Application of Optic Neuritis Diagnostic Criteria in Autoimmune Paraneoplastic CRMP5 Optic Neuropathy and Development of the "CRMP" Score.
6 affiliations
- 1Department of Neurology and Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN.
- 2Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
- 3Department of Ophthalmology, Cleveland Clinic Foundation, OH.
- 4Department of Ophthalmology, Mayo Clinic, Rochester, MN.
- 5Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; and.
- 6Department of Ophthalmology, The Permanente Medical Group, Kaiser Permanente-Northern California, Roseville, CA.
Abstract
Objectives
Collapsin response-mediator protein 5 (CRMP5)-IgG is an acknowledged biomarker in the International Consortium on Optic Neuritis (ICON) diagnostic criteria for optic neuritis (ON), but these criteria have not been validated in CRMP5-IgG+ON.Methods
We evaluated the ICON and Acute Optic Neuritis Network (ACON) criteria for CRMP5-IgG+ON, using patients with late-onset (age ≥50 years) aquaporin-4-IgG-positive (AQP4-IgG+)-ON or myelin-oligodendrocyte glycoprotein antibody (MOG-IgG+)-ON for comparison. We developed the "CRMP score," based on typical CRMP5-IgG+ON clinical features, to guide CRMP5 antibody testing in ON.Results
The study included 17 patients with CRMP5-IgG+, 11 with AQP4-IgG+ON, and 13 with MOG-IgG+ON. Application of ICON criteria yielded no "definite ON" and 1 "probable ON" diagnosis among the 17 CRMP5-IgG+ cases, but definite ON diagnoses for 6 of 11 AQP4-IgG+ (55%, p = 0.003) and 7 of 13 MOG-IgG+ cases (54%, p = 0.001). ACON criteria yielded definite ON diagnoses for 2 (12%) CRMP5-IgG+ON, 10 (91%) of the AQP4-IgG+ON, and 13 (100%) of the MOG-IgG+ON (p < 0.001). A CRMP score ≥1 identified CRMP5-IgG+ON with a sensitivity of 88.2% and a specificity of 87.5%.Discussion
ICON and ACON criteria for ON diagnosis identified only a minority of CRMP5-IgG+ON cases; thus, we developed the "CRMP" score to aid their identification in clinical practice.
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BibTeX
@article{dinoto2026application,
title = {{Application of Optic Neuritis Diagnostic Criteria in Autoimmune Paraneoplastic CRMP5 Optic Neuropathy and Development of the "CRMP" Score.}},
author = {Alessandro Dinoto and Devon A Cohen and Laura Cacciaguerra and Nanthaya Tisavipat and Stephanie B Syc-Mazurek and Vanda A Lennon and M Tariq Bhatti and Deena A Tajfirouz and Kevin D Chodnicki and Sean J Pittock and Eoin P Flanagan and John J Chen},
journal = {Neurology(R) neuroimmunology \& neuroinflammation},
year = {2026},
month = oct,
doi = {10.1212/nxi.0000000000200666},
url = {https://europepmc.org/article/MED/42905998},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Application of Optic Neuritis Diagnostic Criteria in Autoimmune Paraneoplastic CRMP5 Optic Neuropathy and Development of the "CRMP" Score.
AU - Alessandro Dinoto
AU - Devon A Cohen
AU - Laura Cacciaguerra
AU - Nanthaya Tisavipat
AU - Stephanie B Syc-Mazurek
AU - Vanda A Lennon
AU - M Tariq Bhatti
AU - Deena A Tajfirouz
AU - Kevin D Chodnicki
AU - Sean J Pittock
AU - Eoin P Flanagan
AU - John J Chen
PY - 2026
DA - 2026/10/21
JO - Neurology(R) neuroimmunology & neuroinflammation
DO - 10.1212/nxi.0000000000200666
UR - https://europepmc.org/article/MED/42905998
AB - Objectives Collapsin response-mediator protein 5 (CRMP5)-IgG is an acknowledged biomarker in the International Consortium on Optic Neuritis (ICON) diagnostic criteria for optic neuritis (ON), but these criteria have not been validated in CRMP5-IgG+ON.Methods We evaluated the ICON and Acute Optic Neuritis Network (ACON) criteria for CRMP5-IgG+ON, using patients with late-onset (age ≥50 years) aquaporin-4-IgG-positive (AQP4-IgG+)-ON or myelin-oligodendrocyte glycoprotein antibody (MOG-IgG+)-ON for comparison. We developed the "CRMP score," based on typical CRMP5-IgG+ON clinical features, to guide CRMP5 antibody testing in ON.Results The study included 17 patients with CRMP5-IgG+, 11 with AQP4-IgG+ON, and 13 with MOG-IgG+ON. Application of ICON criteria yielded no "definite ON" and 1 "probable ON" diagnosis among the 17 CRMP5-IgG+ cases, but definite ON diagnoses for 6 of 11 AQP4-IgG+ (55%, p = 0.003) and 7 of 13 MOG-IgG+ cases (54%, p = 0.001). ACON criteria yielded definite ON diagnoses for 2 (12%) CRMP5-IgG+ON, 10 (91%) of the AQP4-IgG+ON, and 13 (100%) of the MOG-IgG+ON (p < 0.001). A CRMP score ≥1 identified CRMP5-IgG+ON with a sensitivity of 88.2% and a specificity of 87.5%.Discussion ICON and ACON criteria for ON diagnosis identified only a minority of CRMP5-IgG+ON cases; thus, we developed the "CRMP" score to aid their identification in clinical practice.
SN - 2332-7812
ER -