Multiple system atrophy variant with severe hippocampal pathology.
Multiple system atrophy variant with severe hippocampal pathology.
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DOI：
10.1111/bpa.13002
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Yoshida M
中科院分区：
文献类型：
--
作者：
Ando T;Riku Y;Akagi A;Miyahara H;Hirano M;Ikeda T;Yabata H;Koizumi R;Oba C;Morozumi S;Yasui K;Goto A;Katayama T;Sakakibara S;Aiba I;Sakai M;Konagaya M;Mori K;Ito Y;Yuasa H;Nomura M;Porto KJL;Mitsui J;Tsuji S;Mimuro M;Hashizume Y;Katsuno M;Iwasaki Y;Yoshida M
已知纹状体黑质和橄榄脑桥小脑系统易受多系统萎缩（MSA）的影响，表现为神经元丢失、星形胶质细胞增生和α-突触核蛋白免疫反应性包涵体。在纹状体黑质或橄榄脑桥小脑系统以外的区域显示丰富的神经元胞质内含物（NCIs）的MSA患者偶尔被诊断为MSA变体。在这项研究中，我们报告的临床和病理发现MSA患者的特点是突出的病理参与海马。我们评估了146例连续尸检的MSA患者。抗α-突触核蛋白免疫组织化学半定量分析显示，146例患者中有12例（8.2%）在以下两个或多个区域发生重度NCI：海马颗粒细胞、角区、海马旁回和杏仁核。相比之下，其余134例患者在这些地区均未显示重度NCI。海马严重受累的患者中女性比例较高（9名女性/3名男性; Fisher精确检验，p = 0.0324），疾病持续时间较长（13.1 ± 5.9岁; Mann-Whitney U-检验，p = 0.000157），认知障碍患病率较高（4名患者; Fisher精确检验，p = 0.0222），脑重量（1070.3 ± 168.6 g; Mann-Whitney U检验，p = 0.00911）低于其他患者。海马颗粒细胞和氨角1区/下托几乎总是表现出严重的NCI。NCI似乎为环形或神经纤维缠结样纤维结构。12名患者中有3名患者还具有致密的圆形NCI，其在形态上与镐体相似。有皮克体样夹杂物的患者比无皮克体样夹杂物的患者显示出更严重的内侧颞叶萎缩和更广泛的NCI扩散。过度磷酸化tau蛋白和磷酸化TDP-43的免疫组织化学显示，海马MSA患者的海马中存在最小程度的聚集。我们的观察表明，MSA的病理变异，其特征是严重参与海马神经元。这种表型可能加强了神经元α-突触核蛋白病在MSA发病机制中的重要性。本研究描述了海马多系统萎缩（MSA）的临床病理学表型，其特征为患者海马中存在大量α-突触核蛋白-免疫阳性神经元胞质包涵体和神经元丢失，伴认知障碍。该表型可能是MSA的病理变体，并加强了神经元α-突触核蛋白病在MSA发病机制中的重要性。
The striatonigral and olivopontocerebellar systems are known to be vulnerable in multiple system atrophy (MSA), showing neuronal loss, astrogliosis, and alpha‐synuclein‐immunoreactive inclusions. MSA patients who displayed abundant neuronal cytoplasmic inclusions (NCIs) in the regions other than the striatonigral or olivopontocerebellar system have occasionally been diagnosed with variants of MSA. In this study, we report clinical and pathologic findings of MSA patients characterized by prominent pathologic involvement of the hippocampus. We assessed 146 consecutively autopsied MSA patients. Semi‐quantitative analysis of anti‐alpha‐synuclein immunohistochemistry revealed that 12 of 146 patients (8.2%) had severe NCIs in two or more of the following areas: the hippocampal granule cells, cornu ammonis areas, parahippocampal gyrus, and amygdala. In contrast, the remaining 134 patients did not show severe NCIs in any of these regions. Patients with severe hippocampal involvement showed a higher representation of women (nine women/three men; Fisher's exact test, p = 0.0324), longer disease duration (13.1 ± 5.9 years; Mann–Whitney U‐test, p = 0.000157), higher prevalence of cognitive impairment (four patients; Fisher's exact test, p = 0.0222), and lower brain weight (1070.3 ± 168.6 g; Mann–Whitney U‐test, p = 0.00911) than other patients. The hippocampal granule cells and cornu ammonis area 1/subiculum almost always showed severe NCIs. The NCIs appeared to be ring‐shaped or neurofibrillary tangle‐like, fibrous configurations. Three of 12 patients also had dense, round‐shaped NCIs that were morphologically similar to pick bodies. The patients with Pick body‐like inclusions showed more severe atrophy of the medial temporal lobes and broader spreading of NCIs than those without. Immunohistochemistry for hyperphosphorylated tau and phosphorylated TDP‐43 revealed minimal aggregations in the hippocampus of the hippocampal MSA patients. Our observations suggest a pathological variant of MSA that is characterized by severe involvement of hippocampal neurons. This phenotype may reinforce the importance of neuronal alpha‐synucleinopathy in the pathogenesis of MSA. This study describes a clinicopathological phenotype of the hippocampal multiple system atrophy (MSA) characterized by abundant alpha‐synuclein‐immunopositive neuronal cytoplasmic inclusions and neuronal loss in the hippocampus with concomitant cognitive impairment in the patients. The phenotype may be a pathological variant of MSA and reinforces the importance of neuronal alpha‐synucleinopathy in the pathogenesis of MSA.
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