Skin innervation across amyotrophic lateral sclerosis clinical stages: new prognostic biomarkers.

Autor:	Nolano M; Istituti Clinici Scientifici Maugeri IRCCS, Skin Biopsy Lab, Neurological Rehabilitation Unit of Telese Terme Institute, Telese Terme, Benevento 82037, Italy.; Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples 80131, Italy., Provitera V; Istituti Clinici Scientifici Maugeri IRCCS, Skin Biopsy Lab, Neurological Rehabilitation Unit of Telese Terme Institute, Telese Terme, Benevento 82037, Italy., Caporaso G; Istituti Clinici Scientifici Maugeri IRCCS, Skin Biopsy Lab, Neurological Rehabilitation Unit of Telese Terme Institute, Telese Terme, Benevento 82037, Italy., Fasolino I; Institute of Polymers, Composites and Biomaterials-National Research Council (IPCB-CNR), Naples 80125, Italy., Borreca I; Istituti Clinici Scientifici Maugeri IRCCS, Skin Biopsy Lab, Neurological Rehabilitation Unit of Telese Terme Institute, Telese Terme, Benevento 82037, Italy., Stancanelli A; Istituti Clinici Scientifici Maugeri IRCCS, Skin Biopsy Lab, Neurological Rehabilitation Unit of Telese Terme Institute, Telese Terme, Benevento 82037, Italy., Iuzzolino VV; Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples 80131, Italy., Senerchia G; Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples 80131, Italy., Vitale F; Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples 80131, Italy., Tozza S; Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples 80131, Italy., Ruggiero L; Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples 80131, Italy., Iodice R; Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples 80131, Italy., Ferrari S; Neurology Unit, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Policlinico GB Rossi, Verona 37134, Italy., Santoro L; Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples 80131, Italy., Manganelli F; Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples 80131, Italy., Dubbioso R; Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples 80131, Italy.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2024 May 03; Vol. 147 (5), pp. 1740-1750.
DOI:	10.1093/brain/awad426
Abstrakt:	Over recent decades, peripheral sensory abnormalities, including the evidence of cutaneous denervation, have been reported among the non-motor manifestations in amyotrophic lateral sclerosis (ALS). However, a correlation between cutaneous innervation and clinical features has not been found. The aims of this study were to assess sensory involvement by applying a morpho-functional approach to a large population of ALS patients stratified according to King's stages and correlate these findings with the severity and prognosis of the disease. We recruited 149 ALS patients and 41 healthy controls. Patients undertook clinical questionnaires for small fibre neuropathy symptoms (Small Fiber Neuropathy Symptoms Inventory Questionnaire) and underwent nerve conductions studies (NCS) and 3-mm punch skin biopsies from leg, thigh and fingertip. We assessed intraepidermal nerve fibre (IENF) and Meissner corpuscle (MC) density by applying an indirect immunofluorescence technique. Moreover, a subset of 65 ALS patients underwent a longitudinal study with repeat biopsies from the thigh at 6- and 12-month follow-ups. Serum NfL levels were measured in 40 patients. Sensory symptoms and sensory NCS abnormalities were present in 32.2% and 24% of patients, respectively, and increased across clinical stages. Analogously, we observed a progressive reduction in amplitude of the sensory and motor ulnar nerve potential from stage 1 to stage 4. Skin biopsy showed a significant loss of IENFs and MCs in ALS compared with healthy controls (all P < 0.001). Across the clinical stages, we found a progressive reduction in MCs (P = 0.004) and an increase in IENFs (all P < 0.027). The increase in IENFs was confirmed by the longitudinal study. Interestingly, the MC density inversely correlated with NfL level (r = -0.424, P = 0.012), and survival analysis revealed that low MC density, higher NfL levels and increasing IENF density over time were associated with a poorer prognosis (all P < 0.024). To summarize, in patients with ALS, peripheral sensory involvement worsens in parallel with motor disability. Furthermore, the correlation between skin innervation and disease activity may suggest the use of skin innervation as a putative prognostic biomarker. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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