Predicting disability and mortality in CV2/CRMP5‐IgG associated paraneoplastic neurologic disorders

Abstract

BackgroundWe aimed to investigate the prognostic factors associated with clinical outcomes in CV2/Collapsin response‐mediator protein 5 (CRMP5)‐IgG paraneoplastic neurologic disorders (PND).MethodsThis is a retrospective study of patients with CV2/CRMP5‐IgG PND evaluated between 2002–2022. We examined the association of clinical variables (including age, clinical phenotype [autoimmune encephalopathy, myelopathy, polyneuropathy/radiculopathy, MG, cerebellar ataxia, chorea, optic neuropathy], cancer) with three clinical outcomes (wheelchair dependence, modified Rankin Scale [mRS], mortality) using univariate logistic regression and Cox proportional hazards modeling. Kaplan–Meier estimates were used to determine the probability of survival.ResultsTwenty‐seven patients (56% female) with CV2/CRMP5‐IgG PND were identified with a median follow‐up of 54 months (IQR = 11–102). An underlying tumor was identified in 15 patients (56%) including small cell lung cancer (SCLC) (8, [53%]), thymoma (4, [27%]), and other histologies (3, [20%]). At last follow‐up, 10 patients (37%) needed a wheelchair for mobility and this outcome was associated with myelopathy (HR = 7.57, 95% CI = 1.87–30.64, P = 0.005). Moderate–severe mRS = 3–5 was associated with CNS involvement (encephalopathy, myelopathy, or cerebellar ataxia) (OR = 7.00, 95% CI = 1.18–41.36, P = 0.032). The probability of survival 4 years after symptom onset was 66%. Among cancer subtypes, SCLC (HR = 18.18, 95% CI = 3.55–93.04, P < 0.001) was significantly associated with mortality, while thymoma was not.InterpretationIn this retrospective longitudinal study of CV2/CRMP5‐IgG PND, patients with CNS involvement, particularly myelopathy, had higher probability of disability. SCLC was the main determinant of survival in this population.