Differences Between Patients With Vascular Parkinsonism and Parkinson's Disease

Parkinson's Disease Clinical Trial

Official title:

The Clinical and Neuroimaging Differences Between Patients With Vascular Parkinsonism and Idiopathic Parkinson's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04308135
• Other study ID #: MD209/2019
• Status: Completed
• Start date: September 1, 2019
• Est. completion date: April 1, 2022

Study information

• Verified date: September 2023
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Vascular parkinsonism (VP) is defined as the presence of parkinsonian syndrome, evidence of cerebrovascular disease by brain imaging and an established relationship between the two disorders. However, the diagnosis of VP is problematic. This study aims to distinguish VP from Parkinson's disease (PD) in multiple aspects including clinical features as motor ,non motor symptoms ,response to treatment ,cognitive assessments by using multiple scales, neuro-radiological features of magnetic resonance imaging (MRI) and transcranial color-coded duplex (TCCD) findings. This differentiation will have therapeutic and prognostic implications .

Description:

Type of Study : case -control comparative study. • Study Setting: Patients with VP and patients with PD from movement disorders and stroke outpatient clinics in Ain shams University Hospitals. Sampling Method study of consecutive patients in Ain Shams University clinic, who had been regularly followed up in the clinic and already had a diagnosis either VP or PD at the time of data collection. Sample Size: 30 patients diagnosed as VP, 50 patients diagnosed as PD, and 30 healthy age and sex matched controls. The difference in selected quantitative variables used to evaluate the participants is used to estimate the sample size. This study aims to distinguish VP from Parkinson's disease(PD) in multiple aspects including clinical features as motor ,non-motor symptoms, response to treatment ,cognitive assessments by using multiple scales, neuro-radiological features of magnetic resonance imaging (MRI) and transcranial color-coded duplex(TCCD)findings.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: April 1, 2022
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Patients diagnosed with PD or VP, and healthy controls will be included in the study.
• PD diagnosis will be based on the Queen Square Brain Bank for Neurological Disorders clinical criteria and MDS criteria.
• The VP patients will be included if they fulfill the following criteria (Zijlman's diagnostic criteria)Parkinsonism presentation (at least two of the cardinal features: tremors, bradykinesia, rigidity and postural instability). Cerebrovascular disease, defined as evidence of relevant cerebrovascular disease by brain imaging or the presence of focal signs or symptoms consistent with stroke. A relationship between (1) and (2): acute or delayed progressive onset of parkinsonism. Based on the above criteria, two forms of VP are suggested: one with acute onset, and another one with insidious progression. The diagnosis will be confirmed by assigning a vascular score. Two points or more are essential to diagnose VP. The points will be

assigned as follows:

• Two points: Pathologically or angiographically proven diffuse vascular disease.
• One point: Onset of parkinsonism within 1 month of clinical stroke.
• One point: History of two or more strokes.
• One point: Neuroimaging evidence of vascular disease in two or more vascular territories.
• One point: History of two or more risk factors for stroke (hypertension, smoking, diabetes mellitus, hyperlipidaemia, presence of heart disease associated with stroke [coronary artery disease, atrial fibrillation, congestive heart failure, valvular heart disease, mitral valve prolapse, and other arrhythmias], family history of stroke, history of gout, and peripheral vascular disease)

Exclusion Criteria:

• PD patients with age at onset less than 40 years.
• Any alternative cause that significantly impair gait.
• Inability of the patient to undergo neuroimaging.
• Patients couldn't perform the test or severely demented.
• Atypical and other secondary parkinsonism as patients who had a history of toxin exposure.or antipsychotic drugs treatment by history ,neurological examination and brain MRI .
• Family or patient's refusal to give written consent.

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease
• Parkinsonian Disorders
• Vascular Parkinsonism

Intervention

Diagnostic Test:
• Neuro-radiological tools:
MRI brain: to measure white matter c) Ultrasonographic examination of extracranial vessels: The intimal medial thickness of the common carotid artery (CCA-IMT) will be measured in B-mode. The carotid arteries will be evaluated for the presence of atherosclerotic lesions (plaques) either soft or hard .The residual lumen and degree of stenosis will be measured. The peak systolic velocity will be detected.
• cognitive tests
All patients will be evaluated for global cognitive assessment by: Montreal Cognitive Assessment (MoCA) (Arabic version) Visuospatial skills will be assessed by Clock Drawing Tests from MoCA test and copy the intersecting pentagons from Addenbrooke's test (Arabic version) Language will be examined by semantic fluency from Addenbrooke's test (Arabic version) and similarities from Wechsler Adult Intelligence Scale (WAIS) Attention will be evaluated by digit span from Wechsler test),and by the number of seconds needed to sequence numbers using a pencil (Trail making test A) from MoCA test . For the evaluation of memory, participants will complete Wechsler memory subset , and the investigators also will use their three-item recall from the Mini-Mental State Examination( MMSE). Executive functions will be measured by Wisconsin card sorting test and also verbal fluency test from Addenbrooke's test. Frontal Assessment Battery (FAB) scale
• lab investigations
Each patient will undergo full lab investigations:[lipid profile ,complete blood count, uric acid ,Hemoglobin A1c (HbA1c), liver functions, renal functions, and electrolytes]
• Beck depression inventory (BDI)(Arabic version)
Clinical Tool for depression
• Clinical Tools for Urinary symptoms:
the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) Scale (Arabic version)
• Freezing of gait questionnaire
Clinical Tools for Gait (in on and off state ), Gait will be assessed by: .Freezing of gait questionnaire Berg balance scale. 10 meter walk test . Timed up and go test.
• non-motor symptoms scales (NMSS).
Clinical Tool for assessment of non-motor symptoms of PD
• Movement Disorders Society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS):
Clinical Tools for assessment of the neurological severity and stage of disease Clinical Tool for assessment of the neurological severity and stage of disease during "OFF" and "ON" states, Hoehn and Yahr scale. The presence of lower limb parkinsonism will be determined by a two-point difference between upper limb and lower limb scores of bradykinesia, rigidity or postural instability from part III of the MDS-UPDRS. Patients will be examined in the early morning, in 'OFF' state, with MDS-UPDRS, Hoehn and Yahr and freezing of gait questionnaire(FOG-Q) scales. Immediately afterwards, they will take their regular first dose of levodopa. After 1 hour, patients will be examined again with the same tests and scales. Response to levodopa will be determined as patients who reached a percentage reduction exceeding 25% in part III of the MDS-UPDRS
• ELIZA for alpha-synuclein
measuring serum of alpha-synuclein, tau and their autoantibodoies

Other:
• transcranial color-coded duplex(TCCD)
TCCD using phase array 2.4 Hz probe for evaluation of cerebral vasomotor reactivity (CVR) by measuring the Breath holding index(BHI),flow velocities and pulsatility index of middle cerebral artery and posterior cerebral artery on both sides.
• extracranial carotid duplex
to assess atherosclerosis, stenosis of carotids
• The Arabic version of Parkinson's Disease Questionnaire( PDQ-39)
Clinical tool for quality of life of PD patients

Locations

Country	Name	City	State
Egypt	Ain Shams University	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MDS-UPDRS scale on on and off state	It detects the motor differences between Vascular Parkinsonism and Parkinson's Disease by scores on the scale ...the maxium score is 199 represents the worst (total disability) with a score of zero representing (no disability)	2 year... will be at single point
Primary	Montreal Cognitive Assessment (MoCA) (Arabic version)	MoCA scores range between 0 and 30. .high score more than or equal 26 is normal	2 years....will be at single point
Primary	White matter severity by MRI brain	White matter differences by fazekas scale 0,1,2 or 3 scores	2 years....will be at single point
Primary	Non motor symptoms scale	It detects the non motor symptoms differences between Vascular Parkinsonism and Parkinson's Disease byUsing a distribution of NMSS scores by quartiles, a classification based on levels from 0 (no NMS at all) to 4 (very severe NMS) for 30 itemes ...high score is worst	2 years.....will be at single point
Primary	Addenbrooke's test (Arabic version)	for aassement of Visuospatial skills, Language and verbal fluency result score 16 for visuospatial processing ,26 for language 14 for fluency high score is best	2 year ....will be at single point
Primary	Wechsler Adult Intelligence Scale (WAIS)	The average score for the test is 100, and any score from 90 to 109 is considered to be in the average intelligence range. Score from 110 to 119 are considered to be High Average. Superior scores range from 120 to 129 and anything over 130 is considered Very Superior.	2 year....will be at single point
Primary	Frontal Assessment Battery scale.	Frontal Assessment Battery scale..total score is from a maximum of 18, higher scores indicating better performance.	2 year ....will be at single point
Secondary	Substantia nigra Echogenicity by transcranial doppler	to detect differences of substantia nigra Echogenicity by millimeter and differences of mean flow velocities by centimeter per second	2 years
Secondary	Carotid arties wall thickness by Extra cranial duplex	to detect differences of Intima-media thickness values by millimeter and flow velocities by centimeter per second	2 year