Chronic Idiopathic Axonal Polyneuropathy: Current Evidence and Future Directions
- 1Department of Neurology, Hannover Medical School, 1, Carl-Neuberg-Strasse, 30625 Hannover, Germany
- 2PRACTIS Clinician Scientist Program, Dean’s Office for Academic Career Development, Hannover Medical School, 30625 Hannover, Germany
- 3University Clinical Center of Serbia-Neurology Clinic, 11000 Belgrade, Serbia
Abstract
Chronic idiopathic axonal polyneuropathy (CIAP) is one of the most common diagnostic categories encountered in patients with chronic polyneuropathy, yet it remains insufficiently defined and incompletely understood. CIAP has been regarded as a slowly progressive, length-dependent, predominantly sensory or sensorimotor axonal polyneuropathy affecting middle-aged and older adults after exclusion of recognized acquired and hereditary causes. Increasing evidence suggests that CIAP is unlikely to represent a single disease entity. Instead, it may constitute a heterogeneous clinical phenotype arising from the convergence of several biological pathways on distal axonal degeneration. We summarize current knowledge regarding the definition, epidemiology, clinical presentation, diagnostic approach, pathophysiological hypotheses, and treatment of CIAP. Particular attention is given to metabolic and vascular risk factors, endoneurial microvascular alterations, neurotoxic 1-deoxysphingolipids, inflammatory and immune-mediated mechanisms, oxidative stress, genetic susceptibility, and age-related axonal vulnerability. We also discuss how deeper phenotyping and genetic testing may reclassify a subset of patients initially labeled as having CIAP. No disease-modifying therapy has been established for CIAP. Management focuses on symptomatic treatment and rehabilitation; whether risk-factor modification alters the disease course remains unproven. Future studies should aim to harmonize diagnostic criteria, improve biomarker-based phenotyping, and identify mechanism-defined subgroups that may become accessible to targeted therapeutic strategies.
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BibTeX
@article{bjelica2026chronic,
title = {{Chronic Idiopathic Axonal Polyneuropathy: Current Evidence and Future Directions}},
author = {Bogdan Bjelica and Stojan Peric and Ivo Bozovic and Sonja Koerner and Milica Vukojevic and Susanne Petri and Aiden Haghikia},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15201911},
url = {https://www.mdpi.com/2073-4409/15/20/1911},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Chronic Idiopathic Axonal Polyneuropathy: Current Evidence and Future Directions
AU - Bogdan Bjelica
AU - Stojan Peric
AU - Ivo Bozovic
AU - Sonja Koerner
AU - Milica Vukojevic
AU - Susanne Petri
AU - Aiden Haghikia
PY - 2026
DA - 2026/10/20
JO - Cells
DO - 10.3390/cells15201911
UR - https://www.mdpi.com/2073-4409/15/20/1911
AB - Chronic idiopathic axonal polyneuropathy (CIAP) is one of the most common diagnostic categories encountered in patients with chronic polyneuropathy, yet it remains insufficiently defined and incompletely understood. CIAP has been regarded as a slowly progressive, length-dependent, predominantly sensory or sensorimotor axonal polyneuropathy affecting middle-aged and older adults after exclusion of recognized acquired and hereditary causes. Increasing evidence suggests that CIAP is unlikely to represent a single disease entity. Instead, it may constitute a heterogeneous clinical phenotype arising from the convergence of several biological pathways on distal axonal degeneration. We summarize current knowledge regarding the definition, epidemiology, clinical presentation, diagnostic approach, pathophysiological hypotheses, and treatment of CIAP. Particular attention is given to metabolic and vascular risk factors, endoneurial microvascular alterations, neurotoxic 1-deoxysphingolipids, inflammatory and immune-mediated mechanisms, oxidative stress, genetic susceptibility, and age-related axonal vulnerability. We also discuss how deeper phenotyping and genetic testing may reclassify a subset of patients initially labeled as having CIAP. No disease-modifying therapy has been established for CIAP. Management focuses on symptomatic treatment and rehabilitation; whether risk-factor modification alters the disease course remains unproven. Future studies should aim to harmonize diagnostic criteria, improve biomarker-based phenotyping, and identify mechanism-defined subgroups that may become accessible to targeted therapeutic strategies.
SN - 2073-4409
ER -