Amyotrophic lateral sclerosis with speech apraxia, predominant upper motor neuron signs, and prominent iron accumulation in the frontal operculum and precentral gyrus
Amyotrophic lateral sclerosis with speech apraxia, predominant upper motor neuron signs, and prominent iron accumulation in the frontal operculum and precentral gyrus
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肌萎缩侧索硬化症伴有言语失用、主要上运动神经元体征以及额叶盖和中央前回铁积聚明显
DOI：
10.1111/neup.12763
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发表时间：
2021
期刊：
影响因子：
2.3
通讯作者：
Mochizuki Hideki
中科院分区：
文献类型：
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作者：
Mitani Tomoki T.;Beck Goichi;Kido Kansuke;Yamashita Rika;Yonenobu Yuki;Ogawa Takuya;Saeki Chizu;Okuno Tatsusada;Nagano Seiichi;Morii Eiichi;Hasegawa Masato;Saito Yuko;Murayama Shigeo;Mochizuki Hideki
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病; 43 kDa的反式激活反应DNA结合蛋白（TDP-43）和铁积累被认为在疾病的病理机制中起着至关重要的作用。在这里，我们报告了一个不寻常的情况下，患者与ALS谁提出了言语失用症作为初始症状和上运动神经元缺陷。在早期临床阶段，单光子发射计算机断层扫描显示右额叶盖的局灶性灌注不足，磁共振成像在T2加权图像上识别出额叶沿着的低信号区。神经病理学检查显示，中央前回中经常可见贝茨细胞的神经元吞噬、神经胶质增生、磷酸化TDP-43（p-TDP-43）阳性神经胶质和神经元包涵体的出现以及显著的铁蓄积。在额盖中也可见TDP-43病理学和局灶性铁蓄积，但在延髓舌下神经核和脊髓前角中仅发现轻度神经元丢失和少量p-TDP-43阳性神经元和神经胶质包涵体。免疫印迹分析显示ALS的非典型带型。在我们的病例中，异常的TDP-43和铁积累可能导致了额盖的神经退行性变，这可能是串联的或独立的;然后它可能扩散到初级运动区。我们的研究结果表明，TDP-43和铁蓄积在ALS的病理机制中存在因果关系，表现为上运动神经元体征。
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease; transactivation response DNA‐binding protein of 43 kDa (TDP‐43) and iron accumulation are supposed to play a crucial role in the pathomechanism of the disease. Here, we report an unusual case of a patient with ALS who presented with speech apraxia as an initial symptom and upper motor neuron deficiencies. In the early clinical stages, single‐photon emission computed tomography visualized focal hypoperfusion of the right frontal operculum, and magnetic resonance imaging identified a hypointense area along the frontal lobe on T2‐weighted images. Neuropathological examination revealed that neuronophagia of Betz cells, gliosis, appearance of phosphorylated TDP‐43 (p‐TDP‐43)‐positive glial and neuronal inclusions, and prominent iron accumulation were frequently visible in the precentral gyrus. TDP‐43 pathology and focal iron accumulation were also visible in the frontal operculum, but only a mild neuronal loss and a few p‐TDP‐43‐positive neuronal and glial inclusions were found in the hypoglossal nucleus of the medulla oblongata and anterior horn of the spinal cord. Immunoblot analysis revealed an atypical band pattern for ALS. In our case, abnormal TDP‐43 and iron accumulation might possibly have caused neurodegeneration of the frontal operculum, in tandem or independently; it might then have spread into the primary motor area. Our results suggest a causative association between TDP‐43 and iron accumulation in the pathomechanisms of ALS presenting with upper motor neuron signs.