Clinical Characteristics, Electrophysiology, and Skin Biopsy of 38 Peripheral Neuropathy Cases with Small Fiber Involvement of Various Etiologies

BACKGROUND: In small fiber neuropathy (SFN), thinly myelinated Aδ and unmyelinated C fibers are primarily affected, resulting in sensory and/or autonomic symptoms. Various etiologies have been shown to be associated with SFN. This study was aimed to analyze a variety of features in peripheral neuropathy (PN) with small fiber involvement, and to compare disease severity among patients with idiopathic PN, PN associated with impaired glucose tolerance (IGT), and metabolic syndrome (MS) PN. METHODS: Thirty-eight PN patients with small fiber involvement were enrolled from December 20, 2013 to May 31, 2016. Patients were divided into idiopathic PN, IGT-related PN, and MS-related PN groups. Detailed medical history and small fiber neuropathy were investigated, and symptom inventory questionnaire was conducted, as well as the visual analog scale. Nerve conduction studies and skin biopsies were also performed. The differences among the groups were analyzed using analysis of variance and Kruskal-Wallis test. RESULTS: Eight patients were diagnosed with pure SFN. Intraepidermal nerve fiber density (IENFD) weakly correlated with motor conduction velocity (MCV) (r = 0.372, P = 0.025), and proximal (r = 0.383, P = 0.021) and distal (r = 0.358, P = 0.032) compound muscle action potential (CMAP) of the tibial nerve. IENFD also weakly correlated with MCV of the peroneal nerve (r = 0.399, P = 0.016). IENFD was shown to be significantly different among all groups (χ(2) = 9.901, P = 0.007). IENFD was significantly decreased (χ(2) = 23.000, P = 0.003) in the MS-related PN group compared to the idiopathic PN group. The MCV of the tibial nerve was significantly different among all groups (χ(2) = 8.172, P < 0.017). The proximal (F = 4.336, P = 0.021) and distal (F = 3.262, P = 0.049) CMAP of the tibial nerve was also significantly different among all groups. CONCLUSIONS: IENFD of patients included in the present study weakly correlated with various electrophysiological parameters. Small and large fibers are more involved in patients with MS-related PN than in patients with idiopathic PN.