A case report of hemimegalencephaly with super-refractory status epilepticus and brain atrophy associated with NPRL3 gene mutation.

Abstract

Hemimegalencephaly (HME) is a congenital malformation of cortical development (MCD) commonly associated with early-onset refractory epilepsy. Early functional hemispherotomy is offered to eligible patients with the goal to provide seizure control and improve neurologic outcomes [ [1] Honda R Kaido T Sugai K Long-term developmental outcome after early hemispherotomy for hemimegalencephaly in infants with epileptic encephalopathy. Epilepsy Behav. 2013; 29: 30-35 Abstract Full Text Full Text PDF PubMed Google Scholar ]. Mutations in the GATOR1 protein complex, including the nitrogen permease regulator 3-like protein (NPRL3) gene, cause hyperactivation of the mammalian target of rapamycin (mTOR) signaling pathway, and represent a potential therapeutic target (e.g., mTOR inhibitors) for HME-related epilepsy [ [2] Vawter-Lee M Franz DN Fuller CE Clinical Letter: A case report of targeted therapy with sirolimus for NPRL3 epilepsy. Seizure. 2019; 73: 43-45 Abstract Full Text Full Text PDF PubMed Google Scholar ]. We report an infant with HME and super-refractory status epilepticus (SRSE) secondary to NPRL3 gene mutation who received adjuvant sirolimus therapy without achieving seizure control. Unexpectedly, follow-up neuroimaging showed marked global brain atrophy precluding surgical intervention.