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Perfusion MRI in Reversible Cerebral Vasoconstriction Syndrome

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ClinicalTrials.gov Identifier: NCT02756416
Recruitment Status : Not yet recruiting
First Posted : April 29, 2016
Last Update Posted : July 26, 2016
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
This study aims to quantify perfusion, assess arterial vasoconstriction, and confirm reversibility using 3T ASL-MRI and MRA in 10 patients with suspected RCVS. Acquiring these data at multiple time points during RCVS progression, the investigators will assess the relationship between vasoconstriction and downstream perfusion and determine the role of these imaging techniques in early and accurate diagnosis of RCVS. The investigators also aim to investigate whether early imaging abnormalities can predict RCVS complications and clinical outcomes.

Condition or disease Intervention/treatment
Reversible Cerebral Vasoconstriction Syndrome Device: MRI brain Device: ASL-MRI brain Device: MRA brain

Detailed Description:

Reversible Cerebral Vasoconstriction Syndrome (RCVS) is a group of conditions characterised by prolonged but reversible multifocal narrowing of the cerebral arteries. It presents typically as acute severe headache, usually recurrent and thunderclap in character, with or without additional symptoms and signs. Adverse complications associated with RCVS can be devastating especially if not recognised early; depending on the degree of vasoconstriction, RCVS may be associated with cortical subarachnoid haemorrhage (in approximately 34% of patients), ischaemic infarction (6-39% of patients), or concomitant posterior reversible encephalopathy syndrome (PRES, 9-38% of patients). RCVS may also present as parenchymal brain haemorrhage in 20% of cases. The data on complications rate highlight the uncertainty about the condition and indicate need for more research to better characterise the evolution of the pathology; hence need for this study as it is prospective and longitudinal.

The hallmark of RCVS is vasoconstriction seen on vascular imaging scans and typically reverses within 3 months. Prevalence of radiological vasoconstriction seen on magnetic resonance angiography (MRA) in RCVS is reported to be between 60-90% and typically appears as diffuse segmental constriction of large and medium sized vessels lasting 4-12 weeks. The main advantage of MRA is that it can be performed without the use of a radioactive tracer, thus providing a safe method for repeat observations of vascular pathology. Imaging is often negative in first 4-5 days following the onset of headache; The mean time to detect abnormality on vascular imaging has been reported as 8 days after headache onset. RCVS symptoms usually resolves by 1 month after presentation, however the adverse complications associated with RCVS may have lasting consequences as described above. Magnetic resonance imaging (MRI) is an excellent tool for characterising brain changes during the progression and resolution of RCVS. Standard structural images can identify complications of RCVS, such as bleeding, ischaemia, and PRES.

Finally, Arterial Spin Labeling (ASL) MRI can be used to non-invasively quantify perfusion of brain tissue, providing a measure of the impact of upstream arterial vasoconstriction on local cortical regions.

Cortical perfusion has not yet been extensively studied in RCVS; at time of writing, only two case reports have been published. Rosenbloom and Singhal reported a case of RCVS induced by carotid endarterectomy following a frontal lobe ischaemic stroke. Perfusion MRI showed unilateral hypo-perfusion, mainly affecting internal watershed areas with superficial cortical regions being relatively spared. In a second study, ASL-MRI was performed on a 50-year-old man with RCVS who presented with severe recurrent headaches and neurological deficits (localising to the right hemisphere). ASL-MRI demonstrated significant hypo-perfusion in the right parieto-occipital lobe, but no infarct was seen on diffusion imaging. At 12 weeks, there was complete resolution of cerebral vasoconstriction on angiography and normal perfusion findings on ASL-MRI.

These case studies suggest that perfusion MRI can offer an additional tool to confirm and understand RCVS. ASL-MRI is a non-invasive, radiation and contrast-free technique that can be performed at multiple time points to monitor changes in perfusion over the time period of RCVS resolution and assess response to potential therapeutics.

One of the disadvantages of ASL-MRI is a low signal to noise ratio, this can be addressed by using high-field MRI at 3 Tesla (3T). In addition, 3T MRI can provide very good spatial resolution. The University of Nottingham represents one of the leading international research centres with experience in using high and ultra-high field MRI for investigating different neurological diseases such as multiple sclerosis and brain tumours with excellent results. Applying advanced non-invasive MRI techniques in this study will be a significant advantage as we investigate RCVS, understand the pathophysiology, and assess brain perfusion in multiple time points.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Perfusion MRI in Reversible Cerebral Vasoconstriction Syndrome
Study Start Date : July 2016
Estimated Primary Completion Date : May 2017
Estimated Study Completion Date : May 2017

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U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: ASL MRI and MRA
All participants will undergo ASL-MRI and MRA at three points; baseline, month 1, and month 3.
Device: MRI brain
Standard MRI brain will be performed on each participant to look at brain structure and exclude complications of RCVS (if any).
Device: ASL-MRI brain
ASL-MRI is a non-contrast scan used to measure cortical cerebral blood flow (CBF) in areas supplied by major arteries (Circle of Willis).
Device: MRA brain
MR angiography scan looks at blood vessels structure. We expect to see constriction (narrowing) of the major arteries in RCVS cases.


Outcome Measures

Primary Outcome Measures :
  1. Change in cortical cerebral blood flow (CBF) measured in ml/100g/min using ASL-MRI. [ Time Frame: Baseline, month 1, and month 3 ]
    The process includes detailed imaging analysis.

  2. Change in Circle of Willis arteries and major branches structure, this will be assessed by MRA and examined by a neuro-radiologist. [ Time Frame: Baseline, month 1, and month 3 ]
    Correlation between vascular changes and perfusion levels will be measured.


Secondary Outcome Measures :
  1. RCVS complications, such as ischaemia, bleeding, and posterior reversible encephalopathy syndrome, will be assessed using standard MRI brain sequences. [ Time Frame: Baseline, month 1, and month 3 ]
    Correlation between occurrence of these complications and perfusion levels will be measured.

  2. Headache characteristics; participants will be questioned about their headache using a questionnaire as part of the case report form. [ Time Frame: Baseline, month 1, and month 3 ]
    Correlation between headache characteristics and perfusion levels will be measured.


Eligibility Criteria

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients aged 18-60 years old
  • Able to give informed written consent
  • Clinical presentation suggestive of RCVS
  • Able to understand the requirements of the study, including anonymous publication, and agree to co-operate with the study procedures

Exclusion Criteria:

  • Evidence of brain haemorrhage or significant brain pathology on Computed Tomography (CT) scan performed as standard National Health Service (NHS) care
  • Any history of significant cerebrovascular disease
  • Pregnancy or breastfeeding
  • MRI contraindications (e.g. metal implants or pacemaker) as indicated on the MRI Safety Screening Questionnaire
  • Significant claustrophobia
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02756416


Contacts
Contact: Nikos Evangelou, FRCP, D.Phil 00441159709735 nikos.evangelou@nottingham.ac.uk
Contact: Yasser Falah, MBChB, MRCP 00441158231082 yasser.falah@nottingham.ac.uk

Locations
United Kingdom
Clinical Neurology, Division of Clinical Neuroscience, University of Nottingham, UK Not yet recruiting
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Contact: Nikos Evangelou, FRCP, D.Phil    00441159709735    nikos.evangelou@nottingham.ac.uk   
Contact: Yasser Falah, MBChB, MRCP    00441158231082    yasser.falah@nottingham.ac.uk   
Principal Investigator: Nikos Evangelou, FRCP, D.Phil         
Sponsors and Collaborators
University of Nottingham
More Information

Publications:

Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT02756416     History of Changes
Other Study ID Numbers: 15085
First Posted: April 29, 2016    Key Record Dates
Last Update Posted: July 26, 2016
Last Verified: July 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by University of Nottingham:
Reversible Cerebral Vasoconstriction Syndrome (RCVS)
Arterial spin labeling (ASL) MRI

Additional relevant MeSH terms:
Syndrome
Disease
Pathologic Processes