Neuroradiologic Findings in Patients With S CN2A Disease

BACKGROUND AND OBJECTIVES: phenotypes, their frequency and evolution, and their relevance for prognosis and clinical trials. METHODS: variants, MRI findings, and phenotype. MRI findings were categorized by predefined criteria, and patients were assigned to phenotypic subgroups based on seizure onset and developmental outcomes. RESULTS: disease were included (novel cohort n = 46; literature cohort n = 308). In the novel cohort, the median age was 6 years, and 54% were female. MRI abnormalities were present in 41% (19/46) of the novel cohort and 45% (139/308) of published cases. The most frequent overall findings were supratentorial atrophy (15%), white matter changes (17%), and corpus callosum thinning (10%). Findings differed significantly between phenotypic subgroups. Atrophy occurred mainly in early-onset severe and later-onset infantile phenotypic subgroups, on MRIs performed ≥4 weeks after seizure onset. White matter changes were often transient and nonspecific. Cortical malformations, especially polymicrogyria, were found in 5% (19/354) of patients. Hippocampal alterations were more frequent in the novel cohort (7/46, 15%) than in published cases (5/308, 2%). In episodic ataxia, isolated cerebellar atrophy was occasionally observed (4/23, 17%). DISCUSSION: disease revealed distinct imaging patterns across phenotypic subgroups. Atrophy was typically absent at seizure onset, highlighting progressive disease impact over time. These findings highlight the importance of early seizure control, guide counselling of patients and families, and inform MRI interpretation and biomarker research for future clinical trials. The retrospective design and heterogeneous imaging data represent important limitations.