The Correlation Between Functional and Morphometric Small Fiber Assessment in Mixed Etiology Polyneuropathy

Background and Aims Skin biopsies are the primary diagnostic test for small fiber neuropathy, but recently corneal confocal microscopy ( CCM ) has been developed as an alternative. We compared the correlations of each of these morphometric assessments with peripheral nerve function evaluated through comprehensive quantitative sensory testing ( QST ) in a mixed etiology polyneuropathy cohort. Methods CCM and skin biopsies were performed in a prospective cohort of unselected patients undergoing polyneuropathy diagnostic work‐up. We used predefined criteria to identify patients with small or mixed fiber neuropathy. The correlations between corneal nerve fiber density ( CNFD ), fiber length ( CNFL ), branch density ( CNBD ), and tortuosity ( CNFT ) and the intraepidermal nerve fiber density ( IENFD ) at the distal leg and the results of QST at the foot were determined. Results Two‐hundred and forty‐four patients were included in the analysis. CNFD was negligibly correlated with warm detection threshold ( WDT ) ( r = −0.15; p = 0.023), while there was no statistically significant correlation with other QST measures. There were no statistically significant correlations between neither CNFL nor CNBD and any of the QST measures. CNFT correlated negligibly with WDT ( r = 0.17; p = 0.008) and vibration detection threshold ( VDT ) ( r = −0.13; p = 0.044). IENFD correlated moderately with WDT ( r = −0.33; p < 0.0001) and mechanical pain threshold ( r = −0.37; p < 0.0001) and weakly with cold detection threshold ( r = 0.21; p = 0.0008), mechanical detection threshold ( r = −0.21; p = 0.0008) and VDT ( r = 0.23; p = 0.0004). Interpretation IENFD correlated better with small and large fiber function at the foot than CCM measures in patients with mixed etiology polyneuropathy. Longitudinal studies are needed to assess the clinical utility for neuropathy progression.