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

doi:10.1111/epi.17695

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

Epilepsia. 2023 Sep;64(9):2385-2398. doi: 10.1111/epi.17695. Epub 2023 Jul 4.

Authors

Kelsey M Smith¹, Jeffrey W Britton¹, Smathorn Thakolwiboon¹, Nicholas H Chia¹, Pranjal Gupta¹, Eoin P Flanagan^{1

2}, Anastasia Zekeridou^{1

2}, Alfonso S Lopez Chiriboga³, Cristina Valencia Sanchez⁴, Andrew McKeon^{1

2}, Sean J Pittock^{1

2}, Divyanshu Dubey^{1

2}

Affiliations

¹ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
² Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
³ Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
⁴ Department of Neurology, Mayo Clinic, Phoenix, Arizona, USA.

PMID: 37366270
DOI: 10.1111/epi.17695

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.

Keywords: autoimmune-associated epilepsy; paraneoplastic antibodies; seizures.

MeSH terms

Autoantibodies
Humans
Immunoglobulin G
Limbic Encephalitis* / diagnosis
Limbic Encephalitis* / therapy
Male
Middle Aged
Retrospective Studies
Seizures* / etiology

Substances

Autoantibodies
Immunoglobulin G