Neonatal Seizures: new developments in monitoring and therapy

Abstract

Seizures are common in the neonatal period and represent a most distinctive signal of neurological disease. Seizures in newborns are associated with an increased risk of neurodevelopmental impairment, including cerebral palsy, mental retardation and epilepsy and mortality. Controversy still exists concerning diagnosis and treatment of neonatal seizures. Furthermore the question, regarding the potential detrimental effect of neonatal seizures on the immature brain remains unanswered, although data from animal and human studies show increasing evidence for a detrimental effect of seizures on the brain. During recent years diagnosis of neonatal seizures has improved with techniques like prolonged video EEG and with the introduction of amplitude integraded EEG (aEEG). The aEEG records a single-channel aEEG from two parietal needle electrodes (corresponding to P3 and P4 according to the international 10-20 system of electrode placement). The EEG signal is filtered, rectified, and smoothed before it is written out at slow speed (6 cm/hour) at the cot side. The four main features that are provided with aEEG are 1) the background pattern on admission and the rate of recovery seen during the first 24 to 48 hours after birth; 2) the presence or absence and time of onset of sleep wake cycling (SWC); 3) the presence of electrographic seizure patterns and 4) the effect of treatment with antiepileptic drugs. It has been demonstrated that the technique is reliable in recognizing background abnormalities, which have been shown to be strongly predictive of neurodevelopmental outcome. With this new techniques it is known that most neonatal seizures are subclinical, which means that electrographic seizures are not accompanied by clinical signs. With the studies described in this thesis we have contributed to the improvement of monitoring and treatment of clinical practice in infants with neonatal seizures. With respect to monitoring we have shown that the incidence of status epilepticus in neonates with seizures is around 18%. BGP is the main predictor of outcome. Only in infants with hypoxic ischaemic encephalopathy both duration of the SE and deterioration of the BGP following the status epilepticus is associated with an abnormal outcome. Furthermore we found that 2-channel aEEG recording provides additional value in seizure detection in infants with unilateral brain injury.With respect to treatment of neonatal seizures we developed a new safe dosing regimen for lidocaine, with good anti-epileptic effect. Furthermore we were able to shown that immediate treatment of clinical and subclinical seizure patterns detected on aEEG results in a reduction of total duration of seizure patterns and there is a significant association between duration of seizure patterns detected on aEEG and severity of brain injury as seen on MRI. The observation that treatment of clinical and subclinical seizures results in a reduction of total seizure pattern duration, supports the evidence that subclinical seizures should be treated. Further research on this topic is needed to optimize the precision of detection of neonatal seizures and to find new drugs for treatment of seizures.