Old Epilepsy Drug Emerges as Safer Seizure Shield for Kids on Chemotherapy

When a child with leukemia or lymphoma suddenly develops seizures, blurred vision, and dangerously high blood pressure in the middle of chemotherapy, doctors face one of the most delicate balancing acts in pediatric medicine. The culprit is often posterior reversible encephalopathy syndrome, or PRES, a neurological complication in which the brain’s ability to regulate its own blood supply breaks down under the stress of cancer treatment. Seizures are among the most common and frightening manifestations of the condition, and once they recur, clinicians must decide whether to start long-term antiseizure medication. That decision is far from trivial, because many of the drugs used to quiet the brain interfere with the very chemotherapy regimens keeping the cancer at bay. A new retrospective study from a major Chinese pediatric center now offers a tentative answer, pointing to an old and somewhat unfashionable epilepsy drug, topiramate, as a potentially safer companion for children navigating this dual threat.

The research, conducted at the Chinese People’s Liberation Army General Hospital in Beijing and published in BMC Cancer, examined the records of pediatric patients with hematologic malignancies who developed PRES during chemotherapy between January 2011 and December 2024. Over that fourteen-year window, nineteen children met the criteria for the syndrome, and seventeen of them experienced seizures. The team, led by Lin-Yan Hu, Chen Feng, and senior authors Xiu-Yu Shi and Li-Ping Zou, focused on a specific clinical question: among children who needed ongoing antiseizure therapy after their acute episodes, which medication could be given without sabotaging the cancer treatment itself? Their answer, drawn from a small but carefully documented cohort, was topiramate, a drug with a pharmacological profile that largely sidesteps the metabolic machinery chemotherapy depends on.

To understand why this matters, it helps to consider the biology of the problem. Most chemotherapy agents are metabolized by the cytochrome P450 enzyme family in the liver, a system that also processes many older antiseizure medications. Drugs such as phenytoin, carbamazepine, and phenobarbital are potent inducers of these enzymes, meaning they can accelerate the breakdown of chemotherapeutic agents and reduce their effectiveness below therapeutic thresholds. In a child fighting acute lymphoblastic leukemia or Burkitt lymphoma, that interaction is not a theoretical concern; it can mean the difference between remission and relapse. Even newer agents like levetiracetam, which has become the default choice in many oncology settings because of its benign interaction profile, carry practical challenges, including behavioral side effects in children and dosing adjustments in kidney impairment, which is common in PRES itself.

Topiramate occupies an unusual niche in this landscape. Chemically a sulfamate-substituted monosaccharide, it dampens neuronal excitability through several mechanisms at once: it blocks voltage-gated sodium channels, enhances the inhibitory action of GABA at certain receptors, antagonizes the AMPA subtype of glutamate receptor, and modulates calcium channels. Crucially, it is largely eliminated unchanged by the kidneys rather than extensively metabolized by cytochrome P450 enzymes, which means it exerts minimal induction or inhibition on the pathways that clear chemotherapy drugs. This pharmacokinetic invisibility is precisely what makes it attractive for oncology patients, and it is the theoretical foundation on which the Beijing team built their clinical experience.

The study’s design was straightforward and descriptive. The researchers defined clear criteria for initiating maintenance antiseizure therapy: children who suffered more than two seizures within twenty-four hours, or more than three seizures within three days, were considered at sufficiently high risk of further episodes to warrant ongoing medication. Of the eleven children who met these thresholds, eight received topiramate at a median dose of three milligrams per kilogram per day, while three received levetiracetam at a median of thirty-five milligrams per kilogram per day. Six additional children who experienced only a single seizure did not receive maintenance therapy, reflecting a deliberate strategy of reserving long-term drugs for those with demonstrated recurrence risk.

The outcomes, though drawn from a small sample, tell a striking story. All eight children treated with topiramate completed their planned chemotherapy courses, and no serious adverse events attributable to antiseizure medications were documented anywhere in the cohort. One child in the topiramate group required the drug to be reintroduced after an initial discontinuation and went on to develop secondary epilepsy, a reminder that PRES can leave lasting neurological scars even when the acute imaging findings appear reversible. In the levetiracetam group, the picture was more sobering: one child died from cancer relapse after persistent neurological deficits made it impossible to tolerate further chemotherapy. Among the six children with single seizures who received no maintenance therapy, two likewise died of relapse after being unable to continue treatment.

These numbers must be interpreted with great care, and the authors are refreshingly candid about that. The study is retrospective, meaning the researchers looked backward at records rather than assigning treatments prospectively, and it was not randomized. The choice of topiramate versus levetiracetam was made by treating clinicians, likely influenced by each child’s specific circumstances, introducing selection bias that no statistical adjustment can fully remove. With only nineteen patients in total and just eleven on maintenance therapy, the study lacks the statistical power to demonstrate that topiramate improves survival or chemotherapy completion rates. The authors explicitly frame their findings as hypothesis-generating and descriptive, a scientific way of saying that the results are intriguing enough to justify further study but not definitive proof of benefit.

Nevertheless, the consistency of the signal is worth pausing on. In a population where the inability to tolerate chemotherapy is often the proximate cause of death, the observation that every topiramate-treated child completed their planned cancer treatment is clinically meaningful, even if causation cannot be established. The median dose used, three milligrams per kilogram per day, is modest by epilepsy standards, suggesting that seizure control in PRES may require less aggressive dosing than chronic epilepsy. The absence of serious adverse events is also notable, given that topiramate is known to cause cognitive slowing, kidney stones, and metabolic acidosis in some patients, side effects that could theoretically compound the toxicities of intensive cancer therapy.

The broader context makes this work part of a growing recognition that PRES in children with cancer deserves dedicated research rather than extrapolation from adult neurology. The syndrome arises when chemotherapy-induced hypertension, electrolyte disturbances, and direct endothelial toxicity overwhelm the autoregulatory capacity of the brain’s posterior circulation, leading to vasogenic edema visible on magnetic resonance imaging. Most children recover fully if the syndrome is recognized promptly and blood pressure is controlled, but the seizure burden during the acute phase can be substantial, and the question of how long to continue antiseizure drugs afterward remains unresolved worldwide. Guidelines are sparse, and practice varies widely between centers, which is precisely why even small descriptive studies like this one fill an important gap.

What happens next will determine whether topiramate’s pharmacokinetic advantages translate into real clinical benefit. The authors call for prospective validation, ideally a multicenter trial that randomizes children with PRES-related seizures to different maintenance regimens and tracks chemotherapy tolerance, seizure recurrence, and long-term neurological outcomes. Until such evidence exists, the Beijing experience offers pediatric oncologists and neurologists a reasoned option to consider when the interaction profile of standard antiseizure drugs threatens to undermine cancer therapy. It is a modest finding in a rare and complicated corner of medicine, but for the families of children facing both cancer and seizures simultaneously, even a modest finding can point toward a safer path through an already perilous journey.

Subject of Research: Use of topiramate as maintenance antiseizure therapy in children with hematologic malignancies who develop posterior reversible encephalopathy syndrome during chemotherapy

Article Title: Topiramate use for maintenance antiseizure therapy in children with hematologic malignancies experiencing posterior reversible encephalopathy syndrome during chemotherapy: a single-center retrospective study

Article References: Hu, L.-Y., Feng, C., Cai, R.-Y., Li, Y., Chai, L.-N., He, W., Chen, J., Wan, L., Yang, G., Shi, X.-Y., & Zou, L.-P. (2026). Topiramate use for maintenance antiseizure therapy in children with hematologic malignancies experiencing posterior reversible encephalopathy syndrome during chemotherapy: a single-center retrospective study. BMC Cancer. https://doi.org/10.1186/s12885-026-16999-9

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16999-9

Keywords: posterior reversible encephalopathy syndrome, PRES, topiramate, levetiracetam, anti-seizure medications, pediatric oncology, hematologic malignancies, chemotherapy, seizures, drug interactions, cytochrome P450, retrospective study