Kim Annink

254 Chapter 12 GENERAL DISCUSSION Perinatal asphyxia resulting in hypoxic-ischemic encephalopathy (HIE) is a worldwide problem affecting the future perspectives of many infants and families (1,2). In 2010, an estimated 1.15 million infants developed HIE after perinatal asphyxia: of these infants 287,000 died, 233,000 developed severe neurodevelopmental deficits and 181,000 experienced mild deficits (2). Brain injury already starts during (fetal) hypoxia because of primary energy failure but a substantial second wave of injury occurs after birth when perfusion and oxygenation recover. The reperfusion injury is caused by the formation of free radicals ( e.g. formation of superoxide), neuro-inflammation and secondary energy failure (3,4). Brain injury is commonly assessed using magnetic resonance imaging (MRI), which is an important and indispensable technique to accurately predict neurodevelopmental outcome (5). The only current evidence-based neuroprotective therapy is therapeutic hypothermia. Therapeutic hypothermia has shown to reduce death, severe cognitive problems and cerebral palsy in infants with HIE (1,6–10). Despite therapeutic hypothermia, about 45% of the infants still experience long-term neurodevelopmental problems (1). Therefore, add-on neuroprotective therapies are essential. The aim of this thesis is to provide new insights in neuroimaging, neuroprotection and long-term neurodevelopmental outcome in infants with HIE. In chapter one, the pathophysiology, neuroprotective strategies, neuroimaging and follow-up of infants with HIE are elaborately discussed. Part I of this thesis provides additional information on neuroimaging in HIE and long-term follow-up. In Part II the most important literature on pharmacological neuroprotection with allopurinol in HIE is reviewed and the set-up of the ALBINO trial and the pharmacokinetics of allopurinol are discussed. In part III advanced MRI techniques in neonates are shown and discussed.