Parkinson Disease, Progressive Supranuclear Palsy
Conditions
Keywords
MRI, Parkinson disease, progressive supranuclear palsy, biomarkers
Brief summary
Parkinson's disease (PD) is the most common degenerative Parkinson's syndrome and is linked, among other things, to the excessive accumulation of an abnormally aggregating protein, alpha-synuclein. Progressive Supranuclear Palsy (PSP) is another Parkinson's syndrome, linked, among other things, to the abnormal accumulation of the protein Tau, and expressed clinically by falls, early cognitive impairment and oculomotor disorders, not present in PD. The onset of these disorders is so gradual that differential diagnosis between the two diseases is only possible at a late stage, on average 3 to 5 years after the onset of symptoms. To date, there is a lack of validated imaging biomarkers for diagnosing and monitoring PD and PSP. There is therefore an urgent need for the development of robust biomarkers capable of detecting neurodegeneration at an early stage, in order to aid differential diagnosis as soon as symptoms appear, and to potentially enable these patients to be included in specific therapeutic trials (as these diseases are pathophysiologically different) with potential neuroprotective effects. The development of cutting-edge technologies such as 7T MRI, combined with optimized image processing methods, now enable non-invasive in vivo exploration and analysis of these small structures in terms of ion homeostasis (sodium), microstructure (volumetry, amount of iron and neuromelanin) and connectivity.
Interventions
PROCEDURE7 Tesla MRI
Patients will have a 7T MRI and questionnaires
Sponsors
Assistance Publique Hopitaux De Marseille
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
For Parkinson Disease: Inclusion Criteria: 1. Patients aged between 40 and 80 2. Fulfilling the diagnostic criteria for MPI (Postuma et al., 2015) 3. First motor symptom (rigidity, akinesia, tremor) less than 36 months ago 4. Patient entitled to or affiliated with a social security scheme 5. Patients who understood, completed and signed the consent form for study participation.
Exclusion criteria
1. Patient with a neurological disease of the central nervous system other than those studied (including history of stroke, repeated head trauma, documented encephalitis). In case of doubt, this criterion will be left to the discretion of the principal investigator, who is a neurologist. 2. Contraindications to 7T MRI: presence of an ocular metallic foreign body (accidental shrapnel or other), pacemaker (cardiac simulator) or neurostimulator (pain treatment), cochlear implants or any implanted electronic medical equipment in general, metallic heart valve, vascular clips implanted on a cranial aneurysm. 3. Claustrophobia or any other condition preventing full MRI. 4. Montreal Cognitive Assessment (MOCA) test \< 25/30 5. Pregnant or breast-feeding woman or protected person (under guardianship, curatorship, deprived of liberty). For Progressive Supra-nuclear Palsy: Inclusion criteria: 1. Patients aged 40 to 80 2. Fulfilling the diagnostic criteria for soPSP (Höglinger et al., 2017) : 3. First motor symptom (rigidity, akinesia, tremor) or falls or cognitive impairment (frontal syndrome or language disorder or cortico-basal syndrome) occurring less than 36 months ago 4. Patients benefiting from or affiliated to a social security scheme 5. Patients who have understood, completed and signed the study participation consent form
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sodium accumulation between Parkinson disease patients and Progressive Supranuclear Palsy | Between month 0 and month 3 after inclusion | Comparison of intracerebral sodium accumulation measured by very high-field (7T) cerebral MRI between subjects with Idiopathic Parkinson's Disease and subjects with early-stage Progressive Supra-Nuclear Palsy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sodium accumulation between Parkinson disease patients (MPI) and control subjects | Between month 0 and month 3 after inclusion | Comparison of intracerebral sodium accumulation between subjects with early-stage Parkinson's Disease (PD) and control subjects. |
| Sodium accumulation between Progressive Supra-nuclear patients (soPSP) and control subjects | Between month 0 and month 3 after inclusion | Comparison of intracerebral sodium accumulation between subjects with soPSP and control subjects. |
| Brain atrophy between MPI and soPSP patients | Between month 0 and month 3 after inclusion | 3D mapping of brain atrophy differences measured in Voxel Based Morphometry (VBM), value in cm3 |
| Movement of water molecules between MPI and soPSP patients | Between month 0 and month 3 after inclusion | 3D mapping of differences in mean diffusivity (DM), values in mm2/s |
| Brain atrophy between MPI and control group | Between month 0 and month 3 after inclusion | 3D mapping of brain atrophy differences measured in Voxel Based Morphometry (VBM), value in cm3 |
| Brain atrophy between soPSP and control group | Between month 0 and month 3 after inclusion | 3D mapping of brain atrophy differences measured in Voxel Based Morphometry (VBM), value in cm3 |
| Iron accumulation between soPSP and control group | Between month 0 and month 3 after inclusion | 3D mapping of iron accumulation differences measured by Quantitative Susceptibility Mapping (QSM), values in ppm |
| Iron accumulation between MPI and soPSP patients | Between month 0 and month 3 after inclusion | 3D mapping of iron accumulation differences measured by Quantitative Susceptibility Mapping (QSM), values in ppm |
| Iron accumulation between soPSP patients and control group | Between month 0 and month 3 after inclusion | 3D mapping of iron accumulation differences measured by Quantitative Susceptibility Mapping (QSM), values in ppm |
| Accumulation of neuromelanin between MPI and soPSP patients | Between month 0 and month 3 after inclusion | 3D mapping of neuromelanin differences (signal/MT ratio) |
| Accumulation of neuromelanin between MPI patients and control group | Between month 0 and month 3 after inclusion | 3D mapping of neuromelanin differences (signal/MT ratio) |
| Movement of water molecules between MPI patients and control group | Between month 0 and month 3 after inclusion | 3D mapping of differences in mean diffusivity (DM), values in mm2/s |
| Movement of water molecules between soPSP patients and control group | Between month 0 and month 3 after inclusion | 3D mapping of differences in mean diffusivity (DM), values in mm2/s |
| Structural connectivity between MPI and soPSP patients | Between month 0 and month 3 after inclusion | 3D mapping of anisotropy fraction (AF) differences, values between 0 and 1 |
| Structural connectivity between soPSP patients and control group | Between month 0 and month 3 after inclusion | 3D mapping of anisotropy fraction (AF) differences, values between 0 and 1 |
| Structural connectivity between MPI patients and control group | Between month 0 and month 3 after inclusion | 3D mapping of anisotropy fraction (AF) differences, values between 0 and 1 |
| Measurement of the dependency between sodium accumulation and age | Between month 0 and month 3 after inclusion | Correlation between sodium concentration (mmol/L) and age |
| Measurement of the dependency between sodium accumulation and sex | Between month 0 and month 3 after inclusion | Correlation between sodium concentration (mmol/L) and sex |
| Measurement of the dependency between sodium accumulation and laterality | Between month 0 and month 3 after inclusion | Correlation between sodium concentration (mmol/L) and laterality |
| Measurement of the dependency between brain atrophy and sex | Between month 0 and month 3 after inclusion | Measure by Voxel Based Morphometry (VBM) in cm3 and sex |
| Measurement of the dependency between brain atrophy and age | Between month 0 and month 3 after inclusion | Measure by Voxel Based Morphometry (VBM) in cm3 and age |
| Measurement of the dependency between brain atrophy and laterality | Between month 0 and month 3 after inclusion | Measure by Voxel Based Morphometry (VBM) in cm3 and laterality |
| Measurement of the dependency between iron accumulation and age | Between month 0 and month 3 after inclusion | Measure by Quantitative Susceptibility Mapping (QSM) in ppm and age |
| Measurement of the dependency between iron accumulation and sex | Between month 0 and month 3 after inclusion | Measure by Quantitative Susceptibility Mapping (QSM) in ppm and sex |
| Measurement of the dependency between iron accumulation and laterality | Between month 0 and month 3 after inclusion | Measure by Quantitative Susceptibility Mapping (QSM) in ppm and laterality |
| Measurement of the dependency between accumulation of neuromelanin and age | Between month 0 and month 3 after inclusion | Correlation between ratio of signal/MT and age |
| Measurement of the dependency between accumulation of neuromelanin and sex | Between month 0 and month 3 after inclusion | Correlation between ratio of signal/MT and sex |
| Measurement of the dependency between accumulation of neuromelanin and laterality | Between month 0 and month 3 after inclusion | Correlation between ratio of signal/MT and laterality |
| Measurement of the dependency between structural connectivity and age | Between month 0 and month 3 after inclusion | Correlation between anisotropy fraction (AF) and age |
| Measurement of the dependency between structural connectivity and sex | Between month 0 and month 3 after inclusion | Correlation between anisotropy fraction (AF) and sex |
| Measurement of the dependency between structural connectivity and laterality | Between month 0 and month 3 after inclusion | Correlation between anisotropy fraction (AF) and laterality |
| Measurement of the dependency between structural connectivity and duration of disease progression | Between month 0 and month 3 after inclusion | Correlation between anisotropy fraction (AF) and duration of the disease |
| Measurement of the dependency between accumulation of neuromelanin and duration of disease progression | Between month 0 and month 3 after inclusion | Correlation between ratio of signal/MT and duration of the disease |
| Measurement of the dependency between iron accumulation and duration of disease progression | Between month 0 and month 3 after inclusion | Measure by Quantitative Susceptibility Mapping (QSM) in ppm and duration of the disease |
| Measurement of the dependency between brain atrophy and duration of disease progression | Between month 0 and month 3 after inclusion | Measure by Voxel Based Morphometry (VBM) in cm3 and duration of disease progression |
| Measurement of the dependency between sodium accumulation and duration of disease progression | Between month 0 and month 3 after inclusion | Correlation between sodium concentration (mmol/L) and duration of disease |
| Measurement of the dependency between sodium accumulation and sense of smell | Between month 0 and month 3 after inclusion | Correlation between sodium concentration (mmol/L) and sense of smell (questionnaire) |
| Measurement of the dependency between brain atrophy and sense of smell | Between month 0 and month 3 after inclusion | Measure by Voxel Based Morphometry (VBM) in cm3 and sense of smell (questionnaire) |
| Measurement of the dependency between iron accumulation and sense of smell | Between month 0 and month 3 after inclusion | Measure by Quantitative Susceptibility Mapping (QSM) in ppm and sense of smell (questionnaire) |
| Measurement of the dependency between accumulation of neuromelanin and sense of smell | Between month 0 and month 3 after inclusion | Correlation between ratio of signal/MT and sense of smell (questionnaire) |
| Measurement of the dependency between structural connectivity and sense of smell | Between month 0 and month 3 after inclusion | Correlation between anisotropy fraction (AF) and sense of smell (questionnaire) |
| Measurement of the dependency between structural connectivity and severity of disease | Between month 0 and month 3 after inclusion | Unified Parkinson's Disease Rating Scale (UPDRS), 0 to 199, 0 means better outcome |
| Measurement of the dependency between structural connectivity and quality of life | Between month 0 and month 3 after inclusion | Schwab & England score, 0 to 100%, 0 means better outcome |
| Measurement of the dependency between accumulation of neuromelanin and quality of life | Between month 0 and month 3 after inclusion | Schwab & England score, 0 to 100%, 0 means better outcome |
| Measurement of the dependency between iron accumulation and quality of life | Between month 0 and month 3 after inclusion | Schwab & England score, 0 to 100%, 0 means better outcome |
| Measurement of the dependency between brain atrophy and quality of life | Between month 0 and month 3 after inclusion | Schwab & England score, 0 to 100%, 0 means better outcome |
| Measurement of the dependency between sodium accumulation and quality of life | Between month 0 and month 3 after inclusion | Correlation between Schwab & England score (Schwab & England score, 0 to 100%, 0 means better outcome) and sodium concentration (mmol/L) |
| Measurement of the dependency between accumulation of neuromelanin and severity of disease | Between month 0 and month 3 after inclusion | Unified Parkinson's Disease Rating Scale (UPDRS), 0 to 199, 0 means better outcome |
| Measurement of the dependency between iron accumulation and severity of disease | Between month 0 and month 3 after inclusion | Unified Parkinson's Disease Rating Scale (UPDRS), 0 to 199, 0 means better outcome |
| Measurement of the dependency between brain atrophy and severity of disease | Between month 0 and month 3 after inclusion | Unified Parkinson's Disease Rating Scale (UPDRS), 0 to 199, 0 means better outcome |
| Measurement of the dependency between sodium accumulation and Hospital Anxiety and Depression | Between month 0 and month 3 after inclusion | HAD Echelle (Hospital Anxiety and Depression), 0 to 3, 0 means better outcome |
| Measurement of the dependency between brain atrophy and Hospital Anxiety and Depression | Between month 0 and month 3 after inclusion | HAD Echelle (Hospital Anxiety and Depression), 0 to 3, 0 means better outcome |
| Measurement of the dependency between iron accumulation and Hospital Anxiety and Depression | Between month 0 and month 3 after inclusion | HAD Echelle (Hospital Anxiety and Depression), 0 to 3, 0 means better outcome |
| Measurement of the dependency between accumulation of neuromelanin and Hospital Anxiety and Depression | Between month 0 and month 3 after inclusion | HAD Echelle (Hospital Anxiety and Depression), 0 to 3, 0 means better outcome |
| Measurement of the dependency between structural connectivity and Hospital Anxiety and Depression | Between month 0 and month 3 after inclusion | HAD Echelle (Hospital Anxiety and Depression), 0 to 3, 0 means better outcome |
| Measurement of the dependency between structural connectivity and Sleep Behavior Disorder | Between month 0 and month 3 after inclusion | REM Sleep Behavior Disorder Screening Questionnaire, 0 to 13, 0 means better outcome |
| Measurement of the dependency between accumulation of neuromelanin and Sleep Behavior Disorder | Between month 0 and month 3 after inclusion | REM Sleep Behavior Disorder Screening Questionnaire, 0 to 13, 0 means better outcome |
| Measurement of the dependency between iron accumulation and Sleep Behavior Disorder | Between month 0 and month 3 after inclusion | REM Sleep Behavior Disorder Screening Questionnaire, 0 to 13, 0 means better outcome |
| Measurement of the dependency between brain atrophy and Sleep Behavior Disorder | Between month 0 and month 3 after inclusion | REM Sleep Behavior Disorder Screening Questionnaire, 0 to 13, 0 means better outcome |
| Measurement of the dependency between sodium accumulation and Sleep Behavior Disorder | Between month 0 and month 3 after inclusion | REM Sleep Behavior Disorder Screening Questionnaire, 0 to 13, 0 means better outcome |
| Measurement of the dependency between sodium accumulation and motivation scale | Between month 0 and month 3 after inclusion | Starkstein motivation scale, 0 to 42, 0 means worse outcome |
| Measurement of the dependency between brain atrophy and motivation scale | Between month 0 and month 3 after inclusion | Starkstein motivation scale, 0 to 42, 0 means worse outcome |
| Measurement of the dependency between iron accumulation and motivation scale | Between month 0 and month 3 after inclusion | Starkstein motivation scale, 0 to 42, 0 means worse outcome |
| Measurement of the dependency between accumulation of neuromelanin and motivation scale | Between month 0 and month 3 after inclusion | Starkstein motivation scale, 0 to 42, 0 means worse outcome |
| Measurement of the dependency between structural connectivity and motivation scale | Between month 0 and month 3 after inclusion | Starkstein motivation scale, 0 to 42, 0 means worse outcome |
| Measurement of the dependency between structural connectivity and non-motor fluctuations | Between month 0 and month 3 after inclusion | Number of non-motor fluctuations |
| Measurement of the dependency between accumulation of neuromelanin and non-motor fluctuations | Between month 0 and month 3 after inclusion | Number of non-motor fluctuations |
| Measurement of the dependency between iron accumulation and non-motor fluctuations | Between month 0 and month 3 after inclusion | Number of non-motor fluctuations |
| Measurement of the dependency between brain atrophy and non-motor fluctuations | Between month 0 and month 3 after inclusion | Number of non-motor fluctuations |
| Measurement of the dependency between sodium accumulation and non-motor fluctuations | Between month 0 and month 3 after inclusion | Number of non-motor fluctuations |
| Measurement of the dependency between sodium accumulation and cognitives functions | Between month 0 and month 3 after inclusion | Score Montreal Cognitive Assessment (MoCA), 0 to 30, 0 means worse outcome |
| Measurement of the dependency between brain atrophy and cognitives functions | Between month 0 and month 3 after inclusion | Score Montreal Cognitive Assessment (MoCA), 0 to 30, 0 means worse outcome |
| Measurement of the dependency between iron accumulation and cognitives functions | Between month 0 and month 3 after inclusion | Score Montreal Cognitive Assessment (MoCA), 0 to 30, 0 means worse outcome |
| Measurement of the dependency between accumulation of neuromelanin and cognitives functions | Between month 0 and month 3 after inclusion | Score Montreal Cognitive Assessment (MoCA), 0 to 30, 0 means worse outcome |
| Measurement of the dependency between structural connectivity and cognitives functions | Between month 0 and month 3 after inclusion | Score Montreal Cognitive Assessment (MoCA), 0 to 30, 0 means worse outcome |
| Accumulation of neuromelanin between soPSP patients and control group | Between month 0 and month 3 after inclusion | 3D mapping of neuromelanin differences (signal/MT ratio) |
| Measurement of the dependency between brain atrophy and hypotension | Between month 0 and month 3 after inclusion | Blood pressure test for orthostatic hypotension |
| Measurement of the dependency between iron accumulation and hypotension | Between month 0 and month 3 after inclusion | Blood pressure test for orthostatic hypotension |
| Measurement of the dependency between accumulation of neuromelanin and hypotension | Between month 0 and month 3 after inclusion | Blood pressure test for orthostatic hypotension |
| Measurement of the dependency between structural connectivity and hypotension | Between month 0 and month 3 after inclusion | Blood pressure test for orthostatic hypotension |
| Measurement of the dependency between structural connectivity and hallucinations | Between month 0 and month 3 after inclusion | Miami Questionnaire, 0 to 70, 0 means better outcome |
| Measurement of the dependency between accumulation of neuromelanin and hallucinations | Between month 0 and month 3 after inclusion | Miami Questionnaire, 0 to 70, 0 means better outcome |
| Measurement of the dependency between iron accumulation and hallucinations | Between month 0 and month 3 after inclusion | Miami Questionnaire, 0 to 70, 0 means better outcome |
| Measurement of the dependency between brain atrophy and hallucinations | Between month 0 and month 3 after inclusion | Miami Questionnaire, 0 to 70, 0 means better outcome |
| Measurement of the dependency between sodium accumulation and hallucinations | Between month 0 and month 3 after inclusion | Miami Questionnaire, 0 to 70, 0 means better outcome |
| Measurement of the dependency between sodium accumulation and hypotension | Between month 0 and month 3 after inclusion | Blood pressure test for orthostatic hypotension |
Countries
France
Contacts
Primary ContactStephan Grimaldi, MD
Outcome results
None listed