Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex
Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex
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DOI：
10.1093/brain/awf124
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发表时间：
2002-06-01
期刊：
影响因子：
14.5
通讯作者：
Pickles, A
中科院分区：
文献类型：
--
作者：
Bolton, PF;Park, RJ;Pickles, A
脑硬化症是自闭症谱系障碍的少数几个确定的医学原因之一，是一个独特的神经遗传学模型，用于测试有关该综合征大脑基础的理论。我们进行了一项回顾性病例研究，探讨结节性硬化症患者易患自闭症谱系障碍的神经癫痫危险因素，以检验目前自闭症谱系障碍的神经生物学理论。我们发现，自闭症谱系障碍的诊断与颞叶皮质结节的存在有关，而与大脑其他叶无关。事实上，颞叶结节的存在似乎是自闭症谱系障碍发展的必要但不充分的风险因素。然而，与一些理论的预测相反，结节在颞叶特定区域的位置，如上级颞回或右颞叶，并不能决定哪些患有颞叶结节的个体发展为自闭症谱系障碍。相反，结果与癫痫活动的各种指标相关，包括EEG上颞叶癫痫样放电的证据，出生后3年内癫痫发作的年龄和婴儿痉挛症病史。结果表明，当颞叶结节存在并与颞叶癫痫样放电和早发性持续性痉挛样癫痫发作相关时，结节性硬化症患者患自闭症谱系障碍的风险非常高。这些风险标志物构成了有用的临床预后指标，但需要进一步的研究，以确定其与结果的神经生物学机制。最重要的是，测试是否如研究结果所示，存在大脑成熟的关键早期阶段，在此期间，颞叶癫痫扰乱了支持“社会智力”和其他认知技能的大脑系统的发展，从而诱发自闭症谱系障碍。
Tuberous sclerosis is one of the few established medical causes of autism spectrum disorder and is a unique neurogenetic model for testing theories about the brain basis of the syndrome. We conducted a retrospective case study of the neuro-epileptic risk factors predisposing to autism spectrum disorder in individuals with tuberous sclerosis to test current neurobiological theories of autism spectrum disorder. We found that an autism spectrum disorder diagnosis was associated with the presence of cortical tubers in the temporal but not other lobes of the brain. Indeed, the presence of tubers in the temporal lobes appeared to be a necessary but not sufficient risk factor for the development of an autism spectrum disorder. However, contrary to the predictions of some theories, the location of tubers in specific regions of the temporal lobe, such as the superior temporal gyrus or the right temporal lobe, did not determine which individuals with temporal lobe tubers developed an autism spectrum disorder. Instead, outcome was associated with various indices of epileptic activity including evidence of temporal lobe epileptiform discharges on EEG, the age to onset of seizures in the first 3 years of life and a history of infantile spasms. The results indicated that individuals with tuberous sclerosis are at very high risk of developing an autism spectrum disorder when temporal lobe tubers are present and associated with temporal lobe epileptiform discharges and early-onset, persistent spasm-like seizures. These risk markers constitute useful clinical indicators of prognosis, but further research is required to identify the neurobiological mechanisms responsible for their association with outcome. Most especially, it will be important to test whether, as the findings suggest, there is a critical early stage of brain maturation during which temporal lobe epilepsy perturbs the development of brain systems that underpin 'social intelligence' and possibly other cognitive skills, thereby inducing an autism spectrum disorder.