Objective: The aim of this study was to explore the angiogenetic hypothesis for Levodopa-induced-dyskinesia (LID) using advanced MRI methods in patients with Parkinson’s disease (PD).

Background: The neural basis for the development of LID in PD involves abnormal neuroplastic changes originating in the striatum. Angiogenesis and increased permeability of the blood-brain barrier (BBB) have been reported to occur in animal models of PD and LID. A novel MRI methodology based on delayed contrast extravasation was developed for depicting BBB function through delayed-enhancement-subtraction-maps, with high resolution and sensitivity to changes.

Methods: Levodopa-treated PD patients that developed LID (LID+) were matched (1:1) according to age, gender and levodopa treatment duration to patients that had not developed LID (LID-). Motor symptoms and LID were rated and high resolution 3D FSPGR MRI images were obtained and analyzed using segmentation software that calculates volumes of pre-determined brain structures; these were integrated with the BBB maps, and the mean intensity was calculated for each structure, reflecting its BBB function. Comparison tests were made between the LID+ and LID- pairs and within patients between predominantly affected and less affected hemisphere.

Results: Preliminary results obtained from 9 matched pairs are presented. We could not demonstrate a statistically significant difference in BBB permeability or volumetric measurements of several brain structures between LID+ and LID- matched pairs; neither were there differences between the predominantly affected to the less affected hemisphere within patients.

Conclusions: The preliminary results of our in-vivo study, assessing BBB permeability along with volumetric changes in PD patients treated with L-dopa, failed to show an association between these measures and LID, and thus did not support the angiogenetic theory. The limitations of the study include the small number of patients recruited and initial data analyzed, but it is also possible that the MRI method is not sensitive enough to detect subtle BBB permeability changes. Further studies exploring the angiogenetic theory in PD-LID should be pursued using validated methods for detecting subtle BBB permeability changes and including larger number of patients.

Annual Meeting of the Israel Neurological Association, 2015.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/is-levodopa-induced-dyskinesia-in-parkinsons-disease-associated-with-increased-blood-brain-barrier-permeability-and-volumetric-changes/