Chronic levetiracetam treatment early in life decreases epileptiform events in young GAERS, but does not prevent the expression of spike and wave discharges during adulthood.
OBJECTIVE
In Genetic Absence Epilepsy Rats from Strasbourg (GAERS), age-related absence seizures start to appear from postnatal day (PN) 30 concomitant with 'spike and wave discharges' (SWDs) appearing on cortical EEG recordings. The aim of this study was to investigate the effect of early chronic levetiracetam (LEV) treatment on the development of SWDs in young and adult GAERS.


METHODS
From PN 23 until PN 60, LEV (54 mg/kg, i.p.) was administered once daily to GAERS (n=8), while control GAERS (n=7) received saline (0.9% NaCl, i.p.). All animals were implanted with four epidural EEG electrodes at PN 51. EEG was recorded for 3h daily, during the last 4 days of the treatment (PN 57-PN 60) and during 4 additional days after treatment had been terminated (PN 61-PN 64). The animals were monitored again at the age of 4 months (PN 120-PN 124), about 2 months after the last administration of LEV.


RESULTS
During treatment, epileptiform events in the LEV group were significantly reduced (62%, P<0.05) in comparison with the control group. During the following 4 days, epileptiform events were reduced in the LEV group, with an average difference of 53% (P=0.064). Once the animals had reached adult age, there was no difference in epileptiform events between the LEV group and controls.


CONCLUSIONS
In this study, chronic LEV administration induced a reduction in epileptiform events in young GAERS. This effect persisted to some extent after treatment cessation (PN 61-PN 64), which might indicate a slowing down of epileptogenic processes. However, at the age of 4 months all animals revealed a similar expression of epileptiform discharges.
Dedeurwaerdere
Stefanie
S
Laboratory for Clinical and Experimental Neurophysiology and Reference Centre for Refractory Epilepsy, Department of Neurology, Ghent University Hospital, Ghent, Belgium. Stephanie.Dedeurwaedere@UGent.be
Boon
Paul
P
De Smedt
Tim
T
Claeys
Pieter
P
Raedt
Robrecht
R
Bosman
Tommy
T
Van Hese
Peter
P
Van Maele
Georges
G
Vonck
Kristl
K
D000375:Aging / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001921:Brain / Q000254:growth & development; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics*; D000077287:Levetiracetam; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains
D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam