Perfusion MRI in Reversible Cerebral Vasoconstriction Syndrome

July 25, 2016 updated by: University of Nottingham
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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
        • Clinical Neurology, Division of Clinical Neuroscience, University of Nottingham, UK

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, month 1, and month 3
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.
Baseline, month 1, and month 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, month 1, and month 3
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.
Baseline, month 1, and month 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nottingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2016

Primary Completion (Anticipated)

May 1, 2017

Study Completion (Anticipated)

May 1, 2017

Study Registration Dates

First Submitted

March 2, 2016

First Submitted That Met QC Criteria

April 26, 2016

First Posted (Estimate)

April 29, 2016

Study Record Updates

Last Update Posted (Estimate)

July 26, 2016

Last Update Submitted That Met QC Criteria

July 25, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15085

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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