Epilepsy and epileptiform encephalogram (EEG) abnormalities are common comorbidities in autism spectrum disorders. Sarah Spence at Boston Children’s Hospital proposes that these are important biomarkers of cortical dysfunction involved in the pathogenesis of autism spectrum disorders. Although treatment for epilepsy is always indicated, treating epileptiform EEG abnormalities without seizures is controversial. Data suggest, however, that epileptiform discharges — short bursts of brain activity that resemble EEG patterns during seizures — are associated with deficits in attention, language and behavior, indicating that these discharges may represent a novel treatment target in autism.

Spence and her collaborator, Greg Barnes at Vanderbilt Medical Center in Nashville, plan to test whether an anticonvulsant medication (valproic acid, also known as divalproex sodium or Depakote) can be used to treat children with autism and epileptiform EEGs. The researchers aim to recruit 30 participants between 4 and 8 years old who have been diagnosed with an autism spectrum disorder and who do not have epilepsy or metabolic disorders.

After an overnight EEG screening, children showing frequent epileptiform EEG discharges would be included in the trial. Once enrolled, the children would receive either valproic acid or a placebo for 12 weeks, and then switch to the other treatment for 12 weeks. The children, their families and the investigators would be blind to which treatment the child is getting at which time (active medication or placebo). The researchers predict that administration of valproic acid will reduce epileptiform EEG discharges and may result in improvements in autism symptoms such as sleep, language, mood, irritability, attention, motor skills and sensory symptoms.

This is the first study of its kind and, if successful, may open a new treatment opportunity based on a relatively common and measurable biomarker in autism. Ultimately, results from this trial may be used to design a larger, more definitive clinical study of valproic acid treatment for children with autism and epileptiform EEG.