NEUROPATHOLOGY OF RETT SYNDROME
NEUROPATHOLOGY OF RETT SYNDROME
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DOI：
10.1007/bf00688098
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发表时间：
1988-01-01
影响因子：
12.7
通讯作者：
PERCY, AK
中科院分区：
文献类型：
--
作者：
JELLINGER, K;ARMSTRONG, D;PERCY, AK
瑞特综合征是一种在女性中日益被认识的进行性疾病，始于婴儿期，其特征为孤独症行为、步态共济失调、刻板动作、癫痫发作以及全身性生长发育迟缓和智力低下，可能与中枢生物胺合成障碍有关。瑞特综合征的基因位点和发病机制尚不清楚。对9名死于4至17岁的女孩进行的尸检研究以及对2名3岁和17岁女孩的腓肠神经和肌肉活检显示：弥漫性皮质萎缩/小头畸形，脑重量较年龄匹配的对照组减少12% - 34%，这显然与疾病的持续时间有关；轻度弥漫性皮质萎缩，神经元脂褐素增多，偶见轻度胶质增生，但无储存障碍的迹象；黑质致密带色素沉着不足，与年龄相比，色素沉着良好的神经元减少，每个神经元的黑色素颗粒减少，而黑质神经元总数和神经黑色素的亚结构在年龄上是正常的。在其他递质特异性脑干核中未观察到病理变化；黑质和下丘脑神经元中酪氨酸羟化酶的免疫反应性略有降低，垂体腺中催乳素和生长激素的免疫反应降低；在超微结构上，在额叶皮质和尾状核中，观察到孤立的异常神经突以及反应性或退行性轴突肿胀；后者可能与黑质变化有关，提示多巴胺能黑质 - 纹状体系统存在某种功能障碍，这得到了神经化学数据的支持；初步的生化研究显示丘脑和小脑中β - 内啡肽增加；周围神经显示小纤维增多但无脱髓鞘，轴突中神经丝数量增加，提示远端轴突病，而骨骼肌显示肌浆网改变，Z线中有环形轮廓。这些非特异性变化可被解释为失神经的早期迹象。讨论了瑞特综合征在中枢、神经内分泌和外周神经肌肉系统中的多种病变及其临床和生化意义。
Rett syndrome is an increasingly recognized progressive disorder in females, commencing in infancy and characterized by autistic behavior, gait ataxia, stereotyped movements, seizures and generalized growth and mental retardation, possibly associated with disorders of central biogenic amine synthesis. The gene locus and pathogenesis of Rett syndrome are unknown. Autopsy studies in nine girls dying between 4 and 17 years, and sural nerve and muscle biopsies from two girls aged 3 and 17 years showed: diffuse cortical atrophy/micrencephaly, with a decrease in brain weight by 12% to 34% of age-matched controls, apparently related to the duration of the disorder; mild diffuse cortical atrophy with increased amounts of neuronal lipofuscin and occasional mild gliosis, but without signs of a storage disorder; underpigmentation of the zona compacta nigrae, which showed fewer well-pigmented neurons for age and fewer melanin granules per neuron, while total numbers of nigral neurons and the substructure of neuromelanin were normal for age. No pathological changes were seen in other transmitter-specific brain stem nuclei; immunoreactivity for tyrosine hydroxylase was slightly reduced in nigral and hypothalamic neurons, and the pituitary gland showed decreased immunoreaction for prolactin and growth hormone; ultrastructurally, in frontal cortex and caudate nucleus, isolated abnormal neurites and reactive or degenerative axonal swellings were seen; the latter are possibly related to the nigral changes, suggesting some dysfunction of the dopaminergic nigrostriatal system, which is supported by neurochemical data; preliminary biochemical studies revealed increased .beta.-endorphines in thalamus and cerebellum; peripheral nerves demonstrated increase in small fibers without demyelination and increased numbers of neurofilaments in axons, suggesting distal axonopathy, while skeletal muscle showed alterations in the sarcoplasmic reticulum with circular profiles in the Z-filaments. These nonspecific changes may be interpreted as early signs of denervation. The variety of lesions in the central, neuroendocrine and peripheral neuromuscular systems in Rett syndrome are discussed with regard to their clinical and biochemical significance.