Bolton P F, Griffiths P D
University of Cambridge, Section of Developmental Psychiatry, UK.
Lancet. 1997 Feb 8;349(9049):392-5. doi: 10.1016/S0140-6736(97)80012-8.
Tuberous sclerosis (TS) is a multisystem genetic disorder that is associated with mental retardation, autism, and atypical autism. We investigated the basis for these associations by examining whether the liability to mental retardation and autism or atypical autism is related to the number and distribution of hamartomatous brain growths (cortical tubers) that characterise TS.
18 patients consecutively referred to our clinic were assessed for the presence of autism or atypical autism, and their IQs were estimated (without awareness of brain-scan results). Brain scans were reviewed by a neuroradiologist (unaware of clinical diagnoses), and the number and location of cortical tubers was examined in relation to the liability to psychopathology.
Nine of the 18 patients had autism or atypical autism (two with IQ > or = 70; four with IQ 51-69, three with IQ < or = 50; eight with a history of epilepsy). The remaining patients had various other psychiatric disorders (five with IQ > or = 70; four with IQ 51-69; seven had a history of epilepsy). In the group as a whole, the number of tubers was significantly greater (p = 0.005) in patients with mental retardation (median 6 [IQR 4-9]) than in those of normal intelligence (1 [0-3]), and the degree of mental retardation was significantly correlated with the number of brain tubers (rs = 0.64; p = 0.008). Similarly, the number of tubers was significantly greater (p = 0.02) in individuals with a diagnosis of autism or atypical autism (6 [4-8]) than in those without this diagnosis (2 [1-4]). Eight of the nine patients with autism or atypical autism, but none of the non-autistic individuals, had tubers located in the temporal lobes (p = 0.0004). Otherwise, no particular distribution of cortical tubers was associated with a diagnosis of autism or atypical autism.
Our investigation provides evidence of an association between a gross, focal brain abnormality detectable on neuroimaging and autism or atypical autism. The results show the importance of scan findings in the prognosis of TS, and also suggest that temporallobe neurodevelopmental abnormalities may create a risk for autism or atypical autism.
结节性硬化症（TS）是一种多系统遗传性疾病，与智力发育迟缓、自闭症及非典型自闭症有关。我们通过研究智力发育迟缓、自闭症或非典型自闭症的易感性是否与作为TS特征的错构瘤性脑发育异常（皮质结节）的数量和分布有关，来探究这些关联的基础。
对连续转诊至我们诊所的18例患者进行自闭症或非典型自闭症评估，并估计其智商（在不知脑部扫描结果的情况下）。由一位神经放射科医生（不知临床诊断结果）复查脑部扫描结果，并检查皮质结节的数量和位置与精神病理学易感性的关系。
18例患者中，9例患有自闭症或非典型自闭症（2例智商≥70；4例智商为51 - 69；3例智商≤50；8例有癫痫病史）。其余患者患有各种其他精神疾病（5例智商≥70；4例智商为51 - 69；7例有癫痫病史）。在整个研究组中，智力发育迟缓患者的结节数量（中位数6[四分位间距4 - 9]）显著多于智力正常者（1[0 - 3]）（p = 0.005），且智力发育迟缓程度与脑结节数量显著相关（rs = 0.64；p = 0.008）。同样，诊断为自闭症或非典型自闭症的个体的结节数量（6[4 - 8]）显著多于未诊断为此病的个体（2[1 - 4]）（p = 0.02）。9例自闭症或非典型自闭症患者中有8例的结节位于颞叶，而非自闭症个体中无一例如此（p = 0.0004）。除此之外，皮质结节的特定分布与自闭症或非典型自闭症的诊断并无关联。
我们的研究为神经影像学上可检测到的明显局灶性脑异常与自闭症或非典型自闭症之间的关联提供了证据。结果显示扫描结果在TS预后中的重要性，也提示颞叶神经发育异常可能会增加患自闭症或非典型自闭症的风险。
