In autism, stopping seizures may aid brain development
IT’S been long known that many children with autism also have epilepsy or some form of seizure disorder.
Not so well understood was the relationship between the two.
But a new Penn study suggests that early life seizures may switch on synapses in the brain that can lead to further development delays in children with autism and other intellectual disorders, including language and learning deficits.
The good news is that aggressively treating those seizures – with medicines that already exist or new treatments being developed – may keep those synapses “silent” and allow the brain to develop more normally.
“We now have evidence that seizures appear to be worsening the developmental disorder, and when you block those seizures, you reverse that,” said senior author Frances Jensen, chair of neurology at Penn’s Perelman School of Medicine.
“It appears seizures may exacerbate features common in autism,” said Jensen, whose research conducted with colleagues from Harvard and Carleton University was published online recently in the journal Cell Reports.
According to 2014 data from the Centers for Disease Control and Prevention, autism has a prevalence rate of one in 59 among eight-year-olds in 11 states surveyed, a 15% increase from 2012.
Up to 40% of children with autism and intellectual disabilities also have epilepsy, and about 35% of children who experience infan- tile spasms develop long-term intellectual disabilities, including autism, according to the researchers.
The study findings build on what is already known about brain development. During early childhood, the brain goes through so-called critical periods where synapses linked to language skills are activated gradually.
But if the synapses are activated or “unsilenced” prematurely through seizures, they are less available for learning during those critical periods, the researchers said.
Working with mice, Jensen and her colleagues found that premature activation of the synapses through induced seizures created a disruption days later during a critical period of development for the mice.
The researchers treated the seizure-induced mice with an anti-epileptic, anti-convulsant drug that reduced the premature “unsilencing” of certain synapses and helped restore them, making them available when the mice entered a critical learning period later.
“Understanding the precise synaptic changes following seizures gives an opportunity to find treatments that can prevent this early ‘unsilencing’,” Jensen said. “The timing is important: We need to stop it right after the seizures and before a critical period of development in a child’s life so the brain can develop without any problems that may lead to future impairments.”
While many of these children may already be prescribed anti-epileptic medications to help prevent seizures, researchers are advocating for additional treatment promptly following each individual seizure.
The drug used in the study was experimental and is not approved for use in children, Jensen said. However, she is currently developing a treatment that would block the undesirable impact of seizures on synapses without unwanted side effects.
But Jensen said there are US Food and Drug Administrationapproved medications available that she said should be used rapidly after a seizure to help keep the unwanted brain changes from happening, or at least reduce them.
In the case of a child already diagnosed with autism, Jensen said treatment could prevent unwanted brain changes that could move that child into a more severe range of the autism spectrum.
“As we are learning more about this cellular, molecular cascade of pathways that change synapses after a seizure,” Jensen said, “we are discovering checkpoints to stop the cascade moving forward.” – The Philadelphia Inquirer/Tribune News Service