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June 09, 2015; 84 (23) Article

Side and time variability of intraepidermal nerve fiber density

Giuseppe Lauria, Patrizia Dacci, Raffaella Lombardi, Daniele Cazzato, Carla Porretta-Serapiglia, Michela Taiana, Jenny Sassone, Eleonora Dalla Bella, Sara Rinaldo, Christian Lettieri, Roberto Eleopra, Grazia Devigili
First published May 13, 2015, DOI: https://doi.org/10.1212/WNL.0000000000001666
Giuseppe Lauria
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.
MD
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Patrizia Dacci
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.
MD, PhD
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Raffaella Lombardi
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.
PhD
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Daniele Cazzato
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.
MD
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Carla Porretta-Serapiglia
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.
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Michela Taiana
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.
PhD
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Jenny Sassone
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.
PhD
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Eleonora Dalla Bella
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.
MD
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Sara Rinaldo
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.
Tch
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Christian Lettieri
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.
MD
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Roberto Eleopra
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.
MD
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Grazia Devigili
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.
MD, PhD
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Full PDF
Citation
Side and time variability of intraepidermal nerve fiber density
Giuseppe Lauria, Patrizia Dacci, Raffaella Lombardi, Daniele Cazzato, Carla Porretta-Serapiglia, Michela Taiana, Jenny Sassone, Eleonora Dalla Bella, Sara Rinaldo, Christian Lettieri, Roberto Eleopra, Grazia Devigili
Neurology Jun 2015, 84 (23) 2368-2371; DOI: 10.1212/WNL.0000000000001666

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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.

GLOSSARY

HV=
healthy volunteer;
IENF=
intraepidermal nerve fiber;
IENFD=
intraepidermal nerve fiber density;
SFN=
small fiber neuropathy

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received December 20, 2014.
  • Accepted in final form February 26, 2015.
  • © 2015 American Academy of Neurology
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