Lateralisierter Hypermetabolismus des anterioren Cerebellums beim Idiopathischen Parkinson-Syndrom

Patienten des Idiopathischen-Parkinson-Syndroms (IPS) zeigen einen relativen Hypermetabolismus des Cerebellums, von dem man vermutet, dass er einen kompensatorischen Mechanismus darstellt, um die striatale Dysfunktion auszugleichen. Eine Studie, die dieses Phänomen mithilfe von Positronenemissionsto...

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Bibliographic Details
Main Author: Präger, Lea-Isabell
Contributors: Eggers, Carsten (Prof. Dr. med.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2021
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In Parkinson’s disease (PD), relative hypermetabolism of the cerebellum is hypothesized to represent a compensatory mechanism to balance striatal dysfunction. A recent study used positron emission tomography (PET) imaging in a hemiparkinsonian rat model and found evidence supporting this theory: lesion severity was associated with contralesional cerebellar hypermetabolism and motor symptoms (Kordys et al., Research, 2017). While relatively increased cerebellar metabolism has previously been demonstrated in PD patients, existing studies did not account for laterality of this observation. To test whether striatal dopamine depletion and cerebellar glucose metabolism in PD patients are lateralized in correlation with each other, and if the degree of laterality in limb motor scores is reflected in the cerebellum. PET imaging with [18F]Fluorodeoxyglucose ([18F]FDG) and [18F]-Fluoro-L-Dopa ([18F]FDOPA) was performed in 42 mid-stage PD patients. Analysis: 1) Dopamine influx constants (Ki) were calculated, and the degree of laterality in the posterior putamen estimated by dividing Ki-left/Ki-right: values <1 represented more advanced dopamine depletion on the left, values >1 indicated that the right putamen was more affected. Corresponding values were created by dividing left/right measurements of 2) limb motor scores from the Unified Parkinson’s Disease Rating Scale, part III (UPDRS-III) and 3) [18F]FDG uptake in the anterior cerebellum (lobules IV-V, anatomical VOIs corresponding to findings in rats). Based on the rat model, a positive correlation between laterality values of all three measures was hypothesized. Laterality values for putaminal [18F]FDOPA correlated positively with those for limb UPDRS-III scores (r = .496, p = .001) and cerebellar [18F]FDG (r = .407, p = .007). An association was also found between [18F]FDG and UPDRS-III lateralization (r = .380, p = .013). Clinically left-dominant parkinsonism is associated with right-hemispheric dopamine depletion, and vice versa. The presented approach to assess laterality enabled detection of this fact in a group with mixed left- and right-dominant parkinsonism, even when patients with symmetrical symptoms were included. More importantly, applying the same concept to cerebellar [18F]FDG uptake allowed translation of findings from a hemiparkinsonian rat model to human subjects. To our knowledge, this is the first time that the aspect of laterality has been evaluated in PD-associated changes in cerebellar metabolism. Future studies should investigate whether this might represent compensation for impaired dopamine-mediated motor functions.