DBS and Respiration

Study Overview
=================
Brief Summary
-----------------
Patients referred to neurosurgery routinely and safely undergo deep brain stimulation (DBS) for treatment of neurological conditions, most commonly Parkinson's disease. The investigators have observed that respiratory problems (breathlessness) sometimes occur subsequent to DBS of the subthalamic nucleus (STN). This study aims to determine whether this is indeed a consequence of STN stimulation. Secondary objectives include identification of the respiratory physiological mediators of any interoceptive neuromodulation observed, changes in daily physical activity and MRI structural connectivity analysis.

Detailed Description
-----------------
A continuous cohort of Parkinson disease patients planned to undergo STN-DBS will be approached to participate in this study (i.e. every patient will be offered participation in the study). Over the same time period other DBS patients (GPi and VIM) will be approached before their implantation procedure to participate as controls/comparators. Participants will all be offered the full study, but will also be free to participate in a smaller number of activities if so chosen. Patients will be assessed both pre-operatively and post-operatively where they will complete a compound respiratory questionnaire and tests of respiratory interoception and function. Post-operatively, these tests will be carried out with stimulation ON and OFF, the order of which will be randomised between patients. Data on daily activity will be collected during pre- and post-operative windows, using a wearable pedometer/heart-rate monitor. Positive findings of respiratory neuromodulation will be correlated between patients with structural connectivity (e.g. STN-insula.) from pre-operative MRI scans.

Official Title
-----------------
Deep Brain Stimulation in Parkinson's Disease: Respiratory Testing

Conditions
-----------------
Parkinson Disease

Intervention / Treatment
-----------------
* Device: DBS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant is willing and able to give informed consent for participation in the study. Male or female, aged 18 years or above. Planned for required DBS surgery Fluent in the English language For experimental group: diagnosed with Parkinson's disease Exclusion Criteria: Female who is pregnant Subject is currently participating in a clinical investigation that includes an active treatment arm which may affect the respiratory system. Acute respiratory problem at time of experimental session: e.g. rhinosinusitis, pharyngitis, asthma exacerbation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| STN DBS<br>Patients planned to undergo deep brain stimulation of the subthalamic nucleus | Device: DBS<br>* Patients are tested pre-operatively and the post-operatively with their implanted neurostimulators ON and OFF. DBS implantation itself is part of routine care, and not part of the study.<br>|
| GPi DBS<br>Patients planned to undergo deep brain stimulation of the globus pallidus interna | Device: DBS<br>* Patients are tested pre-operatively and the post-operatively with their implanted neurostimulators ON and OFF. DBS implantation itself is part of routine care, and not part of the study.<br>|
| VIM DBS<br>Patients planned to undergo deep brain stimulation of the ventral intermediate nucleus of thalamus. | Device: DBS<br>* Patients are tested pre-operatively and the post-operatively with their implanted neurostimulators ON and OFF. DBS implantation itself is part of routine care, and not part of the study.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in breathlessness | Dyspnoea questionnaire (D12, MRC) | Pre-operatively and post-operatively (6-months) | 
| Change in breathlessness | Breathlessness ratings (modified-Borg Scale) from experimentally induced breathlessness. 0 = none, 10 maximum. Reported every 15 seconds. | ON and OFF stimulation between 1 and 6 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pulmonary function | Spirometry | ON and OFF stimulation between 1 and 6 months after surgery | 
| Change in airways resistance | Oscillometry | ON and OFF stimulation between 1 and 6 months after surgery | 
| Change in respiratory muscle strength | Maximum inspiratory/expiratory pressures | ON and OFF stimulation between 1 and 6 months after surgery | 
| Change in surface electromyography of respiratory muscles | Signal analysis for evidence of tremor | ON and OFF stimulation between 1 and 6 months after surgery | 
| Change in hypercapnic ventilatory response | Changes in ventilation from incrementally increased inhaled CO2 | ON and OFF stimulation between 1 and 6 months after surgery | 
| Change in breath-hold | Dyspnoea threshold and breakpoint | ON and OFF stimulation between 1 and 6 months after surgery | 
| Change in daily activity | Pedometry | Pre-operatively (10 days) and post-operatively (10 days, within 6 months of surgery once recovered from surgery and programmed) | 
| Change in daily activity | Heart rate | Pre-operatively (10 days) and post-operatively (10 days within 6 months of surgery once recovered from surgery and programmed) | 
| MRI structural connectivity | DTI correlation with respiratory outcomes | Pre-operative scan with post-operative analysis through study completion at an average of 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Parkinson disease, movement disorder, dyspnoea, dyspnea, breathlessness, respiratory