Depakote Treatment for Concurrent Autism and Abnormal EEG

Background:  There is a higher rate of abnormal  sleep EEG in the autism population than the general population with the majority not having clinical seizures but only abnormal interictal EEG.  Abnormal EEG has been linked to neurocognitive deficits including language delays especially in epileptiform spikes involving temporal parietal and central regions in sleep. Valproic acid is an effective intervention to reduce presence of abnormal EEG and improve observed receptive language.

Objectives:  Investigate language levels following Depakote treatment for children with ASD and concurrent abnormal EEG.

Methods:  This retrospective investigation involved a medical records review of male children with autism spectrum disorder (ASD) and no clinical seizures and concurrent abnormal electroencephalogram (EEG) treated in an outpatient specialty center. 50 Males patients without clinical seizures were analyzed for abnormal EEG epileptiform activity with ambulatory or video EEG monitoring for 24 hours as part of their clinical medical evaluation. Age ranged from 15 months to 72 months. All children had ADOs confirmed autism per regional center criteria. None had known genetic disorders or other conditions( extreme prematurity or cerebral palsy as examples). Valproic acid treatment was titrated to trough levels above 85mg/ml and less than 120mg/ml, and EEG studies were repated between 3 and 6 months after original study.

Results:  Clinical follow-up in this retrospective analysis showed clinician and parental reports of improved language processing and eye contact after valproic acid treatment. EEG improvement with normalization or substantially reduced spike activity correlated with clinical improvement. There were no indications of decrease in language for any patient. No major adverse effects were seen, and blood testing results will be discussed. No problem tolerating EEG testing caused failure to obtain studies refuting myth that these children are too hard to test.

Conclusions: This retrospective investigation suggests that children diagnosed with an ASD and concurrent abnormal EEG showed improvements in language after beginning valproic acid. Increases in language including improved comprehension, improved eye contact effort and less irritability may be a factor of improved cortical function related to reduction in seizure activity as shown on post-treatment EEG. Accurate language measurements and placebo controlled treatment trials are needed to establish this important clinical finding that EEG is important as defining possible additional dysfunction in autism and should become a standard of clinical care.