Delayed Cerebellar Injury is Affected by Multiple Organ Dysfunction Syndrome Caused by Heat Stroke, a Retrospective Cohort Study

Objective Nervous dysfunction is the main manifestation of heat stroke (HS). Here we investigated the clinical signs for HS-induced nerve injuries. Methods Retrospective data were collected on 119 patients who got HS from 2016 to 2020. Patients were divided into 4 groups, including the cerebellar injury group, the other nerve injuries group, non-cerebellar injury group and non-nerve injury group. The age, body temperature (Tc), degree of consciousness disorder, liver and kidney function, blood coagulation function, blood routine and cardiac indicators within 24 h after HS were summarized. Moreover, we performed regression analyses to identify risk factors for nervous dysfunction. The Activity of Daily Living (ADL) score was assessed 3 months after HS to evaluate the prognosis of HS. Results Compared with other groups, the cerebellar injury group had shorter Tc recovering time, lower GSC scales, longer coma time and more hypotension, gastrointestinal bleeding, multiple organ dysfunction syndrome (MODS) and metabolic acidosis significantly. The cerebellar injury group had higher myocardial enzymogram and indexes of liver and kidney dysfunction, immune and coagulation dysfunction significantly. Risk factors associated with HS-induced cerebellar injury are Tc, recovery time of Tc, NSE, GCS scale, lymphocyte count, HLA-DR/CD14, coagulation dysfunction, cardiac injury, metabolic acidosis and MODS. The ADL scale of the cerebellar injury group and the other nerve injury group were significantly lower than other groups. Conclusions Patients with severe coma and MODS are more prone to cerebellar injury after HS and the HS-induced nerve injury leaded to a worse prognosis.

The Cerebellum Plays a Role in Cognitive, but Not Affective, Theory of Mind: A Voxel-Based Lesion Mapping Study

Introduction: Theory of Mind (ToM) is a social-cognitive skill that allows the understanding of the intentions, beliefs, and desires of others. There is a distinction between affective and cognitive ToM, with evidence showing that these processes rely on partially distinct neural networks. The role of the cerebellum in social cognition has only been rarely explored. In this study, we tested whether the cerebellum is necessary for cognitive and affective ToM performance. Material and methods: We investigated adults with traumatic brain injury (n=193) and healthy controls (n=52) using voxel-based lesion-symptom mapping (VLSM) and by measuring the impact on functional connectivity. Results: First, we observed that damage to the cerebellum affected Cognitive but not Affective ToM processing. Further, we found a lateralization effect for the role of the cerebellum in cognitive ToM with participants with left cerebellar injury performing worse than those with right cerebellar injury. Both VLSM and standard statistical analysis provided evidence that left cerebellar Crus I and lobule VI contributed to ToM processing. Lastly, we found that disconnection of the left thalamic projection and the left fronto-striatal fasciculus was associated with poor cognitive ToM performance. Conclusions: Our study is the first to reveal direct causal neuropsychological evidence for a role of the cerebellum in cognitive, but not in affective, ToM, processing. It reinforces the idea that social cognition relies on a complex network functionally connected through white matter pathways that include the cerebellum. It supports evidence that the neural networks underpinning cognitive and affective ToM can be differentiated.

Morphological changes in the pons and cerebellum during the first two weeks in term infants with pontine and cerebellar injury and profound neonatal asphyxia

Background The morphological changes in the pons and cerebellum of neonates experiencing profound asphyxia in the early period of life remain to be clarified. Purpose To assess the changes in the size of the pons and cerebellum during the first two weeks of life in term neonates with pontine and cerebellar injury caused by hypoxic-ischemic encephalopathy in comparison with a control group. Material and Methods Two groups were investigated: a group with pontine/cerebellar injury (PCI) (n = 10) demonstrated by magnetic resonance imaging (MRI) diffusion-weighted imaging; and a control group without PCI – focal-multifocal white matter injury and a normal pattern (n = 24). The anteroposterior diameter (APD) and height of the pons and cerebellar vermis, and the transverse width of the cerebellum were measured twice in the first and second weeks of life. Differences between the groups were analyzed statistically using paired and unpaired Student’s t-test at a significance level of P < 0.05. Results In the PCI group, the pontine APD and cerebellar vermian height were significantly decreased in the second week. An increase of pons and cerebellar size was evident during the first two weeks of life in the control groups. Conclusion Infants with PCI and profound asphyxia show rapid decreases in pontine APD and cerebellar vermian height within the first two weeks of life.

A unique cerebellar pattern of microglia activation in a mouse model of encephalopathy of prematurity

Preterm infants often show pathologies of the cerebellum, which are associated with impaired motor performance, lower IQ and poor language skills at school ages. Because 1 in 10 babies is born preterm cerebellar injury is a significant clinical problem. The causes of cerebellar damage are yet to be fully explained. Herein, we tested the hypothesis that perinatal inflammatory stimuli may play a key role in cerebellar injury of preterm infants. We undertook our studies in an established mouse model of inflammation-induced encephalopathy of prematurity driven by systemic administration of the prototypic pro-inflammatory cytokine interleukin-1β (IL-1β). Inflammation is induced between postnatal day (P) 1 to day 5, timing equivalent to the last trimester for brain development in humans the period of vulnerability to preterm birth related brain injury. We investigated acute and long-term consequences for the cerebellum on brain volume expansion, oligodendroglial maturation, myelin levels and the microglial transcriptome. Perinatal inflammation induced global mouse brain volume reductions, including specific grey and white matter volume reductions in cerebellar lobules I and II (5% FDR) in IL-1β versus control treated mice from P15 onwards. Oligodendroglia damage preceded the MRI-detectable volume changes, as evidenced by a reduced proliferation of OLIG2+ cells at P10 and reduced levels of the myelin proteins MOG, MBP and MAG at P10 and P15. Increased density of Iba1+ cerebellar microglia was observed at P5 and P45, with evidence for increased microglial proliferation at P5 and P10. Comparison of the transcriptome of microglia isolated from P5 cerebelli and cerebrum revealed significant enrichment of pro-inflammatory markers in microglia from both regions, but in the cerebellum microglia displayed a unique type I interferon signalling dysregulation. Collectively, these data suggest that in our model that systemic inflammation causes chronic activation of microglia and maldevelopment of cerebellum that includes myelin deficits which is driven in the cerebellum by type I interferon signalling. Future protective strategies for preterm infants should consider sustained type I interferon signalling driven cerebellar inflammation as an important target.