睡眠時棘徐波活性化を示す発達性てんかん性脳症及びてんかん性脳症

A 10-year-old boy with a 6-year history of recurrent seizures and cognitive decline was diagnosed with developmental and epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS). Previous treatments involving multiple anti-seizure medications and repeated high-dose methylprednisolone only provided temporary efficacy. Three weeks ago, he was misdiagnosed with non-convulsive status epilepticus (NCSE) at another hospital due to electrical status epilepticus during sleep (ESES) on electroencephalography (EEG). He was then put into an anesthesia-induced coma in order to convert the EEG to burst-suppression. However, this intervention resulted in severe complications, including ventilator-associated pneumonia. Discontinuing the anesthetics and sedatives, and adjusting his antiepileptic treatment regimens promoted his recovery. Although his seizures resolved, the ESES persisted on EEG. Furthermore, the prolonged induced coma impaired his neurological function, and the stay in intensive care unit imposed a significant medical burden. This case cautions carefully differentiating between ESES and NCSE, and against overreliance on EEG "normalization" without a rigorous risk-benefit assessment of anesthesia-induced coma.

Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS) represents a rare but severe group of childhood onset epilepsies characterized by sleep-potentiated epileptiform activity, seizures, and developmental stagnation or regression affecting cognition, language, and behavior. Once considered a self-limited electroencephalographic (EEG) phenomenon, D/EE-SWAS is now recognized as a disorder of brain network dysfunction in which persistent epileptiform discharges during non-rapid eye movement sleep disrupt synaptic plasticity, sleep-dependent memory consolidation, and neurodevelopmental trajectories. This review synthesizes recent advances in clinical phenotyping, genetics, neurophysiology, and therapeutics. Etiologically, D/EE-SWAS is highly heterogeneous, with pathogenic variants identified in nearly half of affected individuals, including copy number variants and single-gene disorders involving ion channels, synaptic proteins, and transcriptional regulators. GRIN2A is the most frequently implicated gene, although marked intrafamilial and interfamilial variability underscores the role of modifying genetic and network-level factors. Structural lesions-particularly those affecting thalamocortical circuits-represent another major disease substrate and are critical for treatment stratification. At the mechanistic level, abnormal thalamocortical oscillations, impaired sleep architecture, and disruption of slow-wave and spindle activity provide a pathophysiological framework linking EEG abnormalities to cognitive and behavioral deterioration. Neuroimaging and EEG-functional magnetic resonance imaging studies support a model of widespread network inhibition and disconnection extending beyond the primary epileptogenic zone. Therapeutically, corticosteroids currently represent the most effective first-line treatment, demonstrating superior cognitive outcomes compared with benzodiazepines, although relapse after tapering is common, and optimal dosing strategies remain undefined. Precision medicine approaches, including N-methyl-D-aspartate receptor-targeted therapies for GRIN variants and channel-specific treatments such as primidone for TRPM3 gain of function, offer promising avenues toward disease modification. Epilepsy surgery should be considered early in children with unilateral structural etiologies, where it can provide substantial neurodevelopmental benefit. Future priorities include standardized outcome measures, integration of sleep-based biomarkers, refinement of steroid protocols, and international collaborative trials to improve long-term neurodevelopmental outcomes in this vulnerable population.

INTRODUCTION: Previous research suggests that amantadine could be effective as an antiepileptic drug. We evaluate the use of the drug in children with refractory generalised epilepsy. METHOD: Retrospective study of children with developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS) or generalised epilepsy with refractory absence seizures treated with amantadine at a paediatric hospital in Madrid, Spain, over a 3-year period. RESULTS: We studied 12 children treated with amantadine for refractory epilepsy at a median age of 9.5 years (range, 3-11) and a median disease duration of 5 years (range, 1-8). Before initiation of amantadine, the patients had received 9.4 antiepileptic drugs on average (range, 6-14), and 9 had been placed on a ketogenic diet. Brain MRI displayed no structural lesion in any patient, except for one with a thalamic lesion. All patients had idiopathic epilepsy, and MRI results were normal. Five were diagnosed with D/EE-SWAS, and 7 had generalised epilepsy with refractory absence seizures (5 with refractory absence epilepsy, one with eyelid myoclonia with absence seizures, and one with Lennox-Gastaut syndrome). Amantadine was added to other antiepileptic drugs (mean number of drugs administered, 2.7) at a mean dose of 5.6mg/kg/day, with a maximum dose of 300mg/day. In the group with D/EE-SWAS, amantadine therapy achieved EEG activity normalisation and seizure control (myoclonic and absence seizures) in 80% (4/5). Among the patients with refractory epilepsy, only one (14.2%) achieved seizure control (75-99% response). One patient (10%) developed adverse effects (irritability and insomnia), leading to withdrawal of amantadine. CONCLUSION: Amantadine is an effective and safe treatment for drug-resistant generalised epilepsy, especially in patients with D/EE-SWAS.

BACKGROUND: The clinical manifestations and genotype-phenotype correlations of KCNA2 variants in epilepsy patients, particularly those with spike-and-wave activation in sleep (SWAS), remain poorly characterized. METHODS: We analyzed clinical data from our 18 patients with KCNA2 variants and conducted a comprehensive literature review of cases with complete clinical data, resulting in a total of 77 patients. For genotype-phenotype correlation analysis, patients were categorized based on variant localization. Additionally, we summarized and analyzed the clinical characteristics and treatment of 14 patients with SWAS. RESULTS: All our 18 patients presented with epilepsy, with a median seizure onset age of 6 months. Intellectual disability was observed in 83.3% of patients, and developmental delay in 77.8%. Abnormal electroencephalography findings were present in 94.4% of patients, with 44.4% exhibiting SWAS. Genotype-phenotype analysis of total 77 patients revealed that variants in the pore domain were significantly associated with higher rates of motor disorders (P = 0.007) and SWAS (P < 0.001), while S1-S4 segment variants showed a higher incidence of magnetic resonance imaging abnormalities (P = 0.049). Among 18.2% (14/77) patients with SWAS (12 with p. Pro405Leu, one with p. Val369Phe and one with p. Ile409Phe/Leu), only 42.9% responded effectively to treatment, with 28.6% developing drug-resistant epilepsy. Valproic acid was the most commonly prescribed medication, and combination therapies showed promising results in some cases. CONCLUSIONS: Our findings provide strong evidence supporting the association between KCNA2 pathogenic variants and SWAS. The high prevalence of SWAS in our cohort and literature review highlights the importance of considering KCNA2 variants in diagnosing patients with SWAS.

Auditory-triggered motor events in infancy present a significant diagnostic challenge due to overlap between epileptic and non-epileptic startle phenomena. We report the case of a term female infant with neonatal-onset seizures and subsequent development of reproducible sound-triggered jerky movements, raising diagnostic uncertainty between exaggerated startle reflex and reflex auditory epilepsy. The child initially presented with seizures on the third day of life and was treated with phenobarbital. During early infancy, brief motor events consistently precipitated by sudden auditory stimuli were observed, later accompanied by spontaneous seizures and developmental plateauing. Serial electroencephalography (EEG) revealed evolution from focal frontotemporal interictal epileptiform discharges to multifocal epileptiform activity with marked sleep activation, while repeated brain magnetic resonance imaging remained structurally normal. Over time, global developmental delay with hypotonia and impaired motor milestones became evident. The electroclinical trajectory suggested an evolving epileptic encephalopathy within the epileptic encephalopathy with spike-wave activation in sleep spectrum, despite the absence of a classic continuous spike-and-wave during sleep pattern. Whole-exome sequencing identified a homozygous HEXA gene variant of uncertain significance, without definitive biochemical or clinical evidence of GM2 gangliosidosis. The child was managed with multiple antiseizure medications and supportive neurodevelopmental interventions, resulting in partial seizure control but persistent developmental impairment. This case underscores the importance of longitudinal electroclinical correlation in infants with stimulus-triggered motor events and highlights that reproducible auditory-induced events with evolving epileptiform EEG abnormalities and developmental impact strongly favor reflex auditory epilepsy over non-epileptic exaggerated startle, even in the setting of normal neuroimaging and genetic uncertainty.