ROLE OF PIRACETAM IN POST-CONCUSSION SYNDROME A PROSPECTIVE RANDOMIZED STUDY

Deepak Agrawal, K Naveen*, CS Bal*, Deepak Agrawal, K Naveen*, CS Bal*, AK MahapatraAK Mahapatra

Departments of Neurosurgery* and Nuclear Departments of Neurosurgery* and Nuclear medicine*,medicine*,

ALL INDIA INSTITUTE OF MEDICAL ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIASCIENCES, NEW DELHI, INDIA

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INTRODUCTIONINTRODUCTION Post-concussion syndrome remains a Post-concussion syndrome remains a

poorly understood and treated poorly understood and treated conditioncondition

We describe a trial with We describe a trial with ‘‘piracetampiracetam’’, a , a drug drug which has beneficial effects on the CBF by decreasing the adhesivity, aggregation, and deformability of erythrocytes along with flow thrust tension of the blood

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PREVIOUS STUDIES ON PIRACETAM IN PREVIOUS STUDIES ON PIRACETAM IN MINOR HEAD INJURY WERE BASED MINOR HEAD INJURY WERE BASED ONLY ON ‘SUBJECTIVE CRITERIA’ONLY ON ‘SUBJECTIVE CRITERIA’

FIRST STUDY OF ITS KIND BASED ON FIRST STUDY OF ITS KIND BASED ON AN OBJECTIVE PARAMETER LIKE BRAIN AN OBJECTIVE PARAMETER LIKE BRAIN SPECTSPECT

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5

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81

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Investigation

CT Head MRI Brain SPECT

SENSTIVITYSENSTIVITY

•CT scan: 4.6%CT scan: 4.6%(Nedd K et al, 1993)

•MRI: 60%MRI: 60%((Kant R et al, 1997)

•SPECT: 81%SPECT: 81%(Present study)(Present study)

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OBJECTIVEOBJECTIVE

To correlate the symptomatic To correlate the symptomatic improvement with Single Photon improvement with Single Photon Emission Computed Tomography Emission Computed Tomography (SPECT) findings, in patients with post-(SPECT) findings, in patients with post-concussion syndrome (PCS), following concussion syndrome (PCS), following administration of Piracetam administration of Piracetam (Cerecetam(Cerecetam®®))

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MATERIALS AND METHODSMATERIALS AND METHODS

PROSPECTIVE STUDYPROSPECTIVE STUDY

PERIOD- JAN 2002 TO DEC 2002 PERIOD- JAN 2002 TO DEC 2002

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1. Loss of consciousness <30 1. Loss of consciousness <30 minutes.minutes.2. GCS score 13 to 15.2. GCS score 13 to 15.3. Posttraumatic amnesia <24 3. Posttraumatic amnesia <24 hours.hours.

MINOR HEAD INJURYMINOR HEAD INJURY

[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

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HeadacheHeadache Dizziness and vertigoDizziness and vertigo Memory deficitsMemory deficits Behavioral and emotional disturbances.Behavioral and emotional disturbances.

POST CONCUSSION SYNDROME:POST CONCUSSION SYNDROME:

(2 or more of the following)(2 or more of the following)

DSM IV criteria based on recommendation of Brown et al.DSM IV criteria based on recommendation of Brown et al.

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

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MATERIALS AND METHODS (Contd.)MATERIALS AND METHODS (Contd.)

NCCT headNCCT head

INVESTIGATIONINVESTIGATION

SPECT scan brainSPECT scan brain

Within 72 hours of injuryWithin 72 hours of injury

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SPECT scanning was done using SPECT scanning was done using 99Tcm-ECD on a dual headed GE 99Tcm-ECD on a dual headed GE 'Varicam' scanner.'Varicam' scanner.

The final data was displayed on a 10 The final data was displayed on a 10 grade color scale and semi grade color scale and semi quantitative analysis performed. quantitative analysis performed.

SPECTSPECT

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Regional cerebral perfusion <10% of Regional cerebral perfusion <10% of contralateral lobe, or in case of bilateral contralateral lobe, or in case of bilateral involvement, less than 20% of cerebelluminvolvement, less than 20% of cerebellum

ABNORMAL SPECT ABNORMAL SPECT SCANSCAN

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MATERIALS AND METHODS (Contd.)MATERIALS AND METHODS (Contd.)

C LIN IC AL EVALU AT IO N &R EPEAT SPEC T AT 6 W EEK S

2.4 gm s P IR AC ET AM(C ereceta m )

T D S x 6 W EEK S

10 PAT IEN T S

PIR AC ET AM G R O U P

C LIN IC AL EVALU AT IO N &R EPEAT SPEC T AT 6 W EEK S

N O P IR AC ET AM

10 PAT IEN T S

C O N T R O L G R O U P

20 PAT IEN T SW IT H PO ST C O N C U SSIO N SYN D R O ME & AB N O R MAL SPEC T

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Significant rise in the post treatment ratio in the piracetam group (mean: 0.959) as compared to the controls (mean: 0.013)

(p= <.00195% CI -0.0114, -0.038 ).

RESULTSRESULTS

0.013

0.959

Piracetam Group Control group

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RESULTSRESULTS

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Patients

Rad

ionu

clid

e co

unt

Pre Piracetam Post PiracetamP<0.05P<0.05

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RESULTSRESULTS

0

4 4

2

6

3

1

00

1

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Pati

ent

Pre Piracetam Post Piracetam

AsymptomaticMildModerateSevere

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SPECT have been found to persist for as long as one year following minor head injury (Jocobs A, et al, 1996)

Serial SPECT scanning can therefore provide an ideal platform to test the efficacy of various drugs in reversing these perfusion abnormalities in PCS.

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Piracetam

More than 12 g of piracetam has been given as daily dose in acute stroke (De Deyn PP et al, 1997) without significant side effects

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CONCLUSIONSCONCLUSIONS 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.

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THIS PRELIMINARY STUDY SHOWS THAT LOW DOSE PIRACETAM CAN BENEFIT PATIENTS WITH POSTCONCUSSION SYNDROME COST-EFFECTIVELY & WITHOUT APPRECIABLE SIDE EFFECTS.

CONCLUSIONS (Contd.)CONCLUSIONS (Contd.)

A RANDOMISED CONTROLLED TRIAL IS A RANDOMISED CONTROLLED TRIAL IS PRESENTLY UNDERWAY FOR MORE DEFINITIVE PRESENTLY UNDERWAY FOR MORE DEFINITIVE RESULTSRESULTS

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