Department of Neurology, University of Würzburg, Germany.
Department of Psychiatry, Psychosomatics, and Psychotherapy, University of Würzburg, Germany.
Ann Neurol. 2019 Oct;86(4):504-516. doi: 10.1002/ana.25565. Epub 2019 Aug 21.
To assess patterns and impact of small nerve fiber dysfunction and pathology in patients with fibromyalgia syndrome (FMS).
One hundred seventeen women with FMS underwent neurological examination, questionnaire assessment, neurophysiology assessment, and small fiber tests: skin punch biopsy, corneal confocal microscopy, microneurography, quantitative sensory testing including C-tactile afferents, and pain-related evoked potentials. Data were compared with those of women with major depressive disorder and chronic widespread pain (MD-P) and healthy women.
Intraepidermal nerve fiber density (IENFD) was reduced at different biopsy sites in 63% of FMS patients (MD-P: 10%, controls: 18%; p < 0.001 for each). We found 4 patterns of skin innervation in FMS: normal, distally reduced, proximally reduced, and both distally and proximally reduced (p < 0.01 for each compared to controls). Microneurography revealed initial activity-dependent acceleration of conduction velocity upon low frequencies of stimulation in 1A fibers, besides 1B fiber spontaneous activity and mechanical sensitization in FMS patients. FMS patients had elevated warm detection thresholds (p < 0.01), impaired C-tactile afferents (p < 0.05), and reduced amplitudes (p < 0.001) of pain-related evoked potentials compared to controls. Compared to FMS patients with normal skin innervation, those with generalized IENFD reduction had higher pain intensity and impairment due to pain, higher disease burden, more stabbing pain and paresthesias, and more anxiety (p < 0.05 for each). FMS patients with generalized IENFD reduction also had lower corneal nerve fiber density (p < 0.01) and length (p < 0.05).
The extent of small fiber pathology is related to symptom severity in FMS. This knowledge may have implications for the diagnostic classification and treatment of patients with FMS. ANN NEUROL 2019;86:504-516.
评估纤维肌痛综合征（FMS）患者小纤维功能障碍和病理的模式及影响。
117 名 FMS 女性患者接受了神经学检查、问卷调查评估、神经生理学评估和小纤维测试：皮肤活检、角膜共聚焦显微镜、微神经图、包括 C 触觉传入在内的定量感觉测试以及疼痛相关诱发电位。将数据与患有重度抑郁症和广泛性慢性疼痛（MD-P）的女性以及健康女性进行比较。
63%的 FMS 患者（MD-P：10%，对照组：18%；每一项均 p<0.001）不同活检部位的表皮内神经纤维密度（IENFD）降低。我们发现 FMS 有 4 种皮肤神经支配模式：正常、远端减少、近端减少以及远近两端均减少（与对照组相比，每一种模式均 p<0.01）。微神经图显示 1A 纤维在低频刺激时初始活动依赖性传导速度加速，除了 1B 纤维的自发性活动和机械敏化外，FMS 患者还存在这种情况。与对照组相比，FMS 患者的温暖检测阈值升高（p<0.01），C 触觉传入受损（p<0.05），疼痛相关诱发电位的振幅降低（p<0.001）。与皮肤神经支配正常的 FMS 患者相比，广泛 IENFD 减少的患者疼痛强度和疼痛所致损伤更大、疾病负担更高、刺痛和感觉异常更多、焦虑更严重（每一项均 p<0.05）。广泛 IENFD 减少的 FMS 患者的角膜神经纤维密度（p<0.01）和长度（p<0.05）也更低。
小纤维病理的程度与 FMS 患者的症状严重程度相关。这一知识可能对 FMS 患者的诊断分类和治疗具有重要意义。
