The histopathologic evaluation of small fibers in multiple sclerosis patients

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. Neuropathic pain is a common symptom in all MS types.The pathology of multiple sclerosis is the demyelination of central neurons, however the patients may have neuropathic pain in distal extremities similar to A-delta and C fiber dysfunction. It is not known whether the loss of small fiber may have a role in the generation of neuropathic pain in these MS patients. In this study we aim to investigate the small fiber loss and its length dependency. For this purpose, we evaluated the skin biopsies taken proximal and distal leg of MS patients with neuropathic pain. Twenty MS patients including 6 primary progressive MS, 7 relapsing-remitting MS and 7 secondary progressive MS, as control group ten age and sex-matched patients with different neurological disorders without neuropathic pain were included. Neurological examination, electrophysiological evaluation and DN4 questionnaire were performed. Subsequently, skin punch biopsies 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. Sixty-five percent of our MS patients complaint about neuropathic pain and three of them had glove-stocking sensation loss. The mean of IENFD was 8.58 (4.15-17.58) fiber/mm in proximal leg whereas 9.48 (4.92-20.03) fiber/mm in distal leg of MS patients. IENFD did not differ between MS and control groups. Moreover IENFD did not differ among MS subgroups. Although the intraepidermal nerve fiber density tends to be lower in proximal part of the leg in 80% of MS patients, there was not any statistical significance. Intraepidermal nerve fiber density in MS patients did not differ from control group. However IENFD was lower in proximal leg in 80% of MS patients. This finding has to be verified with new studies involving larger patient groups and quantitative sensory tests. Keywords: Small fiber neuropathy, multiple sclerosis, neuropathic pain, DN4 questionnar