Multiple system atrophy variant with severe hippocampal pathology,Brain Pathology

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Multiple system atrophy variant with severe hippocampal pathology
Brain Pathology ( IF 5.8 ) Pub Date : 2021-07-13 , DOI: 10.1111/bpa.13002
Takashi Ando _{1,

2} , Yuichi Riku _{1,

2} , Akio Akagi ₂ , Hiroaki Miyahara ₂ , Mitsuaki Hirano _{2,

3} , Toshimasa Ikeda _{2,

4} , Hiroyuki Yabata _{2,

5} , Ryuichi Koizumi _{2,

6} , Chisato Oba ₇ , Saori Morozumi ₇ , Keizo Yasui ₇ , Atsuko Goto ₈ , Taiji Katayama ₈ , Satoko Sakakibara ₈ , Ikuko Aiba ₈ , Motoko Sakai ₉ , Masaaki Konagaya ₉ , Keiko Mori ₁₀ , Yasuhiro Ito ₁₁ , Hiroyuki Yuasa ₁₂ , Masayo Nomura ₁₃ , Kristine Joyce L Porto ₁₄ , Jun Mitsui ₁₄ , Shoji Tsuji ₁₄ , Maya Mimuro ₂ , Yoshio Hashizume ₂ , Masahisa Katsuno ₁ , Yasushi Iwasaki ₂ , Mari Yoshida ₂

Affiliation

Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan.
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Neurology, Shiga University of Medical Science, Ohtsu, Japan.
Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Neurology, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
Department of Neurology, National Hospital Organization Higashinagoya National Hospital, Nagoya, Japan.
Department of Neurology, National Hospital Organization Suzuka National Hospital, Suzuka, Japan.
Department of Neurology, Oyamada Memorial Spa Hospital, Yokkaichi, Japan.
Department of Neurology, Toyota Memorial Hospital, Toyota, Japan.
Department of Neurology, Tosei General Hospital, Seto, Japan.
Department of Neurology, Kainan Hospital Aichi Prefectural Welfare Federation of Agricultural Cooperatives, Yatomi, Japan.
Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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.

中文翻译：

具有严重海马病理的多系统萎缩变异

已知纹状体黑质和橄榄脑桥小脑系统在多系统萎缩 (MSA) 中易受攻击，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。MSA 患者在除纹状体黑质或橄榄脑桥小脑系统以外的区域显示出丰富的神经元胞质包涵体 (NCI) 时，偶尔会被诊断出患有 MSA 变异。在这项研究中，我们报告了以海马体显着病理受累为特征的 MSA 患者的临床和病理结果。我们评估了 146 名连续尸检的 MSA 患者。抗α-突触核蛋白免疫组织化学的半定量分析显示，146 名患者中有 12 名（8.2%）在以下两个或多个区域有严重的 NCI：海马颗粒细胞、羊角区、海马旁回和杏仁核。相比之下，其余 134 名患者在这些地区均未出现严重的 NCI。严重海马受累患者的女性比例较高（9 名女性/3 名男性；Fisher 精确检验，p = 0.0324）、更长的疾病持续时间（13.1 ± 5.9 年；Mann-Whitney U 检验，p = 0.000157）、更高的认知障碍患病率（4 名患者；Fisher 精确检验，p = 0.0222）和更低的脑重（1070.3 ± 168.6 g；Mann-Whitney U 检验，p = 0.00911) 比其他患者。海马颗粒细胞和羊角区1/下颌几乎总是表现出严重的NCIs。NCI 似乎是环状或神经原纤维缠结状的纤维结构。12 名患者中有 3 名也有密集的圆形 NCI，在形态上与挑体相似。Pick体样包涵体患者的内侧颞叶萎缩更严重，NCIs的扩散范围比没有的患者更广泛。过度磷酸化 tau 和磷酸化 TDP-43 的免疫组织化学显示海马 MSA 患者的海马中聚集最少。我们的观察表明 MSA 的病理变体以海马神经元的严重受累为特征。

更新日期：2021-07-13

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