Kim Annink

63 Cerebellar injury in HIE: MRI versus histopathology Infants with HIE showed staining with monoclonal antibodies for CD68 and HLA-DR in the cerebellar hemispheres, DN and vermis implying microglia and macrophage activation. However, PC injury did not differ between the categories for HLA-DR staining and CD68 staining. This implies that the inflammation is not (solely) caused by PC injury. The PCs are the main output cells of the cerebellum and therefore very important. However, granular cell injury is also described after hypoxic-ischemia and this process might lead to additional inflammation (12,13). CD68 stained macrophages and microglia were in an earlier study especially found in the granular layer and white matter and less frequently in the PC layer, which supports this theory (32). Another explanation might be that CD68 and HLA-DR staining are time dependent (9,32). We did not find an effect of postnatal age at death in our study, except for CD68 staining in the DN but this effect was the opposite of what we expected based on earlier studies (32). The effect of timing between the ischemic insult and death on these CD68 and HLA-DR results cannot be ruled out because of the small sample size. The same applied for histopathological cytotoxic edema. Additional staining methods, such as calbindin, are valuable to further investigate cerebellar injury in the future (12). ADC values and histopathological injury of the cerebellum were not correlated, except for ADC values in the vermis and number and percentage of normal PCs. This means that even if the DWI and ADC values are in the reference range, this does not rule out cerebellar injury. An underestimation of cerebellar injury with MRI in neonates with HIE is in agreement with earlier literature (9,25,33,34). Kwan et al. studied 172 infants with HIE that were treated with therapeutic hypothermia and found cerebellar injury in only 4% of this group using conventional imaging (25). However, histopathological cerebellar injury was found in 72% of the 14 infants that underwent autopsy. This study does support that conventional imaging underestimates cerebellar injury even more than DWI. Alderliesten et al. reported cerebellar abnormalities in 61% of the patients with HIE based on DWI and in 83% of the patients based on histopathological analysis (9). In the same study there was a very good correlation between DWI and histopathology for the supratentorial brain structures (9). The reason for this underestimation in the cerebellum is not entirely clear. We found that ADC values did not significantly differ between infants with no, mild, moderate and severe cytotoxic edema based on histopathology. The two patients with severe histopathological cytotoxic edema in the vermis and DN did have very low ADC values. So, cytotoxic edema is only detectable on DWI if the edema is severe and diffuse. Furthermore, histopathological cytotoxic 3