Exclusion criteria
- Ineligible for subthalamic stimulation
- Over 75 years old
- PD less than 5 years of progression
- Atypical PD or parkinson psychosis
- Severe cognitive impairment or dementia (MOCA <24)
- Severe brain atrophy or MRI abnormality
- Other pathology threatening short term vital prognosis (cancer)
Inclusion criteria
- Patients able to provide free and informed consent
- With imaging
- With social security cover
UPDRS
Unified Parkinson Disease Rating Scale
- one of the assessment tool used to evaluate the severity and the progression of PD
- it assesses motor and non motor symptômes across 4 parts:
1. Non motor experiences of daily living : issue with concentration
2. Motor experiences of daily living : buttoning a shirt
3. Motor examination : tremors at rest
4. Motor complications : dyskinesia
- Scores range from 0 (normal) to a higher number indicating more severe impairment
- It helps track symptoms over time and guide treatment adjustements
L-Dopa
- It consists of a precursor of dopamine associated with a dopa decarboxylase inhibitor such as carbidopa
because dopamine can not across the blood brain barrier (BBB) but L-Dopa can be taken up by cells in the brain and then converted to dopamine by AAAD
AAAD: Aromatic Amino Acid Decarboxylase is also called Dopa Decarboxylase and catalyzes the conversion of L-Dopa to dopamine
This association with carbidopa reduces the peripheral transformation of L-Dopa into dopamine and allows a greater amount of L-Dopa to be available for the brain
Attention ! L-Dopa is also converted to dopamine in the peripheral nervous system
→ side effects
UPDRS III
- Motor examination section of the UPDRS
- It evaluates motor symptoms such as tremor, rigidity, bradykinesia, postural instability and gait
- Scores range from 0 (normal) to 132 (maximum severity) with higher score indicating more severe motor impairment
- It is widely used to monitor disease progression and assessment treatment efficacy in PD
The score is measured in the states «on» and «off» to assess the patient’s response to dopaminergic treatments.
Improving the UPDRS III score between these 2 states can provide valuable information on patient dopa-sensitivity, helping to adjust doses and anticipate treatment effects.
«On» state: period during which treatment is effective and relieves motor symptoms
«Off» state: period when the effect of treatment fades and motor symptoms reappear or intensify
MoCA
Montreal Cognitive Assessment Score
- Brief screening tool designed to evaluate cognitive abilities
- It assesses domains such as memory, attention, language and executive fonction.
- Total score ranges from 0 to 30, with a score of 26 or above generally considered normal.
PREDISTIM
Cohort widely used in our lab
Directed by David Devos
With data already extracted
With subthalamic stimulation
An average progression of 9 years
PPMI
- international cohort
- heterogeneity of profiles (early, middle and late stage of the disease)
Inclusion criteria : - patients with a certain PD diagnosis
- with a DopaS between 0 and 100%
- who passed UPDRS III and MoCA
- with imaging data
AIM of the projet
For the same patient: heterogeneous response on different symptoms
No waiting for typical profile: unbiased approach
Study the heterogeneity of profiles to highlight signatures to stratify patient and thus predict the evolution of their disease
Non motor symptoms ?
Study wether there is a correlation between dopa-sensitivity and non motor symptoms
In our study mainly cognition
Because it’s know that even if Levodopa is basically a motor/targeted treatment, it also has effects on non motor symptoms of patient.
TEP DOPA ?
Used in Parkinson diagnosis to visualise structure where there is a decrease in dopamine production
BUT
In our study, the patients diagnosis is proven and we want to see the entire brain
Other study of the lab
Can dopamine responsiveness be predicted in PD without an acute administration test ?
• Test with acute Levodopa administration after drug withdrawal
Aim: develop a predictive model combining clinical scores and imaging
Results: Modeling is potentially a simple way to estimate dopa-sensitivity but requires confirmation in a larger population including patient with dopa-sensitivity under 30%
