Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.
Department of Neurology, National Hospital Organization, Chibahigashi National Hospital, Chiba, Japan.
Neuropathology. 2019 Aug;39(4):286-293. doi: 10.1111/neup.12559. Epub 2019 May 24.
We report the neuropathology of a patient with a family history of amyotrophic lateral sclerosis (ALS) and a p.N345K mutation in the transactivation response DNA-binding protein 43 kDa (TDP-43) gene (TARDBP). A 62-year-old man had bulbar palsy with progressive weakness in the extremities. Neurological examination revealed evident upper motor neuron signs and lower motor neuron involvement corroborated by needle electromyography. The patient was diagnosed as having probable ALS according to the revised El Escorial diagnostic criteria and was eventually diagnosed with familial ALS. At 65 years of age, respiratory failure became critical, and artificial ventilation was initiated. At 70 years of age, the patient died from a urinary tract infection. Histopathological investigation showed Bunina bodies in the remaining motor neurons and anterolateral funicular myelin pallor in the spinal cord. TDP-43-positive cytoplasmic inclusions were quite rare in the spinal cord motor neurons, being predominantly present in the glial cells (especially astrocytes) of the spinal cord anterior horn. Although the reason for the preferential vulnerability of spinal glial cells to TARDBP mutations remains unclear, our findings indicate that TARDBP p.N345K mutation could have an influence on the topography of TDP-43 aggregation.
我们报告了一名有肌萎缩侧索硬化症（ALS）家族史和 TDP-43 基因（TARDBP）p.N345K 突变的患者的神经病理学。一名 62 岁男性出现延髓性瘫痪，四肢进行性无力。神经系统检查显示明显的上运动神经元征和下运动神经元受累，肌电图证实。根据修订后的埃尔埃斯克罗尔诊断标准，该患者被诊断为可能的 ALS，最终被诊断为家族性 ALS。65 岁时，呼吸衰竭变得危急，开始进行人工通气。70 岁时，患者死于尿路感染。组织病理学研究显示，脊髓中残留运动神经元中有 Bunina 体，前外侧束髓鞘苍白。TDP-43 阳性细胞质包涵体在脊髓运动神经元中相当罕见，主要存在于脊髓前角的神经胶质细胞（尤其是星形胶质细胞）中。虽然脊髓神经胶质细胞对 TARDBP 突变易感性的原因尚不清楚，但我们的研究结果表明，TARDBP p.N345K 突变可能对 TDP-43 聚集的拓扑结构有影响。
