Abstract
Small-fibre neuropathy (SFN), a disorder of thinly myelinated Aδ-fibres and unmyelinated C-fibres, is clinically characterized by neuropathic pain symptoms and autonomic complaints. Diagnosis of SFN is challenging as the clinical picture can be difficult to interpret and results from nerve conduction studies are often normal. In cases of suspected SFN, measurement of intraepidermal nerve fibre density and/or analysis of quantitative sensory testing can enable diagnosis. New diagnostic techniques (including measurement of nerve fibre density using corneal confocal microscopy, and nociceptive evoked potentials) may contribute to the diagnostic work-up. SFN can be associated with systemic diseases such as immune-mediated disorders, but remains idiopathic in a substantial proportion of patients. Gain-of-function variants in the Nav1.7 sodium channel have recently been found in nearly 30% of patients with idiopathic SFN, but the mechanisms of axonal degeneration in the disorder remain under investigation. Identification of the systemic diseases underlying SFN will enable development of drugs that target affected pathways to improve the management of neuropathic pain and autonomic dysfunction. In this Review, we discuss recent advances in the diagnosis and pathophysiology of SFN, highlighting how improved understanding of these aspects of the disorder will contribute to better patient management.
Key Points
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Small-fibre neuropathy (SFN) is a disorder of thinly myelinated Aδ-fibres and unmyelinated C-fibres
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SFN is diagnosed on the basis of presence of typical SFN-related symptoms, normal nerve conduction studies, reduced intraepidermal nerve fibre density at the ankle, and/or abnormal quantitative sensory testing
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SFN can be associated with systemic diseases, with an immune-mediated basis proposed in some cases; however, the cause remains unclear in a substantial number of patients
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Mutations in SCN9A, which encodes the sodium channel Nav1.7, were found to underlie SFN in a subset of patients
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Therapy for SFN focuses mainly on pain relief, management of autonomic dysfunction, and disease modification where possible
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Future studies into therapies for SFN should address the efficacy of immunomodulating agents and selective sodium channel blockers
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Hoeijmakers, J., Faber, C., Lauria, G. et al. Small-fibre neuropathies—advances in diagnosis, pathophysiology and management. Nat Rev Neurol 8, 369–379 (2012). https://doi.org/10.1038/nrneurol.2012.97
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DOI: https://doi.org/10.1038/nrneurol.2012.97
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