Abstracts der Jahrestagung SNG Aarau

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183. Jahrestagung der
Schweizerischen Neurologischen Gesellschaft SNG
183e réunion annuelle de la Société Suisse de Neurologie SSN
(181e réunion)
Aarau, 5.–7. November 2009

Freie Mitteilungen                                         FM 2 Multicentric tumor manifestations of                    traventricular). The patterns showed individual
                                                           high grade gliomas: independent proliferation                and location specific time gaps to metachronous
Donnerstag, 5.11.2009, 17.30–18.30 Uhr
                                                           or hallmark of extensive disease?                            manifestation.
                                                                                                                            Calculated from the time of first tumor di-
FM 1 Motor imagery in older adults, a new                  M. Hefti1, G. von Campe2, C. Schneider4,
                                                                                                                        agnosis, the median survival was longer for pa-
way to assess higher-level gait and balance                H. Landolt3, U. Roelcke3
                                                                                                                        tients with metachronous MC lesions (353 days,
disorders                                                  1
                                                               Universitätsklinikum Schleswig-Holstein                  p <0.05) compared to patients with synchronous
G. Allali1, F. Assal1, C. Annweiler2,                          Campus Kiel, Kiel, Germany                               MC lesions (110 days) or patients without mul-
S. Bridenbaugh3, F. R. Herrmann4,                          2
                                                               Universitätsklinik für Neurochirurgie, Graz,             ticentricity (234 days). Patients with metachro-
R. W. Kressig3, O. Beauchet2                                   Austria                                                  nous lesions showed similar survival (72 days)
                                                               Kantonsspital, Aarau, Switzerland                        as patients with synchronous MC lesions (110
    Department of Neurology, Geneva,                       4
                                                               Kantonsspital, Winterthur, Switzerland                   days) once they developed MC disease.
                                                                                                                            Conclusion: The topographical patterns and
    Department of Internal Medicine                        Objective: Improvements in microneurosurgical
                                                                                                                        temporal characteristics of MC disease suggest
    and Geriatrics, Angers, France                         techniques, radiotherapy and chemotherapy for
                                                                                                                        that all manifestations share common mecha-
    Department of Geriatrics, Basel, Switzerland           high grade gliomas result in better local tumor
                                                                                                                        nisms such as an active migratory process. Our
    Department of Rehabilitation and Geriatrics,           control and longer progression free survival. Multi-
                                                                                                                        data therefore do not support the concept of
    Geneva, Switzerland                                    centric (MC) lesions located distant from the ini-
                                                                                                                        an independent MC development of multiple
                                                           tial resection area, contribute to treatment failure
Objectives: To measure and compare the time need-                                                                       gliomas.
                                                           in a growing number of patients. These MC le-
ed to complete the Timed Up & Go test (TUG),
                                                           sions may develop within the course of the disease
the time needed to imagine performing the same
                                                           (metachronous) or may already be present at the
test (iTUG) in a sample of young and older adults,                                                                      FM 3 Stress hormones to predict
                                                           time of first tumor manifestation (synchronous).
and to examine whether there was an association                                                                         cerebrovascular Re-events in TIA patients
                                                           To look for mechanisms and regular patterns be-
between the Timed Up & Go test results (TUG and
                                                           hind MC glioma manifestations and to investigate             M. Katan1, F. Fluri2, N. Morgenthaler3,
iTUG), age and cognitive decline.
                                                           whether they are “a second primary tumor” or                 N. Nigro1, Ph. Schütz1, S. Neidert1,
     Methods: This study included 162 subjects (38
                                                           the result of continuous diffuse glioblastoma cell           F. Jax4, S. Meckel4, A. Gass4, R. Bingisser5,
healthy young adults, mean age 25.7 ± 2.3 years,
                                                           invasion, we retrospectively analyzed the initial            L. Kappos2, A. J. Steck2, S. Engelter2,
73.7% women and 124 older inpatients, mean
                                                           and all follow up MR studies of our high grade               B. Müller6, M. Christ-Crain1
age 85.3 ± 6.5 years, 76.6% women). The mean
                                                           glioma (HGG) patients.
± SD of TUG and iTUG, age and the Mini Men-                                                                             1
                                                                                                                            Department of Endocrinology University
tal State Examination (MMSE) score were used                    Patients and methods: MR studies of 247 con-
                                                                                                                            Hospital Basel, Basel, Switzerland
as outcomes. The height, the number of drugs               secutive patients treated for HGG at a single in-            2
                                                                                                                            Department of Neurology, University Hospital
taken per day, the use of psychoactive drugs, the          stitution were analysed. MC tumor manifesta-
                                                                                                                            Basel, Basel, Switzerland
use of a walking aid and a history of falls in the         tion was defined as more than one gadolinium                 3
                                                                                                                            Research Department, Brahms AG,
previous year were used as covariables.                    enhancing lesion within the brain on MRI with-
                                                                                                                            Hennigsdorf/Berlin, Germany
     Results: Older adults performed the TUG               out a connecting signal alteration in T2 sequenc-            4
                                                                                                                            Department of Neuroradiology, University
slower than young adults (P <0.001), as the                es and/or without a connecting hypointense
                                                                                                                            Hospital Basel, Basel, Switzerland
imagined TUG (P <0.001). Multivariate linear               mass in T1 sequences. The minimal distance to                5
                                                                                                                            Department of Internal Medicine University
regressions showed that age was associated with            define two solitary lesions was set at >10 mm.
                                                                                                                            Hospital Basel, Basel, Switzerland
an increase in time of TUG (P <0.001) and with             The MR studies were retrospectively analyzed                 6
                                                                                                                            Department of Internal Medicine,
a decrease in time of iTUG (P <0.001). There               for patterns in MC tumor manifestation and pro-
                                                                                                                            Kantonsspital Aarau, Aarau, Switzerland
was an increase in time of TUG (P <0.001) for              gression. Topographical specifications and delay
                                                           in manifestation were used to explain possible               Background: Transient-ischemic-attack (TIA) is a
subjects who used a walking aid and who fell in
                                                           pathways of development. Kaplan Meyer sur-                   strong predictor of subsequent stroke. It has been
the previous year.
                                                           vival graphs for metachronous and synchronous                shown that copeptin, a hypothalamic-stress-hor-
     Conclusion: These results provide the first
                                                           MC disease were calculated.                                  mone, is an accurate prognostic marker in acute
evidence that iTUG is clinically feasible among
                                                                Results: According to specifications 40 pa-             stroke. This study assessed prognostic reliability
frail older adults and may quickly contribute to
                                                           tients showed MC tumor manifestations in their               of two distinct stress hormones, copeptin and
assess higher-level changes in control of gait and
                                                           MR studies on admission or during treatment                  cortisol, for the risk-stratification of re-events in
balance in older adults.
                                                           of their disease. 24 patients showed MC tumor                TIA-patients.
                                                           manifestation at the time of admission. 16 of                    Methods: We conducted a prospective study
                                                           the cases developed MC manifestation within a                in patients admitted to the emergency depart-
                                                           follow up period of 3 to 57 months. The location             ment with acute TIA. Clinical risk scoring using
                                                           of all lesions could be categorized into three dis-          the ABCD2-score was determined and both hor-
                                                           tinct patterns (white matter, subependymal, in-              mones were measured on admission. The pri-

                   S C H W E I Z E R A R C H I V F Ü R N E U R O L O G I E U N D P S Y C H I A T R I E 2009;160(7):305–18 |                305

mary endpoint was a cerebrovascular re-event               (48%), or cured (16%), with a significant pre-               sclerosis was diagnosed on the basis of three clini-
within 90 days. The secondary composite end                ponderance of women (73% versus 50%, p =                     cal relapses, progression of the MRI lesion load
point consisted of stroke, death, or presence of           0.047). There was no difference regarding out-               and oligoclonal bands in the cerebrospinal fluid
a high-risk stroke mechanism requiring specific            comes between the three treatment groups in                  (CSF) [1]. From 2003, he was treated with in-
early intervention (i.e. 50%> stenosis in the rel-         men and women. The most robust difference                    terferon-b1b, mitoxantrone (40 mg/m2 body sur-
evant vessel or a cardioembolic source).                   was achieved with CBT, which was associated                  face) and azathioprine, before monotherapy with
    Results: We included 107 consecutive TIA-              with a significantly higher rate of recovery (23%            natalizumab was begun in 2007 in the presence
patients. Re-events occurred in 10 patients                vs 9%), and improvement (53% vs 42%) (p =                    of normal blood cell counts. At this time, he had
(9%). The composite endpoint occurred in 33                0.024), and with a significant gender difference             experienced 16 multiple sclerosis relapses in total,
patients (31%). Copeptin levels were higher in             (p = 0.01), being more effective only in women               and the expanded disability status score (EDSS)
patients with a re-event compared to patients              (p = 0.004, men: p = 0.69). All treatments signifi-          was 3.5 [2]. During treatment with natalizumab,
without re-event (p = 0.02). In patients fulfilling        cantly improved pain intensity (VAS: p = 0.01,               no further relapses occurred, the EDSS improved
the combined endpoint (n = 33), copeptin levels            p = 0.003 and p = 0.000 and McGill total: p =                to 3.0, and the one-year follow-up MRI in 2008
were higher compared to patients without (p =              0.004, p = 0.122 and p = 0.014 for infiltration,             showed a stable lesion load.
0.03). There was no difference in cortisol levels          medication and physiotherapy, respectively)                       In May 2009, the patient developed fever and
between these groups (p = 0.53, respectively p =           without significant differences between the                  meningism. MRI showed a new T2-hyperintense
0.78). Copeptin revealed a higher area under the           groups. Also, working ability improved overall               lesion in the left occipital lobe (fig. 1a). CSF showed
receiver-operating-characteristics curve (AUC)             (p = 0.023) in the infiltration and physiotherapy            pleocytosis of 106 cells/µl, mostly lymphocytes,
to predict re-events compared to the ABCD2                 groups, but not in the medication group. CBT                 and no JC virus (JCV) DNA, but HSV-2 DNA (1037
score (AUC of 0.73 versus 0.43; p <0.01). The              had a favorable influence independent of the                 copies/ml). HIV-screening was negative. A relapse
combination of the clinical score and the bio-             primary treatment group (p = 0.003).                         of HSV-2 meningoencephalitis was suspected and
marker showed an even higher overall prog-                     Conclusion: Intensive therapy in late whip-              treated with valaciclovir. Three weeks later, HSV-
nostic accuracy with an AUC of 0.77(p = 0.002).            lash syndrome can achieve improvement in two                 2 and JCV DNA were undetectable in the CSF,
    Conclusion: Measurement of plasma co-                  thirds of patients which is maintained beyond 6              and control MRI showed no progression (fig. 1b).
peptin, but not cortisol levels in TIA-patients            months in half of them. Overall, women showed                Natalizumab treatment was continued under val-
provides additional prognostic information be-             a higher rate of improvement. Additional CBT                 acyclovir prophylaxis (500 mg/day). In July 2009,
yond the ABCD2-clinical-risk-score alone. Rou-             was the most effective treatment modality in-                follow-up MRI revealed a progression of the oc-
tine Copeptin measurement could be an addi-                dependent of the concomitant therapies, with a               cipital lesion, which was asymptomatic except for
tional tool for risk-stratification after TIA.             significant effect on outcome, including working             increased light sensitivity (fig. 1c). Lumbar punc-
                                                           capacity.                                                    ture revealed 7 cells/µl, no HSV-2 DNA, but of JCV
                                                                                                                        in three laboratories (87–297 copies/ml), proving
FM 4 Late Whiplash – a Study comparing                                                                                  PML. Plasmapheresis was performed with three
Randomized Treatments                                      FM 5 Relapse of herpes simplex type 2 menin-                 exchanges of the double plasma volume each, and
                                                           goencephalitis and progressive multifocal                    mefloquine was initiated (250 mg at day 1, 2, 3, 8,
U. Pato , G. Di Stefano , N. Fravi , M. Arnold ,
         1               1           1            1
                                                           leukoencephalopathy in a patient treated with                and every 7th day thereafter) [3].
M. Curatolo1, B. P. Radanov1, M. Sturzenegger1
                                                           natalizumab for multiple sclerosis                                The CSF cell count and the detection of HSV-2
    Universitätsklinik Berne, Berne, Switzerland                                                                        suggest that, in May, the patient had suffered a
                                                           Ilijas Jelcic, Christian Baumann,
                                                                                                                        relapse of HSV-2 meningoencephalitis. However,
Background: To compare four different treatment            Michael Weller, Michael Linnebank
                                                                                                                        the newly evolved lesion might already have been
strategies in patients suffering from chronic whip-
                                                           Corresponding author:                                        due to PML accompanied by a negative CSF result
lash injury (symptoms persisting for more than
                                                           PD Dr. Michael Linnebank,                                    for JCV. It remains speculative whether HSV-2
6 months after injury, Grade I or II, Quebec Task          University Hospital Zurich, Dept. Neurology,                 meningoencephalitis or other conditions like the
Force classification).                                     Subdivision of Neuroimmunology,                              preceding immunosuppressive therapy might
     Methods: Patients fulfilling the inclusion            Frauenklinikstrasse 26, CH-8091 Zurich,                      have disposed this individual to PML, which is a
criteria were randomly assigned to one of the              Switzerland. E-mail:               rare, but serious adverse event during natalizu-
following treatment groups: 1) local anesthetic            Phone: 0041 44 2551111                                       mab treatment [4, 5]. A history of viral meningo-
infiltration, 2) physiotherapy, and 3) medica-             Fax: 0041 44 2554507
                                                                                                                        encephalitis may be considered as a contraindica-
tion. Group allocation was stratified according
                                                           A now 41-year-old, male Caucasian patient ex-                tion for natalizumab treatment.
to gender, age, and education. Additionally, pa-
tients of each treatment group were randomized             perienced herpes simplex virus type 2 (HSV-2)
1:1 to cognitive behavioral therapy (CBT) or no            meningoencephalitis in 2000. He recovered com-
CBT. Patients were assessed at baseline, after             pletely, but the MRI then also revealed T2 lesions
                                                           suggestive of inflammatory disease as an inciden-            1   Polman CH, Reingold SC, Edan G, et al.
an 8 week treatment period, and then 3 and 6
                                                           tal finding. In 2002, relapsing-remitting multiple               Diagnostic criteria for multiple sclerosis:
months later, as follows: general physical and
neurological examination, cervical spine MRI
(at baseline), evaluation of psychosocial factors
                                                           Axial MRI from 2009, 05/07 (1a, T2-FLAIR), 05/22 (1b, T2-FLAIR) and 07/22 (1c, T2; axial FLAIR not done).
and litigation status (at baseline), subjective
outcome rating (cured, improved, unchanged,
worse), standardized pain assessment question-
naire (Mc Gill Pain Questionnaire), visual ana-
logue scale (VAS), and self-assessment scores
(well-being scale, self-rated cognitive ability, ac-
tivities of daily living). Main outcome measures
were: subjective outcome rating, pain intensity,
and working ability.
     Results: Of 91 enrolled patients 73 completed
the study and 62% were women. After treat-
ment (irrespective of the treatment group),
47 patients (64%) were subjectively improved                                 1a                                      1b                                      1c

                   S C H W E I Z E R A R C H I V F Ü R N E U R O L O G I E U N D P S Y C H I A T R I E 2009;160(7):305–18 |                   306

      2005 revisions to the “McDonald Criteria”.            tralateral changes were observed in the striatal             to further examinations. The mammography
      Ann Neurol 2005;58:840–6.                             indirect pathway neither with enkephalin nor                 showed microcalcifications in both mammary
2     Kurtzke JF. Rating neurologic impairment              with D2R gene expression. We also did not find               glands, but biopsy showed no evidence of a ma-
      in multiple sclerosis: an expanded dis-               any significant contralateral changes with TH,               lignant tumor; PET scan of the whole body was
      ability status scale (EDSS). Neurology                glutamatergic receptors or vGluT1.                           normal. In the clinical examination, livedo ra-
      1983;33:1444–52.                                           Conclusion: Our results suggest a role of the           cemosa and diffuse subcutaneous oedema were
3     Brickelmaier M, Lugovskoy A, Kartikeyan               striatal direct pathway on the healthy side to               noticeable. Skin biopsy attested typical changes
      R, et al. Identification and characterization         compensate the ipsilateral dopaminergic lesion               attributed to lupus erythematosus but the vas-
      of mefloquine efficacy against JC virus               and improve motor symptoms. This finding may                 culitis parameters, including testing for ANA and
      in vitro. Antimicrob Agents Chemother                 be important to understand the course of PD in               antiphospholipid-antibodies, were negative.
      2009;53:1840–9.                                       humans. The direct pathway could play a role in                    Considering a non classifiable collagenosis,
4     Biogen. Tysabri Update. http://phx.                   compensatory mechanisms of the less affected                 we started a high dose steroid pulse therapy with             side slowing down the clinical progression of                500 mg methylprednisolone per day for 5 days.
      W50SUQ9MTEwODd8Q2hpbGRJRD0tMXxU                       the disease.                                                 The neurocognitive deficits declined.
      eXBlPTM=&t=1                                                                                                             Conclusion: Collagenosis should be consid-
      (accessed on 3th August 2009).                                                                                     ered in a patient with acute focal neurological
5     Yousry TA, Major EO, Ryschkewitsch                                                                                 deficit and additional symptoms, even if vascu-
      C, et al. Evaluation of patients treated                                                                           litis parameters show negative results.
                                                            Freitag, 6.11.2009, 13.00–14.00 Uhr
      with natalizumab for progressive multifo-
      cal leukoencephalopathy. N Engl J Med                 Gruppe 1
      2006;354:924–33.                                                                                                   02 A subtype of Creutzfeldt-Jakob disease
                                                            01 A case report: Cerebral manifestation                     presenting with higher order visual
                                                            of non classifiable collagenosis                             disturbance including Balint syndrome
FM 6 Parkinson’s disease: adaptive gene
                                                            B. Erdèlyi1, A. Felbecker1, O. Coco1,                        C. Häubling1, F. Donati2, M. Braunschweig3,
expression changes in the healthy striatum
                                                            B. Tettenborn1                                               J. Haybaeck4, A. Aguzzi4, J. Rutishauser5,
C. Capper-Loup1, D. Rebell1, A. Kaelin-Lang1                                                                             H. Pihan2
                                                                Dep. of Neurology, St. Gall, Switzerland
    Department of neurology, University Hospital,           2
                                                                Dep. of Neurology, St. Gall, Switzerland                 1
                                                                                                                             Universitätsklinik für Allgemeine Innere Medi-
    Inselspital, Berne, Switzerland                         3
                                                                Dep. of Neurology, St. Gall, Switzerland                     zin, Inselspital Berne, 3010 Berne,
                                                                Dep. of Neurology, St. Gall, Switzerland                     Switzerland
Introduction: A unique feature of Parkinson›s dis-                                                                       2
                                                                                                                             Spitalzentrum Biel, Abteilung Neurologie,
ease (PD) is its asymmetry. In human, PD symp-              A 65-year-old-woman was admitted to our hospi-
                                                                                                                             2501 Biel/Bienne, Switzerland
toms only appear after a very large striatal dopa-          tal with acute focal neurological symptoms with              3
                                                                                                                             Spitalzentrum Biel, Abteilung Radiologie,
mine depletion. Several ipsilateral compensatory            left sided hemiparesis, hemianopsia to the right,
                                                                                                                             2501 Biel/Bienne, Switzerland
mechanisms could counteract dopamine denerva-               dysarthria and an NIHSS of 13 points. In the am-             4
                                                                                                                             Institut für Neuropathologie, Departement
tion on the same side. However it is not yet known          bulance during transfer to the hospital, focal epi-
                                                                                                                             Pathologie, UniversitätsSpital Zurich,
whether compensatory mechanisms of the less af-             leptic seizures of the left arm were observed for
                                                                                                                             8091 Zurich, Switzerland
fected side could also play a role in the process.          the first time.                                              5
                                                                                                                             Spitalzentrum Biel, Abteilung Medizin,
Our hypothesis in this study is that the healthy                 Perfusion-CT showed decreased perfusion in
                                                                                                                             2501 Biel/Bienne, Switzerland
side of a unilateral PD rat model shows adaptive            the territory of the right arteria cerebri posterior
behaviorally important gene expression changes              and part of the dorsal territory of the right arteria        Introduction: Creutzfeldt Jakob disease (CJD) is a
in direct and indirect pathways.                            cerebri media. Native CT-scan showed no early                prion disease typically presenting with progres-
     Methods: We analyzed the rat spontaneous               signs of ischemia and bleeding, so the patient               sive dementia accompanied by other neurological
locomotor behaviour four weeks after a unilat-              was administered intravenous thrombolysis.                   features such as cerebellar ataxia and myoclonus.
eral 6-hydroxydopamine (6-OHDA) lesion and                  The focal neurological signs disappeared after               In 1929, Heidenhain described a variant of the dis-
then studied the contralateral striatal expression          thrombolysis, the NIHSS showed 0 points. Re-                 ease characterized by an initially predominating
of dynorphin (DYN) and D1 dopamine recep-                   sidual neurocognitive deficits with anosognosia,             visual disorder and a rapid progression. We report
tors (D1R) mRNA for the direct pathway and                  short term memory problems and disorientation                the findings in a 64-years-old man admitted for in-
enkephalin and D2 dopamine receptors (D2R)                  were still present.                                          vestigation of progressive visual disturbances. Five
mRNA for the indirect pathway. We also ana-                      MRI-DWI showed no ischemia, only diffuse                months prior to admission, unspecific behaviour
lyzed contralateral expression of several striatal          hyperintensity of the parietal lobe, the brain-              changes such as listlessness, insomnia, decline of
and cortical glutamatergic markers, as well as              stem and the temporal lobe with normal ADC.                  interests and a slightly clumsy gait had started
nigral tyrosine hydroxylase (TH), to see whether                 The status epilepticus could be interrupted             to develop and had been attributed to a possible
contralateral changes in PD were due either to              by administering Lorazepam. Anticonvulsive                   episode of depression.
cortico- or nigrostriatal connections. The stria-           treatment was started intravenously with Leve-                    Results: Clinical evaluation at admission re-
tum was divided into two parts, medial (limbic)             tiracetam and changed to Carbamazepine.                      vealed a right-homonymous hemianopsia and a
and lateral (motor).                                             Medical history showed a 6 month history                color vision disturbance. The patient presented
     Results: Mean velocity was decreased in                of depression and B-symptoms with weight loss                difficulties in performing visual guided grasping
6-OHDA rats compared to other experimental                  and inappetence.                                             (optic ataxia) and could not name the elements
groups, although not significantly. However,                     Lab results showed pancytopenia, high CRP               of the Poppelreuter figure (simultaneous agno-
we found a positive and significant correlation             and increased erythrocyte sedimentation rate.                sia). Identification of single objects, spontaneous
between D1R mRNA expression in the lateral                  Cerebrospinal fluid revealed pleocytosis with 13             grasping as well as coordination of non visual
part of the contralateral healthy striatum and              cells/µl and elevated lactate (3.5 mmol/l) and               guided movements were intact. Tendon reflexes
mean velocity both measured four weeks after                protein (0.64 g/l) levels. Cytology, viral, bacte-           were increased on the left side.
surgery, in 6-OHDA rats only. Moreover we ob-               rial and parasitic antibodies and PCR showed                      Diffusion MRI demonstrated a gyriform sig-
served a significant increase in DYN and GAD                normal results. Paraneoplastic antibodies were               nal predominantly in the left-parietooccipital
mRNA in the lateral part of the contralateral               absent.                                                      cortex. The EEG revealed 1-2 Hz periodic theta/
parkinsonian striatum in absence of changes in                   Differential diagnosis of paraneoplastic syn-           delta activity with recurrent sharp wave com-
other direct pathway genes. In contrast no con-             drome or cerebral vasculitis/collagenosis led                plexes (PSWCs) strongly left-lateralized in the

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parietooccipital cortex. Cerebrospinal fluid con-          too showed DWI hyperintensities and reduced                  little activity. The natural CD95 ligand (CD95L) is
tained increased levels of CSF 14-3-3 and S-100            ADC although less marked (fig. 2).                           a cytokine which needs to trimerize to mediate a
protein.                                                        NCSE was refractory to extensive anti-con-              cell death signal. Mega-Fas-Ligand, now referred
     Further neuropsychological evaluation                 vulsive therapy. The patient died 4 days later               to as APO010, is a synthetic hexameric CD95 ago-
was limited by a rapid progressive decline in              from multi-organ failure.                                    nist that exhibits strong antitumor activity in vari-
visual and cognitive function culminating in                    Conclusions: SE may damage the brain by ex-             ous tumor models.
cortical blindness. Later, myoclonus and ataxia            citotoxicity resulting from glutamate spillover                    Methods: The cytolytic activity of APO010
emerged. The patient died 5 weeks after admis-             and an increase of intracellular calcium. Mem-               was assessed by crystal violet assays in the gli-
sion in a mutistic and blind state.                        brane peroxidation and energy exhaustion with                oma cell lines LNT-229, U87MG and LN-308.
     At autopsy the diagnosis of a spongiform              breakdown of electrolyte and water homeostasis               Induction of apoptosis in these cell lines and 9
encephalopathy was confirmed. Pathological                 eventually lead to acute cell death. These mech-             primary glioblastoma cell cultures from freshly
structural changes including accumulation of               anisms may be visualised by MRI, especially by               resected human tumors was quantified by stain-
proteinase-K resistant material were detected              means of DWI which may show laminar corti-                   ing with annexin V and flow cytometry. The
in both occipital cortices while frontal and tem-          cal cytotoxic swelling. Proposed mechanisms of               activation of caspases 8 and 3 and cleavage of
poral areas were relatively spared.                        CCD were glutamatergic propagation of hyper-                 PARP was assessed by immunoblot. The activa-
     Conclusion: The Heidenhain variant of spo-            excitation through the corticopontocerebellar                tion of caspase 3 was assessed additionally by
radic CJD may clinically develop from unspecific           tracts and/or GABAergic disinhibition of these               DEVD-amc cleavage assay. LNT-229 cells were
changes in comportment. Following thorough                 tracts after lesions of the controlling inhibitory           co-treated with temozolomide and APO010,
behavioural neurological assessment, the ten-              interneurons. Our findings based on imaging                  the fraction of surviving cells was assessed fol-
tative diagnosis can be further consolidated by            techniques like DWI may help to visualize the                lowing annexin V staining and flow cytometry.
a combination of electrophysiological, neurora-            pathophysiological and neuroanatomical under-                Synergy of temozolomide and APO010 was cal-
diological and laboratory findings.                        standing of CCD during SE.                                   culated using the fractional product method.
                                                                                                                        For in vivo experiments, 100.000 U87MG cells
                                                           Figure 1                                                     were implanted orthotopically in the right stria-
03 Acute crossed cerebellar diaschisis                                                                                  tum of nude mice. Locoregional treatment with
(CCD) as a network phenomenon in status                                                                                 APO010 was performed on days 7 and 14 after
epilepticus demonstrated by DWI                                                                                         tumor inoculation. Systemic treatment was per-
                                                                                                                        formed on three days per week by intraperito-
S. Rüegg1, N. Rastalsky2, S. Wetzel2, A. Gass2
                                                                                                                        neal injection of APO010 until the mice had to
    Division of clinical Neurophysiology, Depart-                                                                       be sacrificed. Histologic analysis included H&E
    ment of Neurology, University Hospital Basel,                                                                       and TUNEL staining and immunohistochemical
    Basel, Switzerland                                                                                                  assessment of cleaved caspase 3.
    Division of Neuroradiology, Department                                                                                    Results: Here, we studied the effects of
    of Radiology, University Hospital Basel,                                                                            APO010 in human glioma models in vitro and
    Basel, Switzerland                                                                                                  in vivo. Compared with a cross-linked soluble
                                                                                                                        CD95L or a CD95-agonistic antibody, APO010
Rationale: The term “diaschisis” refers to the phe-
                                                                                                                        exhibited superior activity in glioma cell lines ex-
nomenon of transient/permanent loss of function            Figure 2                                                     pressing CD95 and triggered caspase-dependent
in a brain region distant from the area of the corti-
                                                                                                                        cell death. APO010 reduced glioma cell viability
cal/subcortical primary brain lesion. Crossed cer-
                                                                                                                        in synergy when combined with temozolomide
ebellar diaschisis (CCD) was observed in several
                                                                                                                        (TMZ). The locoregional but not the systemic
supratentorial brain pathologies. CCD is rare in
                                                                                                                        administration of APO010 induced glioma cell
adults with chronic epilepsy; only two case reports
                                                                                                                        death in vivo and prolonged the survival of tu-
deal with CCD after status epilepticus (SE). Dif-
                                                                                                                        mor-bearing mice by induction of apoptosis on
fusion weighted imaging (DWI) allows to detect
                                                                                                                        tumor cells but not in normal brain.
acute tissue changes revealing energy metabolism
                                                                                                                              Conclusion: A further exploration of APO010
compromise secondary to ictal activity. We report
                                                                                                                        as novel anti-glioma agent is warranted.
for the first time CCD findings during SE by means
of DWI, although CCD was clinically not detect-
able because of non-convulsive SE (NCSE).
                                                                                                                        05 Autoimmune myasthenia gravis
     Case: A 74-year-old woman was found unre-
                                                                                                                        after sternal fracture
sponsive and she had a generalized-tonic-clonic
seizure on emergency admission. Examination                                                                             J. A. Petersen1, M. Linnebank1
revealed unresponsiveness and right, but not
                                                           04 APO010, a synthetic hexameric CD95                        1
                                                                                                                            University Hospital, Zurich, Switzerland
left, arm movements to painful stimuli. She had
                                                           ligand, induces human glioma cell death in
fixed left-upward gaze and right-sided pupillary                                                                        Clinical case: We report a 54-year-old woman who
                                                           vitro and in vivo
dilatation. She was transferred to the intensive                                                                        developed blurry vision two months after suffering
care unit for monitoring and therapy                       G. Eisele1, P. Roth1, W. Wick2, M. Weller1                   a sternal fracture due to a car accident. Thereafter,
     Results: Her EEG showed right-hemispheric                                                                          she complained fluctuating generalized weakness.
                                                               University Hospital Zurich, Department of
focal NCSE (fig. 1). CSF was normal. MRI re-                                                                            Five years later, the diagnosis of myasthenia gravis
                                                               Neurology, Zurich, Switzerland
vealed widespread cortical DWI hyperintensi-                                                                            made by detection of significant concentrations of
                                                               University Hospital Heidelberg, Department of
ties and corresponding apparent diffusion coef-                                                                         acetylcholine receptor antibodies in the blood, and
                                                               Neuro-oncology, Heidelberg, Germany
ficient (ADC) reductions in the right hemisphere                                                                        the patient came to our hospital. Treatment with
including thalamus, hippocampus, head of the               Introduction: Death receptor targeting has emerged           pyridostigmine normalized the muscular strength.
caudate, and parts of the occipital areas together         as one of the promising novel approaches of can-                  Discussion: Speculatively, the damage of
with pronounced cortical swelling of affected              cer therapy. The activation of one such prototypic           atrophic thymic remnants due to a sternal frac-
areas. This pattern of DWI abnormality and nor-            death receptor, CD95 (Fas/APO-1), has remained               ture might induce an autoimmune response
mal MR-angiography excluded brain ischemia.                controversial because CD95 agonistic molecules               to thymic acetylcholine receptor molecules or
Contralaterally, the left cerebellar hemisphere            have exhibited either too strong toxicity or too             might increase an existing subclinical antibody

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response. Similar mechanisms have been pro-                07 Comparative judgement of time:                            Background/aim: Small GTPases of the Rho family,
posed for the occurrence of autoimmune myas-               the impact of spatial neglect and caloric                    such as Rac1 and Cdc42, are key regulators of actin
thenia gravis after cardiac surgery. The knowl-            stimulation                                                  cytoskeleton that have been known to mediate
edge about such putative associations may be                                                                            cell death after ischemic stroke. The goal of this
                                                           E. Huberle1, P. Brugger1
helpful for diagnostic procedures and may be                                                                            study was to determine changes in localisation of
relevant from a medicolegal perspective.                   1
                                                               UniversitätsSpital Zurich, Zurich, Switzerland           Rac1 and Cdc42 in the rat brain after ischemia.
                                                                                                                             Methods: Transient focal ischemia was in-
                                                           Temporal information has become an important
                                                                                                                        duced by occluding the middle cerebral artery
                                                           element for the majority of people in the 21st cen-
06 Cervical muscle area measurements in                                                                                 for 90 minutes (damage mainly in the striatum).
                                                           tury. Recent observations indicated that cultures
whiplash patients – acute, 3 and 6 months                                                                               Rats were sacrificed 24h after reperfusion and
                                                           with a left-to-right written language map the past
follow-up                                                                                                               brains were used for immunohistochemistry
                                                           to the left side of space and the future to the right
                                                                                                                        analysis. Double immunostaining of Rac1 and
E. U. Ulbrich1, R. A. Aeberhard1, S. W. Wetli1,            (Santiago et al., 2007). In contrast to patients with
                                                                                                                        Cdc42 with TUNEL (apoptotic cells) and a neu-
A. B. Busato1, C. B. Boesch1, S. A. Anderson1,             neglect, healthy individuals show a perceptual
                                                                                                                        ronal marker NeuN was used to identify the cel-
H. Z. Zimmermann1, P. H. Heini1, J. H. Hodler1,            bias towards the left side (“Pseudoneglect”; Bow-
                                                                                                                        lular localization in the ischemic side.
P. V. Vock1, M. S. Sturzenegger2                           ers & Heilman, 1980), which also exists for the
                                                                                                                             Results: Rac1 was upregulated in the peri-
                                                           processing of time. In particular, the first presenta-
    Department of Diagnostic, Interventional                                                                            infarct region. Co-immunostaining studies
                                                           tion of two light-flashes with identical durations is
    and Pediatric Radiology, Inselspital, Berne,                                                                        showed that Rac1+ve cells were also TUNEL+ve
                                                           typically perceived longer (Rose et al., 1995). The
    Switzerland                                                                                                         and NeuN+ve. Expression of Rac1 in core area
                                                           present study investigated temporal information
    Institute for Evaluative Research in Orthope-                                                                       of infarct was not observed. Cdc42 was slightly
                                                           processing in patients with neglect. In addition,
    dic Surgery, University of Berne, Berne,                                                                            reduced in the ischemic region, and only a small
                                                           we manipulated the processing of time in healthy
    Switzerland                                                                                                         group of Cdc42+ve cells were TUNEL+ve. In ad-
                                                           observers by applying caloric stimulation, which
    Department of Emergency, Inselspital, Berne,                                                                        dition, most of the Cdc42+ve cells were not la-
                                                           has been shown to produce a rightward shift in
    Switzerland                                                                                                         belled with NeuN.
                                                           the sense of neglect-like behaviour (Karnath et
    Department of Orthopedics, Inselspital, Berne,                                                                           Conclusion: These results suggest that Rac1
                                                           al., 2003).
    Switzerland                                                                                                         and Cdc42 may play differential role in isch-
                                                                A train of three identical auditory stimu-
    Department of Neurology, Inselspital, Berne,                                                                        emia-related apoptotic pathway.
                                                           li, separated by intervals of different lengths,
                                                           was delivered to patients with neglect as well
    University of Berne, Berne, Switzerland
                                                           as healthy participants. Intervals were of the
                                                                                                                        09 Epic dreaming: clinical and
Introduction: The role of the cervical spine muscles       following durations (first/second; in msec): 1)
                                                                                                                        polysomnographic findings in three patients
in whiplash injury is disputed. We hypothesized            1500/1500, 2) 1400/1600, 3) 1300/1700, 4)
to find cervical muscle atrophy in the long-term,          1200/1800, 5) 1600/1400, 6) 1700/1300, 7)                    F. Siclari1, C. Bassetti1
probably related to pain or inactivity.                    1800/1200. Participants were required to per-                1
                                                                                                                            University Hospital Zurich, Zurich, Switzerland
     Methods: 90 symptomatic patients (48 fe-              form a comparative judgement of the interval
males) were recruited from our emergency                   durations. The healthy participants were test-               Introduction: Epic dreaming (ED) is a disorder of
department and examined within 48 hours,                   ed under caloric stimulation, for which warm                 unknown origin that has been reported in two
and 3, and 6 months after a motor vehicle ac-              (44 °C) or cold (30 °C) water was injected in the            full-length articles and two abstracts. It is char-
cident. MRI cross-sectional muscle area (CSA)              left and right auditory canal.                               acterized by dreams that are experienced as ex-
measurements were performed bilaterally of                      Unlike healthy individuals, the patients with           cessive and continuous throughout the night, re-
the cervical extensor muscles using axial STIR             neglect showed a preference to perceive the sec-             sulting in daytime fatigue. We report the clinical
(Short Tau inversion Recovery) sequences on                ond interval longer than the first one. In accord,           and polysomnographic features of three patients
level C2 (deep and total dorsal cervical extensor          neglect-like behaviour could be produced under               with ED.
muscles), C4 (sternocleidomastoid muscles) and             bithermal caloric stimulation of the right but not                Methods: Three patients with ED were identi-
C5 (deep and total dorsal cervical extensor mus-           the left ear in the healthy participants.                    fied out of over 1000 consecutive patients seen
cles) using Picture Archiving and Communica-                    The present findings indicate a spatio-tem-             in our outpatient sleep clinic. Assessment in-
tion System (PACS). Two blinded trained raters             poral interaction for comparative judgements of              cluded a detailed neurological examination and
independently performed the measurements.                  temporal information in patients with neglect                polysomnography (PSG).
CSAs were correlated with clinical outcomes                and healthy individuals. In accord with earlier                   Results: Patient 1: A 20-year-old woman re-
(EuroQuol, Whiplash Disability Score, neck pain            work, they strengthen the notion of a general                ported a three-year history of excessive neutral-
intensity [VAS], cervical spine mobility).                 magnitude system (Walsh, 2003; Conson et al.,                content dreaming. Dreams had long, complicat-
     Results: There was a high agreement be-               2008) and support the idea of a common neural                ed plots and involved multiple dream characters
tween the two raters (intra class correlation:             basis for the representation of space, quantity              that she could interpret from different perspec-
0.815–0.980). There were no significant changes            and time in the parietal lobes (Hubbard et al.,              tives. Patient 2: A-24-year-old woman had
of muscle CSAs at the three levels over time.              2005).                                                       been experiencing exhausting nightmares for
Women consistently had smaller CSAs than                                                                                two years, in which she would witness violent
men. There were no consistent significant cor-                                                                          scenes, such stabbing or fighting, as an observer.
relations of CSA values with the clinical scores           08 Differential localization of RhoGTPases                   Patient 3: A 69-year-old man related a 5-year
at all time points except with the BMI.                    after focal cerebral ischemia in rats                        history of excessive dreaming involving his past
     Conclusion: Our results do not support a                                                                           activity as a cook, in which he would mentally
                                                           A. Hodor1, B. Gao1, O. O. Ogunshola2,
major role of cervical muscles in the genesis of                                                                        rehearse the sequence of steps involved in the
                                                           C. Grimm3, E. Cam1, C. L. Bassetti1
symptoms after whiplash injury.                                                                                         preparation of a meal.
                                                               Department of Neurology, University Hospital                  Patients 1 and 2 had a history of depression
                                                               Zurich, Zurich, Switzerland                              and cardiac arrhythmias, while patient 3 was
                                                               Institute of Veterinary Physiology,                      known for recurrent vertigo, essential tremor
                                                               University of Zurich, Zurich, Switzerland                and prostate cancer. Neurological examination
                                                               Lab of Retinal Cell Biology, Department of               was normal in patient 1, revealed attention defi-
                                                               Ophthalmology, University of Zurich, Zurich,             cits in patient 2 and short term memory loss in
                                                               Switzerland                                              patient 3. PSG documented sleep fragmentation

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in patients 2 and 3 (due to bruxism and PMLS                Postersession,                                               emia has been associated with various neurologi-
respectively). All patients had persistent epic             Freitag, 6.11.2009, 13.00–14.00 Uhr                          cal disorders including Alzheimer’s disease (AD).
dreaming on follow up interviews after 0.5–2                                                                             One central phenomenon of AD is the formation
                                                            Gruppe 2
years.                                                                                                                   of amyloid plaques. These plaques are composed
    Conclusion: ED appears to be a heterogenous                                                                          of fibrillar amyloid-beta peptides (Abeta peptides),
                                                            11 Hemispheric lateralization of the
disorder, in which sleep fragmentation might                                                                             other proteins and transition metal ions like Zn(II)
                                                            corticostriatal glutamatergic system
play a major role. Our observations support                                                                              and Cu(II). Levels of extracellular zinc and copper
                                                            in the rat
the existence of at least two subtypes, includ-                                                                          are normally low.
ing “story epic dreaming” and “non-story epic               C. Capper-Loup1, D. Rebell1, A. Kaelin-Lang1                      The impact of homocysteine, zinc and cop-
dreaming”.                                                                                                               per on Abeta peptide aggregation was analyzed
                                                                Department of neurology, University Hospital,
                                                                                                                         using a microtiter plate-based Thioflavin T ag-
                                                                Inselspital, Berne, Switzerland
                                                                                                                         gregation assay.
10 Evolution of sleep spindles after                        Introduction: Inhibitory gamma-aminobutyric acid                  The presence of Hcy did not relevantly
paramedian thalamic stroke                                  (GABA)-ergic medium spiny projection neurons                 change the aggregation behaviour of Abeta pep-
                                                            in the striatum receive glutamatergic afferents              tides. When observed in the absence of Hcy, the
R. P. Poryazova1, R. K. Khatami1, E. W. Werth1,
                                                            from the cortex. N-methyl-D-aspartate (NMDA)                 transition metals Zn(II) and Cu(II) inhibited the
P. B. Brugger1, R. H. Huber2, C. B. Bassetti1
                                                            receptors are implicated in many neurological                aggregation of Abeta peptides. Co-incubation
    University Hospital Zurich, Zurich, Switzerland         disorders, including Parkinson’s disease (PD).               with Hcy reduced the effects of Zn(II) and Cu(II).
    University Children’s Hospital Zurich, Zurich,          Recently, we described a specific lateralization of          This effect depended on the molar ratio between
    Switzerland                                             the striatal direct pathway, with a predominance             metal ions and Hcy. With Hcy concentrations
                                                            of the left striatum, related to non-motor func-             corresponding to pathophysiologically occur-
Introduction: Thalamus is a key structure in the
                                                            tion. The hypothesis of the present study is that            ring hyperhomocysteinemia, Zn(II) and Cu(II)
generation of sleep spindles. Sleep spindles have
                                                            the lateralization of striatal direct pathway is due         in physiological concentrations were no longer
been associated with cognition and learning. Re-
                                                            to a lateralization of glutamatergic corticostriatal         able to reverse aggregation behaviour. Other
covery in sleep spindles after hemispheric stroke
                                                            projection.                                                  ions studied (Na, K, Ca, Fe, Mg) did not change
has been reported and a role in plastic recovery
                                                                 Methods: In healthy rats, we investigated the           Abeta peptide aggregation.
changes has been suggested. We aimed at inves-
                                                            striatal gene expression of three different NMDA                  By binding Zn(II) and Cu(II), Hcy can pro-
tigating the evolution of sleep spindles after para-
                                                            receptors subunits (NR1, NR2A and NR2B). We                  mote the formation of Abeta peptide fibrils. This
median thalamic stroke and at comparing them to
                                                            also analyzed the vesicular glutamate transport-             observation may be an explanation of the associ-
healthy controls.
                                                            er 1 (vGluT1), a presynaptic component of the                ation between hyperhomocysteinemia and AD.
     Patients and methods: Eight patients, two with
                                                            corticostriatal projection in the limbic cingulate
bilateral paramedian thalamic stroke (PMTS)
                                                            cortex (Cg), the medial agranular cortex (AGm),
and six with unilateral PMTS and six age and
                                                            an association premotor cortex, and the primary              13 Imaging blood-brain barrier transporters
gender matched controls underwent high-den-
                                                            motor cortex (M1).                                           in low-grade glioma patients with positron
sity EEG (hd-EEG) examination with 128 elec-
                                                                 Results: We found a significantly higher ex-            emission tomography, tyrosine and choline
trodes during sleep. Seven patients were studied
                                                            pression of NR2A mRNA in the medial sector
twice and six patients three times: in the acute                                                                         U. Roelcke1, M. Bruehlmeier1, M. Hefti1,
                                                            of the left striatum. No difference between the
phase after stroke, 3 and 6 months later. Sleep                                                                          Th. Hundsberger2, E. Nitzsche1
                                                            right and left striatum was detected either with
spindles power was averaged over all electrodes
                                                            NR1 or NR2B mRNA. In the cingulate cortex,                   1
                                                                                                                             Cantonal Hospital, Aarau, Switzerland
and analyzed as previously reported.
                                                            vGluT1 mRNA expression was also higher in the                2
                                                                                                                             Cantonal Hospital, St. Gall, Switzerland
     Results: There were two patients, one with
                                                            left hemisphere. We did not observe any side
unilateral and one with bilateral PMTS with no                                                                           Introduction: Amino acids are actively transported
                                                            difference neither in AGm nor in M1.
peak in the spindle frequency range. The patient                                                                         across the blood-brain barrier (BBB). Increased
                                                                 Conclusion: Our study demonstrates a lateral-
with bilateral PMTS was studied three times and                                                                          transport in low-grade gliomas (LGG, WHO II)
                                                            ization of both the striatal glutamatergic recep-
in none of the tests a spindle peak was detected.                                                                        gives rise to detect these tumors with positron
                                                            tors and the cortical presynaptic glutamatergic
In all control subjects a spindle peak was de-                                                                           emission tomography (PET) and amino acid ana-
                                                            system, probably related to limbic function, with
tected. Repeated measures ANOVA showed no                                                                                logues, e.g. F18-fluoro-ethyl-tyrosine (FET). In a
                                                            a predominance on the left side. We suggest that
difference in the patients group over time (p =                                                                          clinical setting FET PET may be applied to define
                                                            this lateralization concerns the direct pathway.
0.65, F2 = 0.303). T-tests showed no difference                                                                          targets for stereotactic biopsy, and for follow-up
                                                            Lateralization of the corticostriatal projection of
in the spindle peak power between patients and                                                                           of LGG during treatment. However, up to 20% of
                                                            the direct pathway could be implicated in the
control subjects either.                                                                                                 LGG are FET-negative. Here we assessed whether
                                                            pathophysiology of asymmetric diseases like PD.
     Conclusion: Sleep spindles, if decreased, do                                                                        FET-negative tumors can be visualized with PET
                                                            Further studies are required to relate this finding
not recover after PMTS. Complete loss of sleep                                                                           and radiolabeled choline. Choline is involved in
                                                            to behaviour.
spindles was observed only in two patients with                                                                          intracellular signalling associated with prolifera-
PMTS, one with unilateral and one with bilateral                                                                         tion, and is incorporated into membrane lipids of
lesions. This suggests that a unilateral thalamic                                                                        dividing cells.
                                                            12 Homocysteine alters the effects of Zinc
lesion is enough for the complete loss of sleep                                                                               Methods: We analyzed the uptake of F18-flu-
                                                            and Copper on recombinant amyloid-beta
spindles, depending on its specific location.                                                                            oro-choline (CHO) in six patients with FET-neg-
                                                            peptide aggregation
     Support: The study is supported by the Zu-                                                                          ative LGG (three fibrillary astrocytomas, three
rich Center for Integrative Human Physiology                S. Keskitalo1, M. Farkas1, M. Hanenberg2,                    oligodendroglial tumors, age 42–60 yr). The di-
(ZIHP).                                                     M. Linnebank1                                                agnosis of LGG was confirmed histopathologi-
                                                                                                                         cally in all patients. None of the tumors showed
                                                                University Hospital Zurich, Department of
                                                                                                                         gadolinium enhancement on MR. Uptake of FET
                                                                Neurology, Zurich, Switzerland
                                                                                                                         and CHO was quantified by normalizing the tu-
                                                                University of Zurich, Division of Psychiatry
                                                                                                                         mor tracer uptake to the mean of the cerebellar
                                                                Research, Zurich, Switzerland
                                                                                                                         uptake. Values >1.0 indicate increased transport
                                                            Homocysteine (Hcy) is a nonessential amino acid              relative to the normal brain.
                                                            formed as an intermediate during the metabolism                   Results: The mean FET tumor uptake was
                                                            of methionine to cysteine. Hyperhomocystein-                 0.95 (range 0.91–1.00). By visual inspection

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none of the six tumors showed increased CHO                15 Is lymphocytosis a predictor for good
uptake. In accordance the mean CHO tumor up-               response to Natalizumab treatment in
take was 0.89 (0.73–1.15).                                 Multiple Sclerosis?
    Conclusions: In this series imaging with CHO
                                                           S. L. Lienhard1, G. S. Schwegler1
was not superior to FET in detecting LGG. Our
data indicate that a subset of LGG has a very              1
                                                               Neurologische Klinik, Kantonsspital Aarau,
low metabolic demand for both substrates, and                  Aarau, Switzerland
suggest that neither amino acid nor choline
                                                           Introduction: Treatment with Natalizumab (Nb), a
pathways are significantly upregulated inde-
                                                           monoclonal antibody blocking the migration of T
                                                           and B cells into the CNS, leads to an elevation of
                                                           lymphocytes, monocytes, eosinophiles and baso-
                                                           philes in peripheral blood in many patients. The
14 Impaired digital dexterity in Parkinson’s
                                                           mechanisms underlying these findings are not
disease is associated with higher-order praxis
                                                           completely understood, but several hypotheses
                                                           exist: It’s thought to be a sequestration in periph-
T. Vanbellingen1, M. Bellion1, P. Temperli1,               eral blood by inhibition of migration into the tis-
F. Baronti1, S. Bohlhalter2                                sue, a reaction to latent virus activation or even
                                                           a particular Nb induced activation. We analyzed
    Klinik Bethesda, Tschugg, Switzerland
                                                           if a lymphocytosis (LS) has a predictive value for
    Inselspital, Berne, Switzerland
                                                           a good response to Nb in patients with Multiple
Background: A controversial concept suggests that          Sclerosis (MS).
impaired digital dexterity in PD may be explained               Methods: This is a retrospective study. Inclu-
by limb kinetic apraxia (LKA) as it is little respon-      sion criteria were treatment with Nb for at least
sive to dopaminergic treatment. The goal of the            one year, two differential blood examinations
present study was to explore the relationship of           under treatment and a baseline and follow up
digital dexterity (as measured by coin rotation,           MRI after one year. We statistically analyzed the
CR) with praxis function (assessed by the test of          sensitivity, specificity, positive predictive value
upper limb apraxia, TULIA) and parkinsonian                and negative predictive value for good response
symptoms (MDS-UPDRS).                                      to Nb using the parameters absolute LS, relative
     Methods: Ten PD patients (3 women, mean               LS and relative granulocyte count <50% sepa-
age 63.4 ) with wearing off fluctuations were as-          rate and in combination.
sessed on both arms separately. Testing was done                Results: We will present preliminary results.
in OFF and ON state as defined by MDS-UPDRS                The interpretation of our findings is hampered
(average decrease of scores 66%). In the CR task           by a small sample size and difficulties to establish
patients were requested to rotate a 50 Rappen coin         reliable criteria for insufficient response in Nb
as fast as possible between their thumb, index and         treated patients.                                            ties (image 2) which were partially ameliorated
middle finger. CR performance was analyzed by                   Conclusion: It is desirable to have reliable lab-       2½ weeks later after antiepileptic therapy with
measuring the frequency during three 10 second             oratory markers for insufficient response to Nb              levetiracetam, phenytoin, topiramate and pre-
periods. Gesture production was assessed by the            treatment in MS patients. LS probably is such a              gabalin. The patient remained seizure-free and
TULIA, balanced for predominant finger and hand            reliable marker. To clarify this issue further stud-         EEG normalized.
postures. Both CR and TULIA were assessed by a             ies with higher sample size are needed.                           Follow-up MRI three months showed a fur-
blinded rater based on video recordings. Within-                                                                        ther resolution of abnormalities but remaining
subject analyses were done by Pearson’s correla-                                                                        tissue damage.
tion between summed scores of measurements                 16 Multifocal reversible MRI Abnormalities                        Etiology of seizures remained unclear. The
and by paired t-tests for comparisons between OFF          in prolonged Status epilepticus                              patient had mild preexisting cognitive impair-
and ON state.                                                                                                           ment. There was no evidence of encephalitis,
                                                           J. Bontadelli1, M. Tröger1
     Results: CR scores significantly correlated with                                                                   meningitis, vasculitis or brain tumor.
TULIA scores (r = 0.63 p = 0.05) and not with              1
                                                               Kantonsspital Aarau Neurologie, Aarau,                        Conclusions: Prolonged status epilepticus can
MDS-UPDRS (r = –0.32 p = 0.37), irrespective of                Switzerland                                              cause pronounced damage in involved brain
the motor state, although only 4 patients scored                                                                        structures. Corresponding abnormalities in im-
                                                           Introduction: Refractory status epilepticus is a dev-
slightly below the cut off for apraxia. The correla-                                                                    aging are variable. Our patient showed wide-
                                                           astating disorder leading to variable damage of the
tion of CR and TULIA scores was even stronger,                                                                          spread abnormalities of MRI imaging and a very
                                                           brain. Various patterns of MRI abnormalities have
if considered in OFF only (r = 0.77 p = 0.01). CR                                                                       striking reversibility of most changes.
                                                           been reported but there are quite few follow up
and finger gestures did not change between OFF                                                                               Further systematic studies are needed for a
                                                           investigations published.
and ON state (p = 0.56 and p = 0.35, respectively),                                                                     better understanding of pathogenetic and prog-
                                                                Methods: Single patient MRI series and case
while hand gestures improved in ON (p <0.001).                                                                          nostic relevance of these findings
     Conclusions: The significant association of
                                                                Results: A 20-year-old woman presented to
CR with TULIA but not MDS-UPDRS indicates
                                                           our department after two generalized epilep-
that impaired dexterity in PD may be indeed                                                                             17 Olfactory function in patients with
                                                           tic seizures. MRI showed left temporal T2 hy-
apraxic rather than bradykinetic in nature. Fur-                                                                        dopamine and/or hypocretin deficit and in
                                                           perintense and T1 hypointense abnormalities
thermore, digital dexterity did not improve with                                                                        patients with excessive daytime sleepiness
                                                           (Image 1).
dopaminergic treatment supporting the notion
                                                                After therapy with levetiracetam. the pa-               E. G. Ghielmini1, R. P. Poryazova1, C. B. Bassetti1
of LKA underlying dexterous difficulties in PD.
                                                           tient initially recovered. Ten days later the                1
                                                                                                                            University Hospital Zurich, Zurich, Switzerland
                                                           patient developed fluctuating aphasia, somno-
                                                           lence and vomitus and the diagnosis of non-                  Introduction: Hyposmia is common in patients with
                                                           convulsive status epilepticus was confirmed by               Parkinson’s disease (PD). Olfactory deficits were
                                                           electroencephalography (EEG). Follow-up MRI                  recently reported also in patients with narcolepsy
                                                           demonstrated a profound increase of abnormali-               and linked to hypocretin deficit/neuronal degen-

                   S C H W E I Z E R A R C H I V F Ü R N E U R O L O G I E U N D P S Y C H I A T R I E 2009;160(7):305–18 |              311

eration. The role of daytime sleepiness, dopamine               In addition, Hcy incubation led to a reduc-             score is 20/30) paraphasias and neologisms ap-
and hypocretin on olfactory function is poorly             tion of oxidized glutathione of more than 50 %               peared.
known.                                                     of the control value while it did not influence the               Conclusion: The association between narco-
     Aim: to examine olfactory function in pa-             levels of total glutathione. This effect was seen            lepsy, PD and AD has not been reported in the
tients with narcolepsy, restless legs syndrome             in transfected as well as in wildtype HEK cells.             literature and while probably fortuitous suggests
(RLS), PD, excessive daytime sleepiness (EDS)                   There are many candidates for speculative               a need for systematic study on the long term
and healthy controls.                                      interactions between Hcy metabolism and AD                   evolution of patients with hypocretin-deficient
     Patients and methods: We studied 14 patients          pathogenesis. Our results support the hypothesis             narcolepsy.
with PD, 11 patients with narcolepsy, 10 patients          that Hcy leads to an up-regulation of gamma-
with RLS, 8 patients with EDS and 15 controls.             secretase activity. However, effects of Hcy on
Olfactory threshold, discrimination and identifi-          the redox system may further contribute to an                20 Psychopathologische Befunde bei
cation were assessed using standardized “Sniffin’          influence of Hcy on neurodegeneration.                       Patienten mit idiopathischem Restless-legs-
sticks” test. Sleepiness was assessed using Ep-                                                                         Syndrom
worth sleepiness scale (ESS), Karolinska (KSS)
                                                                                                                        A. Seiz1, U. Kallweit1, E. Werth1, U. Ehlert2,
and Stanford sleepiness scale (SSS).                       19 Parkinson’s disease and Alzheimer’s
                                                                                                                        C. L. Bassetti1
     Results: One-way ANOVA showed a signifi-              dementia in patients with narcolepsy
cant difference between groups for threshold                                                                            1
                                                                                                                            Neurologische Klinik, Universitätsspital
                                                           N. T. Economou1, M. Raimondi1, J. Ghika2,
(p <0.001, F4 = 7.1), discrimination (p <0.001, F4                                                                          Zürich, Zürich, Switzerland
                                                           F. Bornatico-Valsangiacomo1, C. L. Bassetti1
= 13.5) and identification (p <0.001, F4 =16.2).                                                                        2
                                                                                                                            Psychologisches Institut, Universität Zürich,
Post-hoc t-tests revealed that patients with PD            1
                                                               Neurology Department, Neurocenter of the                     Zürich, Switzerland
performed significantly worse for all three ol-                Southern Switzerland, Lugano, Switzerland
                                                                                                                        Hintergrund: Das Restless-legs-Syndrom (RLS) ist
factory parameters than all other groups. Only             2
                                                               Neurology Department, University of Lau-
                                                                                                                        eine häufige neurologische Erkrankung, die oft-
for threshold PD patients were not significantly               sanne, Lausanne, Switzerland
                                                                                                                        mals mit psychischen Störungen assoziiert ist.
different from patients with EDS (p = 0.066).
                                                           Background: The etiology of narcolepsy is un-                Ergebnisse aus Studien belegen ein überdurch-
Olfactory functions were similar in patients
                                                           known. An autoimmune but also a neurodegen-                  schnittlich häufiges gemeinsames Auftreten von
with narcolepsy, EDS, RLS when compared to
                                                           erative process involving the hypocretin (orexin)            RLS und Angst- und depressiven Störungen, aber
healthy controls.
                                                           neurons of the hypothalamus are currently dis-               auch somatoformen Störungen sowie eine Auf-
     Conclusion: We confirm the presence of olfac-
                                                           cussed. Hypocretin deficiency is known to occur              merksamkeits-/Hyperaktivitätsstörung (ADHS).
tory deficits in PD but not in narcolepsy, who as
                                                           in Parkinson’s disease (PD) and other neurode-                    Ziel: Ziel der Studie war es, psychopatholo-
patients with RLS and EDS- performed similarly
                                                           generative disorders.                                        gische Befunde auf Symptom- sowie Diagnose-
to healthy controls.
                                                                Aim: To report two patients with a long his-            ebene bei RLS-Patienten aufzuzeigen. Der Fokus
                                                           tory of narcolepsy with cataplexy, in which Par-             liegt dabei auf den Störungsbildern der depres-
                                                           kinson Disease (PD) and Alzheimer’s dementia                 siven, Angst-, und somatoformen Störungen
18 On the interaction of homocysteine
                                                           (AD) subsequently developed.                                 sowie der ADHS.
metabolism and Alzheimer’s disease:
                                                                Patients and methods: Two male patients un-                  Methoden: 49 Patienten mit der Diagnose ei-
in vitro and in vivo experiments
                                                           derwent an assessment which comprised a clini-               nes idiopathischen RLS wurden prospektiv mit-
M. Farkas1, S. Keskitalo1, L. Kulic1, M. Weller1,          cal and neurological evaluation with detailed                tels des diagnostischen Expertensystems DIA-X
M. Linnebank1                                              sleep history; both patients received the diag-              bezüglich der Häufigkeit psychischer Störungen
                                                           nosis of narcolepsy on clinical and laboratory               in den letzten 12 Monaten befragt sowie anhand
    University Hospital Zurich, Department of
                                                           basis (CSF Hypocretin-1 levels, PSG/MSLT in-                 diverser Fragebogen zur psychischen und physi-
    Neurology, Zurich, Switzerland
                                                           vestigations).                                               schen Befindlichkeit untersucht.
Sporadic Alzheimer’s disease (AD) is the most                   Results: The first patient, a 67-year-old male,              Ergebnisse: Die Resultate des diagnostischen
common cause of dementia. Increased homocys-               suffers from narcolepsy with cataplexy since the             Expertensystems DIA-X ergaben auf Störungs-
teine (Hcy) plasma and CSF levels are a risk factor        age of 17. He has a typical clinical narcoleptic             gruppenebene bei insgesamt 18,3% der un-
for AD. Although the association between hyper-            tetrade and typical neurophysiological findings.             tersuchten RLS-Patienten eine somatoforme
homocysteinemia and AD is well established, the            The HLA typing is positive (HLA DQB1*0602)                   Störung, bei 16,3% eine depressive Störung,
underlying pathophysiology is unexplained. In              the and CSF hypocretin-1 is undetectable. At the             bei 12,2% eine Angststörung, bei 4,1% eine
particular, it is not known whether Hcy itself or          age of 60 he developed resting tremor, micro-                posttraumatische Belastungsstörung sowie bei
other components of the homocysteine metabo-               graphia and right bradykinesia; the brain MRI                2,0% eine Essstörung. Es zeigten sich keine sig-
lism, e.g., S-adenosylmethionine (SAM), folate             was normal. The motor symptoms responded                     nifikanten soziodemographischen Unterschiede
or vitamin B12, play a role in the development             to L-DOPA and the diagnosis of PD was made.                  zwischen Probanden mit psychischen Störun-
of AD. The objective of this study was to define           Narcoleptic symptoms, especially cataplexia,                 gen und Probanden ohne psychische Störungen.
the major player of Hcy metabolism in respect to           also improved with L-DOPA treatment.                              RLS-Patienten mit auffälligen depressi-
relevance for AD.                                               The second patient, a 69-year-old male, suf-            ven Symptomen (gemäss HADS-D/D) zeigten
    We manipulated different parts of Hcy me-              fers from narcolepsy with cataplexy since ado-               ein signifikant schwereres RLS, eine höhere
tabolism in human embryonic kidney (HEK) cell              lescence. The diagnosis was made only at the                 Erschöpfung sowie eine grössere psychische
lines by adding Hcy or SAM to the cell culture             age of 62. He has a typical clinical narcoleptic             Beeinträchtigung der Lebensqualität. Dieser
media and by dietary changes in transgenic mice            tetrade and typical neurophysiological findings.             Gruppenunterschied konnte bei Probanden mit
over-expressing the amyloid-precursor protein              The HLA typing is positive (HLA DQB1*0602)                   Angstsymptomen (gemäss HADS-D/A) nicht
(APP) and analyzed AD-specific parameters e.g.,            the and CSF hypocretin-1 is undetectable. At                 festgestellt werden.
APP-processing, gene expression patterns and               the age of 65 he presented early signs of demen-                  Schlussfolgerung: Psychische Störungen, ins-
markers of oxidative stress. Our cell culture re-          tia, characterized by spatial disorientation, short          besondere Depression, Angst- und somatoforme
sults suggested that Hcy influences processing             term memory deficit, reduced attention and re-               Störungen sind eine häufige Ko-Morbidität bei
and expression of APP in HEK cells, i.e., in a             duced verbal fluency. Brain MRI evidenced dif-               RLS und sollten vermehrt bei der Diagnostik
dose-dependent manner, Hcy concentrations of               fused cortical atrophy without focal lesions. The            und Therapie der Erkrankung berücksichtigt
1, 2.5, 5 and 10 mM, 4 h incubation, lead to               diagnosis of Alzheimer disease, probably familiar            werden.
a significant decrease of both C-terminal APP              type (his mother had the same clinical picture)
fragments.                                                 was made. As AD progressed (his actual MMSE

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Postersession,                                              Gasper, 2002). In this study, we investigated                immunoglobuline (IVIG) therapy is often only of
Freitag, 6.11.2009, 13.00–14.00 Uhr                         whether inducing positive or negative emotions               short duration.
                                                            while bisecting lines may have opposite effects on                Methods: Case study of a single female patient
Gruppe 2
                                                            the direction of participants’ displacements.                with myasthenia gravis case.
                                                                 Methods: Participants (40 healthy right-                     Results: We report a female patient, who pre-
21 Recurrent tumefactive demyelination
                                                            handed adults) were required to mark the mid-                sented for the first time with bulbar symptoms
without evidence for multiple sclerosis or
                                                            point of each of 24 horizontal lines (line length            at our hospital at the age of 43 years (2005). The
brain tumor
                                                            26 cm) with a sharp pencil held in the dominant              diagnosis of an anti-MuSK positive seronega-
A. Häne1, M. Bargetzi1, E. Hewer1, M. Bruehl-               right hand (one line per sheet). While executing             tive Myasthenia gravis was made and therapy
meier1, A. Khamis1, U. Roelcke1                             this task, subjects were asked to try to remem-              with low dose steroids and azathioprin initi-
                                                            ber and contemplate once a positive (during                  ated. Under IVIG therapy the patient improved
    Cantonal Hospital, Aarau, Switzerland
                                                            12 lines) and once a negative autobiographical               to a remission. During the following years the
Introduction: The differential diagnosis of single          event (during 12 lines; order of emotion coun-               disease generalised with recurrent neurological
space occupying lesions comprises multiple scle-            terbalanced). The number of leftward vs right-               impairments, severe loss of weight and dyspnea,
rosis (MS) in younger patients, and primary or              ward deviations were recorded in each run, and               despite accompanying therapy with inhibitors
secondary brain tumor at any age. We present                an average deviation from the midline over all               of cholinesterase, azathioprin and low dose ste-
a 70-year-old man with recurrent tumefactive                24 lines was obtained for each participant, again            roids and repeated cycles of IVIG.
demyelination (TD), which is considered to re-              for each run.                                                     The clinical course was complicated by mul-
sult from demyelination. Some authors suggest                    Results: ANOVA of the number of leftward vs             tiple embolic events that led to the diagnosis of
that TD may evolve into MS or primary CNS lym-              rightward displacements with induced emotion                 an antiphospholipid antibody syndrome.
phoma.                                                      (positive or negative) as the repeated measure                    So therapy was switched to Rituximab. A
     Methods: This patient developed four single            revealed significantly more leftward displace-               first cycle was given in 10/2008 under which re-
tumor-like, gadolinium enhancing lesions at dif-            ment under negative emotion, and no system-                  mission could be achieved. A consolidating cycle
ferent sites of the brain over three years. There           atic directional bias under positive emotion (see            was given in 5/2009 and the patient is still in
was no preceding viral infection or vaccination.            figure).                                                     remission. The accompanying immunosuppres-
From the initial appearance on MRI CNS lym-                      Conclusion: Over both emotion conditions,               sive therapy as well as the therapy with cholin-
phoma was suggested. However, biopsy at first               there were more left-sided than right-sided dis-             esterase inhibitor could be tapered.
presentation revealed perivascular lymphocytic              placements (“pseudoneglect”). This result con-                    Conclusion: Our patient responds well to the
cuffs and macrophages. Over two years three                 firms previous findings of a leftward bias in nor-           treatment with Rituximab. Therefore a therapy
CSF analyses showed mild lymphocytic pleocy-                mal participants when bisecting horizontal lines             with Rituximab should be considered in pa-
tosis, elevated protein, but no oligoclonal bands.          (Jewell, 2000). Pseudoneglect was significant                tients, who appear to be refractory to a therapy
FDG PET was negative at two, and positive at                only for the run during which subjects contem-               under other immunosuppressive therapy.
one manifestation. 14 months after onset of TD              plated the negative autobiographical event. This
the patient also developed myelodysplastic syn-             observation is in line with “valence theories” of
drome (MDS) with isolated genomic deletion of               emotional hemispheric processing, which pos-                 24 Restless-legs-Syndrom (RLS) oder «RLS-
5q-. In addition renal cancer was diagnosed 11              tulate a right hemisphere mediation of negative              like»? – Psychobiologische Untersuchungen
months later.                                               emotions. The reason(s) why positive emotions                bei Patienten mit idiopathischem RLS
     Results: All cerebral lesions responded within         could not overcome pseudoneglect remain to be
                                                                                                                         S. Trulec1, U. Kallweit1, E. Werth1, U. Ehlert2,
2 to 3 months to dexamethasone. The patient                 elucidated in future research.
                                                                                                                         C. L. Bassetti1
died after 33 months due to metastatic renal
cancer. The final histopathological diagnosis               Figure                                                       1
                                                                                                                             Neurologische Klinik, Universitätsspital
obtained from autopsy of the brain was identi-                                                                               Zürich, Zürich, Switzerland
cal to the initial diagnosis from the biopsy. No                  Number of Leftward / Rightward deviations              2
                                                                                                                             Psychologisches Institut, Universität Zürich,
tissue changes consistent with brain tumor – in                   depending on the type of induced emotion                   Zürich, Switzerland
particular lymphoma – were found.
                                                                                                                         Hintergrund: Die Diagnose Restless-legs-Syndrom
     Conclusions: Age, clinical course with re-
                                                                                                                         (RLS) wird primär anhand klinischer Diagnose-
current single lesions and negative oligoclonal
                                                                                                                         kriterien gestellt. Supportive Kriterien wie das
bands suggest that TD must be considered dif-
                                                                                                                         Auftreten von periodischen Beinbewegungen im
ferently from MS. A relationship between TD
                                                                                                                         Schlaf («PLMS») unterstützen die Diagnose. Bei
and MDS or malignant cancer in our patient
                                                                                                                         RLS-Patienten besteht oftmals eine psychiatri-
remains speculative but may have an immu-
                                                                                                                         sche Ko-Morbidität. Einzelne Studie weisen für
nological dysbalance as cause. Treatment other
                                                                                                                         diese Gruppe von RLS-Patienten auf starke
than steroids is not established for TD.
                                                                                                                         Ausprägungen bezüglich subjektiv eingeschätz-
                                                                                                                         ter Variablen (Schweregrad des RLS, Müdigkeit,
                                                                                                                         Beeinträchtigung der Lebensqualität, Somatisie-
22 Remembering negative events induces
                                                                                                                         rungstendenzen) und schwache Ausprägungen
leftward deviation in a line bisection task                 23 Remission of an anti-MuSK positive
                                                                                                                         bezüglich objektiv messbarer Variablen (z.B.
                                                            seronegative Myasthenia gravis under
C. T. Tamagni , S. C. Croce , V. W. Wettstein ,
                1              1                    1
                                                                                                                         PLMS) hin («RLS-like«).
                                                            Rituximab therapy
P. B. Brugger1                                                                                                               Ziel: Ziel der Studie war es, RLS-Patienten
                                                            T. Betz1, M. Tröger1                                         ohne und mit psychischen Störungen hinsicht-
    Neuropsychology Unit, Department of
                                                                                                                         lich der unterschiedlichen Ausprägungen psy-
    Neurology, University Hospital Zurich, Zurich,          1
                                                                Kantonsspital Aarau, Neurology, Aarau,
                                                                                                                         chobiologischer Faktoren zu untersuchen.
    Switzerland                                                 Switzerland
                                                                                                                             Methoden: In dieser prospektiven Studie
Introduction: Previous studies suggest a relation           Introduction: It is well known that patients with            wurden 49 «de novo»-Patienten mit der Diag-
between emotion and spatial attention. More                 anti-MuSK positive seronegative Myasthenia gra-              nose eines idiopathischen RLS mit dem diagnos-
specifically, personality traits like optimism or           vis often do not respond sufficently to a therapy            tischem Expertensystem DIA-X in die Gruppen
positive mood were found to be associated with              with inhibitors of cholinesterase and immunosup-             «ohne psychische Störungen» (N = 30) und «mit
a rightward orientation preference (Drake, 1992;            pressive therapy. Remission under intravenous                psychischen Störungen» (N = 19) kategorisiert.

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Der Vergleich der beiden Gruppen bezüglich                 26 Sepsis induces long-term verbal memory                    27 Serum Copeptin levels correlate with
psychobiologischer Faktoren erfolgte anhand                deficits and left-sided hippocampal volume                   disability in Multiple Sclerosis
verschiedener Fragebogen (RLS-DI, IRLS, RLS-               reduction in quantitative voxel-based brain
                                                                                                                        M. Katan1, J. Kuhle1, N. Morgenthaler2,
6, SOMS, BSI, FSS, SF-12 und Schlaffragebo-                MRI
                                                                                                                        M. Christ-Crain3, L. Kappos1
gen) wie auch mittels Aktimetrie (PLMS) und
                                                           A. S. Semmler1, K. F. Fliessbach2, J. W. Weide2,
Blutanalysen.                                                                                                           1
                                                                                                                            University Hospital, Neurology, Basel,
                                                           M. T. H. Heneka2
    Ergebnisse: Die Resultate ergaben für die                                                                               Switzerland
Gruppe «ohne psychische Störungen» signi-                  1
                                                               University Zurich, Zurich, Switzerland                   2
                                                                                                                            Research Department, BRAHMS AG,
fikant mehr PLMS. Für die Gruppe «mit psy-                 2
                                                               University Bonn, Bonn, Germany                               Hennigsdorf/Berlin, Germany
chischen Störungen» zeigten sich stärkere Aus-                                                                          3
                                                                                                                            University Hospital, Endocrinology, Basel,
                                                           Background: Until recently, critical care practitio-
prägungen bezüglich Schweregrad des RLS,                                                                                    Switzerland
                                                           ners have focused on the survival of patients and
Müdigkeit, Beeinträchtigung der Lebensqualität
                                                           not on long-term outcomes. However, current                  Background: The degree of activation of the hy-
und Somatisierungstendenzen. Es wurden kei-
                                                           research indicates that critical illness can lead to         pothalomo-pituitary-axis (HPA) has been help-
ne signifikanten Gruppenunterschiede bezüg-
                                                           permanent cognitive impairment. Cognitive im-                ful in assessing disease severity and prognosis in
lich klinischer Hauptkriterien, positiver Fami-
                                                           pairment may be particularly common in survi-                several diseases but the measurement of circulat-
lienanamnese, Altersverlauf, Schlafstörungen
                                                           vors of sepsis. Long-term follow-up examination              ing Corticotrophin-releasing hormone (CRH) and
und der Blutanalysen (inkl. Eisenstatus) gefun-
                                                           in rodents indicated that experimental induction             arginine-vasopressin (AVP) levels, the main secre-
                                                           of sepsis induces permanent behavioural deficits             tagogues of the HPA-axis, is challenging. Copeptin
    Schlussfolgerung: Das Auftreten von perio-
                                                           and neuroanatomical changes, such as reduced                 is released in an equimolar ratio to AVP from the
dischen Beinbewegungen ist ein potentieller
                                                           density of hippocampal neurons and reduced cor-              same precursor peptide and is more stable in the
Marker zur Unterscheidung von RLS und «RLS-
                                                           tical cholinergic innervations.                              circulation and easier to determine. We investi-
                                                                Patients and methods: In this mono-center,              gated if copeptin levels correlate with disability
                                                           retrospective study we recruited 51 patients be-             in multiple sclerosis and if it predicts conversion
                                                           tween 18 and 75 years old for testing of cognitive           to clinically definite multiple sclerosis (CDMS) in
25 Reversible cerebral vasoconstriction
                                                           functions and quantitative voxel-based brain                 patients with a first demyelinating event (CIS).
syndrom as a cause for atypical subarachnoid
                                                           MRI 9 to 18 months after treatment on an inten-                   Methods: We measured Copeptin levels in the
hemorrhage – two case reports
                                                           sive care unit (ICU). During acute disease 25 pa-            serum of 28 patients with a CIS (EDSS 0–2.5:
D. Müntener1, L. Remonda1, H. Hungerbühler1                tients were diagnosed with sepsis. The remaining             normal to minimal disability) and 15 MS pa-
                                                           26 patients were treated for non-inflammatory                tients with clinically confirmed diagnosis (CD-
    Kantonsspital Aarau, Aarau, Switzerland
                                                           diseases and served as control group. Cognitive              MS) and EDSS scores of >/= 3.5 (at least moder-
Introduction: Reversible cerebral vasoconstriction         testing was performed by NeuroCogFx, Trail                   ate disability) using a highly sensitive sandwich
syndrome (RCVS) is a disorder characterised by             making Test-A and B (TMT-A, TMT-B). Test                     immunoassay.
sudden-onset and servere headache with or with-            results were compared with specific normative                     Results: Median Copeptin levels in MS pa-
out additional neurologic symptoms and signs. Im-          data and between groups. Magnetic resonance                  tients were significantly higher compared to
aging techniques show multifocal and reversible            imaging measurements were performed using a                  patients with a CIS (4.4 pmol/l (IQR 3.1–8.6
vasoconstriction of cerebral arteries. The etiology        1.5-T scanner with sagittal T1-weighted image                pmol/l) versus 3.3 pmol/l (IQR 2.4–4.2 pmol/l),
is frequently idiopathic. RCVS can cause ischemic          sequences yielding 200 slices and a voxel size               p = 0.035). Time of conversion to CDMS was not
strokes, parenchymal hemorrhages and nonaneu-              of 0.9 x 0.9 x 0.9 mm, followed by statistical               mirrored by Copetin levels (Converters, n = 14:
rysmal cortical subarachnoid hemorrhages (SAH).            parametric mapping.                                          3.2 pmol/l (2.6–3.8), No-Converters, n = 14: 3.2
     Methods/Results: We describe two patients                  Results: Both, sepsis and other ICU survivors           pmol/l (2.3–4.4)).
with idiopathic RCVS presenting with thunder-              show significant deficits in almost all cognitive                 Conclusion: The raised Copeptin levels ob-
clap-headaches and additional neurologic symp-             domains. To test for sepsis-specific effects, we             served in patients with established MS and dis-
toms. In both cases magnetic resonance imaging             analysed the different patient groups separately             ability may reflect, disease activity related re-
(MRI) delineated a small cortical SAH. Transcra-           (sepsis-survivors, survivors of severe sepsis, and           lease of inflammatory mediators, or a secondary
nial duplex sonography (TCD) and digital sub-              non-septic ICU-survivors). Survivors of severe               response to disability, or both. Further studies
traction angiography (DSA) revealed segmen-                sepsis showed verbal memory deficits in com-                 comparing MS patients with different levels of
tal stenoses of multiple cerebral arteries with            parison to non-septic ICU-survivors (p = 0.01),              disability progression must show if copeptin lev-
complete resolution after a few weeks. There               and in comparison to survivors of sepsis for trend           els are a useful – maybe even prognostic marker
was no evidence for a different etiology of SAH            (0.07). This was accompanied by a volume re-                 for disability and disease severity in MS
or vasospasms such as intracranial aneurysms,              duction of the left-sided hippocampal and para-
other vascular malformations, cerebral venous              hippocampal areas (p <0.05) in sepsis survivors
                                                                                                                        28 Sleep disturbance impedes stroke
thrombosis or drugs.                                       in quantitative MRI brain volumetry.
                                                                                                                        recovery in the rat
     Conclusions: RCVS can cause SAH, which,                    Discussion: In this study we confirmed that
in contrast to aneurysmal SAH, have a cortical             ICU treatment leads to long-term cognitive im-               C. Zunzunegui1, B. Gao1, E. Cam1, A. Hodor1,
localisation. Vasoconstriction is likely a cause           pairment in various cognitive domains. More                  C. L. Bassetti1
and not a result of the hemorrhage, although               importantly, it shows that survivors of severe               1
                                                                                                                            Department of Neurology, University Hospital
the pathophysiology is not clearly understood.             sepsis show an impairment of verbal memory
                                                                                                                            of Zurich, Zurich, Switzerland
                                                           associated with a reduction of left sided hippo-
                                                           campal volume. These findings argue for sepsis-              Introduction: Sleep disturbance (SDis) represents
                                                           specific effects of cognitive impairment after ICU           a risk factor for stroke recovery. We have previ-
                                                           treatment and demonstrate that survivors of se-              ously showed that SDis over 3 days aggravates
                                                           vere sepsis are at particular risk for long-term             brain damage in the rat. The aim of this study is
                                                           cognitive impairment after full recovery.                    to further investigate the effects of SDis on the
                                                                                                                        function recovery.
                                                                                                                             Methods: 17 male Sprague Dawley rats were
                                                                                                                        subjected to ischemic surgery by occlusion of
                                                                                                                        the distal branches of Middle Cerebral Artery
                                                                                                                        (MCAo). 12 hours after ischemia, one group of

                   S C H W E I Z E R A R C H I V F Ü R N E U R O L O G I E U N D P S Y C H I A T R I E 2009;160(7):305–18 |                314

rats (n = 9) was subjected to SDis (12 h of sleep           of nocturnal breathing and leg movements).                   Postersession,
deprivation over 3 days) by gentle handling and             However, REM sleep behavior disorder (RBD)                   Freitag, 6.11.2009, 13.00–14.00 Uhr
another group (n = 8) left undisturbed after                was found in six PD patients with SW (in all 4
                                                                                                                         Gruppe 4
ischemia to serve as control. Single Pellet Reach-          with de novo SW).
ing test (SPR) was used to assess motor function.               Conclusion: SW in PD appears to be associ-               31 Suppression of gesture pantomiming by
     Results: After two-three weeks of training,            ated with depression, night-time hallucinations              inhibitory theta-burst rTMS over left inferior
the success of SPR reached about 50% (nor-                  and RBD. No differences were found, however,                 frontal lobe
malized as 100% for baseline). It dramatically              in polysomnographic parameters between PD
                                                                                                                         S. Bohlhalter1, M. Bertschi1, T. Vanbellingen2,
dropped to 4% of baseline after MCAo in both                patients with and without SW.
                                                                                                                         P. Wurtz3, T. Nyffeler1, C. W. Hess1, R. Müri1
groups. SPR continually recovered in the con-
trol group, reaching 50.36% ± 23.95 at the end                                                                           1
                                                                                                                             Department of Neurology, Inselspital, Berne,
of 4 weeks. In contrast, it remained at 24.70%              30 Soluble CD70: a novel immunotherapeutic                       Switzerland
± 24.34 in the SDis group. Repeated measures                agent for experimental glioblastoma                          2
                                                                                                                             Klinik Bethesda, Neurorehabilitation Centre,
ANOVA indicated a significant difference (p =                                                                                Tschugg, Switzerland
                                                            J. Miller2, G. Eisele1, G. Tabatabai1,
0.001) in group*time interaction (F [6, 90] =                                                                            3
                                                                                                                             Perception and Eye Movement Laboratory,
                                                            S. Aulwurm3, G. von Kuerthy1, L. Stitz4,
4.470). Post hoc independent t-tests showed                                                                                  Departments of Neurology and Clinical Re-
                                                            P. Roth1, M. Weller1
that group difference was significant at day 14                                                                              search, Inselspital, Berne, Switzerland
(Control 44.54 ± 16.52 vs SDis 19.36 ± 25.5,                1
                                                                University Hospital Zurich, Department
                                                                                                                         Background: The traditional view of a predominant
p = 0.031), 21 (Control 55.3 ± 25.57 vs SDis                    of Neurology, Zurich, Switzerland
                                                                                                                         inferior parietal control of gesture production has
21.05 ± 20.89, p = 0.008) and 28 (Control 50.36             2
                                                                Department of Neurosurgery, Indiana Univer-
                                                                                                                         been recently challenged by neuroimaging stud-
± 23.95 vs SDis 24.70 ± 24.34, p = 0.045), but                  sity, Indianapolis, United States
                                                                                                                         ies demonstrating that gesture pantomime may
not at days 1, 4 and 7.                                     3
                                                                Department of General Neurology, Hertie In-
                                                                                                                         critically depend on inferior frontal function. The
     Conclusion: Sleep disturbance over 3 days has              stitute for Clinical Brain Research, Tuebingen,
                                                                                                                         aim of the present work was therefore to investi-
a significant detrimental effect on long term re-               Germany
                                                                                                                         gate the effect of transient disruption by repetitive
covery of motor function in the rat.                        4
                                                                Institute of Immunology, Friedrich Loeffler
                                                                                                                         transcranial magnetic stimulation (rTMS) over
                                                                Institute, Tuebingen, Germany
                                                                                                                         these brain sites on pantomime and imitation of
                                                            Purpose of the study: Expression of CD70 on the sur-         gestures.
29 Sleepwalking in patients with Parkinson’s                                                                                  Methods: In 10 right handed healthy subjects
                                                            face of glioma cells was shown to induce a potent
disease                                                                                                                  (5 women, aged 25–39) an inhibitory continu-
                                                            anti-tumor immune response in a murine glioma
N. D. Di Fabio1, R. P. Poryazova1, M. O. Ober-              model in vivo. There is evidence that also the               ous theta-burst protocol of rTMS (cTBS) was
holzer1, C. B. Baumann1, C. B. Bassetti1                    soluble form of CD70 is active in vivo. A soluble            applied over left inferior parietal lobule (IPL)
                                                            co-stimulatory ligand is attractive as it might have         and inferior frontal gyrus (IFG) versus baseline
    University Hospital Zurich, Zurich, Switzerland
                                                            a wider distribution into the tissue surrounding             (BSL).We employed a repeated measures design
Introduction: Sleepwalking (SW) corresponds to a            the tumor in vivo.                                           with 1 week intervals between the 3 sessions in
complex sleep-associated behavior, characterized                 Methods: The murine glioma cell line SMA-               balanced order. Gesturing was assessed off-line
by locomotion, mental confusion, and amnesia. In            560 was engineered to produce a soluble from                 within 15 minutes after cTBS using a recently
a single center series of 165 consecutive patients          of CD70 (sCD70). The expression of sCD70 was                 developed test of upper limb apraxia (TULIA),
with Parkinson’s disease (PD), we found de novo             confirmed by immunoblot. Markers of immune                   which includes a pantomime and imitation
SW in 6 subjects (4%, Arch Neurol 2008). In a               cells were assessed by flow cytometry. The pro-              subtests. Based on its highly sensitive scoring
questionnaire survey supported by the patient’s             liferation of immune cells was investigated in a             method the TULIA test shows no ceiling effect
organization Parkinson Switzerland, 36 (9%) out             3H-Thymidine assay. The secretion of IL-2 and                (cut off for apraxia <194, maximum score 240).
of 417 patients with SW were identified. The clini-         IFN-gamma was assessed by ELISA. SMA-560                     Performance was assessed by a blinded rater
cal and polysomnographic characteristics of PD              cells were implanted stereotactically in the right           based on video recordings.
patients with SW are essentially unknown.                   striatum of syngeneic VM/Dk mice. The infiltra-                   Results: The findings revealed that cTBS sig-
     Aim: To assess the polysomnographic char-              tion of immune cells in gliomas was assessed by              nificantly affected total TULIA scores (F = 9.350,
acteristics of SW in PD patients.                           immunohistochemistry. CD8+ or NK cells were                  p = 0.02, repeated measures ANOVA), which is
     Patients and methods: Out of 417 patients              depleted by the injection of appropriate antibod-            mainly explained by the effect on the panto-
participating in the survey, 8 PD patients with             ies intraperitoneally.                                       mime subtest (F = 11.082, p = 0.009), as imita-
SW (in four of them since childhood) and 6 PD                    Results: In vitro expression of sCD70 en-               tion scores remained unchanged (F = 1.887, p =
patients without SW were assessed. A detailed               hances proliferation of syngeneic splenocytes                0.2). Furthermore, significant differences were
clinical examination (including UPDRS III and               and their secretion of IL-2 and IFN-gamma.                   found between left IFG and IPL stimulation for
mini mental state examination), standardized                In syngeneic VM/Dk mice bearing intracranial                 total scores (225.6 ± 7.8 and 231.0 ± 6.4, p =
questionnaires (including validated sleep ques-             gliomas, sCD70 enhances the survival rate. The               0.02, post hoc paired t-test) and particularly
tionnaires, the Beck depression and anxiety                 infiltration of CD8+ cells is enhanced compared              pantomime subscores (111.7 ± 4.8 and 115.0
inventory) and a conventional overnight poly-               to controls. Depletion of CD8+ cells abrogates               ± 3.9, p = 0.004). When contrasted with BSL, a
somnography were performed.                                 the survival advantage.                                      decrease of total scores at the level of a statistical
     Results: Compared to PD patients without                    Conclusion: These data suggest that sCD70               trend was found for cTBS of IFG (225.6 ± 7.8
SW, those with SW had a similar disease dura-               is a potent stimulator of anti-glioma immune                 and 228.6 ± 5.5, p = 0.09) or a just significant
tion and motor symptom severity (UPDRS III),                response with cytotoxic CD8+ T-cells playing a               increase for cTBS of IPL (231.0 ± 6.4 and 228.6
but higher scores on the Beck Depression Inven-             major role.                                                  ± 5.5, p = 0.05).
tory (p <0.001). Mini mental state examination                                                                                Conclusion: The suppression of gesture pan-
scores did not differ between the two groups.                                                                            tomiming by cTBS over left IFG points to an in-
Night-time hallucinations were reported in 7 out                                                                         ferior frontal rather than inferior parietal gesture
of 8 patients with SW, but only in 1 PD patient                                                                          representation. Furthermore, the findings sug-
without SW.                                                                                                              gests that inhibition of IPL favours the inferior
     There were no differences in polysomno-                                                                             frontal function during gesture pantomime in-
graphic sleep parameters (sleep latency, sleep                                                                           dicating that such intrahemispherical facilitation
efficiency, sleep stages percentages, and indices                                                                        may have clinical implications.

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32 The NADPH oxidase Nox-1 is a mediator                        Introduction: Amyotrophic lateral sclerosis             not be an exclusion criteria for thrombolytic
of brain injury in experimental stroke                     (ALS) is characterized by progressive neuronal               therapy after stroke.
                                                           degeneration. This study aimed at analyzing
T. Kahles1, A. Kohnen1, S. Heumueller1,
                                                           whether genetic variants of homocysteine me-
A. Rappert1, I. Bechmann1, S. Liebner1,
                                                           tabolism are associated with the development                 35 Varicella zoster virus – hide and seek in an
I. M. Wittko1, K.-H. Krause2, T. Neumann-
                                                           of ALS.                                                      immunocompetent patient
Haefelin1, H. Steinmetz1, R. P. Brandes1
                                                                Subjects and Methods: 162 patients diagnosed
                                                                                                                        A. Becker, S. Biethahn, U. W. Buettner
    JW Goethe University, Frankfurt, Germany               with ALS by modified Airlie House El Escorial
    Centre Medical Universitaire, Geneva,                  criteria and 162 healthy subjects were enrolled.             Kantonsspital Aarau, Aarau Switzerland
    Switzerland                                            Genomic DNA from peripheral leucocytes was
                                                                                                                        Introduction: Encephalitis and angiitis are possible,
                                                           used for genotyping of seven genetic variants
Cerebral ischemia and reperfusion is associated                                                                         but uncommon complications of varicella-zoster-
                                                           of Hcy metabolism by allele specific PCR with
with the generation of reactive oxygen species                                                                          virus (VZV) infection, usually proceeded by a rash
                                                           subsequent restriction analysis. In binominal
(ROS). ROS are considered to contribute to the                                                                          [1, 2]. Cerebro-spinal fluid (CSF)-PCR is an im-
                                                           regression analysis, the association between the
brain damage process. Mitochondria and the clas-                                                                        portant diagnostic tool to confirm the diagnosis.
                                                           genetic variants and ALS was analyzed with age
sic leukocyte-type NADPH oxidase are thought                                                                            We present a patient with a history suggestive of
                                                           and gender as covariables and threshold = 0.05.
to be the significant sources of ROS in this sce-                                                                       VZV-angiitis and -encephalitis without a rash and
                                                                Results: The frequency of the genotypes of
nario. Although the NADPH oxidase Nox-1 also                                                                            negative PCR.
                                                           the variant MTHFR c.677C>T (p.A222V) was
produces ROS, little is known regarding its role                                                                             Case report: The immunocompetent patient
                                                           different between patients and controls, i.e., the
for cerebral ROS formation and ischemia/reper-                                                                          presented with a history of headache, tempera-
                                                           T-allele was more frequent in the patients than
fusion-induced brain injury. We studied this as-                                                                        ture up to 38 °C, ataxia with falls and a progres-
                                                           in controls: patients, CC/CT/TT: 0.40/0.48/0.13;
pect in Nox-1 knockout-mice and their wildtype                                                                          sive confusional state with reduced vigilance
                                                           controls, CC/CT/TT: 0.50/0.44/0.06 (Wald =
littermates.                                                                                                            for three weeks. The CSF was abnormal with
                                                           5.39; p = 0.020).
     After isolation of cells from the murine                                                                           42 cells (mononuclear) and a protein of 2 g/l.
                                                                Discussion: In this study we found the ther-
brain, we demonstrated the expression of Nox-                                                                           A broad search for pathogenic agents revealed
                                                           molabile variant of MTHFR as possible risk factor
1 in astrocytes, neurons as well as endothelial                                                                         positive values for VZV IgM in Serum, CSF-PCR
                                                           for ALS. This polymorphism is known to lower
cells using RT-PCR. Transient focal cerebral isch-                                                                      was negative. On MRI, multiple small ischemias
                                                           MTHFR activity and to contribute to elevated
emia was induced by the middle cerebral artery                                                                          were present. On MR-angiography, convention-
                                                           plasma Hcy levels, which have been observed
filament occlusion followed by reperfusion. Le-                                                                         al angiography and neurosonology multiple ste-
                                                           in ALS patients. These results suggest that the
sion volume was assessed using TTC staining.                                                                            noses of the basal arteries were found.
                                                           T-allele of MTHFR c.677C>T may contribute a
Furthermore, we examined the integrity of the                                                                                A therapy with acyclovir was initiated, four
                                                           risk of ALS, which should be tested in additional
blood-brain-barrier in vivo with sodium fluores-                                                                        days later the patient was orientated, awake,
                                                           study samples.
cein (SF) and Evans blue (EB) as permeability                                                                           GCS 15. However, after discussion of the PCR
markers.                                                                                                                and IgM-results concerning VZV, a non-specific
     Vascular architecture was similar between                                                                          polyclonal stimulation was assumed, and acy-
                                                           34 Thrombolytic therapy in stroke patients
WT and KO animals as were filament-induced                                                                              clovir was stopped. In the course of another
                                                           older than 85 years
changes in cerebral blood flow in this model of                                                                         three days the patient deteriorated again, this
transient focal cerebral ischemia. Lesion volume           A. Häne1, H. Hungerbühler1, G. Schwegler1                    time also developing a slight hemiparesis on the
after one hour of ischemia and 23 hours of re-                                                                          left side. Acyclovir was initiated again. Over a
                                                               Kantonsspital Aarau, Aarau, Switzerland
perfusion however was significantly reduced in                                                                          period of 10 days the patient recovered, was
brains of KO as compared to those of WT mice               Introduction: There is only few data about the out-          alert, orientated, able to walk with slight ataxia,
(WT 77 mm3 ± 10, KO 43 mm3 ± 10 mean ± sem;                come of very old patients being treated by throm-            the hemiparesis wore off. Furthermore, the ste-
p <0.05). In line with this observation, the clini-        bolysis after stroke.                                        noses decreased. The neurosonologic examina-
cal brain injury score was significantly lower in               Methods: We retrospectively analyzed the                tion before discharge was normal. Additionally,
KO than in WT mice (modified Bederson score,               outcome of patients aged over 85 years, who                  no further ischemic lesions occurred on MRI.
WT: 1.5, KO: 0.9; p <0.05). Early BBB damage               underwent intravenous (IV) or intraarterial                       Discussion: Most likely this patient suffered
was significantly smaller in brains of KO as com-          (IA) thrombolysis in our stroke center between               from VZV-angiitis and encephalitis, despite the
pared to those of WT littermates (SF: WT 149 ng            February 2004 and November 2008.                             lack of a rash or a positive PCR-result. How-
± 19, KO 72 ng ± 17; p <0.05). Accordingly, brain               Results: Of 34 included patients, 71% (n =              ever, a rash has been described to occur in only
edema formation was attenuated in KO mice                  24) were aged 85 to 90 years and 29% (n = 10)                about 60% of patients [2], and the sensitivity
(WT: 57 mm3 ± 7, KO: 35 mm3 ± 5; p <0.05).                 were older than 90 years. 44% had an occlusion               of VZV-PCR varies between 50 and 90% in the
     These data demonstrate that the Nox-1-                of the middle cerebral artery (M1 segment 21%,               literature.
containing NADPH oxidase is expressed in the               M2 segment 23%). 82% of the patients were                         Conclusion: In a patient with typical clinical
murine brain and contributes to the pathophysi-            treated by IV thrombolysis, 15% by IA throm-                 features of a VZV-angiitis and -enzephalitis, the
ology of stroke. Inhibition of the NADPH oxidase           bolysis. One patient underwent a combined IV                 lack of a rash or a negative PCR does not neces-
may serve as a new approach to reduce brain                and IA thrombolysis. Favourable outcome was                  sarily rule out the diagnosis.
injury after stroke.                                       defined as modified Ranking Scale (mRS) <=2
                                                           or mRS 3 for the subgroup of patients with
                                                           historical prestroke mRS 3. Three months after
33 The thermolabile variant of                             stroke 29% of the patients reached a favourable              1   The neurotropic herpes viruses: herpes sim-
5,10-methylenetetrahydrofolate reductase as                outcome. 21% had a mRS of 4 or 5 and 26%                         plex and varicella-zoster. I. Steiner,
possible risk factor for amyotrophic lateral               died. In the subgroup of patients older than 90                  PGE Kennedy, AR Pachner.
sclerosis: a case-control study                            years outcome was favourable in 40%.                             Lancet Neurology. 2007;6:1015–28.
                                                                Conclusion: As expected, mortality is high-             2   The varicella zoster virus vasculopathies:
B. I. Ineichen1, P. K. Kühnlein2, M. F. Farkas1,
                                                           er and the outcome of patients aged over 85                      Clinical, CSF, imaging and virologic features.
S. K. Keskitalo1, A. S. Semmler1, M. W. Weller1,
                                                           years after thrombolysis is not as beneficial as in              MA Nagel et al. Neurology. 2008;70:853–60.
A. L. Ludolph2, H. J. Jung1, M. L. Linnebank1
                                                           younger patients. Nonetheless, our data suggest
      University Zurich, Zurich, Switzerland               that some very old patients might benefit from
      University Ulm, Ulm, Germany                         thrombolysis. Therefore very high age should

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36 The increased number of regenerated                     craniectomy. It consists of neurologic symptoms              group. However, the decrease in ESS scores was
axons after thyroid hormone treatment of                   and deficits like controlateral weakness.                    higher in the treatment group (–2.3 ± 2.3 vs 0.7
transected sciatic nerve is accompanied                         We report the case of a 37-year-old man                 ± 1.8, p = 0.005). Objective estimation in the
by improvement of muscle reinnervation                     who had suffered severe traumatic brain injury,              MWT confirmed the amelioration of EDS only
                                                           needing a large craniectomy because of right                 in the treatment group. Psychomotor vigilance
P. A. Panaite, T. Kuntzer, I. Barakat-Walter
                                                           hemispheric oedema. He presented with discrete               test results were similar in both groups.
Laboratory of Neurology Research, Neurology                left hemiparesis and neglect; his gait was safe.                  Conclusion: Modafinil appears to be effective
Service, CHUV, and Department of Cell Biology              During the following weeks, left-sided weak-                 in the treatment of posttraumatic EDS and fa-
and Morphology, University of Lausanne,                    ness became more important with plegia of the                tigue.
Lausanne, Switzerland                                      hand and increasing difficulties to walk. A CT
                                                           revealed no new lesion and EEG showed no epi-
Injuries of peripheral nerves are common in clini-
                                                           leptic activity.                                             39 State space mapping of sleep and
cal practice, and axonopathy is the usual mecha-
                                                                Following cranioplasty, his condition im-               wakefulness in Parkinson patients and
nism explaining loss of motor function and muscle
                                                           proved markedly: within a few days, hemiple-                 healthy controls
atrophy. Since reinnervation is essential for the re-
                                                           gia nearly fully recovered and neglect improved
turn of nerve function, the main goal of peripheral                                                                     Johannes Sarnthein1, Esther Werth2,
nerve repair is to induce as many axons as possible                                                                     Christian R Baumann2
                                                                Grant and Norcross (Ann Surg 110, 1939)
to regenerate, enter the distal stump and proceed
                                                           first described the syndrome of the trephined.               1
                                                                                                                            Neurochirurgische Klinik, UniversitätsSpital,
to reinnervate the end organs.
                                                           The physiopathology remains unclear: direct                      Zurich, Switzerland
     In our previous works, we have already
                                                           influence of the atmospheric pressure, altered               2
                                                                                                                            Neurologische Klinik, UniversitätsSpital,
shown that the administration of thyroid hor-
                                                           CFS circulation, decreased cerebral perfusion,                   Zurich, Switzerland
mone (T3) in either silicon or biodegradable
                                                           metabolic changes, have been proposed to ex-
nerve guides significantly increased the num-                                                                           Background: Sleep is commonly scored in stages,
                                                           plain the syndrome.
ber and the myelination of regenerated axons                                                                            but the succession of behavioural states is only
                                                                In our patient, the very large defect and
(J Neurotrauma. 2007;24:567–77). Therefore,                                                                             poorly understood. For a better description of
                                                           prolonged upright body position have probably
it is important to investigate whether the in-                                                                          sleep-wake dynamics, we have adapted state space
                                                           contributed to the occurrence of the syndrome.
crease in number of regenerated axons after                                                                             analysis (SSA, originally applied in rodents) to
T3-treatment of transected rat sciatic nerve is                                                                         analyze sleep in patients with Parkinson’s disease
accompanied by an improvement in hind limb                                                                              (PD) and healthy controls.
                                                           38 Modafinil ameliorates posttraumatic
muscle reinnervation, as assessed by changes                                                                                 Methods: We obtained polysomnographic re-
                                                           sleepiness and fatigue: A double-blind,
in morphology and number of neuromuscular                                                                               cordings from 7 PD patients and 7 age-matched
                                                           randomized, placebo-controlled pilot study
junctions (NMJ).                                                                                                        healthy controls. 30-s epochs were scored vi-
     NMJ were examined in PBS-control and in               Philippe Kaiser, MSc, Philipp Valko, MD,                     sually. EEG data were Fourier-transformed to
T3-treated rats on serial longitudinal hind limb           Esther Werth, PhD, Janine Thomann, MSc,                      obtain the power spectral density for each epoch.
muscles (gastrocnemius and plantar) stained                Judith Meier, Claudio L. Bassetti, MD,                       Thereafter, we calculated 3 ratios of frequency
with rhodamine-conjugated a-bungarotoxin                   Christian R. Baumann, MD                                     bands. While these ratios aim at capturing specif-
and anti-neurofilament antibody: At 4 weeks                                                                             ic spectral features, their final nature is heuristic.
                                                           Department of Neurology, University Hospital
of sciatic nerve regeneration, only rare regen-                                                                         After data processing via principal component
                                                           Zurich, Switzerland
erated axons were observed in PBS-control                                                                               analysis, smoothed time series were plotted as
rats, and all end-plates were still denervated.            Background: Excessive daytime sleepiness (EDS)               clusters and trajectories in a three-dimensional
In T3-treated rats, few reinnervated NMJ can               and fatigue are frequent complaints following                state space. The congruence between visual scor-
be observed. Fourteen weeks following nerve                traumatic brain injury (TBI). In our prospective             ing and the classification based on EEG spectra
regeneration, the histological analysis revealed           study on sleep-wake-disturbances 6 months after              was quantified with discriminant analysis (DA).
the presence of a higher number of regenerated             trauma, we found EDS in 38%, and fatigue in                  We assessed ratios with best cluster discrimi-
axons in T3-treated rats than in control rats. The         17% of 65 consecutive TBI patients. Given the                nation (optimized for maximal surface of the
morphometric measurement and the statistical               high frequency of TBI in the population and the              triangle spanned between the centroids of the
analysis revealed a significant increase in the            enormous socioeconomic impact of vigilance im-               DA) and congruence.
size and shape complexity of NMJ in T3-treated             pairment in TBI patients, treatment strategies are                Results: Power spectra revealed only small
rats as compared to PBS-controls. Moreover,                urgently warranted but do not exists until now.              differences between PD patients and controls.
the density of acetylcholine receptors on post-            We aimed at studying the effect of daily modafinil           Congruent scoring was obtained for a median of
synaptic membrane was significantly higher in              on posttraumatic EDS and fatigue.                            90% of epochs in PD patients, and 93% in con-
T3-treated rats.                                                Methods: We ran a double-blind, randomized,             trols. The median surface of the triangle between
     These results suggest that the T3-treatment           placebo-controlled pilot study in 20 TBI patients            centroids was 49 units for PD patients, and 180
stimulates not only the number of regenerated              with posttraumatic EDS or fatigue. Fatigue was               units for controls. In all subjects, trajectory ve-
axons but also improves hind limb muscle rein-             diagnosed with the fatigue severity scale (FSS),             locity within clusters was low for deep and REM
nervation.                                                 and EDS with the Epworth sleepiness scale                    sleep, indicating that EEG spectra of subsequent
     This work was supported by a special grant            (ESS). The Beck Depression and Anxiety Inven-                epochs in these sleep states show low variability.
from the SUVA.                                             tory was used to assess depression and anxiety               Highest velocities were found for wakefulness
                                                           symptoms. At baseline and six weeks following                and epochs adjacent to state transitions.
                                                           treatment initiation (100–200 mg modafinil vs                     Conclusion: SSA can be applied to sleep re-
37 Syndrome of the Trephined
                                                           placebo), we applied these questionnaires and                cordings of both healthy controls and PD pa-
A. Tanga, B. Leemann, A. Schnider                          performed actigraphy, conventional nocturnal                 tients. Embedding of further polysomnographic
                                                           polysomnography, maintenance of wakefulness                  parameters such as submental muscle tone may
Hôpital Cantonal de Genève,
                                                           tests (MWT), and psychomotor vigilance tests.                improve discriminatory power. The further de-
Service de Neurorééducation
                                                                Results: Demographic, psychiatric and sleep             velopment of this method may improve our un-
After a large craniectomy, a cranioplasty is not           baseline characteristics did not differ between              derstanding of regulation of sleep and wakeful-
only cosmetic but also prevents or improves the            the two groups (each: n = 10). After 6 weeks                 ness in health and disease.
syndrome of the trephined. This syndrome is a              of treatment, there was no significant effect on
possible delayed complication of decompressive             fatigue (as assessed by the FSS) in the modafinil

                   S C H W E I Z E R A R C H I V F Ü R N E U R O L O G I E U N D P S Y C H I A T R I E 2009;160(7):305–18 |                317

40 Population-based study of acute phase                    41 Restless legs syndrome in pregnancy:                      42 Experience of Moyamoya angiopathy
blood pressure after TIA and stroke in relation             A prospective, systematic study                              in Zurich
to pre-morbid measurements, underlying
                                                            A. Hübner1, A. Krafft2, S. Gadient1, E. Werth1,              Y. Yonekawa, M. Hug, M. Wiesli, M. Fujioka,
pathology and long-term outcome
                                                            R. Zimmermann2, C. L. Bassetti1                              J. Fandino
U. Fischer1, L. Bull2, L. Silver2, Z. Metha2,               1
                                                                University Hospital Zurich, Department of                University of Zurich, Kinderspital Zurich,
P. M. Rothwell2
                                                                Neurology, Zurich, Switzerland                           Klinik im Park Zurich, Kantonsspital Aarau
    Department of Neurology, Inselspital, Univer-           2
                                                                University Hospital Zurich, Obstetrics, Zurich,
                                                                                                                         Introduction: Moyamoya angiopathy MMA (Moya-
    sity Hospital Berne, Berne, Switzerland                     Switzerland
                                                                                                                         moya disease, Moyamoya syndrome and Moya-
    Stroke Prevention Research Unit, John Rad-
                                                            Introduction: Three retrospective studies suggested          moya moid [unilateral pathology]) has been
    cliffe Hospital, University Department of Clini-
                                                            a high frequency (11–26%) of restless legs syn-              considered to be prevalent in Japan and Asian
    cal Neurology, Oxford, United Kingdom
                                                            drome (RLS) in pregnancy. None of these studies              countries. Now we know its existence also in Eu-
Background: Blood pressure (BP) is elevated in              used standardized methods for assessment of RLS              ropean countries. Since 1993 we have experienced
many patients with acute stroke, but the mecha-             and sleep. Characteristics and determinants of RLS           68 cases submitted to multiple microvascular ex-
nism is uncertain. Moreover, the extent of “post-           during pregnancy are poorly known.                           tracranial – intracranial EC-IC bypass revascular-
stroke” hypertension has not previously been re-                 Methods: Women during (from the 1st tri-                ization procedures. We present the management
lated to detailed records of pre-morbid BP, and so          mester) and after pregnancy (8 weeks post-                   of patients with MMA and the postoperative re-
it is uncertain how many patients have exhibited            partum) are prospectively studied. Assessment                sults based on our experience.
a tendency to similar or higher BPs in the past in          includes 1) interview about RLS-symptoms                          Method: Definitive diagnosis according to di-
the absence of stroke. In the first ever popula-            and sleep habits/disturbances: 2) standardized               agnostic criteria can be done now with magnetic
tion-based study of pre- and post-stroke BPs, we            questionnaires (incl. the international RLS-scale            resonance angiography MRA along with clinical
compared acute post-stroke BPs with all recorded            [IRLSS], Epworth sleepiness scale [ESS], and                 symptomatology. Digital subtraction angiogra-
pre-stroke measurements.                                    Pittsburgh Sleep Quality Questionnaire [PSQI]);              phy DSA is still important to know the delicate
      Methods: We collected all acute phase post-           3) blood tests (incl. hemoglobin, estrogen, C-               angiopathology and for the planning of surgical
event systolic (SBP) and diastolic (DBP) read-              reactive protein and ferritin), 4) leg actigraphy            revascularization procedure. H215O PET is car-
ings in all patients with an acute stroke or TIA            (3rd trimester and post-partum).                             ried out for measurement of regional cerebral
in the Oxford Vascular Study and related these                   Results: So far 498 women were screened.                blood flow rCBF and hemodynamic reserves.
to clinical characteristics, stroke subtype and all         RLS was diagnosed in 52 women (10.4%), 38                    Non-invasive Doppler-sonography is important
recorded pre-stroke measurements by access to               were included in the study. 37% of them had                  for regular following-up to know the hemody-
life-long general practice patient records. We              a positive family history for RLS, 34% reported              namic situation.
also assessed the association between early post-           onset of RLS-symptoms before the 20th week,                       Multiple bypass procedures of direct vascu-
stroke BP and risk of recurrent vascular events             18% suffered from RLS before pregnancy, 45%                  larization have been performed as therapy of
during long-term follow-up.                                 had RLS-symptoms daily, 42% had an IRLSS                     choice for augmentation of CBF.
      Results: 18,035 premorbid BP measurements             >20, and 100% had a PSQI >5 (all values in the                    Results: The series contains 45 children (0.1–
were available from 1047 (98%) of 1069 con-                 3rd trimester). Anemia (defined as Hb <11 g/dl               17 yrs Av 6.8 yrs; f/m 1.36) and 23 adults(21–66
secutive eligible patients. First SBP in the acute          in pregnant women) was found in 18% of                       yrs Av 39 yrs; f/m 4.75). The patients are also
phase was higher than the most recent pre-event             affected and unaffected women. Ferritin levels               from Germany (14), Holland (8), Austria (5),
reading in 65.4% (95% CI: 62.5–68.3) of pa-                 <35 ug/l were found in 75% of RLS positive and               Denmark (3), Italy (3), Norway (1), Sweden (1),
tients but only exceeded the highest pre-event              in 94% of RLS negative women. Women with                     Qatar (1): besides Caucasian, middle east origin
reading in 26.3% (95% CI: 23.6–29.0). This lat-             (pRLS) and without RLS (nRLS) had similar val-               (4) and Asian origin (3). One thirds of patients
ter proportion varied with TOAST subtype of                 ues in hemoglobin CRP, and ferritin (mean Hb                 have basic disease such as neurofibromatosis
stroke (p = 0.001), ranging from 16.7% in car-              11.7 mg/dl in pRLS, 12 mg/dl in nRLS; Ferritin               type 1, trisomy 21, hemoglobinopathy etc, so
dioembolic stroke to 34.2% in lacunar stroke.               22.6 μg/l in pRLS, 19.1 in nRLS). No signifi-                that these cases can be categorized as Moyamoya
In patients with a first post-event SBP measured            cant difference of estrogen levels between pRLS              syndrome. Two adult patients presented with
within 3 hours of the ictus, mean (SD) acute SBP            and nRLS (measured in 15 pRLS and 10 nRLS                    intracerebral hemorrhage. Almost all other pa-
was higher in patients with TIA and minor stroke            in 3rd trimester. Leg actigraphy was performed               tients presented with ischemia-infarction.
(NIHSS ≤3) than in those with major (NIHSS                  in 7 cases pre and post partum, PLMI dropped                      One adult patient died of perioperative isch-
>3) ischaemic stroke (163.9 vs 156.5 mm Hg, p               dramatically.                                                emic edema. Among others, three other patients
= 0.017), but was otherwise unrelated to stroke                  Conclusion: Preliminary results of this ongo-           had perioperative ischemic complication but
severity. First post-event BP was unrelated to              ing study suggest that RLS in pregnancy: 1) is               showed good recovery. Other patients profited
risk of recurrent stroke or other vascular events.          present in 10% of women; 2) frequently appears               from augmentation of CBF by multiple bypass
      Conclusions: Acute post-event SBP is lower            early in pregnancy; 3) is often severe/ frequent;            surgery.
than highest recorded pre-morbid SBP in the                 4) may not be related (only) to anemia/low fer-                   Conclusions: We present the state of the art
majority of patients, and is highest in patients            ritin levels or estrogen levels; 5) has a significant        of management of MMA including diagnosis,
with TIA and minor ischaemic stroke, suggesting             impact on sleep quality.                                     surgical treatment and the consequential re-
that post-stroke hypertension is not a unique                                                                            sults. In addition, long term follow-up results
physiological response to major cerebral infarc-                                                                         are presented along with distinctions in clini-
tion.                                                                                                                    cal pathophysiology of MMA between patients
                                                                                                                         from Europe and Japan.

                    S C H W E I Z E R A R C H I V F Ü R N E U R O L O G I E U N D P S Y C H I A T R I E 2009;160(7):305–18 |                318