To determine prognostic biomarkers in CRMP5-IgG associated paraneoplastic neurological disorders (PND)

There are limited data on longitudinal outcomes in CRMP5-IgG PND due to their rarity.

This is a retrospective cohort study of patients with CRMP5-IgG PND evaluated between 2002-2022. All participants had serum or cerebrospinal fluid CRMP5-IgG positivity by Western Blot or tissue immunofluorescence. Kaplan Meier curves and logistic regression were utilized to determine the probability of survival and prognostic biomarkers associated with disease outcomes including wheelchair dependence, modified Rankin Scale (mRS) ≥3 and death.

There were 24 patients (54% female) with CRMP5-IgG PND included with a median age at onset of 61.5 years (IQR=53-70). Median follow up was 9 months (IQR=2-53). Nineteen were smokers (80%). Cancers were identified in 13 (54%) including small cell lung cancer (SCLC) (8, [62%]) and thymoma (4 [31%]). Of those without cancer, 55% had pulmonary nodules. 

Clinical phenotypes included: neuropathy (14, [58%]), encephalopathy (9, [38%]), ataxia (9, [38%], myasthenia (AChR-IgG+) (7, [29%]), myelopathy (6 [25%], and optic neuropathy (5, [21%]).

Probability of wheelchair dependence at 4 years was 34% and was associated with myelopathy (OR=14, CI=1.2-163.37, p=0.035). Median mRS at last follow-up was 3 (IQR=1-4). mRS≥3 was associated with encephalopathy (OR=7, CI=1.04-46.95, p=0.045).

Thirteen patients (54%) received immunosuppressants, however this did not impact probability of survival (p>0.05). Probability of survival at 4 years after symptom onset was 70%. Predictors of death included cancer diagnosis (OR=16, CI=1.54-166.04, p=0.02) and specifically SCLC (OR=13, CI=1.7-99.37, p=0.013), but not clinical phenotype. Probability of survival at 4 years with cancer was 46% compared to 100% without cancer. Age was not associated with any of the outcomes.

In CRMP5-IgG PND, the presence of cancer, especially SCLC, is a significant prognostic marker of mortality. Probability of wheelchair dependence is associated with myelopathy. Moderate-severe disability (mRS≥3) is associated with encephalopathy.