Seizure characteristics and outcomes in patients with neurological conditions related to high-risk paraneoplastic antibodies

Kelsey M. Smith, Jeffrey W. Britton, Smathorn Thakolwiboon, Nicholas H. Chia, Pranjal Gupta, Eoin P. Flanagan, Anastasia Zekeridou, Alfonso S. Lopez Chiriboga, Cristina Valencia Sanchez, Andrew McKeon, Sean J. Pittock, Divyanshu Dubey

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Seizures are a common manifestation of paraneoplastic neurologic syndromes. The objective of this study was to describe the seizure characteristics and outcomes in patients with high-risk paraneoplastic autoantibodies (>70% cancer association) and to determine factors associated with ongoing seizures. Methods: Patients from 2000 to 2020 with seizures and high-risk paraneoplastic autoantibodies were retrospectively identified. Factors associated with ongoing seizures at last follow-up were evaluated. Results: Sixty patients were identified (34 males, median age at presentation = 52 years). ANNA1-IgG (Hu; n = 24, 39%), Ma2-IgG (n = 14, 23%), and CRMP5-IgG (CV2; n = 11, 18%) were the most common underlying antibodies. Seizures were the initial presenting symptom in 26 (43%), and malignancy was present in 38 (63%). Seizures persisted for >1 month in 83%, and 60% had ongoing seizures, with almost all patients (55/60, 92%) still being on antiseizure medications at last follow-up a median of 25 months after seizure onset. Ongoing seizures at last follow-up were associated with Ma2-IgG or ANNA1-IgG compared to other antibodies (p =.04), highest seizure frequency being at least daily (p =.0002), seizures on electroencephalogram (EEG; p =.03), and imaging evidence of limbic encephalitis (LE; p =.03). Death occurred in 48% throughout the course of follow-up, with a higher mortality in patients with LE than in those without LE (p =.04). Of 31 surviving patients at last follow-up, 55% continued to have intermittent seizures. Significance: Seizures in the setting of high-risk paraneoplastic antibodies are frequently resistant to treatment. Ongoing seizures are associated with ANNA1-IgG and Ma2-IgG, high seizure frequency, and EEG and imaging abnormalities. Although a subset of patients may respond to immunotherapy and achieve seizure freedom, poor outcomes are frequently encountered. Death was more common among patients with LE.

Original languageEnglish (US)
Pages (from-to)2385-2398
Number of pages14
JournalEpilepsia
Volume64
Issue number9
DOIs
StatePublished - Sep 2023

Keywords

  • autoimmune-associated epilepsy
  • paraneoplastic antibodies
  • seizures

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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