The diagnostic challenge of small fibre neuropathy: clinical presentations, evaluations, and causes

Lancet Neurol. 2017 Nov;16(11):934-944. doi: 10.1016/S1474-4422(17)30329-0.


Small fibre neuropathies are a heterogeneous group of disorders affecting thinly myelinated Aδ-fibres and unmyelinated C-fibres. Although multiple causes of small nerve fibre degeneration have been reported, including via genetic mutations, the cause of small fibre neuropathy remains unknown in up to 50% of cases. The typical clinical presentation of small fibre neuropathy is that of a symmetrical, length-dependent polyneuropathy associated with sensory or autonomic symptoms. More rarely, the clinical presentation is characterised by non-length-dependent, focal, or multifocal symptoms. The diagnostic tests to identify small fibre neuropathy include skin biopsy, quantitative sensory, and autonomic testing. Additional tests, such as those measuring small fibre-related evoked potentials and corneal confocal microscopy, might contribute to a better understanding of these neuropathies. Biochemical markers can also help in screening patients for the presence of small fibre neuropathy and to assess disease progression.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy / methods
  • Female
  • Humans
  • Male
  • Microscopy, Confocal
  • Neural Conduction / physiology
  • Skin / pathology
  • Small Fiber Neuropathy / diagnosis*
  • Small Fiber Neuropathy / etiology*
  • Small Fiber Neuropathy / genetics
  • Small Fiber Neuropathy / physiopathology