Background

We studied the natural history, genotype influence, and inter-relationship of epilepsy and neuropsychiatric disorders in tuberous sclerosis complex.

Methods

Patients were identified using the TSC Natural History Database, the largest repository of longitudinally studied patients enrolled by the TSC Clinics Consortium.

Results

A cohort of 1657 TSC Natural History Database patients was analyzed. Eighty-eight percent patients (91% TSC2 vs 82% TSC1; P = 0.002) had epilepsy; TSC2 was more frequent with epilepsy onset at age less than two years (TSC2 82% vs TSC1 54%; P < 0.001) and infantile spasms (TSC2 56% vs TSC1 27%; P < 0.001). Frequency of intellectual disability (intelligence quotient less than 70) was higher when epilepsy coexisted (P < 0.001), but was not impacted by genotype (P = 0.08). Severe intellectual disability (intelligence quotient less than 50) was associated with epilepsy onset at age less than two years (P = 0.007), but not with the epilepsy duration (P = 0.45). Autism was diagnosed in 23% and was associated with epilepsy (P < 0.001), particularly with epilepsy onset at age less than two years (P = 0.02) but not with genotype (P = 0.06). Attention-deficit/hyperactivity disorder (age greater than four years) was diagnosed in 18% and was associated with epilepsy (P < 0.001), but genotype made no difference. Nine percent had anxiety (age greater than seven years) and 6% had depression (age greater than nine years), but neither showed association with epilepsy or genotype.

Conclusions

Epilepsy is associated with intellectual disability, and when epilepsy begins before age two years the frequency and severity of intellectual disability is much higher. Epilepsy is also associated with autism and attention-deficit/hyperactivity disorder but not with anxiety and depression. Additional trials, blinded, prospective, and adequately powered, will help clarify if early and effective treatment of epilepsy may also mitigate intellectual disability, autism, and attention-deficit/hyperactivity disorder.

中文翻译：

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结节性硬化症中的癫痫和神经发育合并症：自然史研究。

背景

我们研究了结节性硬化症患者的自然史，基因型影响以及癫痫和神经精神疾病的相互关系。

方法

使用TSC自然历史数据库（TSC临床联合会招募的最大的纵向研究患者资料库）识别患者。

结果

分析了1657名TSC自然史数据库患者的队列。88％的患者 患有癫痫病（91％TSC2 vs 82％TSC1；P = 0.002）；TSC2在两岁以下发作的频率更高（TSC2 82％vs TSC1 54％；P  <0.001）和婴儿痉挛症（TSC2 56％vs TSC1 27％；P  <0.001）。癫痫并存时智力残疾的频率（智商小于70）较高（P  <0.001），但不受基因型影响（P = 0.08）。严重智力障碍（智商小于50）与小于两年的癫痫发作有关（P  = 0.007），但与癫痫持续时间无关（P  = 0.45）。自闭症的诊断率为23％，与癫痫有关（P  <0.001），特别是与小于两年的癫痫发作有关（P  = 0.02），而与基因型无关（P  = 0.06）。注意缺陷/多动障碍（年龄大于4岁）被诊断为18％，并与癫痫相关（P <0.001），但基因型没有差异。9％的人患有焦虑症（年龄大于7岁），而6％的人患有抑郁症（年龄大于9岁），但均未显示出与癫痫或基因型有关。

结论

癫痫与智力残疾有关，当癫痫发作在两岁之前开始时，智力残疾的频率和严重性要高得多。癫痫还与自闭症和注意力不足/多动症有关，但与焦虑和抑郁无关。盲法，前瞻性和足够动力的其他试验将有助于阐明癫痫的早期和有效治疗是否还可以缓解智力障碍，自闭症和注意力不足/多动症。