Anti-inflammatory may combat glioma-related seizures
Epileptic seizures—a common and poorly understood comorbidity for people with primary brain tumors—may be related to the release of excess levels of the brain chemical glutamate, and may be controlled with the drug sulfasalazine.
According to a statement from the National Institutes of Health (NIH), which funded the study yielding these findings, approximately 80% of people with glioma will experience at least one seizure during their illness, often as the first symptom. About one-third of patients will develop tumor-associated epilepsy—that is, recurring seizures.
Excess glutamate can cause abnormal electrical activity in the brain, setting the stage for epileptic seizures. In particular, excess release of glutamate from glia cells appears to play a role in some types of epilepsy. Gliomas result from an overgrowth of glia, leading researchers to theorize that tumor-produced glutamate might cause seizures.
Neurobiologist Harald Sontheimer, PhD, of the University of Alabama Birmingham, and colleagues sought to investigate peritumoral seizure etiology by implanting human-derived glioma cells in mice. Within 14 to 18 days, the mice developed spontaneous and recurring abnormal electroencephalogram events consistent with progressive epileptic activity. The brains of these mice showed marked release of glutamate from the tumor. Biophysical and optical recording showed that the glutamate over stimulated neurons near the tumor, triggering seizures.
Sontheimer's group then inhibited glutamate release from the tumors using sulfasalazine, an anti-inflammatory agent. They found that administering the drug at concentrations equivalent to those used to treat Crohn disease reduced epileptic event frequency in the tumor-bearing mice compared with untreated controls.
These results led the investigators to recommend in Nature Medicine that sulfasalazine be considered as an adjuvant treatment to relieve peritumoral seizures associated with glioma.