Primary Motor Cortex Involvement and Its Association With Seizure Risk in Patients With Brain Metastases

Seizures are common in patients with brain metastases (BMs), causing significant morbidity and reduced quality of life. The relationship between BM location and seizure risk remains unclear. Nononcologic literature suggests that primary motor cortex disruption may predispose to seizures. This study evaluated whether BM in primary motor cortex display increased seizure risk relative to BM in other locations.

In this retrospective cohort study, patients with radiographic evidence of BM managed at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2003 and 2022, and maintained in a database, were included. Abstracted covariables spanned demographic (age, sex, and race), clinical (comorbidities and performance status), oncologic (cancer type, extracranial/intracranial disease extent, and prior systemic therapy), radiotherapeutic/neurosurgical (employment and type of radiation, presence of preceding brain-directed surgery), and outcome/seizure-related (presence, timing, and nature of seizures) domains. The exposure variable was BM in the primary motor cortex, and the outcome measure was seizures on a per-patient level. The effect of primary motor cortex involvement on seizure risk, at diagnosis and thereafter, was evaluated using univariable/multivariable logistic, and Fine and Gray competing risks regression, respectively. To limit confounding by lesion number, analyses were repeated in patients with a single BM at diagnosis (n = 1,174).

Among 3,043 patients with (n = 570, 18.7%) vs without (n = 2,473, 81.3%) BM in primary motor cortex, the mean age was 60 vs 61 years, and 61% vs 62% of patients were female, respectively. Primary motor cortex involvement was associated with increased seizure risk at diagnosis (24.4% vs 10.3%, odds ratio 2.87, 95% CI 2.23-3.98, p < 0.001) and after initial diagnosis (hazard ratio [HR] 1.95, 95% CI 1.56-2.43, p < 0.001). Of 1,446 patients who developed additional BM after initial intracranial oncologic involvement, those with disease involving primary motor cortex were more likely to develop seizures thereafter (HR 2.11, 95% CI 1.56-2.86, p < 0.001).

Patients with BM in the primary motor cortex may display increased seizure risk. As this study was retrospective, routine use of antiseizure medications in patients with BM in primary motor cortex in the off-trial setting is not recommended. However, dedicated trials evaluating prophylactic antiseizure medications in this population may be warranted.