Spinocerebellar ataxia type 4 (SCA4):: Initial pathoanatomical study reveals widespread cerebellar and brainstem degeneration
Spinocerebellar ataxia type 4 (SCA4):: Initial pathoanatomical study reveals widespread cerebellar and brainstem degeneration
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DOI：
10.1007/s00702-005-0362-9
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发表时间：
2006-07-01
影响因子：
3.3
通讯作者：
Rueb, U.
中科院分区：
文献类型：
--
作者：
Hellenbroich, Y.;Gierga, K.;Rueb, U.
脊髓小脑性共济失调4型（SCA4），也被称为“遗传性共济失调伴感觉神经病”，是一种非常罕见、进行性和不可治疗的常染色体显性遗传性小脑性共济失调（ADCA）。由于缺乏尸检病例，尚未在SCA4中进行神经病理学或临床病理学研究。在本研究中，第一个可用的小脑和脑干组织的临床诊断和基因确认的德国SCA4患者进行了病理解剖学研究，使用连续厚切片。在这次系统的尸检调查中，随着小脑和脑干纤维束的明显脱髓鞘，我们观察到广泛的小脑和脑干神经变性，在黑质和腹侧被盖区，中缝和脑桥核，所有听觉脑干核，外展神经，三叉神经，三叉神经脊束，面神经，上前庭，内侧前庭，间质前庭，背侧迷走神经运动核、舌下神经核和舌下神经前置核，以及中缝间位核、所有背柱核和下橄榄主亚核和内侧亚核。在小脑浦肯野细胞层、小脑顶核、红核、trophilar核、前庭外侧核和外侧网状核、脑桥网状被盖核和Roller核中观察到严重的神经元丢失。此外，使用抗多聚谷氨酰胺抗体1C2的免疫细胞化学分析未能检测到任何多聚谷氨酰胺相关的免疫反应性在中枢神经区域的SCA4患者的研究。鉴于已知受累核团和相关纤维束的功能作用，本研究结果不仅为SCA4患者的已知疾病症状提供了解释，（即共济失调症状，构音障碍和体感缺陷），但首次有助于解释为什么复视，凝视诱发的眼球震颤，听觉障碍和病理改变的脑干听觉诱发电位，扫视平滑追踪，在SCA4的过程中可能发生面部躯体感觉功能受损和吞咽困难。最后，我们的免疫细胞化学研究结果支持SCA4不是CAG重复或多聚谷氨酰胺疾病的成员的概念。
Spinocerebellar ataxia type 4 (SCA4), also known as 'hereditary ataxia with sensory neuropathy', represents a very rare, progressive and untreatable form of an autosomal dominant inherited cerebellar ataxia (ADCA). Due to a lack of autopsy cases, no neuropathological or clinicopathological studies had yet been performed in SCA4. In the present study, the first available cerebellar and brainstem tissue of a clinically diagnosed and genetically-confirmed German SCA4 patient was pathoanatomically studied using serial thick sections. During this systematic postmortem investigation, along with an obvious demyelinization of cerebellar and brainstem fiber tracts we observed widespread cerebellar and brainstem neurodegeneration with marked neuronal loss in the substantia nigra and ventral tegmental area, central raphe and pontine nuclei, all auditory brainstem nuclei, in the abducens, principal trigeminal, spinal trigeminal, facial, superior vestibular, medial vestibular, interstitial vestibular, dorsal motor vagal, hypoglossal, and prepositus hypoglossal nuclei, as well as in the nucleus raphe interpositus, all dorsal column nuclei, and in the principal and medial subnuclei of the inferior olive. Severe neuronal loss was seen in the Purkinje cell layer of the cerebellum, in the cerebellar fastigial nucleus, in the red, trochlear, lateral vestibular, and lateral reticular nuclei, the reticulotegmental nucleus of the pons, and the nucleus of Roller. In addition, immunocytochemical analysis using the anti-polyglutamine antibody 1C2 failed to detect any polyglutamine-related immunoreactivity in the central nervous regions of this SCA4 patient studied. In view of the known functional role of affected nuclei and related fiber tracts, the present findings not only offer explanations for the well-known disease symptoms of SCA4 patients (i.e. ataxic symptoms, dysarthria and somatosensory deficits), but for the first time help to explain why diplopia, gaze-evoked nystagmus, auditory impairments and pathologically altered brainstem auditory evoked potentials, saccadic smooth pursuits, impaired somatosensory functions in the face, and dysphagia may occur during the course of SCA4. Finally, the results of our immunocytochemical studies support the concept that SCA4 is not a member of the CAG-repeat or polyglutamine diseases.