The evaluation of small fibers in multiple sclerosis

Bekircan-Kurt C. E., Jahanroshan J., Tuncer A., ERGÜL ÜLGER Z., Gunes G., ERDEM ÖZDAMAR S., ...More

Multiple Sclerosis and Related Disorders, vol.72, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 72
  • Publication Date: 2023
  • Doi Number: 10.1016/j.msard.2023.104602
  • Journal Name: Multiple Sclerosis and Related Disorders
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE
  • Keywords: Intraepidermal nerve fiber density, Multiple sclerosis, Neuropathic pain, Small fiber neuropathy
  • Hacettepe University Affiliated: Yes


Background: Dysesthetic or ongoing extremity pain is a common symptom in all multiple sclerosis (MS) types. Although the pathology of the disease is the demyelination of central neurons, the patients may also complain of neuropathic pain in distal extremities that is generally related to A-delta and C fiber dysfunction. It is not known whether thinly myelinated and unmyelinated fibers are affected in MS patients. We aim to investigate the small fiber loss and its length dependency. Methods: We evaluated the skin biopsy taken from proximal and distal leg of MS patients with neuropathic pain. Six patients with primary progressive MS (PPMS), seven with relapsing-remitting MS (RRMS), seven with secondary progressive MS (SPMS) and as a control group ten age and sex-matched healthy controls were included. Neurological examination, electrophysiological evaluation and DN4 questionnaire were performed. Subsequently, skin punch biopsy from 10 cm above the lateral malleolus and proximal thigh were done. The biopsy samples were stained with PGP9.5 antibody and intraepidermal nerve fiber density (IENFD) was determined. Results: The mean proximal IENFD was 8.58±3.58 fibers/mm among MS patients and 14.72±2.89 fiber/mm among healthy controls (p=0.001). However, the mean distal IENFD did not differ between MS patients and healthy controls (9.26±3.24 and 9.75±1.6 fiber/mm respectively. Although proximal and distal IENFD tends to be lower in MS patients with neuropathic pain, there was no statistically significant difference between MS patients with and without neuropathic pain Conclusion: Although MS is a demyelinating disease, unmyelinated fibers can also be affected. Our findings suggest non-length dependent small fiber neuropathy in MS patients.