Application of Optic Neuritis Diagnostic Criteria in Autoimmune Paraneoplastic CRMP5 Optic Neuropathy and Development of the "CRMP" Score.

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.