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Updated: Jun 16, 2025
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Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers
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Intraepidermal Nerve Fiber Density as an Indicator of Neuropathy Predisposition: A Systematic Review with
Alexandros Samolis1, Theodore Troupis1, Constantinus Politis2
1Department of Anatomy, School of Medicine, Faculty of Health Sciences, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Diagnostics (Basel, Switzerland)
|June 13, 2025
Summary
Intraepidermal nerve fiber density (IENFD) in skin biopsies is a key diagnostic tool for small fiber neuropathy. This study provides precise reference values for IENFD in healthy and neuropathic individuals, accounting for age and gender, to guide future research and clinical application.
Area of Science:
- Neurology
- Dermatology
- Pathology
Background:
- Skin spot biopsy is the gold standard for diagnosing small fiber neuropathy.
- Intraepidermal nerve fiber density (IENFD) assessment is crucial for understanding neuropathy.
- Establishing precise IENFD values is vital for accurate diagnosis and predisposition assessment.
Purpose of the Study:
- To precisely estimate intraepidermal nerve fiber density (IENFD) values in healthy and neuropathic subjects.
- To investigate the influence of age, gender, and neuropathy on IENFD.
- To provide a guidance model for IENFD as an indicator of neuropathy predisposition.
Main Methods:
- Systematic literature search of PubMed, Web of Science, and ScienceDirect (1997-2022).
- Inclusion of longitudinal cohort studies with healthy and neuropathic adult populations.
- Multilevel meta-regression analysis to assess associations between anatomical region, age, gender, and IENFD.
Main Results:
- Established reference IENFD values (fibers/mm) across various anatomical regions in healthy and neuropathic populations.
- Identified a significant decrease in IENFD with aging in healthy individuals (1.35 fibers/mm per 5 years).
- Observed gender dimorphism in IENFD, with females showing higher values in the distal leg compared to males.
Conclusions:
- The meta-analysis integrates IENFD data, reconciling findings from diverse methodologies and populations.
- Recommends using the thigh for biopsy to minimize heterogeneity and suggests international standardization of biopsy sites.
- Highlights the need for further research into IENFD in neurodegenerative diseases and its prognostic value for neuropathy.
