Risk of Seizures and Epilepsy in the Leukodystrophies

IF 2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology Pub Date : 2026-01-01 Epub Date: 2025-10-07 DOI:10.1016/j.pediatrneurol.2025.09.021

Ashley N. Hackett MD , Helena Yan MD , Katie Liu MSPH , Camille Corre MD , Kerry Gao BA , Chloe Grzyb BS , Jordan Goodman MS , Daniel Kelly BS , Cassandra R. Ingemansson MSN, FNP-C , Gabrielle Ghabash BS , Kerry DiBenardo BA , Gerald V. Raymond MD , William Benko MD , Robert Thompson-Stone MD , Ali Fatemi MD, MBA , Florian S. Eichler MD , Stephanie Keller MD , Joshua L. Bonkowsky MD, PhD , Maria Escolar MD, MS , Eric J. Mallack MD

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Abstract

Background

Seizures and epilepsy in leukodystrophies are poorly understood. This multisite study aimed to capture the prevalence of seizures in a nationwide cohort of patients, identify factors associated with increased seizure and epilepsy risk, and quantify prevalence of refractory seizures.

Methods

Retrospective data was extracted from leukodystrophy clinics across eight pediatric health centers from January 1, 2013, to March 31, 2020. Patients 18 years old and younger and diagnosed with leukodystrophy, including those identified by newborn screening, were eligible. Epilepsy was defined as two or more unprovoked seizures. Clinical variables including patient age, diagnosis, imaging features (binary: normal vs abnormal), electroencephalogram (EEG) findings, the presence/absence, and diagnoses of seizures/epilepsy were obtained.

Results

Data from 704 patients were analyzed. At least one seizure occurred in 29% of all patients. Epilepsy developed in 80% of patients with at least one seizure. EEG abnormalities were present in 84% of patients with seizures versus 54% without (P < 0.001). In a multivariate analysis of seizure risk, higher increased likelihoods were associated with every one-year increase in age (1.13 times higher; 95% confidence interval [CI]: [1.07, 1.19], P < 0.001), generalized epileptiform discharges (13.4 times higher; 95% CI: [2.22, 259], P = 0.019), focal and multifocal epileptiform discharges (3.56 times higher; 95% CI: [2.04, 6.36], P < 0.001), and focal slowing (3.57 times higher; 95% CI: [1.58, 8.58], P = 0.003). Diffuse slowing was not significantly associated with seizure in the multivariate analysis (odds ratio 1.45, 95% CI: [0.85, 2.45], P = 0.170). In a comparison of different pathological classifications, seizures, but not epilepsy, were more common in astrocytopathies compared to myelinopathies (seizures 41% vs 28%, P = 0.046; epilepsy 89% vs 79%, P = 0.376). Two or more antiseizure medications were required to control seizures in multiple leukodystrophies.

Conclusions

Age, focal slowing, and epileptiform discharges, but not generalized slowing or abnormal brain magnetic resonance imaging, were significant predictors for seizure in this population. Patients with generalized discharges have a higher risk of seizures compared to those with focal discharges. Seizure burden, age at first seizure, number of antiseizure medications needed, and presence of EEG abnormalities vary based on underlying leukodystrophy. Our findings suggest the need for targeted strategies for monitoring seizures and epilepsy in the leukodystrophies.

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脑白质营养不良患者癫痫发作的风险。

背景：脑白质营养不良患者的癫痫发作和癫痫尚不清楚。这项多地点研究旨在捕捉全国患者队列中癫痫发作的患病率，确定与癫痫发作和癫痫风险增加相关的因素，并量化难治性癫痫发作的患病率。方法：从2013年1月1日至2020年3月31日，从8个儿科健康中心的脑白质萎缩症诊所提取回顾性数据。18岁及以下被诊断为脑白质营养不良的患者，包括通过新生儿筛查确定的患者，均符合条件。癫痫被定义为两次或两次以上的无端发作。临床变量包括患者年龄、诊断、影像学特征（二元：正常与异常）、脑电图（EEG）结果、有无发作/癫痫诊断。结果：分析了704例患者的资料。29%的患者至少发生一次癫痫发作。80%的患者至少有一次癫痫发作。脑电图异常在癫痫发作患者中占84%，未发作患者占54% （P < 0.001）。在癫痫发作风险的多变量分析中，年龄每增加1岁（1.13倍，95%可信区间[CI]: [1.07, 1.19], P < 0.001）、全局性癫痫样放电（13.4倍，95% CI: [2.22, 259], P = 0.019）、局灶性和多灶性癫痫样放电（3.56倍，95% CI: [2.04, 6.36], P < 0.001）和局灶性减慢（3.57倍，95% CI: [1.58, 8.58], P = 0.003）的可能性增加越高。在多变量分析中，弥漫性减慢与癫痫发作无显著相关性（优势比1.45,95% CI: [0.85, 2.45], P = 0.170）。在不同病理分类的比较中，星形细胞病中癫痫发作比髓鞘病更常见（癫痫发作41%比28%，P = 0.046；癫痫89%比79%，P = 0.376）。多发性脑白质营养不良患者需要两种或两种以上的抗癫痫药物来控制癫痫发作。结论：年龄、局灶性慢化和癫痫样放电是该人群癫痫发作的重要预测因素，但不是全局性慢化或异常脑磁共振成像。与局灶性放电患者相比，全身性放电患者癫痫发作的风险更高。癫痫发作负担、首次发作的年龄、所需抗癫痫药物的数量和脑电图异常的存在根据潜在的脑白质营养不良而变化。我们的研究结果表明需要有针对性的策略来监测脑白质营养不良患者的癫痫发作和癫痫。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric neurology 医学-临床神经学

CiteScore

4.80

自引率

2.60%

发文量

176

审稿时长

78 days

期刊介绍： Pediatric Neurology publishes timely peer-reviewed clinical and research articles covering all aspects of the developing nervous system. Pediatric Neurology features up-to-the-minute publication of the latest advances in the diagnosis, management, and treatment of pediatric neurologic disorders. The journal''s editor, E. Steve Roach, in conjunction with the team of Associate Editors, heads an internationally recognized editorial board, ensuring the most authoritative and extensive coverage of the field. Among the topics covered are: epilepsy, mitochondrial diseases, congenital malformations, chromosomopathies, peripheral neuropathies, perinatal and childhood stroke, cerebral palsy, as well as other diseases affecting the developing nervous system.