Abstracts

Rationale: Benign Familial Neonatal Epilepsy (BFNE) is a neonatal epilepsy with favorable prognosis. Mutation of KCNQ2 accounts for the vast majority of cases. It has been demonstrated that the seizures in KCNQ2-Encephalopathy respond remarkably well to carbamazepine (CBZ). Given that the two conditions lie on opposite ends of a spectrum of disease resulting from mutations of the same gene, we evaluated the response to medication in BFNE.Methods: Retrospective clinical details of a cohort of patients with BFNE for whom neonatal records were available are presented.Results: 14 patients were identified who met criteria for BFNE. Eight patients had KCNQ2 mutations, three had KCNQ2 deletions and one had deletion in KCNQ3. Nine patients, including a set of twins, had a family history of neonatal seizures. Two patients had a family history of idiopathic generalized epilepsy in infancy, one had a family history of idiopathic focal epilepsy in childhood and one patient had a negative family history, mother being asymptomatic. Seizure onset was between 1-10 days (mean 3.6 days). Seizures were brief and focal in onset in all cases consisting of tonic and/or clonic movements, accompanied in many cases by apnea and desaturation. Seizures occurred multiple times per day in all patients and four patients developed status epilepticus. Neuroimaging and EEG background was normal in all cases. Interictal spikes were recorded in eight cases. All patients were trialed with IV loads of phenobarbital (PB) and 2/14 responded, one of whom was continued on oral PB and one of whom was switched to oral CBZ. The other 12/14 patients did not respond to IV PB. Additional treatments without response included IV pyridoxine in three patients, IV levetiracetam in two patients, and high dose IV benzodiazepines (diazepam or midazolam) in two patients. One patient did respond to IV thiopental. Two patients treated with IV phenytoin responded to the loading dose, but seizures recurred at the first attempt to wean and these patients were subsequently treated with oral CBZ. Persistence of seizures in the neonatal period was invariably associated with prolonged hospitalization. In 12/14 patients, became seizure free within hours of administration of low-dose oral CBZ (10 mg/kg/day). Treatment was initiated based on electroclinical presentation. No laboratory abnormalities or side effects were reported during treatment with CBZ. Two patients had seizure recurrence in the first year of life following an attempt to stop CBZ. Mean follow up was eight years (six months to 16 years). All patients had normal development and were seizure free after discontinuation of drugs between 12 and 18 months of life (CBZ in 12 and PB in 2. One patient developed benign epilepsy with centrotemporal spikes at three years of age, which did not respond to clobazam but responded to CBZ. Two patients developed febrile seizures.Conclusions: Our results confirm that sodium channel blockers are effective in KCNQ2 related neonatal epilepsies. Oral CBZ, though rarely used in the neonatal period, was well tolerated and rapidly effective, even in cases with status epilepticus.