Small-fiber sensory neuropathies: clinical course and neuropathology of idiopathic cases

Ann Neurol. 1998 Jul;44(1):47-59. doi: 10.1002/ana.410440111.


We describe the clinical features, natural history, and neuropathology of 32 patients presenting with "burning feet," for whom no specific cause was identified. All had neuropathic pain in the feet and morphological abnormalities of cutaneous innervation in skin obtained using punch biopsy. Most (29) had an abnormal sensory examination. All had normal strength, proprioception, tendon reflexes, and nerve conductions. Two clinical patterns were apparent, based on natural history and spatial distribution of cutaneous denervation. Most (28) patients presented with neuropathic pain initially restricted to the feet and toes but extending more proximally to involve the legs and hands with time. Intraepidermal nerve fiber (IENF) density was most severely reduced distally, with more normal IENF densities in skin from proximal sites. In contrast, a minority (4) presented with the abrupt onset of generalized cutaneous burning pain and hyperesthesia. In these patients, IENF densities were reduced in skin from both proximal and distal sites. Absolute IENF densities in calf skin were reduced below the lower limit of normal (5th percentile) in 26 (81%). Of the 6 who underwent sural nerve biopsy, 4 had selective loss of small myelinated and/or unmyelinated axons and 2 had normal histology and fiber densities despite reduced IENF densities in skin biopsy specimens. Punch skin biopsy from proximal and distal sites is a useful means of assessing these distinctive patients and may provide further insight into pathophysiology.

Publication types

  • Case Reports
  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Biopsy
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neural Conduction
  • Pain / etiology
  • Pain / physiopathology*
  • Peripheral Nervous System Diseases / complications
  • Peripheral Nervous System Diseases / diagnosis*
  • Peripheral Nervous System Diseases / physiopathology
  • Proprioception
  • Reference Values
  • Reflex, Stretch
  • Sensation Disorders / etiology*
  • Skin / innervation*
  • Skin / pathology
  • Statistics, Nonparametric
  • Sural Nerve / pathology