Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.
Department of Neurology, National Hospital Organization Chibahigashi National Hospital, Chiba, Japan.
BMC Neurol. 2021 Jul 9;21(1):273. doi: 10.1186/s12883-021-02306-5.
Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Pathologically, it is characterized by eosinophilic hyaline intranuclear inclusions in the cells of the visceral organs as well as central, peripheral, and autonomic nervous system cells. Recently, a GGC repeat expansion in the NOTCH2NLC gene has been identified as the etiopathological agent of NIID. Interestingly, this GGC repeat expansion was also reported in some patients with a clinical diagnosis of amyotrophic lateral sclerosis (ALS). However, there are no autopsy-confirmed cases of concurrent NIID and ALS.
A 60-year-old Taiwanese woman reported a four-month history of progressive weakness beginning in the right foot that spread to all four extremities. She was diagnosed with ALS because she met the revised El Escorial diagnostic criteria for definite ALS with upper and lower motor neuron involvement in the cervical, thoracic, and lumbosacral regions. She died of respiratory failure at 22 months from ALS onset, at the age of 62 years. Brain magnetic resonance imaging (MRI) revealed lesions in the medial part of the cerebellar hemisphere, right beside the vermis (paravermal lesions). The subclinical neuropathy, indicated by a nerve conduction study (NCS), prompted a potential diagnosis of NIID. Antemortem skin biopsy and autopsy confirmed the coexistence of pathology consistent with both ALS and NIID. We observed neither eccentric distribution of p62-positive intranuclear inclusions in the areas with abundant large motor neurons nor cytopathological coexistence of ALS and NIID pathology in motor neurons. This finding suggested that ALS and NIID developed independently in this patient.
We describe a case of concurrent NIID and ALS discovered during an autopsy. Abnormal brain MRI findings, including paravermal lesions, could indicate the coexistence of NIID even in patients with ALS showing characteristic clinical phenotypes.
神经元核内包涵体病（NIID）是一种罕见的神经退行性疾病。病理学上，它的特征是内脏器官以及中枢、周围和自主神经系统细胞中的嗜酸性透明核内包涵体。最近，NOTCH2NLC 基因中的 GGC 重复扩增被确定为 NIID 的病因。有趣的是，这种 GGC 重复扩增也在一些临床诊断为肌萎缩侧索硬化症（ALS）的患者中被报道。然而，尚无同时患有 NIID 和 ALS 的尸检确诊病例。
一位 60 岁的中国台湾女性，诉右下肢进行性无力 4 个月，逐渐累及四肢。她符合修订后的 El Escorial 诊断标准，明确诊断为 ALS，伴有上、下运动神经元受累，病变部位涉及颈、胸和腰骶部。她在出现 ALS 症状后 22 个月因呼吸衰竭死亡，享年 62 岁。脑部磁共振成像（MRI）显示小脑半球内侧、蚓旁部位有病变（旁蚓部病变）。神经传导研究（NCS）提示亚临床神经病，提示有 NIID 的潜在诊断。生前皮肤活检和尸检证实了同时存在符合 ALS 和 NIID 的病理改变。我们未观察到大量大运动神经元区域内 p62 阳性核内包涵体的偏心分布，也未观察到运动神经元中 ALS 和 NIID 病理的细胞病理学共存。这一发现提示 ALS 和 NIID 在该患者中是独立发展的。
我们描述了一例尸检中发现的同时患有 NIID 和 ALS 的病例。异常的脑部 MRI 表现，包括旁蚓部病变，可能提示即使在表现出典型临床表型的 ALS 患者中也存在 NIID 的共存。
