Abstracts

Rationale: More than 10 years ago, furosemide was found to have antiepileptic activity in a variety of animal models of acute seizures (D. Hochman et al. Science 270:99, 1995). The mechanism of this action was related to the blockade of the NKCC1 cotransporter, though other molecular targets, such as a glial cell potassium channel inward rectifier may also play a role. Clinical follow-up to this work has been limited. We evaluated the efficacy of standard doses of furosemide in a group of pediatric patients with intractable epilepsy. Methods: Patients were selected from the pediatric epilepsy clinic at Cedars-Sinai Medical Center in Los Angeles. All patients had poor seizure control, i.e. >15 seizures/month, and had failed 5 antiepileptic drugs (AED). Oral administration of furosemide was started at 1 mg/kg/day in two divided doses. If seizure control did not improve in 2 weeks, the furosemide dose was increased to 1.5 mg/kg/day. No patient exceeded 2 mg/kg/day. For the lone adult patient, a standard adult dose of 40 mg was used. A seizure log was prepared for all patients. Serum and urine electrolytes and BUN and creatinine levels were obtained 1 week, 1 month and 2 months after the start of furosemide. All patients had baseline EEG and neuroimaging studies. Results: Ten patients (4F, 6M) with intractable epilepsy were given furosemide in addition to their standard AED. The average age was 14.7 years (range: 5-42 years). Only one patient was older than 21 years. Three patients had normal intelligence, one had mild MR, one had moderate MR and five had severe MR. Seizure classification was: simple (n=1), complex partial (n=1), primary generalized (n=1) and mixed epilepsy (n=7). Seizure frequency ranged from 5-10 daily seizures to 2-3 seizures every other day before furosemide. Patients were treated with furosemide for an average of 4.6 months (range: 1-14 months). Improved seizure control occurred initially in 8/10 patients. Onset of seizure reduction was evident within 3-5 days of starting furosemide. Seizures decreased by 75-90% in 4 patients and >50% in 4 patients. Daily seizures declined to monthly seizures in half and to occasional weekly seizures in the other half. Treatment failure occurred in patients with simple partial and mixed epilepsy. In another patient, the effect was transient, lasting only 1 month, and, in another, 6 months of good seizure control ended with increasing seizure activity. Furosemide was stopped in both cases. The remainder of the patients show continued good seizure control. Electrolyte levels were normal in all patients on furosemide except one. This severely handicapped patient was fed by gastrostomy tube and required potassium supplements. Urination frequency increased for most but was not deemed a problem in light of the decreased seizures. Conclusions: Furosemide was well-tolerated and showed sustained seizure improvement in 7/10 patients with intractable epilepsy. Its rapid onset of action and freedom from cognitive side-effects make furosemide a promising novel anticonvulsant that warrants further clinical study.