NLD-SFN is a chronic neuropathic condition with heterogeneous clinical manifestations. The relationship between intraepidermal nerve fiber density (IENFD), the spatial distribution of somatosensory symptoms, and patient quality of life (QoL) and functional burden remains unclear.

A retrospective analysis was conducted using the Tufts Neuromuscular Registry to identify 47 patients with NLD-SFN evaluated over a 5-year period. All patients underwent skin biopsies at the proximal thigh and distal leg and were categorized as: 1) abnormal IENFD, 2) normal IENFD with abnormal distal-to-proximal ratio, or 3) normal ratio and count. Patients completed a body map, self-reporting the location and severity of discomfort across 72 regions encompassing the body. Patients answered functional and QoL PROs (SFN-RODS, SFN-SIQ, Norfolk ADL, and COMPASS-31). Applying the Lund and Browder framework, we computed 5 topographic metrics– Total Body Surface Area (TBSA), Area-Weighted Mean Intensity (AWMI), Intensity-Adjusted Surface (IAS), Dispersion, and Contiguity. Spearman correlations were performed between these metrics and PROs, and Kruskal-Wallis tests were used to compare spatial metrics and PROs across biopsy groups.

TBSA, AWMI, IAS, and Dispersion significantly correlated with SFN-RODS, SFN-SIQ, Norfolk ADL, and COMPASS-31 (p < 0.01), indicating that more widespread and intense symptoms were associated with functional and autonomic deficits related to small fiber dysfunction. Contiguity did not significantly correlate with PROs, and no significant differences were found in topographic metrics or PROs across biopsy groups.

This study proposes a novel quantitative methodology for topographical assessment of symptom burden in NLD-SFN. Spatial metrics correlate with functional and autonomic measures, indicating their ability to capture disease aspects more comprehensively than skin pathology alone. Body-map-based measures show promise not only as a tool for phenotypic classification, but in informing management and treatment.