RESUMEN
OBJECTIVE: Pathogenic variants in SCN8A have been associated with a wide spectrum of epilepsy phenotypes, ranging from benign familial infantile seizures (BFIS) to epileptic encephalopathies with variable severity. Furthermore, a few patients with intellectual disability (ID) or movement disorders without epilepsy have been reported. The vast majority of the published SCN8A patients suffer from severe developmental and epileptic encephalopathy (DEE). In this study, we aimed to provide further insight on the spectrum of milder SCN8A-related epilepsies. METHODS: A cohort of 1095 patients were screened using a next generation sequencing panel. Further patients were ascertained from a network of epilepsy genetics clinics. Patients with severe DEE and BFIS were excluded from the study. RESULTS: We found 36 probands who presented with an SCN8A-related epilepsy and normal intellect (33%) or mild (61%) to moderate ID (6%). All patients presented with epilepsy between age 1.5 months and 7 years (mean = 13.6 months), and 58% of these became seizure-free, two-thirds on monotherapy. Neurological disturbances included ataxia (28%) and hypotonia (19%) as the most prominent features. Interictal electroencephalogram was normal in 41%. Several recurrent variants were observed, including Ile763Val, Val891Met, Gly1475Arg, Gly1483Lys, Phe1588Leu, Arg1617Gln, Ala1650Val/Thr, Arg1872Gln, and Asn1877Ser. SIGNIFICANCE: With this study, we explore the electroclinical features of an intermediate SCN8A-related epilepsy with mild cognitive impairment, which is for the majority a treatable epilepsy.
Asunto(s)
Epilepsia/genética , Mutación Missense , Canal de Sodio Activado por Voltaje NAV1.6/genética , Anticonvulsivantes/uso terapéutico , Ataxia/genética , Niño , Preescolar , Disfunción Cognitiva/genética , Electroencefalografía , Epilepsia/tratamiento farmacológico , Epilepsia/fisiopatología , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Discapacidad Intelectual/genética , Trastornos del Desarrollo del Lenguaje/genética , Trastornos del Movimiento/genética , Hipotonía Muscular/genética , Linaje , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Hemidecortication is a therapeutic option in patients with drug-resistant structural epilepsy. If surgery is performed early enough in left-hemispheric pathology, the plasticity of the developing brain may enable the right hemisphere to take over language-if this has not occurred before surgery. A systematic overview of potential predictors of language outcome after left hemidecortication in children is warranted. METHODS: In a systematic literature review, we analyzed 58 studies on language lateralization after congenital or postneonatally acquired left-hemispheric pathology, and on language outcome after left-sided hemidisconnection, such as hemispherotomy. Single-subject data were pooled to determine the distribution of lateralization across etiologies in congenital lesions and across age groups in acute postneonatal lesions. A hierarchical linear regression assessed the influence of age at surgery, lesion type, age at seizure onset, and presurgery language function on language outcome after left hemidecortication. RESULTS: In acute postneonatal lesions, younger age at injury was significantly associated with right-sided language lateralization (Cramér V = 0.458; p = 0.039). In patients with hemidecortication, age at surgery was not significantly associated with language outcome (Cramér V = -0.056; p = 0.584). Presurgical language function was the most powerful predictor for postsurgical language outcome (F 4,47 = 7.35, p < 0.0001), with good presurgical language bearing the risk of postsurgical deterioration. In congenital pathology, right-sided language lateralization was most frequent in pre-/perinatal stroke (Cramér V = 0.357; p < 0.0001). CONCLUSIONS: We propose a presurgical decision algorithm with age, presurgical language function, language lateralization, and left-hemispheric structural pathology as decision points regarding surgery.