A multi-center, multinational age- and gender-adjusted normative dataset for immunofluorescent intraepidermal nerve fiber density at the distal leg

V. Provitera, C. H. Gibbons, G. Wendelschafer-Crabb, V. Donadio, D. F. Vitale, A. Stancanelli, G. Caporaso, R. Liguori, N. Wang, L. Santoro, W. R. Kennedy, M. Nolano

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Background and purpose: Quantification of intraepidermal nerve fibers (IENFs) in skin biopsies is now the tool of choice to diagnose small fiber neuropathies. An adequate normative dataset, necessary to assess normality cutoffs, is available for brightfield microscopy but not for immunofluorescence. Methods: Intraepidermal nerve fiber density data in distal leg skin samples processed with immunofluorescence were collected from 528 healthy individuals from four experienced laboratories worldwide. In all laboratories skin samples were collected, processed and analyzed according to standard procedures. Quantile regression analysis was employed to tailor the fit of the 5° percentile as the normal cutoff value and to test and measure the effect of age, gender, body mass index, race, biopsy site (lateral distal lower leg or medial posterior mid-calf) and participating laboratory as possible influential variables. Results: Age, gender and biopsy site showed an independent linear correlation with IENF density. For each decade the 5° quantile IENF cutoff showed a 0.54 fibers/mm decrease, whilst females exhibited a 1.0 fiber/mm cutoff greater than males. Compared to the lateral distal lower leg, biopsies from the calf showed a 3.4 fibers/mm lower 5° percentile cutoff, documenting a variation linked by site. Conclusions: An age- and gender-adjusted normative dataset for IENF density at the lateral distal lower leg obtained with indirect immunofluorescence is presented for the first time by sharing data from four experienced laboratories worldwide. This dataset can be used as reference for laboratories processing skin biopsies with this technique. European Journal of Neurology

Original languageEnglish
Pages (from-to)333-338
Number of pages6
JournalEuropean Journal of Neurology
Volume23
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

Fingerprint

Nerve Fibers
Leg
Biopsy
Skin
Information Dissemination
Indirect Fluorescent Antibody Technique
Neurology
Fluorescence Microscopy
Fluorescent Antibody Technique
Reference Values
Body Mass Index
Regression Analysis
Datasets

Keywords

  • Immunofluorescence
  • Intraepidermal nerve fibers
  • Neuropathology
  • Skin biopsy
  • Small fiber neuropathy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

A multi-center, multinational age- and gender-adjusted normative dataset for immunofluorescent intraepidermal nerve fiber density at the distal leg. / Provitera, V.; Gibbons, C. H.; Wendelschafer-Crabb, G.; Donadio, V.; Vitale, D. F.; Stancanelli, A.; Caporaso, G.; Liguori, R.; Wang, N.; Santoro, L.; Kennedy, W. R.; Nolano, M.

In: European Journal of Neurology, Vol. 23, No. 2, 01.02.2016, p. 333-338.

Research output: Contribution to journalArticle

Provitera, V. ; Gibbons, C. H. ; Wendelschafer-Crabb, G. ; Donadio, V. ; Vitale, D. F. ; Stancanelli, A. ; Caporaso, G. ; Liguori, R. ; Wang, N. ; Santoro, L. ; Kennedy, W. R. ; Nolano, M. / A multi-center, multinational age- and gender-adjusted normative dataset for immunofluorescent intraepidermal nerve fiber density at the distal leg. In: European Journal of Neurology. 2016 ; Vol. 23, No. 2. pp. 333-338.
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AU - Provitera, V.

AU - Gibbons, C. H.

AU - Wendelschafer-Crabb, G.

AU - Donadio, V.

AU - Vitale, D. F.

AU - Stancanelli, A.

AU - Caporaso, G.

AU - Liguori, R.

AU - Wang, N.

AU - Santoro, L.

AU - Kennedy, W. R.

AU - Nolano, M.

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N2 - Background and purpose: Quantification of intraepidermal nerve fibers (IENFs) in skin biopsies is now the tool of choice to diagnose small fiber neuropathies. An adequate normative dataset, necessary to assess normality cutoffs, is available for brightfield microscopy but not for immunofluorescence. Methods: Intraepidermal nerve fiber density data in distal leg skin samples processed with immunofluorescence were collected from 528 healthy individuals from four experienced laboratories worldwide. In all laboratories skin samples were collected, processed and analyzed according to standard procedures. Quantile regression analysis was employed to tailor the fit of the 5° percentile as the normal cutoff value and to test and measure the effect of age, gender, body mass index, race, biopsy site (lateral distal lower leg or medial posterior mid-calf) and participating laboratory as possible influential variables. Results: Age, gender and biopsy site showed an independent linear correlation with IENF density. For each decade the 5° quantile IENF cutoff showed a 0.54 fibers/mm decrease, whilst females exhibited a 1.0 fiber/mm cutoff greater than males. Compared to the lateral distal lower leg, biopsies from the calf showed a 3.4 fibers/mm lower 5° percentile cutoff, documenting a variation linked by site. Conclusions: An age- and gender-adjusted normative dataset for IENF density at the lateral distal lower leg obtained with indirect immunofluorescence is presented for the first time by sharing data from four experienced laboratories worldwide. This dataset can be used as reference for laboratories processing skin biopsies with this technique. European Journal of Neurology

AB - Background and purpose: Quantification of intraepidermal nerve fibers (IENFs) in skin biopsies is now the tool of choice to diagnose small fiber neuropathies. An adequate normative dataset, necessary to assess normality cutoffs, is available for brightfield microscopy but not for immunofluorescence. Methods: Intraepidermal nerve fiber density data in distal leg skin samples processed with immunofluorescence were collected from 528 healthy individuals from four experienced laboratories worldwide. In all laboratories skin samples were collected, processed and analyzed according to standard procedures. Quantile regression analysis was employed to tailor the fit of the 5° percentile as the normal cutoff value and to test and measure the effect of age, gender, body mass index, race, biopsy site (lateral distal lower leg or medial posterior mid-calf) and participating laboratory as possible influential variables. Results: Age, gender and biopsy site showed an independent linear correlation with IENF density. For each decade the 5° quantile IENF cutoff showed a 0.54 fibers/mm decrease, whilst females exhibited a 1.0 fiber/mm cutoff greater than males. Compared to the lateral distal lower leg, biopsies from the calf showed a 3.4 fibers/mm lower 5° percentile cutoff, documenting a variation linked by site. Conclusions: An age- and gender-adjusted normative dataset for IENF density at the lateral distal lower leg obtained with indirect immunofluorescence is presented for the first time by sharing data from four experienced laboratories worldwide. This dataset can be used as reference for laboratories processing skin biopsies with this technique. European Journal of Neurology

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