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

Ann Clin Transl Neurol. 2024 Mar;11(3):710-718. doi: 10.1002/acn3.51991. Epub 2024 Jan 22.

Abstract

Background: We aimed to investigate the prognostic factors associated with clinical outcomes in CV2/Collapsin response-mediator protein 5 (CRMP5)-IgG paraneoplastic neurologic disorders (PND).

Methods: This 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.

Results: Twenty-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.

Interpretation: In 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.

MeSH terms

  • Autoantibodies
  • Cerebellar Ataxia*
  • Female
  • Humans
  • Immunoglobulin G
  • Longitudinal Studies
  • Lung Neoplasms* / complications
  • Lung Neoplasms* / diagnosis
  • Male
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Nervous System Diseases* / etiology
  • Retrospective Studies
  • Small Cell Lung Carcinoma*
  • Spinal Cord Diseases*
  • Thymoma* / complications
  • Thymus Neoplasms* / complications

Substances

  • Nerve Tissue Proteins
  • Microtubule-Associated Proteins
  • Autoantibodies
  • Immunoglobulin G