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

Deepak Agrawal, K Naveen*Deepak Agrawal, K Naveen*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

AIIMS 2003AIIMS 2003

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

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

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

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

5

50

81

0

20

40

60

80

100

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)

AIIMS 2003AIIMS 2003

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®®))

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

MATERIALS AND METHODSMATERIALS AND METHODS

PROSPECTIVE STUDYPROSPECTIVE STUDY

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

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

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

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

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

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

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

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

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

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

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

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

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

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

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

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

RESULTSRESULTS

0

20

40

60

80

100

1 2 3 4 5 6 7 8

Patients

Rad

ionu

clid

e co

unt

Pre Piracetam Post PiracetamP<0.05P<0.05

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

RESULTSRESULTS

0

4 4

2

6

3

1

00

1

2

3

4

5

6

Pati

ent

Pre Piracetam Post Piracetam

AsymptomaticMildModerateSevere

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

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.

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

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

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

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.

AIIMS 2003AIIMS 2003

PIRACETAM IN MINOR HEAD INJURYPIRACETAM IN MINOR HEAD INJURY

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

THANK YOUTHANK YOU