title: Side and time variability of intraepidermal nerve fiber density.
abstract: OBJECTIVE
  To assess the right-to-left and short-term variability of intraepidermal nerve fiber density (IENFD) at the distal site of the leg.
  
  
  METHODS
  Patients with possible or probable small fiber neuropathy (SFN) and healthy volunteers (HVs) underwent skin biopsies at the right and left distal leg. A subgroup of participants underwent follow-up biopsies 20 days later. Biopsies were immunostained by polyclonal anti-protein gene product 9.5 antibodies, and IENFD was quantified in nonconsecutive sections following published guidelines by operators blinded to the participants' condition (diagnosis, side, and time of biopsy). Findings were referred to sex- and age-adjusted normative values.
  
  
  RESULTS
  Forty patients and 17 HVs underwent bilateral skin biopsies; 15 patients and 8 HVs underwent follow-up skin biopsies. Sural nerve and dorsal sural nerve conduction studies were normal in all participants. Interside IENFD did not differ both in patients (median 2.45 IENF/mm ± 1.45 SD right; 2.2 IENF/mm ± 1.32 SD left) and HVs (median 6.3 IENF/mm ± 2.81 right; 6.2 IENF/mm ± 2.3 SD left). The right-to-left correlation coefficients were excellent (Pearson 0.95 in SFN and 0.97 in HVs). The analysis of IENFD at 20-day follow-up biopsy showed no difference between sides in both groups and yielded excellent correlation coefficients.
  
  
  CONCLUSIONS
  The diagnosis of SFN can be reliably ascertained by unilateral skin biopsy at the distal site of the leg, and IENFD is not expected to vary within 3 weeks.
authors.affiliation: From the 3rd Neurology Unit and Skin Biopsy (G.L., P.D., R.L., D.C., C.P.-S., M.T., J.S., E.D.B.), Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation Carlo Besta Neurological Institute, Milan; and Neurological Unit (S.R., C.L., R.E., G.D.), University Hospital S. Maria della Misericordia, Udine, Italy. glauria@istituto-besta.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauria
authors.affiliation: From the 3rd Neurology Unit and Skin Biopsy (G.L., P.D., R.L., D.C., C.P.-S., M.T., J.S., E.D.B.), Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation Carlo Besta Neurological Institute, Milan; and Neurological Unit (S.R., C.L., R.E., G.D.), University Hospital S. Maria della Misericordia, Udine, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dacci
authors.affiliation: From the 3rd Neurology Unit and Skin Biopsy (G.L., P.D., R.L., D.C., C.P.-S., M.T., J.S., E.D.B.), Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation Carlo Besta Neurological Institute, Milan; and Neurological Unit (S.R., C.L., R.E., G.D.), University Hospital S. Maria della Misericordia, Udine, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Lombardi
authors.affiliation: From the 3rd Neurology Unit and Skin Biopsy (G.L., P.D., R.L., D.C., C.P.-S., M.T., J.S., E.D.B.), Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation Carlo Besta Neurological Institute, Milan; and Neurological Unit (S.R., C.L., R.E., G.D.), University Hospital S. Maria della Misericordia, Udine, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Cazzato
authors.affiliation: From the 3rd Neurology Unit and Skin Biopsy (G.L., P.D., R.L., D.C., C.P.-S., M.T., J.S., E.D.B.), Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation Carlo Besta Neurological Institute, Milan; and Neurological Unit (S.R., C.L., R.E., G.D.), University Hospital S. Maria della Misericordia, Udine, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Porretta-Serapiglia
authors.affiliation: From the 3rd Neurology Unit and Skin Biopsy (G.L., P.D., R.L., D.C., C.P.-S., M.T., J.S., E.D.B.), Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation Carlo Besta Neurological Institute, Milan; and Neurological Unit (S.R., C.L., R.E., G.D.), University Hospital S. Maria della Misericordia, Udine, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Taiana
authors.affiliation: From the 3rd Neurology Unit and Skin Biopsy (G.L., P.D., R.L., D.C., C.P.-S., M.T., J.S., E.D.B.), Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation Carlo Besta Neurological Institute, Milan; and Neurological Unit (S.R., C.L., R.E., G.D.), University Hospital S. Maria della Misericordia, Udine, Italy.
authors.forename: Jenny
authors.initials: J
authors.lastname: Sassone
authors.affiliation: From the 3rd Neurology Unit and Skin Biopsy (G.L., P.D., R.L., D.C., C.P.-S., M.T., J.S., E.D.B.), Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation Carlo Besta Neurological Institute, Milan; and Neurological Unit (S.R., C.L., R.E., G.D.), University Hospital S. Maria della Misericordia, Udine, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dalla Bella
authors.affiliation: From the 3rd Neurology Unit and Skin Biopsy (G.L., P.D., R.L., D.C., C.P.-S., M.T., J.S., E.D.B.), Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation Carlo Besta Neurological Institute, Milan; and Neurological Unit (S.R., C.L., R.E., G.D.), University Hospital S. Maria della Misericordia, Udine, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Rinaldo
authors.affiliation: From the 3rd Neurology Unit and Skin Biopsy (G.L., P.D., R.L., D.C., C.P.-S., M.T., J.S., E.D.B.), Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation Carlo Besta Neurological Institute, Milan; and Neurological Unit (S.R., C.L., R.E., G.D.), University Hospital S. Maria della Misericordia, Udine, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Lettieri
authors.affiliation: From the 3rd Neurology Unit and Skin Biopsy (G.L., P.D., R.L., D.C., C.P.-S., M.T., J.S., E.D.B.), Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation Carlo Besta Neurological Institute, Milan; and Neurological Unit (S.R., C.L., R.E., G.D.), University Hospital S. Maria della Misericordia, Udine, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Eleopra
authors.affiliation: From the 3rd Neurology Unit and Skin Biopsy (G.L., P.D., R.L., D.C., C.P.-S., M.T., J.S., E.D.B.), Peripheral Neuropathy and Neuropathic Pain Clinic, IRCCS Foundation Carlo Besta Neurological Institute, Milan; and Neurological Unit (S.R., C.L., R.E., G.D.), University Hospital S. Maria della Misericordia, Udine, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Devigili
mesh_terms: D000328:Adult; D001706:Biopsy / Q000592:standards*; D004817:Epidermis / Q000294:innervation / Q000473:pathology*; D006801:Humans; D007866:Leg / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D009431:Neural Conduction; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis*; D015203:Reproducibility of Results; D055815:Young Adult