SCN2A encephalopathy clinical and electroencephalographic response to ketogenic diet: a case report

*Correspondence: [e-mail].

Abstract

Case Presentation: A two-year-old presented with refractory seizures since the neonatal period. She was born at 37 weeks to unrelated healthy parents and had clinical seizures since the 18th day of life associated with developmental delay. Gene testing revealed a pathogenic variant in the SCN2A gene at chr2:165.313.655 G>GT. Electroencephalogram (EEG) showed persistent paroxysms of multifocal epileptiform activity intermixed with high amplitude and irregular theta slow wave constituting a discontinuous pattern of “pseudo burst-suppression”, typical of SCN2A-developmental and epileptic encephalopathy (DEE). She had been treated with Phenobarbital, Valproate, Levetiracetam and Clobazam with no response. High dose carbamazepine partially reduced the seizure frequency, but she persisted with at least ten events per day. Classic ketogenic diet was started and after a week of 3:1 ratio the patient became completely seizure-free. Besides seizure control, epileptiform discharges disappeared from EEG and cerebral electrical activity almost normalized, with only mild background abnormality remaining.

Discussion: Mutations in the SCN2A gene have been associated with a number of encephalopathy phenotypes, and are often related to refractory epilepsy. Sodium-blockers may reduce the seizures in patients with gain-of-function mutations, but seizure-freedom is extremely rare in this phenotype. In our report, the infant had never achieved full control of the seizures until the introduction of ketogenic diet. Importantly, the interictal epileptiform discharges on EEG also completely disappeared. Normalization of EEG patterns in the DEEs is the exception. Since there is at least a theoretical understanding that frequent epileptiform discharges contribute to the encephalopathy in these patients, treatments that improve not only clinical seizures but also the EEG abnormalities are very much needed.

Final Comments: Despite the lack of larger scale studies, we believe ketogenic diet could be an early choice in treatment of refractory epilepsy related to the SCN2A gene when antiepileptic drugs are ineffective.

Publication History

Article published online:
12 May 2025