Reversible cerebral vasoconstriction syndrome
Reversible cerebral vasoconstriction syndrome (RCVS) is a group of condition with a common clinical and radiologic presentation. It is characterised by thunderclap headache and reversible vasoconstriction of the cerebral arteries.
A number of terms have been used to describe this entity or subsets: benign angiopathy of the CNS, CNS pseudovasculitis, Call-Fleming syndrome, drug-induced cerebral arteritis, migrainous vasospasm, postpartum cerebral angiopathy, sexual headache and thunderclap headache associated vasospasm.
It should not be confused with posterior reversible encephalopathy syndrome (PRES), although there is overlap both in the presumed underlying mechanisms and predisposing factors, and association of PRES with RCVS has been described.
It affects women more commonly than men (2.4F:1M) and usually presents between 20-50 years of age, although it has also been described in children and adolescents. The mean age of presentation is 42 years. The mean age of presentation in men is a decade younger (~30 years) than the mean age of presentation for women.
Thunderclap headache is the usual primary symptom, often occipital but also potentially diffuse. There may be a history of recurrent thunderclap headaches over days or weeks. Headaches may be associated with photophobia, nausea and vomiting. Focal neurological deficits can occur, secondary to ischaemia or convexity subarachnoid haemorrhage. CSF studies are normal or near normal.
In 2016, a study proposed a set of criteria to diagnose RCVS and to distinguish it from primary angiitis of the central nervous system (PACNS) with a specificity of 98-100% and a similarly high PPV 7:
- recurrent thunderclap headaches or;
- single thunderclap headache with either normal neuroimaging study or watershed infarct/vasogenic oedema or;
- no thunderclap headache but abnormal angiographic findings with a normal neuroimaging study
- this basically rules out PACNS as neuroimaging is always abnormal
Criteria have also been proposed by the International Headache Society.
- pregnancy and puerperium
- early puerperium / late pregnancy
- eclampsia / pre-eclampsia / delayed postpartum eclampsia
- exposure to drugs and blood products
- 'recreational drugs'
- IV Ig
- red blood cell transfusion
Neuroimaging at the onset of symptoms is normal in a significant percentage of patients, but this varies from one study to the other (21-55%) 2,6. A practical approach for the diagnosis of RCVS on imaging is listed in a section below.
The findings on imaging consist of either direct visualisation of the vascular narrowings and/or complication(s) related to vascular narrowings such as:
- nonaneurysmal and convexal subarachnoid haemorrhage (22-34%) 2,6
- lobar haemorrhage (6-20%) 2,6
- vasogenic oedema (38%) 6
- watershed infarct (29%) 6
Transcranial Doppler may show increased arterial velocities suggesting vasospasm and decreased luminal calibre of ICA, MCA and ACA 8. Bedside ultrasound has been used for the follow-up of vasospasm 9.
CT-scan and CTA are useful to rule out aneurysmal subarachnoid haemorrhage. As previously noted, CT-scan can be entirely normal with RCVS. The following can be seen:
- convexal subarachnoid haemorrhage
- watershed infarct
- lobar haemorrhage
- vascular narrowings on CTA (see DSA)
Cortical oedema and/or vascular FLAIR hyperintensities may precede vasoconstriction on MRI.
- sulcal hyperintensities may reflect cortical convexal subarachnoid haemorrhage or vascular hyperintensities (an early sign) 11
- cortical hyperintensities related to cortical oedema (an early sign) 11
- vasogenic oedema related to vasoconstriction or cytotoxic
- useful as it does not show normal cortical vessels and meninges (versus T1 C+), and may reflect blood-brain barrier breakdown 12
- variable patterns of sulcal enhancement have been described 12
- MRA: vascular narrowings can be seen (see DSA)
- DWI: watershed infarcts can be seen
DSA - angiography
Smooth, tapered narrowings involving large to medium-sized arteries followed by abnormally dilated segments of second-order and third-order branches is the most characteristic finding 13. This dilatation gives the typical beaded or sausage-shaped appearance of cerebral arteries. Normalisation of the angiographic findings is usually seen within 8-12 weeks 6,12.
Vasoconstriction following subarachnoid haemorrhage involves longer segments of more proximal branches without alternating areas of narrowing 13. It is worth noting that intracranial atherosclerosis causing vascular narrowings is seen in 7.5-30% of the asymptomatic population thus potentially complexifying evaluation on DSA 12.
Treatment and prognosis
Spontaneous resolution usually occurs, with improvement in angiographic findings within three months. The natural history of the condition has not however been well characterised. Complete long-term resolution of the symptoms with no neurological deficit is the most common outcome in up to 90% of patients 6.
Although no randomised controlled trials are available, treatment with calcium channel blockers seems to be efficacious and are thought to be a reasonable first-line therapy. Short course glucocorticoid therapy has also been advocated.
History and etymology
It was first described by Calabrese et al. in 1993, and named “benign angiopathy of the central nervous system”. Afterwards, in 1998, Call and Flemming described a series of patients with severe headaches and reversible cerebral segmental vasoconstriction 15. The term RCVS was coined later in 2007 by Calebrese 1.
When vascular imaging has been obtained, the differential narrows to conditions that can cause intracranial arterial beading, namely:
- subarachnoid haemorrhage with intracranial vasospasm
- arterial dissection
- partially or untreated treated fungal or bacterial meningitis
No validated radiological criteria have been defined for diagnosis confirmation. However, the following guidelines are reasonable when applied to the clinical context:
- neurovascular imaging demonstrates multifocal narrowings in the circle of Willis and its branches
- there is a suggestion of centripetal propagation of the narrowings when comparing initial neurovascular imaging at the onset of thunderclap headache with postremission neurovascular imaging 5
- if subarachnoid haemorrhage is present, it is usually mild and only involves the cerebral convexity
- validation of the diagnosis rests on eventual resolution of neurovascular findings within 8-12 weeks 6-14
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- 2. Ducros A, Boukobza M, Porcher R et-al. The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patients. Brain. 2007;130 (Pt): 3091-101. doi:10.1093/brain/awm256 - Pubmed citation
- 3. Marder CP, Donohue MM, Weinstein JR et-al. Multimodal imaging of reversible cerebral vasoconstriction syndrome: a series of 6 cases. AJNR Am J Neuroradiol. 2012;33 (7): 1403-10. AJNR Am J Neuroradiol (abstract) - doi:10.3174/ajnr.A2964 - Pubmed citation
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- 11. Murase S, Gon Y, Watanabe A, Todo K, Kohara N, Mochizuki H, Sakaguchi M. Isolated cortical vasogenic edema and hyperintense vessel signs may be early features of reversible cerebral vasoconstriction syndrome: Case reports. (2017) Cephalalgia : an international journal of headache. doi:10.1177/0333102417731779 - Pubmed
- 12. Lee MJ, Cha J, Choi HA, Woo SY, Kim S, Wang SJ, Chung CS. Blood-brain barrier breakdown in reversible cerebral vasoconstriction syndrome: Implications for pathophysiology and diagnosis. (2017) Annals of neurology. 81 (3): 454-466. doi:10.1002/ana.24891 - Pubmed
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