Use of ketogenic diet in patients with SCN8A-related epilepsy: report in two clinical cases

Purpose: To describe ketogenic diet (KD) efficacy in two patients with drug-resistant epilepsy suffering from SCN8A -related developmental and epileptic encephalopathy. Method: We performed a retrospective evaluation collecting electroclinical data. Results: Patient 1 presented at age 4 months with subsequent seizures characterised by generalized hypertonus, desaturation, cyanosis and staring. EEG showed theta-delta activity and isolated bilateral fronto-temporal delta-waves and spikes. Psychomotor development remained normal until 10 months of age when, after status epilepticus, he lost previously-acquired developmental milestones and EEG deteriorated. He developed drug-resistant epilepsy, despite therapeutic approaches with phenytoin, nitrazepam, oxcarbazepine, lamotrigine and carbamazepine, the latter at supramaximal dosage according to literature. At age 15 months KD was added and seizures’ duration and frequency progressively lowered in accordance with KD ratio increase. At last follow-up, he has been seizure-free for six months and EEG showed physiologic sleep pattern. Patient 2 presented at 4 months with subsequent seizures characterised by generalised tonic-clonic jerks, loss of consciousness and desaturation, followed by high frequency seizures. He showed severe developmental delay, with wax and wane in his ability according to seizures’ frequency. EEG showed diffuse, unresponsive delta-band activity and no differentiation between wakefulness and sleep. Focal evolving to generalised tonic-clonic seizures persisted with multiple-daily frequency. Several antiseizures medication were tried: phenobarbital, valproic acid, topiramate, and oxcarbazepine, the latter at supramaximal dosage. At the age of 27 months KD was introduced and marked reduction in seizure frequency was recorded, with up to two weeks seizure freedom periods. The last EEG showed diffused theta activity with sporadic epileptic discharges. Conclusion: Evidence of KD’s efficacy in patients with SCN8A -related epilepsy was reported in few anecdotal cases (Gardella et al. Neurology , 91(12), E1112–E1124), however the precise action mechanism and long-term efficacy are not yet known. In this study we describe two cases in which KD showed a significant positive electro-clinical effect.