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A Meta-Analysis of Intraepidermal Nerve Fibre Density in Healthy and Neuropathic Subjects: A Proposed Guidance Model

21 Pages Posted: 2 Jan 2019

See all articles by Alexandros Samolis

Alexandros Samolis

National and Kapodistrian University of Athens - Department of Anatomy and Surgical Anatomy

maria Piagkou

National and Kapodistrian University of Athens - Department of Anatomy and Surgical Anatomy

Constantinus Politis

KU Leuven - Faculty of Medicine

Nikolaos Pantazis

National and Kapodistrian University of Athens

Theodore Troupis

National and Kapodistrian University of Athens - Department of Anatomy and Surgical Anatomy

Thomas Tegos

Aristotle University of Thessaloniki

Konstantinos Natsis

Aristotle University of Thessaloniki

More...

Abstract

Background: Skin spot biopsy is the gold standard for diagnosis of small fibre neuropathy. Here we systematically approached intraepidermal nerve fibre density (IENFD) with the aim of precisely estimating its value in healthy and neuropathic subjects. The present findings will serve as a guidance model for further use of IENFD, as an indicator of neuropathy predisposition. We also investigated how IENFD was influenced by age, gender, and neuropathy.

Methods: We conducted a systematic search of PubMed, Web of Science, and ScienceDirect to identify clinical studies published during the last twenty years (1997-2017), which investigated IENFD in healthy and neuropathic adult population. Data were retrieved from longitudinal cohort studies including 5-188 healthy adult subjects and 6-40 neuropathic adult patients. We used meta-analysis techniques including multilevel meta-regression.

Findings: In the healthy population, the estimated (95% CI) IENFD values (in fibres/mm) were 21.4 (19.9, 22.9) in the thigh, 17*7 (15.3, 20.1) in the forearm, 12*9 (11.8, 14.0) in the distal leg, 11*3 (6.1, 16.5) in the fingers, and 6*5 (4.4, 8.6) in the toes. The corresponding estimates in the neuropathic population were 17*2 (15.2, 19.2) in the thigh, 6*3 (2.3, 10.2) in the forearm, 5*1 (3.8, 6.4) in the distal leg, and 2*0 (0.0, 5.7) in the toes. In the healthy population, IENFD decreased with ageing, by 1*4 fibres/mm every 5 years (p<0.001). We detected gender dimorphism in IENFD, with females showing higher IENFD values in the distal leg (13*6-10*5 fibres/mm) compared to males (9*3-7*2 fibres/mm).

Interpretation: The present meta-analysis results highlighted the IENFD alterations in neurodegenerative disease, suggesting that IENFD may be a reliable prognostic marker for the timely diagnosis of neuropathy.

Funding Statement: The authors state: "There was no funding source for this study."

Declaration of Interests: There is no conflict of interest.

Keywords: intraepidermal nerve fibre density, neuropathy, skin biopsy, small fibre neuropathy, healthy, meta-analysis

Suggested Citation

Samolis, Alexandros and Piagkou, maria and Politis, Constantinus and Pantazis, Nikolaos and Troupis, Theodore and Tegos, Thomas and Natsis, Konstantinos, A Meta-Analysis of Intraepidermal Nerve Fibre Density in Healthy and Neuropathic Subjects: A Proposed Guidance Model (December 29, 2018). Available at SSRN: https://ssrn.com/abstract=3307648

Alexandros Samolis

National and Kapodistrian University of Athens - Department of Anatomy and Surgical Anatomy

Athens
Greece

Maria Piagkou (Contact Author)

National and Kapodistrian University of Athens - Department of Anatomy and Surgical Anatomy ( email )

Athens
Greece

Constantinus Politis

KU Leuven - Faculty of Medicine

Campus gasthuisberg ON2
Herestraat 49 - bus 400
Leuven, 3000
Belgium

Nikolaos Pantazis

National and Kapodistrian University of Athens

5 Stadiou Strt
Athens, 12131
Greece

Theodore Troupis

National and Kapodistrian University of Athens - Department of Anatomy and Surgical Anatomy

Athens
Greece

Thomas Tegos

Aristotle University of Thessaloniki

Thessaloniki
Greece

Konstantinos Natsis

Aristotle University of Thessaloniki

Thessaloniki
Greece

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