prevent actin disorganization indicating that it may be involved into an alternative mechanism of 02-2000 and CONICET PIP-2580 Grants.


 Evaluation of the neurorestorative effects of the murine beta-nerve growth factor infusions in old rat with cognitive defic it.

María R. Castellanosa, Jorge Aguiarb , Caridad I. Fernándeza, William Almaguera, Carmen Mejiasc,
Alfredo Varela c.
  International Center of Neurological Restoration, Havana City, Cuba, b Center for Genetic
Engineering and Biotechnology. Havana City, Cuba, cUNAM Neurobiology Institute, Queretaro,
Nerve Growth Factor (NGF) is known to participate in the regulation of the expression levels and
activity of the choline acetyltransferase (ChAT) in the Nervous System. This enzyme is sensitive to
the degenerative changes found in Alzheimer‟s disease. We compared the effectiveness of
intraparenchymal and intracerebroventricular administration of the murine b-NGF (b-NGFm)
purified in our laboratories, through the evaluation of ChAT expression levels by reverse
transcription and polymerase chain reaction (RT-PCR), the determination of ChAT activity by a
radiochemical method, and through the evaluation of spatial memory and learning of aged rats with
cognitive deficit in the Morris water maze tasks. Our results indicate that intracerebroventricular
infusion of b-NGFm stimulates the expression levels of ChAT gene in the striatum of old rats.
Remarkable losses in the ChAT activity was observed in the septum and striatum of old rats. b-
NGFm infusions produced significant increases of ChAT activity in these brain regions
differentially according to the administration pathway. The molecular and biochemical changes
observed in the expression levels and activity of ChAT after b-NGFm infusions is related with the
significant reversion of the memory deficiency. The results of the behavioral test suggest that the
intraparechymal pathway offers the best results for a neurorestorative treatment.

     Evaluation of bone marrow mononuclear cells surviving when are transplanted in rats injured w ith quinolinic acid

Esteban Albertia Rocío García a, Teresa Serranob , Lissette Blancoc, Lisis Martíneza , Yssel Mendoza d ,
Juan Carlos Rosilloa , Karelys de la Cuétara a, Lázara Castilloa
  Department. of Neurobiology, International Center for Neurological Restoration, Havana City,
Cuba, bDepartment of Neuroinmunochemestry, International Center for Neurological Restoration,
Havana City, Cuba cDepartment of Experimental Neurophysiology, International Center for
Neurological Restoration, Havana City, Cuba, d Growth Factor Department., Center for Genetic
Engineering and Biotechnology, Havana City, Cuba
The transplant of bone marrow mononuclear cells is one of the novel alternative therapeutic options
for the treatment of neurodegenerative diseases, and its aim is to achieve a substitution of neural
cells lost during the development of the disease. The objective of this work was to study the
capacity of BMMC to survive the transplant and to look for a method that allow in vivo detection of
implanted cells. BMMC were extracted from rat‟s femur using a Ficoll - Hypaque gradient. These
cells were genetically modified with an adenovirus, which expresses the Green Fluorescent Protein
(GFP), or they were labelled with Hoechst reagent. Labelled cells were implanted in the striatum of
rats with lesions caused by quinolinic acid. The viability of genetically modified cells was low,
while the viability of the labelled cells with Hoechst reagent was bigger than 90%. Implanted cells
survived, at least one month, after transplant and they were dispersed from the entrance place
toward corpus callosum and cortex in the brain. In conclusion, BMSC has characteristics, which
allow them to be considered as novel cellular source for transplantation. In our conditions, we
consider more advantageous the use of Hoechst reagent for in vivo detection of these cells.

  Comparison of fresh and hibernated rat ventral mesencephalon cells transplanted in a rat model of Parkinson’s disease.

Karelys de la Cuétara-Bernal, Lázara Castillo-Díaz, Lisis Martínez-Martí, Lisette Blanco-Lezcano,
Nancy Pavón-Fuentes, Juan C. Rosillo- Martí, Yosvany Coro-Grave de Peralta, Alain Y. García-
Centro Internacional de Restauración Neurológica (CIREN) Havana, Cuba
Despite the therapeutic potential of such transplants, there remain practical difficulties for
widespread adoption of this promising therapy. One approach to overcome some of these
constraints is to develop tissue storage procedures, which also have several further advantages. To
evaluate whether hibernation of rat ventral mesencephalon cells influences graft survival and
function in vivo, we transplanted either freshly and prepared or hibernated cells suspension into the
striatum of 6-hydroxydopamine-lesioned rats. Fragments of rat ventral mesencephalon were stored
in hibernation medium at 4°C for 3 and 7 days. The cells suspension was prepared and implanted in
lesioned animals. To monitor graft function amphetamine-induced rotation was measured. After
sacrifice, histological methods were used to compare fresh cell and hibernated cell transplants with
respect to graft survival, differentiation and integration. Hibernated cells were founded to be either
equivalent to fresh cells with respect to rotational correction, graft survival, total graft volume, total
cell number (TH+), neuronal diameter and neuronal area. There was no significant difference
between fresh and hibernated grafts (F(2,28) =2.96 p>0.05 n.s.). There were significant differences
(p<0.05, U Mann Whitney) between neuronal density in fresh and hibernated 7 days grafts, showing
an increase of neuronal density at 7 days of hibernation. In conclusion, these results indicate that it
is feasible to hibernate rat ventral mesencephalon cells for a week prior to transplantation in animal
model of Parkinson‟s disease without a loss of their survival and functionality.

In vitro survival of dopaminergic neurons hibernated for 7 days.

Karelys de la Cuétara-Bernala, Lázara Castillo-Díaza , Lisis Martínez Martíb , Alain Y. García-
  Departamento de Cultivo de Tejido Nervioso, b Departamento de Neuromorfología, CIREN,
Havana, Cuba
The use of fresh tissue in neural transplantation presents considerable logistical difficulties and
limits their clinical applicability. One approach to overcome some of these problems is to develop
tissue storage protocols that did not affect the viability and survival of dopaminergic cells after
transplantation. In this study we examined the influence of hibernation for 7 days on in vitro
survival of mesencephalic tissue compared with fresh tissue. Fragments of rat ventral
mesencephalon were stored in hibernation medium at 4°C for 1, 3, 5 and 7 days. We determined the
TH+ cells in fresh as well as in hibernated cultures. Comparison of hibernated with fresh ventral
mesencephalon cell suspensions showed no significant difference with respect to cell viability. The
morphology of cultured dopaminergic neurons after hibernation was very similar to that of fresh
cells. There was no significant difference between the TH+ immunoreactive cells at 1, 3 and 5 days
of hibernation. The lower survival was observed at 7 day of hibernation. There were significant
differences between the TH+ cells in fresh and hibernated tissue. Despite the significant differences
founded when compared fresh and hibernated tissue, this procedure guaranty the in vitro survival of
TH+ neurons at first 5 days of hibernation. This method could be considered a useful procedure for
conserving neural tissue to be used in clinical transplantation. Moreover, further research is needed
on survival and functionality of hibernated cells after being transplanted into animal models, in
order to evaluate their application in the neurorrestorative therapy.

                           Rat bone marrow stromal cells produces NGF and GDNF

Rocío García a , Jorge Aguiarb , Esteban Albertia , Karelys de la Cuétaraa, Nancy Pavónc, Lázara
Castilloa, Alain García a
  Department. of Neurobiology, International Center for Neurological Restoration, Havana City,
Cuba, bGrowth Factor Department., Center for Genetic Engineering and Biotechnology, Havana
City, Cuba, cDepartment. of Neuroinmunochemestry, International Center for Neurological
Restoration, Havana City, Cuba.
Bone marrow stromal cells (BMSC) have attracted interest through their possible use for cell
therapy in neurological diseases. Recent reports demonstrated that these cells are able to migrate
and have potential for neuronal differentiation after transplantation into brain parenchyma. The
objective of this work was determine whether rat BMSC express NGF and GDNF, in order to study
its potential application for treatment of neurodegenerative diseases. BMSC were harvested from
male rats and cultured in DMEM supplemented with 20 % fetal bovine serum. At passage 6 the
total RNA was isolated using TriZol reactive. RT-PCR reactions to evaluate the expression of NGF
and GDNF using specific primers were carried out. The PCR reaction products were run in an
agarose gel and compared with DNA molecular weight markers. Ours results indicate that rat
BMSC have potential to produce NGF and GDNF. The production of NGF by these cells was
reported in the literature; nevertheless, we have not found any report in favor of GDNF production
by rat BMSC. Whether rat BMSC could produce CNTF, IGF-1 and BDNF is currently under
                           Bone Marrow stromal cells cultured in N2-supplemented medium

Lazara Castillo- Diaz, Karelys de la Cuétara-Bernal, Alain García-Varona
Centro Internacional de Restauración Neurológica , Cuba
Generation of brain cells from adult bone marrow stromal cells (MSCs) has evidenced their great
plasticity and potential usefulness for cell therapy in the nervous system. Most of the culture system
for in vitro maintenance and neural differentiation of MSCs use synthetic media supplemented
with 10 or 20% fetal bovine serum. Serum, however, is comprised of unknown quantities of
undefined substances, which could interfere the effect of exogenous substances on neural
differentiation of MSCs. Here we describe survival of MSCs cultured in culture conditions where
serum was reduced at 0.5 and 1 % using Bottenstein and Sato´s N2 formula (1979) and poly-L-
lysine (PLL)-coated substrate. Survival of MSCs cultured in N2 supplement was reduced at about
40% of that observed in 10% FBS containing medium. Under these conditions cell morphology was
also affected. However, when N2 containing medium was supplemented with FBS at 0.5 or 1% a
significant increase of survival with respect to that observed in N2- supplemented cultures was
observed. Cells seeded on PLL -coated surface increased their survival by contrast with their
homologous cultures seeded on uncoated surface. This culture system, which combines N2 formula
with FBS 1% and PLL-coated surface, is useful for the maintenance of MSCs. We speculate that
these conditions could offer advantages for the study of neural differentiation of these cells.
Currently, experiments aimed to evaluate the effect of EGF and FGF on MSCs using this culture
system are being carried out.

               Transplantation of cultured fetal human brain cells into injured spinal cord of adult rats.

Maria Aleksandrova a, Oleg Podgornya , Rimma Poltavtseva a, Aleksandr Revishchinb , Maria Mareyd ,
Dmitry Karpenkoc , Georgiy Stepanovc , Leonid Korochkinc , Gennadiy Sukhikhd .
  Koltsov Institute of Developmental Biology, Russia, b Institute of Gene Biology, Russia, cCentral
Institute of Traumatology and Orthopedy, Russia, dCenter of Obstetrics and Perinatology, Russia
We examined the survival ability of in vitro-expanded human neural stem/progenitor cells
transplanted into damaged spinal cord of adult rats. Experimental group was undergone mechanical
injury at the spinal cord level T-8-9 and bilateral injection of 6 ml suspension (300000 cells/ml)
fetal cells expanded in culture during 14 days and control group was undergone damage only.
Grafts were investigated after 7, 15, 30 and 60 days following the surgery by histology and
immunohistochemistry. The control animals had damage zone with necrosis and forming cysts and
glial scar. In experimental group human nuclei-immunopositive grafted cells located alone or by
groups and migrated along white matter fiber and blood capillaries. Double immunostaining for
nestin and human nuclei revealed that part of transplanted cells maintained non-differential
phenotype. Double immunostaining for human nuclei and GFAP and immunostaining for β-III-
tubulin revealed glial and neuronal differentiation. In this group we did not observe forming cysts.
There was glial reaction in the damage zone, but glial scar was absent. Thus, our results show that
human neural stem/progenitor cell grafted into damaged adult rat spinal cord successful survive and
positive influence for posttraumatic processes.

           9-O-acetyl ganglioside is expressed by prolif erating cells in the subventricular zone of adult rats

Ana C. M. Leão, Marcelo F. Santiago and Rosalia Mendez-Otero
Laboratório de Neurobiologia Celular e Molecular, Instituto de Biofísica Calos Chagas
Filho, Centro de Ciências de Saúde, Universidade Federal do Rio de Janeiro and
Millennium Institute for Tissue Bioengineering, Brazil.
9-O-acetyl GD3 ganglioside is important in migration and neuritogenesis during the development of
the nervous system and remains expressed in adult brain SVZ, described as a niche of neurogenesis
and from where neural stem cells have been isolated. In this work we are trying to characterize SVZ
cells by the expression of known markers and 9-O-acGD3. To identify proliferating cells in the
CNS, adult rats were treated with BrdU. The brains were sliced or the tissue was dissociated into
single cells. After immunocytochemistry we were able to observe BrdU incorporation and 9-O-
acGD3 expression in situ and in single cells and that both are present preferentially on the same
regions of the lateral ventricles. By confocal microscopy, we could detect colocalization of these
antigens. To characterize 9-O-acGD3 positive cells, we performed immunocytochemistry reactions
for antigens present in SVZ cells, like GFAP, nestin and PSA-NCAM and for the ganglioside. By
confocal microscopy, some 9-O-acGD3 positive cells were also positive for those antigens. In this
work, we could observe that the expression of 9-O-acGD3 occurs at the same regions of high cell
proliferation in adult brain. The colocalization of the ganglioside and BrdU shows that it is
expressed by proliferating cells in the SVZ. The co-expression of 9-O-acGD3 and GFAP or nestin
suggests that it could be present in the cells described as neural stem in the adult brain and may
remain expressed by neuroblasts as some was positive for PSA-NCAM. At the moment, we are
quantifying all those populations by flow citometry.

                 Effect of sw im stress on 5-HT1A receptor density in different mouse brain regions

Alfredo Brionesa, Luisa Rocha b , Joel Lomelía , Ofir Picazoa.
  Escuela Superior de Medicina del I.P.N; b Departamento de Farmacobiología, CINVESTAV,
México D.F, Mexico.
Several stressful agents induce synthesis and expression of 5-HT1A receptor; for example, forced
swimming-induced stress produces changes in RNAm synthesis, as well as modifications in 5-
HT1A binding in the hippocampus rat. In the present work we have studied the effect of an acute
swim stress session on 5-HT1A receptors in amygdala, dorsal and ventral raphe nuclei,
hippocampus, hypothalamus and thalamus. Swiss Webster male mice were used. The stressful
session consisted on putting each mouse into a cylinder filled with water at 25ºC. Mice were
divided in two groups; one of them was forced to swim for 15 min and 24 hr after, sacrificed by
cervical dislocation. A non-stressed second group was used as a control. The brains of all animals
were removed and immediately frozen. Slices measuring 20 µm were obtained in a -20oC cryostat.
Quantitative autoradiography experiments were carried out labeling the 5-HT1A receptor of the
above mentioned regions with [3H]8-OH-DPAT. An increase in density of 5-HT1A receptors in
hypothalamus, thalamus and amygdala was observed in stressed animals, accompanied by a
diminution of this subtype receptor in raphe nuclei and hippocampus. These findings can be
interpreted as a compensatory mechanism of the diminution in the serotonin levels observed after
stressing. Furthermore, it has been reported that stress induces an increase in corticosteroids brain
levels, which diminishes the synthesis of 5-HT1A receptor in hippocampus rat. Taken together,
these evidences show that some aversive agents such as forced swimming-induced stress are able to
induce synaptic changes in the central nervous system. This work was supported by CGPI and

                  Pinacidil reduces neuropathic pain by activation of different potassium channels

Teresa Mixcoatl-Zecuatl, Vinicio Granados-Soto
Departamento de Farmacobiología, CINVESTAV-IPN, México, DF., MEXICO.
Previous studies have shown that peripheral administration of pinacidil reduces carragenin- and
prostaglandin E2-induced mechanical hyperalgesia in the rat. Besides, spinal or supraspinal
administration of pinacidil produces antinociception in mice. It is believed that pinacidil-induced
antinociception is produced only by activation of ATP-sensitive K+ channels. However, it is likely
that other K+ channels could participate in its antiallodynic effect. In this work we assessed the
effect of different K+ channel blockers on pinacidil-induced antiallodynia. L5 and L6 left spinal
nerves were ligated to female Wistar rats and fifteen days later animals were anesthetized to insert a
spinal catheter. Five days after surgery, withdrawal threshold was assessed (with von Frey
filaments) as a measure of allodynia. Reduction of withdrawal threshold was considered as the
antiallodynic effect. Spinal administration of pinacidil (1-10 µg) reduced withdrawal threshold in a
dose-dependent manner in neuropathic rats. Glibenclamide (50 µg, ATP-sensitive K+ channel
blocker), apamin (3 ng) and charybdotoxin (1 ng, small- and large-conductance Ca2+-activated K+
channel blocker, respectively), but not margatoxin (10 ng, voltage-gated K+ channel blocker),
partially reversed spinal pinacidil-induced antiallodynia. K+ channel blockers, by themselves, were
not able to modify neuropathic pain. In conclusion, data suggest that the antiallodynic effect of
pinacidil could be produced by opening of ATP-sensitive, small- and large-conductance Ca2+-
activated, but not voltage-gated, K+ channels. In addition, K+ channel openers could be useful to
treat neuropathic pain in humans.

          Synergistic interaction between spinal gabapentin and oral B vitamins in a neuropathic pain model.

H.I. Rocha-Gonzáleza , G. Reyes-Garcíab , R. Medina-Santillánb and V. Granados-Sotoa.
  Departmento de Farmacobiología and bSección de Estudios de Posgrado e Investigación, ESM-
IPN, México, D.F. CINVESTAV-IPN, México, D.F.
Experiments in animals have shown that vitamins B1 (thiamin), B6 (pyridoxine) and B12
(cyanocobalamin) and their combination have antinociceptive activity against chemical- and heat-
induced pain. The mixture of B vitamins is often used in neuropathic pain, however, there is no
evidence about the efficacy of this preparation in this kind of pain. Therefore, the purpose of this
study was to assess the analgesic activity of B vitamins (B1, B6 and B12), gabapentin and the co-
administration of gabapentin and B vitamins in a neuropathic pain model. Rats were submitted to
the ligation of the left L5 and L6 spinal nerves. Tactile allodynia was assessed daily by von Frey
testing on the injured paw. B vitamins (75-600 mg/kg, p.o.) and gabapentin (25-200 µg, i.t.)
produced a dose-dependent reduction of tactile allodynia. However, the antiallodynic effect of
gabapentin was significantly higher than that produced by B vitamins. The co-administration of
gabapentin and B vitamins also produced a dose-dependent reduction in allodynia. Isobolographic
analyses revealed a synergistic interaction between spinal gabapentin and oral B vitamins,
suggesting that this combination could be useful to relive neuropathic pain in humans.

                         Participation of peripheral and spinal cox-1 in the inflammatory pain.

J.E. Torres-Lópeza,b and V. Granados-Sotob .
  DACS-UJAT, Villahermosa, Tabasco México, bDepto. De Farmacobiología CINVESTAV-INP,
Formalin produce a biphasic nocifensive response of the injected paw. Whilst peripheral
inflammation following formalin injection is evident. Nonsteroidal anti-inflammatory drugs
(NSAIDs), when administered systemically or intrathecally, fail to affect the first phase of the
formalin response, but attenuate the second phase. It is not clear whether this is peripherally or
centrally-mediated. The aim of the present study was to improve the understanding the contribution
of peripheral and spinal ciclooxigenases 1 and 2 (COX-1 and COX-2) to the development of
inflammatory pain. Female Wistar rats aged 6-8 weeks were used in this study. All experiments
followed the IASP guidelines for investigation of pain in animals. 50 µl, 1% formalin was injected
into the dorsal surface of right hind paw. Local injection of the selective COX-1 inhibitor,
resveratrol and the non-selective COX inhibitor, diclofenac produced antinociception, while the
selective COX-2 inhibitor celecoxib was ineffective. Inthrathecal injection of COX-1 or COX-2
inhibitors produced antinociception as well as the non-selective COX inhibitor. In summary, these
data suggest that the participation of COX-1 rather than COX-2 is important at peripheral level,
whilst, both COX participate at spinal level. The analgesic effect of conventional NSAIDs is not
accounted for solely by COX-2 inhibition and requires the inhibition of both COX-1 y COX-2.

B vitamins increase the anti-allodynic effect of dexamethasone in neurophatic rats.

Nadia L. Caram-Salasa, Gerardo Reyes-Garcíab , Roberto Medina-Santillanb , and Vinicio Granados-
  Departamento de Farmacobiología, CINVESTAV-IPN and bSección de Estudios de Posgrado e
Investigación, Escuela Superior de Medicina-IPN, México, D.F., Mexico.
In this work we evaluated the antiallodynic effect of dexamethasone and B vitamins in a
neuropathic pain model in female Wistar rats (Chung Model). Neuropathy was produced by tight
ligation of L5 and L6 left spinal nerves. Twelve days after surgery, the withdrawal threshold was
assessed (with von Frey filaments) as a measure of allodynia. Reduction of withdrawal threshold
was considered as an antiallodynic effect. Subcutaneous administration of dexamethasone (4-32
mg/kg), vitamin B1 (75-600 mg/kg) and vitamin B12 (0.75-12 mg/kg), but not vitamin B6 (75-600
mg/kg), significantly reduced in a dose-dependent manner withdrawal threshold in neuropathic rats.
Doses necessary to produce a 30% of reduction of allodynia (ED30) were 5.41 ± 1.2, 178.4 ± 20.1
and 1.26 ± 0.0 mg/kg for dexamethasone, vitamin B1 and vitamin B12, respectively. In addition,
co-administration of dexamethasone and either vitamin B1 or B12 reduced in a dose-dependent
manner mechanical allodynia. Experimental ED30 for the dexamethasone-vitamin B1 and
dexamethasone-vitamin B12 combinations were (50.1 ± 3.4 and 1.8 ± 0.0 mg/kg, respectively)
significantly lower than theoretical ED30 (91.9 ± 10.1 and 3.7 ± 0.6 mg/kg, respectively), thus
suggesting a functional synergism between these drugs to reduce allodynia. In conclusion, our
results suggest that these combinations could be useful to treat neuropathic pain in humans.

Abstract not available


  Neural plasticity in the MPTP-treated parkinsonian monkey: dissociated responses of cognitive and motor performances

Sebastián J. Lipina, Jorge A. Colombo.
Unidad de Neurobiología Aplicada (UNA)(CEMIC-CONICET), Buenos Aires, Argentina
Evidence of dissociation in cognitive and motor performances was found in three groups of adult
Cebus apella monkeys: females (Group1: N=3), males (Group2: N=4; Group3: N=3). A spatial
delayed response task (SDR) was administered at A (pre-MPTP), B (post-MPTP) and C (post-
surgery) stages. Performance was recorded until reaching the maximum possible delay (<1, 2, 4 , 6,
8, 10 seconds). Before B all groups received MPTP hydrochloride (0.5 mg/kg i.m. per day; total
dose: 21 mg). After B astroglial or "sham" transplants into the neostriatum were performed [Group
1: unilateral; Group 2: bilateral (N=2) and "sham" (N=2); Group 3 with no surgical intervention and
two series of testing in A]. All monkeys performed efficiently in SDR with delays of up to 8-10
seconds in A. Non spontaneous motor recovery was observed [6 to 10 points in Smith et al. (1993)
scale of parkinsonism]. Efficiency was severely altered in Groups 1 and 2 in B. The "sham"
individuals did not modify this performance. Animals from Groups 1 and 2 receiving transplants
improved their performance nearly reaching the levels of delay observed in A. No statistical
differences were observed between groups in the number of sessions and trials received in A.
Mesencephalic sections showed significant reduction of TH-immunoreactivity in all MPTP-treated
cases. Residual plasticity in system(s) subserving cognitive performances was apparent in MPTP-
treated monkeys expressing a full fledged motor parkinsonism. Results encourage the possibility of
cognitive improvement in clinical parkinsonism, in which a combination of interventions could be
applied. Acknowledgements. Emprendimientos San Jorge, Chevron-Texaco, Fundación Conectar,
FONCYT (PICT # 01-03465), Fundación René Barón.

               Neurogenesis and gliogenesis in the spinal cord of juvenile turtles : A multidisciplinary study

Anabel Fernándezab , Milka Radmilovichc , Raul Russob , Cecilia Realia , Omar Trujillo-Cenózab
  Lab. Neuroanatomía Comparada Instituto de Investigaciones Biológicas Clemente Estable,
Montevideo-Uruguay, b Universidad de la Republica Facultad de Ciencias, Uruguay cDpto.
Embriología e Histología , Facultad de Medicina. Uruguay
Since the 60' it has been demonstrated postnatal neurogenesis at several brain regions of vertebrates.
However few are known about spinal cord postnatal neurogenesis. Studies in turtles have provided
novel evidences of postnatal neurogenesis at the spinal cord level. We have recently demonstrated
by the use of " in vivo" BrdU injections that proliferating neural cells are present both in the gray
and white matter along the spinal cord. Larger densities of BrdU- labeled- nuclei occurred in the
so-called central gelatinosa (CG).Different methods have been applied to know the cellular
composition of CG. Two morphological types can be recognized by mean of Golgi technique that
could correspond to different stages of differentiation of neuronal or glial lineages. Electron
microscopy studies demonstrated synaptic contacts on putative Golgi-stained neuroblast.
Immunohistochemical labeling allowed us to clearly confirm that S-100 positive cells (early glial
marker) and Huc/d positive cells (early neuronal marker) are intimately associated in the ependymal
epithelium of spinal cord. Double-labeling experiments indicated that BrdU labeled cells expressed
S-100 in animals fixed 1-hour post injection, however the BrdU labeled cells only expressed Huc/d
30 to 60 days after. Double labeling immunocytochemical studies revealed GABAergic and
serononinergic botouns making contact with Huc/d positive somas. Whole cell patch clamp
recording from CG showed three different electrophysiological phenotypes: 1) cells without signs
of membrane active properties (putative glial or stem cells); 2) cells with high input resistance and
outward rectification that did not generate spikes (putative neuroblast) and 3) cells that generate
action potential (neurons).

Epidemilogy, accelerators and risk factors in AD

  The primary pathogenetic role of vascular hypoperfusion, mitochondria failure and oxidative stress in Alzheimer disease

Gjumrakch Alieva , George Perrya, Jiankang Liubc , Mark E. Obrenovicha, Mark A. Smitha, Bruce N.
Amesb,c and Jack C. de la Torre a
  Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA and bDepartment of
Molecular Cell Biology University of California, Berkeley, CA & cChildren Hospital Oakland
Research Institute, Oakland, CA, USA
Vascular insufficiency, with concomitant chronic hypoxia/hypoperfusion, may play a key part in the
initiation of Alzheimer disease (AD). However, the role of vascular abnormalities and their
participation as pathogenic factors during the development and maturation of AD is controversial.
Adding to this complexity are the mechanisms by which reactive oxygen species (ROS) participate
in the development of vascular insufficiency-induced chronic hypoxia/hypoperfusion, which also
may play an important role in the pathogenesis of AD. We studied the cellular and subcellular
features of vascular lesions and mitochondria in brain vascular wall cells from human AD brain
biopsies, human short postmortem brain tissues, yeast artificial chromosome (YAC) and
C57B6/SJL transgenic positive (Tg+) mice overexpressing amyloid beta precursor protein (AbPP)
and in aged rats given selective mitochondrial antioxidants (Lipoic Acid and ALCAIR). In situ
hybridization, using mitochondrial DNA (mtDNA) probes for human wild type, 5kb deleted and
mouse mtDNA, was performed in conjunction with immunocytochemistry using antibodies against
AbPP, 8-hydroxyguanosine (8OHG) and cytochrome c oxidase (COX). We found a higher degree
of amyloid deposition in the cerebrovascular walls in the human AD cases, YAC and C57B6/SJL
Tg (+) mice when compared to aged-matched controls. In addition, vessels with more severe
lesions showed immunopositive staining for AbPP and possessed large, lipid-laden vacuoles in the
cytoplasm of endothelial cells. Significantly more mitochondrial abnormalities were seen in
microvessels, where lesions occurred, in human AD specimens, YAC and C57B6/SJL Tg (+) mice
and old aged rats without treatment. However, the animals that received treatment showed an
absence of any cellular or subcellular abnormality in brain cellular compartments. In situ
hybridization, using wild type and chimera (recognizing mtDNA with the 5 kB deletion) mtDNA
probes, revealed positive signals in the damaged mitochondria from the vascular endothelium and in
perivascular cells of lesioned microvessels in human AD, YAC and C57B6/SJL Tg (+) mouse
tissues. This damage was proximal to regions of large amyloid deposition. Interestingly, these
features were absent in undamaged regions of human AD tissues, YAC and C57B6/SJL Tg (+)
mouse tissues and in aged-matched control subjects. In addition, vessels with atherosclerotic
lesions revealed endothelium and perivascular cells, which stained positively and in clusters when
probed with wild and deleted mtDNA probes. These mtDNA deletions were associated with
increased amounts of immunoreactive AbPP, 8OHG and COX in the same cellular and subcellular
compartments. The mtDNA deletion and expression of oxidative stress markers in vascular wall
cells of the AD brain indicate that energy deficiency and oxidative stress, in AD, selectively affects
the brain vascular tree and whole populations of vulnerable neurons. We hypothesize that vascular
abnormalities, especially mitochondrial lesions and increased oxidative stress, in the cellular and
subcellular compartment are responsible for regional blood flow alterations. Further, this alteration
can lead to blood brain barrier failure and breakage during the development of AD. We theorize
that by using selective pharmacological agents to block the underlying oxidative stress stimuli and
damage that it will be possible to normalize the actions of the endogenous antioxidant systems in
vascular wall cells. We theorize also that similar stimuli-blocking intervention strategies will help
to normalize the antioxidant systems in AD patients and in aged individuals. Future studies, which
examine the importance of mitochondrial pathophysiology in different cellular compartments may
provide important insight not only into neurodegenerative and/or cerebrovascular disease
pathobiology but may provide targets for treatment approaches in these conditions.

                          The Cuban Dementia and Alzheimer’s Study Playa (EDAP).

LLibre Rodríguez, Juan de Jesús; Fernández García, Yuriem; López Medina, Ana M; Otero Esteve
Marta; Marcheco Teruel Beatriz; Contreras Hernández, Nereyda; Alvarez Rodríguez, José; Collado
Fernández, Hector; Bayarre Vea, Hector ; Guerra Hernández Milagros; Ortiz Calderón Zeylin.
University of Medical Sciences, Habana, Cuba
Background and Objectives: Cuba is a developing country, with a health profile similar to that of
developed countries. With a population of 12 million people Cuba will become the second oldest
country in Latin America by the year 2020, when those aged 60 years and over will account for
25% of the population. The Cuban Dementia and Alzheimer‟s Study Playa is a multicenter,
population-based study with a sample of 18 351 people over the 65 years. It constitutes one of the
most extensive prevalence studies in Cuba and Latin American. The core objectives were to know
the prevalence of Cognitive disorders, the dementia syndrome and its different causes in people
over 65 in Playa municipality, Havana City, as well as risk factors including the genetic factors and
the impact that these dementia syndromes cause in families. Methodology: A door to door study
was carried out, in which 18 351 people over 65 were studied by means of the application of the
Mini Mental State Examination (MMSE), the Clinical Dementia Rating Scale (CDR) and an
interview based on risk factors. Different criteria such as: the DSM-IV, the NINCDS-ADRDA, the
NINCDS-AIREN and others established for specific dementias were used in the diagnosis of
dementia syndrome. Conclusions: The prevalence of dementia syndrome was 9,25/100 people over
65. Alzheimer‟s disease followed by vascular dementia were the most frequent causes.
Stroke, Parkinson disease, advanced age, occupation, family history of dementia, depression, the
antecedent of cranial trauma, and the low school level were the factors that mostly influenced on the
appearance of the dementia syndrome.

A rat model of MCI upregulates hippocampal nitric oxide and precedes memory loss and Ab 1-40 accumulation after chronic
                                                   brain hypoperfusion

J.C. de la Torre a M.R. Emmerlingb G.B. Stefanoc G. Alieva
  Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, USA, b Pfizer Global
Research, Ann Arbor, Michigan, USA, cState University of New York, Neuroscience Research
Institute, New York, USA
Chronic brain hypoperfusion (CBH) using permanent occlusion of both common carotid arteries in
an aging rat model, has been shown by us to mimic human mild cognitive impairment (MCI), an
acknowledged transition stage that often converts to Alzheimer‟s disease. Purpose: An aging rat
model was used to determine whether hippocampal nitric oxide (NO) is abnormally expressed
following CBH for 2 or 8 weeks. At each time point, spatial memory, hippocampal A$ 1-40/1-42
and amperometric measures of constitutive NO were measured. Results: Two weeks after CBH, NO
hippocampal levels were upregulated nearly 4-fold when compared to non-occluded rats but no
alteration in spatial memory or A$ products were observed at this time point. By contrast, NO
concentration had returned to control levels by 8 weeks but spatial memory was significantly
impaired and A$ 1-40 (but not A$ 1-42) had increased in the CBH group when compared to control
non-CBH rats. Since changes in shear stress are known to upregulate eNOS but generally not
nNOS, these results suggest that shear stress induced by CBH hyperactivated vascular NO derived
from eNOS in the first 2 weeks as a reaction by the capillary endothelium to maintain homeostasis
of local cerebral blood flow. The return of vascular NO to basal levels after 2 weeks of CBH may
have triggered metabolic changes within hippocampal cells resulting in spatial memory impairment
and accumulation of A$ 1-40 peptide. These findings support the notion that CBH in aging rats
mimics human MCI and may explain, at least in part, some of the molecular events that can trigger
memory impairment at a pre-clinical stage to Alzheimer‟s disease.

                                    Role of reactiv e oxygen species in brain ageing

Gregorio Martínez-Sánchez, Eduardo Candelario Jalil and Olga Sonia León-Fernández
Centre for Research and Biological Evaluations, Institute of Pharmacy and Food Sciences,
Havana University, Cuba.
There are more than 300 theories to explain the aging phenomenon. Many of them originate from
the study of changes that accumulate with time. Among all the theories, the free radical theory of
aging, postulated first by Harman, is the most popular and widely tested, and is based on the
chemical nature and ubiquitous presence of free radicals. Tight linkage between aging and oxidative
stress is indicated by the observations that reactive oxygen species generated under various
conditions of oxidative stress are able to oxidize nucleic acids, proteins, and lipids and that aging is
associated with the accumulation of oxidized forms of cellular constituents, and also by the fact that
there is an inverse relationship between the maximum life span of organisms and the age-related
accumulation of oxidative damage. Nevertheless, validity of the oxidative stress hypothesis of aging
is questioned by (i) the failure to establish a causal relationship between aging and oxidative
damage and (ii) lack of a consistent correlation between the accumulation of oxidative damage and
aging. The present discussion is focused on the complexity of the aging process and suggests that
discrepancies between various studies in this area are likely due to the fact that aging is not a single
process and that the lack of consistent experimental results is partly explained by individual
variations. Even so, there is overwhelming support for a dominant role of oxidative stress in the
aging of some individuals.

                         Aluminum-triggered structural modifications and aggregation of b-amyloid

Paolo Zatta and Fernanda Ricchelli
CNR-Institute for Biomedical Technologies, “Metalloproteins” Unit, Department of Biology
of the University of Padova, Padova, Italy
Amyloid b-peptides, as insoluble fibril deposits, is the major component of the senile plaques that
characterize Alzheimer‟s disease brain [Behl (1999) Progress Neurobiology 57: 301] The
amyloid (Ab) fragments 1-40 and 1-42 have been studied at physiological pH, with the aim to get
clues into the modality of metal binding. As probes of conformation we used the variations of the
intrinsic tyrosine (Tyr) fluorescence and the fluorescence quenching by acrylamide. Ca2+ and
Mn2+ did not affect the amyloid conformation. Cu2+, Zn2+, though binding to the same
hydrophilic N-terminal domain [Miura et al., (2000) Biochemistry 39: 7024] caused, respectively, a
burial and a high degree of exposure of Tyr residues. The most relevant effects on the peptides
conformation were found upon binding of Al3. Amyloids 1-40 and 1-42 were also tested for their
hydrophobicity and aggregation properties by following the increase of the fluorescence intensity of
8-anilino-1-naphthalene sulfonic acid (ANS) and Thioflavin-T (ThT), respectively. The surface
hydrophobicity and the assembly process were more pronounced for the 1-42 peptide, as compared
to 1-40, and Al3+ was the most efficient cation in inducing aggregation. Electron microscopy
experiments ascertained that only Zn2+ and Al3+-induced Ab1-42 aggregates led to formation of
fibrils with Al3+ promoting the process at much lower concentration than Zn2+. The
conformational and aggregational effects of Al3+ were specifically abolished in the presence of
desferoxamine mesylate, a trivalent metal ion chelator used in therapy to treat toxic Fe3+ and Al3+
overload conditions.
   Excitotoxicity and oxidative stress induce activ ation of cell-cycle proteins and DNA repair systems in primary neurons

Maurizio Memo
Department of Biomedical Sciences and Biotechnologies, University of Brescia Medical
School, Brescia, Italy
The possible link between excitotoxicity, oxidative stress and the induction of cell cycle-related
factors has been matter of extensive investigation during the last 5-10 years and it is now supported
by several in vivo and in vitro data offering significant answers in the AD ethiopathogenic
mechanisms. In particular, in vitro studies have elucidated the role of p53 in apoptosis induced by
excitatory amino acids (EAA). Exposure of primary cultures of cerebellar granule neurons to
neurotoxic concentrations of glutamate was found to induce a significant, short-lasting increase of
p53 expression (Uberti et al. 1998; Grilli and Memo, 1999). Transcriptional activity of the over-
expressed p53 was demonstrated by an increased p53 DNA binding activity and the concomitant
enhancement of waf1/cip1 kinase inhibitor p21. The direct correlation between p53 expression and
glutamate-induced apoptosis in cerebellar granule cells, has been suggested by the finding that
under the same experimental conditions, a p53 specific antisense oligonucleotide prevented both
glutamate-induced p53 expression and apoptosis. We have recently further extended this concept by
demonstrating the induction of p53 and Gadd45 in primary cortical neurons exposed to NMDA.
The mechanism(s) by which glutamate induces activation of cell cycle related factors and apoptosis
is not clear. We hypothesize that over-stimulation of ionotropic glutamate receptors, possibly by
generating oxygen free radicals (ROS), may induce DNA damage. A single and/or double-strand
DNA breaks caused by excitotoxicity has indeed been suggested by numerous studies (Didier et al.,
1996, Liu et al., 1996, Chen et al., 1997). In summary, we suggest that, similarly to proliferating
cells, postmitotic neurons may respond to (EAA-induced) DNA damage by activating a cascade of
events involving DNA damage sensors and repairing factors. In this regard, we have found that the
expression of the DNA mismatch repair factor MSH2, which is a p53 downstream gene functioning
in recognition and repair of a several types of DNA damage, is significantly increased in primary
cultures of cerebellar granule cells after glutamate exposure as well as in CA3 hippocampal neurons
after kainate treatment.

Challenging views of AD therapy I

 Current status and future development of pharmacological treatment of AD: Strategies towards dis ease modifying therapy

M. Windisch, B. Hutter-Paier, E. Schreiner, R. Wronski
JSW-Research GmbH, Graz, Austria
Most approved drugs for treatment of mild to moderately severe Alzheimer‟s disease (AD) are
choline-esterase inhibitors, showing modest but reproducible improvement of cognitive
performance, global function, and activities of daily living. Their effect size is similar, but they
differ in the side effect profile. Expectations about long term effects were not fulfilled. The new
choline-esterase inhibitors Phenserine induces decrease of APP expression by direct interaction
with the 5‟UTR on translational level, lowering Aß 1-42 and Aß 1-40. The ongoing clinical
program is designed to investigate, if this results in fast cognitive improvement and slowing of
disease progression. Memantine modulating NMDA signalling has been recently approved by FDA
for treatment of severe AD patients. Targeting amyloid metabolism, new compounds to block
activity of gamma- or beta-secretase are under development. The enthusiasm about the anti-amyloid
vaccination cooled down after occurrence of severe side effects in the phase II clinical study.
Approaches for safer vaccination are under investigation, stimulated by reports about cognitive
effects in the initial clinical trial. Passive immunisation is explored as safe alternative. Cholesterol
lowering and modulating drugs are addressing Aß-production and aggregation. Recent drug
developments are investigating inhibitors of GSK-3ß to prevent tau hyperphosphorylation.
Substances interfering with formation of paired helical filaments and stimulators of phosphatases
are also discussed. These developments are promising because cytoskeletal pathology shows good
correlation to disease severity. Enormous efforts of basic research and industrial drug development
give raise to the hope that in the near future efficacious therapy of AD might be available.

                               Neural stem cell surviv al is compromised in the aged brain

Daniel A. Peterson, Letia D. Peterson
Laboratory of Neural Repair and Neurogenesis, Department of Neuroscience, The
Chicago Medical School, North Chicago, IL 60064, USA
Most research investigating the competence of neural stem cells to differentiate and the capacity of
the brain to support their survival and differentiation has been conducted in neonatal or young adult
brain. However most patients likely to benefit from structural repair by neural stem cells require
therapy for stroke or neurodegenerative disease would be in the sixth decade of life or older. Little
is known of the capacity of the aged brain to support either endogenous or grafted stem cells. We
examined the rate of neurogenesis by confocal stereology and investigated the ability of this region
to support the survival and differentiation of grafted young neural progenitor cells. Aging
profoundly impairs neurogenesis in the olfactory bulb with a 70% decline in new cells. Over 90%
of newly generated cells differentiate into mature neurons in both young and aged animals
suggesting that differentiation signals remain intact. We grafted neural progenitor cells derived from
young adult animals into the aged bulb and hippocampus to determine if these regions could
support their differentiation. In contrast to robust neuronal differentiation in young adult recipients,
few cells survived in the aged brain and differentiated into astrocytes. These results suggest that it is
not only the competence of the stem cell, but the environment in which that cell is placed that must
be considered for the development of structural brain repair strategies. The aged brain may require
environmental enhancement before use of neural stem cells for brain repair will be possible.
Supported by: NIH-AG20047.

   Restoring complex circuits and functional recovery with cell replacement and environmental manipulation in aging and
                                               disease: A unifying hypothesis

C.I. Fernándeza, J. Collazoa , E. Albertib , M.E. Gonzálezc , M.R. Castellanosb , , L. Lorigadosc , Y.
Bauzac , L. Martínezb J.C. Rosillob
  Biomodels Lab; b Molecular Biology Dpt; cNeuroimmunochemistry Dpt, Basic Division . Intl Ctr
Neurological Restoration (CIREN) Havana City, Cuba
Neurodegenerative diseases, including Parkinson's disease and Alzheimer‟s disease exhibit a
selective loss/dystrophy of specific subsets of neuronal populations whose underlying causes are not
clear but they are key features to the impaired condition. Over most of the past century, it was
thought that the adult brain was completely incapable of generating new neurons. New research
showing that (i) neurogenesis is not restricted to embryonic development, but normally also occurs
in limited regions of the adult mammalian brain (ii) that there are significant numbers of
multipotent neural precursors in many parts of the adult mammalian brain (iii) that it is possible to
induce functional recovery even in the aged brain, via manipulation of endogenous multipotent
precursors in situ with complex stimulus i.e. housing environment complexity and; (iv) that non
neural stem cells can survive and differentiate to neurons after grafting. Results from
motor/cognitive impaired aged rats as recipient of bone marrow stem cells (BMSCs) grafting and/or
long term housing in complex environment in relation to biochemical, functional and behavioral
concerns (Submitted Ann NY Acad. Sci). Our hypothesis attempts to explain, at least in part, the
observed results after two different neurorestoration modalities evidencing that age, oxidative
damage, and altered neuroimmunotrophic signaling contribute to the age-associated functional
impairments which can be reversed after direct/indirect manipulation of affected neuronal
populations, demonstrating that the aged brain still has appreciable plasticity in terms of functional
recovery. The hypothesis contribute to novel concepts and programs in prevention/reduction both,
incidence/severity and outcome of age-associated neurodegenerative

                  Neuroprotection of adult human sensory neurons against prolonged anoxia and trauma

Ivan Sosaa, Onix Reyesb , and Damien P. Kufflerc
  Section of Neurosurgery, b Dept. of Orthopedic Surgery, cInstitute of Neurobiology, Medical
Sciences Campus, University of Puerto Rico, San Juan PR.
CNS injury due to trauma, anoxia, and disease leads to unpredictable and unpreventable
neurological deficits. Ischemia and trauma kill neurons immediately, while over the subsequent 48
hours secondary causes related to the trauma and ischemia kill an even greater number of neurons.
To minimize ischemia/trauma-induced immediate and long-term neurological losses, the number of
neurons killed during ischemia and reperfusion must be reduced. Clinical attempts to reduce neuron
death have focused on decreasing the energy requirements of spinal cord neurons using protective
agents such as hypothermia, barbiturates, and antioxidants. However, none are so successful as to
become the standard of care. Work on animal and in vitro models have found that alkalinization,
calcium channel blockers, and NMDA receptor antagonists also provide neuroprotection. But, most
neuroprotective procedures involve only the use of one such agent and still many neurons die. In
experiments on isolated intact adult human DRG we found combinations of neuroprotective
methods that increase the yield of viable neurons through prolonged ischemia and glutamate insult
by more than a 500 fold. The primary neuroprotectors are hypothermia (20oC) and alkalinization
(pH 9.3), although together with sodium channel blockers and NMDA receptor blockers
neuroprotection is enhanced. Currently we are studying the influences of additional agents,
including antioxidants and neurotrophic factors, for their ability to further enhance neuroprtection of
adult human neurons, and will begin testing these combinations for their efficacy on the adult swine
spinal cord model. We believe some of these combinations of agents will also be effective in
assisting in recovery from various neurological diseases. Subsequently, successful methods will be
tested clinically.

Zn2+ dyshomeostasis and neuronal injury

Stefano Sensi
Dept. of Neurology, University of California-Irivine, Irvine., USA, Dept. of Neurology,
University “G. d’Annunzio”, Chieti, Italy
Zn2+ is potently neurotoxic “in vitro”and “in vivo” trans-synaptic movement of Zn2+ from pre- to
post-synaptic neurons contributes to ischemic neural injury. Zn2+ can enter neurons through
NMDA channels, voltage sensitive calcium channels (VSCC), and AMPA/kainate channels (Ca -
A/K channels). Mechanisms by which Zn2+ exerts its potent neurotoxic effects are still largely
unknown. We have recently suggested that an important factor could be the Zn2+ dependent
disruption of mitochondrial function. Neuronal mitochondria play an important role in restoring
Zn2+i homeostasis but this Zn2+ uptake leads also to prolonged mitochondrial depolarization and
free radicals generation. These injurious and likely necrotic effects are particularly evident upon the
large and rapid Zn2+i rises (D[Zn2+]i) resulting from Zn2+ entry via the Ca-A/K channels.
Interestingly, more moderate D[Zn2+]i, triggered by Zn2+ entry via VSCC, promote release of pro-
apoptotic factors such as cytochrome-C or Apoptosis Inducing Factor, suggesting that different
degrees of cytosolic D[Zn2+]i might activate distinct injurious pathways. In addition to roles in
acute injury, Zn2+ might play roles in the selective neurodegeneration associated with aging and
and Alzheimer‟s disease (AD). Indeed, cumulative effects of repeated Zn2+ exposures could
contribute to the oxidative damage and mitochondrial dysfunction seen in AD. Moreover, recent
studies have suggested that the cation promotes the aggregated state of b-amyloid peptide. Zn2+ is
in fact found in high concentrations in mature amyloid plaques in human tissue, and its chelation
favors the disaggregation and dissolution of the plaques. A better understanding of the mechanisms
involved in neuronal Zn2+ homeostastasis seems therefore highly desirable.

              Reversal of symptoms of Alz heimer disease follow ing omentum transposition to the brain

H.S. Goldsmith
University of Nevada School of Medicine Reno, Nevada. USA
Objective: To show that patients who have Alzheimer‟s disease (AD) can have their cognitive and
neurological symptoms reversed by placing the omentum directly on the brain Method: The
omentum is separated from the transverse colon and from the proximal portion of the stomach
leaving the gastroepiploic vessels in the omental apron. The omentum is surgically lengthened and
then brought up through a subcutaneous tunnel developed along the chest and neck and behind the
ear. A craniotomy is performed, the dura opened and the omentum laid on the brain. Results:
Alzheimer patients can have their symptoms reversed most probably because of increased CBF
following omental transposition (OT) to the brain. It is theorized that improvement in cognitive
symptoms results from increased vascular and biochemical substances originating from the
omentum which allow viable but deteriorating neurons to be “rescued” by augmenting neuronal
energy (ATP production) that leads to cognitive improvement. Conclusion: It is possible to reverse
cognitive and neurological symptoms of biopsy-proven AD patients as a result of OT to the brain.
 vessels in the omental apron. The omentum is surgically lengthened and then brought up through a
subcutaneous tunnel developed along the chest and neck and behind the ear. A craniotomy is
performed, the dura opened and the omentum laid on the brain. Results: Alzheimer patients can
have their symptoms reversed most probably because of increased CBF following omental
transposition (OT) to the brain. It is theorized that improvement in cognitive symptoms results
from increased vascular and biochemical substances originating from the omentum which allow
viable but deteriorating neurons to be “rescued” by augmenting neuronal energy (ATP production)
that leads to cognitive improvement. Conclusion: It is possible to reverse cognitive and neurological
symptoms of biopsy-proven AD patients as a result of OT to the brain.


                  CDK5 and GSK3 are key factors in tau aggregation and tangle formation in vivo

Wendy Noblea , Veeranna a, Dennis Dicksonb and Karen Duffa
  Center for. Dementia Research, Nathan S Kline Inst., Orangeburg, NY, 10962 USA bMayo Clinic,
Jacksonville, FL, USA
Cdk5 and GSK3 are implicated in tau hyperphosphorylation and pathogenesis. To examine whether
phosphorylation impacts tauopathy in vivo, transgenic mice over-expressing the cdk5 activator,
p25, were crossed with the JNPL3 line that over-expresses mutant (P301L) tau. JNPL3 mice
accumulate insoluble, somatodendritic tau in several brain regions and develop tangles, mainly in
the brainstem and spinal cord. P25/JNPL3 double transgenics showed significantly enhanced
pathogenic tau formation, including an increased number of argyrophilic neurons in the brainstem
and cortex relative to matched JNPL3 controls. This suggests that overactive cdk5 enhances tau
aggregation and tangle formation in mice with abnormal tau. We then examined the effect of
lithium-mediated GSK3 inhibition on pathogenic tau formation in the JNPL3 line. Mice with
moderate tauopathy treated with LiCl for one month showed a dramatic reduction in insoluble tau,
whereas younger mice with milder pathology treated for the same time showed an increase in
insoluble tau. Interestingly, LiCl treatment of younger mice resulted in induced cdk5 activity and as
tau in younger JNPL3 mice is more axonally distributed compared to older mice, the combination
of axonal tau under the influence of enhanced cdk5 may explain the unexpected increase in
insoluble tau in these animals. These results suggest that kinases such as cdk5 and GSK3 are
involved in pathogenic tau formation, but other factors (tau distribution, conformational or
aggregation status, or the action of other modulating agents) may impact the outcome. These
findings may have significant implications for the timing of administration of kinase inhibitors for
therapeutic use.

                 Caloric restric tion in primates and practical implications for aging and age-related disease

George S. Roth
GeroTech Inc., Baltimore, MD, USA
If the dozen major causes of death in developed countries were eliminated today, the gain in mean
lifespan would only be about fifteen years. Moreover, since the quality of life in those extra years
is equally, if not more, important than the quantity, it will be necessary to attack both the
diseases/disabilities of aging and the underlying mechanisms. For many years, our own research
focus has been on dietary caloric restriction (CR), the ONLY intervention conclusively shown to
slow aging and maintain health and vitality. CR studies have spanned the evolutionary scale of
experimental animal models from invertebrates to primates. Most recently, optimistic researchers
have extrapolated from this work to include the possibility of CR benefits for humans. In theory, at
least, there is much to be said for lowering the risk of diabetes, cardiovascular disease, cogn itive
deterioration, and cancers, all of which can be reduced by CR. However, in practical terms, it
would be very difficult for most people to adopt the thirty to forty percent reduction in caloric
intake necessary for optimal health and life prolongation effects in animals. For this reason, we
introduced the concept of CR mimetics in 1998. These agents, which include potential
pharmaceuticals, nutraceuticals, and other dietary supplements, exert many of the same beneficial
effects as CR (including anti-disease effects such as neuroprotection and reduction in circulating
insulin levels), but WITHOUT limiting food essence, "having one's cake and
eating it too." The race to develop CR mimetics for human use has recently become extremely
competitive, with many academic, government, and industrial laboratories now actively pursuing
this quest. The history and current status of the field will be critically reviewed and prospects for
the future realistically assessed.

New evidences on the role of cyclooxygenase isoenzymes in oxidative stress and neuronal injury follow ing cerebral ischemia

E. Candelario-Jalil, O. S. León
Department of Pharmacology, University of Havana (CEIEB-IFAL), Havana, Cuba.
Three cyclooxygenase isoenzymes (COX-1, COX-2, and a recently-identified COX-1 splice variant
termed COX-3) are involved in the biosynthesis of prostaglandins and thromboxanes from
arachidonic acid. Brain is one of the few tissues that constitutively express COX-2 under normal
conditions and several evidences suggest that COX-2 expression is related to synaptic function.
Unlike COX-1, COX-2 has been shown to be rapidly and significantly increased within neurons and
vascular cells after cerebral ischemia and other insults that result in neurodegeneration. COX-2
mediates ischemic brain injury by producing reactive oxygen species and toxic eicosanoids,
supporting and sustaining the inflammatory response after cerebral ischemia. We emphasize the
most recent findings linking COX-2 activity to increased oxidative stress and neuronal death
following cerebral ischemia. A summary of the main results obtained by our research group is
discussed. In addition, the role of the constitutive isoform COX-1 on ischemic cerebral damage is
also discussed. A clearer understanding on the precise role of each COX isoform in cerebral
ischemia could potentially influence treatment choices and care of patients suffering from stroke.

   Transplantation of human neural stem cells into rat brain after hypoxy: approach to the vascular dementia and stroke

Oleg Podgornya , Maria Aleksandrova a , Irina Heyfetsb , Rimma Poltavtseva a, Maria Mareyd ,
Aleksandr Revistchinc , Elena Loseva b , Leonid Korochkinc, Gennadiy Sukhikhd
 Koltsov Institute of Developmental Biology, Russia, b Institute of Higher Nervous Activity and
Neurophysiology, Russia, cInstitute of Gene Biology, Russia, dCenter of Obstetrics and
Perinatology, Russia.
The goal of study was to reveal the possibility of human neural stem cells (HNSC) survival in the
brain of rats submitted to acute hypoxic hypoxia, and their effect on recipient cognitive functions.
Four animal groups passed experiments: hypoxia; hypoxia + HNSC transplantation; hypoxia +
physiological solution; and the norm. Next day HNSCs, initially cultured 65 days in vitro, were
transplanted into hippocampal region (volume about 3 µl, containing 1.5 x 105 cells/µl). All rats
were conditioned to bilateral escape (BEC) on 4, 9 and 23 days after hypoxy. On the 27th day
cryosections of rat brain were investigated by immunohistochemically. Results demonstrated that
transplanted HNSCs survived in all cases. They were found in the cortex, hippocampus and
partially in thalamic structures by stain with human nuclear antibodies. Expression of nestin, ß –
tubulin Ш and vimentin had been observed in them. Transplants did not resolve from recipient
tissue by glial scar. In some cases migration of HNSCs in cortex and hippocampus was observed.
Behaviour tests demonstrate that HNSC transplantation does not affect activity of rats submitted to
hypoxia, and significantly normalizes conditioning to BEC. HNSCs transplantation may provide a
cell source to treat stroke and vascular dementia.

Abstract not available

    Effects of nutritional supplementation on the aging mammalian brain: in vivo magnetic resonance spectroscopy of brain
                                                    mitochondrial metabolism

Chardonnay J. Vance a,c, Moriah E. Thomasonb , David B. Claytonc , Bruce N. Amesa,
  Division of Biochemistry and Molecular Biology, University of California at Berkeley, USA,
  Neurosciences Program, cDepartment of Radiology, Stanford Medical School, Stanford CA, USA
Mitochondrial decay in tissues and organs, including the human brain, can impair the cellular
processes of detoxification, DNA replication and repair, osmotic balance, and the capacity to
generate ATP. Despite the critical role of mitochondria in the aging process, there currently exists
no protocol for non-invasive in vivo assessment of mitochondrial metabolism in the mammalian
brain. With recent advances in large bore high field nuclear magnetic resonance (NMR) hardware
and instrumentation, it is now possible to monitor in vivo brain metabolites with high spatial and
temporal resolution. Concentrations of key mitochondrial metabolites (ATP, ADP,
phosphocreatine, and inorganic phosphate) contain phosphorous (31P) and are indicators of normal
or abnormal mitochondrial function. 31P and proton (1H) NMR spectroscopy at a field strength 3
Tesla will allow researchers to non-invasively acquire information on the immediate and long term
changes in brain mitochondrial metabolism after ingestion of the mitochondrial cofactors alpha-
lipoic acid and acetyl-l-carnitine. A dual-tuned volume coil has been custom built in order to
acquire both 1H-decoupled 31P NMR spectra and high-resolution 1H and 31P NMR images. This
hardware enables the registration of changes in mitochondrial function localized within brain
substructures and with a temporal resolution of approximately 30 minutes. Current progress in the
performance testing of the coil and preliminary results obtained from subject and control rats will
be presented. After testing in rats, a similar protocol will be used with populations of healthy aging
primates and humans.

Restoration of motor function in adult patients

                               Reorganization of cortical motor function in patients after stroke
Lázaro Gómez Fernández, Eduardo Alvarez González, René Macías González, Reynaldo Galvizu,
Elizabeth Padilla Puentes.
International Centre for Neurological Restoration. Havana. Cuba
Changes in cortical maps are related to motor recovery in patients after stroke as an expression of
neuronal plasticity, and physical rehabilitation can modulate some of these changes. To find out
which are the effects of a neurological rehabilitation program in cortical motor maps in patients
after stroke, we studied 2 groups of patients who suffered a cerebral ischemic stroke 1-3 years ago,
with partial recovery of their motor function (Barthel index >85, modified Rankin scale =<2); all of
them gave their written informed consent. One group of 5 patients was evaluated twice without any
treatment; and another group of 15 was included in an intensive and integral rehabilitation program
10 hours a day for 28 days, and were evaluated before and after treatment. Besides clinical
evaluation, we carried out a motor mapping procedure with transcranial magnetic stimulation
(TMS) of the resting first dorsal interoseus muscle in all of them. Enlargement of motor cortical
map with displacement of its center in the affected hemisphere was the most frequent finding in
patients; ipsilateral motor responses to TMS was observed only in three patients. After treatment
significant changes in motor area determined by TMS were seen in both hemispheres (affected and
not affected (non affected: Z=2.36, p=0.017; affected: Z=2.66, p=0.007) in the group of treated
patients. No significant differences were detected in the non-treated group between evaluation 1 and
2(p>0.05). In conclusion motor recovery in patients after stroke in response to therapy is related to
an enlargement of motor responses area.

       Multidisciplinary approach to stroke sequels : Evaluation of efficacy of the Neurological Restorative Program

Álvarez E, Rodríguez L, Palmero R, Carballo M, Fernández E.
Internacional Center for Neurologic Restoration. Havana, Cuba.
Introduction: Stroke is a main source for impairment disability and handicap for patients. Motor
sequels and speech disturbances are the most common consequences, which are liable to change,
based on the brain plasticity properties. An intensive, multidisciplinary and personalized therapy
program has been developed at our hospital in the last ten years to improve disability, handicap,
motor and language performance in chronic stages of stroke, this program was called Neurological
Restorative Program (NRP). Patient and Methods: A pilot open-label and controlled clinical trial in
29 patients with chronic sequels of stroke was conducted to assess the efficacy. This assessment
included Barthel Index (BI) and Scandinavian Stroke Scale (SSS) at the beginning and after 4
weeks of treatment. The data obtained were analyzed by descriptive statistic; match pairs test and
correlations variables. Results: The mean of age was 56±14.4, the mean of the disease was 2±2.43,
and 72% of the patients have severe and moderate disability. Average improvement was 15% for
the BI and 10% for SSS after 4 weeks of treatment. The patients with severe and moderate disability
obtained the most important benefit, which was dependent of a bigger recovery of the walk. The
patients with lesions of dominant hemisphere and non-hemisphere showed a bigger improvement in
the SSS (16%) that was dependent of a bigger recovery of the language and capability of walk.

Round table: Restoration in neuro pediatrics

                                  Integral approach to pervasive development disorders

Carlos Maragoto Rizo, Maria Eugenia Navarro García, Idelys Sarduy, Gabriel Rodríguez García.
International Center for Neurological Restoration, Havana, Cuba
Pervasive development disorders include interesting and numerous conditions. Autism and
autism/like behavior were under research in the last ten years. Based on the demonstrated concept
of neuroplasticity, we applied in our clinic an integral, personalized an intensive program called
Neurorestoration program. In PDD we include the diet therapy (gluten and casein-free foods),
pharmacological therapy for symptoms (hyperactivity, repetitive movements and so on), a TEACH
method and a speech therapy and kinesiologic therapy. We show the preliminary results of 9
children under this program.

                                      Integral management of cerebral palsy

Gabriel Rodríguez García, Carlos Maragoto Rizo, Andrés Garcia Cruz, Lilia Esther Dulzaides,
Verónica Morales, Nayoy Rodríguez Verde
Center: International Centre of Neurological Restoration. Havana, Cuba.
Cerebral palsy is one of the most common causes of disability in children. Two to 5 of 1000
children at school age have motor disability. Several evidence support the concept of neuroplasticity
in children. In our clinic we develop a strategy that help to recover function in this patients, called
Restoration Program. We discuss the step and explain how can we manage these patients.
Neurorestorative program have 2 steps: evaluation according to neurological sequels and
application of standard scale, the second is the pharmacological, neurosurgical and
neurorehabilitation of the patients. Besides, we expose preliminary results of a blind and controlled
study of 18 patients treated with this program. Further studies will tray to demonstrate this fact.

                              Integral Handling of Dystonia in physical rehabilitation

Tamara B. González Ramírez, Mirbia Marichal Figueroa, Carlos Maragoto Rizo
International Center for Neurologic Restoration (CIREN), Havana.Cuba.
Dystonia is a neurological syndrome characterized by involuntary, sustained muscle contractions
that provoke trunk repetitive muscular contractions or abnormal postures. Dystonic movements can
affect various muscular groups, are present at rest, and can be enhanced during voluntary
movements (action dystonia). Dystonia fluctuates and its clinical expression can be modified by
diverse sensorial stimuli, being frequently associated to tremor. Local or distal pain is usually
associated, being one of the principal causes of discapacity. Objective: To present our experience
and results with dystonic patients assisted at CIREN´s Neurology Clinic for Children. Patients and
methods: A retrospective study was performed on 15 cases with the same diagnosis, which were
evaluated using motor tests (gross motor) at the beginning and the end of treatment. Results: In all
cases, positive changes were observed in socializing, on gross motor and in quality of life.
Conclusions: The results achieved can be considered satisfactory, keeping in mind, the complexity
of the disease.

Restauration of motor function in children

                  Comprehensive physical therapy management of young children with brain injury

Karen R. Voogt
Old dominion University, Norfolk, Virginia, USA
The purpose of this oral presentation is to describe the comprehensive physical therapy management
of the very young child with severe neurological impairment. The subsequent motor sequelae is
well documented, however, long-term physical therapy management and intervention are less
understood and must be established to ensure optimal outcome and recovery. The cognitive
emotional communication and behavioral issues surrounding neurological impairment significantly
complicates the role of physical therapy intervention. A comprehensive approach to physical
therapy will be presented for infants through adolescents. The objectives of this presentation are to:
1. Demonstrate the impact of motor sequelae on the child's daily life routine, 2. Demonstrate the
integral role of the parents or caregivers on motor outcome, 3. Demonstrate various therapeutic
interventions including handlign, positioning, casting and recreatonal activities to enhance motor

                              Integral management of spinal cord lesion in paediatric age

Gabriel Rodríguez García, Carlos Maragoto Rizo, Andrés García Cruz, Maria de los Ángeles
Ortega, Ernesto Cossio, Carlos Sánchez.
International Center for Neurological Restoration, Havana, Cuba
Spinal cord lesions are relative uncommon in people under 16 years. Several evidence support the
concept of neuroplasticity in children. In our clinic we develop a strategy that help to recover
function in this patients, called restoration program. We discuss the step and explain how can we
manage these patients. Neurorestorative program have 2 steps: evaluation according to neurological
sequels and application of standard scale, the second is the pharmacological, neurosurgical and
neurorehabilitation of the patients. We presented our experience in 41 patients with spinal cord
lesion, 18 of them with mylomeningocele, 12 with traumatic spinal cord lesion. The results of the
program were measure throughout ASIA scale, Barthel index. Further studies will tray to
demonstrate this fact.

                Utility of the tiz anidine in the treatment of the spasticity in children with cerebral palsy

Vásquez A. Pérez A., Arellano M. Renán L.
Centro Nacional de Rehabilitación. DF, Mexico
Objective: To evaluate the effect of Tizanidine on spasticity of patients with cerebral palsy. Material
and Methods: We included for randomized assignation in a double blind study 10 children‟s treated
with Tizadine ( 1 mg per day) and 30 with placebo for a 6 month period and the same physical and
occupational therapy scheme. Both groups were matched in age ( p=0.54), weight (p=0.64), height
(p=0.81), and gender ( p=0.29) with basal p>0.05 in all the depend variables ( spasticity Asworth
scale, length of lower limbs, posture control scale, reflex scale, contractures, activity of daily living,
and liver function test OGT, PGT). Results: From the second through to seventh measurement
spasticity in Tizadine group reducing spasticity at 78.85% vs. 7.64% of placebo. (p=0.0001 for
differences between groups and p=0.0001 for differences between time of administration) Without
reported adverse effects. The liver function test remain normal. Conclusion: Tizanidine produce
significant reduction of spasticity in pediatric patients.

                         Prevalence and incidence rate of the Spinocerebellar Ataxia in Cuba

Luis Velázquez Pérez, Gilberto Sánchez Cruz, Luis Almaguer Mederos, Edilberto Martínez
Góngora, Mercedes Velázquez Manresa, Karel Escalona Batallán, Yosvanis Rodríguez Almira,
Julio Rodríguez Díaz, Lisandra Prieto Avila, Rubén Reynaldo Armiñán
Center for Research and Rehabilitation of the Hereditary Ataxias. Holguín,.Cuba.
The most frequent molecular form in Cuba is the Spinocerebellar Ataxia type 2 (SCA2). The SCA2
is caused by a trinucleotide (CAG) expansion in the coding region of the ataxin 2 gene on
chromosome 12q. It is characterized by a dominant autosomic pattern of inheritance. This
epidemiological study is aimed at determining the prevalence and incidence of hereditary ataxias in
Cuba and comprise a descriptive study of 757 patients suffering from this disease and 7 068 at risk
in the country. 1548 non-symptomatic first-degree relatives of SCA2 patients from 101 families
with SCA2 were identified by polymerase chain reaction. As a result, it was found out that the rate
of prevalence in Cuba is 7 cases per 100 000 inhabitants with one province having the highest rate
reaching 43 cases per 100 000 inhabitants, whereas the mean incidence was 4.39 cases per 100 000
inhabitants in Holguin Province and one municipality (Cacocum) has the impressive figure of 18
cases per 100 000 inhabitants. The age group most affected was that between 30-39 years old. The
prevalence in this group is about 64 cases / 100 000 inhabitants. Approximately 62 is the rate / 100
000 inhabitants of sick people living in the rural area, practically the double of the rate of
prevalence in those living in Urban areas. The most frequent symptoms in the SCA2 are gait ataxia,
cerebellar dysarthria, dysmetria and adiadochokinesia.

Cuban national-international cooperative study on clinical, epidemiological, virological and inmunogenetical data in Multiple
                                          Sclerosis and demyelinating diseases

Cabrera-Gómez, JA, Pérez-Ruiz L, Luis-González S, Echazábal-Santana N, Ocaña-Gil MA,
Apollinaire-Pennini M, Hernández E, González-Quevedo A, Porrero P, Aguilera O, Herrera O,
Gómez A, Martínez-Góngora G, De la Vega W, Batista-Iturriaga A, Rivas-López V
Multiple Sclerosis Society of Cuba (CUBACTRIMS. Havana, Cuba)
BACKGROUND: Multiple sclerosis (MS), optic neuromyelitis syndrome (NMO) and inflammatory
myelopathies (IM) are one of the most commonly diagnosed disabling neurological disorders of
young to middle-aged adults in Cuba. OBJECTIVES: To assess the epidemiological, clinical,
virological and immunogenetic data of MS, NMO syndrome and IM data in the population of
Cuba. MATERIAL AND METHODS: The study population consists of patients identified with
MS, ONM syndrome and IM in Cuba (11 millions inhabitants). The national health system structure
in last years has changed to the organization based on family doctors who are the general
practitioners. Patients will be identified from different sources. We will compare the frequency of
immunogenetic markers in the patients as well as in two unrelated healthy from de same areas. The
diagnostic criteria will be for Multiple Sclerosis, (McDonald et al); NMO (Wingerchuck et al) and
for IM according to the primary diseases. A Case Report Form (CRF) will be used to record the
history of each patient: the personal data, ethnicity, family history, date and age at onset, type of
onset, symptoms, clinical course, functional systems, the clinical localization & diagnosis, EDSS,
complementary tests (blood, CSF, evoked potentials, MRI), final diagnosis and clinical evolution.
The genealogical questionnaire will be performed by the genetics and, for the immunogenetical
studies, appropriate patients for blood sampling will be choosing, when the family history is known.
For the epidemiological study the day of the prevalence will be determinate. RESULTS: The final
data will be available by October 2004. CONCLUSIONS: This is the most expansively national
cooperative study on clinical, epidemiological, immunogetical and virological data on MS and other
demyelinating diseases in a Latin-American country.


                                 Evaluation of the rehabilitation method applied to patient

Leonardo Alemán
International Health Center La Pradera , Cuba
The different rehabilitation methods face the challenge of presenting evidences of their
effectiveness, in this work a sample of 20 paraplegic patients is presented assisted in the
International Center of Health "La Pradera ", which received two months of intensive rehabilitation
that it includes a program of integral physical preparation in a personalized way and in group,
preparation program and training for the march with ortesis and other auxiliary devices, pre-sports
games, psychological attendance, pharmacological modulation and employments of biophysical
means as ozone therapy, magneto therapy and electric stimulation, with a frequency of Monday to
Friday (6 daily hours). These patients were evaluated with simple and reliable scales as index of
Barthel, ambulatory index of Hauser, scale of Ashworth before and after the treatment, with the
objective of measuring the effectiveness of the used rehabilitation method. 85% of the patients
achieved a functional march that allowed them the independent displacement inside the house and
95% obtained a final qualification in the index of Barthel of more than 60 points, what means that
these people are qualified to carry out most of the activities of the daily life.

    Qualitative and quantitative analysis of the gait in patient hemiplegics as consequence of cerebrovascular disease

Roberto Díaz Capoteª, Roberto Díaz Márquezª
International Center for Neurological Restoration (CIREN), Havana City, Cuba
The work was carried out at the International Center for Neurological Restoration (CIREN)
selecting a sample of ninety patients, with the objective of checking the effectiveness of the current
program of physical rehabilitation on hemiplegic patients after stroke to promote the recovery of
gait, as well as on its qualitative aspects. Patients received two months of physical rehabilitation
while two standard evaluation tests were measured at the beginning and at the end of the treatment.
The results were statistically processed using the method of two-way ANOVA and MANOVA. A
biomechanical study of the gait for using the Movement Analysis System (designed and validated at
the ISCF) was also carried out. The cinematic analysis of the gait cycle showed improvements in
the quality of gait. The treatment resulted in very significant differences in the measured tests,
appreciating an increase of the autovalidism and contributing to the social reincorporation of the

    The use of the Tinetti scale to evaluate the recovery of the gait in patients with static lesions of the nervous system

Roberto Díaz Capote, Joaquín García Martínez, Roberto Díaz Márquez, Eduardo Álvarez González
International Center for Neurological Restoration (CIREN), Havana City, Cuban
This investigation was developed at the Adult Brain Static Lesions Clinic belonging to the
International Center for Neurological Restoration (CIREN) in Cuba. We selected 20 patients with
static lesions as consequence of stroke to evaluate the recovery gait after applying a physical
restoration program designed in our institution. At the beginning and at the end of the treatment (4
weeks) the Tinetti Scale was applied. The results were processed using the Wilcoxon´s non-
parametric test to verify the significance of the results. Patients were divided into two groups of ten
each. The first group formed with those showing focal motor deficits (hemiplegics) and the other
with different sequels (ataxias and paretic disorders). Once the treatment was concluded the
effectiveness of the program of Physical Rehabilitation was evaluated, as well as the sensibility and
viability of the Tinetti Scale to evaluate the recovery of the gait and the balance in patients with
Static Lesions of the Central Nervous System.

 Alternativ es for augmenting the mobility and articulatory amplitude of fingers in patients with hemipharesis-like sequel of
                                                   encephalic static lesions

Estela Quesada Rodríguez, J. Nodarse Ravelo, Y. Vizcay Valiente, M. Torres, T. Francia González,
M. Crespo Molinelo
International Center for Neurological Restoration (CIREN), Havana, Cuba
In order to achieve one of the objectives of the occupational therapy program at CIREN for treat
patients with sequels of encephalic static lesions, we have elaborated a system of activities to
accomplish an improvement of amplitude, and articulatory movements of the fingers in the affected
hands. These activities were applied to twenty cases with common characteristics: normal intellect,
traces of movements, important hemiparesis (as main motor deficit), pain in different levels of
fingers and time of evolution from zero to 3 years. Two treatment periods of twenty-four days, six
frequencies a week, one hour daily, were applied. Initial goniometric and active final exams were
performed at the Psychomotor Integral Evaluation Laboratory (LEIS) measuring: flexion
(methacarpophalangical, interphalangical and distal), abduction and adduction to compare the
results before and after treatment. The cases studied improved significantly, both quantitatively and
qualitatively. The results were analyzed comparing average improvement of each controlled
variable using the Wilconxon Matched Pairs non-parametric test to determine the degree of
significance of the final results.

Treatment w ith occupational therapy increase mobility and articulation of shoulders in patients w ith sequels we to Encephalic
                                                        Static Lesions

Jenny Nodarse Ravelo, Maydané Torres Aguilar, Tania Francia González, Mercedes Crespo
Moinelo, Estela Quesada Rodríguez
International Center for Neurological Restoration (CIREN), Havana, Cuba
One of the main objectives included in the program for the treatment with occupational therapy
applied to patients with sequels of Encephalic Static Lesions. We elaborate a system of activities to
increase the width and mobility to articulate the shoulder. This program was applied to 20 cases
with the following characteristics: normal intellect, hemiplegia or hemiparesia, and time of
evolution from 0 to 5 years. With this system we carried out an experimental study to demonstrate
their influence during two months of treatment. We performed an initial and final goniometrical test
for the flexion (L.E.I.S), extension, abduction and adduction of this articulation. The patients
improved considerably according to results of statistical comparisons (Wilcoxon Matched Pairs
statistical test).

Treatment w ith occupational therapy to increase mobility and movement degree of the wrist applied to patients with Sequels
                                                of Encephalic Static Lesions

Maydané Torres Aguilar, Jenny Nodarse Ravelo, Tania Francia González, Mercedes Crespo
Moinelo, Estela Quesada Rodríguez
International Center for Neurological Restoration (CIREN) Havana, Cuba
We present the results of the program for the treatment with occupational therapy to hemiplegics
patients bearing motor sequels. A system of activities has been elaborated to increase the movement
degree of the wrist. This was applied to 15 patients with common hemiplegic characteristics and
motor deficits, but showing normal intellect, between 0-3 years of age. The treatment was applied
one hour daily for two months. We performed initial and final goniometrical tests measuring:
extension, abduction and adduction of the wrist pain in order to compare results. The patients
improved considerably and we results were significant (Wilcoxon Matched Pairs test).

                           Training in w riting for patient with right hemiparesis as a result of stroke

Tania Francia González, A. Vernis González. Calvo, Mercedes Crespo, Jenny Nodarse, Maydané
Torres, Estela Quesada
International Center for Neurological Restoration(CIREN),Havana, Cuba.
Vascular brain diseases are considered to be the most frequent disorders resulting from a primary
lesion of brain blood vessels. In most cases, the neurological damage is unilateral, manifesting itself
in hemiplegia or hemiparesis of contra lateral hemibody, with total or partial loss of voluntary
motor ability, affecting writing among other abilities. In our work we intend to evaluate the
improvement of the writing ability through a training program for the setup and automation of
correct patterns of writing in hemiparetic patients due to stroke. The investigation was carried out in
a sample of 10 patients between 40 and 60 years. These were subjected to an initial and a final test
in writing and evaluated through a quantified scale for writing (created at Ciren‟s Occupational
Therapy Department). During the intermediate period they received an occupational therapy
rehabilitation treatment for 35 days of 1 hour daily. The treatment consisted of an initial physical
preparation followed by the setting-up and automation for correct patterns of writing. The results
obtained showed considerable improvements in the ability to represent basic forms of writing of
patients under study, which demonstrate that the activities applied in the study were effective.

Evidences on the modulating effect of treatment in occupational rehabilitation in the
neuroplastic process. A case report

Yoanne Vizcay Valiente, Lázaro Gómez, Estela Quesada, Maydané Torres, Jenny Nodarse, Ana M.
Centro Internacional de Restauración Neurológica (CIREN Havana, Cuba
The recovery of motor functions in the hemiparetic patient through the practice of certain
movements, induces plastic changes in the "cortical representation of movement", an aspect of
transcendental importance which gives way to the design of therapies, aimed at facilitating the
expression of certain processes, and to inhibit others. We present the treatment of a patient at the
International Center of Neurological Restoration (CIREN), with a patient suffering from left
hemiparesis as a sequel of a brain attack in the right medial cerebral artery territory. The patient
received a rehabilitative program for 28 days as part of an intensive multifactorial neurological
restoration program that included the strategy of intervention through the development of manual
dynamic coordination activities. The influence of this strategy on the recovery of motor functions
on patients with cerebral lesion was assesed. The motor mapping using transcranial magnetic
stimulation showed positive evidences about the modulatory effect of occupational and physical
therapy on the reorganization of the activity from motor function to cortical level.

                 Kinesiolgic Handling of patients with Cerebral Palsy at CIREN Neurology Clinic for Children

Lilia Esther Dulzaides Reyes, Maritza Alonso Vasquez,
International Center of Neurologic Restoration ( CIREN), Havana, Cuba
We can assert that the neurorestorative program used at clinic is valid for the handling Cerebral
palsy. This condition is characterized by movement alterations and posture along with other
affectations as: epilepsy, mental retardation, motor affections, etc. It is necessary to give the patients
a series of activities allow the achievement of habits and motor abilities. Objective: To demonstrate
the effectiveness of intensive-integral kinesiologic treatment for patients with Cerebral Palsy.
Materials and methods: A sample of 20 children, diagnosed with cerebral palsy, was used. These
children received kinesiologic treatment at our clinic for an average period of 84 days. They all
received the neurorestorative program developed at our Center for this type of pathology. By using
the Motor Gross Functional Evaluation Scale (at the beginning and end of each period) the motor
evolution reached by these children was assessed. Results: Positive results were obtained in all the
patients included in the sample. Conclusions: This study demonstrates the validity of the intensive
and integral rehabilitation program used for therapy of Cerebral Palsy.

Efficacy in the application of the physic al rehabilitation program of CIREN'S neuropediatric c linic of spastic ity and increase of
                                       the motorial capacity in children w ith cerebral pals y
Ivette Martínez Rodríguez , Gisela Castellanos Torres
Rehabilitation Department, International Center for Neurologic Restoration, Havana, Cuba
Cerebral palsy (cp) is one of the symptoms that most frequently cause physical or mental limitations
among the children's population. Its occurrence varies from 1.5 to 2.5 for 1000 born alive, without
the evidence of a tendency to diminish through the years. Spasticity can be defined as a hyper-
excitability of the muscular stretching reflex, whose result is an increase of "dependent speed" of
the muscular tone or tonic-stretching reflex, with an exaggeration of osteondinosic reflexes. At our
center there is an outstanding experience in the treatment of spastic cp. related with reached
evidences in the last decade that there are neuroplastic properties during pediatric ages. and that one
of the forms of plasticity is obtained through the treatment of cortical areas; we apply an intensive
multifactorial program of physical rehabilitation. To make this work come true we performed a
retrospective study of two years' time, on all spastic patients with cp selecting 35 of them. It has as a
main objective to evaluate the effects of the program according to their neurological conditions and
functional capacities. Scales were applied before starting therapy and after 8 weeks of the
rehabilitation program, where there were improvements in each of the evaluated areas. Preliminary
results demonstrate that in the evaluated patients there was a diminishing of one point in Asworth's
scale and the percentage of improvement increased. In a preliminary way, the efficacy of the
physical rehabilitation program applied to children with cp of the spastic quadriparesia and diparetic
type can be appreciated.

                   Ethiological characterization of a hundred patients with diagnosis of Cerebral Palsy

Reinaldo Galvizu Sánchez, Rene Macías Betancourt, Teresa Morgado Vega, Judith Plá Morét,
Velasco Acosta, Ohilda Rodríguez Coca, Alexander Valdés Trejo.
International Center for Neurological Restoration (CIREN) Havana, Cuba
The Cerebral Palsy (CP) is a non-progressive overthrough of the muscular tone, the posture and the
movement, due to an aggression to the CNS in a period when the maturation and development of
the System is not yet finished. A hundred children with this diagnose were studied at the CIREN for
an etiological classification. The diagnose of all the patients was confirmed. The etiological agents
of this pathology were established through interview to their relatives. EEG and cranial CAT were
also done. The frequency distribution and the test x2 according to the used variable were
analyzed. It is found that the perinatal etiology was the most frequent. Among the main etiological
agents were: premature childbirth (42 cases) and low-born-weight (38 cases). The ephastic diplegia
was the more frequent clinical form (56 cases), 46% of the patients presented convulsive crisis, and
36% of them had epilepsy. A significant association between these variables and the different
etiological groups were not found (x2=1.611, P=0.4470; x2=0215, P=0.8982 respectively). It is
concluded that EEG alterations had a real preponderance in the anterior regions (fronto-temporal)
and the tomographic study showed to be a useful diagnostic method in the identification of the
structural alterations in children with CP. It was also found that the periventricular leucomalacy and
the cortico- sub-cortical atrophy are the more frequent in the newborn etiological group. It is
recommended to do a correct etiological characterization of the patients with CP and a careful
search of the etiological agents mainly in the patients that come to the Health Tourism Centers.
These results were compared with the one reported in a national research done in Cuba in the year
2002-2003 showing similar results with those reported in this work.

        Occupational Therapy Treatment for Children w ith Cerebral Palsy after the use of Botulinic Toxin Type-A
Verónica Morales Pedroso, Noelia Romero Borrego, Leonides Castellanos Fuentes, Carlos
Maragoto Rizo, Niurka Junco Cortés
International Center for Neurological Restoration, Havana, Cuba
Cerebral palsy (CP) is defined as “a movement and posture disorder due to a defect or lesion of the
immature brain”. According to its clinical manifestations it is classified in: spastic, of cerebellose
basal ganglia-type, or mixed. The application of Botulinic Toxin type-A on these patients is
supposed to have therapeutic advantages over other treatments, as it permits to act directly on
affected muscles without repercussion over the patients‟ general status. Objective: To demonstrate
the effectiveness of the use of Botulinic Toxin Type-A for allowing occupational therapy treatment.
Material and Method: We performed a retrospective study where all clinical and defectologic
records of the patients hospitalized at the International Center of Neurologic Restoration at the
Neurology Clinic for Children, at Havana, Cuba, were revised. The sample was composed of 13
patients (8 males and 5 females) diagnosed with Spastic Cerebral Palsy. Their ages ranged from 2 to
10 years that received treatment for a period of 3 months. At the beginning and end of treatment, the
modified Asworth‟s Scale and Susana Matas‟ Early Intervention Forms were used to evaluate the
degree of spasticity. Conclusion: We appreciate a favorable evaluation as to the variation in the
muscular tone and the development of new manipulative abilities. The patients with Spastic CP
were benefited with the application of Botulinic Toxin Type-A and occupational therapy
rehabilitation treatment, which comprises an Early Stimulation Program.

Neurophysiological Markers for the identif ication of modifiers genes and other factors of the clinical expression of the SCA2

Luis Velázquez Pérez, Gilberto Sánchez Cruz, Luis Almaguer Mederos, Edilberto Martínez
Center for Research and Rehabilitation of the Hereditary Ataxias. Holguín,.Cuba.
The SCA2 is a dominantly inherited cerebellar ataxia. It has a prevalence of 43 per 100 000
inhabitants in Holguín province, which is the highest one reported worldwide. 202 patients from 56
families with SCA2 and Fifty-five non- symptomatic first-degree relatives of SCA2 patients were
identified by polymerase chain reaction and sequenced. First-degree relatives (sons) were studied 5
times over a period of 17 years. The Peripheral and Central Nervous System of these patients were
subject to clinical studies and electrophysiological eva luation. Correlation analysis were made
between the CAG repeat and various electrophysiological parameters. In 188 of them, ataxia of the
gait was the first symptom of the disease, while gait ataxia with cerebellar dysarthria was present in
12 patients. All patients had ataxic gait, cerebellar dysarthria, dysmethria and dysdiadochokinesia.
The main abnormality found in the patients and presymptomatic relatives was a reduction of
sensory action potential as well as increase in the latency of the P40 component. The severity of
these electrophysiological changes was found to be related to the CAG repeat. Our
electrophysiological results agree with the loss of ganglion cells in the dorsal root ganglia. This
studies have proved that while the number of CAG repetitions increase, bigger electrophysiological
alterations are produced in patients, until they get to total blockade of the afferent conduction as a
sign of severe neurodegeneration. It is speculated that a rise in CAG repeat might lead to increased
toxicity of the SCA2 gene product which subsequently accounts for more neuronal loss in the
Peripheral and Central Nervous System.

                                     Phenotipical characteriz ation of the Cuban SCA2

Gilberto Sánchez Cruz, Luis Velázquez Pérez, Edilberto Martínez Góngora, Mercedes Velázquez
Center for Research and Rehabilitation of the Hereditary Ataxias. Holguín,.Cuba.
Autosomal Dominant Cerebellar Ataxias are a heterogeneous group of neurodegenerative disorders
characterized by varying degrees of brainstem and cerebellar pathology and dysfunction. Translated
CAG repeat expansions encoding polyglutamine tracts are found in the six genes: SCA1, SCA2,
SCA3, SCA6, SCA7 and SCA17. The Cuban SCA2 is the highest prevalence in the world. The
study was performed in 553 patients from 101 families with a molecular diagnosis of SCA2. This
group of patients was composed by 284 male and 269 female, onset age mean 32,75 (range 2-75).
The mean time of evolution was of 14.6 years. The studied included clinical, biochemical studies
and electrophysiological evaluation. All patients were gait ataxia, cerebellar dysarthria, dysmetria,
adiadochokinesia, tremor, hypotonia, abnormal reflexes and slowed and limited eye movements.
No patients had optic atrophy, spasticity, pigmentary retinal degeneration and endocrine
dysfunctions. In patients with severe disability there was involvement of the peripheral and central
nervous system regulating autonomic function, such as vasomotor disorders, constipation, urinary
and rectal incontinence, tachycardia at rest, exocrine gland disorders, and a syndrome of cachexia
with bulimia and sleep disorders. Biochemical finding demonstrated oxidative stress. The main
abnormality found in the experimental group was the reduction of the sensitive potential amplitude,
in all studied sensitive nerves. This electrophysiological characteristic continues evolving and it is
more accentuated in the patients with the longer evolution time in the disease. The increase in the
sensitive potential latency and the slowing of the sensitive conduction velocity were the other two
abnormal characteristics also seen in this group of subjects. The analysis of the changes in the
variability of the heart rhythm demonstrated a hyperfuntion of the Simpatetic Nervous System with
slight hypofuntion of the Parasimpatetic.

                           Multidisciplinary Approach to Cerebellar Ataxias: Preliminary Report

Diaz de la Fe A.,Morgado T.,Padron A.,Pedroso I.,Alvarez L.
Movement Disorders Clinic,CIREN,Ciudad Havana,Cuba
Cerebellar Ataxia is the second most frequent movement disorder in our Clinic. This syndrome is
associated with impaired locomotion, manipulation, and communication as well as severe disability.
Non-pharmacological or surgical approaches are useful to control the motor impairments or to
improve functional capabilities. Conventional physical therapy, training of gait by different
techniques and isolated speech therapy has demonstrated transitory improvement but there is no
report describing the effect of combined techniques to train motor performance. From June 2002 to
June 2003 we conducted and open, uncontrolled, clinical trial to assess the efficacy of a
multidisciplinary therapy, structured in periods of 4 weeks. The study includes 23 patients with this
motor disorder. The follow up protocol define the same battery of evaluation, i.e.: the International
Cerebellar Ataxia Rating Score (ICARS, WHO, 1999), the subtest for coordination and gait from an
standard system for motor performance (LEIS), the Bartell Index and the SF-36 Questionnaire to
asses both functional state and quality of life, at baseline and after ending each cycle of treatment.
The preliminary results show an average improvement of motor performance of 31,6% in the group
with higher degree of reduction in the ICARS total value for most handicapped patients and better
results for the patients who extend the training for more than two periods. Bartell Index improves in
about 20 %and the Qlo (Sf-36) do not reach statistical significance. In conclusion, multidisciplinary
therapy can improve both motor performance and functional capabilities but further studies with
more patients should be done.

 Use of the International Cooperative Ataxia Rating Scale to evaluate the recovery of movement of upper limbs in patients
                                   with ataxia as a result of neurodegenerative disorders

Yoanne Vizcay Valiente, Amado Díaz de la Fe, Ana M. Montero Suárez, Estela Quesada Rodríguez
Centro Internacional de Restauración Neurológica, Havana, Cuba
Ataxia is a common landmark for a group of degenerative diseases. These illnesses can have a
progressive course, however, some symptoms can be alleviated by a skilled and rational treatment.
This investigation has the objective of checking the effectiveness of the International Cooperative
Ataxia Rating Scale, ICAR (World Neurology Federation) to measure the evolution of ataxic
patients after being subjected to rehabilitation treatment. A sample of 12 patients, were treated with
occupational therapy (one daily hour) for 45 days. We applied ICAR scale to evaluate movement in
superior limbs. A comparison was carried out between results with this scale and coordinative
capacities tests performed at the Psychomotor Integral Evaluation Laboratory (LEIS). Indicators of
manual skills as: dismetry, tremor, and irregularity of movements were measured. The decrease of
the punctuation of these indicators coincides with the decrease in the number of errors (evaluation
indicator) of the coordinative capacities tests (LEIS). Both evaluations showed 52,9 and 27,2% of
improvement respectively, with regard to initial evaluations. ICAR scale supplemented our
information about the evolution of the ataxic patient.

                A comparative study on the physiatric treatments of bell´s peripheral facial paraly sis

Carlos Rafael Leyva Barrientos.
M. C. H. Dr Luis Días Soto, Habana, Cuba
A descriptive-retrospective study was made in patients assisted at the Military Central Hospital Dr:
“Luis Díaz Soto” referred by neurological services in order to evaluate the physiatric treatment
effectiveness in those who underwent a 1-year-long-peripheral facial paralysis. Two groups of
patients were treated; in the first one prevailed 20-year-old males (66.6%), while in the second one
there were 11 individuals within 30 to 39 accounting for (36.6%). Hyperesthesia was present in 20
patients (66.6%) following retro-auricular pain and hyperacusis present in 18 and 17 cases in each
age group, as major neurological signs related to the hemiface damaged. Whilst lip and eye
orbicular muscles were seriously damaged in (100%) of the cases, the (90%) of them did not show
muscular contraction at the beginning of the physiatric treatment, however, at the end of it (46.6%)
of the cases presented “normal” contractions and only 7 individuals (23.33%) had a “poor”
muscular contraction level. Ultra-frequency treatment; electric stimulus, facial massage and
mimicry exercises exerted optimal effects (46.6%), while the other treatment reached only (36.6%)
of effectiveness. The healing process was evident in 20 patients (66.67%) being 14 cases under the
first group and only 6 in the second one. 5 patients (16.6%) of the first group and 4 of the second
one were grouped under the middle-level healing process. The latter proved to have the worst
diagnosis as permanent sequels occurred.

                               Congenital Multiple Arthogriposis. A case presentation

Carmen Rosa Alvarez Gonzalez, Erduy J Infante Velásquez, Gilda Martinez Aching
International Center for Neurologic Restoration (CIREN). Havana, Cuba
Congenital Multiple Arthogriposis (CMA) is a term that defines the presence of contractures in the
articulations at a child‟s firth. The objective of our work is the presentation of a clinical case.
Material and Method. A case under pediatric age with a Congenital Multiple Arthogriposis
diagnosis is presented. We applied the evaluation of motor function (at the beginning and end of
neurorestorative treatment). A 4 year old female patient at nine months of pregnancy, the mother
had a delayed birth work, delayed crying of the baby after birth, cyanosis and low weigh of only
2800 grams, remaining in an incubator for 10 days. The patient presented an evolutive retardation in
psychomotor development in all the spheres of neurodevelopment. At the moment, the child
presents significant disorders is her self-validism, especially in gross and fine motor functions,
language and its psychopedagogig learning. At the physical exam, retardation in the maturation and
language requisition was observed. She did not sit up; sedestation and standing up biped station
were impossible. A 28-day cycle of the Neurorestorative Program was performed. She obtained
some improvement of the muscular strength and superior limbs (scapular waist) and improvement
of the articular amplitude of limbs and the child remains seated without support. Conclusions. The
evaluation of function initially showed a 10,5% level and a final 15,2%, for a 5,3% increase in only
one cycle of rehabilitative treatment.

 Gait evaluation at the integral psychimotor evaluation lab on patients w ith motoric sequels due to cranioencephalic trauma

Gilda T. Martínez Aching, Armando Sentmanat Belison, Carlos Suárez Monteagudo, Alexander del
Valle Echemendía, Carmen Rosa Alvarez González, Bárbara Sánchez González
International Center of Neurologic Restoration (CIREN) Havana, Cuba
Nature and environment expose us to multiple situations that can cause cranioencephalic trauma.
Gait alterations are often derived from accidents, which also can hinder the normal capacities to
develop motor skills impairing the patient‟s social life. The fundamental objective of this work was
to evaluate patients with gait motor sequels caused by encephalic trauma. These evaluations were
carried out in a sample of 52 patients assisted at CIREN. We have collected numerical eva luations
of the patients gait problems. These evaluations were performed at the initial state and after
evolution in their rehabilitation. Evaluated tests on gait were: amplitude of average steps and
frequency of steps in 10 meters (amount of steps and frequency of performance). Of the 52
evaluated patients, 38 changed their gait amplitude.

          Inflammation and multiple sclerosis. An integral survey from intratecal immunity and antioxidant activity

Maria Robinson-Agramonte, Milena Rodriguez Álvarez, Martha Nápoles, Teresa Serrano Sánchez.
Bertha Willson, Elizabeth Hernández. Hansotto Reibera, Yozvany Bouza, Reynaldo Galvizu
Centro Internacional de Restauración Neurológica. Ave 25. No 15805 e/ 158 y 160, Playa. CP
11300. Ciudad de la Habana. Cuba. a Neurochemistry Lab, Gottingen University, Germany.
Inflammation and oxidative stress are refereed as biological markers from different fluids in ME,
looking for some evidences helping to a more integral understanding of the course of the disease.
CSF analysis is a main tool in the study of these biological markers; nevertheless, no less important
markers from peripheral fluids add information on the pathological events of the disease. We show
an integral result of the immune-inflammatory response and oxidative stress in-patients with the
diagnosis of ME and control subjects. The analysis included the evaluation of intrathecal immune
response using Reibergram program, the quantitative determination of cytokines (IL 1b, TNFa)
following ELISA method as well as the quantitative estimation of antioxidant activity referred to
the evaluation of variables relatives to oxidative (GPX) and nitrative (ON) stress. The probable
interaction between all this parameters was analyzed too. A differential Reibergram pattern of
oligoclonal intrathecal fraction was observed while the antibody polyspecific response to
neurotrophic viruses showed an increased AI with a differential frequency of combination to each
patient. Also, ME patients showed a significant difference to TNF a and GPX activity (p<0.05) as
well as some interaction level with the former with antioxidant nitrative activity The results
underline the inflammatory mechanism in ME and tag the reactive oxygen species as cellular
messenger instead a simple pathogenic agents to the disease, in add to their potentiality to evaluate
the progression/ activity of the disease.

                                      Acupuncture treatment for neurologic restoration

Carlos M. Méndez Alonso, Tahimí Cardoso Suárez, Irene Jiménez Ortiz
Holistic Medicine Department, International Center of Neurological Restoration. Habana,
Introduction: Asian Traditional Medicine (ATM) and within it Acupuncture is a diagnosis and
treatment system approved by WHO and promoted by our National Public Health System. There is
a growing interest on ATM efficacy in chronic affections of the CNS, as its use has been reflected
in the clinical practice, and in the increasing number of investigation on this issue. Our center is one
of the pioneers in incorporating this source of knowledge so much in attention care as in
investigation. Objective: to describe and analyze the diagnostic, the therapeutic strategy, and the
patient s´ evolution in some of the more frequent neurological affections at our Center.
Development: The bases for ATM are described here, so much as to the traditional conception as
from the results of present-day investigations. The diagnosis process is described here, the design of
the therapeutic strategy and treatment as well as evolution of different affections are explained in
detail in relation with encephalic static lesions due to occlusive cerebrovascular disease.
Conclusions: Acupuncture implies an individualized and therapeutic approach based on diagnosis.
there are investigation in which acupuncture seems to have a neuroprotective action and its use
favor recovery of patient neurological affections. Basing ourselves on our experience, we can assert
the value of its integration to the Intensive Multifactorial Rehabilitation Program.

                                 Risk factors and carotid steno-occlusive lesions

Liván Rodríguez Mutuberría, Carlos Suárez Monteagudo, Yusimí Serra Valdés
International Center for Neurologic Restoration(CIREN),Havana, Cuba.
Cerebro – vascular disease is one of the most frequent issues of urgent neurological assistance,
which constitutes a serious problem for public health. According to World Health Organization,
Cerebro – vascular disease is the third cause of death and the first of disability in adults.
Aterotrombosis stroke due to carotidean ateromatosis is a frequent form of presentation of such
disease. We performed a prospective study on 60 patients hospitalized at the Clinic of Encephalic
Static Lesions, all affected with aterotrombotic stroke, to evaluate the behavior of carotid steno –
occlusive lesions as a risk factor of ictus recurrence, as well as those factors that condition this type
of lesion. Data were conformed according to the medical exam practiced on these patients and other
complementary studies, including carotid Doppler study of the Duplex – type. Work was performed
on age and sex variables, risk factors, percentage of patients with carotidean lesions and severity of
stenosis. We based ourselves on the study performed by the North American Symptomatic Carotid
Endarterectomy Trial (NASCET) and the lineal descriptive method was used for the registering and
tabulation of the data. The results showed the presence of steno – occlusive lesions in 58.3 % of
studied patients, the greatest amount corresponded to lesions above 50 % and most important risk
factors were Essential Arterial Hypertension and hyperuricemia.

                          Spirometric alterations in patients w ith high spinal cord lesions

Gilda T. Martínez Aching, Ma. del Carmen Padín Hernández
International Center of Neurologic Restoration (CIREN). Havana, Cuba
Breathing inadequacy is a frequent complication in the medullary lesioned patient. The fundamental
objective of this work was to study the results of spirometric evaluations of the Breathing Vital
Capacity on patients with high medullar lesions. We use a sample of 30 medullary-lesioned patients
assisted at CIREN. Tests to evaluate the breathing capacity (vital strength capacity by using a
Multispiro Sensor with an international scale: ECCS). Results. After initial and final evaluations,
we verified the majority of cases were not able to vary their category as to restrictions (severe,
moderate, slight) of the breathing capacity, however we observed positive modifications in all cases
after receiving breathing therapy.

                    Response to the breathing therapy in the cervical medullary injured patient

María del Carmen Padín Hernández, Mayda Nelia López Hernández
International Center for Neurological Restoration, Havana, Cuba
OBJECTIVE: to Demonstrate the utility of the logopaedic therapy on the recovery of patients with
Cervical Medullar Lesions. MATERIAL AND METHOD: We use a sample of 20 patients with
cervical medullar lesions, assisted in the Raquimedullar Clinic in our center during the year 2000.
Patients received from 1 to 4 treatment cycles (28 days each), with a frequency of a daily hour. An
initial study was carried out that included chronometric, inspirometry, numeric count, spirometry,
vocalizations during an espiration and the evaluation of the possibility of coughing, to expectorate
and to sneeze. DISCUSSION: It was possible to establish the appropriate breathing type
(costodiafragmatic). The inhaling exercises and exhaling resulted in the increase of the breathing
capacity in an average of 300 cc and the appropriate coordination. The exercises for the dosage of
the air during verbal emission contributed to normalize the vocal emission in 100% of the cases.
The whole group of procedures allowed the variation of the rest of the controlled vital functions:
50% achieved expectoration without help; 45% achieved audible cough. CONCLUSION: Improved
the quality of life of the patients with cervical medullary lesions can be achieved with our
therapeutic program.

                    Determination of the antigen HLA-DR2 15 in patients w ith multiple sclerosis

Guadalupe Zaldívara, Julio Granadosb , Carlos Sosa c.
  Facultaty of Medicine, Autonomous University of Querétaro, bDepartment of Inmunología and
Reumatología National Institute of the Nutrition "Salvador Zubirán", cDirector of the Natural
Faculty of Sciences of the University Autónoma of Querétaro.
The Multiple sclerosis (MS) is an inflammatory demyelinating disease of the nervous central
system (SNC), characterized generally for an initial boss of exasperations and cyclical references,
evolving to a chronic progressive course. Even that the MS is one of the most common neurological
diseases, it is an entity of which, the reason and the pathogenesis are unknown. Is observed with
major frequency in persons that carry the antigen HLA-DR2-15, by which there is presumed that
the persons who carry this antigen are more capable of suffering MS. The aim of this work was to
determine the above mentioned antigen in hybrid Mexicans with diagnosis of clinical MS and by
magnetic resonance. Material and Methods: one determined the antigen HLA-DR, 15 with PCR
(Polymerase Chain Reaction) in 8 subjects with MS. Also it was determined: age, sex, place of birth
and time of residence, personal precedents of sufferings, family precedents of sufferings, nourishing
habits, alcoholism, nicotine poisoning, current place of residence, trips, education, profession,
socioeconomic status, anomalies of the sexual function and if they live together or not with animals.
Result: The analyzed patients are 6 women(wives) and 2 men, of socioeconomic average way.
Nobody has MS's familiar(family) precedents. They all have lived in cities of the country, none
lived out of the country during its infancy, and they come from latitudes that do not correspond to
the areas of high.
Friday 27 febraury 2004

Plenary lecture

        Compensatory mechanisms and motor functions of the basal ganglia: lessons from Parkinson´s disease

Jose A. Obeso
Department of Neurology-Neurosurgery, Clinica Universitaria and Medical School,
University of Navarra, Pamplona, Spain.
The revitalization of surgery for Parkinson´s disease (PD) has provided new opportunities to
examine the effects of focal lesion of the basal ganglia and the adequacy of current
pathophysiological concepts. Modern studies have shown that pallidotomy in Parkison´s
disease(PD) induces significant improvement of movement parameters, restores thalamo-cortical
activity and eliminates levodopa-induced dyskinesias without causing any major deficit of
movement control. In patients with hemichorea-ballism or dystonia, pallidotomy also induce
marked amelioration of the dyskinesias with no associated deficit. Lesion of the subthalamic
nucleus(STN) in PD is also associated with marked motor benefit. Subthalamotomy may produce
hemichorea.ballism in many patients but this is usually self-resolving over a few days or weeks.
Thus, there is a spontaneous resolution of the dyskinesias. In a few patients, the hemiballism may
be severe and long-lasting. In such cases, as it is well known from the experimental literature in the
40´and 50´s, a subsequent pallidotomy will eliminate the hemiballism without loosing the
antiparkinsonian benefit. Such patients, who are literally deprived of basal ganglia output in one
hemisphere appear to perform remarkably well.. On the other hand, bilateral surgery of the basal
ganglia is usually associated with important side effects. In addition, striatal dopamine depletion has
to surpass over 90%(in the MPTP intracarotid injection model) in order to produce parkinsonian
symptoms but much milder (i.e. 50%) bilateral depletion causes clinically relevant motor symptoms
in PD. I conclude by suggesting that unilateral disruption of the basal ganglia is tolerated very well
by the primate brain. This may be understood as a result of the distributive and bilateral distribution
of the motor system, which does not depend upon unilateral BG output activity to perform motor
routines indicating the importance of the BG-frontal cortex loops in guiding movement and

From Basic Neuroscience to clinical practice

         The role of progesterone and related neurosteroids in the treatment of traumatic brain injury and stroke

Donald G. Stein
Emory University, Dept. Emergency Medicine, Atlanta, Georgia 30322, USA
We are now examining the role of progesterone‟s precursors and metabolites to determine their‟
specific mechanisms of action in the damaged central nervous system. We are also testing patients
in an NIH sponsored, Phase II (a), single-center trial for safety and efficacy. The functional,
physiological and genomic mechanisms underlying progesterone‟s beneficial effects and still being
discovered and some of the newer findings will be described as a part of the presentation. There is
now increasing, experimental evidence that this neurosteroid can play a role in reducing immune
inflammatory disorders of the brain as well as providing benefits to the victims of stroke. We are
currently examining these injury models in both laboratory rats and mice. In laboratory animals,
females with traumatic brain injury have better functional and morphological outcomes than males
with the same extent of injury. Naturally occurring levels of progesterone in females appear to
mediate these beneficial effects. Treatment with exogenous progesterone in both adult males and
females will lead to better outcomes after traumatic brain injury. The beneficial effects of
progesterone treatment are related to its ability to reduce post-injury cerebral edema caused by the
cytotoxic cascade caused by the trauma. Progesterone and its constituents act by reducing immune-
inflammatory reactions, membrane lipid peroxidation, apoptosis and necrosis. Progesterone and it‟s
metabolite, allopregnanolone, stimulate remelination of damaged axons and enhance regeneration.
Phase IIa trial with progesterone sponsored by the U.S. National Institutes of Health is currently
being conducted.

                       The growth of the Hebb Synapse: Evidence from the hippocampus

Aryeh Routtenberg
Northwestern University, USA
Since the time of Cajal it has been thought that learning leads to an input-dependent neuronal
growth process. The extent of growth of new synaptic connections has been speculated to be
directly related to the long-lasting nature of the memory for that learning experience. Here we test
this hypothesis by focusing on one particular synaptic junction, the mossy fiber –CA3 pyramidal
cell synapse in the stratum lucidum of the hippocampus, which is known to process information that
is critical for long-term memory. Initial evidence from this and other laboratories indicates that
new growth has occurred such that ectopic mossy fibers are present in the stratum oriens. But this
growth only occurs with overtraining. Why does new growth require overtraining, not simply
training, to propel the apparent formation of new synapses formed consequent to spatial learning? A
general framework for a specific answer may be in the formation of duplicate traces as initially
proposed by Hebb. According to this view, the long-lasting nature of the memory trace depends on
the formation of multiple representations of that trace. This implies that the mossy fiber system
could be part of the network that represents the memory, or more accurately, a facet of the attributes
of memory. A provisional working hypothesis is that learning begins the process of mossy fiber
growth and that such growth provides the development of new circuits that overtraining activate,
which in turn allow for reduplication of traces, involving mossy fibers in part, which are necessary
for the long-term storage of information. Thus, available evidence on mossy fiber growth in rats
makes it attractive to think that enhanced learning after overtraining may be both a consequence and
a cause of the growth of mossy fibers. One over-arching long-term goal of this research is to specify
the molecular determinants of this learning-induced growth. The readily identifiable characteristic
features of the presynaptic and postsynaptic elements make them ideal for studying the role of
growth proteins and their regulatory kinases. By using this tractable model, the proposed research
provides the infrastructure to determine whether training-induced mossy fiber growth represents a
specific instance of a more general event that occurs after learning in key memory storage locations
throughout the brain.

                      The 'emotive brain', the noradrenergic system and functional plastic ity

Susan J. Sara
University of Paris 6, Paris, France
Motivation and attention can have a profound influence on perception, learning and memory.
Neuromodulatory systems, especially the noradrenergic (NE) system, covary with psychological
states to modulate cortical arousal, influence sensory processing and promote synaptic plasticity.
There is even some suggestion that the NE system might facilitate functional recovery after brain
damage. Post-synaptic effects of NE in its ubiquitous projection regions have been well-studied, but
factors controlling activation of NE neurons are less known.The pontine nucleus Locus Coeruleus
(LC) contains the entire population of NE neurons projecting to the forebrain and all cortical and
thalamic regions receive NE input. Using single unit recording in freely moving rats, we have been
studying neuroanatomical circuits, along with sensory stimuli within their cognitive contexts that
control LC firing. Rats are implanted with movable microelecrodes to record activity during a
variety of behavioral situations: exploration of novelty in a hole-board, response to tones or odors
that predict reward or absence of reward, extinction or reversal of stimulus-reward association. We
find that LC-NE neurons respond to novel or salient stimuli, habituate rapidly to respond anew
when the stimulus is associated with reward (CS+), particularly in the early stage of learning.
Recent experiments suggest that these responses are more related to reward expectancy than to the
CS+. Importantly, there is robust LC response to any change in the predictive value of the stimulus,
i.e. when new learning must occur. NE released by LC activation will promote the underlying
synaptic plasticity.

                         Neuroplasticity and depressiv e disorders. Efficacy of tianeptine.

Clara Lucia Abreu de la Torre, Jorge Bergado Rosado, Eduardo Alvarez González, Carlos Suárez
Monteagudo, Rene Macias Betancourt, Roidel Alessandrini González, Rolando Palmero Camejo,
Centro Internacional de Restauración Neurológica (CIREN), La Habana, Cuba
Introduction. Depressive disorders have a prevalence of 15-20% in the general population. The rate
of depression in cerebro-vascular disease (CVD) increase to 30 and 50% Recovery of affected
functions depend mostly on neuroplastic mechanisms which can be enhanced by therapeutic
interventions. Recent evidence has indicated that neural plasticity depends on affective factors,
which modulate its strength and duration. It is therefore important to correct depressive disorders in
patients under rehabilitation treatment. Objective. To evaluate the efficacy of different
antidepressive in CVD patients under treatment in our clinic. Method. The severity of depression
was evaluated using the Hamilton Scale for Depression before and after conclusion of the
therapeutic program. Antidepressive therapy with tianeptine (25 mg, average dose) was introduced
in a group of 30 patients, which were previously without medication. Other patients under
antidepressive treatment continue using the same drugs and dose. Results: Tianeptine revealed to be
the most effective drug considering the improvement in their affective condition, the better results
in rehabilitation and the reduced side effects.

                                    Redefining the self after neurological insult

Robert D. Voogt
Robert Voogt & Associates, Inc., Virginia Beach, Virginia, USA
For almost 10,000 years, the medical community has been involved in the understanding of the
human nervous system. The most devastating aspect of neurological insult is the historical loss of
who the individual was. Whether it is an alteration in how one ambulates or the ability to interact
and be a part of the community, these changes require a redefinition of the self. Throughout the
ages, literature and the arts have portrayed the progression from ancient medicine and healing to
modern scientific technology. Seeking cures through medicine and potions was seen as early as
2100 B.C. Our success at controlling nature has created a world of disabilities because of much
higher survival rates. We struggle every day to defy mortality and end up failing and living with
people who are handicapped. They remain handicapped because the environment and community
around them have failed to integrate them. In fact, the community often seeks to shut them out and
reject them as less than able. Both, the community of abled and those disabled, lose.The goal of
21st century medicine must be more than the desire to control nature. It must unite the healer with
those in need of healing and mend the relationship between patient, healer and the community. This
presentation takes a historical look at the healing process and healing profession in an attempt to
define the absolute goal in neurological rehabilitation.

Institutional and social aspects of neurological restoration

             Cognitive and behavioral rehabilitation of children and adolescents with traumatic brain injury

Mark Ylvisaker
College of Saint Rose, Albany, New York, USA
Cognitive impairments and associated problems with communication, behavioral self-regulation,
and academic performance are among the most common consequences of traumatic brain injury in
children and adolescents. For families and teachers, the behavioral consequences of TBI tend to be
most problematic. Attempts to restore isolated cognitive functions with discrete trial cognitive
training exercises have yielded disappointing results in both children and adults with TBI.
Similarly, attempts to improve behavioral regulation with traditional contingency management
behavior modification strategies have yielded disappointing results with this population. I will
briefly review alternative approaches to cognitive rehabilitation and behavior management, and
describe a context-sensitive and support-oriented approach that is consistent with the
neuropsychological profiles of many children and adolescents with TBI. Study Purpose: to test the
effectiveness of a combined cognitive, behavioral, and executive function intervention, delivered
within school settings and the academic curriculum; The intervention highlighted context supports
(e.g., supportive interactive style of education staff) as well as compensatory strategies and general
executive function routines for the child. Study Methods: single subject experimental methodology
was used to test the intervention with young children and adolescents. Study Results: In each case,
the intervention resulted in a reduction of negative behaviors and an increase in school work
completed. Furthermore, the intervention was judged to be easily delivered within the context of
everyday school routines.

               Cognitive Rehabilitation Outcomes for Traumatic Brain Injury – Evidence Report Update

Nancy Carneya, Hugo du Coudraya,b
  Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science
University, Portland, Oregon, USA, b Department of Psychology, Portland Sate University,
Portland, Oregon, USA
In 1998 the Evidence-Based Practice Center (EPC) of Oregon Health & Science University
(OHSU) conducted a systematic review of the scientific literature about the effectiveness of
cognitive rehabilitation for the treatment of traumatic brain injury (TBI) in adults. In 2002 we
updated that report. We conducted an electronic search of MEDLINE, PsychINFO, CINAHL, and
the Cochrane Controlled Trials Register to capture literature from 1998 to 2002. We sought
randomized controlled trials, non-randomized comparative trials, and systematic reviews.
Publications were excluded in which samples included non-trauma brain injury and did not
distinguish data for those patients from data for patients with TBI. Of 1,904 abstracts, and 24
additional references provided by peers, 9 publications met the inclusion criteria and were
abstracted for evidence. In this presentation we will discuss the findings from the update, and will
compare the quality of the literature generated between 1998 and 2002 with that of the previous
evidence report.

                                   The Brain Injury Day Treatment Program (BIDTP)
Virginia Balbona a, John Sassb
  Department of Rehabilitaion Medicine, Emory University, Atlanta, Georgia, USA, b Restore
Neurobehavioral Center, Roswell, Georgia, U.S.A.
Patients who have suffered traumatic brain injury (TBI) are participating in an intense program that
considers their cognitive, social/emotional, and vocational rehabilitation. This innovative program
based on the work of Yehuda Ben-Yishay, Ph.D. consists of an Initial Comprehensive Evaluation
during which the patient undergoes a neuropsychological assessment. The evaluation reveals what
cognitive deficits the patient may have as a result of their TBI and which skills have remained
intact. The First Phase of the program (The Intensive Remedial Treatment) involves daily
Orientation, Interpersonal Communication Skills, Cognitive Remedial Training, and Community
Meeting Classes. Weekly Multiple Family Group sessions are attended by all the patient‟s
significant others and the staff. The patient and family/significant others also receive counseling on
a weekly basis. Twice during the program, the patient prepares, writes and rehearses a presentation
given before an audience of guests and significant others. The presentations are videotaped and used
as a tool to learn communication skills. The Second Phase of the program (The Guided Work
Trials) transfers what the patient has learned in the remedial phase to a less structured environment.
The goal is to discover the patients‟ potential for returning to work. Patients receive personal and/or
small-group counseling. They receive guidance in areas that encourage independent living and
performing activities of daily living. The Third Phase of the program (Post-Discharge,
Maintenance/Follow-up Therapy) aims at helping the patient find work in the community and
following their progress.

   Cross-cultural analysis of predic tors of outcome from traumatic brain injury: an Argentina/United States collaboration

Nancy Carney
Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science
University, Portland, Oregon, USA
In 1998 researchers from Oregon Health & Science University (OHSU) initiated a prospective
observational study of traumatic brain injury (TBI). They established a system to collect data about
patients with TBI spanning field transport, emergency department, intensive care unit, and hospital
ward, and extending to post-discharge and long-term functional outcome measures. The objective
was to compare outcomes for patients who received rehabilitation with those who did not. The
investigators developed complex acute care measures of severity to improve their ability to
associate severity with outcome, in order to control for the influence of this variable on outcome. In
2000 this group formed a collaboration with physicians from the Neurocritical Care Group of
Sociodad de Argentina Terapia Intensiva (SATI) to initiate a similar study in Argentina, where
rehabilitation for TBI is rare. There are 105 patients in the Oregon dataset and 278 in the Argentine
dataset. In this conference we will present initial findings from these studies. We will compare
treatment and outcomes for TBI patients between the two samples, and will present results of our
analysis of predictors of outcome within and between both populations.

                               Latin-American Brain Injury Consortium. A brief presentation

Caridad Soler Morejón,
Cuban Section of Neurointensivism. National Council of Scientific Societies, Cuba
The Latin-American Brain Injury consortium is a free association of Latin-American professionals,
dedicated to the attention of brain damaged patients. This non lucrative organization was founded
last month in Rosario, Argentina, and up to now, it joins medical doctors from 11 Latin-American
countries, including Cuba. The main objectives are the following: 1) To promote the training of
professionals who assist patients with brain injury, (courses, and meetings). 2)To promote and
address researches for the improvement of the outcome of adult and pediatric patients suffering
acute brain injury. 3) To establish close collaboration between centers and researchers in Latin
America, for the management of brain trauma and other acute brain diseases. 4) To negotiate and
participate with the sponsors of the researches to assure the excellence in design, conduction,
analysis, and publication of essays and researches. 5) To act as a supervisor in theoretical and
practical aspects related with the different studies. 6) To promote the diffusion of Guidelines for the
management of different brain acute diseases. 7) To promote the cooperation with other
consortiums or Brain Injury Groups from our region and other countries. Finally, our purpose is to
present the goals and possibilities for the integrative and collaborative work that this organization
could mean to our countries in order to achieve the better prognosis for our patients. Scientific
researches and training are the most important tasks focused in this program.


Strategy for communication and integral attention in the service to the neurologic patient.
CIREN’s experience

Rosa María Medina, Víctor Manuel González, María del Pilar Vilá, Farah María Paredes, Juan
Miguel Avellanet
International Center for Neurological Restoration (CIREN), Havana, Cuba
A patient, who decides to receive most adequate medical and rehabilitation services in another
country, needs to find well-structured programs with communicative actions and an integral
attention to fill the gap for his/her habitual environment. CIREN‟s staff - inspired in the
characteristics of the Cuban health and social systems - offer love and human warmth to contribute
to the fulfillment of objectives for the patient‟s Neurological Restoration Program, for a safer and
more pleasurable stay. This facilitates his/her recovery – which can also become a means of
promotion. This issue is verified through different and systematic tools to know the patient‟s own
satisfaction and to perfect the quality of offered services. Some results were: between 85% to 93%
valued as suitable and pleasant the following communication actions as: reception and welcoming,
transfer, information, attention, invoicing, visas, and other services pertaining to International
Relations. An internal investigation of its staff on optimum communicational capacity showed
80%. More than 60% of incomes are the result of recommendations from relatives, friends,
neurologists and others who know about this original and successful therapeutic experience. More
than 35% are re-entering, and an 83% formulate notable differences as compared to other
institutions; between a 98% and a 100% consider excellent the quality of diagnosis, the physician‟s
work, as well as efficacy of physical therapy and nursing personnel. More than a 95% express their
desire to come back and to recommended CIREN to others “because the attention and medical
service are the best we have ever received”.

           Process for Quality Certific ation of Work Groups as an Strategy of CIREN’s management System

C Vázquez, B Castro, M Peña, E Cabrera
International Center for Neurological Restoration, Havana, Cuba
Quality is to achieve the user‟s satisfaction. Quality Management is an institutional organization
that influences all technical and non-technical activities that take place within the institution. Since
l994, CIREN has a Quality System where each group, department or clinic, uses a Manual of
Norms and Procedures, along with a Plan for Quality Protection. This strategy has permitted us, for
two years, to achieve a documentary organization within the quality process, and since 2002, we
started to work on the design and implementation of the Quality Management System according to
established requisites at NC ISO 9001:2000 “Requisites of the Quality Management System”. In
order to guarantee all this process, we have designed a Quality Certification Procedure for all work
groups, whose objectives are: to establish the methodology for Evaluation and Certification of the
Quality in the integral work of all groups, and consequently, to achieve greater efficacy and quality
in the services offered to the patients. This descriptive study is based on data of variables, obtained
through Inspections for Certifications of Work Groups, and more comprehensive Integral
Inspections expressing the quantitative and qualitative results.

        Use of informatics as a strategy for communication in the relation w ith the neurological patients: website

María del Pilar Vilá Cienfuegos, Mayra Llanes Govín, Víctor Manuel González Albear, Juan
Miguel Morales Oliva, Emilio Villa Acosta, Elías Valdés Llanes, Martha Cristófol Corominas
International Center for Neurological Restoration (CIREN); Havana, Cuba
We performed a revision on the Theory of Information and its relation with the sciences of Social
Communication, strategies and objectives. This issue is a link to work strategies at a health
institution where services offered to neurological patients. The three types of necessary
information for this type of patient as to most important moments for him-her to pass through in
relation to the institution are as follows: search for updated information to request medical attention,
establishing a communication link with the institution while he-she receives attention there, and
maintenance of a communicative link with the attention center for the patient to know about
scientific advances and the introduction of new technologies that may take place at any moment in
relation to his-her needs. All the above mentioned is linked to the established design for the center‟s
website in order to take at advantage of its capacity for diffusion of the type of informatics tool in
the satisfaction of relation that the center may have with all neurological patients interested in this
type of attention. After a necessary analysis and the discussion on the contents of our work, we got
to conclusions as to its usefulness and therefore recommendations are made as to its importance for
professionals linked to this issue.

                               Community-Based Cognitive Rehabilitation of TBI patients

Bringas M.L., Pedroso I.
International Center for Neurological Restoration, Havana, Cuba
This program intends to provide long-term cognitive rehabilitation services to patients with TBI
after discharge of the hospital which final goal were the employment or social insertion of them.
Cognitive rehabilitation is a set of therapies used to help improve damaged intellectual, perceptual,
psychomotor and behavioral skills and usually is offered only at the hospital environment. The
program has three phases: 1st relaxation or general preparation (are stimulated activities to reduce
stress and tension, relaxation, artistic skills, games, hydrotherapy, music and physical exercises).
2nd stimulation of cognitive functions (Exercises of Attention, Memory, Thinking and Calculus are
structured on four levels of complexity). 3rd stabilization of the cognitive outcomes (consolidation
of intellectual strategies, independence, self-esteem to prepare the social insertion). Transition
between phases is individual and the objectives of the program are adapted to patient needs after an
extensive neuropsychological and psychopathological evaluation. We designed this program using
one relative or retired teachers as provider of the services, who received training for delivering the
tasks, management of the frustration and to know how obtain the results and register the data. We
showed results of this program with a sample of 5 TBI patients who followed this program after
their discharge of the Clinic for Cuban Patients of CIREN. All of them improved their initial
neuropsychological scores and are doing social activities now. The most important variables
influencing the outcomes were severity of brain damage, age, evolution, pre-morbid personality,
family support and marital status.

                   The Institutionalization and its Relation w ith Mental Problems and Conduct Disorder

Luciana Mara C. Andrioti , Marcos Tomanik Mercadante
Master Program in Development Disturbances, Mackenzie Presbyterian University, Brazil
The inexistence of public health control in infants‟ psychiatry compromises the development of
great part of the Brazilian population. Researches made in some institutions reveal 49,2%
psychiatric disorder rates(and it represents 14,3% of the controls). The most common disorder is
depression (28,6%) (Abreu 2000). In the Southeast of Brazil was identified the prevalence of 12,5%
of one or more disorders, and if it is projected in the nation it suggests 3,4 million people with these
problems (Bilyk, 2002). The aim of this research has been to identify the prevalence of mental
problems and conduct disorder in children and teenagers between 4 and 17 years old who live with
their family and go to school, throughout the role of interviews called Development and Well-Being
Assessment, DAWBA. Not only the definition of these children‟s profile, but also the determination
of parameters in the interventions that could be re-evaluated, they will contribute to decrease the
number of disorders and the impact they cause on these people, as well as their family and the

                      Nursing care and neuro-rehabilitation for patients with Parkinson’s syndrome

Miyares Paz Luanda, Morgado Teresa, Rojas Morales Juana M.
International Center for Neurological Restoration (CIREN) Havana, Cuba
The nurse is an important link within the team involved in neurorehabilitation carrying out multiple
functions and achieving improvements in abilities as well as language and rehabilitation and
treatment of patients with Parkinson‟s syndrome because of this we felt motivated to conduct a
descriptive, retrospective and transversal study involving twelve patients admitted to CIREN‟s
Clinic Movement Disorders and Degenerative Diseases during the period from march 2002 to July,
2003. The results obtained from the majority of these patients showed great improvement in
physical mobility by combining the pharmacological adjustment with the neurorehabilitation,
achieving improvements in mastication and absorption of food. Almost all patients achieved
adequate elimination through an education in healthy habits in diet, the taking of medication, etc.
They were also able to regulate their sleep patterns and better able to utilize mechanisms of problem
solving to deal with family issues.

    Risks in chronic neurological patients. Experience at the International Center of Neurological Restoration (CIREN)

Lissette Miranda Lara, Maria Ángeles Peña Figueredo, Maria Isabel Garrote Lee
International Center for Neurological Restoration, Habana, Cuba
At the International Center of Neurological Restoration we attend patients with several neurological
and neurosurgical diseases. They are exposed to many risks that can create additional
complications. We made a review, in a retrospective study, using the reports to the Program for
Prevention and Control of Accidents in use at CIREN. We include all reports made during year
2002. The mayor risk was falling down (21 cases) and infections (72) from the total of 1039
patients hospitalized during that year. The greatest incidence was found at the Clinic for Spinal
Lesions, followed by the Clinic for Adult Static Lesions. This analysis lead to the introduction of
strategies applied in our institution, by a team of nurses to decrease the risks of the patient based on
the application of the Nurse Attention Process.
                                   Evaluation of quality of life in Parkinson’s disease

Leisa Díaz, Lázaro Álvarez, A Martínez, David Castañeda
International Center for Neurological Restoration (CIREN), Havana, Cuba
The present tendency to examine the impact of treatment on the quality of life of persons with
Parkinson‟s disease includes the development of specific instruments of measurement (PDQ-39).
Recently, Martinez and his collaborators have adapted the English version of this instrument into
Spanish, using 37 items, validating them appropriately, demonstrating a strong correlation between
the clinical variables and the well- being of Parkinson‟s patients. It is highly sensitive and specific.
Between January 2003 and August 2003 we developed a protocol to evaluate this Spanish version
for our work. For this purpose, we have applied the Spanish version of the PDQ scale to 30 patients
with Parkinson‟s disease, 10 who only received a pharmacological treatment, 10 who were treated
with a multidiscipline approach, and 10 were operated using the technique of stereotactic surgery.
We observed a high correlation with the sub sections of daily activities and motor condition on the
Unified Scale for the evaluation of Parkinson‟s PDQ. We obtain a reduction of 40% of the PDQ
scale before treatment in operated group, and strong correlation whit UPDRS scale (Spearman R
0,515). We also noted the sensitivity of the PDQ in its ability to measure the patient‟s ability to
distinguish between ON and OFF and to note the usefulness of the above treatments. We can
conclude that the Spanish version of PDQ is a useful instrument for the evaluation of the effects of
any treatment on Parkinson‟s and is well designed to examine the utility of any clinical treatment.

         Appraisal of the development and growth in childen with cerebral palsy. Nursing care to these patients

Norbert Sosa García, Luis Hernández Ramos, Mónica Hernández Díaz, Mirna Álvaro- Díaz
CIREN,Habana, Cuba
We performed a retrospective and descriptive study for the evaluation of 103 patients bearers of
cerebral palsy, hospitalized at CIREN's Neurology Clinic for Children during January 2000 to
December 2002. This issue aims at demonstrating the existence of nutritional deterioration in these
children, to relate them with a psychomotor commitment and to establish specific nursing cares for
their neurological rehabilitation. We selected a group of pediatric patients with ages ranging from 1
to 15 years of age. We defined the absolute frequency and percentage according to sex and applied
gross motor function scale for their psychomotor assessment and clinical diagnosis, as to the type of
cerebral palsy and its distribution. The evaluation of their nutritional status in relation to weight and
height (according to Jordan‟s Scale) was performed and we determined it predominates in the
psychomotor affectation in males and in those patients with a greater compromise We evidenced in
these children important nutritional affectations –where 26 patients were in the percentile range
from O to 25, which means a 25 % of the total of evaluated cases. Our team kept in mind, that for
the sake of nursing, fundamentally educative work with the parents as to their children‟s nutrition
and its immediate importance during the course of their neurological restoration was necessary.

                  An experience in the treatment of Autism at CIREN’S Neurology Clinic for Children

Idelys Sarduy , M. Eugenia García, Carlos Maragoto
Internacional Center for Neurologic Restoracion (CIREN), Havana, Cuba
Introduction: Autism is a relative mental impairment that typically appears during the first three
years of life and it is the result of a neurobiological disorder that affects brain functioning. Main
characteristics of this disease are: qualitative hindrance in the social interaction and in the
development of language and communication, as well as a restricted range of activities and interests
with the use of repeated and stereotyped patterns. Objective: To present our experience and results
of the work with 5 cases diagnosed with Autistic Specter Disorder assisted at CIREN‟S Neurology
Clinic for Children. Patients and Methods: A retrospective study was performed on 5 cases, starting
from the revision of defectologic records where we collected data related with treatment and
responses by the patients to this treatment and to initial and final neuropsychological evaluations.
Results: In all the cases favorable changes are observed as to social, intellectual and conduct
relations. Conclusions: The results achieved can be considered significant by keeping in mind, time
of treatment and severeness of the disorder.

                     Nurse management to patients w ith temporal and extra temporal epilepsy

Miriam Esther Guevara Pérez, Mercedes Frontela Hernández, Digna Pérez Madrigal, Lilia Morales
Centro Internacional de Restauración Neurológica (CIREN), La Habana, Cuba
Introduction: One important goal of the nurse‟s action in a Telemetry Unit is to identify the type of
epileptic seizures of patients under long-term follow up with video-EEG.
Objectives: To describe the differential handling of patients with temporal or extra temporal
epilepsy. Material and Method: Twelve patients were studied, from them 6 were previously
classified as temporal and 6 as extra temporal epilepsy. The clinical, motor, automatic and
autonomic signs, as well as the presence of aura, response degree and memory of events during the
crisis were evaluated. Results: All patients with temporal epilepsy showed automatic movements
during the ictus. The most prominent pattern at the beginning is locked gaze (90%) and aura (90%).
Extra temporal crisis showed tonic-clonic generalized crisis (83.3%). None showed automatic
behavior and none of them recall aura. Conclusions: In the handling of the epileptic patients with
temporal seizures, it is important to keep a constant observation and verbal communication with the
patient in order to detect behavioral alterations and to recognize automatic patterns (oro-facial
gesture, feeding-like behavior, walking without a purpose) to allow an early detection of the crisis
and to prevent trauma. Extra temporal seizures require extreme security measures, because in most
cases the patients suffer loss of consciousness, along with body convulsion and rapid, uncontrolled
movements. The nurse must, in every case; act to prevent self inflicted injuries, falling dawn and
other potentiality noxious consequences.

                       Intervention strategy for the training of the hemiplegic patient’s family

Tania Francia González, A. Vernis González
International Center for Neurological Restoration (CIREN) Havana,Cuba
In this study we propose an intervention strategy, which centers its attention in training and on the
basis of orientation through the occupational therapist, to those persons in charge of caring for
patients who suffer the results of stroke. It is indispensable for there to be instructed on the
knowledge of the disease‟s characteristics, the techniques for the handling them and how to help
patients in the acquisition of abilities for the development of daily life activities as important as:
getting dressed, self-validism, and feeding. The method used in this investigation was the
experimental one for which a sample of 30 patients was used and divided into two groups: one
control group and an experimental one, each one with a total of 15 patients. Barthel`s index was
used to measure self-validism level in the selected population. We arrived to the conclusion that
with this type of combined therapy among specialists, family and patient the experimental group
improved considerably because they were able to establish and to automate in a short period of
time, the daily abilities of feeding, self-validism and dressing. It facilitated the patient‟s
independence and it increased the level of the relatives' knowledge in the correct handling of the

                          Integral Handling of Sialorrhea on patients with Cerebral Palsy

Nayoy Rodríguez Verde, Giselle Núñez González, Edgar Ney Galarraga
International Center for Neurological Restoration, Havana, Cuba
Introduction. Sialorrhea may have a significant negative effect in the quality of life, of patients
suffering from cerebral palsy, hindering their adequate social interactions. This disease is an
impairment of saliva flux. Objective. Our purpose is to contribute to the control of sialorrhea
through the application of different therapeutic procedures. Materials and methods. We presented a
sample of 18 children, ranging from 2-10 years of age hospitalized at the Clinic of Neuropediatrics
for a 28 days stay during years 2001-2003. We used therapy of different kinds for approximately 15
minutes, and evaluated the patients at the beginning and end of the rehabilitation cycle. The applied
techniques for treatment were: intra-buccal massage, crymotherapy (in such cases where orolingual
muscles were hypotonic), lemon drops and mechanical stimulation of facial points with the use of a
point vibrator. Results. We obtained a great increase in the mobility of orolingual structures that
intervene in saliva swallowing. Most favored categories: labial, velar and lingual praxis, where we
obtained 83,3 %, 100% and 59,3 % of improvement, respectively. Conclusions. The application of
different procedures to favor the control of sialorrhea on pediatric patients with cerebral palsy is
considered effective in speech therapy.

                           Disphagia in the neurological dysfunctions of communication

Mayda Nelia López Hernández, Mª del Carmen Padín Hernández, Ernesto Bennett Rodríguez
International Center for Neurological Restoration, Havana, Cuba
Dysphagia is a symptom present in alterations of neurological origin, and with certain frequency,
overlaps with dysfunctions of communication. The objectives of the investigation were: to establish
the relationship between the pathology of the communication and dysphagia and to validate an
intervention strategy. The study included 170 patients assisted at CIREN that were explored
integrally in the service of language therapy. The clinical records were reviewed to obtain the
pertinent neurological information, with the purpose of establishing the correspondence among
neurological pathology, of the language disturbances and deglutition. 59 were subjected to study
and, from them, therapy was applied at 29 to check effects. They reached 74 with dysphagia, which
was statistically significant as tendency (47.4) and prediction (7.3). The study was made by
neurological pathology and for pathology of the language, what is of interest for the diagnosis and
rehabilitation prediction. In correspondence with the characteristics of the dysphagia a Plan of
Language Therapy that improves the quality of life of the patient and it facilitates a better
communication was applied. As a result of the application of the program a positive evolution was
evidenced. Coincidence between pathology of the language and dysphagia was statistically
significant. The application of the language therapy evidenced a positive result.

                      Logopedic suggestions for the physical rehabilitation in neuropediatrics

A. Aguiar Rodríguez, M. López Hernández, A. Rodríguez Aldama
International Center for Neurologic Restoration. Havana, Cuba
Most of the children who receive multifactorial attention in our center show speech disorders like
dysarthria or oral retardation. For a better prognosis, an early stimulation of all areas of minor
development is required. A close relationship of all the specialists is necessary to reach a positive
result. For instance, we suggest a series of activities that the physical therapist can perform to
improve communication and language development. Objective: To study the development in the
patient communication and language skills acquisition during physical rehabilitation, guiding the
physical therapist in the fulfillment of the logopedic objectives. Material and Methods: Suggestions
were made to the physical therapist so that, during the physical rehabilitation logopedic objectives
would also be accomplished. The sample was composed by 67 patients in prelinguistic stage of
development. Patients took part in a three days a week, one-month rehabilitation cycle. Results: The
children showed a good response the combined physical therapy. Conclusions: The physical
therapist can become a language-stimulating agent during the therapy.

             Contribution of nursing to improve the communication of patients with dysarthria or aphasia

Nancy Mustelier Carbonell, Juana María Rojas Morales, Susana Martínez Segón, Ismilet Varela
Rosell, Luz Marina Lombillo, Tania Paredes Polo
Clinic of Adult Static Encephalic Lesions, International Center for Neurological Restoration,
Havana Cuba.
Language sequels were studied in 96 adult patients of both sexes from different countries with
cerebrovascular affections: 68 Encephalic Vascular Accidents, 23 Cranioencephalic Traumas and 5
Children‟s Cerebral Palsy, assisted at International Center of Neurological Restoration Havana
Cuba, Clinic of Encephalic Static Lesions from 2001-2002. By means of descriptive prospective
studies, of which their demurrage lapsed approximately 3 cycles and an average of 21 years of age
for (Encephalic Trauma and Children‟s Cerebral Palsy (CCP), 58 years for Encephalic Vascular
Accidents (EVA), with the purpose of applying nursing actions to improve communication, thus
relating rules to be followed for their effectiveness, specifying the family role and therefore,
evaluating the fulfillment of objectives. This was carried out with the participation of the nursing
personnel, from the different houses at night schedules from 7:00-9:00 pm, from 5 minutes up to 1
hour when logopedic tasks are completed. We consulted specialists in logopedics at our center and
different bibliographies were revised that approach the topic, which makes our study coincide with
these issues. The nursing staff filled out the forms for data collection with qualitative and
quantitative variables. By means of an interview, the nurse formulated his/her evaluative criteria as
to the entrance, at the end of each cycle and discharge from hospital. The results are expressed in
charts and graphics through percentages. Aphasia turned out to be the more impacting sequel, and
repetition the most frequent action, and good results were obtained.

            Effects of Early Stimulation Program on Spastic Cerebral Palsy outcome. A retrospectiv e study

Idelys Sarduy, Maria E. Garcia
NeuroPediatric Rehabilitation Service, International Center for Neurological Rehabilitation
(CIREN) Cubanacan, Playa, La Habana, Cuba
Cerebral palsy in the earliest childhood leads to retard or to stop the psychomotor development
according to the biological age. The early identifications and diagnosis of spastic cerebral palsy
(SCP) facility to the inclusion of patients to multifactorial rehabilitation program one them is the
well-known Susana Matas‟s early stimulation program (ESP) in which the psychomotor condition is
classified according to different fields or areas for better diagnosis and training as well as regarding
to age ranks. A retrospective study was carried out in patients with diagnosis of spastic cerebral
palsy (sample: 20; 0-5 years old) in order to appraise the incidence/impact of the Occupational
Therapy specialty in this kind of patients as well as to evaluate the improvement of the psychomotor
condition after early stimulation treatment (1-3 months). Evaluations al the beginning/end of
training included: self-validity, cognition, social behavior and fine movements. Other concerns of
the rehabilitation program were assumed by other specialties. Those mentally retard children
submitted to the ESP showed a general amelioration of the above-cited conditions, particularly in
the execution of movement tasks. Other functions such as those associated with cognition exhibited
relevant improvement too. As conclusive comment it is important to point out that several factor
affects the outcome of children with SCP i.e. age, time of evolution, temporal course between
diagnosis and submission to the ESP, treatment period, etc. Obviously, the functional recovery
observed after ESP is very heterogeneous but always it will have a positive balance for patients.

    Neuropsychological evaluation in a sample of children between fiv e to twelve years w ith bilingual school instruction

Francisco Javier Galarza del Angel, Luis Alfredo Padilla López, Julieta Bonilla, Gilberto Manuel
Galindo Aldana, Connie Payán Domínguez, Belén Elena Preciado Yánez
Universidad Autonoma de Baja California, Mexico
As a part of a wider study, 176 children were evaluated through a neuropsychological battery.
Children were 5 to 12 year-old (both sex), they were in medium socio-economic level and they were
in a bilingual school. Children were divided by sex, and by age group (5-6, 7-8, 9-10 and 11-12
year-old). Neuropsychological battery included the Boston Naming Test, Token Test,
Superimposed Figures (Poppelreuter type), a Verbal Fluency Test (FAS Test) and a Sequencial
Verbal Memory Test. No differences were found between sex in any of the applied tests. There was
a significant difference among age groups for all the tests that were applied. Results are compared
with some other reported (Ardila & Rosselli, 1994). This study will continue in evaluation of
another socio-economic levels and school education.

                               Psychosocial Factors associated to the Confrontation Process

Vivian Blanco, Ileana Trevín, Caridad Valladares, Gabriel Olazarra, Lisette Blanco
Servicio de Psiquiatría, Hospital Clínico Quirúrgico 10 de Octubre, Ciudad Habana, Cuba
A research was carried out making a cuali-quantitative study of 40 patients belonging to the
Intervention Crisis Unity in a Cuban General Hospital, during the last four months of 2001 and the
three first months 2002. The main objectives of the present work were to evaluate the significance
conceded to the vital events, the type of control employed and the kind of confrontation showed by
the subjects included in the study. In addition, it was studied the relationship among these variables.
In relation to the vital events significance, the category “very important” was exhibited by the
majority of patients (62.5%). Simultaneously, these patients had “internal control” (55%) and they
used a “central confrontation” in the problem (75%). It was found a strong correlation (r>65%)
between the significance “very important” for the vital events and the central confrontation in the
problem as kind of confrontation. In addition, the patients which exhibited a “complex
confrontation with tendency to the problem” (7.5%) and “complex confrontation with tendency to
the emotion” (2.5%); also conceded a “very important” or “important” significance to their vital
events. In connection with the relationship between kind of control and kind of confrontation, a
great number of patients showed “central confrontation in the problem” had “internal control”
(45%) whereas only a 30% exhibited “external controls”. The present work evidenced that the very
important strategies to solve the problems in relation to the mental health in the population studied
were: 1. to establish the new concept about his disease, 2. to found new ways in order to develop a
better confrontation of their problems and 3. to locate the people in the center of the problem.

Restoration of sensory functions

                              Specific ity and plasticity in human neurocognitive development
Helen Neville
Psychology Department, University of Oregon, Eugene, Oregon, USA
I will review ERP and fMRI results of visual and auditory and processing in normal adults and in
those who have had different sensory and/or language experience. Taken together these studies
suggest that within vision and audition different neural systems display considerable variability in
the degree to which they are modified by early experience. Within vision, early auditory
deprivation has most marked effects on the organization of systems important in processing motion
information. Within the visual and auditory systems sensory deprivation has more effects on the
representation of the peripheral than of the central fields. In addition, different subsystems within
language display varying degrees of modifiability by experience. These results converge with
other lines of evidence that suggest it is important to distinguish these different aspects of language,
and they raise hypotheses about the initial development of these different language systems. Parallel
studies of normal infants, children, and adults and studies of those with abnormal development
provide further evidence for the roles of genetic factors and experience in human neurobehavioral
development. The results of these several different types of experiments provide evidence that
some systems within the human brain retain the ability to change, adapt, and learn throughout life,
while other aspects of human neural and behavioral development display multiple, specific and
different critical periods.

          Children w ith cochlear implants; effects of age at implantation on speech and language development

Robert V. Harrison, Richard J. Mount, Blake Papsin
Auditory Science Laboratory, Department of Otolaryngology, the Hospital for Sick Children
and the University of Toronto, Canada
Cochlear implantation is a standard intervention for restoring hearing in children with severe to
profound deafness. With congenital hearing loss, early intervention is universally accepted as being
beneficial, but is not always possible because of late detection, socio-economic constraints, etc. An
important practical question is whether there is a critical period or cut-off age of implantation after
which hearing outcomes are significantly reduced. To date we have followed more than 200 pre-
lingually deaf children (mostly congenital) implanted at ages ranging from 1-17 years. Each child
was tested with auditory and speech understanding tests before, and at intervals up to 5 years post-
implantation. Closed-set speech perception tests included TAC and WIPI; open-set tests included
PBK and GASP. We have compared the rate of improvement in performance of speech
understanding tests in younger implanted children compared with those implanted at a later age. To
compare these groups we have split the data arbitrarily at an age of implant of 6 years. We have also
used a binary partitioning algorithm to divide the data systematically at all ages at implant to
determine the optimum split, i.e. to determine the age at implant which best separates performance
of early implanted versus later implanted children. Using simple closed set tests, this age at
implantation was found to be 4.4 years. For more difficult open set tests, the age ranged from 5.6 to
8.4 years. In any case we do observe age cut-off (some might say "critical period") for cochlear
implantation in the congenitally deaf child.

                              Electroaudiometry: Advances and new clinical applications

Pérez-Abalo M.C.
Cuban Neuroscience Center. Havana, Cuba
Over the last decade important advances have occurred within the field of electroaudiometry (use of
auditory evoked responses for objective hearing assessment). As a result new technologies have
become available for early detection and characterization of hearing losses. The present paper will
focus on one of such methodologies, based on the recording of the fast rate (80-110 Hz) auditory
steady state evoked responses (ASSR) elicited by multiple AM tones. With this technique several
frequency specific thresholds (between 0.5 and 4 KHz) can be simultaneously evaluated, with the
consequent reduction in testing time. Also the responses (represented as distinct spectral peaks) can
be easily identified by different statistical indexes, thus allowing automatic threshold detection.
Here we summarize the main findings obtained in the clinical validation of the technique in three
different groups: normal and hearing-impaired adults, 2) well babies 3) high-risk babies. In the
adults results indicate that the MSSR can reliable predict the behavioral pure tone thresholds (at 0.5,
1, 2 and 4KHz). Mean differences between response and behavioral thresholds ranged between 7-
to15 dB in the normal hearing adults, and between 5 to 9 dB in the hearing impaired. Also the
MSSR can accurately estimate different audiometric configurations in mild, moderate and severe
hearing impairments. In the well babies (between 0 and 12 month of age) different maturational
changes were evidenced for the low and high frequency MSSR. Finally within the context of a
targeted screening protocol the role of MSSR was investigated by means of a long term follow up
study of 513 high-risk babies. Results showed that the technique provided valuable information for
the diagnosis and management of infants with hearing losses, and further developed, might become
useful as a frequency specific screening procedure.

                                    Objects, Attention and Brain Dysfunction

Mitchell Valdes-Sosa
Cuban Center for Neuroscience, Havana, Cuba
Substantial progress has been made in the last decade in understanding the neural mechanisms
underlying visuo-spatial attention, and in how these mechanisms are affected by brain lesions.
However, traditional experimental paradigms focussing on spatial selection of visual information
are blind to important strategies employed by observers when processing complex real-life scenes.
Here we describe new developments using a paradigm dubbed 'rapid serial object-transformation',
which provides new insights into the neural mechanisms of object-based visual attention. Moreover,
we argue how this method can contribute to the understanding of attentional dysfunction in several
diseases and present data about deficient attentional strategies in autism and subsequent to brain
plasticity induced by sensory deprivation.

                            Impact of Visual Field Defects on Activities of Daily Living

Jennifer Ullrich, Erich Kasten, Bernhard Sabel
Institute of Medical Psychology, Medical Faculty, Otto-von-Guericke University,
Magdeburg, Germany
There are about 550,000 patients suffering from brain lesions in Germany every year (Kasten,
2002), many of them result in visual deficits. The most frequent kind of visual impairment are
visual field defects (VFD). Patients with VFD report various difficulties in activities of everyday
life (ADL). We have designed a questionnaire for the self-assessment of these restrictions due to
VFD. In this questionnaire the patient is asked to estimate the degree of the impact of his/her VFD
on ADL. At the moment the questionnaire is used in a prae-post design for the purposes of a study
testing the Visual Restitution Training (VRT) developed at our Institute. VRT is a computer-
assisted training for patients suffering from VFD stimulating the transition zone between the intact
and the blind area of the visual field. So far, 17 patients and 12 relatives of the patients have filled
in the questionnaire before starting the VRT. Two main areas of impairment could be indentified -
driving a vehicle and reading. E. g. 11 patients (64.7%) reported that they have given up driving a
car due to their VFD, 10 of these patients (58.8%) said that their doctor advised them to do so;
82.4% reported that their reading was very slow sometimes, often or very often. On the base of
these data a computer-assisted test containing photos of everyday life scenes in which subjects have
to search for certain objects has been developed and is being evaluated at the moment.

       fMRI of the human sensorimotor cortex before and after subsensory whole-hand afferent electric al stimulation

V. Gonzáleza , S.M. Golaszewskib , W. Struhalc, C.M. Siedentopfd , F. Koppelstaetterd , M. Veriusd ,
F.M. Mottaghye, S.R. Felberd , F. Gerstenbrandf, M.R. Dimitrijevic g
  Department of Neurology, Heinrich Heine University Düsseldorf, Germany b Department of
Neurology, University Hospital of Graz, Austria cDepartment of Neurology, Kaiser Franz Josef
Hospital, Vienna, d Department of Neuroradiology, University Hospital of Innsbruck, Austria,
  Department of Nuclear Medicine, Research Center Jülich, Germany, f Ludwig Boltzmann Institute
for Restorative Neurology and Neuromodulation, Otto Wagner Hospital Vienna, Austria, gDivision
of Restorative Neurology and Human Neurobiology, Baylor College of Medicine, Houston, Texas,
Introduction: Stimulation of propriozeptive pathways using whole-hand electrical stimulation with a
mesh-glove has been shown to improve motor performances of stroke patients with chronic
neurological deficits. The aim of the study was to elaborate, whether changes in the motor cortex
activation pattern can be demonstrated after electrical stimulation of the hand in volunteers.
Materials and Methods: All experiments were performed on a 1.5Tesla MR-scanner in 10 healthy
subjects. The motor-paradigm was self-paced finger-to-thumb-tapping of the left hand. Firstly, a
baseline fMRI-examination and secondly subthreshold electrical stimulation with 0.9mA was
applied for 20 minutes outside the magnet to the left hand using a mesh-glove. Thirdly, an identical
fMRI run to the baseline and the second run 12 hours post stimulation was performed. Post
processing was done with SPM99. Results: Group-analysis of fMRI-data showed: 1. Baseline
fMRI-examinations revealed brain activation of the primary and secondary sensorimotor cortex as
previously described. 2. After electrical stimulation of the left hand, there was an increase of
activated pixels in these areas. 3. In addition, there was activation of regions not visible on the
baseline studies. These involved the ipsilateral inferior parietal lobule, the pre- and postcentral
gyrus and the superior parietal lobule. 4. These changes disappeared twelve hours post stimulation.
Conclusions: fMRI reflects an increased BOLD-response due to an increase of local-field-potentials
within the sensorimotor cortex due to electrical stimulation. Thus, local-field-potentials can be
successfully influenced by subsensory stimulation of afferent pathways. This holds promise for the
application of fMRI in the planning of neurorehabilitation strategies.

                                    Perispinal TNF-alpha inhibition for discogenic pain

Tobinick, E. L. and S. Britschgi-Davoodifar
Institute Research Associates, A Medical Group, Inc., Los Angeles, California 90095, USA.
OBJECTIVE: To examine the potential of etanercept, a biological inhibitor of tumour necrosis
factor-alpha (TNF), delivered by perispinal administration, for the treatment of pain associated with
intervertebral disc disease. METHODS: Charts from 20 selected patients treated at our private clinic
by perispinal delivery of etanercept 25 mg for severe, chronic, treatment-resistant discogenic pain
were reviewed. Therapeutic benefit was assessed clinically and was documented by changes in a
validated pain instrument, the Oswestry Disability Index. The patients were treated off-label with
etanercept as part of our usual practice of medicine. Five detailed case reports are presented,
including three additional patients. RESULTS: Rapid, substantial and sustained clinical pain
reduction was documented in this selected group of patients. The cohort of 20 patients had a mean
age of 56.5 and mean duration of pain of 116 months. Nine of the patients had undergone previous
spinal surgery; 17 had received an epidural steroid injection or injections (mean 3.2). This group of
patients received a mean of 1.8 doses (range 1-5, median 1.0) of etanercept during the observation
period. The mean length of follow-up was 230 days. Clinical improvement was confirmed by a
decrease in the calculated Oswestry Disability Index from a mean of 54.85 +/- 12.5 at baseline,
improving to 17.2 +/- 15.3 (p <0.003) at 24 days and ending at 9.8 +/- 13 (p <0.003) at 230 days.
CONCLUSIONS: TNF inhibition by etanercept delivered by perispinal administration may offer
clinical benefit for patients with chronic, treatment-resistant discogenic pain. Further study of this
new treatment modality is warranted.

Challenging views of AD therapy I

                       Present and Future of cholinesterase inhibitors in the treatment of AD

Ezio Giacobini
Department .of Geriatrics and Rehabilitation , University of Geneva , Medical School
Geneva, Switzerland
Eighteen years after the first report of Summers, several million Alzheimer Disease (AD) patients,
have been treated with cholinesterase inhibitors (ChEI).Approximately 50% of these patients have
shown evidence of improvement (NICE, 2002 ) ,clinical stabilization up to one year in 20 % , up to
two years in 10 % .There is no sharp distiction between responders vs non-responders and 50 %
non-responders to ChEI–A will respond to ChEI-B or -C.Single dose ChEI produces f-NMR signs
of activation of memory tasks in most patients (Rombouts et al. 2002 ) . CSF-ChE inhibition
correlates to changes in most treated patients ( Giacobini 2002 ).This suggests that the number of
non-responders is probably smaller than 50% particularly since AChE inhibition in brain at
therapeutic doses reaches only 27-40% (PET). The recent discovery of the role of
butyrylcholinesterase in brain points to this enzyme a as a new target for AD treatment in advanced
AD cases. Based on the functional role of the cholinergic system indication for ChEI treatment
should be extended to those diseases or syndromes showing a cholinergic deficit such as Lewy
Body Disease, Vascular Dementia, Parkinson Dementia, Delirium , Brain injury etc. Most
interesting is the possibility of applying ChEI therapy to MCI subjects ( Minimal Cognitive
Impairment ) or to potentiate beta-amyloid reducing therapies such as immunization.

                                 Executive function and cholinesterase inhibitors

Roger Bullock, Anna Marriott
Kingshill Research Centre, VictoriaHospital, Swindon, UK
The cholinergic system has been implicated in the pathophysiology of Alzheimer‟s disease (AD)
and new treatments have been developed around restoration of cholinergic function. Because AD is
predominantly a memory disorder, cognitive measurements of efficacy have primarily concentrated
on episodic and semantic memory, with little regard to working memory or executive function. The
latter have been more frequently associated with vascular dementia (VaD). However attention, a
useful indicator of executive function, declines over time in a predictable fashion and increased
rates of this decline may herald more noticeable clinical deficits. The objective of the first study
presented is to demonstrate executive dysfunction in AD, from memory clinic patient assessments
in Swindon. This found that all tests on information processing in the test battery were as bad for
AD as VaD. A review of data from studies on cholinesterase inhibitors, which included measures of
executive function, will demonstrate that the cholinergic system is involved in attention and that
deficits may respond to cholinergic enhancement. Differential effects between cholinesterase
inhibitors will then be discussed using randomised data from a one year comparison of donepezil
and galantamine. This showed similar improvements in simple reaction time, but a significant
improvement of galantamine beyond any improvement achieved by donepezil in choice reaction
time. As choice reaction time involves dopaminergic relays as well, this may be the first clinical
demonstration of the reported nicotinic modulation by galantamine of the cholinergic system in a
human population.


           Self-dependence and identity of symptoms of myofacial pain syndrome (MPS) and fibromyalgia (F)

A.Y. Filyuk
Moscow State Medico-Stomatological University, Moscow, Russia
MPS may be occurred in 30-85 % of population (Han S.C., Harrison P., 1997), F in 2-6% (Wolfe F.
et al., 1995).Number of investigators proposes MPS and F to be the one pathology. We suggest this
problem to be discussing in the base of literature review, our clinical experience and the materials of
our investigation work.Similarity: MPS and F are chronical conditions with pain symptoms in 100%
cases. Infiltrative zones in muscles called muscular trigger points (MTPs) have place both in MPS
and F. Main part of patients with MPS and F suffers from psychological disturbances. Thermal
procedures in alterative muscles are used to treat both these pathologies. Difference: F is
characterized by generalized muscle pain, in MPS case the pain is local. According to our clinical
experience in 33 F patients and 350 patients with MPS we find out the level of psychological
disturbances prevalent in F-group. Pain threshold is significantly reduced in F-group compared with
MPS-group. Cerebral disturbances in electroencephalographic investigation prevalent in F-group
too.Peripheral changes are expressed in MPS-group: synopsis transmission is highly affected;
muscle damages are more expressed. Changes of electrical qualities in MTPs usually have place in
case of MPS.

          Myofacial pain syndrome’s prosopalgia w ith oral pathology on the background. Patients’ rehabilitation

A.Y. Filyuk, S.A. Filyuk
Moscow State Medico-Stomatological University, Moscow, Russia
We examine 290 volunteers with loss of occlusal support. 62 of them are diagnosed to suffer from
prosopalgia as a result of myofacial pain syndrome (MPS) of the masticatory system. The patients
are divided into two groups (31 individuals each). Both groups get cold-agents on myofacial trigger
points (MTPs), lidocaine-nicotine blockades on MTPs, antidepressants, tranquilizers, myorelaxants,
laser therapy of MTPs, non-steroid analgesics, prosthetic occlusal correction. Temporomandibular
joint normalization is performed in the 1st group by the post isometric relaxation (PIR) gymnastics
complex for masticatory muscles. Then we teach these patients to do the gymnastics by themselves
for prophylaxes. Duration of our investigation is 2-5 years. All of the patients are delivered from
pain. Pain release is attained in 10,2 days in the 1st group and in 15,5 days in the 2nd group. 20
individuals from the 2nd group and 2 ones from the 1st group are found out to have season
worsening of MPS lasted 7-20 days and 3-15 days consequently. 2 of 4 patients from the 1st group
with season worsening don‟t practice the gymnastics. 11 patients from the 2nd group and 1 patient
from the 1st one repeat worsening without any season dependence. Thus, in case the rehabilitation
measures are included in MPS treatment the number of recovers increases as well as the duration of
the disease decreases significantly. Regular gymnastics exercises let to prevent MPS worsening.

                     The consequence of rehabilitation in myofacial pain syndrome (MPS) patients
A.Y. Filyuk, S.A. Filyuk
Moscow State Medico-Stomatological University, Moscow, Russia.
As a result of our longitudinal observation of 350 MPS patients we can formulate 3 periods of the
rehabilitation. The period of decreasing MPS symptoms. It includes: maximal myorelaxation (first
3-4 days); kinetic therapy; psychotherapy; manual therapy; laser therapy; using of some medicines
and subsidiary methods. The period of identification and liquidation of MPS reasons: a consultation
of different medical specialists and a treatment of common pathology; the examination of spinal
cord (in the static and dynamic positions); an investigation of vitamins and minerals deficit. The
period of MPS prophylaxis: working out of the correct moving stereotypes; a prophylaxis of
common diseases; a trauma prophylaxis; the nutrition hygiene; a prophylaxis of psychological
disturbances; teaching of a patients to the post isometric relaxation gymnastic complex. This
consequence of rehabilitation helps practitioners to get good results in the rehabilitation of their

     The blood concentration of tyrosine hydroxylase enzyme (TH) in myofacial pain syndrome (MPS) patients for the
                                             assessment of their adaptation

A.Y. Filyuk, S.A. Filyuk
Moscow State Medico-Stomatological University, Moscow, Russia
Statement of problem: Tyrosine hydroxylase (TH) is a special enzyme that regulates catecholamine
synthesis. There are four isoenzymes of TH: TH1, TH2, TH3, TH4. TH is usually determined in
liquor. At the same time leukocytes were found to contain TH. In our literature review we have no
information on any clinical investigations of the blood concentration of TH in MPD patients.
Purpose: The aim of our study was to investigate the blood concentration of TH in MPD patients
for the assessment of their adaptation. Methods: We examined the blood of 30 volunteers 15-55
aged with different symptoms of MPD in analyzing device FP-901 “Labsistems” (Finland) with
spectrofotometrical method. Results: Thus in patients with MPD we revealed the prevalence of
TH3 and TH4. The increased concentration of TH3 and TH4 pointed to stress, distress and
breakdown of adaptation mechanisms.

               Targeted etanercept for discogenic neck pain: uncontrolled, open-label results in two adults

Tobinick EL.
Institute Research Associates, A Medical Group, Inc., Los Angeles, California 90095, USA
BACKGROUND: Etanercept, a recombinant biologic anti-tumor necrosis factor (TNF)-alpha
therapeutic, is approved for the treatment of certain autoimmune arthritides by subcutaneous (SC)
injection. TNF-alpha has been suggested to play a central role in neuropathic pain and neuronal
damage associated with intervertebral disc herniation. Directed local administration of etanercept, in
anatomic proximity to the site of disc and neuronal abnormality, may result in an enhanced
therapeutic response. OBJECTIVE: This study reviews findings from 2 patients with chronic,
severe, discogenic cervical pain who were treated with a targeted cervical injection of etanercept
with the objective of obtaining relief from their treatment-resistant pain. METHODS: In this
uncontrolled, open-label study, the case histories of 2 patients (1 woman and 1 man) presenting
with a history of chronic neck pain refractory to various treatments are reviewed. Both patients were
treated with etanercept 25 mg by SC injection to the cervical region (case 1) or the posterior neck
overlying the spine (case 2). RESULTS: Both patients experienced almost complete pain relief as
assessed subjectively. In case 1, the Oswestry score decreased from 58 before treatment to 6 one
day following treatment. In addition, 1 day after treatment the patient reported a subjective
assessment of 98% pain improvement, 100% sensory improvement, and 100% weakness
improvement. She has remained asymptomatic for >1 year. In case 2, the Oswestry score decreased
from 44 before treatment to 4 two months after treatment. The patient reported 100% pain relief and
90% sensory improvement 1 day after treatment. At 8-month follow-up, pain improvement
continued to be 100% and sensory improvements was 75%. CONCLUSIONS: Etanercept, delivered
by targeted SC injection, may be of benefit for selected patients with resistant pain associated with
cervical disc disease. Further study of this new treatment modality is warranted.

            Targeted Etanercept for Treatment-Refractory Pain Due to Bone Metastasis: Two Case Reports

Edward Lewis Tobinick
Institute for Neurological Research, Los Angeles, California
Background: Parallel bodies of research suggest both a central role for osteoclasts in tumor-induced
destruction of bone and the ability of biologic tumor necrosis factor–alpha (TNF-alpha) antagonists
to attenuate the osteoclastmediated bone destruction that accompanies a variety of nonmalignant
disorders. Additional studies have implicated TNF-alpha in the promotion of osteoclastmediated
malignant osteolysis and the pathogenesis of neuropathic pain. TNFalpha antagonists have the
potential to interfere in both processes. Objective: This article reviews the cases of 2 patients with
treatment-refractory pain due to cancer metastases to bone who were given targeted injections of the
biologic anti-TNF agent etanercept based on its potential to interfere directly with both malignant
activation of osteoclasts and neuropathic pain. Methods: One patient had a diagnosis of non–small
cell lung cancer and the other had a diagnosis of breast cancer. Both presented with treatment-
refractory pain due to bone metastases. The 2 patients received etanercept 25 mg by targeted SC
injection in anatomic proximity to the site of spinal metastasis for relief of their treatment-refractory
pain. Results: Both patients experienced rapid, substantial, and sustained relief of chronic refractory
pain at the treatment site after targeted administration of etanercept. Symptomatic improvement was
correlated with objective measures of improvement, including weight gain in 1 patient and
decreased uptake of radioactive tracer at the targeted site on positron emission tomography in the
other. Conclusions: Etanercept delivered by targeted SC injection may be of clinical benefit in
selected patients with treatment-refractory pain caused by bone metastases. Clinical trials are
needed to define the potential benefit of biologic TNFalpha antagonists in the treatment and
prevention of malignant osteolysis.

              Visual search for images in Alternative Communication System in girls w ith Rett syndrome

Patricia M. Baptista, Elizeu C. Macedo and José S. Schwartzman
Master Program in Development Disturbances, Mackenzie Presbyterian University, Brazil
Rett Syndrome is a disorder that in its typical form affects mainly girls. It is characterised by neuro-
behavioural regression, loss of manual skills and severe psychomotor and language retardation.
These children show significant handicap in their communication capacity and may benefit from
using Alternative and Augmentative Communication (AAC). The purpose of this work was to
verify the possibility of choice through visual search patterns of images of an AAC system shown
on a computer monitor. Visual search patterns were analysed on two girls with Rett Syndrome, aged
eight and nine, who were both in stage three of the syndrome. The computer used was a Pentium III
PC with eye-tracking Eyegaze®, which consists of a camera that registers the movement of the
pupil, calibrated accordingly to the user‟s profile. The images were shown using Trace software,
which enables visual search patterns on the screen to be registered and recovered. The girls had to
look at an image similar to the model, look at an image chosen by the examiner, or even, look at the
image they liked the most. The results showed a systematic and correct, visual search pattern when
using simple tasks in the two children. These preliminary results point to the possibility of using the
direction in which they look as a way of establishing communication through computerised
communication systems. Furthermore, it seems that they show a preserved capacity in
understanding simple orders.

                 Regeneration of the sciatic nerve in rats after transplantation of bone-marrow cells

Victor T. Ribeiro-Resende; Pedro M. Pimentel-Coelho; Raquel M.B. Mendez e Rosália Mendez-
Instituto de Biofísica Carlos Chagas Filho and Millennium Institute for Tissue
Bioengineering, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Transection of the sciatic nerve in adult animal's results in incomplete regeneration and often results
in loss of function. We investigated whether bone-marrow cells inserted into the lesion site improve
and facilitate axonal regeneration after nerve transection. Adult Lister male rats were anaesthetized
and had their right sciatic nerves exposed, transected and the two nerve stumps were connected
inside a polyethylene tube. In one group of animals, the tube was filled with Matrigel and a
suspension of 108 bone-marrow cells (mononuclear fraction) previously labeled with DAPI. The
control group received only Matrigel. After 7, 21 and 42, the animals were perfused with 4%
paraformaldehyde. Sciatic nerves, dorsal root ganglia (DRG) and spinal cord were removed,
sectioned using a cryostat and processed for histochemistry or imunohistochemistry for S100,
NF200 and NOSn. Results showed that in the proximal stump, axonal growth in the experimental
animals was more than five times higher than in the control group 7 and 21 days after
transplantation (7days: exp:1,2mm n=6; control: 0,2mm n=4; p>0,01 ANOVA; 21 days: exp:
1,7mm, n=6; control: 0,3mm, n=4; p>0,001 ANOVA). 42 days after transplantation the
regenerating axons were observed growing into the distal stump in the experimental group but not
in the control. In addition, the number of surviving neurons in the DRGs of the experimental
animals was 20% higher than in the control. Our conclusion is that transplantation of bone-marrow
cells improves the regeneration of sciatic nerve axons and also improves the survival rate of DRG
neurons after transection.

              Effects of an induced deafness in the spiral ganglion cells’ density: a morphometric study

Sandra Rodrígueza, Tania Valdésa, Yahima Harveya, Odelsa Ancheta a, Rosa Ma Coroc, Valia
  Electron Microscopy Department, Biotechnology Division, National Center of Scientific Research,
Havana, Cuba. bCognitive Neuroscience Department, Cuban Neuroscience Center, Havana, Cuba.
  Pathology Department, Institute of Neurology and Neurosurgery, Havana, Cuba
Although most of the sensorineural hearing losses are caused by damage to the hair cells, the
resulting sensory deprivation induces important degenerative changes at different levels of the
auditory pathway, including loss of spiral-ganglion cells (the first relay in the pathway). However
these studies have been mainly carried out in neonatal animals but needs further replications in
adults. The aim of the present study was to explore the temporal dynamic of spiral ganglion
degeneration in adult rats after an induced deafness. Thirty Wister rats were used in this study. The
animals were divided into five treatment groups. Animals in three of these of groups were deafened
using a co-administration of Kanamycin and Frusemide. These groups were sacrificed two, four and
sixteen weeks after the induction and cochleas were removed for histopathological analysis. The
other two groups were used as non-treated controls (GN1, GN2), sacrificing the animals for
cochlear harvesting at the beginning (GN1) and at the end (GN2) of the study. The functional
integrity of the auditory pathway was confirmed with electrophysiological techniques (Auditory
Brainstem responses) at the beginning of the study for all animals and one week after the hearing
loss in the treated groups. For histopathology, cochleas were embedded in Spurr resin and serial
semi-thin slices were obtained. Cell density (cells/mm3) was calculated from Rosenthal‟s canal at
the cochlear upper medial turn. The results showed that ototoxicity in adult rats produced a
substantial reduction in the spiral ganglion cell density that significantly increased from the second
to the sixteenth week. Besides proving the efficacy of the selected deafening model, the
standardization of the used techniques and the degenerative changes observed constitute the
necessary basis to conduct further studies on the required conditions to preserve the auditory system
function despite sensory deprivation.

   Effect of the duration of deafness and neural survival on the response of the auditory system in deafened guinea pigs

Pavel Prado-Guitierreza,d , Leonie M. Fewstera, John M. Heasmanb , Colette M. McKaya, Robert K.
  Department of Otolaryngology, The University of Melbourne, Australia. bCochlear Ltd, Australia.
  The Bionic Ear Institute, Australia, dCuban Neuroscience Centre, Havana, Cuba
Eighteen guinea pigs were deafened by co-administration of kanamycin and frusemide. Each animal
was implanted with an 8-electrode array at 1, 4 or 12 weeks following deafening. EABR
input/output functions were recorded in response to biphasic current pulses. We measured the
current change required to equalize EABR amplitude when pulse duration was doubled from 104 to
208µs per phase or interphase gap increased from 8 to 58µs. Following the completion of each
experiment the animal was euthanased and the cochleae examined for auditory nerve survival.
There was a reduction in the effect of changing pulse duration and interphase gap with increasing
duration of deafness. However, this trend was not significant (one-way ANOVA), perhaps due to
the large variance in the group of long-term deafened animals. There was a significant decrease in
the effect of interphase gap between the 1- and 4-week deafened groups (t-test). It is possible that
the large variance in the data for guinea pigs of equal duration of deafness may be due to variations
in neural survival. Then, the effect of both, pulse duration and interface gap, on the EABR of
deafened individuals would be correlated with of the neural survival more than the duration of
deafness. These results, when applied to cochlear implantees, may provide a tool for investigating
the role of neural survival in variations in performance with the implant. Support for this research
was provided by the Garnett Passe and Rodney Williams Memorial Foundation, the National Health
& Medical Research Council of Australia and the National Institutes of Health (NO1-DC-0-2109

                  Critical revision of induced modific ation by acupuncture in the Central Nervous System

Tahimí Cardoso Suárez , Carlos M. Méndez Alonso, Irene Jiménez Ortiz
Holistic Medicine Department, International Center of Neurological Restoration. Havana,
Acupuncture has been used to treat different affections as: zosterian disease, sacrolumbar pain of
diverse etiologies and other diseases that commit the CNS in an important way. How can
acupuncture induce a therapeutic response has not yet been revealed, but there is an accumulated
experience as to its action, which is still unsystematic and thus, scarcely accessible for its
integration. The aim of this work was to analyze some of the action and changes provoked by
acupuncture in the CNS reviewed in different articles. 35 papers published between 1985 and 2003
were revised. An analysis was performed on published data, in relation to the changes provoked by
acupuncture in the CNS, so much on animal basic (12 papers) as on human clinical investigation
(23 papers). The modulation of the expression of neurotrophic factors, and the variation of cellular
sub-populations in the CNS areas were found in diverse paper. Also studied were the regulation by
the liberation of neurotransmitter, the modification of cerebral blood flow and variation in the
excitability of determined neuronal groups. Acupuncture seems induce changes in different areas
and functions of CNS, a fact likely related to the therapeutic response observed in different studies.

Transcraneal magnetotherapy as therapeutic alternative in the psycho-physiologic insomnia.
A preliminary report

Coralina Martínez Hidalgoa , Trinidad Virues Alba b , Roidel Alessandrinia , Armando Sentmanat
Belisóna , Anairis Rodrígueza , Jorge Torres Hernándeza.
  International Center of Neurological Restoration(CIREN). b CubanNeuroscience Center. Havana,
The present investigation was worked out between the groups of Physiotherapy from the
International Center of Neurological Restoration (CIREN) and the Clinic of Sleep Disorders from
the Cuban Neurosciences Center (CNC). Objective: To corroborate the possible therapeutic effect
of transcranial magneto therapy on patients suffering from psycho-physiological insomnia (PI) in
the improvement of sleep quality. Material and Methods: The leading study included 5 patients with
psycho-physiological insomnia treated with transcranial magneto therapy in 20 sessions of a 30–
minute duration with an intensity of 30 gauss, pulsating, sinusoidal wave on a CM-1750-01
Magnetic-stimulation bed. The patients were evaluated before and after treatment with surveys and
psychological tests, besides being submitted to a polysomnographic study in the lab for sleep
disorders at CNC-CIREN. In this test, the following variables were assessed: latency as the
beginning of total sleep and REM, amount of awakenings and total sleep time. The data were
processed with application of non-parametric tests (Wilcoxon, for paired series, Kruskall-Wallis and
Spearman´s correlation by multiple ranges). Results: Preliminary results show that the effects of
magneto therapy have an incidence on the increase of effectiveness during sleep, sleep soundness
and in the number of cycles that become similar to those of healthy subjects. These results also
show a diminishing in vigil states and their duration, as well as, Arousal‟s Index. They all show a
tendency to the recovery of sleep structures, an issue that indicates that this technique of treatment
can activate those centers involved with sleep generators. Conclusions: In a preliminary way, it can
be appreciated that transcranial magneto therapy can constitute a therapeutic alternative in this

        Integration of orthopedic structural manipulation techniques with acupuncture in the handling of lumbar pain

Carlos M. Méndez Alonso, Tahimí Cardoso Suárez, Irene Jiménez Ortiz
Holistic Medicine Department, International Center for Neurological Restoration. Havana,
Lumbar pain is a frequent health problem. In some patients, the conventional therapy does not
release pain and collateral events appear because of medication. This works aims to integrate two
common therapeutic procedures from holistic therapies and to describe the outcome of the lumbar
chronic pain treated with orthopedic structural technique (OST) and Acupuncture (AC). 25 patients
with chronic lumbar pain (more than three weeks evolution) with or without sciatica, were treated in
our department, nine women and sixteen men, between 24-83 years old. According to clinical
features and imagenologic test, patients were distributed in 3 groups: 1- facetary cause- ten patient
(there is not clinically or imagenologic evidence of discal pathology); 2-protusion of the
intervertebral disc- seven patient; 3- extrusion of the disc –eight patients (extruded hernia). It was
applied a cycle of 8 to 16 sessions according to the individual requirements: pain‟s outcome was
evaluated by subjective pain scale: 10- the most intensive pain at the beginning, and 0- no pain. In
the group 1, the release was in 2 weeks. In the group 2, in 5 weeks. Both groups finished without
medication. The group 3 had a poor evolution, needing other procedures. In the chronic lumbar pain
non-responsive to the habitual medication, the first two groups had a positive outcome with the
integration of the therapeutic procedures. The OST acts more deeply in the etiology of pain, but is
insufficient in the treatment of pain due to extrusion of the disc.

           Auditory evoked responses in temporal lobe epileptic patients and definite multiple sclerosis patients

M.M.Báez Martín, I.Cabrera Abreu, L.Morales Chacón, E.Infante
International Centre for Neurological Restoration. Havana, Cuba.
There are controversial reports about the characteristics of auditory evoked responses in epileptic
patients depends on epilepsy classification, the chronicity of the illness, the response to antiepileptic
drugs, and the generators of the different components. On the other hand, studies in patients with
multiple sclerosis (MS) have reported an improvement in the diagnostic sensibility of auditory
evoked potentials with the use of the middle-latency evoked response, but there is no consensus.
Auditory brainstem response (ABR) and middle-latency auditory evoked response (MLR) were
studied in ten patients with temporal lobe epilepsy, and an equivalent number of healthy subjects.
ABR and MLR of thirteen MS patients with positive MRI were compared with the normative data
of our Lab, according to sex and gender. Epileptic patients showed a significant increase of I-III and
I-V interpeak intervals duration with decrement of III wave amplitude, prolonged latency of all
MLR components, and increased Pa-Pb interpeak interval respect to control group with reduction of
Na component amplitude. Eight of the MS patients (61.5%) showed abnormalities of the MLR, but
only five showed anomalies of the ABR. Considering ABR and MLR together the sensibility of the
tests increased until 76.9%. Our results confirm the compromise of auditory pathway structures at
different levels in temporal lobe epileptic patients. MLR improved the diagnostic sensibility of
auditory tests in MS patients.

                              Somatosensory cortical evoked potentials to laser stimulation

Ana Fernández Nina , Marta Brown Martineza, Aymee Hernández Hernándeza, Rebeca Hernández
Toranzob , Ramón Cabalb , Luis Marti Lopezb
  Hospital Universitario Dr. Carlos J. Finlay, La Habana, Cuba. b Centro de Neurociencias de Cuba,
La Habana, Cuba
Somatosensory cortical evoked potentials were elicited stimulating A-delta and C nerve fibers of
the skin by means of a laser stimulation device (Estimula-2). These fibers convey information about
temperature and pain to the central nervous system. The objective exploration of these pathways can
be very helpful to diagnose many neurological diseases. The present study reports the first
experiences on this field in our country. Forty-five adult healthy volunteers were studied to
construct a normative group, and 8 patients with thermal and pain dissociation caused by different
illness were also explored. The Estimulas-2 was used to generate CO2 –laser pulses synchronized
with a Neuronica 02 EP recording machine. The stimulation sites were the backs of hands and foots,
as well as, the elbows and knees. Ten pulses were given in every site and after every stimulus an
800 ms EEG segment was recorded from the scalp. Single trials were averaged to obtain replicable
responses. Latency, amplitude and conduction velocities were calculated for every response. The 8
patients exhibited cortical responses with longer latencies, lower amplitude and slowed conduction
velocity compared to controls. The topography of the alterations varied according to the localization
of the affected areas, but there was a high correlation between clinical and electrophysiological
variables. It was concluded that the presented methodology is safe, reliable and of great help to
neurological diagnosis.

 Humoral intrathecal immunity, in the diagnosis exclusion of dementia. Cytokines and antioxidant activity interaction in AD
Maria de los A Robinson-Agramonte, Maria E Gonzáles Fraguela, Martha Nápoles , Teresa Serrano
Sanchez, Bertha Willson.
Centro Internacional de Restauración Neurológica. Ave 25. No 15805 e/ 158 y 160, Playa. CP
11300. Ciudad de la Habana. Cuba
Beside the utility of intrathecal immunity as a tool for the diagnosis exclusion of dementia,
Inflammation and oxidative stress are refereed as biological markers from different fluids in AD
looking for evidences helping to the following of disease progression. Nevertheless, no less
important markers from peripheral fluids add information on the pathological events of the disease.
We show an integral result of the immune-inflammatory response and oxidative stress in AD and
others type of dementia. The analysis included the evaluation of intrathecal immune response using
Reibergram program in different type of dementia and the quantitative estimation of pro-
inflammatory cytokines (IL 1b, TNFa) following ELISA method as well as the quantitative
estimation of antioxidant enzyme from serum in AD patients. The probable interaction between all
these parameters was analyzed too. A Reibergram differential pattern was observed to each type of
dementia. AD patients showed a significant difference to TNF a (p<0.05) as well as a significant
interaction level to this variable with CAT antioxidant activity (p<0.05). The results underline the
inflammatory mechanism in AD and tag the reactive oxygen species as cellular messenger instead a
simple pathogenic agents to the disease, in add to the potential value of these markers to evaluate
disease progression.

    Prevalence, risk factors and predictiv e models of demential syndrome and Alzheimer’s disease in the Municipality of

J.J. Llibre Rodríguez, H. Herrera Domínguez, H. Bayarre Vea, Héctor; T. Laucerique Pardo, M.A.
Guerra Hernández, J.A. Samper Noa, C. Moreno Carbonell, G. Lluis Ramos, S. Sosa Pérez Saily;
Medical University of Havana, Havana City, Cuba
The risk predictive models of dementia syndrome and AD allowed us to determine from individual
risk the probability that an old person develops these diseases. Aims of the investigation: To know
the prevalence of the dementia syndrome in the population over 60 years from Marianao
Municipality in Havana City and the relation of some biosocial factors that are associated with its
prediction. Methodology: A transversal cutting descriptive study was done in which 779 old adults
were evaluated in theirs home. The dementia syndrome diagnosis was based on the DSM-IIIr
criteria as well as the criteria established for the different sub-types. A predictive model of the
dementia syndrome and the Alzheimer‟s disease (AD) was elaborated and validated in efficiency
terms. Conclusions: The prevalence rates founded are as follow: dementia syndrome was 8,22%, the
prevalence of Alzheimer‟s disease was 5,13% and vascular dementia was 1,93%. Age, female sex,
family history of dementia, hypertension, antecedent of depression, and the low school level were
the factors that mostly influenced on the appearance of probable AD in the population that was

 BM88 a cell-intrinsic determinant that regulates initiation of pan-neuronal and subtype-specific differentiation of spinal cord

Politis P.a, Geissen M.b , Rohrer H.b , Matsas R.a
  Department of Biochemistry, Hellenic Pasteur Institute, Vas. Sofias 127, 11521, Athens. bMax-
Planck-Institute for Brain Research, Deutschordenstr. 46, 60528 Frankfurt/Main, Germany
Identification of molecules that control neurogenesis is of paramount importance for designing
therapies for nervous system lesions and abnormalities. We have identified BM88 as a neuron-
specific protein that drives neural precursors towards commitment to specific differentiation
pathways in vivo. Specifically, gain-of-function experiments by which BM88 was expressed in the
neuroepithilium of the developing chick spinal cord, by means of retroviral infection and in ovo
electroporation of the neural tube, demonstrated a dramatic phenotypic effect in the developing
CNS. In particular, BM88 over-expression caused a substantial decrease in BrdU incorporation
indicating that forced expression of BM88 drives progenitors to prematurely become post-mitotic
neurons. Consistently, BM88 led to a significant reduction in the size of the electroporated side of
spinal cord compared to the GFP electroporated. Interestingly enough, BM88 over-expression was
sufficient to produce ectopic neurons in the ventricular zone of spinal cord, manifested by down-
regulation of Notch, and up-regulation of the pan-neuronal markers ß-III-Tubulin, SCG10 and
NF160. The effect was more pronounced in the ventral spinal cord where over-expression of BM88
was sufficient to initiate a programme of motor neuron differentiation characterized by ectopic
expression of the transcription factor Islet1 and of the cholinergic transmitter phenotype. Moreover,
a significant reduction in the pool of spinal motor neurons was evident, possibly due to a premature
depletion of motor neuron precursors and/or an effect in motor neuron migration. These results
suggest that BM88 regulates qualitative and quantitative aspects of neurogenesis driving neuronal
precursors to terminally differentiated neurons with a correct functional phenotype.

                  Magnetic resonance spectroscopy as a diagnosis aid in early Alz heimer disease

Martina W.S. Nasruna; Patricia Widjaya b .
  Department of Psychiatry, Faculty of Medicine University of Indonesia, Jakarta, Indonesia,
  Department of Radiology, Husada Hospital, Jakarta, Indonesia.
Diagnostic procedures in Alzheimer Disease (AD) are mainly based on clinical assessment and a
series of neuro-psychological tests. There is a need to develop a technique in detecting early stage
of Alzheimer Disease which can be used as a standard diagnostic procedure accurately. The tools
should be practice, not expensive and not invasive. One of the possibilities is Magnetic Resonance
Spectroscopy (MRS). This is a preliminary study to find out in which region of the brain showing
prompt bio-metabolite decreased that correlate with AD pathogenesis (N-Acetyl Aspartate
decreased and Myo-Inositol elevated) in people with early dementia Alzheimer type. The
correlation of NAA, MI and its clinical presentation (including neuropsychological test) was
examined. There was sixth subjects with early AD examined by MRS and a set of psychometric
(MMSE, CDR, GDS and Verbal Fluency). Result of MRS examination showed that posterior
parietal lobe was the region with the most marked NAA decreased, while MII elevated not specified
yet. Clinical presentation and neuropsychological tests seems in line with brain bio-metabolite
decreased detected by MRS.

           Perineuronal Nets : A possible neuroprotective structure against oxidative stress in human brain

Markus Morawski, Martina K. Brückner, Gert Brückner and Thomas Arendt
Paul-Flechsig-Institute for Brain Research, University of Leipzig, Jahnallee 59, D-04109
Leipzig, Germany
Perineuronal nets are lattice-like aggregations of extracellular matrix components, originally
described by GOLGI and RAMON Y CAJAL as a reticular structure covering cell bodies and
proximal dendrites of certain neurons. These matrix components mainly consist of large
aggregating chondroitin sulphate proteoglycans connected to hyaluronan. PNs are associated with
different types of neurons in region dependent patterns in the brain of many vertebrate species
including man. In the human cerebral cortex, PNs surround several types of interneurons as well as
subpopulations of pyramidal cells, which are most frequently found in motor and primary sensory
cortical areas. Due to their glycosaminoglycan components, the perineuronal nets form highly
negative charged structures in the immediate microenvironment of neurons and might be involved
in local ion homeostasis. Perineuronal nets might also potentially be able to scavenge and bind
redox-active iron, and to reduce the local oxidative potential in the neuronal microenviroment, thus
providing some neuroprotection to net- associated neurons. Here, we show that neurons enwrapped
by a perineuronal net in the human cerebral cortex are less frequently affected by lipofuscin
accumulation than neurons devoid of a net both in normal aged brain and Alzheimer´s disease. As
lipofuscin is an intralysosomal pigment mainly composed of cross-linked proteins and lipids
generated through iron-catalyzed oxidative processes, this study proposes a possible
neuroprotective effect of perineuronal nets against oxidative stress potentially involved in the
pathomechanism of Alzheimer´s disease and related disorders.

               Association of Multiple Sclerosis (MS), diabetic autonomic neuropathy (DAN) and Stroke

Dimitrios Kountouris
Center For Neurological Diagnosis, Athens, Greece.
The co-existence of MS and diabetes is well known . However, it is also known that the DAN
appears as well as to diabetes patient very often. In 3 MS patients with DAN in a period of
exacerbation appeared symptoms of stroke. We evaluated the relationship between MS-DAN and
stroke in 3 patients (2 female and 1 male) having used neurophysiological (evoked potential) and
neuroradiological (MRI, SPECT, CTS) examinations. Simultaneously, we recorded the results of
the clinical parameters of different stroke factor as hypertension, diastolic blood pressure,
cholesterol level and smoking. In the period of the follow up in the 3 patient we attempted an
intense recording of all examination and therapeutic parameters.2 of the patients showed
deterioration of their clinical condition and they suffered 3 episodes of strokes which they appeared
in the cerebral computer tomography. The man while showing a general improvement he
subsequently had a stroke after which he had a slight deterioration. The results showed that the
appearance of DAN in MS patients could be due to genetic predisposition. They also indicate
therapeutic resistance and bad prognoses.

         Medial Temporal and Parietal N-acetylaspartate Reduction in Elderly Adults Mild Cognitive Impairment

Linda Chaoa, Norbert Schuffa, Diana Sacreya, Helena Chuib , Bruce Millera, William Jagustc,
Michael Weinerd
  Univeristy of California, San Francisco, b University of Southern California, cUniversity of
California, Berkeley, USA, dSan Francisco Veterans Affairs Medical Center, USA
There has been growing interest in elderly adults who suffer from cognitive impairment greater than
that which accompanies normal aging because these subjects have higher rates (12-15% per year) of
developing Alzheimer's disease (AD) than elderly subjects who are cognitively normal (1-2% per
year). It is likely that cognitively impaired elderly adults have pathologic brain changes that
correspond to an early phase of AD. The current study used magnetic resonance spectroscopic
imaging to examine N-acetylaspartate (NAA) concentrations in different regions of the brain. NAA
is a neuronal marker; therefore a decrease in its concentration suggests neuronal loss or dysfunction.
We also investigated the relationship between NAA concentration and performance on the Memory
Assessment Scales word list learning test because memory impairment is a cardinal feature of AD.
Twenty-four AD patients, 21 cognitive impaired but not demented (CIND) subjects, and 24 age-
matched cognitively normal subjects were studied. Relative to controls, CIND and AD and subjects
both had lower NAA concentrations in parietal (p=0.01) and medial temporal lobe gray matter
(p=0.001). Moreover, there were no significant differences in NAA concentrations between AD and
CIND subjects in these brain regions. This suggests that CIND subjects have AD-like pathology in
brain regions predominately impacted by the disease. In CIND subjects, medial temporal lobe NAA
concentration correlated positively (r=0.44, p<0.05) with performance on delayed list recall. This
finding underscores the functional significance of reduced NAA in the brains of CIND subjects.

                              Calcium is the unifying molecule in neurodegenerative dis orders

András Palotás, Botond Penke, Lajos Kemény, Zoltán Janka, János Kálmán
University of Szeged, Szeged, Hungary
Efforts to elucidate the pathomechanism of Alzheimer‟s disease and other neurodegenerative
disorders have yielded an increasing pile of hypotheses. When analyzing thousands of scientific
papers, the involvement of the central secondary messenger, calcium, becomes apparent. We
demonstrate that disturbed calcium homeostasis might be a common underlying factor in brain
pathologies. By targeting calcium, this new information promises to broaden our understanding of
health and illness and the approaches we take to treating disease.

  Complications of the Pharmacological manipulations in aged people w ith paraly tical sequels of chronic al brain-vascular
                  diseases submitted to Neurological Restauration Programs. Five years of experience

René Macias Betancourt, Reinaldo Galvizu Sánchez, Yamilka Velazco Acosta, Judith Pla Moret
Centro Internacional de Restauración Neurológica (CIREN), Havana, Cuba
A retrospective study was done in aged people with paralytic sequels of chronic brain-vascular
diseases that were submitted to Neurological Restoration Programs (4 weeks) in the CIREN in the
last 5 years (118 patients), to know the main complications of the pharmacological manipulations in
relation to the control of risk factors, sequels and self-complications of this type of affection, to
determine the poly-pharmacy level in the studied sample and its possible relationships with adverse
effects. It is found a real poly-pharmacy prevalence in the studied sample (25.75 of the cases had
indicated 6 or more medicaments daily). The main adverse manifestations related to the medication
were: gastric troubles, ortosthatic hipotension, constipation, somnolence and delirium. The main
groups of medicaments involved in adverse reactions in order of frequency were: the
benzodiazepines, tricyclic antidepressives, homorreologics, beta-blockers and anti-aggregants. It
calls the attention the low incidence of secondary effects in the aspirin use. It is shown a high
incidence in the adverse effects related to the quantity of used medicaments (57.1 % of the cases
consumed 6 or more medicaments). The age also represented an easy condition for the appearance
of adverse reactions (47.8% of the patients of 70 years or more presented some negative effect
related with the therapy). Then, it is necessary a more rational and individualized use of the doses of
the medicaments in aged poly-medicated people, paying special attention to tolerance.

Parkinson‟s disease

 Bilateral subthalamic nucleus lesion reverses levodopa-induced motor fluctuations and facilitates dyskinetic movements in
                                          an experimental model of parkinsonism

Concepció Marin, Anna Jiménez, Mercè Bonastre, Eduardo Tolosa
Laboratori de Neurologia Experimental, Fundació Clínic-Hospital Clínic, Institut
d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170, 08036
Barcelona, Spain
Glutamatergic overactivity might be involved in levodopa-induced motor complications since
glutamate antagonists reverse and prevent levodopa-induced a shortening in motor response
duration in 6-hydroxydopamine-lesioned (6-OHDA) rats and improve levodopa induced
dyskinesias in parkinsonian monkeys and in patients with Parkinson‟s disease (PD). An increase in
the subthalamic nucleus (STN) glutamatergic activity is believed to contribute to the
pathophysiology of PD. However, the role of STN activity in levodopa-induced motor
complications is not clear. In this study, the effect of STN lesions on levodopa-induced motor
response complications has been investigated in rats with a nigrostriatal pathway lesion induced by
6-OHDA. Animals were injected with 6-OHDA in the medial forebrain bundle and treated with
levodopa or saline for 22 days. On day 16, animals were randomly distributed in groups that were
under surgery in the STN ipsilateral or contralateral to 6-OHDA lesion, or bilateral. Rotational
behavior was measured on days 1, 15 and 22. Attenuation of STN activity by contralateral and
bilateral, but not ipsilateral, STN lesion reversed the shortening in motor response duration induced
by levodopa (p<0.01). Levodopa administration, but not saline, induced prominent dyskinesias in 6-
OHDA-lesioned rats with additional bilateral STN lesions (p<0.05). The results indicate that
bilateral lesions of STN potentiate the duration of levodopa-induced motor response and facilitate
chronic levodopa-induced abnormal involuntary movements in 6-OHDA-lesioned rats.

                        Epidemiological assessment of levodopa use in cuba, 1993-1998

G Lara Fernándeza, EM Esteban Hernándeza, S Luis Gonzaleza , JI Cuadrado-Gamarra b , J de Pedro-
Cuestab,c, S Giménez-Roldand , M. Estrada Suáreze
 Instituto Nacional de Neurología y Neurocirugía, La Habana, Cuba, bNational Centre for
Epidemiology, Instituto de Salud Carlos III, Madrid, Spain, c Division of Neurology,
NEUROTEC, Karolinska Institute, Stockholm, Sweden, dDepartment of Neurology,
Hospital Gregorio Marañon, Madrid, Spain, e Hospital Militar Luis Díaz Soto, Habana, Cuba
OBJECTIVE: To assess the use of levodopa in Cuba in the period 1993-1998. METHODS: We
obtained data on annual number of packages, units and strength of plain and combined, levodopa
delivered from the central state own laboratory to fifteen provincial distributors to hospital and
community pharmacies. An internationally established drug classification system and a reported
method for epidemiological assessment of levodopa sales were applied. The reference population
was Sweden in 1994. RESULTS: National crude rates of levodopa use remained basically stable
since 1994, being in 1998 0.11 DDD per 1000 inh /day, approximately fifteen times lower than the
corresponding figure in the reference population. Provincial annual use of levodopa showed
considerable geographical variation with lowest rates in Guantánamo, Santiago de Cuba and La
Habana, highest in Ciudad de La Habana, and increasing trends in Ciudad de La Habana and
Camagüey. Adjustment for age reduced approximately 50% such differences. CONCLUSIONS:
Despite some methodological limitations, the results show that levodopa use in Cuba is low and
consistent with reported low prevalence of PD diagnoses. If PD prevalence in Cuba is within the
range described worldwide, results suggest that there is a wide space for improvement of PD
diagnosis and treatment in Cuba.

                          Clinical and genetic features of Parkinson's dis ease in Cuba

José Luis Giroud Beníteza ,Aída María Bertolíb,c , Vincenzo Bonifatic ,e , Eduardo Alvarez Gonzálezd ,
Luis Herederob , Peter Heutink f.
  University hospital" Dr. Carlos J. Finlay., Service of Neurology, Cuba. b National Center of
Medical Genetics ISCM-Havana, Cuba. cDpto. of Clinical Genetics of the University of Erasmus,
Rotterdam, Holland. d International Center of Neurological Restoration, Cuba. eUniversity The
Sapienza, Rome, Italy. fSection Medical Genomics, University of Vrije, Ámsterdam, Holland
Introduction. The etiology of Parkinson's disease is unknown yet; there are many factors that
increase the risk to suffer it, as genetic factors are. Objectives. To expose the clinical-genetic
characteristics of this entity in our country. Methods. We were carried out a genetic clinical study of
series of cases in 200 consecutive patient with Parkinson's disease, from January of the 1999 to
December of the 2002, in the Hospital" Dr. Carlos J. Finlay". In the patients that it was possible we
was carried out a simple segregation analysis, and in the detected families it was carried out a
molecular study according to the established protocols, the samples of DNA were made a will with
markers for well-known loci. Results. 31.3% of the cases had family history. The autosomal
recessive inheritance was observed in 3 families one of them with a heterozygotic new parkin
mutation and another with a mutation of the DJ-1 gene. Autosomal dominant. Linkage and
haplotype analysis allowed us to exclude the Park1 (alpha-synuclein gene), Park2 (parkin gene,
6q25-27), Park3 (2p13), Park 5, and UCH-L1 gene (4p14-15). No mutations were found by direct
sequencing of Park1. A whole genome search is almost completed. We found linkage to
chromosome 19q13.3-12p. Conclusions. The inheritance is an outstanding factor in the Parkinson's
disease, the genetic and allelic heterogeneity of this entity it is characteristic of the genetically
complex illnesses.

                     Neuropsychiatric disorders in Parkinson’s disease. A study of 111 patients

Enrique Michel Esteban Hernandeza,Gloria Esther Lara Fernandeza, Nayibe Curi Mendozab
  Clinica de Trastornos del Movimiento Instituto de Neurologia y Neurocirugia, La Habana,Cuba.
  Policlínico “Elpidio Berovides” Municipio la Lisa, La Habana, Cuba
Objective: To describe the presence and features of some Neuropsychiatric disorders (NPD) in a
group of 111 patients with Parkinson‟s disease (PD). Background: NPD are commonly described
among the non-motor expressions of PD and frequently they could be even more disabling than
motor dysfunction itself. Methods: We studied one hundred eleven patients (56% male, non
demented, ages from 30 to 80 years old) who fulfilled the clinical criteria for primary PD, in
different stages of the disease (Hoehn &Yahr modified). The assessment scales used in the study
were the UPDRS score for motor disability, Activities of the daily life score (Schwab-England),
Cumming Neuropsychiatric Inventory, Diagnostic criteria of mood disorders (DSM IV), Beck
depression inventory and Minimental State Examination (MMSE). Results: 65,7% of the patients
had at least one NPD. The disorders more frequently found were: depression (45,9%); Anxiety
(35,1%); Irritability (23,4%) and Hallucinations (12,6%). The presence of NPD did not correlated
nor with gender neither with age, but it did significantly correlated with the duration of the disease.
Conclusions: According to our data, depression is the most common NSD in PD patients and it has
a higher incidence in patients with a worse motor control.

                             Functional MRI and other images in Parkinson’s disease

Rafael Rodríguez-Rojasa, Rolando Palmerob , Lazaro Alvarezc, Mario Alvarezc, Raul Macíasc,
Maylen Carballoa.
  Brain Images Processing Group, bStatic Lesions Clinic, cMotor Disorders Clinic, International
Center for Neurological Restoration, Havana, Cuba
BACKGROUND: Recent developments in high-resolution functional magnetic resonance imaging
(fMRI) provide a powerful tool to map the cortical activation in healthy and parkinsonian subjects.
In this research we study the cortical activation maps in patients with Parkinson‟s Disease (PD) and
we compare them with a group of normal subjects. The effect of DOPA medication and the
correlation with clinical motor improvement were also tested.
METHODS: fMRI data were acquired in 12 patients with PD and 4 normal subjects performing a
motor task, consisting in finger opposition sequential movement followed of repetitive flexion-
extension movements of the hand. Statistical Parametric Mapping (SPM) package was used to
detect differences in the cortical activity of patients when is compared with both normal pattern and
after DOPA supply. Clinical improvement was evaluated through UPDRS motor scale and
correlation with changes in fMRI signal was tested. RESULTS: Patients with PD show abnormal
activation intensities in Primary Motor cortex (M1), Pre-motor cortex (PM), Supplementary Motor
Area (SMA), inferior orbitofrontal cortex and associative parietal areas. DOPA medication induced
a greater activation in motor cortical areas. Improvement in clinical outcome correlated with
increase in fMRI signal in SMA, M1 and PM. Changes in SMA are particularly correlated with
improvement of hypokinesia in UPDRS motor scores. CONCLUSIONS: The study indicates that
fMRI enables quantitative evaluation of abnormal activation pattern in PD and the effect of
therapeutic intervention. PD patterns are partially normalized in ON medication state.

                                 Ablative procedures for Parkinson’s dis ease treatment

Macías R., Alvarez L., López G., Teijeiro J., Carballo M., Rodríguez R., Pavón N., Alvarez E.,
Maragoto C., Rodríguez Oroz MC., Guridi J., Obeso JA.
International Center for Neurological Restoration (CIREN) Havana, Cuba
Ablative procedures for Parkinson´s disease (PD) have been used for many years. Different targets
have been selected for these treatments: VIM thalamus (VIM), Medial Globus palidum (GPm) and
Subthalamic nucleus (STN). We had treated more than 347 patients with different movement
disorders meanly PD with more than 415 surgical procedures. Patient selection is crucial for
functional neurosurgery and the correct target choice to treat according with the clinical
characteristic of each patient. According to our experience (82 VIM thalamotomies, 205
Palidotomies and 126 subthalamotomies): VIM thalamotomy must be very carefully chosen for
those patients with advanced age and invalidating tremor as a main sign. GPm lesion could be
decided for patient with very intense LDOPA induced dyskinesia. STN lesion has the most
powerful effect over parkinsonian symptoms, signs, and permit maximal reductions in drug dosage.
Bilateral lesions in VIM and GPm are hazardous but bilateral STN lesions do not produce speech or
neuropsychological impairments. The efficacy of the procedures are higher than 90% (with
reduction in UPDRS motor score between 40 and 80%), morbidity is less than 8% and mortality
less than 1%.

       Motor response to levodopa and oscillatory activ ity in the subthalamic nucleus in parksinson´s disease (PD)

MC.Rodriguez-Oroza , F.Alonso-Frecha, I.Zamarbide a, M.Valencia a , M.Alegrea, M Rodriguez Diazb
J.Artiedaa, JAObesoa
  Neuroscience Center, Clinica Universitaria and Medical School, University of Navarra,
Pamplona. Spain. bSchool of Medicine, La Laguna, Tenerife, Spain
The study of oscillatory activity in the basal ganglia and motor cortex in the physiology of motor
control and pathophysiology of PD may help to understand some unexplained issues of the classical
model of the basal ganglia. We studied 7 PD patients treated with electrodes for chronic
stimulation. Local field potentials (LFP) from the subthalamic nucleus (STN) were recorded with
the implanted macroelectrode (Medtronic). All patients were continuously recorded during the
“off” to a fully “on” (following levodopa) medication state. The power spectrum of the dominant
frequency of LFP activity in several frequency bands (5-10Hz, 10-20Hz, 20-30Hz, 30-40Hz,
>60Hz) along the “OFF-ON” cycle were analyzed.All patients exhibited the same patron of LFP
activity changing from a dominant 10-30 Hz oscillations in the “off” motor state to a higher activity
(60-80 Hz) in the “on” motor state. Frequencies in the range of 5–10 Hz may have two different
evolutions: A consistent peak during “off” was observed with a 4-6 Hz resting tremor (46%).
Patients with coreic dyskinetic movements during the “on” showed a 5-10 Hz peak coinciding with
the movements. Patients with alternating movements of the legs (“diphasic dyskinesias”) exhibited
a drastic drop in all frequencies. Basal ganglia oscillatory activity is dependent on dopamine
deficiency. The “off” and “on” motor states in PD are not only related to hyper/hypo activity of the
STN but also to changes in oscillatory patterns, that may be included in a more precise revision of
the pathophysiological model of the basal ganglia.

                            Surgery for Parkinson´s disease: Lesion or stimulation?

Marwan Hariz
Institute of Neurology, Queen Square, London, UK
Purpose: To analyze the evolution of lesional and deep brain stimulation (DBS) surgery in
Parkinson´s disease (PD), with respect to effects and side-effects, and to examine the rational for
using either method in thalamus, pallidum and subthalamic nucleus (STN). Methods: Review of the
author´s own experience as well as the literature on DBS and on thalamotomy, pallidotomy and
subthalamotomy was conducted. Emphasis was put on analysing trends in choice of surgical targets
and procedures as well as the reported clinical results and side-effects. Results: There is only one
randomised study comparing lesion with DBS: it compares thalamotomy and thalamic DBS for
tremor showing less side-effects for the latter. For all other targets and procedures, only historical
information is available, and shows that DBS has re-emerged and seems to be preferred to lesions.
The reasons for increased popularity of DBS may be the possibility for safe bilateral and adjustable
surgery, the alledged lower frequency of adverse events, the potential offered by DBS as a research
tool for mapping basal ganglia, the enthusiasm of many neurologists for non-ablative procedures,
the decreased experience of many neurosurgeons in performing proper stereotactic lesions, and the
promoting role of companies involved in DBS. Conclusions: Although DBS is increasingly popular,
it is not accessible to all PD patients in need of surgery. Lesional surgery, especially in pallidum
and possibly in STN, still has a role in surgical treatment of PD, provided judicious selection of
patients by neurologists, and proper neurosurgical skills in performance of stereotactic lesions.

                           Rehabilitation in Parkinson's Disease: A Rational Approach

Lazaro Alvarez Gonzalez
Movement Disorders Clinic. CIREN, Havana, Cuba
Before the introduction of L-Dopa in the late 60's,physical therapy was widely consider to be an
option in the treatment of Parkinson's Disease but the development of more efficient drugs or
surgical strategies in the last 40 years led to decrease interest in alternative therapies. Now is well
know that the efficacy of drugs does not last indefinitely and surgery is only indicated in less than
10 % of the patients so in addition to the standard drug regimen ,physical therapy is often prescribed
to help in the management of the disease.
In recent years, there have been an increase in reports of physical therapy combined with various
techniques (sensory cues, treadmill training with body weight support, instructional sets and others)
with promising results who are consistent with our own experiences using rehab techniques in PD.
Since 1988 to date we have been explored the efficacy and indications of the most recognized
alternative methods alone or combined with standards treatment. In this review we summarized the
evidence obtained from our experience and from the literature, in regarding to clinical efficacy and
potential therapeutic mechanisms and propose and integral rehabilitation program to improve PD

                        Chiropractic intervention on parkinson's rehab treatment program

Raul Carrillo Rodrigueza , Raul Alvarez Valerob
  Northwestern College of Chiropractic, USA, bChristus Muguerza Hospital, Saltillo Coahuila
Parkinsonism, described in 1867 by Dr. James Parkinson, is recognized worldwide among the
movement disorders, the symptoms experienced are: resting tremor, bradikinesia, simioid posture,
frozen shoulder, seborrhoea, sialorrhea, dementia, visua l dyspraxia, orthostatic hipotension,
disphagia, esophageal dismotility, constipation, etc. Patient classification has been done considering
their motor, neuropsychological and cognitive capabilities. Through this observations, the motor
dysfunction is considered as one of the base line symptoms to treat for the Parkinson‟s patient, thus
chiropractic treatment plays a significant role on the restoration of proper biomechanics of the
patient, through the chiropractic adjustment for the subluxation complexes presented by the patients
due to the muscle tone imbalance that Parkinson‟s patients develop through mechanoreceptor
activity and adaptation secondary to simioid posture and tremors present. The rehab program should
involve an integral model in order to maintain muscle and biomechanical balance, in order to
achieve improvements in balance, speed, coordination, dexterity and posture. The chiropractic
adjustment in particular, functions to re-establish function at the motion unit involved (joint) and
also the physiological effects that come along with the mechanical dysfunction of the sublimation
complex. Adjustments are performed previous detection of the specific vertebral subluxation
complexes or dysfunctional joints, through ortho-neurologic, radiological, dermathermography,
bone density scans, bone scans, motion palpation, x-ray, MRI, all to trying to make the best and
most accurate diagnosis. At integral health center, diverse specialist in different areas like
orthopaedics, neurosurgery, neurology, chiropractic, physical medicine and rehab, radiologist, etc.

                  Influence of attention and motor planning in the activ ity of primary motor cortex

Magdalena Sabaté a, Belén Gonzáleza a Ramón Muñiz c, and Manuel Rodríguezb
  Department of Physical Medicine and Pharmacology, b Department of Physiology and Faculty of
Medicine, University of La Laguna; cIMETISA, Canary University Hospital, Tenerife, Canary
Islands, Spain.
The primary motor cortex (M1) is the main cortical output for the executive motor orders coming
from cortical and subcortical pre-motor centres. The objective of this work was to study with
functional magnetic resonance imaging the possible pre-motor activity of M1 in relation to its motor
functions. Data show that the dimension of the M1 area activated and the intensity of response were
higher during activities that need pre-motor planning (phasic movements of the forefinger, motor
imagery that consisted of imagining the performance of phasic movements of the forefinger but
without real movements) than during motor activities (tonic flexion of the forefinger) that
practically do not need of pre-motor planning. Distracting concurrent task (numeric calculus) that
did not disturb the finger movements decreased the activation of M1 induced by the phasic
movements of the forefinger. There was a mosaic-like distribution for pre-motor M1 functions, with
the movement of individual fingers being controlled from several M1 loci. Attention induced a fast
functional reconfiguration of M1, adding M1-subsets to motor programming but excluding others.
Taken together, present study show that human M1 is involved in motor activities but also in the
pre-motor planning of movements.
               Nursing Attention Process to Parkinsonian patients candidates to selectiv e pallidotomy

Antonio D. Villa Juárez and Janett Benavides Barbosa
Neurosurgery Service, International Center of Neurologic Restoration Center, CIREN,
Havana, Cuba.
The Parkinsonian Syndrome is a degenerative disease of the CNS, characterized by abnormal
involuntary movements. At the present moment this disease is treated surgically at different targets
including the internal pallidum. The use of a personalized nursing attention process allows to
achieve a superior attention care in the parkinsonian patient. The objective of this paper was to
evaluate the impact of the nursing diagnosis and planned personalized attention on patients that will
receive surgical treatment. For this issue, 22 patients with dyskinesia, submitted to selective
pallidotomy, of which 16 were males and 6 females respectively, ranging from 35 to 65 years of
age, were studied. The application of the nursing attention process allowed us to detect in those
patients a 100% impairment of the hystic integrity, a 100% deficit for self-care, a 75% alteration in
verbal communication, a 100% anxiety and a 100% risk of lesion. The role of nursing is
fundamental in the evolution of these patients for their fast return to society.

                Subthalamotomy in Parkinson´s Disease(PD): Effect on L-Dopa induced dyskinesias

E.Alvarezª; L.Alvarezª; R.Maciasª; N.Pavonª; M.C.Rodriguezb ; J.Guridib ; J.A.Obesob
  International Center For Neurological Restoration,Havana;Cuba; bClinica Universitaria de
Navarra.Pamplona, Spain
Dyskinesias are a common complication of advanced PD due to both long term L-dopa treatment
and disease progression. Lesion of the subthalamic nucleus (STN) in humans is associated with
hemichorea-ballism. In parkinsonian monkeys STN cytotoxic or thermolytic lesions were
associated with mild dyskinesia or HCB. More recently, studies using deep brain stimulation (DBS)
of the STN reports low ocurrence of HCB but improvement on previously existing L-Dopa induced
dyskinesias(LID). In order to better define the relationship between dyskinesias and lesion of the
STN in PD we conducted an open study during the last 5 years in 17 PD patiens submitted to
bilateral lesion of STN (Staged or Simultaneous) using the UPDRS and the Dyskinesias Scale. We
observe a transitory increase in Peak Dose Dyskinesias , a reduction of 50 % of diphasic diskinesias
and an arrest of dystonic dyskinesias coinciding with the frecuent presence of spontaneous off
dyskinesias related to the surgery, at short term follow up. At one, two and three years follow up
global rating of LID decreased by 50%,with more marked effect on dystonic dyskinesias and a
significant improvement in both, disphasic and peak dose dyskinesias. We can conclude that
subthalamotomy reduce LIDs at long therm follow up. Whether or not this only related to the
reduction in the total daily dose of L-Dopa is open to discussion.

                         Subthalamotomy in Parkinson¢s Disease: The CIREN experience

L.Alvareza ,R.Maciasa and JA Obesob (on behalf of the CIREN subthalamotomy study group).
  International Center for Neurological Restoration, Havana, Cuba. bUniversidad de Navarra, Spain
Surgery for Parkinson's disease is not a new concept. Ever since scientists discovered that many of
the symptoms of the disease can be traced to chemical imbalances deep in the brain, there has been
theoretical support for the idea of restoring a balance by removing or disabling certain overactive
areas.Palidotomy is accepted as a typical example but destroying areas implicated in Parkinson's
disease may has been effectively bypassed by improvements in drugs and technologies such as deep
brain stimulation (DBS). In the last few years, however, the lesion of the Subthalamic nucleus
(STN) has emerged as a new alternative for special circumstances. In our first study, published in
the Movement Disorders Journal (2001) , we were able to demonstrate that unilateral lesion of the
STN can be performed safely and improve motor function without major complications. The next
goal was to assess the safety and efficacy of bilateral subthalamtomy , which was done by
performing staged surgery(at least one year apart) in 7 patients. This also resulted in marked
symptomatic relief without noticeable side-effects. Recently, we have assessed the effect of
bilateral, simultaneous subthalamotomy in 11 patients, followed for 36 months after surgery. As a
group those patients were still scoring well over 50 percent better on movement tests than they had
before surgery. Significant improvement was seen on other tests and the average daily L-dopa dose
had been reduced by 70%, greatly reducing some of the side-effects of the drug. Up to now we have
performed subthalamotomy in 90 patients (a third bilaterally) with similar good results. In fact,
experience and refinement of the technique have led to shortening the intraoperatory time and more
reliable clinical results.

           Bilateral dorsal subthalamotomy in Parkinson’s disease: initial response and long-term evolution

Alvarez La, Macias Ra, Lopez Ga , Alvarez Ea, Pavon Na, Rodriguez-Oroz MCb , Juncos Jc, Maragoto
Ca , Guridi Jb ,Litvan Id , Tolosa ESe, Koller Wf,Vitek Jc, DeLong MRc, Obeso JAb .
  Movement Disorders and Neurophysiology Units, Centro Internacional de Restauracion
Neurologica(CIREN), La Habana, Cuba. b Departments of Neurology and Neurosurgery,
Neuroscience Center, Clinica Universitaria and Medical School, University of Navarra,
Pamplona,Spain. cDepartment of Neurology, Emory University School of Medicine, Atlanta, USA.
  Department of Neurology, University Hospital, Barcelona, Spain. f Parkinson’s Disease Research
Center, University of Miami Medical School, Miami,USA.
We conducted an open, pilot study of the effect of bilateral stereotactic subthalamotomy in 18
patients with advanced Parkinson‟s disease (PD) uncontrolled with the available pharmacological
means. In 7 patients, the first subthalamotomy antedated the second by 12-24 months (“Staged
surgery”). A second group of 11 patients received bilateral subthalamotomy on the same day
(“Simultaneous surgery”). Patients were assessed according with the CAPIT (Core Assessment
Program for Intracerebral Transplantation) and a battery of timed motor tests and
neuropsychological tests. Evaluations were performed in the “off” and “on” states before surgery
(base line) and at 3, 6, 12, 18, 24 and 36 months postoperatively. Compared with baseline, bilateral
subthalamotomy induced a significant (p<0.001) reduction of 50,8 % in the “off” and 33 % in the
“on” UPDRS motor scores at the last assessment. Blind rating of videotapes showing the motor
status in the “off” and “on” medication states pre and at 2 years postoperatively also revealed a
significant improvement. All cardinal features of PD were significantly ameliorated and Activities
of Daily Living (ADL) significantly (p<0.01) improved. The mean daily levodopa dose was
reduced by 48 % (p<0.0001) at 3 years after surgery. Five patients stopped taking levodopa.
Dyskinesias occurred intraoperatively in 14 patients (72%) but were mild and short lasting in all but
3 of the patients from the simultaneous surgery group. These patients developed severe generalized
chorea associated with fairly large lesions of the subthalamic region. The generalized chorea
improved spontaneously after some 3-6 months in these 3 patients. For the whole group, levodopa-
induced dyskinesias were reduced by 50 %(p<0.01) .No permanent cognitive defect or speech
deterioration was detected except in three patients who exhibited dysarthria. The motor benefit has
maintained after 3 years. Bilateral subthalamotomy may induce a significant and long-lasting
improvement of patients with severe PD but the clinical outcome is not homogeneous. Further
refinement of the procedure is mandatory before establishing it as a part of the surgical option for

                  Actions of Nursing in the neurorehabilitation of patients w ith Parkinson’s dis ease
Leisa Díaz Gálvez, Deimi Reconde, Yusimí Serra Valdez, Teresa Morgado, Amneris Figueras
International Center for Neurological Restoration (CIREN), Havana, Cuba
The team of nursery plays an important role in the neurorehabilitation of patients with Parkinson‟s
disease (PD). The keys of our approach are the principles of neural plasticity of the Nervous System
and our concept of multifactorial neurorehabilitation. The nurse‟s work its not the simple
prolongation of physical therapy or occupational therapy which create the automation to adequate
pattern of walk, stand, language and manipulative abilities; all the which are decreased in PD. The
nurse‟s contribution is to make the learned abilities integrated in every aspect of daily life and self
care. The nurse‟s actions search also to improve the integration of the new behavior patterns to his
family and to appreciate the better quality of life.

                               Post-surgic al rehabilitation of Parkinsonian patients

Roberto Díaz Márquez, Mario Carballosa Coré, Lázaro Álvarez Gonzálezª
International Center for Neurological Restoration (CIREN), Havana City, Cuba
The work was carried out at International Center of Neurological Restoration (CIREN. A sample of
60 Parkinsonian operated patients was selected, with the objective of evaluating the results of their
physical rehabilitation. A random retrospective study was carried out from 1993 to 2002. It
conformed a control and an experimental group of 30 patients respectively, by using 12 standard
tests. Measures were taken before and after treatment in the Integral Psychomotor Evaluation
Laboratory. The patients of the experimental group received a post-surgical rehabilitation for a
month. The results were statistically processed to check the differences at the beginning and at the
end of the rehabilitation, to compare the results with operated on patients that did not receive
physical therapy. Patients who were rehabilitated after surgery, improved their initial results by
increasing their mobility, ba lance and coordination. In both groups of patients significant
differences were obtained, and the experimental group had better results in functional tests, which
indicates that post-surgical physical rehabilitation contributes to a better recovery of patients.

The Parkinson¢s Disease Gait Disorders Scale .Version 3.1(Spanish Version by Martinez et
al,2000): Introduction and Validation. Preliminar report

Morgado T.,Reconde D.,Figueras A.,Enamorado I.,Alvarez L.,Martinez.P.
Movement Disorders and Degenerative Disease Clinic,CIREN,Havana,Cuba
Gait disturbance is a main problem in advanced PD. Short steps, difficulties to turn, start hesitation,
motor blocks and freezing induce important impairtments and falls. Some of them are refractary to
drug treatment and partially responsive to surgery or trainning.To better define the overall impact of
these disorders some methods and rating systems has already been developed. An integral score to
assess gait in PD has been contructed and validated by Martinez et al in Spain. This instrument has
strong consistence, reability and sensitivity to cuantificate the impairment to walk. From Jan 03 to
June 03 we were conducting an open pilot study to introduce and validate the score in our clinic.The
results show high correlation with the related items of the motor section of the UPDRS and appears
as a very sensitive method to evaluate the impact of diferent therapeutical techniques on gait
disturbances, better than the Tinetti score. In consecuence, we recomended the inclusion of this
rating score in the follow-up of Clinical Trails in PD and to follow the response to treatment during
inpatient care.

                        The physical exercise in patients with amyotrophic lateral sclerosis
Alexander Echemendia del Valle, Reinaldo Gómez Pérez, Jorge Luis Torres, Gilda Martínez
Aching, Carlos Fernández
International Center of Neurological Restoration, Havana, Cuba
Introduction: The use of the physical exercise with therapeutic and health purposes is known from
the antiquity but only in the last years it has begun to establish their authentic physiologic and
preventive repercussion. Among the illnesses that have been benefited by the contribution of the
physical exercise is the amyotrophic lateral sclerosis. This is a degenerative disease of unknown
etiology that affects the superior and inferior neurons, and is characterized by the weakness, muscle
atrophy, hyperreflexia, and spasticity. Onset can occur at any moment after maturity. Objective: To
analyze the effect of the physical exercise on the vital capacity, the muscular force and in the
functionality of the patients with amyotrophic lateral sclerosis treated at the CIREN. Material and
Methods:We used a sample of 6 patients diagnosed with amyotrophic lateral sclerosis with an age
55 year-old average and an evolution time of 2 years. All patients were evaluated in tests of:
spirometry, hand dynamometry and back, application of ALS Functional Rating Scale, before
beginning the treatment. The program of physical exercises was performed during 28 days. All tests
were repeated after finishing the therapy. Results: A significant improvement was obtained in the
vital capacity and in the functionality of the patients, while the muscular force remained almost
unalterable. Conclusion: It is inferred that the properly dosed physical exercise can attenuate the
effects of illness.

                 Progresive Supranuclear Palsy (PSP):A Descriptive Study and implications for Treatment

Álvarez E., Maragoto C., Arteche ME., Carballo M., Álvarez L.
Centro Internacional de Restauración Neurológica (CIREN). Habana. Cuba
PSP is an uncommon ad sporadic degenerative disease, usually observed after 50 years as a
parkinsonian syndrome with refractory response to L-Dopa. Main features include axial
Parkinsonism and dystonia, supranuclear oftamoplegia, pseudo bulbar palsy, dementia and
imbalance with frequent falls. First described by Steel, Richardson and Olzewski at early 60` shows
no or minimal response to L-Dopa, a rapid course and marked impairment due to the falls and
dysphagia. The better comprehension of the semiologic and pathofisiology of cardinal
manifestations allow us to design more efficient treatment approach. Based on this premises, we has
been conducted a descriptive clinical and epidemiological study in 18 patients who fully complete
the NINDS-SPSP Operative Diagnostic Criteria. An exhaustive clinical evaluation using the Golbe
Score and a battery of complementary studies were performed and results were summarized to
characterize the common picture and to analyze its pathophysiological basis in order to obtain
suggestion for further approach. The average age to start was 58.6 ± 8.2 years; the mean evolution
time at diagnosis was 4.39 ± 2.3 years. Gait disorders, falls and slowness were the predominant
features at early stages and dysphagia and dementia were late. None of them respond to
dopaminergic stimulation but some of them partially respond to cholinergic and NMDA antagonist
drugs. Validism were conserved by 4 years in the 75% of the patients and ambulation and
communication promotes the disability, falls and imbalance improve after rehabilitation speech not.
Some pathophysiologic and therapeutic considerations can be defined in consequence.

  Nursing contribution to reduce the surgical time during stereotactic and functional neurosurgery for movement disorders

Ángel L. Aquino Ávila, M. Cristina Grandal López
Surgical Department, International Center for Neurologic Restoration, Havana, Cuba
The surgical time is a main factor increasing infection risks, patient‟s psychological stress, and
economic costs. Stereotactic and functional neurosurgery for movement disorders has several
procedures that require a long time in the operating room. This paper describes the nursing
contribution to reduce this time, and describes the time evolution between years 1996 to 2003.
Actions carried out by the nurses are simultaneous to the surgical planning made by the
neurosurgeon, or during the surgical act: That helps the physician to reduce general time of the
surgical procedure. Time of surgeries made before and after the use of these nurse actions, is
compared here. It is known that other factors also have influence on this variable, but a reduction of
surgical time was reached with the nursing contribution. This experience has also been transmitted
to other surgical teams, which have received training for stereotactic and functional neurosurgery at
our center.

                                Conscious sedation in generalised dystonia surgery

Alexei Villegas Achón, Juan Piedra García, Gerardo López Flores, Carlos Maragoto, Lázaro
International Centre for Neurological Restoration, Havana, Cuba
In the surgical treatment of patients suffering from generalized dystonia, the patient must be still
and conscious in order to allow an ongoing assessment of their state throughout the surgery. We
employ the method of conscious sedation in order to ensure the mentioned surgical procedure as
required, using Diprivan as the agent of sedation. We proposed, via this research, to demonstrate the
use of this method in addition to defining the correct dosage of the agent employed, corroborating
the level of cerebral hypnosis via the bispectral index. In the ten patients studied a favorable state
was obtained for the surgical procedure by defining the range of dosage of Diprivan as between 0.8
y 1.2mcg/ml to acquire a state of tranquility and a safe level of consciousness, corresponding with a
Bispectral index of 82-98. The results achieved in this study are unprecedented.

                  Current situation of Parkinson Disease in Habana Vieja municipality 2000 -2001

G Lara Fernándeza, EM Esteban Hernándeza, M. Estrada Suárezb , S Luis Gonzaleza , A. Hernández
Péreza, J. Mena Pedrosob , M. Blanco Pegoc
 Instituto Nacional de Neurología y Neurocirugía, La Habana, Cuba, b Hospital Militar Luis
Díaz Soto, La Habana, Cuba, c Municipio de Salud Habana Vieja
OBJECTIVE: Evaluation of Current situation of Parkinson Disease in an urban municipality of
Cuba. METHODS: At this municipality, the population of 105650 inhabitants and 18% of them
with more than 60 years old, which is distributed into five areas of health and 162 doctor and nurse
offices; a research was developed in two phases 1) recording of all patients with Parkinson Disease
diagnosis made by those doctor´s offices and 2) evaluation of all patients made by a special team of
the Institute of Neurology and Neurosurgery of Cuba for a diagnosis confirmation. RESULTS: The
diagnosis for 28 patients was confirmed, predominating the group of 60 to 69 years with 25% of
pathological familiar antecedents of first and second degree for the disease; 92,86% of good answer
to levodopa and motor complications after 3 years of treatment cycle. The 30% of patients
presented parkinsonisms by medicines. CONCLUSIONS: It was detected a low disease prevalence,
with a 41.6% of over diagnosis. The hand tremor was the most frequent initial symptom and the
presence of motor fluctuations was more related with long exposures to levodopa than diskynesias.
The diagnosis capacity of the medical personal of primary attention must be raised.

              Functional magnetic resonance imaging in Parkinson´s disease before and after levodopa
Mario Álvarez, Lázaro Álvarez, Rolando Palmero
International center for Neurological Restoration (CIREN) Havana, Cuba
Functional Magnetic Resonance (fMRI) was used to study blood oxygen level dependent cortical
signal changes associated with volitional limb movements with and without levodopa in
Parkinson‟s disease. Twelve patients with early stage akinetic Parkinson‟s disease and four
volunteers underwent functional imaging while performing movements of the hand. We repeated
the scanning procedure in the Parkinson‟s disease patients when akinesia improved after oral
levodopa. Compared with the control group, patients both off and on levodopa showed movement
related impaired activation in the rostral supplementary motor area, primary motor cortex and
cerebellum, and increased activation in parietal cortex. We conclude that levodopa improves
impaired motor initiation in the supplementary motor area and decreases hyperfunction of lateral
premotor associated with Parkinson´s disease during simple volitional movements. The cortical
areas cited above are not primary damaged in Parkinson‟s disease thus could be the target for
further new rehabilitation programs.


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