Imaging Blood Brain Imaging Dysfunction in Parkinson's Disease
Imaging Blood Brain Imaging Dysfunction in Parkinson's Disease
The purpose of this study is to evaluate the blood brain barrier in the striatum of patients
 that have other types of movement disorders compared to patients with Parkinson's Disease
 that are receiving similar treatment, to determine if a there is a disruption of the blood
 brain barrier in patients with Parkinson's Disease.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder of aging. Its
 cause is unknown. Current evidence supports a stress-diathesis model of pathogenesis whereby
 some yet-to-be identified environmental trigger conspires with a permissive genetic
 background to initiate the disease process. Based on neuropathological observations in other
 neurodegenerative diseases, such as chronic traumatic encephalopathy where pathological
 protein aggregates form in close association with damaged blood vessels, investigators have
 hypothesized that the environmental trigger resides in the bloodstream. As a corollary of
 this hypothesis, investigators propose that the PD pathological process begins in the brain
 of affected individuals only after disruption of the blood brain barrier (BBB), thereby
 allowing access of the inciting agent to nigrostriatal axon terminals in the neostriatum.
 This forms the foundation for the investigators' hypothesis that the BBB in the neostriatum
 of PD patients is disrupted. Indeed, in a post-mortem study, investigators demonstrated
 histopathological evidence for significant striatal BBB disruption in sections of striatum
 from PD subjects relative to age-matched controls. Critics of this study indicate that
 post-mortem effects may result in artefactual disruption of the BBB, calling into question
 the validity and relevance of this potentially important finding to PD pathogenesis and
 progression. Therefore, investigators are performing this imaging study of live PD patients
 as a follow-up of their convincing post-mortem study to definitively establish whether BBB
 dysfunction is a feature of PD.

 The neostriatal BBB is dysfunctional in PD patients relative to controls and this can be
 demonstrated by significantly increased parenchymal enhancement on magnetic resonance imaging
 (MRI).

 The results of these studies could have important implications for the understanding of PD
 pathogenesis. There is emerging evidence that the key pathogenetic event in PD pathogenesis,
 aggregation of alpha-synuclein, begins within the axon terminals of neurons. The neurons most
 severely affected in PD reside in the substantia nigra and project to the neostriatum.
 Demonstrating disruption of the BBB in the PD striatum would render nigrostriatal axon
 terminals susceptible to a blood-borne disease trigger and allow researchers to generate
 hypotheses regarding the identity of this trigger. Immune/inflammatory candidates are
 particularly attractive in this regard. The results this study may also have therapeutic
 implications. For example, if alpha-synuclein disaggregating agents achieve therapeutic
 utility in the coming years, our studies may indicate that such agents may be capable of
 accessing nigrostriatal axon terminals without requiring pharmaceutical or mechanical
 disruption of the BBB.
Inclusion Criteria:

 -  Disease burden is dominated by motor symptoms such as rigidity, bradykinesia,
 akinesia, and tremor;

 -  Medications have been optimized by a movement disorder neurologist;

 -  Adequate social support to assist with preoperative recovery and problems during
 subsequent programming;

 -  No major mood disorder and any mood disorders are medically optimized;

 -  No major cognitive impairment;

 -  No underlying medical conditions that would preclude surgery;

 -  Adequate response to levodopa, as assessed by UPDRS-3 on and off levodopa. All
 participants has at least a 30% improvement;

 -  eGRF>30

 Exclusion Criteria:

 -  Disease burden is not dominated by motor symptoms such as rigidity, bradykinesia,
 akinesia, and tremor;

 -  Medications have not bee optimized by a movement disorder neurologist;

 -  There is not adequate social support to assist with pre-operative recovery or problems
 during subsequent programming;

 -  Presence of major mood disorders or any mood disorders not medically optimized;

 -  Presence of major cognitive impairment;

 -  Presence of underlying medical conditions that would preclude surgery;

 -  Inadequate response to levodopa;

 -  eGFR<30