Seizures and the Neonatal Brain

Abstract

Neonatal seizures are a common and serious problem in infants. Seizures have the highest incidence in the first month after birth and often reflect severe underlying brain injury. Neonatal seizures are difficult to recognise and treat, and can lead to impaired neurodevelopment. The general aim of this thesis was to provide new insights to support evidence based guidelines for the diagnosis, treatment and prognosis of neonatal seizures. Diagnosis Seizures are usually diagnosed with electroencephalography (EEG). In extremely preterm infants (born before 28 completed weeks’ gestation) little is known about the morphology of seizures on EEG. We discovered that classic EEG seizures are rare in the first 72 h after birth in extremely preterm infants (1.3%) but they have the same morphology as in older infants. A specific EEG pattern, called periodic epileptiform discharges (PEDs), is much more common (44%), but proved to be a benign phenomenon in extremely preterm infants, while in older infants it has been associated with brain injury and poor outcome. We also discovered that it is important to perform a brain MRI in all infants presenting with neonatal seizures to find the origin of seizures. A diagnosis or important additional brain lesions will be missed in more than 50% if an MRI is not performed. Treatment Prompt treatment of neonatal seizures is important to reduce the total duration of seizures. This may ultimately reduce exacerbation of brain damage by seizure activity. However, no optimal treatment protocol exists. We discovered that lidocaine is safe to use in full-term and preterm infants as an antiepileptic drug; it leads to cardiac side effects in only 0.4% when modern reduced dose regimens are used. It can stop seizures in up to 70% of infants, but the efficacy increases significantly when given in combination with midazolam, another antiepileptic drug. Prognosis An MRI-scan is also important to predict neurodevelopmental outcome in infants with neonatal seizures, because the location and extent of brain injury can be determined. In infants with hypoxic-ischaemic encephalopathy (HIE), the most common cause of seizures in full-term infants, we saw that poor outcome is mainly determined by injury to the deep grey matter of the brain. The level of brain activity on EEG, in combination with MRI, can aid in the prediction of neurodevelopmental outcome in these infants as well. However, in infants with HIE treated with hypothermia, the level of brain activity on EEG is only a reliable outcome predictor after 36 h of age. We did not find a high seizure burden (total duration of seizures) to be invariably associated with a poor outcome in infants with HIE.