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.

  1. Severe, acute headaches, with or without additional neurologic signs or symptoms
  2. Uniphasic disease course with no new symptoms after 1 month of onset
  3. No evidence for aneurysmal SAH
  4. Normal or near-normal findings on CSF analysis
    • protein level <80 mg/dL
    • leukocyte level <10/mm3
    • normal glucose level
  5. Multifocal segmental cerebral artery vasoconstriction demonstrated on either catheter angiography or CTA/MRA
  6. 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.
  • 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