Intraepidermal nerve fiber density at the distal leg: A worldwide normative reference study

Giuseppe Lauria, Mayienne Bakkers, Christoph Schmitz, Raffaella Lombardi, Paola Penza, Grazia Devigili, A. Gordon Smith, Sung Tsieh Hsieh, Svein I. Mellgren, Thirugnanam Umapathi, Dan Ziegler, Catharina G. Faber, Ingemar S J Merkies

Research output: Contribution to journalArticle

Abstract

The diagnostic reliability of skin biopsy in small fiber neuropathy depends on the availability of normative reference values. We performed a multicenter study to assess the normative values of intraepidermal nerve fiber (IENF) density at distal leg stratified by age deciles. Eight skin biopsy laboratories from Europe, USA, and Asia submitted eligible data. Inclusion criteria of raw data were healthy subjects 18 years or older; known age and gender; 3-mm skin biopsy performed 10-cm above the lateral malleolus; bright-field immunohistochemistry protocol, and quantification of linear IENF density in three 50-μm sections according to published guidelines. Data on height and weight were recorded, and body mass index (BMI) was calculated in subjects with both available data. Normative IENF density reference values were calculated through quantile regression analysis; influence of height, weight, or BMI was determined by regression analyses. IENF densities from 550 participants (285 women, 265 men) were pooled. We found a significant age-dependent decrease of IENF density in both genders (women p <0.001; men p = 0.002). Height, weight, or BMI did not influence the calculated 5th percentile IENF normative densities in both genders. Our study provides IENF density normative reference values at the distal leg to be used in clinical practice.

Original languageEnglish
Pages (from-to)202-207
Number of pages6
JournalJournal of the Peripheral Nervous System
Volume15
Issue number3
DOIs
Publication statusPublished - Sep 2010

Keywords

  • intraepidermal nerve fiber density
  • neuropathic pain
  • neuropathology
  • neuropathy
  • skin biopsy
  • small fiber neuropathy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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    Lauria, G., Bakkers, M., Schmitz, C., Lombardi, R., Penza, P., Devigili, G., Smith, A. G., Hsieh, S. T., Mellgren, S. I., Umapathi, T., Ziegler, D., Faber, C. G., & Merkies, I. S. J. (2010). Intraepidermal nerve fiber density at the distal leg: A worldwide normative reference study. Journal of the Peripheral Nervous System, 15(3), 202-207. https://doi.org/10.1111/j.1529-8027.2010.00271.x