Advances in diagnosis and management of distal sensory polyneuropathies

Abstract

Distal sensory polyneuropathy (DSP) is characterised by length-dependent, sensory-predominant symptoms and signs, including potentially disabling symmetric chronic pain, tingling and poor balance. Some patients also have or develop dysautonomia or motor involvement depending on whether large myelinated or small fibres are predominantly affected. Although highly prevalent, diagnosis and management can be challenging. While classic diabetes and toxic causes are well-recognised, there are increasingly diverse associations, including with dysimmune, rheumatological and neurodegenerative conditions. Approximately half of cases are initially considered idiopathic despite thorough evaluation, but often, the causes emerge later as new symptoms develop or testing advances, for instance with genetic approaches. Improving and standardising DSP metrics, as already accomplished for motor neuropathies, would permit in-clinic longitudinal tracking of natural history and treatment responses. Standardising phenotyping could advance research and facilitate trials of potential therapies, which lag so far. This review updates on recent advances and summarises current evidence for specific treatments.

Publication DOI: https://doi.org/10.1136/jnnp-2021-328489
Divisions: College of Health & Life Sciences
Funding Information: MSilsby, ELF, RDD, AR, SV, ALO and NGS reports no competing interests. SH reports personal fees from Rafa Laboratories, Vertex Pharmaceuticals and GW Pharmaceuticals, and research grants from Eli Lilly, outside the scope of this work. YAR has received speaker/consultancy honoraria from LFB, Polyneuron and Argenx and has received educational sponsorships from LFB and CSL Behring and has obtained research grants from LFB and CSL Behring. MShy has no competing interests related to this publication. He serves as a consultant for Applied Therapeutics, DTx Pharma, Mitochondria in Motion, Swan Biosci and Inflectis. RDD reports funding from the US Department of Defence (PR211292), US Department of Health and Human Services, National Institutes of Health, National Centre for Advancing Translational Sciences (R21 TR003312) and the Barrow Neurological Foundation. ELF is supported by the US Department of Health and Human Services National Institutes of Health (R24DK082841, R01DK130913) and the Juvenile Diabetes Research Foundation (5-COE-2019-861-s—B). SH reports funding from US Department of Health and Human Services, National Institutes of Health, National Institute of Neurological Disorders and Stroke (R01NS104500-01) and the US Department of Defence (W81XWH2110736). ALO reports funding from US Department of Health and Human Services National Institutes of Health (R01NS093653), US Department of Defence (GW140169) and the Curvey, Cutler and Mayday Foundations. MES reports funding from US Department of Health and Human Services, National Institutes of Health, National Centre for Advancing Translational Sciences for the Inherited Neuropathy Consortium ((U54NS065712) MES also receives support from the Muscular Dystrophy Association and Charcot-Marie-Tooth Association. MES also receives support from US Department of Health and Human Services, National Institutes of Health, National Institute of Neurological Disorders and Stroke (grant numbers R01NS105755 and U01 NS1094301). SV reports funding support from the Department of Health, Australian Government, National Health and Medical Research Council (project grant numbers 1024915, 2001261).
Additional Information: Copyright © 2023, Author(s) (or their employer(s)). Published by BMJ. This article has been accepted for publication in the Journal of Neurology, Neurosurgery & Psychiatry, 2023, following peer review, and the Version of Record can be accessed online at: https://doi.org/10.1136/jnnp-2021-328489. Reuse of this manuscript version (excluding any databases, tables, diagrams, photographs and other images or illustrative material included where a another copyright owner is identified) is permitted strictly pursuant to the terms of the Creative Commons Attribution-Non Commercial 4.0 International (CC-BY-NC 4.0) https://creativecommons.org/licenses/by-nc/4.0/.
Uncontrolled Keywords: Neurogenetics,Neuroimmunology,Neuromuscular,Neuropathy,Peripheral Neuropathology,Surgery,Clinical Neurology,Psychiatry and Mental health
Publication ISSN: 1468-330X
Last Modified: 09 Feb 2026 08:11
Date Deposited: 09 Jun 2023 14:24
Full Text Link:
Related URLs: https://jnnp.bm ... nnp-2021-328489 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Review article
Published Date: 2023-12-01
Published Online Date: 2023-03-30
Accepted Date: 2023-02-23
Authors: Silsby, Matthew
Feldman, Eva L.
Dortch, Richard D.
Roth, Alison
Haroutounian, Simon
Rajabally, Yusuf A. (ORCID Profile 0000-0002-7170-8343)
Vucic, Steve
Shy, Michael E.
Oaklander, Anne Louise
Simon, Neil G.

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