*Correspondence: isabellecastellano@gmail.com.
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.
