CMT1A与RFC1疾病中不同的小纤维功能障碍特征：一项多模态研究。
Distinct small-fiber dysfunction profiles in CMT1A and RFC1 disease: a multimodal study.
文献信息
| PMID | 42749946 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Sara Massucco |
| 作者单位 | Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy. |
| 期刊 | Journal of neurology |
| SCI 分区 | Q1 |
| IF | 5.3 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 耳科 |
中文摘要
背景： 腓骨肌萎缩症1A型（CMT1A）和小脑性共济失调、神经病、前庭无反射综合征（CANVAS）/复制因子复合体亚基1（RFC1）相关疾病影响大神经纤维，但小纤维功能障碍可能参与疼痛和自主神经功能障碍。我们应用了一种多模态方案，包括由微图案电极靶向表皮内神经末梢所诱发的电位，以表征小纤维受累。
方法： 在这项横断面研究中，健康对照（HC）以及CMT1A或RFC1疾病患者接受了神经系统检查、使用复合自主神经症状评分-31（COMPASS-31）和复合自主神经功能障碍试验（CADT）进行的自主神经评估、电化学皮肤电导（ESC）、伤害性诱发电位（NEPs）、疼痛相关诱发电位（PREPs）、躯体感觉诱发电位（SEPs）以及皮肤活检。
结果： 共纳入21例CMT1A患者、16例RFC1疾病患者和21例HC。神经病理性疼痛发生于33%的CMT1A患者和81%的RFC1患者。自主神经功能障碍在RFC1疾病中突出，94%的患者CADT评分异常，COMPASS-31评分为7-46，63%的患者ESC异常，而CMT1A中为24%。与HC相比，两组患者的N40 NEP潜伏期均延长（p<0.001），分别有33%和44%的患者反应缺失。PREPs显示CMT1A中N2潜伏期延长（p=0.003），57%的患者N2反应缺失；在RFC1疾病中，50%的患者N2反应缺失。皮肤活检显示CMT1A中呈长度依赖性表皮内神经纤维密度丢失，而RFC1疾病中为严重的非长度依赖性表皮去神经支配。
讨论： 整合ESC、NEPs、PREPs和皮肤活检的多模态评估可识别CMT1A和RFC1疾病中不同的Aδ纤维和C纤维功能障碍模式，并可能支持周围神经病中的表型分型和 小纤维生物标志物开发。
英文摘要
BACKGROUND: Charcot-Marie-Tooth disease 1A (CMT1A) and Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS)/Replication Factor Complex subunit 1 (RFC1)-related disease affect large nerve fibers, but small fiber dysfunction may contribute to pain and dysautonomia. We applied a multimodal protocol, including potentials elicited by a micropatterned electrode targeting intraepidermal nerve endings, to characterize small fiber involvement.
METHODS: In this cross-sectional study, healthy controls (HC) and patients with CMT1A or RFC1 disease underwent neurologic examination, autonomic assessment with the composite autonomic symptom score-31 (COMPASS-31) and compound autonomic dysfunction test (CADT), electrochemical skin conductance (ESC), nociceptive evoked potentials (NEPs), pain-related evoked potentials (PREPs), somatosensory evoked potentials (SEPs), and skin biopsy.
RESULTS: Twenty-one patients with CMT1A, 16 with RFC1 disease, and 21 HC were included. Neuropathic pain occurred in 33% of CMT1A and 81% of RFC1 patients. Dysautonomia was prominent in RFC1 disease, with abnormal CADT scores in 94%, COMPASS-31 scores of 7-46, and abnormal ESC in 63%, compared with 24% in CMT1A. N40 NEP latencies were prolonged in both patient groups versus HC (p<0.001), with absent responses in 33% and 44%, respectively. PREPs showed prolonged N2 latencies in CMT1A (p=0.003), with absent N2 responses in 57%; in RFC1 disease, N2 responses were absent in 50%. Skin biopsy showed length-dependent intraepidermal nerve fiber density loss in CMT1A and severe non-length-dependent epidermal denervation in RFC1 disease.
DISCUSSION: Multimodal assessment integrating ESC, NEPs, PREPs, and skin biopsy identifies distinct Aδ- and C-fiber dysfunction patterns in CMT1A and RFC1 disease and may support phenotyping and small-fiber biomarker development in peripheral neuropathies.