Successful treatment of intractable life-threatening seizures with perampanel in the first case of early myoclonic encephalopathy with a novel de novo SCN1A mutation

Abstract

Early myoclonic encephalopathy (EME) is a form of developmental and epileptic encephalopathy with myoclonic seizures and a suppression burst on electroencephalogram, which occurs during the neonatal or early infantile period and is characterized by highly intractable seizures and severe development impairment. Although multiple genetic aetiologies of EME have been identified, no SCN1A mutation has been reported. Methods: We described a female patient with EME due to an SCN1A mutation. Results: She developed frequent myoclonic and apnoeic seizures during the neonatal period. As her seizures were refractory to many antiepileptic drugs, she underwent a tracheotomy and has since been treated with continuous mechanical ventilation. Eventually, perampanel was added, which resulted in the cessation of the apnoeic seizures. Genetic analysis revealed a heterozygous de novo missense mutation in the SCN1A gene (c.2588 T > C:p.Leu863Ser). Conclusion: This is the first patient with EME due to anSCN1A mutation to be successfully treated with perampanel. Recently, perampanel was reported to be effective in treating Dravet syndrome, including cases with an SCN1A mutation. Perampanel may contribute to seizure reduction in patients with intractable epilepsy carrying the SCN1A mutation.

Long-term Efficacy of Perampanel in a Child with Dravet Syndrome

“…Besides, Ishikawa reported a newborn with an early myoclonic epilepsy with a SCN1A mutation with excellent response to perampanel, suggesting that this effect could be also SCN1A-mutation-specific. 18 However, up to 33% of patients in the previous reports showed no benefit or even deterioration with perampanel in patients with mutations in SCN1A. [12][13][14][15][16][17] More studies are needed to investigate if there is an association between the response to certain drugs as perampanel and the patient's genotype.…”

Precision Medicine: from Molecular Diagnoses to Treatment Opportunities in Medical Genetics

“…A girl with frequent myoclonic and apneic seizures during the neonatal period (early myoclonic encephalopathy) and a heterozygous de novo missense mutation in the SCN1A gene (c.2588 T > C:p.Leu863Ser) responded well to a combination of potassium bromide, phenobarbital, clobazam, and perampanel, after phenytoin (followed by phenobarbital) provided transient effects and topiramate, clonazepam, potassium bromide, and cloba-zam (administered serially) exerted little effect [Ishikawa et al, 2019]. Perampanel is a noncompetitive α-amino-3hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist.…”