Kim Annink

51 Cerebellar injury in HIE: MRI versus histopathology INTRODUCTION Despite therapeutic hypothermia, hypoxic-ischemic encephalopathy (HIE) following perinatal asphyxia is still an important cause of mortality and morbidity in term- born neonates (1). HIE can lead to different long-term neurodevelopmental deficits, such as motor impairment, cognitive and behavioral problems and epilepsy (1–3). Future neurodevelopmental outcome can be predicted based on early injury patterns seen on neuroimaging (4,5). Magnetic Resonance Imaging (MRI) is a very accurate and reliable neuroimaging technique to visualize supratentorial patterns of hypoxic-ischemic brain injury (5,6). Especially, diffusion weighted imaging (DWI) is a frequently used MRI sequence in HIE, that has shown to be accurate in detecting brain injury in infants with HIE (7). DWI can visualize the diffusion restriction of water molecules caused by acute cytotoxic edema (8). Furthermore, diffusion restriction can be quantified by lower Apparent Diffusion Coefficient (ADC) measurements (6). Research until now has shown that supratentorial DWI is very well correlated with histopathology (9). Furthermore ADC values of the basal ganglia and thalami are predictive for neurodevelopmental outcome in HIE (10,11). During the past decades, the main focus of neuroimaging in HIE has been on the supratentorial brain structures. However, recent literature has emphasized the vulnerability of the developing cerebellum for hypoxic-ischemic events (12,13). The cellular and network organization in the cerebellum change rapidly in the third trimester and first months after birth (14–16). The cerebellar cortex receives afferent inputs from the cerebrum, spinal cord, and vestibular nuclei via mossy and climbing fibers (17,18). The Purkinje Cells (PC) are the only output neurons of the cerebellar cortex (19) and are connected to the cerebellar nuclei (the largest is the dentate nucleus (DN)), which predominantly via thalamus are connected back to the cerebral cortex (18). Historically, the cerebellum is especially known for its role in motor control because cerebellar damage leads to impairments in motor control and posture. However, it has become apparent that the cerebellum also plays an important role in various cognitive functions (20,21). Multiple studies have shown that there is an association between peripartum cerebellar injury and autism spectrum disorders in preterm born infants (22). In a meta-analysis including preterm born infants, hemorrhages in the vermis led to cognitive problems in 80% of the infants (23). Nevertheless, studies about cerebellar injury on MRI in term neonates with HIE are scarce. Clinical MR- sequences as DWI and T1-weighted imaging found little cerebellar injury in neonates 3