Abstracts

RATIONALE: Whether the cerebral cortex or subcortical structures, specifically the thalamus, play the dominant role in generating primary generalized seizures has been the subject of long debate. Most experimental data supports a predominant role for cerebral cortex in generation of the spike and wave activity, with the thalamus quickly recruited to sustain generalized spike and wave oscillations in a reverberating thalamocortical network. A focal cortical generator or a multifocal cortical [dsquote]hyperexcitability[dsquote] have been postulated to underlie the presumed cortical initiation. There is little clinical evidence to support either of these hypotheses. We present video-EEG recordings of 6 generalized tonic-clonic seizures in 3 patients with proven primary generalized epilepsy (PGE), all of whom showed a consistent pattern of lateralized seizure onset compatible with a unifocal frontal lobe generator.
METHODS: Among 300 patients referred for video-EEG monitoring, 3 were found to have PGE with tonic-clonic convulsions. All had a positive family history for epilepsy and no other epilepsy risk factors. Epilepsy onset was during childhood (1/3) or adolescence (2/3): duration was 35, 19 and 5 years. All had absence spells and tonic-clonic convulsions; 1 had occasional myoclonic absences accompanying daily morning myoclonic jerks. Patients were taking 1-4 AEDs at admission, none of which was valproic acid. 2/3 are now seizure free on valproate monotherapy (f/u [gt]12 months). One patient refused valproate but has improved on lamotrigine and phenobarbital.
RESULTS: Interictal EEG showed very active bilaterally synchronous generalized spike and wave or polyspike and slow wave discharges between 2.5-4.5 Hz, maximal over the midfrontal structures symmetrically in all patients. Coherence analyses showed no hemispheric time leads. Ictal EEG showed a generalized tonic recruiting pattern maximal over the anterior hemispheres without lateralization. Surprisingly, in all 6 recorded tonic-clonic seizures there was a distinct, stereotyped, sustained (10-15 seconds) clinical lateralization at onset which took the form of a tonic [dsquote]fencing posture[dsquote] in 2 patients (3 seizures) and forced head/eye/torso version in the third (3 seizures).
CONCLUSIONS: Tonic-clonic seizures are presumed to be generalized from onset in patients with PGE. However, because patients with PGE are not surgical candidates video-EEG is rarely performed, and the clinical features of primary generalized seizures are likely underappreciated. The findings of distinct and sustained lateralization at onset, with features clinically indistinguishable from focal onset frontal lobe seizures, is compatible with the hypothesis of a focal region of cortical [dsquote]hyperexcitability,[dsquote] situated in the frontal lobes of patients with PGE. Whether this cortical generator is autonomous or [dsquote]triggered[dsquote] by ascending, possibly normal, thalamocortical volleys is unresolved, but a cortical predominance for the generation of tonic-clonic seizures in PGE appears evident.
Objective: At the end of this activity participants should be able to discuss thalamocortical relationships in primary generalized epilepsy, with video data illuminating the clinical features of primary generalized seizures.
[Supported by: Bloorview Epilepsy Research Program (PC, RW)]