Associations between brain structure and motor-related manifestations of rapid-onset dystonia-parkinsonism (P3.015)

Objective: To evaluate the relationship between brain structure and motor-related manifestations of rapid-onset dystonia-parkinsonism (RDP). Background: RDP is caused by ATP1A3 gene mutations and characterized by bradykinesia, postural instability and dystonic movements. The aim of this study was to investigate the neuroanatomical substrates underlying RDP-associated dystonia and motor manifestations. We hypothesized that RDP may affect components of the cerebello-thalamo-cortical (CbTC) pathway thought to be affected in other movement disorders. Design/Methods: In this preliminary investigation, standard brain MRI voxel-based morphometry was used to measure gray matter (GM) volume in cortical motor (precentral gyrus, supplementary motor cortex), deep gray nuclei (caudate, putamen, pallidum, thalamus) and cerebellar structures among eight RDP patients (age: mean±SD=43±19 years; 50% female) in a larger ongoing study of brain structure and RDP-associated clinical manifestations. Dystonia/motor function was evaluated with Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Unified Parkinson’s Disease Rating Scale motor subscore (UPDRS), and International Cooperative Ataxia Rating Scale (ICARS). Results: Uncorrected Spearman correlations were greatest in portions of the cerebellum compared to cortical motor and deep gray structures. Specifically, the largest correlation coefficients were identified in lobule 9 of the cerebellum for BFMDRS ( r =0.46), lobule 6 of the cerebellum for UPDRS ( r =0.56), and crus 1 of the cerebellum for ICARS ( r =0.74). Conclusions: These data suggest that the cerebellum may play a larger role in the motor manifestations of RDP compared to other portions of the CbTC pathway. Replication of these results using a larger population of RDP patients will be necessary to confirm these preliminary findings and explore potential mechanisms underlying this devastating disease. Study Supported by: R01 NS058949 (Brashear) Disclosure: Dr. Whitlow has nothing to disclose. Dr. Cook has nothing to disclose. Dr. Snively has nothing to disclose. Dr. Sweadner has nothing to disclose. Dr. Haq has received research support from Boston Scientific, Merz USA, and Solvay S.A. Dr. Stacy has received personal compensation for activities with Allergan, Avid, Best Doctors, Biotie, Eli Lilly, Lundbeck, Merz, Neuronova, Novartis Pharma (Japan), Osmotica, Pfizer, Saraepta Therapeutics, SK Life Sciences, Sunovion Pharmaceuticals, Inc., and Benign Essential Blepharospasm. Dr. Stacy has received personal compensation in an editorial capacity for Journal of Clinical Investigation (JCI). Dr. Stacy has received royalty payments from Informa Press and Duke University. Dr. Stacy has received research support from IMPAX, Pfizer, and Pharma2B. Dr. Ozelius has nothing to disclose. Dr. Brashear has received personal compensation for activities with Ipsen, Worldmeds and Revance as a consultant.