Objective: Quantitatively evaluate the gross morphology of individual cerebellar lobules, determine whether cerebellar anatomical changes occur early in the disease and whether changes were related to the primary motor phenotypes.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease. Characterised by motor dysfunction, the disease is notoriously heterogenous with no two cases identical. An increasing body of research suggests that abnormal changes in motoric brain regions other than the basal ganglia are responsible for differences in symptomatology. Functional and metabolic imaging studies have suggested hyperactivity of motoric regions of the cerebellum.

Method: Using data from the PPMI, we analysed MRI and clinical data from patients with PD at diagnosis and 2 years follow up and healthy controls at a single timepoint. The PD group was stratified into tremor-dominant (TD) and postural instability/gait difficulty (PIGD) groups to assess motor-symptom specific alterations. U-Net with locally constrained optimization (ACAPULCO) was used for cerebellum parcellation. Analysis focused on cerebellar motor regions. Group differences between patients and controls, and between PD motor phenotypes were assessed.

Results: We included 146 patients with TD-PD, 33 patients with PIGD-PD and 99 controls. At 2-year follow up 71 patients with TD-PD and 19 patients with PIGD-PD were included. Patients with PD had a significant increase in volume of the left (t=2.63, p=0.043) and right lobule V (t= 3.29, p= 0.017) relative to controls. Patients with TD-PD had a significant volume increase in the right lobule V (t= 3.64, p=0.001) and trending towards an increase in the left (t=2.18, p=0.094) and right lobule VI (t=2.34, p=0.089) compared to controls. Patients with TD-PD had a significant volume increase in left lobule VI (t=2.89, p=0.048) compared to PIGD-PD. No longitudinal effects (p=<0.05) were observed at 2-year follow up.

Conclusion: These findings indicate lobules V and VI – areas involved in motor control – are enlarged at the time of PD diagnosis, particularly in patients with TD-PD. This enlargement may be an anatomical manifestation of a cerebellar compensatory mechanism consistent with previous reports of cerebellar hyperactivation. Limited participant data or cerebellar degeneration appearing later in the disease course could explain the lack of observed volume change at follow-up.

References: Balsters, J.H., Laird, A.R., Fox, P.T., Eickhoff, S.B., 2014. Bridging the gap between functional and anatomical features of cortico-cerebellar circuits using meta-analytic connectivity modeling: Meta-Analytic Connectivity Modeling of Cortico-Cerebellar Circuits. Hum. Brain Mapp. 35, 3152–3169.

Han, S., Carass, A., He, Y., Prince, J.L., 2020. Automatic cerebellum anatomical parcellation using U-Net with locally constrained optimization. NeuroImage 218, 116819.

Meles, S.K., Renken, R.J., Janzen, A., Vadasz, D., Pagani, M., Arnaldi, D., Morbelli, S., Nobili, F., Mayer, G., Leenders, K.L., Oertel, W.H., the REMPET Study Group, 2018. The Metabolic Pattern of Idiopathic REM Sleep Behavior Disorder Reflects Early-Stage Parkinson Disease. J Nucl Med 59, 1437–1444.

Stebbins, G.T., Goetz, C.G., Burn, D.J., Jankovic, J., Khoo, T.K., Tilley, B.C., 2013. How to identify tremor dominant and postural instability/gait difficulty groups with the movement disorder society unified Parkinson’s disease rating scale: Comparison with the unified Parkinson’s disease rating scale: PIGD and The MDS-UPDRS. Mov Disord. 28, 668–670.

Teune, L.K., Renken, R.J., de Jong, B.M., Willemsen, A.T., van Osch, M.J., Roerdink, J.B.T.M., Dierckx, R.A., Leenders, K.L., 2014. Parkinson’s disease-related perfusion and glucose metabolic brain patterns identified with PCASL-MRI and FDG-PET imaging. NeuroImage: Clinical 5, 240–244.

Wu, T., Hallett, M., 2013. The cerebellum in Parkinson’s disease. Brain 136, 696–709.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/automated-parcellation-of-the-cerebellum-in-patients-with-newly-diagnosed-parkinsons-disease/