Is Autonomic Nervous System Involved in the Epileptogenesis in Preterm Neonates?

Autonomic nervous system dysfunction has been described with focal and generalized epileptic seizures; occurring during their ictal, interictal, or postictal states. International League Against Epilepsy Seizure Classification Manual defines autonomic seizures as a distinct alteration of autonomic nervous system function involving cardiovascular, pupillary, gastrointestinal, sudomotor, vasomotor, and thermoregulatory functions. Autonomic seizures represent a great challenge for neonatologists and neurophysiologists; and distinguishing between ictal and non-ictal autonomic changes in neonates is rarely straightforward, especially in the premature ones. To avoid overdiagnosis and overtreatment, International League Against Epilepsy and the American Clinical Neurophysiology Society currently require electrographic correlation for any seizure diagnosis, including preterm neonates. There is very little scientific evidence about the pathophysiology of autonomic seizures. The data reporting on their incidence, clinical features, and diagnostic pathway is also insufficient. In this paper, we hypothesize that in the developing brain of preterm neonates, seizures involving deeper autonomic networks and subcortical structures might not propagate sufficiently to the cortex, and therefore the association of the seizures with specific ictal electrographic changes on surface electroencephalogram might be lacking. We propose considering autonomic seizures in the differential diagnosis of unexplained autonomic changes in neonates, especially preterm neonates, even in the absence of clear initial electrographic correlation. Unexplained autonomic changes could therefore be thought of as a "seizure alarm" in this population.