SPECT IN CONCUSSION VERTEBRO BASILAR INSUFFICIENCY AND OTHER NEUROLOGICAL DISORDERS Novel applications and insights Deepak Agrawal MBBS MS MCh Fellow Ped by li3490

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									 SPECT IN CONCUSSION, VERTEBRO-
BASILAR INSUFFICIENCY AND OTHER
    NEUROLOGICAL DISORDERS

    Novel applications and insights



       Deepak Agrawal, MBBS, MS, MCh.
           Fellow, Pediatric Neurosurgery
               BC Children‘s Hospital, UBC
        LEARNING OBJECTIVES

   To understand uses of Single Photon
    Emission Computed Tomography (SPECT)
    in patients with post-concussion syndrome
    and vertebrobasilar insufficiency

   To be familiar with the use of SPECT as an
    investigative and research tool in
    neurosciences
Imaging Brain function using SPECT




       All India Institute of Medical Sciences, New Delhi
Imaging Brain function using SPECT

All India Institute of Medical Sciences, Delhi
 1200 bed tertiary centre
 Annual budget of CAD $250 million
Imaging
 6 CT scanners
 2 1.5 T MRI scanners, a 4.7 Tesla animal
  MRI/MRS scanner, and a 9.4 Tesla NMR
  spectrometer.
 1 PET, 2 SPECT scanners
Imaging Brain function using SPECT



IMAGING TECHNIQUES

   STRUCTURAL- MRI, CT

   FUNCTIONAL- SPECT, PET, fMRI
(SPECT-Single Photon Emission Computed Tomography)
Imaging Brain function using SPECT


  Functional Imaging

   PET-      Gold standard

   SPECT -  More widely available
           - Much cheaper
           - Still able to provide much of the same
             information
Imaging Brain function using SPECT



    UNDERLYING PRINCIPLES OF SPECT

   Biochemical interactions between brain
    tissue and injected substance (HMPAO,
    ECD, Iophane)

   These substances are labeled with
    radioactive tracers (99mTc-HMPAO, 99mTc-
    ECD, 123I-iophane)
Imaging Brain function using SPECT


    UNDERLYING PRINCIPLES

 Radiopharmaceutical injected IV
 Crosses BBB proportionate to blood flow
 Enters Neuronal tissue – stereoisomeric
  change
 Become ‗trapped‘ inside the neurons
Imaging Brain function using SPECT


    UNDERLYING PRINCIPLES

   Increased neuronal activity = increased
    neuronal uptake of radiopharmaceutical =
    Increased perfusion on SPECT

   This image of cerebral perfusion indirectly
    reflects cerebral metabolism
Imaging Brain function using SPECT



    BRAIN SPECT

   Brain perfusion - HMPAO,ECD
HMPAO-Hexa Methyl Propylene Amine Oxine; ECD-Ethylene Cysteinate Dimer

   Imaging of neurotransmitter systems -
    Ioflupane
Imaging Brain function using SPECT

APPLICATIONS
 Dementias
  Alzheimers:↓perfusion TP regions B/L
                 Normal perfusion Subcortical region


  Vascular Dementia:↓perfusion Subcortical
                     regions
Imaging Brain function using SPECT

APPLICATIONS
 Epilepsy
  Established role in epilepsy
  SISCOM (Subtraction Ictal SPECT
  Coregistered with MRI)
Imaging Brain function using SPECT

    APPLICATIONS
   Trauma
    Can show abnormalities in pts with
    normal CT & MRI
    Sensitivity can reach 80% compared to
    5% for CT and 60% for MRI in minor
    head injuries
    Kant R, Smith-Seemiller L, Isaac G, Duffy J. Tc-HMPAO SPECT in
    persistent post-concussion syndrome after mild head injury: comparison
    with MRI/CT. Brain Inj 1997;11:115.
Imaging Brain function using SPECT

APPLICATIONS
 Parkinsonism
  Dopamine transporter imaging- assessing
  the presynaptic dopaminergic function
Imaging Brain function using SPECT

  APPLICATIONS
 Research tool
  before & after pharmacotherapy,
  psychotherapy & surgery
Imaging Brain function using SPECT

  APPLICATIONS
 Dementias
 Epilepsy
 Trauma
 Parkinsonism
 Stroke
 Research tool-(before & after
  pharmacotherapy, psychotherapy,
  surgery)
Imaging Brain function using SPECT

APPLICATIONS
 Dementias
 Epilepsy
 Trauma
 Parkinsonism
 Stroke
 Research tool-(before & after
  pharmacotherapy, psychotherapy,
  surgery)
SPECT in TRAUMA
 Imaging Brain function using SPECT

TRAUMA
 90% of all HI are supposedly ‗minor‘
 Post concussion syndrome—including symptoms
  such as headache, irritability, poor concentration,
  memory disturbances, dizziness, anxiety, and
  depression—has been reported to occur in up to
  80% of the patients following minor HI.

  Hugenholtz H, Stuss DT, Stethem LL, Richard MT: How long does it take to recover from a
  mild concussion? Neurosurgery 22:853–858, 1988
  Wood RL. Understanding the 'miserable minority': a diasthesis-stress paradigm for post-
  concussional syndrome. Brain Inj.2004;18(11):1135-53
 Medial Temporal Injury In
 Pediatric Postconcussion
         Syndrome


         Deepak Agrawal, Naveen K*, C S Bal*, A K Mahapatra
Departments of Neurosurgery and *Nuclear medicine, All India Institute of Medical
                            Sciences, New Delhi
WHY MEDIAL TEMPORAL LOBE?
•Hippocampus is especially vulnerable
to insults such as ischemia, hypoxia,
and seizures
•Extent of hippocampal damage can be
correlated with severity of memory
impairment
Rempel-Clower NL, Zola SM, Squire LR, Amaral DG. Three cases of enduring memory
impairment after bilateral damage limited to the hippocampal formation. J Neurosci
1996;16:5233-5255.
OBJECTIVES
 Look for medial temporal hypoperfusion
  (MTH) on SPECT in children with minor
  head injury

   To evaluate MTH on SPECT as a risk
    factor for development of persistent
    postconcussion syndrome (PPCS) at
    three months
MATERIALS AND METHODS

   PROSPECTIVE STUDY
   One year period
   Children ≤ 18 yrs of age
  MINOR HEAD INJURY
   Loss of consciousness <30 minutes.
   GCS score 13 to 15.
   Posttraumatic amnesia <24 hours.

[criteria published by the members of the Mild Traumatic brain injury Interdisciplinary
Special Interest Group (BISIG)]

        Kay T, Harrington DE, et al. Definition of mild traumatic brain injury. J Head
Trauma Rehabil 1993;8:86
  POST CONCUSSION SYNDROME:
  (2 or more of the following)
    Headache
    Dizziness and vertigo
    Memory deficits
    Behavioral and emotional disturbances.
                               DSM IV criteria


Brown SJ, Fann JR, Grant I: Postconcussion disorder: time to acknowledge a common
 source of neurobehavioural morbidity. J Neuropsychiatry Clin Neurosci 6:15-22, 1994
INVESTIGATIONS


       CT   head


       SPECT   scan brain
       (Within 72 hours & at 3 months)
        SPECT METHODOLOGY
 SPECT scanning was done using 99Tcm-
  ECD on a dual headed GE 'Varicam'
  scanner.
 The final data was displayed on a 10
  grade color scale and semi quantitative
  analysis performed.
                         STUDY DESIGN
                  30 Children with minor head injury
                          Normal CT head &
                   Post concussion Syndrome (PCS)

                              SPECT scan
                             (within 72 hrs)

   Medial temporal hypoperfusion       No Medial temporal hypoperfusion
          (n=14 )(―MTH‖)                     (n=16 )(―control”)

         3 months later                         3 months later
Repeat SPECT & clinical evaluation     Repeat SPECT & clinical evaluation
            (PPCS)                                 (PPCS)
    RESULTS (SPECT)

   13/14 (93%) patients with initial MTH
    continued to have persistent MTH

   0/16 (0%) of patients in control group
    developed subsequent MTH at 3
    months
Baseline   At 3 months
RESULTS
Persistent post concussion syndrome (PPCS)

12/14 (86%) children developed PPCS in the
MTH group, compared to 2/16 (12.5%) children
in the control group


P=0.0003
CONCLUSIONS
 Children with MTH are more likely to
  develop persistent post concussion
  syndrome
 SPECT may help in identification and
  prognostication in this subgroup of
  children
SPECT AS A PLATFORM FOR TESTING
     VARIOUS INTERVENTIONS
ROLE OF PIRACETAM IN
 POST-CONCUSSION
     SYNDROME
A PROSPECTIVE RANDOMIZED STUDY

    Deepak Agrawal, K Naveen*, CS Bal*, AK Mahapatra
        Departments of Neurosurgery* and Nuclear medicine*,
     ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA
Piracetam
 Discovered 30 years ago by UCB pharma
 GABA derivative, does not work via GABA
  pathways.
 Mechanism of action remains unknown
 Has beneficial effects on the CBF by
  decreasing the adhesivity, aggregation, and
  increasing the deformability of
  erythrocytes.
 ―Nootropic‖
Why Piracetam?
 Already approved for use in Europe & India for a
  variety of disorders including head injury
 Minimal side effects- More than 12 g of
  piracetam has been given as daily dose in
  acute stroke without appreciable side effects

De Deyn PP, Reuck JD, Deberdt W, Vlietinck R, Orgogozo JM. Treatment of acute
   ischemic stroke with piracetam. Members of the Piracetam in Acute Stroke Study
   (PASS) Group. Stroke 1997; 28: 2347-52.
   OBJECTIVE
    To look for changes in cerebral perfusion on
    SPECT, following administration of
    Piracetam, in patients with post-concussion
    syndrome (PCS),
   MINOR HEAD INJURY
   1. Loss of consciousness <30
   minutes.
   2. GCS score 13 to 15.
   3. Posttraumatic amnesia <24
   hours.
[criteria published by the Mild Traumatic brain injury Interdisciplinary Special
Interest Group (BISIG)]

        Kay T, Harrington DE, et al. Definition of mild traumatic brain injury. J Head
Trauma Rehabil 1993;8:86
   POST CONCUSSION SYNDROME:
   (2 or more of the following)
    Headache
    Dizziness and vertigo
    Memory deficits
    Behavioral and emotional disturbances.

    DSM IV criteria based on recommendation of Brown et al.
Brown SJ, Fann JR, Grant I: Postconcussion disorder: time to acknowledge a common
 source of neurobehavioural morbidity. J Neuropsychiatry Clin Neurosci 6:15-22, 1994
    MATERIALS AND METHODS

 Prospective study
 Adult patients (18-60 yrs)
INVESTIGATION
CT head
SPECT scan brain

Within 72 hours of injury
             SPECT

Circular region of interest (ROI) with a
radius of 9.1mm (6 pels) in the basal
ganglia, thalamus, temporal lobe, visual
cortex and brain stem were used.
Semiquantitative analysis of the data
done using semiautomatic brain
quantification programs (Xpertpro,
Entegra with Neurogam).

ABNORMAL SPECT SCAN
Regional cerebral perfusion <10% of
contralateral lobe, or in case of bilateral
involvement, less than 20% of cerebellum
                    STUDY DESIGN


                       20 PATIENTS
     WITH POSTCONCUSSION SYNDROME & ABNORMAL SPECT

   PIRACETAM GROUP                 CONTROL GROUP

      10 PATIENTS                    10 PATIENTS

   800 mg PIRACETAM
       (Cerecetam)                  NO PIRACETAM
     TDS x 6 WEEKS

 CLINICAL EVALUATION &          CLINICAL EVALUATION &
REPEAT SPECT AT 6 WEEKS        REPEAT SPECT AT 6 WEEKS
  RESULTS
            rise in the post treatment ratio in the
 Significant
 piracetam group (mean: 0.959) as compared to
 the controls (mean: 0.882)          (p= <.001)

 Nine patients (90%) also had improvement in
 their symptoms of PCS, compared to only three
 patients in the control group      (p=0.01).
CONCLUSIONS
 Cerebral perfusion defects occur in
  majority of the cases of postconcussion
  syndrome following minor head injury.
 Piracetam reverses cerebral perfusion
  deficits and may result in accelerated
  symptomatic improvement in patients
  with postconcussion syndrome.
CONCLUSIONS

 THIS PRELIMINARY STUDY SHOWED
 OBJECTIVELY THAT LOW DOSE
 PIRACETAM MAY BENEFIT PATIENTS
 WITH POSTCONCUSSION SYNDROME
Imaging Brain function using SPECT
CRANIO-CERVICAL JUNCTION
 ANOMALIES AS A CAUSE OF
    VERTEBRO-BASILAR
      INSUFFICIENCY


      Deepak Agrawal, Naveen K*, SS kale, C S Bal*,
                          A K Mahapatra
     Departments of Neurosurgery and *Nuclear medicine,
    All India Institute of Medical Sciences, New Delhi-110029
                SPECT IN VERTEBROBASILAR
                      INSUFFICIENCY

Can SPECT reliably assess the posterior fossa?
                    YES!
1.   Delecluse F, Voordecker P, Raftopoulos C.Vertebrobasilar insufficiency revealed by xenon-133
     inhalation SPECT. Stroke 1989;20:952-6.
2.   Foster NL, Mountz JM, Bluelein LA, Ackermann RJ, Petry NA, Kuhl DE. Blood flow imaging of a
     posterior circulation stroke. Use of technetium Tc 99m hexamethylpropyleneamine oxime and
     single photon emission computed tomography. Arch Neurol 1988;45:687-90.
3.   Shuke N, Nagasawa K, Yamamoto W, Usui K, Sako K, Nakai H, Tanaka T, Aburano T.
     Demonstration of positional posterior cerebral ischemia on cerebral blood flow SPECT. Clin Nucl
     Med 2001;26:559-60.
SPECT In vertebrobasilar insufficiency



BACKGROUND
 Association of VBI with CCJ
  anomalies is severely underestimated
 X-rays of the Cx spine are done in only
  30% of pts with VBI & only 11% pts
  have proper flexn/extn x-rays done

  Lorenstan KJ, Schrospshire LC, Ahn HS. Congenital odontoid aplasia and
  posterior circulation stroke in childhood. Ann Neurol 1988;23-410-413
SPECT In vertebrobasilar insufficiency



BACKGROUND

 Posterior circulation ischemia has a higher
  morbidity and mortality
 Fifty percent of these patients who are
  managed conservatively progress to
  develop infarction
SPECT In vertebrobasilar insufficiency



BACKGROUND

   Diagnosing even a percentage of the
    patients with VBI as having CCJ anomalies
    may have major therapeutic & prognostic
    implications.
SPECT In vertebrobasilar insufficiency



Pathogenesis VBI in CVJ Anomalies
          Chronic low grade micro-trauma
           Repeated flex/extn of vessel

              Intimal damage

                Thrombosis

                Embolisation
SPECT In vertebrobasilar insufficiency

Clinical rarity of posterior circulation infarcts in
CCJ anomalies is thought to be due to
duplication of VA and the adequacy of the
circulation of Willis

However we feel that
patients symptomatic for VBI are not
routinely evaluated for CCJ anomalies
which remain undiagnosed
SPECT In vertebrobasilar insufficiency



Aims and Objectives:

   Using 99Tc ECD brain SPECT to document
    the presence of posterior circulation
    cerebral ischemia in patients with CCJ
    anomalies and correlate with symptoms of
    VBI.
SPECT In vertebrobasilar insufficiency




   PROSPECTIVE STUDY DONE OVER A
    SIX MONTH PERIOD
SPECT In vertebrobasilar insufficiency



VBI GROUP
 Pts with features suggestive of VBI (Drop
  attacks, episodic vertigo, visual
  disturbances and dysarthria)

CONTROL GROUP
 Patients without symptoms of VBI
 SPECT In vertebrobasilar insufficiency


                        STUDY DESIGN

                 19 PATIENTS WITH IRREDUCIBLE AAD

               Clinical assessment & Brain SPECT on admission

                   CONTROL GROUP                VBI GROUP
                       (7 PTS)                   (12 PTS)


               Transoral Odontoidectomy   Transoral Odontoidectomy
                   + Posterior Fusion         + Posterior Fusion


              Rpt SPECT at 4 weeks        Rpt SPECT at 4 weeks



AAD: Atlanto-axial dislocation
SPECT In vertebrobasilar insufficiency



Operative procedure
   Combined TOO and Occipito-cervical
    fusion from occiput to C3, using contoured
    loop and sublaminar wiring with bone
    graft placement.

   Both procedures were carried out in a
    single sitting.
SPECT In vertebrobasilar insufficiency



   Patients with reducible AAD, requiring only
    occipito-cervical fusion were excluded
    from the study to maintain pt uniformity.

   Postoperatively the neck was immobilized
    using a Philadelphia collar for a period of
    three months.
SPECT In vertebrobasilar insufficiency

    SPECT
 SPECT scanning was done using 99Tcm-ECD on
  a dual headed GE 'Varicam' scanner.
 ROI were drawn in the cerebellum and basal
  ganglia and C/BG calculated on each side.
SPECT In vertebrobasilar insufficiency

OBSERVATIONS

Radiology (Preop)
 AAD                               19
 BI                                15
 Occipitalisation of atlas         14
 Klippel-Feil anomaly              9
 Small cerebellar infarcts         2
    (Both in VBI group)
SPECT In vertebrobasilar insufficiency
                              10                             9
                               8

                               6


RESULTS
                               4

                               2         1
(Preoperative SPECT)           0
                                   Control Gp            VBI Gp

                                             Number of pts


   Decreased cerebellar perfusion in
    75% (9/12) of the patients in the
    VBI group compared to 14% (1/7)
    in the control group
    (p=0.019)
SPECT In vertebrobasilar insufficiency



RESULTS
 Following surgery, eight patients (88.9%)
  in the VBI group and none in the control
  group had improvement in cerebellar
  perfusion.
 All eight patients showing improvement on
  SPECT also had improvement in their
  symptoms of VBI following surgery
SPECT In vertebrobasilar insufficiency




 Baseline




  At 1 month
  postop
    SPECT In vertebrobasilar insufficiency



   Two pts in VBI group developed meningitis in
    the postoperative period & had a further
    decrease in cerebellar perfusion on the follow
    up SPECT scan.

   Another 2 pts in VBI group had small cerebellar
    infarcts on preop MRI & did not show
    improvement in cerebellar hypoperfusion
    following surgery.
SPECT In vertebrobasilar insufficiency



 Ours is the only study of its kind
  documenting hypoperfusion in posterior
  circulation territory in patients with CCJ
  anomalies.
 This hypoperfusion may represent a state
  of chronic VBI, expected in such patients
  & MAY BE REVERSIBLE following surgery.
SPECT In vertebrobasilar insufficiency



CONCLUSIONS

   Our study shows that rigid immobilization
    (provided by occipito-cervical fusion in our
    patients) by itself may confer protection
    from VBI
SPECT In vertebrobasilar insufficiency




RECOMMENDATION
 CCJ anomalies-potentially treatable cause
  of VBI
 Recommend that in patients with VBI, a
  high index of suspicion be kept for CCJ
  anomalies and x-rays of the cervical spine
  with flexion-extension views be done on
  all patients.
Agrawal D, Gowda NK, Bal CS, Kale SS,
Mahapatra AK. Have Cranio-Vertebral Junction
Anomalies Been Overlooked as a Cause of
Vertebro-basilar Insufficiency? Spine (In print)
Acknowledgements
 Naveen K Gowda (Nuclear Medicine)
 Prof A K Mahapatra (Neurosurgery)
THANK YOU

								
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