Background

Epilepsy in tuberous sclerosis complex (TSC) typically presents with early onset, multiple seizure types, and intractability. However, variability is observed among individuals. Here, detailed individual data on seizure characteristics collected prospectively during early life were used to define epilepsy profiles in this population.

Methods

Children aged zero to 36 months were followed longitudinally. Caregivers kept daily seizure diaries, including onset and daily counts for each seizure type. Patients with >70% seizure diary completion and >365 diary days were included. Developmental outcomes at 36 months were compared between subgroups.

Results

Epilepsy was seen in 124 of 156 (79%) participants. Seizure onset occurred from zero to 29.5 months; 93% had onset before age 12 months. Focal seizures and epileptic spasms were most common. Number of seizures (for median 897 days) ranged from 1 to 9128. Hierarchical clustering based on six metrics of seizure burden (age of onset, total seizures, ratio of seizure days to nonseizure days, seizures per seizure day, and worst seven- and 30-day stretches) revealed two distinct groups with broadly favorable and unfavorable epilepsy profiles. Subpopulations within each group showed clinically meaningful differences in seizure burden. Groups with higher seizure burden had worse developmental outcomes at 36 months.

Conclusions

Although epilepsy is highly prevalent in TSC, not all young children with TSC have the same epilepsy profile. At least two phenotypic subpopulations are discernible based on seizure burden. Early and aggressive treatments for epilepsy in TSC may be best leveraged by targeting specific subgroups based on phenotype severity.

中文翻译：

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早期结节性硬化症患者的癫痫是异质性的

背景

结节性硬化症 (TSC) 中的癫痫通常表现为早发、多种癫痫发作类型和难治性。然而，在个体之间观察到变异性。在这里，在早期生活中前瞻性收集的关于癫痫发作特征的详细个人数据用于定义该人群的癫痫特征。

方法

对 0 至 36 个月的儿童进行纵向跟踪。护理人员保留每日癫痫发作日记，包括每种癫痫发作类型的发作次数和每日计数。包括> 70％的癫痫发作日记完成和> 365个日记日的患者。比较亚组间 36 个月时的发育结果。

结果

156 名 (79%) 参与者中有 124 名出现癫痫。癫痫发作发生在 0 到 29.5 个月；93% 在 12 个月前发病。局灶性发作和癫痫痉挛最为常见。癫痫发作次数（中位数为 897 天）范围为 1 到 9128。基于癫痫发作负担的六个指标（发病年龄、总癫痫发作、癫痫发作天数与非癫痫发作天数的比率、每次癫痫发作日的癫痫发作以及最差的 7 和30 天延伸）揭示了两个不同的组，具有广泛有利和不利的癫痫特征。每组内的亚群在癫痫发作负担方面表现出具有临床意义的差异。癫痫发作负担较高的组在 36 个月时的发育结果较差。

结论

尽管癫痫在 TSC 中非常普遍，但并非所有患有 TSC 的幼儿都具有相同的癫痫特征。根据癫痫发作负担，至少有两个表型亚群是可辨别的。通过基于表型严重程度针对特定亚组，可以最好地利用 TSC 中癫痫的早期和积极治疗。