Management of cancer-associated seizures requires careful confirmation that tumors are the cause of convulsions, and subsequent tumor-targeted treatment with surgical resection, chemotherapy and/or radiotherapy. While the evidence base for the use of antiepileptic drugs for cancer-associated seizures is scant, a key consideration is the potentially harmful interaction between antiepileptics, corticosteroids, and many chemotherapy agents.
Epileptic seizures—potentially life-threatening, transient disruptions of motor control and neurocognitive function caused by aberrant neuronal activity (synaptic firing) patterns in the brain—are common among patients with cancer, particularly those with primary or metastatic solid tumors in the brain or subarachnoid space (leptomeningeal disease).1 Seizures are the most common initial symptom of primary brain tumors among adult patients; moreover, patients with primary or metastatic brain tumors face a 20% to 80% lifetime risk of developing seizure disorders.1 Brain tumors in these patients tend to be associated with tonic-clonic generalized (“grand mal”) seizures.1
The underlying etiology of seizures in patients with cancer can be complex, involving anatomic and metabolic disruptions caused by brain tumors themselves, tumor- or medication-related stroke or opportunistic infection, chemotherapy, or neuroradiotherapy.1 Primary solid brain tumors appear to be more strongly associated with seizures than metastatic tumors, which Michael Weller, MD, of the University Hospital Zurich in Switzerland, and colleagues suggest might be due to metastatic tumors’ “less infiltrative growth and their inability to biochemically modulate neuronal excitability.”1
“New-onset seizures in patients with known brain metastases may indicate hemorrhage into a metastatic lesion, notably in patients with metastatic melanoma, or tumor progression with associated edema,” Dr. Weller and his coauthors note.1
Risk of seizures can also vary depending on tumor location in the brain.2 For example, primary meningiomas occurring in the premotor cortex are more likely to be associated with seizures than are tumors found in other brain regions.2 Larger-diameter meningioma tumors are also more likely to trigger seizures, but this may not be the case with other types of brain tumors; glioma tumor grade, for example, does not appear to affect the risk of seizure, according to one recent retrospective study.2
Cancers outside the brain can also cause seizures or seizure-like symptoms. In very rare instances, hepatic carcinoma–associated hypoglycemia reportedly can present as seizures, for example.4 Spinal cord tumors may cause involuntary tremors or twitching of the extremities, which can be mistaken for mild (focal) epileptic seizure activity.5