A case of early-onset GABRB3-related epilepsy with characteristic EEG fast activity and its effective treatment with potassium bromide

Abstract

  The GABRB3 gene encodes the β3 subunit of the γ-aminobutyric acid (GABA) _A receptor, and its mutation causes developmental and epileptic encephalopathy. Intractable focal epilepsy associated with a characteristic interictal EEG pattern started at 2 months of age in a female pediatric patient who exhibited a novel de novo GABRB3 variant, NM_000814.5:c.778C＞A:p. (Leu260Met). Her epilepsy was characterized by multifocal onset seizures with rare migrating foci. The seizures were refractory but were suppressed at 15 months of age by the administration of potassium bromide (KBr), and she is currently seizure-free at 4 years and 5 months of age. Although her development had been stagnant during the active epilepsy period, it progressed after seizure termination ; she became able to sit by herself before 19 months and stand without support at 35 months of age. The interictal EEG continued to show unique multifocal spikes and prominent fast activity, which was observed before treatment was initiated and remarkably intensified in amplitude even after seizure suppression. We believe that her EEG pattern, which contained a large amount of fast activity, was characteristic, and we speculated that such unusual fast activity might be related to dysfunction of the GABA system associated with the GABRB3 variant. This is the first report on the efficacy of KBr in GABRB3-related epilepsy, and it suggests a treatment option for this intractable epilepsy.