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Epileptic encephalopathies and their relationship to developmental disorders: do spikes cause autism?

Barry R Tharp¹

¹Departments of Neurology and Pediatrics, The M.I.N.D. Institute, University of California, Davis, Sacramento, California 95817, USA. barry.tharp@ucdmc.ucdavis.edu

Mental Retardation and Developmental Disabilities Research Reviews

|September 14, 2004

Insights

Epileptiform discharges in children with autism spectrum disorder do not cause behavioral issues. Treating these EEG abnormalities without seizures offers no therapeutic benefit for autism or PDD.

Area of Science:

Neuroscience
Developmental Pediatrics
Clinical Neurophysiology

Background:

Epileptic encephalopathies involve progressive neurological decline linked to seizures and EEG abnormalities.
Children with pervasive developmental disorders (PDD) have a higher incidence of seizures and epileptiform EEG activity.
Regression in social behavior and language is observed in some children with PDD, with some linking it to subclinical epileptiform activity.

Purpose of the Study:

To review the association between interictal epileptiform discharges and clinical dysfunction.
To examine the implications of these findings for autistic behavioral abnormalities.
To evaluate the efficacy of interventions for autism with epileptiform EEG abnormalities.

Main Methods:

Literature review of studies on epileptic encephalopathies and PDD.
Analysis of data linking interictal epileptiform discharges to transient clinical dysfunction.
Review of surgical and medical interventions for autism with epileptiform EEG abnormalities.

Main Results:

Interictal epileptiform discharges are associated with transient clinical dysfunction.
No evidence supports the hypothesis that interictal discharges cause the complex behavioral phenotype of autism.
Surgical and medical interventions targeting EEG abnormalities in non-seizing children with PDD showed no behavioral improvement.

Conclusions:

Interictal epileptiform discharges do not cause or contribute to autism's behavioral phenotype.
There is no evidence to support treating children with PDD and autism who do not have seizures with anticonvulsants or surgery to eliminate EEG spikes.
Current evidence does not justify interventions aimed at eliminating EEG spikes for behavioral improvement in PDD and autism.

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Abstract:

Epileptic encephalopathies are progressive clinical and electroencephalographic syndromes where deterioration is thought to be caused by frequent seizures and abundant EEG epileptiform activity. Seizures occur in approximately 10-15% of children with pervasive developmental disorders (PDD) and 8-10% have epileptiform EEG abnormalities without seizures. Thirty percent of children with PDD have regression of social behavior and language at 2-3 years of age. Some authors speculate that the regression is caused by epileptiform activity even in the absence of overt clinical seizures ("autism with epileptic regression") and suggest that elimination of the epileptiform activity, either medically or surgically, should lead to improvement in behavior. This review examines the data showing that interictal epileptiform discharges are associated with transient clinical dysfunction and discusses the implications of these observations for autistic behavioral abnormalities. The results of resective surgery, vagal nerve stimulation, and multiple subpial transaction on children with autism and epileptiform EEG abnormalities are also discussed. I conclude that there is no evidence that interictal discharges per se cause (or contribute to) the complex behavioral phenotype of autism. There is no justification to support the use of anticonvulsant medication or surgery in children with PDD without seizures; that is, there is no evidence that treatment to eliminate EEG spikes will have a therapeutic effect on the behavioral abnormalities of PDD and autism.

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