Spinocerebellar Ataxia Type 2 (SCA2): Identification of Early Brain Degeneration in One Monozygous Twin in the Initial Disease Stage
Spinocerebellar Ataxia Type 2 (SCA2): Identification of Early Brain Degeneration in One Monozygous Twin in the Initial Disease Stage
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DOI：
10.1007/s12311-010-0239-9
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发表时间：
2011-06-01
期刊：
影响因子：
3.5
通讯作者：
Melegh, Bela
中科院分区：
文献类型：
--
作者：
Hoche, Franziska;Baliko, Laszlo;Melegh, Bela
脊髓小脑共济失调 2 型 (SCA2) 是一种进行性常染色体显性遗传小脑共济失调，属于 CAG 重复或多聚谷氨酰胺疾病。最近的形态学研究描述了杂合子 SCA2 患者的病理解剖学特征，并揭示了多种小脑和小脑外脑部位的严重神经元损失。在本研究中，我们检查了匈牙利 SCA2 大家族的单合双胞胎的脑部病理解剖学，该家族的两个 SCA2 等位基因中均存在病理性延长的 CAG 重复序列。这位独特的患者处于 SCA2 的初始临床阶段，并在 SCA2 发病后近 3 年后死亡。经过病理解剖学研究，我们观察到初级运动皮质中巨大 Betz 锥体细胞的丧失，感觉丘脑核、浦肯野细胞层和小脑深部核团的变性，以及选定的脑干核团（即黑质、动眼神经核、脑桥网状被盖核、面部、前庭外侧和中缝间核、下核）橄榄）。所有这些退化的大脑灰质结构都被认为是杂合子 SCA2 患者潜在病理过程的一致目标。由于他们在我们的患者发病后 3 年内就已经参与其中，我们认为我们第一次能够识别 SCA2 病理过程的早期大脑靶点。
Spinocerebellar ataxia type 2 (SCA2) is a progressive autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG repeat or polyglutamine diseases. Recent morphological studies characterized the pathoanatomical features in heterozygous SCA2 patients and revealed severe neuronal loss in a large variety of cerebellar and extra-cerebellar brain sites. In the present study, we examined the brain pathoanatomy of a monozygous twin of a large Hungarian SCA2 family with pathologically extended CAG repeats in both SCA2 alleles. This unique patient was in the initial clinical stage of SCA2 and died almost 3 years after SCA2 onset. Upon pathoanatomical investigation, we observed loss of giant Betz pyramidal cells in the primary motor cortex, degeneration of sensory thalamic nuclei, the Purkinje cell layer, and deep cerebellar nuclei, as well as select brainstem nuclei (i.e., substantia nigra, oculomotor nucleus, reticulotegmental nucleus of the pons, facial, lateral vestibular, and raphe interpositus nuclei, inferior olive). All of these degenerated brain gray matter structures are known as consistent targets of the underlying pathological process in heterozygous SCA2 patients. Since they were already involved in our patient within 3 years after disease onset, we think that we were for the first time able to identify the early brain targets of the pathological process of SCA2.