Brain tumor and seizures: pathophysiology and its implications for treatment revisited

Seizures affect approximately 50% of patients with primary and metastatic brain tumors. Partial seizures have the highest incidence, followed by secondarily generalized, depending on histologic subtype, location, and tumor extent. The underlying pathophysiologic mechanisms of tumor-associated seizures are poorly understood and include theories of altered peritumoral amino acids, regional metabolism, pH, neuronal or glial enzyme and protein expression, as well as immunologic activity. An involvement of changed distribution and function of N-methyl-d-aspartate subclass of glutamate receptors also has been suggested. The often unpredictable responses to seizures after surgical tumor removal add substantial evidence that multiple factors are involved. The therapy of tumor-related seizures is far from perfect. Several factors contribute to these treatment difficulties, such as tumor growth and drug interactions; however, one of the main reasons for poor seizure control may result from the insufficient or even absent influence of the currently available antiepileptic drugs (AEDs) on most of the pathophysiologic mechanisms of tumor-related seizures. Studies are needed to elucidate more clearly the pathophysiologic mechanisms of tumor-related seizures and to identify and develop the optimal AEDs.