The effects of malignant glioma on the EEG and seizure thresholds: an experimental study.
Generalised or partial seizures are a common problem with many supratentorial gliomas. Their underlying pathophysiological mechanisms are poorly understood. To investigate this problem clinical and EEG seizure thresholds were investigated in experimental rodent gliomas using the epileptogenic drug pentylenetetrazole (PTZ). Mixed C6/A15A5 malignant gliomas were grown in adult Wistar rats after unilateral stereotactic implantation of a 50:50 cell mix into the caudoputaminal region. Eleven to 14 days later EEG (raw and spectrally analysed) was recorded bilaterally from the frontal and parietal regions under mixed alpha-chloralose and urethane anaesthesia. Baseline EEG (15 minutes), EEG during and after (30 minutes) PTZ infusion (100 microliters/min) and the time to appearance of seizure manifestations after starting PTZ were recorded. Fourteen animals were studied (5 normal, 5 with tumours, 4 sham implants) and mean BP, PaCO2, PaO2 and temperature were similar in the three groups. Baseline raw EEG showed predominate slow wave activity with lower amplitude and less spontaneous activity overlying tumours. Following PTZ infusion a sequence of vibrissal twitching (following a mean of 14.5 mg/kg PTZ in control and sham animals); jaw/nasal twitches (17.5 mg/kg); fore and hind limb jerking (46 mg/kg); myoclonic jerking (47 mg/kg); and status (77.5 mg/kg) was observed. The seizure thresholds for all PTZ induced seizure phenomena were, except for status epilepticus, highest in the tumour bearing animals. The time to 70% seizure activity on the EEG was also significantly longer in the tumour bearing animals. Spectral analysis of the EEG, although showing increased alpha and theta activity after PTZ infusion, did not discriminate between the three experimental groups either before or after PTZ activation. These studies have confirmed that experimental gliomas alter baseline EEG and both the EEG and behavioural response to PTZ. The reasons for the raised seizure threshold in the glioma bearing animals and the relevance of this experimental paradigm to human tumour associated epilepsy are discussed.
Beaumont
A
A
Department of Clinical Neurosciences, Western General Hospital, Edinburgh, U.K.
Clarke
M
M
Whittle
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IR
D000328:Adult; D000818:Animals; D001931:Brain Mapping; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D003292:Convulsants; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005910:Glioma / Q000503:physiopathology*; D006801:Humans; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009368:Neoplasm Transplantation; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D012815:Signal Processing, Computer-Assisted; D015173:Supratentorial Neoplasms / Q000503:physiopathology*
D003292:Convulsants; D010433:Pentylenetetrazole