Reversible Cerebral Vasoconstriction Syndrome (RCVS)
- Clinical and radiologic syndrome characterised by hyperacute-onset headache and segmental vasoconstriction of cerebral arteries that resolves by 3 months.
- Common presentation of a diverse group of disorders, including:
- Call-Fleming syndrome
- Postpartum angiopathy
- Migrainous vasospasm
- Benign angiopathy of CNS
- Drug induced angiopathy
- Unknown exact incidence but not rare, and may be underdiagnosed.
- Mean age at presentation is 42-45 years. Commonly affects ages 20-50 years but other ages, including children may be affected
- Female/male ratio is approximately 2.4:1. Male patients tend to be about a decade younger than female
- An identifiable trigger is found in 25-60% of cases. Development of RCVS after exposure to a trigger may sometimes be delayed for several days to months
- Exposure to vasoactive drugs (50%) and postpartum state (9-10%) account for more than half of the cases
- RCVS in the postpartum period may be encountered 1-3 and up to 6 weeks following an uncomplicated pregnancy
- Pathophysiology is unknown. Alterations in cerebral vascular tone are thought to be a key mechanism
- No histopathologic changes are found in arterial biopsies
- Overlap between posterior revercible encephalopathy syndrome (PRES) and RCVS point to possible endothelial dysfunction
- Prognosis for most patients is good.
- Typically monophasic self-limited disease
- Resolution of symptoms by 3 weeks
- Resolution of vasoconstriction by 3 months
- A minority of patients may have delayed clinical worsening
- 5%–10% of patients will have a fulminant course leading to permament disability or death
- RCVS encountered in postpartum period is more likely to follow a fulminant course
- Recurrence or RCVS is rare but some patients may have chronic mild headaches and fatigue on follow-up
Diagnostic criteria for RCVS
Proposed by Calabrese et al in 2007, modified by International Headache Society. Have not yet been validated in any prospective studies.
- Severe, acute headaches, with or without additional neurologic signs or symptoms
- Uniphasic disease course with no new symptoms after 1 month of onset
- No evidence for aneurysmal SAH
- Normal or near-normal findings on CSF analysis
- protein level
<
80 mg/dL - leukocyte level
<
10/mm3 - normal glucose level
- protein level
- Multifocal segmental cerebral artery vasoconstriction demonstrated on either catheter angiography or CTA/MRA
- Reversibility of angiographic abnormalities within 12 weeks after onset
- If death occurs before the follow-up studies are completed, postmortem should rule out vasculitis, intracranial atherosclerosis, and aneurysmal SAH
Potential triggers of RCVS
- Vasoactive drugs
- Sympathomimetics, bromocriptine, ergotamine, pseudoephedrine, SSRI, interferon, triptans, diet pills, NSAID
- Alcohol
- Cocaine
- Amphetamines
- Cannabis
- Ecstasy
- Nicotine
- Pregnancy and postpartum state
- Migraine
- Trauma
- Vascular pathology
- Carotid dissection
- Unruptured intracranial aneurysm
- Tumors
- Paraganglioma
- Pheochromocytoma
- Head and neck surgery
- HELLP syndrome
- Antiphospholipid syndrome
- Thrombotic thrombocytopenic purpura
- Blood transfusion
- Erythropoetin
- Intravenous immunoglobulin
Clinical presentation
- Thunderclap headache is reported in 94-100% of patients
- Peak intensity within 60 seconds
- Severe, often throbbing, bilateral and diffuse
- May originate in the occipital region
- Sole presenting symptom in 70-76% of patients
- Often there is a delay (mean 7 days) between onset and patient seeking medical help
- A minority of patients may suffer a milder, subacute headache but complete absence of headache is rare
- Contrary to aneurysmal SAH, RCVS-related headache typically has a waxing and waning course
- May completely resolve within minutes to days, only to recur repeatedly in 1-3 weeks
- Typically there may be 1-20 such exacerbations, often triggered by specific activities (sexual intercourse, coughing, stress, positional change, bathing, etc)
- The exact cause of the headache in RCVS is unknown
- Nausea/vomiting
- Diplopia
- Photosensitivity
- Elevated blood pressure
- Seizures
- Encephalopathy
- Focal neurologic deficits
- Altered mental state
- Cerebral infarction
- TIA
- Subarachnoid hemorrhage
- Intraparenchymal hemorrhage
- Cerebral edema
- PRES
- Reversible cerebral edema resembling PRES is encountered in 9-38% of patients with RCVS
- The majority of patients with PRES (>85%) demonstrate some element of RCVS-like cerebral vasoconstriction on angiography or CTA/MRA
Diagnosis
- Conventional angiography is by definition 100% sensitive since it defines the diagnosis
- However, up to a third of patients will have normal angiography in the first week from symptom onset.
- It is hypothesized that segmental vasoconstriction starts in small peripheral arteries and moves centripetally to involve medium and larger caliber arteries
- The presence of centripetal propagation of vasoconstriction is associated with an increased risk of brain lesions and longer interval from first to last thunderclap headache.
- However, up to a third of patients will have normal angiography in the first week from symptom onset.
- CTA/MRA sensitivity ~80% compared to conventional angiography
- Vessel wall imaging MRI may distinguish between CNS vasculitis (contrast enhancing wall) and RCVS (no enhancement)
- Blood and CSF tests are typically unremarkable
Treatment recommendations
- Withdrawal of any suspected exogenous trigger
- Avoidance of triggering activities
- Symptom relief
- Analgesia
- Blood pressure control
- Consider sseizure prophylaxis
- Calcium channel blockers (eg. nimodipine) oral or iv.
- Have been shown to provide symptom relief but do not influence the evolution of nor the risk for complications from RCVS
- All vasodilators should be used with caution as drops in systolic BP may impair cerebral perfusion in patients with severe vasoconstriction
- Intraarterial administration of vasodilators and baloon angioplasty have been used in severe cases but their indication and efficiency remain uncertain
- Recurrence of vasospasm after successful intraarterial treatment may occur and necessitate repeated treatment
- Glucocorticoids do not improve symptoms or sequelae and may be associated with worse outcomes
References
- Reversible cerebral vasoconstriction syndrome Lancet Neurol. 2012 Oct;11(10):906-17. doi: 10.1016/S1474-4422(12)70135-7
- Reversible cerebral vasoconstriction syndrome: A review of pathogenesis, clinical presentation, and treatment Int J Stroke . 2023 Dec;18(10):1151-1160. doi: 10.1177/17474930231181250
- Reversible cerebral vasoconstriction syndrome: review of neuroimaging findings Radiol Med. 2022 Sep;127(9):981-990. doi: 10.1007/s11547-022-01532-2
- Pathophysiology of reversible cerebral vasoconstriction syndrome J Biomed Sci. 2022 Sep 21;29(1):72. doi: 10.1186/s12929-022-00857-4
- Posterior Reversible Encephalopathy Syndrome: A Review of the Literature Intern Med. 2022 Jan 15;61(2):135-141. doi: 10.2169/internalmedicine.7520-21