Yuting Ren1,2, Wenxiu Liu1, Yifan Li1, Bo Sun1, Yanran Li1, Fei Yang1, Hongfen Wang1, Mao Li1, Fang Cui1, Xusheng Huang3. 1. Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China. 2. Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 3. Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China. lewish301@sina.com.
Abstract
OBJECTIVE: To evaluate the involvement of the sensory and autonomic nervous system in amyotrophic lateral sclerosis (ALS) and to determine whether TDP-43/pTDP-43 deposits in skin nerve fibers signify a valuable biomarker for ALS. METHODS: Eighteen patients with ALS and 18 age- and sex-matched control subjects underwent physical examinations, in addition to donating skin biopsies from the distal leg. The density of epidermal, Meissner's corpuscle (MC), sudomotor, and pilomotor nerve fibers were measured. Confocal microscopy was used to determine the cutaneous somatic and autonomic nerve fiber density and TDP-43/pTDP-43 deposition. RESULTS: Intraepidermal nerve fiber density (IENFD) was reduced in individuals with ALS (P < 0.001). MC density (MCD) (P = 0.001), sweat gland nerve fiber density (SGNFD) (P < 0.001), and pilomotor nerve fiber density (PNFD) (P < 0.001) were all reduced in ALS patients. The SGNFD correlated with the small-fiber neuropathy Symptoms Inventory Questionnaire (SFN-SIQ), VAS and age. The SFN-SIQ was higher in ALS with sensory symptoms than without sensory symptoms (P = 0.000). Furthermore, the SFN-SIQ was higher in ALS with autonomic symptoms than without autonomic symptoms (P = 0.002). SFN-SIQ was higher in ALS patients that were pTDP-43 positive than pTDP-43 negative (P = 0.04), respectively. CONCLUSIONS: We established in the peripheral nervous system that higher SFN-SIQ and VAS was involved in ALS, indicating the loss of SGNF. The deposition of TDP-43/pTDP-43 in ALS nerve fibers may indicate an important role in the underlying pathogenesis of ALS. This observation might be used as a potential biomarker for diagnosing ALS.
OBJECTIVE: To evaluate the involvement of the sensory and autonomic nervous system in amyotrophic lateral sclerosis (ALS) and to determine whether TDP-43/pTDP-43 deposits in skin nerve fibers signify a valuable biomarker for ALS. METHODS: Eighteen patients with ALS and 18 age- and sex-matched control subjects underwent physical examinations, in addition to donating skin biopsies from the distal leg. The density of epidermal, Meissner's corpuscle (MC), sudomotor, and pilomotor nerve fibers were measured. Confocal microscopy was used to determine the cutaneous somatic and autonomic nerve fiber density and TDP-43/pTDP-43 deposition. RESULTS: Intraepidermal nerve fiber density (IENFD) was reduced in individuals with ALS (P < 0.001). MC density (MCD) (P = 0.001), sweat gland nerve fiber density (SGNFD) (P < 0.001), and pilomotor nerve fiber density (PNFD) (P < 0.001) were all reduced in ALSpatients. The SGNFD correlated with the small-fiber neuropathy Symptoms Inventory Questionnaire (SFN-SIQ), VAS and age. The SFN-SIQ was higher in ALS with sensory symptoms than without sensory symptoms (P = 0.000). Furthermore, the SFN-SIQ was higher in ALS with autonomic symptoms than without autonomic symptoms (P = 0.002). SFN-SIQ was higher in ALSpatients that were pTDP-43 positive than pTDP-43 negative (P = 0.04), respectively. CONCLUSIONS: We established in the peripheral nervous system that higher SFN-SIQ and VAS was involved in ALS, indicating the loss of SGNF. The deposition of TDP-43/pTDP-43 in ALS nerve fibers may indicate an important role in the underlying pathogenesis of ALS. This observation might be used as a potential biomarker for diagnosing ALS.
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