Ratio of Distal to Proximal Epidermal Nerve Fiber Density in Small Fiber Neuropathy

Intraepidermal nerve fiber density (IENFD) assessment is an important tool for diagnosing small fiber neuropathy (SFN), with distal leg and proximal thigh biopsies commonly performed to evaluate length dependency. Although age-dependent normative data exist for distal leg IENFD, some patients with paresthesias exhibit normal values at both sites but a markedly lower distal IENFD compared to proximal density. The aim of this study is to assess the diagnostic value of the distal-to-proximal IENFD ratio in SFN. Charts of patients who underwent skin biopsy for evaluation of SFN between May 2020 and May 2023 at the Neurology Department, University of Kansas Medical Center, were retrospectively reviewed. IENFD was measured at the distal leg and proximal thigh, and the distal-to-proximal ratio calculated. Patients were classified as having possible or probable SFN based on NEURODIAB criteria, or as not meeting diagnostic criteria. Of 64 charts reviewed, 56 were enrolled, the female-to-male ratio was 3:1 and mean age was 50±26 years. Forty-six patients met clinical criteria for SFN (16 possible, 30 probable), with IENFD abnormal in 23 and normal in 23, showing mean ratios of 0.5 and 0.6, respectively. Patients without a clinical diagnosis of neuropathy had a mean ratio of 0.9, and among patients with clinical SFN but normal biopsy results, the mean ratio was significantly lower than in those without clinical SFN (p=0.02). These findings suggest that, in patients with normal IENFD but high clinical suspicion for SFN, the distal-to-proximal IENFD ratio may serve as an additional parameter to improve diagnostic sensitivity.