Journal
NEUROLOGY
Volume 73, Issue 14, Pages 1142-1148Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3181bacf05
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Funding
- GBS/CIDP International Foundation
- Pzifer, Inc.
- Formenti-Grunenthal
- Agave
- Italian Ministry of Health [RF-2005/51]
- BERCO S.pA.
- Copparo
- Fondazione Cassa di Risparmio di Ferrara
- Prinses Beatrix Fonds
- Transnational University Limburg
- Genmab
- European Union [30973317E, 2005105, LSHM-CT-2006037833]
- Profileringsfonds MUMC
- Maastricht University Medical Center, The Netherlands [062053]
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Background: Intraepidermal nerve fiber density (IENFD) is considered a good diagnostic tool for small fiber neuropathy (SFN). Objectives: To assess stratified normative values for IENFD and determine the reliability and validity of IENFD in sarcoidosis. Methods: IENFD was assessed in 188 healthy volunteers and 72 patients with sarcoidosis (n = 58 with SFN symptoms, n = 14 without SFN symptoms). Healthy controls were stratified (for age and sex), resulting image groups (20-29, 30-39, ... up to >= 70 years) containing at least 15 men and 15 women. A skin biopsy was taken in each participant 10 cm above the lateral malleolus and analyzed in accordance with the international guidelines using bright-field microscopy. Interobserver/intraobserver reliability of IENFD was examined. In the patients, a symptoms inventory questionnaire (SIQ; assessing SFN symptoms) and the Vickrey Peripheral Neuropathy Quality-of-Life Instrument-97 (PNQoL-97) were assessed to examine the discriminative ability of normative IENFD values. Results: There was a significant age-dependent decrease of IENFD values in healthy controls, with lower densities in men compared with women. Good interobserver/intraobserver reliability scores were obtained (kappa values >= 0.90). A total of 21 patients with sarcoidosis had a reduced IENFD score (<5th percentile; 19 [32.8%] in patients with SFN symptoms, 2 [14.3%] in patients without SFN symptoms). The validity of the normative IENFD values was demonstrated by distinguishing between the SIQ scores and various PNQoL-97 values for the different patient groups. Conclusion: This study provides clinically applicable distal intraepidermal nerve fiber density normative values, showing age-and sex-related differences. Neurology (R) 2009; 73: 1142-1148
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