Conference Coverage

High infantile spasm risk should contraindicate sodium channel blocker antiepileptics



Sodium channel blocker antiepileptic drugs increase the risk of infantile spasms sevenfold in children with Down syndrome, tuberous sclerosis complex, hypoxic-ischemic encephalopathy, and other nonsyndromic epilepsy conditions with infantile spasms, according to a case-control review from the University of California, Los Angeles. “This is scary and warrants caution,” said senior investigator and pediatric neurologist Shaun Hussain, MD, a pediatric neurologist at Mattel Children’s Hospital at UCLA. Because of the findings, “we are avoiding the use of voltage-gated sodium channel blockade in any child at risk for infantile spasms. More broadly, we are avoiding [them] in any infant if there is a good alternative medication, of which there are many in most cases.”

There have been a few previous case reports linking voltage-gated sodium channel blockers (SCBs) – which include oxcarbazepine, carbamazepine, lacosamide, and phenytoin – to infantile spasms, but they are still commonly used for infant seizures. There was some disagreement at UCLA whether there really was a link, so Dr. Hussain and his team took a look at the university’s experience. They matched 50 children with nonsyndromic epilepsy who subsequently developed video-EEG confirmed infantile spasms (cases) to 50 children who also had nonsyndromic epilepsy but did not develop spasms, based on follow-up duration and age and date of epilepsy onset.

The team then looked to see what drugs they had been on; it turned out that cases and controls were about equally as likely to have been treated with any specific antiepileptic, including SCBs. Infantile spasms were substantially more likely with SCB exposure in children with spasm risk factors, which also include focal cortical dysplasia, Aicardi syndrome, and other problems (HR 7.0; 95%; CI 2.5-19.8; P less than .001). Spasms were also more likely among even low-risk children treated with SCBs, although the trend was not statistically significant.

In the end, “we wonder how many cases of infantile spasms could [have been] prevented entirely if we had avoided sodium channel blockade,” Dr. Hussain said at the annual meeting of the American Epilepsy Society.

With so many other seizure options available – levetiracetam, topiramate, and phenobarbital, to name just a few – maybe it would be best “to stay away from” SCBs entirely in “infants with any form of epilepsy,” said lead investigator Jaeden Heesch, an undergraduate researcher who worked with Dr. Hussain.

Jaeden Heesch, pediatric continuity clinic intern at UCLA Mattel Children's Hospital. M. Alexander Otto/MDedge News

Jaeden Heesch

It is unclear why SCBs increase infantile spasm risk; maybe nonselective voltage-gated sodium channel blockade interferes with proper neuron function in susceptible children, similar to the effects of sodium voltage-gated channel alpha subunit 1 mutations in Dravet syndrome, Dr. Hussain said. Perhaps the findings will inspire drug development. “If nonselective sodium channel blockade is bad, perhaps selective modulation of voltage-gated sodium currents [could be] beneficial or protective,” he said.

The age of epilepsy onset in the study was around 2 months. Children who went on to develop infantile spasms had an average of almost two seizures per day, versus fewer than one among controls, and were on an average of two, versus about 1.5 antiepileptics. The differences were not statistically significant.

The study looked at SCB exposure overall, but it’s possible that infantile spasm risk differs among the various class members.

The work was funded by the Elsie and Isaac Fogelman Endowment, the Hughes Family Foundation, and the UCLA Children’s Discovery and Innovation Institute. The investigators didn’t have any relevant disclosures.

SOURCE: Heesch J et al. AES 2019. Abstract 2.234.

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