Parkinson's Disease Clinical Trial
Official title:
Contribution of Magnetic Resonance Imaging (Diffusion Tensor Imaging and Magnetic Susceptibility Imaging and Resting Activation Imaging) in the Diagnosis of Parkinsonian Syndromes in Elderly Subjects.
Parkinsonian syndrome is clinically characterized by the presence of resting tremor,
rigidity, bradykinesia and postural instability. Parkinsonian disorders include Parkinson's
disease (PD), progressive supranuclear palsy (PSP), corticobasal dementia (CBD), multiple
system atrophy (MSA) and vascular parkinsonism (VP). Each of these diseases has a singular
physiopathological origin, course and prognosis. Numerous imaging studies consequently aimed
at finding markers to early make the distinction between the different types of
parkinsonism, in order to identify patients who could benefit from dopaminergic agonist
therapy.
Excessive iron deposition in the subcortical and brainstem nuclei has been described in
numerous neurodegenerative disorders including Parkinson's disease. Increased iron levels
are more frequent in area that are rich in dopaminergic neurons and have been implicated in
the development of movement disorders, the distribution of areas with increased iron
deposition however varying according to parkinsonism types. Iron deposition quantification
could thus potentially help in differentiating parkinsonism types and could improve therapy
guidance. Quantitative susceptibility mapping (QSM) locally estimates the magnetic
susceptibility of brain tissues based on gradient-echo signal phase. The local
susceptibility being sensitive to the presence of paramagnetic susbtances, QSM allows the
non-invasive evaluation of iron distribution and quantification in the brain with high image
quality (Liu et al., 2013). However, since iron deposition followed an exponential curve
during normal aging in most of the basal ganglia the potential of QSM to distinguish between
healthy and parkinsonian subjects in elderly remains unclear.
The aim of this study was thus to determine susceptibility values in the basal ganglia of
elderly patients with parkinsonian syndromes, to compare these values to healthy
aged-matched controls and between parkinsonian syndrome types. Secondly, investigators aimed
to evaluate microstructural changes in the basal ganglia using diffusion tensor imaging
(DTI) in the same population and to determine whether susceptibility and DTI parameter
changes are correlated. Finally investigators sought to assess the relation between
susceptibility/DTI parameter values in the basal ganglia and behavioral measures of motor
and cognitive abilities.
Elderly patients with parkinsonian syndrome and healthy age-matched controls are enrolled in
this study. The subjects all undergo a brain MRI exam. Controls are selected to match the
age distribution of patients.
Clinical evaluation The day of the brain MRI examination, all patients undergo a
neurological and neuropsychological evaluation. Diagnoses are established by a neurologist
experienced with parkinsonian syndromes according to established guidelines: the UK
Parkinson's Disease Society Brain Bank criteria for idiopathic PD, the National Institute of
Neurological Disorders and Stroke and the Society for Progressive Supranuclear Palsy
criteria for progressive supranuclear palsy, Lang's criteria for corticobasal dementia,
Gilman's criteria for multiple system atrophy and Zijlmans's criteria for vascular
parkinsonism.
Impairment of the motor function related to parkinsonian syndrome is assessed using the
Hoehn and Yahr scale (range 0-5), the Schwab and England Activities of Daily Living scale
(range 0-100%), the Unified Parkinson's Disease Rating Scale (UPDRS, range 0-199) and the
Short Motor Disability scale (range 0-17).
Cognitive impairment is assessed using the Mini Mental Sate Examination (MMSE) score (range
0-30), the Grober and Buschke verbal-learning test (range 0-16), a semantic-processing task
(LEXIS test, range 0-64), the forward/backward Digit span task (range 0-17) of the third
Wechsler Adult Intelligence Scale and the Rey-Osterrieth Complex-Figure (ROCF) test (range
0-36) to assess visuospatial abilities, attention, executive function and working memory.
The Mattis Dementia-Rating scale (range 0-144) and the Beck Depression Inventory (range
0-63) are performed to look for depression. The Educational Attainment and the National
Institute of Health Stroke Score (NIHSS) (range 0-42) are also recorded.
MRI acquisition and processing. All patients undergo a brain MRI on a 3-Tesla scanner
including 3D triple echo gradient echo acquisition to generate susceptibility weighted
images, T1-weighted magnetisation-prepared rapid 3D gradient-echo (MPRAGE) and diffusion
tensor imaging acquisition.
Susceptibility weighted imaging raw data are preprocessed to obtain magnitude and phase
images for each echo time. Quantitative susceptibility maps are then generated using SPM8
software (Statistical Parametric Mapping, Wellcome Department of Cognitive Neurology,
Institute of Neurology, London, UK; http://www.fil.ion.ucl.ac.uk/spm/, Matlab 2014a, The
MathWorks, Natick, MA, USA).
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