Retinal Patterns in Reversible Cerebral Vasoconstriction Syndrome

Study Overview
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Brief Summary
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Reversible cerebral vasoconstriction syndrome (RCVS) is a clinico radiological entity characterized by severe headaches (associated or not with neurological complications) during one to 3 weeks, associated with a characteristic 'string and beads' appearance on cerebral arteries, which resolves spontaneously in 3 months. The pathway is unknown. At early stage of the disease (at the first medical consultation) cerebral arterial abnormalities which are necessary for diagnosis are identified in only 20% of patients (brain magnetic resonance imagery (MRI) ,CT scan angiography), appearing with a delay on 2th or 3rd week after the first severe headache.. Retinal artery network is considered to be a window on brain microvasculature by sharing the same embryologic origin and physiopathology. A retinal arteriolar examination at early stage of RCVS could provide non invasively early clue to confirm diagnosis by identifying anatomical change and /or functional abnormalities at the microvascular level, whereas large cerebral artery abnormalities are still normal.

Detailed Description
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Reversible cerebral vasoconstriction syndrome (RCVS) is a clinico radiological entity characterized by severe headaches (associated or not with neurological complications) during one to 3 weeks, associated with a characteristic 'string and beads' appearance on cerebral arteries, which resolves spontaneously in 3 months. The pathway is unknown. One strong hypothesis is that RCVS is a vasospasm and-vasodilatation disorder starting from small distal cerebral arteries progressing toward to medium sized and large sized cerebral arteries, and disappearing in 3 months. At early stage of the disease (generally at the first medical consultation round 7 days after the first headache), arterial caliber anomalies cannot be identified on usual investigation (brain MRI, angioscan) in most of the case (80%). They are appearing secondary on repeated angiogram around the 2nd week or 3rd week, permitting to confirm the diagnosis, but with delay. Currently, small cerebral vessel arteries can't be studied directly . Retinal artery network is easy to study. It is considered to be a window on brain microvasculature by sharing the same embryologic origin and physiopathology. The investigators thus hypothesized that retinal arteriolar examination a early stage of RCVS could provide non invasively early clue to confirm diagnosis by identifying anatomical change and /or functional abnormalities at the microvascular level, whereas large cerebral artery abnormalities are still normal. Hypothesis Arteriolar caliber and vasoreactivity abnormalities at the retinal microvascular level could be an early, non invasive and sensitive diagnostic marker of the RCVS at the first medical consultation in emergency.

Official Title
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Non Invasive Assessment of Morphological and Functional Retinal Patterns in Reversible Cerebral Vasoconstriction Syndrome Using Transorbital Echotomography Doppler, Retinography and Retinal Vessel Analyser

Conditions
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Reversible Cerebrovascular Vasoconstriction Syndrome

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: repetitive thunderclap headache highly suggestive of RCVS (clinical syndrome) maximum delay of ten days between the first thunderclap headache (qualifying event) and patient's inclusion. informed written consent Exclusion Criteria: intracranial aneurism on angiography (Brain MRI or angioscan) severe atheroma with cervical stenosis up to 80% medical history of diabetes and/or hypertension minor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The frequency of retinal morphological microvascular abnormalities | The frequency of retinal abnormalities will be described at early stage of RCVS (< 10 days following the first thunderclap headache = qualifying event) • by measuring the retinal arteriolar caliber at baseline (micrometer, µm) | < 10 days | 
| The frequency of retinal functional vascular abnormalities | The frequency and type of retinal abnormalities will be described at early stage of RCVS (< 10 days following the first thunderclap headache = qualifying event) • by measuring the meanflow value in central retinal artery (cm/s), ciliar arteries (cm/s) and ophthalmic arteries(cm/s) at baseline • by measuring the diameter variation of retinal microvascular network (% of variation) during a vasoreactivity test (flicker stimulation with RVA) | < 10 days | 
| The type of retinal morphological microvascular abnormalities | The type of retinal abnormalities will be described at early stage of RCVS (< 10 days following the first thunderclap headache = qualifying event) • by measuring the retinal arteriolar caliber at baseline (micrometer, µm) | < 10 days | 
| The type of retinal functional vascular abnormalities | The type of retinal abnormalities will be described at early stage of RCVS (< 10 days following the first thunderclap headache = qualifying event) • by measuring the meanflow value in central retinal artery (cm/s), ciliar arteries (cm/s) and ophthalmic arteries(cm/s) at baseline • by measuring the diameter variation of retinal microvascular network (% of variation) during a vasoreactivity test (flicker stimulation with RVA) | < 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The kinetic of morphological retinal abnormalities during RCVS | The kinetic of morphological retinal abnormalities during RCVS course from the first neurological evaluation to final neurological follow up at 3 months (Day10, Day14, Day21 and Day 90) using the same morphological and functional measurements at the retinal level (RVA, retinography, and transorbital echo Doppler) | at Day10, Day14, Day21 and Day 90 | 
| the kinetic of morphological patterns on Brain RMI during RCVS course during RCVS course | The kinetic of morphological patterns at the cerebral level: Brain RMI (Magnetic resonance Imaging) at Day10 Day14 Day21 and Day 90 : existence or not and number of vasopasm , existence or not of ischemic lesions, existence or not of hemorrhagic lesions. | at Day10, Day 14, Day 21 and Day 90 | 
| the kinetic of functional patterns on cervico transcranial duplex evaluation during RCVS course | The kinetics of functional patterns at the cerebral level (men velocities cm/s for MCA CAA, BA, maximum systolic peak values on MCA, CAA and BA )using cervico transcranial duplex | at Day10, Day 14, Day 21 and Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reversible cerebral vasoconstriction syndrome, Anatomic and morphological retinal network analysis, Retinal vessel analyser, retinography, Prospective analysis