Topiramate in drug‐resistant complex partial status epilepticus

Dear Sir, Options for the maintenance of anticonvulsant therapy have increased considerably over recent years but complex partial status epilepticus (CPSE) sometimes remains dicult to treat. We report a patient who responded to topiramate after diazepam, phenytoin, carbamazepine, clobazam, paraldehyde, sodium valproate, phenobarbitone and thiopentone anaesthesia had failed. Eight days after a nephrectomy for renal carcinoma, a 68-year-old female with no previous history of epilepsy suered bilateral occipital infarcts, perhaps secondary to basilar artery thrombosis. She developed cortical blindness and had three generalized tonic clonic seizures (GTCS). She received intravenous (iv) diazepam and phenytoin (15 mg/kg followed by 400 mg/day). On day 12 post-op she had a further GTCS and frequent complex partial seizures (CPS) characterized by right-sided jerking associated with reduced consciousness. The electroencephalogram (EEG) showed generalized slowing with an active left parieto-occipital sharp wave focus. The addition of clobazam (30 mg/ day) and carbamazepine (400 mg/day) had no eect. On day 21 post-op the patient was transferred to a neurological centre having several CPS per hour. The EEG showed almost continuous generalized epileptiform discharges with left-sided emphasis, consistent with CPSE. Increasing phenytoin to the usual treatment range or giving diazepam 10 mg iv had no electroclinical eects. The addition of iv sodium valproate (600 mg followed by 1600 mg/day, serum level 65mg/l) did not help. Paraldehyde, 10 mg per rectum, had no eect. On day 29, the patient was intubated and given thiopentone (450 mg followed by an infusion titrated to burst suppression pattern for 24 h). After discontinuation of thiopentone, the EEG reverted to electrical status epilepticus with frequent left-dominant spike wave discharges and periods of generalized epileptiform activity. Phenobarbitone had no eect (600 mg/day for 4 days followed by 300 mg/day, serum level 38.3 mg/l). On day 37, a trial of extubation failed. On day 38 topiramate 400 mg twice daily was commenced by nasogastric tube. Within 2 days the EEG changed signi®cantly, the background activity was faster, epileptiform discharges were now intermittent and multifocal and there were no more generalized discharges. Three days after starting topiramate the patient was extubated. One day later the topiramate dose was reduced to 400 mg/ day. Ten days after commencing this drug the EEG showed no epileptiform changes. At the time of discharge 6 weeks later, she had been seizure-free for 7 weeks. Our patient developed drug-resistant CPSE following bilateral occipital infarction. Complex partial status epilepticus could not be controlled with conventional anticonvulsant treatment. In the past, propofol (Brown and Levin, 1998), lidocaine (Walker and Slovis, 1997), midazolam (Hanley and Kross, 1998), chloral hydrate (Lampl et al., 1990), lamotrigine (Pisani et al., 1991) and ketamine (Sheth and Gidal, 1998) have been recommended for use in drug-resistant convulsive status epilepticus (SE). We tried topiramate on account of its potency in focal epilepsies (Marson et al., 1997). Animal experiments have demonstrated the possible usefulness of this drug in SE (Niebauer and Gruenthal, 1999). We observed a de®nite electroclinical improvement in our patient, shortly after starting topiramate. Whilst it is possible that commencement of topiramate coincided with a natural resolution of the condition, we feel justi®ed in recommending a trial of topiramate in the treatment of CPSE when more conventional treatments have failed.