Abstract
Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) and developmental EE-SWAS (DEE-SWAS) are characterized by variable combinations of cognitive, language, behavioral, and/or motor regression associated with continuous or near-continuous diffuse spike-and-wave complexes during sleep. Glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) variants have been associated with EE-SWAS. It encodes the most relevant GluN2 subunit of the N-methyl-D-aspartate receptor (NMDAR). Sulthiame reduces NMDAR-mediated neuronal excitability and has been progressively used as monotherapy in self-limited epilepsy with centrotemporal spikes (SeLECTS) or as add-ontherapy in EE-SWAS/DEE-SWAS. A five-year-old female, with family history of epilepsy, was initially diagnosed with SeLECTS and medicated with valproic acid (VPA). One year later, she presented a focal to bilateral tonic-clonic seizure during sleep and learning difficulty. The electroencephalogram revealed continuous spike-and-wave during sleep leading to the diagnosis of EE-SWAS. Prednisolone was effective, but there was repeated recurrence after its discontinuation and associated adverse effects. As an alternative, sulthiame was added to VPA. Four years later, she remains clinically stable. Genetic testing revealed a GRIN2A missense variant, C.3228C>A (p.Asn1076Lys). Sulthiame appeared effective in this recurrent EE-SWAS child, who presented a GRIN2A missense variant with possible NMDAR gain-of-function and adverse effects of corticosteroids. Functional studies of GRIN2A variants might become a future tool for individualized therapies.