Epidermal nerve fibers: Confidence intervals and continuous measures with nerve conduction

Ja Nean K. Engelstad, Sean W. Taylor, Lawrence V. Witt, Belinda J. Hoebing, David N. Herrmann, P. James B. Dyck, Christopher J. Klein, David M. Johnson, Jenny L. Davies, Rickey E. Carter, Peter J. Dyck

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Objectives: Our first objective was to explore the value of estimating 95% confidence intervals (CIs) of epidermal nerve fibers (ENFs)/mm for number of sections to be evaluated and for confidently judging normality or abnormality. Our second objective was to introduce a new continuous measure combining nerve conduction and ENFs/mm. Methods: The 95%CI studieswere performed on 1, 1-2, 1-3 - - - 1-10 serial skip sections of 3-mm punch biopsies of leg and thigh of 67 healthy subjects and 23 patients with diabetes mellitus. Results: Variability of differences of ENFs/mm counts (and 95% CIs) from evaluation of 1, 1-2, 1-3 - - - 1-9 comparedwith1-10 serial skip sections decreased progressively without a break point with increasing numbers of sections evaluated. Estimating 95% CIs as sections are evaluated can be used to judge how many sections are needed for adequate evaluation, i.e., only a fewwhen counts and 95% CIs are well within the range of normality or abnormality and more when values are borderline. Also provided is a methodology to combine results of nerve conduction and ENFs/mm as continuous measures of normality or abnormality. Conclusion: Estimating 95% CIs of ENFs/mm is useful to judge how many sections should be evaluated to confidently declare counts to be normal or abnormal. Also introduced is a continuous measure of both large-fiber (nerve conduction) and small-fiber (ENFs/mm) normal structures/functions spanning the range of normality and abnormality for use in therapeutic trials.

Original languageEnglish (US)
Pages (from-to)2187-2193
Number of pages7
Issue number22
StatePublished - Nov 27 2012

ASJC Scopus subject areas

  • Clinical Neurology


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