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Abstract
Objective To investigate small fiber innervation of the skin and its relationships with clinicometry of autism and peripheral afferents for contact heat-evoked potential (CHEP) and psychophysical measures of thermal thresholds.
Methods We recruited 32 men with autism (26.5 ± 5.9 years) and conducted small fiber assessments of skin biopsy with quantifying intraepidermal nerve fiber (IENF) density, CHEP, quantitative sensory testing, and large fiber physiology of nerve conduction studies. Results were compared with age-matched controls and analyzed with clinical measures of autism.
Results Patients with autism showed a lower IENF density than controls (5.53 ± 2.09 vs 11.13 ± 3.49 fibers/mm, p < 0.0001). The IENF density was reduced in 17 (53.1%) men with autism classified as skin denervation group. On psychophysics, 9 (28%) men with autism had elevated thermal thresholds, and the warm threshold of the big toe was negatively correlated with IENF density (p = 0.0073), indicating functional impairments of small fiber sensory nerves. IENF density was negatively correlated with CHEP amplitude in autism (p = 0.003), in contrast to the pattern of positive correlation in controls, indicating different processing of nociceptive afferent in autism. Clinically, IENF density was related to distinct tactile symptom patterns in the skin denervation vs normal innervation group, respectively. Furthermore, IENF density was associated with autistic symptoms measured by the Autism Spectrum Quotient in a U-shaped model (p = 0.014).
Conclusions These observations indicated that a substantial portion of individuals with autism had small fiber pathology, which was associated with tactile and autistic symptoms, providing structural and physiologic evidence for the involvement of peripheral sensory nerves in autism.
Glossary
- CHEP=
- contact heat evoked potential;
- FDR=
- false discovery rate;
- IENF=
- intraepidermal nerve fiber;
- NCS=
- nerve conduction studies;
- PGP=
- protein gene product 9.5;
- QST=
- quantitative sensory testing;
- SP=
- Sensory Profile
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Editorial, page 851
CME Course: NPub.org/cmelist
- Received November 22, 2019.
- Accepted in final form July 15, 2020.
- © 2020 American Academy of Neurology
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