Background

The neurodevelopmental impairment in tuberous sclerosis complex (TSC) has a multifactorial origin. Various factors have been proposed as predictors of neurological outcome such as tuber load, seizure onset, and TSC2 mutation. Cerebellar lesions have been associated with worse neuroradiological phenotype, but their contribution is not well understood.

Methods

A partly retrospective and partly prospective pediatric cohort study was conducted at three hospitals in Greece between 2015 and 2020. Patients aged ≤ 18 years with a confirmed TSC daignosis were included and underwent brain imaging, a semistructured interview (authorized Greek version of the tuberous sclerosis-associated neuropsychiatric disorders, or TAND, checklist), and intellectual ability assessment.

Results

The study populations consisted of 45 patients with TSC (22 females, 23 males; mean age 9.53 years). Twenty patients (44.4%) had cerebellar lesions. Cerebellar involvement was the most powerful predictor of tuber load (P = 0.03). Cerebellar lesions were associated with giant cell astrocytomas (SEGAs) (P = 0.01) and severe neurological outcome (P = 0.01). Even though in the univariate analysis early seizure onset, tuber load, and cerebellar involvement were associated with intellectual impairment and neurological severity, none of them was an independent predictor of cognitive outcome and neurological severity.

Conclusions

Cerebellar lesions are common among individuals with TSC. Cerebellar involvement correlates with supratentorial derangement and the development of SEGAs, which is suggestive of a more severe clinical and neuroradiological phenotype. Cerebellar involvement and early seizure onset were not independent predictors of either neurological severity or intellectual disability or neurobehavioral outcome; their role in TSC clinical phenotype should be further investigated.

中文翻译：

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结节性硬化症患儿队列中皮层、小脑和年龄的复杂相互作用

背景

结节性硬化症 (TSC) 中的神经发育障碍具有多因素起源。已经提出各种因素作为神经系统结果的预测因子，例如块茎负荷、癫痫发作和 TSC2 突变。小脑病变与更差的神经放射学表型有关，但它们的贡献尚不清楚。

方法

2015 年至 2020 年期间，在希腊的三家医院进行了一项部分回顾性和部分前瞻性的儿科队列研究。纳入了年龄≤18 岁且确诊为 TSC 的患者，并接受了脑成像、半结构化访谈（经授权的希腊版结节性硬化症-相关的神经精神疾病，或 TAND，清单）和智力评估。

结果

研究人群包括 45 名 TSC 患者（22 名女性，23 名男性；平均年龄 9.53 岁）。20 名患者（44.4%）有小脑病变。小脑受累是块茎负荷最有力的预测因子（P  = 0.03）。小脑病变与巨细胞星形细胞瘤 (SEGA) ( P  = 0.01) 和严重的神经系统后果 ( P  = 0.01) 相关。尽管在单变量分析中，早期癫痫发作、结节负荷和小脑受累与智力障碍和神经系统严重程度相关，但它们都不是认知结果和神经系统严重程度的独立预测因子。

结论

小脑病变在 TSC 患者中很常见。小脑受累与幕上紊乱和 SEGAs 的发展相关，这表明更严重的临床和神经放射学表型。小脑受累和早期癫痫发作不是神经系统严重程度或智力障碍或神经行为结果的独立预测因子；应进一步研究它们在 TSC 临床表型中的作用。