Neonatal Seizures: Gaps Between the Laboratory and the Clinic

Abstract

Summary: Seizures in neonates (NBs) remain the most frequent neurological problem in the nursery. Considerable debate about their consequences exists between data and deductions reached through animal experimentations and those obtained through clinical investigations. The main conflicting issues are whether seizures in NBs can plant the roots for epileptogenesis and cause long-term deficits. The purpose of this chapter is to evaluate both laboratory and clinical results. Methods: Clinical data will be presented, including a 20-yearlong cohort of NBs. This will be followed by the main seminal discoveries obtained in neonatal models. The phenomenon of transient or persistent dysmaturity following NB seizures will be discussed in relation to etiological factors. Results: The findings and deductions from animal models support the notions that epileptogenesis and cognitive deficits result from NB seizures. These conclusions contrast with clinical investigations maintaining that NB seizures, per se, are symptomatic markers of preexisting or of ongoing morbidities. The reasons for contrasting views will be discussed. Suggestions will be advanced for more animal models whose seizures are consistent with the etiologies and the phenotypes of human NB seizures.

Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome

“…[14][15][16] Poorer neurodevelopmental outcome has been associated with greater number of seizures per day but usually in the presence of severe neuroanatomical findings. 17 By contrast, in our study, neonatal seizures were usually single events and independent of underlying major structural brain pathology.…”

Hub GABA Neurons Mediate Gamma-Frequency Oscillations at Ictal-like Event Onset in the Immature Hippocampus

“…Although there is more resistance to acute seizure-induced cell loss than in the adult brain, both clinical (Baram, 2003; Lombroso, 2007) and experimental (Holmes et al, 1998) studies have confirmed that frequent or prolonged seizures lead to long-term impairments in brain development and functional abnormalities. Transient gamma-frequency oscillations (GFOs; > 40Hz) occurring at the onset of most seizures are a marker of a chronic epileptic condition (Worrell et al, 2004).…”

Independent role of neonatal seizures in subsequent neurological outcomes: a population‐based study

“…Previous studies reported that neonatal seizures have an increased risk of developing long‐term morbidity, including epilepsy and neurodevelopmental disorders . However, the underlying causes of seizures, rather than seizures per se, have been considered as the critical determinant of neurological abnormalities later in life . While two prior randomized controlled studies found that increasing electrographic seizure burden was significantly associated with severe brain injuries and poor neurodevelopmental outcomes, only term neonates with hypoxic‐ischemic encephalopathy were investigated in the studies.…”