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

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-02-23 DOI:10.1002/alz.14596

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, Chen Liu, Yanjiang Wang, Yuming Xu, Jing Yang

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引用次数: 0

Abstract

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 innervation.
Small fiber densities, especially intraepidermal nerve fiber density, demonstrated high diagnostic accuracy in distinguishing NIID patients from healthy controls and other disease groups.
Findings suggest that small fiber neuropathy may play a role in the pathogenesis of NIID.

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引言神经元核内包涵体病（NIID）表现为痴呆并伴有其他神经症状。然而，小纤维神经病（SFN）和病理在 NIID 中仍不为人知。方法共纳入 294 名受试者，包括 NIID、帕金森病、阿尔茨海默病、糖尿病周围神经病变患者和健康对照组（HCs）。研究人员进行了临床量表、感觉和自主神经功能测试以及皮肤活检。结果 NIID 患者的感觉和自主神经功能障碍比其他组更严重。在 NIID 患者中观察到表皮内、汗腺和皮层运动神经纤维密度大幅降低，且与长度无关。详细分析显示，去甲肾上腺素能、胆碱能、肽能和再生神经纤维明显减少。小纤维密度在区分 NIID 和 HC 及其他疾病方面显示出很高的诊断准确性。讨论本研究首次发现了 NIID 中广泛而严重的小纤维缺失，提示 SFN 参与了 NIID 的发病机制。亮点我们的研究首次在神经元核内包涵体病（NIID）患者中发现了广泛而严重的非长度依赖性小纤维神经病。约50%的NIID患者表现为纯粹的小纤维神经病变，而无大纤维或混合型神经病变。 NIID 患者的去甲肾上腺素能、胆碱能、肽能和再生纤维神经支配明显减少。小纤维密度，尤其是表皮内神经纤维密度，在区分 NIID 患者与健康对照组和其他疾病组方面具有很高的诊断准确性。研究结果表明，小纤维神经病变可能在 NIID 的发病机制中起到一定作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.