Neuroradiologic Findings in Patients With SCN2A Disease: A Systematic Review and Retrospective Multicenter Cohort Study.

Systematic characterization of the spectrum of neuroradiologic abnormalities in SCN2A disease has not been performed.

尚未对SCN2A疾病中的神经放射学异常谱系进行系统性特征描述。

This study aimed to delineate MRI findings across SCN2A phenotypes, their frequency and evolution, and their relevance for prognosis and clinical trials.

本研究旨在明确SCN2A表型的MRI发现、其频率和演变，以及它们对预后和临床试验的相关性。

Methods

This retrospective multicenter cohort study recruited individuals with (likely) pathogenic SCN2A variants and available MRI data from the SCN2A Natural History Study (Bonn/Melbourne) and an international research network ("novel cohort").

这项回顾性多中心队列研究招募了来自SCN2A自然史研究（波恩/墨尔本）和国际研究网络（“新队列”）的携带（可能）致病性SCN2A变异且有可用MRI数据的个体。

Two blinded pediatric neuroradiologists evaluated all brain MRIs.

两位经过盲评的儿科神经放射科医生评估了所有脑部MRI。

In addition, we performed a systematic literature review (PubMed, search term "SCN2A," last updated January 31, 2026) including patients with available data on SCN2A variants, MRI findings, and phenotype.

此外，我们进行了一项系统性文献综述（PubMed，搜索词“SCN2A”，最后更新日期为2026年1月31日），包括有SCN2A变异、MRI发现和表型数据的患者。

MRI findings were categorized by predefined criteria, and patients were assigned to phenotypic subgroups based on seizure onset and developmental outcomes.

MRI发现根据预设的标准进行分类，患者根据癫痫发作的开始和发育结果被分配到表型亚组。

Results

A total of 354 individuals with SCN2A disease were included (novel cohort n = 46; literature cohort n = 308).

共有354名SCN2A疾病患者被纳入研究（新队列n=46；文献队列n=308）。

In the novel cohort, the median age was 6 years, and 54% were female.

在新队列中，中位年龄为6岁，女性占54%。

MRI abnormalities were present in 41% (19/46) of the novel cohort and 45% (139/308) of published cases.

新队列中有41%（19/46）的患者和已发表病例中有45%（139/308）的患者存在MRI异常。

The most frequent overall findings were supratentorial atrophy (15%), white matter changes (17%), and corpus callosum thinning (10%).

最常见的总体发现是幕上萎缩（15%）、白质改变（17%）和胼胝体变薄（10%）。

Findings differed significantly between phenotypic subgroups.

表型亚组之间的发现存在显著差异。

Atrophy occurred mainly in early-onset severe and later-onset infantile phenotypic subgroups, on MRIs performed ≥4 weeks after seizure onset.

萎缩主要发生在早期发病严重和晚期发病婴儿表型亚组中，在癫痫发作后≥4周进行的MRI中。

White matter changes were often transient and nonspecific.

白质改变通常是短暂的且非特异性的。

Cortical malformations, especially polymicrogyria, were found in 5% (19/354) of patients.

皮质畸形，特别是多小脑回畸形，在5%（19/354）的患者中发现。

Hippocampal alterations were more frequent in the novel cohort (7/46, 15%) than in published cases (5/308, 2%).

海马结构的改变在新队列中更为频繁（7/46，15%）相比于已发表的病例（5/308，2%）。

In episodic ataxia, isolated cerebellar atrophy was occasionally observed (4/23, 17%).

在发作性共济失调中，偶尔观察到孤立的小脑萎缩（4/23，17%）。

Discussion

This comprehensive characterization of brain MRI abnormalities in SCN2A disease revealed distinct imaging patterns across phenotypic subgroups.

对SCN2A疾病脑MRI异常的全面特征描述揭示了表型亚组之间不同的影像模式。

Atrophy was typically absent at seizure onset, highlighting progressive disease impact over time.

在癫痫发作开始时，萎缩通常不存在，这突显了疾病随时间的逐渐影响。

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.

这些发现强调了早期癫痫控制的重要性，指导患者和家庭的咨询，并为未来临床试验的MRI解释和生物标志物研究提供信息。

The retrospective design and heterogeneous imaging data represent important limitations.

回顾性设计和异质性影像数据代表了重要的局限性。