Levetiracetam May Extend Survival in Brain Tumor Patients

A recent study led by researchers at Stanford Medicine has discovered a potential link between the seizure medication Keppra (levetiracetam) and extended survival in patients with diffuse midline glioma, a type of brain tumor. The research, published in Nature Medicine, suggests that Keppra works by disrupting the electrical connections between tumor cells and healthy nerve cells, a mechanism that does not appear to benefit patients with tumors in other parts of the brain. The study’s findings are based on an analysis of records from 218 children treated for high-grade glioma at Stanford University and the University of Michigan between 1990 and 2021.

Survival rates vary among treated patients

The researchers found that among the 119 children with diffuse midline glioma, those who had taken Keppra (15 patients) had a median survival rate of 20.96 months, compared to 9.92 months for the 104 patients who had not taken the medication. In contrast, the survival rates for children with high-grade gliomas in the cerebral hemispheres were similar, regardless of whether they had taken Keppra or not. The median survival rate for the 40 children who had taken Keppra was 24.0 months, compared to 22.2 months for the 59 children who had not.

Additional data from other patient groups supported these findings. At the University Medical Center Hamburg-Eppendorf in Germany, six children who took Keppra had a median survival rate of 24.0 months, compared to 11.0 months for 19 children who did not take the medication. Similarly, at the University of California, San Francisco, five children who took Keppra had a median survival rate of 15.5 months, compared to 12.2 months for 30 children who did not.

International data confirms the trend

The study’s results suggest that Keppra’s effectiveness in treating diffuse midline glioma may be due to its ability to disrupt the GABAergic synapses that form between tumor cells and healthy nerve cells. This type of synapse is characteristic of diffuse midline glioma and is not found in other types of brain tumors. The researchers used mouse models to demonstrate that Keppra can slow tumor growth and extend survival in diffuse midline glioma, but has no effect on tumors in other parts of the brain.

How Keppra targets tumor cells

The study found that Keppra does not appear to work through the same mechanism that makes it effective against seizures. Briviact (brivaracetam), a medication that targets the same pathway as Keppra, had no effect on tumor cells. Additionally, two other seizure medications, Zarontin (ethosuximide) and Dilantin (phenytoin), did not slow tumor growth. The researchers concluded that Keppra’s ability to disrupt GABAergic synapses is the key to its effectiveness in treating diffuse midline glioma.

The clinical portion of the study measured overall survival rates and compared children who had a history of Keppra use with those who had not. Tumor diagnoses were confirmed by a board-certified neuropathologist in cases where tissue was available. The patient groups studied predated the arrival of CAR-T cell therapy for these tumors.

Study limitations and next steps

The researchers noted that the clinical data was collected retrospectively, rather than through a controlled trial, and that the number of children who had taken Keppra was small at every site. They wrote that “prospective clinical trials are required to validate this conclusion.” The team also raised the possibility that the children who received Keppra may have had seizures, and that tumors causing seizures may be more responsive to the medication. Tumor location could also play a role, as the brain stem, thalamus, and spinal cord carry more GABAergic input that Keppra appears to interrupt. An unrecognized factor in the patient records could account for part of the result.