Early-life seizures are known to be associated with autism, and studies indicate that about 40 percent of patients with autism also have epilepsy. A study from Boston Children's Hospital finds a reason for the link, and suggests that an existing drug, already shown to be safe in children, could help prevent autism from developing in newborns who have seizures.
Led by Frances Jensen, MD, in the Department of Neurology and the F.M. Kirby Neurobiology Center at Boston Children's Hospital, the study suggests that seizures over-activate a biochemical pathway previously linked to autism, known as the mTOR pathway, and that this alters the fast-forming circuitry in infants' developing brains.
In a rat model, Jensen and colleagues showed that early seizures not only resulted in epilepsy later in life, but also produced autistic-like behavior. They further showed that disabling the mTOR pathway – by giving the drug rapamycin before and after seizures – prevented development of abnormal patterns of connections (synapses) between brain cells, reduced later-life seizures and eased autistic-like symptoms.
Findings were published May 2 in the online journal PLoS ONE.
"In children, there is overlap between epilepsy and autism, and epilepsy early in life has been linked to later autism," says Jensen of Boston Children's Hospital. "Our findings show one of probably many pathways that are involved in this overlap – importantly, one that is already a therapeutic target and where treatment can reverse the later outcome."
Specifically, the study demonstrated that a group of signaling molecules, known collectively as the mTOR pathway, shows increased activation after a seizure. This increased signaling – above and beyond the surge that normally occurs early in life – disrupted the normal balance of synapse and circuit development to produce epilepsy and altered social behavior. Rapamycin treatment inhibited mTOR signaling, reducing susceptibility to seizures and preventing seizure-induced changes in the synapses.