Neonatal stroke: Neonatal neuroimaging & brain plasticity

Abstract

Despite major improvements in perinatal care, perinatal stroke remains a severe problem of the newborn and is commonly encountered in the care of these infants in the neonatal intensive care setting. The reported incidence of perinatal arterial ischemic stroke (PAIS) varies from 1:1600-1:5000, and most likely depends on how often neuroimaging studies are performed. Periventricular haemorrhagic infarction (PVHI) has a lower incidence, but still occurs in 1-10% of the very preterm born infants, depending on the gestational age and birth weight. In the absence of evidence-based treatment, therapy during the neonatal period mainly involves supportive measures, including the treatment of seizures and in case of PVHI, early intervention of post-haemorrhagic ventricular dilatation. During this time, MRI plays an important role, as it allows visualisation of the size and site of the injury and may assist in predicting outcome. In this thesis MRI data of infants with PAIS and PVHI are studied and, where possible, related to neurodevelopmental outcome. The first part of the thesis focuses on neonatal MRI in infants with PAIS. We demonstrate which physiological changes take place after an ischemic stroke and speculate how these findings may contribute to novel therapies in PAIS. Furthermore we describe how diffusion tensor imaging (DTI), an MRI technique that allows visualisation of white matter tracts, including the corticospinal tracts, can contribute in predicting motor outcome following PAIS. We found that DTI at 3 months is a better predictor than the currently used conventional and diffusion weighted MR imaging performed during the first week. The long-term follow-up of infants with PVHI or PAIS is described in the second part of the thesis. First, we studied the cognitive outcome of these infants and related these findings to characteristics of their neonatal MRI. We were able to compare their early neurodevelopmental outcome with their cognitive outcome at school age. In infants with PVHI, the early outcome (18-24 months) was already below average (associated with early development of PHVD), with similar findings at school age. In the PAIS group, outcome at the early test was normal, but below average at school age. A decline in outcome was associated with involvement of the basal ganglia and thalami and with development of epilepsy. In the same group of patients, we studied plasticity of the corticospinal trajectory. It is known that following perinatal injury, ipsilateral corticospinal tracts from the healthy hemisphere may be retained at a cost of contralateral tracts arising from the affected hemisphere. This reorganisation may result in complete motor control by the unaffected hemisphere, which is associated with a poor hand function of the affected hand. We demonstrate how neonatal MRI can be used to predict the type of reorganisation following perinatal brain injury. As animal models have shown that early intervention may prevent contralesional reorganisation, early identification of infants at risk of corticospinal reorganisation may be a first important step for initiating novel therapies aiming at restoring the balance between ipsi- and contralateral corticospinal tracts.