Long term survival and outcomes in patients with paraneoplastic neurologic syndromes.

Objective: It is unknown whether delay in diagnosis affects morbidity reportedly in paraneoplastic syndromes (PNS). We aimed to explore various aspects of PNS, including prevalence, clinical characteristics, diagnostic criteria, and treatment outcomes.

Methods: We studied n-PNS diagnosis between 2016 to 2023, and included only patients with positive onconeural antibodies, who developed cancer, and exhibited a recognizable PNS phenotype.

Results: We identified 12 patients with positive Abs and co-occurring cancer, most prevalent PNS antibodies included anti-GAD65, anti-Recoverin and anti-Yo. The most common phenotypes were limbic encephalitis (n=5, 42%) and encephalomyelitis (n=4,33%). Cancer preceded neurological presentation in 6 cases. Among the 6 patients who initially presented with n-PNS, median time from neurological presentation to oncologic diagnosis was 73 days, as five of them (83%) were diagnosed with cancer during oncological evaluation prompted by the PNS diagnosis or suspicion. Lymphoma was the most frequent cancer (n=3, 25%), followed by lung cancer (n=2, 17%), and ovarian cancer (n=2, 17%). Among patients who received immunotherapy as n-PNS treatment (n=9, 75%), steroids were a part of the management at 78% (n=7). Another immunotherapy used included plasmapheresis (n=5, 55%) and steroid sparing immunosuppressant (n=2, 29%). Four (33%) patients had short term therapeutic benefit with improvement or stabilization at mRS ≤ 4. Median Disability-adjusted life years (DALYs), as disease burden value, was 13 years. Death occurred in 9 of the 12 patients, with most cases deaths attributed to cancer progression. Compering to the expected median survival by type and stage of tumor, from 9 deceased patients, 56% (n=5) died younger than expected. Median survival was 410 days (range 29-2738 days), and 152 days since the appearance of n-PNS (range 8-1434 days). There were no differences in survival between patients who initially presented with n-PNS versus cancer (p=0.39).

Conclusion: In up to 8 years of follow up, there was no difference in mortality among patients who presented initially n-PNS. There was a significant decline in the quality of life, most face substantial disability and functional impairment long term.