Epileptic Metastatic Brain Tumors: Current Concepts in Pathogenesis, Clinical Assessment, Diagnosis, Therapeutic Strategies, and Contemporary Challenges

Epileptic seizures are among the most disabling neurological complications associated with metastatic brain tumors and constitute a major source of morbidity, neurocognitive decline, functional deterioration, and impaired quality of life in oncologic patients. Brain metastases are currently the most common intracranial neoplasms in adults, with increasing incidence attributable to improved systemic cancer survival, advances in neuroimaging, and expanding use of targeted and immunotherapeutic agents. Seizures may occur at presentation, during disease progression, following neurosurgical intervention, after radiation therapy, or secondary to treatment-related neurotoxicity.

Tumor-related epilepsy in metastatic brain disease differs substantially from epilepsy associated with primary brain tumors because of heterogeneous tumor histologies, multifocal disease patterns, distinct inflammatory microenvironments, systemic oncologic interactions, and varying neuroanatomical distributions. Contemporary evidence suggests that epileptogenesis in metastatic brain tumors is mediated through complex interactions involving cortical irritation, glutamatergic excitotoxicity, neuroinflammation, blood–brain barrier disruption, peritumoral edema, synaptic remodeling, metabolic dysfunction, and tumor-induced neuronal hyperexcitability. Clinical manifestations vary from focal aware seizures to generalized convulsive status epilepticus and nonconvulsive epileptic states, frequently complicating diagnosis in critically ill patients. Modern diagnostic approaches incorporate advanced magnetic resonance imaging, continuous electroencephalographic monitoring, molecular profiling, functional neuroimaging, and multidisciplinary neuro-oncologic assessment. Current treatment paradigms emphasize individualized management strategies integrating antiseizure medications, neurosurgical resection, stereotactic radiosurgery, whole-brain radiotherapy, targeted systemic therapies, corticosteroids, rehabilitation, and palliative interventions.

Despite major advances in neuro-oncology, important controversies persist regarding prophylactic antiseizure therapy, management of drug-resistant tumor-related epilepsy, neurocognitive toxicity, treatment-associated epileptogenesis, and optimization of quality-of-life outcomes. This review comprehensively examines the epidemiology, pathogenesis, clinical presentation, diagnostic evaluation, differential diagnosis, treatment strategies, prognostic determinants, and contemporary controversies surrounding epileptic metastatic brain tumors while highlighting limitations in current evidence and future research priorities.