Epilepsy and autism: How does age at seizure onset factor in?

Abstract

SUMMARY Introduction. Three neuropathological conditions and two neurosurgical situations have been reported to present significantly earlier seizure onset in cases with autism than without. These are tuberous sclerosis, Angelman syndrome, the PCDH19 mutation, vagal nerve stimulation and epilepsy surgery. Method. We reviewed the case-report literature to determine the extension of this autism-specific early seizure onset effect across all relevant neuropathological conditions. Published clinical cases were collected fulfilling two inclusion criteria: age at seizure onset stated and presence (N = 1885 cases) or absence (N=4907 cases) of autism. We also documented the type and tractability/intractability of the epilepsy, genetic abnormality, neurologic syndrome, structural brain imaging findings and presence of intellectual disability when available. Results. Cases with autism presented significantly earlier seizure onset than cases without autism in 38 neuropathological conditions out of 162, including the previously established five. These 38 neuropathological conditions typically involved intractable epilepsy caused by focal cortical dysplasia located in the social brain, with the ictal or interictal electrical focus also located in the social brain. Within these 38 neuropathological conditions, in the cases with autism, the median seizure onset occurred between 50 days and 24 months after birth. Conclusion. Onset of severe seizure disorder during an early critical post-natal interval, caused by brain damage specifically located in the social brain, strongly associates with subsequent autism.