Abstracts

RATIONALE: Tiagabine (TGB) is an anti-epileptic drug with a novel mechanism of action to block the pre-synaptic reuptake of the inhibitory neurotransmitter, GABA. Several cases of non-convulsive status epilepticus have been reported in connection with TGB, initially in patients with generalized seizures but more recently in patients with partial epilepsies. METHODS: Two cases of TGB associated stupor have been observed. Both cases had their epilepsy syndromes well characterized with inter-ictal EEG, EEG-video monitoring, and MRI. EEG-video monitoring occurred during both cases of stupor. RESULTS: Case 1 was an 18 year old man with partial seizures since the age of 18 months. Interictal EEG showed right temporal sharp waves. Pathology report after right temporal lobectomy indicated a hamartoma. Seizures, a throat sensation and then altered awareness, recurred during medication taper. His seizures remained refractory and tiagabine was added. TGB was increased to a total daily dose of 72 mg/day. He developed an episode of altered awareness and lip smacking beginning one hour after a tiagabine dose. Video showed a young man tremulous with lip smacking who was verbally unresponsive. EEG showed long runs of spike-wave at 1.5 Hz. He, and his EEG, showed rather sudden improvement about two hours after symptom onset. TGB was lowered to 48 mg/day without recurrence of stupor. Case 2 was a 65 year old woman admitted for EEG-video monitoring for 40 years of refractory seizures. MRI showed no significant lesion. A seizure was recorded with loss of awareness and prominent lip smacking with EEG showing evolution of rhythmic theta over the right temporal derivations. On the day of discharge, she inadvertently received 64 mg of TGB. One hour later she was verbally unresponsive and tremulous. EEG showed high amplitude delta slowing admixed with frontal sharp and slow waves. The symptoms resolved over about 24 hours. CONCLUSIONS: TGB at high doses may produce a state of unresponsiveness associated with lip smacking and tremulousness. EEG shows bifrontal sharp and slow waves. This TGB effect may be due to excessive activity at GABA-B receptors in thalamocortical circuits.