Identification of small fiber neuropathy in neuronal intranuclear inclusion disease: A clinicopathological study

作者：Minglei Liu, Ruoyu Liu, Yanpeng Yuan, Xiaojing Liu, Lanjun Li, Yangyang Wang, Jing Yuan, Ke Zhang, Shuo Li, Ting Yang, Yanlin Wang, Yuan Gao, Han Liu, Yinge Xue, Lin Cheng, Tianyuan Yang, Ying Kong, C. Liu, Yan‐Jiang Wang, Yuming Xu, Jing Yang · 发表于：Alzheimer s & Dementia · 年份：2025 · DOI：10.1002/alz.14596 · 被引用次数：7 · 研究领域：Genetic Neurodegenerative Diseases、Parkinson's Disease Mechanisms and Treatments、Amyotrophic Lateral Sclerosis Research

INTRODUCTION: Neuronal intranuclear inclusion disease (NIID) manifests as dementia combined with other neurological symptoms. However, small fiber neuropathy (SFN) and pathology remain unknown in NIID. METHODS: A total of 294 subjects, including patients with NIID, Parkinson's disease, Alzheimer's disease, diabetic peripheral neuropathy, and healthy controls (HCs), were included. Clinical scales, sensory and autonomic function testing, and skin biopsy were performed. RESULTS: NIID patients had more severe sensory and autonomic dysfunction than other groups. Substantial reductions in intraepidermal, sweat gland, and pilomotor nerve fiber densities were observed in NIID patients, with a non-length dependent pattern. Detailed analysis revealed marked reductions in noradrenergic, cholinergic, peptidergic, and regenerative nerve fibers. Small fiber densities showed high diagnostic accuracy in distinguishing NIID from HCs and other diseases. DISCUSSION: This study is the first to reveal wide and severe loss of small fibers in NIID, suggesting the involvement of SFN in the pathogenesis of NIID. HIGHLIGHTS: Our study is the first to identify wide and severe non-length dependent small fiber neuropathy in neuronal intranuclear inclusion disease (NIID) patients. Approximately 50% of NIID patients exhibited pure small fiber neuropathy without large fiber or mixed neuropathy. NIID patients showed a significant reduction in noradrenergic, cholinergic, peptidergic, and regenerative fiber in...