title: Epidermal nerve fibers: confidence intervals and continuous measures with nerve conduction.
abstract: OBJECTIVE
  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 studies were 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 compared with 1-10 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 few when 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Peripheral Neuropathy Research Laboratory, Mayo Clinic, Rochester, MN, USA.
authors.forename: JaNean K
authors.initials: JK
authors.lastname: Engelstad
authors.forename: Sean W
authors.initials: SW
authors.lastname: Taylor
authors.forename: Lawrence V
authors.initials: LV
authors.lastname: Witt
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Hoebing
authors.forename: David N
authors.initials: DN
authors.lastname: Herrmann
authors.forename: P James B
authors.initials: PJ
authors.lastname: Dyck
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Klein
authors.forename: David M
authors.initials: DM
authors.lastname: Johnson
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Davies
authors.forename: Rickey E
authors.initials: RE
authors.lastname: Carter
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dyck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016001:Confidence Intervals; D004568:Electrodiagnosis / Q000379:methods* / Q000592:standards*; D004817:Epidermis / Q000294:innervation* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009412:Nerve Fibers / Q000473:pathology / Q000502:physiology*; D009431:Neural Conduction / Q000502:physiology*; D015203:Reproducibility of Results; D055815:Young Adult