Epilepsy in autism: A pathophysiological consideration

Eighty cases of idiopathic autism with epilepsy and 97 cases without epilepsy were studied to evaluate the pathophysiology of epilepsy in autism. The initial visit to this clinic ranged 8 months-30 years 3 months of age, and the current ages are 5 years 8 months-42 years 3 months, 60% reaching to over 30 years of age. The average follow up duration is 22.2 years +/- 9.4 years. The ages of onset of epilepsy were from 7 months to 30 years of age, with the two peaks at 3.2 years and 16.7 years. EEG central focus appeared earlier than frontal focus. Abnormality of locomotion and atonic NREM were observed more frequently in epileptic group. These suggest the neuronal system related to abnormality of locomotion and atonic NREM, which are the hypofunction of the brainstem monoaminergic system, is the pathomechanism underling the epilepsy in autism. By showing the abnormal sleep-wake rhythm and locomotion being the very initial symptoms in autism, we had shown the hypofunction of the brainstem monoaminergic system is the initial pathomechanism of autism. Thus, epilepsy in autism is not the secondary manifestation, but one of the pathognomonic symptoms of autism. The brainstem monoaminergic system project to the wider cortical area, and the initial monoaminergic hypofunction may lead to the central focus which appears earlier. The failure of the monoaminergic (serotonergic) system causes dysfunction of the pedunculo-pontine nucleus (PPN) and induces dysfunction of the dopamine (DA) system, and with development of the DA receptor supersensitivity consequently disinhibits the thalamo-frontal pathway, which after maturation of this pathway in teens cause the epileptogenesis in the frontal cortex. (C) 2010 Elsevier B.V. All rights reserved.