Non-invasive electrodiagnostic testing for small fibre neuropathy in long COVID-19, 2026, Khoo et al.

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Non-invasive electrodiagnostic testing for small fibre neuropathy in long COVID-19
Anthony Khoo; Kisani Manuel; Tracy Ng; Maria Crotty

BACKGROUND
Long COVID-19 is associated with a diverse range of debilitating neuropathic and autonomic symptoms that may indicate small fibre neuropathy (SFN). We aimed to assess the utility of multimodal non-invasive electrodiagnostic techniques in evaluating symptomatic individuals.

METHODS
People with confirmed long COVID-19 who scored >10 points on the Small Fibre Neuropathy Screening List (SFNSL) questionnaire underwent routine neurophysiological testing and a non-invasive SFN protocol of (a) sympathetic skin responses, (b) cutaneous silent period, (c) quantitative thermal thresholds and (d) electrochemical skin conductance. Clinical and demographic information was collected on all individuals who underwent comprehensive physical and psychometric evaluation, including a 6-min walk test, National Aeronautics and Space Administration (NASA) Lean Test, Composite Autonomic Symptom Score-31 (COMPASS-31), European Quality of Life 5-Dimension 5-Level Questionnaire (ED-5D-5L), Modified Fatigue Impact Scale (MFIS) score and Patient Health (depression) Questionnaire (PHQ-9).

RESULTS
We assessed nine individuals, of whom three (33%) had neurophysiological evidence of SFN. Median age was 47.8 (range 26.3–67.6) years, duration from COVID-19 infection 23.0 (range 8.5–35.7) months and median SFNSL 34/84. All individuals scored highly in disability measures.

CONCLUSIONS
Long COVID-19 is associated with functional disability and reduced quality of life. SFN should be considered in all individuals with a suggestive clinical phenotype of neuropathic and autonomic symptoms.

Web | DOI | PDF | BMJ Neurology Open | Open Access

 

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Short report. Small numbers.

Routine nerve conduction studies in all individuals were normal. We detected neurophysiological evidence of SFN in three (33%) individuals. This included two individuals with bilaterally absent lower limb sympathetic skin responses (SSRs), two individuals with prolonged cutaneous silent period (CSP) onset latency with normal duration in both upper and lower limbs, and two individuals with reduced electrochemical skin conductance (ESC) on Sudoscan.

There was no significant difference across symptom scores between people with and without SFN, with both groups scoring highly in disability measures (median EQ-5D-5L 40/100; MFIS 69/84; PHQ-9 18/27).

Notably, we demonstrated different combinations of abnormality among the four small fibre neuropathy tests illustrating the benefit of multimodal SFN testing protocols which interrogate different small nerve fibres.

Despite widespread limitations in testing for SFN, we have nonetheless provided proof of concept that there is utility to a multimodal neurophysiological testing protocol assessing SFN in long COVID-19. Although numbers are small, our results indicate that demonstrable abnormalities can be detected in a proportion of those complaining of both neuropathic and autonomic symptoms. This result is particularly notable given many of these individuals undergo extensive and often unremarkable investigations.