Risk of false-positive findings in the assessment of small nerve fibers in healthy subjects

Twenty volunteers (12 women) were examined at Geneva University Hospitals (2019‑2023). Inclusion criteria: age ≥ 18 yr, no neurological symptoms or chronic disease, normal neurological examination. Written informed consent and ethics approval were obtained; 2024 follow‑up confirmed persistent absence of symptoms. ESC. Palms and soles were tested bilaterally (Sudoscan®, Impeto, France). Abnormal values: < 60 µS (hands) or < 70 µS (feet) [ 11 , 12 ]. LEP. An Nd:YAP laser (5 ms, 3 mm, 14 J cm⁻ ) stimulated each hand and foot dorsum. EEG responses (10–20 system; band‑pass 0.3–50 Hz, 256 Hz) were averaged over 20 artefact‑free trials. Latencies and amplitudes of N1 and N2‑P2 were compared with laboratory norms [ 13 ]. QST. CDT and WDT were measured at both ankles and thenar eminences with the level‑tracking algorithm (Medoc Advanced Medical System, Minneapolis, MN, USA) [ 14 ]. Values > 95th (WDT) or < 5th (CDT) percentiles of age‑matched controls were abnormal. Statistics employed t‑tests and Spearman correlations (two‑sided p < 0.05). Median age was 31.5 year -old (IQR 29.8–40.8). Nine participants (45%) exhibited at least one abnormal ESC value—hands < 60 µS in 4 / 9 cases and feet < 70 µS in 8 / 9—yet remained asymptomatic at two‑year follow‑up. LEP latencies/amplitudes and QST thresholds were normal in all 20 subjects (Table 1 ). Participants were categorised as decreased ESC (n = 9) or normal ESC (n = 11). Sex, height and weight did not differ; the decreased‑ESC group was older (median 43.0 vs 31.0 yr, p = 0.011). No systematic abnormalities emerged on LEP latencies or amplitudes, and CDT/WDT remained within reference ranges for every subject. Correlation analyses did not reveal consistent linear relationships between ESC, LEP and QST across limbs (Tables 2 , 3 and 4 ).