Predictors of Clinical Outcomes of Deep Brain Stimulation in Parkinson's Disease

A Prospective Observational Study for the Predictors of Clinical Outcomes of Deep Brain Stimulation in Parkinson's Disease

The goal of this observational study is to identify factors in blood that are associated with response to deep brain stimulation (DBS) surgery in patients with Parkinson's disease. The main questions it aims to answer are:

1. What factors in blood (proteins and RNA) are associated with good vs poor response to DBS?
2. Are these factors able to predict response to DBS?
3. How do these factors change before and after DBS?

Blood and leftover brain tissue (which spontaneously adhere to the surgical instruments) will be taken and routine clinical data (including scores from routine assessments) will be collected from consenting participants who undergo DBS.

This is a prospective observational study that investigates the clinical, proteomic, transcriptomic, and genomic profiles that are associated with DBS response with regards to motor symptoms, axial symptoms, non-motor symptoms, change in medications, activities of daily living (ADLs), and quality of life (QOL). The investigators will take blood samples from participants but will not take extra brain tissue; only leftover brain tissue (which is routinely discarded) that spontaneously adheres to surgical instruments will be collected. Study participation will not change the surgical procedure in any way. The investigators also aim to characterize the change in these multiomic profiles before versus after DBS treatment, to evaluate the ability of these multiomic profiles to predict and stratify response to DBS, and to identify modifiable factors to improve response to DBS. Additionally, the investigators will use these multiomic profiles, patient demographics, and clinical presentation to develop a DBS prediction model with advanced explainable AI (XAI) techniques.

Inclusion Criteria:

1. Diagnosis of "Clinically Established PD" as defined by the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (MDS-PD criteria)
2. Referred for DBS according to standard local clinical guidelines 2a. Significant motor complications despite optimized pharmacological treatment 2ai. UPDRS motor score >30/108 in the off-medication state 2aii. Hoehn and Yahr staging >2.5/5 in the off-medication state 2b. Dopamine responsive 2bi. >33% improvement in UPDRS motor score after levodopa administration 2c. Age ≤75 years 2d. No contraindication to surgery or other significant comorbidity with limited life expectancy 2e. No significant psychiatric problems or cognitive impairment 2f. No structural lesions or features suggestive of atypical parkinsonism or other mimickers of idiopathic PD on neuroimaging

Exclusion Criteria:

1. Unwilling to undergo blood sampling for study purposes
2. Evidence of Parkinsonism due to heavy metal exposure
3. History of neurodevelopmental disorder, neurodegenerative disease other than PD, CNS infection, neuroinflammatory disease (e.g. multiple sclerosis, CNS lupus), malignancy within the last 10 years, cerebrovascular accident, HIV infection, systemic autoimmune disease, alcohol dependence or other substance use
4. Unable to pass DBS pre-operative assessment or unwilling to undergo DBS