Patients with Anti-Hu/ANNA1 Paraneoplastic Neurological Syndromes Develop Progressive Disability but Have Increased Survival Compared to SCLC Patients Without Paraneoplastic Syndromes
Kimberly DiMauro1, Nicolas Thompson1, Glen Stevens1, Amy Kunchok1
1Cleveland Clinic Foundation
Objective:

We aimed to 1) examine disability and survival in patients with ANNA1/Hu-IgG paraneoplastic neurological syndromes (PNS), and 2) compare survival to small cell lung cancer (SCLC) without PNS.

Background:

ANNA-1/Hu-IgG PNS are rare and factors associated with disability and survival outcomes are unknown. 

Design/Methods:

This is a retrospective cohort study of ANNA1/Hu-IgG+ patients with PNS. Cox proportional hazard models examined clinical predictors of disability and survival. Kaplan-Meier curves examined time to mortality, wheelchair dependence, mRS>2. Log-rank tests assessed differing survival among groups. 

Results:

Forty-five patients with ANNA/Hu1-IgG PNS were identified (73% female, mean age=63 years [SD=13]). Phenotypes included; neuropathy (16, 36%), cerebellar ataxia (11, 24%), limbic encephalitis (10, 22%), myasthenia gravis/Lambert-Eaton myasthenic syndrome (3, 7%), myelopathy (2, 4%), enteric neuropathy (2, 4%), myoclonus (1, 2%).

Cancers were identified in 78%; SCLC (26, 74%), non-SCLC (4, 11%), other (5, 14%). Immunosuppressive therapy for PNS was given in 53%.

At PNS onset, disability was mild (mRS=0-2) in 67%, however at 5-year follow-up 72% had mRS>2 and 63% were wheelchair-dependent. Limbic encephalitis had greater hazard of reaching mRS>2 at last follow-up (HR=7.37, [95% CI=2.09-26.00], p=0.002). At 5-year follow-up, 58% had died. Survival was not influenced by phenotype or immunosuppressive treatment. 

Patients with SCLC and ANNA1/Hu-IgG PNS (n=26) compared to SCLC without ANNA1/Hu-IgG PNS (n=1513) had 59% lower hazard of death (HR =0.41, [95% CI = 0.25–0.69], p<0.001). Five-year survival was 36% for ANNA1/Hu-IgG and 13% for SCLC without PNS. A sensitivity analysis of patients matched 3:1 by age and sex demonstrated similar results. 

Conclusions:

This study demonstrates that patients with ANNA1/Hu-IgG PNS develop progressive disability and risk of disability is greater in patients with limbic encephalitis. However, patients with SCLC and ANNA1/Hu-IgG PNS survived longer than those without PNS, possibly due to earlier cancer detection or increased antitumor immunity.

10.1212/WNL.0000000000204710