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Curr Opin Neurol. 2012 Oct;25(5):542-9. doi: 10.1097/WCO.0b013e32835804c5.

Small fibre neuropathy.

Author information

  • 1Neuromuscular Diseases Unit, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy. glauria@istituto-besta.it



This review summarizes the most recent advances in classification, diagnostic assessment, and treatment of small fibre neuropathy (SFN).


Clinically based diagnostic criteria for SFN have been proposed and reliably supported by the recent availability of age-adjusted and sex-adjusted normative values for intraepidermal nerve fibre density. Apart from skin biopsy, corneal confocal microscopy and nociceptive evoked potentials have been implemented to investigate SFN of different causes, and correlated with skin biopsy findings, especially in diabetic patients. The association between SFN and several metabolic and immune-mediated systemic diseases, and drugs toxic to this subset of peripheral nerve fibres has been reported. An exciting advance has been the identification of gain-of-function mutations in the SCN9A gene encoding for Nav1.7 sodium channel in patients with SFN, leading to the definition of a new genetic channelopathy.


SFN represents a distinct condition encountered in patients with different acquired and genetic disorders. The recent improved definition of clinical and skin biopsy criteria allows clinicians to reliably meet the diagnosis, identify the underlying cause, and prescribe appropriate treatments. This meaningful approach permits the correct management of patients in clinical practice and the design of symptomatic and disease-modifying clinical trials.

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