Risk Factors for Seizure Development Among Patients With Brain Metastases

Study researchers evaluated the incidence and risk factors for seizure development among patients with brain metastases.

Patients with brain metastases are at a significantly increased risk for seizures, with a higher incidence among patients with melanoma, African American patients, those with significant intracranial disease burden, and those with metastases in epileptogenic intracranial locations, according to study results published in Neurology.

Previous studies provided varying estimates of the proportion of patients diagnosed with brain metastases that present with seizures. The objective of the current study was to assess the incidence and risk factors for seizure development among seizure-naïve patients with brain metastases. 

In this retrospective study, researchers used the Surveillance, Epidemiology, and End-Results-Medicare data to identify 15,863 patients who were at least 66 years old and diagnosed with brain metastases between 2008 and 2016. In addition, an institutionally-based analysis was conducted and 1453 seizure-naïve patients with newly diagnosed brain metastases treated at Brigham and Women’s Hospital/Dana-Farber Cancer Institute between 2000 and 2015 were included.

Among 15,863 Medicare patients without seizures at diagnosis of brain metastases, 1588 (10%) then developed seizures, with increased one-year rates of seizure development among patients with melanoma than those without (13.0% vs 8.3%, respectively; P <.001), and increased rates among African-American patients than non-African American patients (10.9% vs 8.4%, respectively; P =.005).

In the adjusted regression models, African American patients vs White patients (hazard ratio[HR], 1.45; 95% CI, 1.22-1.73; P <.001), higher zipcode-level household income (HR, 1.04; 95% CI, 1.02-1.07; P =.001), urban vs non-urban/unknown residency (HR, 1.41; 95% CI, 1.17-1.70; P <.001), melanoma vs non-small cell lung cancer (HR, 1.44; 95% CI, 1.20-1.73; P <.001), and receipt of brain-directed stereotactic radiation vs non-stereotactic brain directed radiation (HR, 1.67; 95% CI, 1.44-1.94; P <.001) were associated with an increased risk for seizure development.

Among 1453 seizure-naïve patients at diagnosis of brain metastases, 169 (11.6%) subsequently developed seizures. Similarly, the risk for seizures was higher for patients with melanoma than those without melanoma (15.0% vs 5.9%, respectively; P <.001).The risk was higher for those with more than 4 brain metastases compared with patients with no more than 4 brain metastases (8.4% vs 6.9%, respectively; P =.05) and in those with metastases in high than low risk locations (9.8% vs 2.0%, respectively, P <.001).

In the adjusted regression models, melanoma vs non-small cell lung cancer (HR, 1.70, 95% CI, 1.09-2.64; P =.02), greater than 4 brain metastases at intracranial presentation (HR, 1.60, 95% CI, 1.12-2.29; P =.01), presence of brain metastases in a high-risk location at intracranial presentation (HR, 3.62, 95% CI, 1.60-8.18; P =.002), and lack of local brain-directed therapy (HR, 3.08, 95% CI, 1.45-6.52, P =.003) were associated with greater risk of seizure development.

The study had several limitations, including those secondary to using claims to identify cancer metastases, incomplete data availability, and missing data on the risk for seizure development throughout the patients’ disease course.

“Given that seizures have the potential to cause serious harm and also profoundly decrease quality of life for patients with BrM [brain metastases], these findings may be useful in counseling patients about individual seizure risk and may inform future studies evaluating the role of upfront initiation of ASMs [anti-seizure medications] for particularly vulnerable subgroups,” concluded the study researchers.

Disclosure: One of the study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures


Lamba N, Catalano PJ, Cagney DN, et al. Seizures among patients with brain metastases: a population- and institutional-level analysis. Neurology. Published online, January 5, 2021. doi:10.1212/WNL.0000000000011459