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Does AED prophylaxis delay seizure onset in children with brain tumors?



Among children with brain tumors, prophylaxis with an antiepileptic drug (AED) is associated with a longer time between brain tumor diagnosis and first seizure diagnosis within the first 6 months of follow-up, according to research presented at the annual meeting of the Child Neurology Society. Levetiracetam, oxcarbazepine, and phenytoin are the most common initial prophylactic AEDs administered to children with brain tumors, the researchers said.

The literature indicates that between 20% and 35% of children with brain tumors have seizures, and up to half of these patients have seizure as their presenting symptom. Common practice is to prescribe antiseizure medication after a child has had a first seizure, because the risk for recurrence is high. In 2000, the American Academy of Neurology discouraged prophylactic use of AEDs in children, citing a lack of evidence for efficacy. Most of the data that it reviewed, however, came from adults.

Michelle Yun, a medical student at Weill Cornell Medical College, New York, and colleagues used national Medicaid claims data that had been collected between 2009 and 2012 for children with seizures to conduct a retrospective, observational, case-control study. They included children aged 0-20 years with a diagnosis of brain tumor, a seizure diagnosis within 6 months after brain tumor diagnosis, an AED prescription, and 12 continuous months of Medicaid coverage following brain tumor diagnosis in their analysis. The investigators defined seizure prophylaxis as AED prescription within 30 days after brain tumor diagnosis but before a first seizure diagnosis.

The exposure in the study was AED prescription within 45 days of diagnosis, and the outcome was the time to first seizure. Ms. Yun and colleagues also analyzed the most common initial prophylactic AEDs and the proportion of cases with first seizure diagnosis after prophylactic AED discontinuation, which was defined as a treatment gap longer than 30 days. The study covariates included age, sex, race, ethnicity, and medical comorbidities.

In all, 218 children were included in the study; 40 received AED prophylaxis and 26 received it within 45 days of brain tumor diagnosis. Patients with and without AED prophylaxis were well matched on all covariates.

At 1 year, Ms. Yun and colleagues saw no difference in time to first seizure between the two groups. The median time to first seizure was 75 days in the prophylaxis group and 80 days in the no-prophylaxis group. The researchers observed a transient separation between the two groups, however, in the early months after brain tumor diagnosis. When they examined children who had a seizure during the first 6 months of follow-up, the median time to diagnosis of first seizure was 68 days in children with prophylaxis and 34 days in the no-prophylaxis group. The difference between groups was statistically significant. “When we added all the covariates of interest, we found that there was a protective effect in these children with early seizures,” said Ms. Yun.

Among the study limitations that Ms. Yun acknowledged were its observational, retrospective design and its small sample size. Medicaid data themselves are limited, since states do not report them in a uniform manner, and the data do not include much clinical information. “Something that would be helpful is a prospective clinical study,” Ms. Yun concluded.

The Weill Cornell Clinical and Translational Science Center and the American Academy of Neurology provided funding for the study. The Pediatric Epilepsy Research Foundation provided the Medicaid data. Ms. Yun had no relevant disclosures.

SOURCE: Yun M et al. CNS 2019, Abstract PL2-1.

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