Blood-Brain Barrier Opening with Focused Ultrasound in Parkinson’s Disease Dementia: A Safety and Feasibility Study (1131)

Objective: To evaluate safety and feasibility of MR guided focused ultrasound (MRgFUS)-blood brain barrier (BBB) opening in PDD and putative changes in cognition and PET. Background: The prevalence of dementia in Parkinson’s disease (PD), reaches about 80% 20 years after diagnosis. In PD dementia (PDD), there is high combination of mixed Alzheimer’s and PD pathology and current treatments provided very modest benefit. BBB penetration limitations is a major restriction for many putative therapeutic agents. Low frequency/energy MRgFUS in combination with parenteral microbubbles administration leads to focal temporarily BBB opening, becoming a putative therapeutic tool for drug delivery. Design/Methods: This is an open, proof-of-concept, safety and feasibility pilot study of focal BBB opening in PDD. Five patients underwent MRgFUS procedure to open BBB at the right parietooccipitotemporal cortex twice, separated by at least two weeks. Immediately and 1 and 7 days after the procedure, brain MR with gadolinium was taken to detect enhancement indicating BBB opening. Amyloid and fluordeoxyglucose PET were performed before treatment and 3 weeks after the second BBB opening session. Results: Five patients were included in the study. BBB was opened satisfactorily after the treatmentand was closed in all cases by day 7th. There were no major side effects and mild improvement in several cognitive domains was observed. Discrete round hypointensities on MRI SWAN sequences (sonicated region) were seen immediately after treatment. These disappeared progressively except for one patient who still showed some minor abnormalities after 2 months. There were no major changes from pre to post treatment in PET studies. Conclusions: This study suggests that MRgFUS-BBB opening in PDD is safe, reversible and can be done repeatedly. Therapeutic trials combining parenteral drug delivery and BBB opening can be envisaged to treat neurodegenerative dementia. Disclosure: Dr. Gasca-Salas has nothing to disclose. Dr. Fernandez-Rodriguez has nothing to disclose. Dr. Pineda-Pardo has nothing to disclose. Dr. Rodriguez-Rojas has nothing to disclose. Dr. Hernandez-Fernandez has nothing to disclose. Dr. Obeso has nothing to disclose. Dr. Mata Marin has nothing to disclose. Dr. Guida has nothing to disclose. Dr. del Alamo has nothing to disclose. Dr. Ordas Bandera has nothing to disclose. Dr. Rachmilevitch has nothing to disclose. Dr. Obeso has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Over the last few years has received honorarium for lecturing in meetings organized by BIAL, Zambon and Boston Scientific in Spain. Received honorarium as member of Insighect ’s advisory board and from Biogen(USA) as member of the Adverse Event Committee. Dr. Obeso has received personal compensation in an editorial capacity for Chief editor of the Movement Disorders Journal.