I searched PubMed with the terms “reversible cerebral vasoconstriction”, “thunderclap headache”, “postpartum angiopathy”, “posterior reversible encephalopathy syndrome”, and “benign angiopathy of the central nervous system” for papers published between Jan 1, 1980, and April 30, 2012. Older relevant reports were also included. I also searched the reference lists of identified reports and my own files. Only papers published in English or French or with an English abstract were reviewed. I chose
ReviewReversible cerebral vasoconstriction syndrome
Introduction
Reversible cerebral vasoconstriction syndrome (RCVS) is characterised by severe headaches, with or without other acute neurological symptoms, and diffuse segmental constriction of cerebral arteries that resolves spontaneously within 3 months.1, 2 Manifestations are attributed to a transient disturbance of the regulation of cerebral arterial tone. Thunderclap headache—severe pain peaking in seconds—is usually the first symptom and typically recurs for 1–2 weeks.3, 4, 5 Ischaemic and haemorrhagic stroke are the major complications of the syndrome.5, 6, 7, 8, 9 In 2007, Calabrese and colleagues2 proposed the name RCVS and a set of diagnostic criteria to regroup all similar cases that had been reported since the 1970s under several other names (panel 1).10, 11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 Since then, large case series of the syndrome have been published.5, 7, 8, 9, 24 In this Review, I focus on the clinical and radiological features of RCVS. I describe the clinical heterogeneity of the syndrome, appropriate investigations, and approaches to diagnosis (including possible differential diagnoses) and management. I aim to show that, although the pathological process is unknown and no specific diagnostic test or proven treatment is available, diagnosis is easy and an important step in the care of patients with RCVS.
Section snippets
Epidemiology
RCVS has been reported in people aged from 10 to 76 years,7, 25, 26 but occurrence peaks at around 42 years and the syndrome is more common in women than in men.5, 7, 9 Incidence is unknown, but the syndrome does not seem to be especially rare—the first large series5 included 67 patients who presented to the same institution during 3 years. Cases have been reported on every continent, and three large series from Asia, Europe, and North America have shown the broad range of presentations, from
Clinical features
Clinical manifestations typically follow an acute and self-limiting course without new symptoms after 1 month.5 Headache is the main symptom and often remains the only manifestation of RCVS (table).5 Onset is acute with thunderclap headache—extreme head pain peaking in less than 1 min, mimicking that of a ruptured aneurysm.12, 13 Screaming, crying, agitation, confusion, and collapse are common because of the excruciating pain. Typical headache is bilateral (although it can be unilateral), with
Laboratory investigations
The results of blood counts, measurements of ESR and concentrations of serum electrolytes, and liver and renal function tests are usually normal in patients with RCVS. A few patients have a transient inflammatory response, which might be due to the clinical situation preceding the clinical onset of RCVS (eg, cold treated with nasal decongestants6 or skin rash treated with steroids13). Tests for angiitis, including measurements of rheumatoid factor, antinuclear and antineutrophil cytoplasmic
Neuroimaging
Brain scans of many patients with RCVS look healthy despite the presence of diffuse vasoconstriction on concomitant cerebral angiograms. Lesions are noted in 12–81% of patients, dependent on patterns of study recruitment (table, figure).5, 7, 8, 9 Lesions include three types of stroke—convexity subarachnoid haemorrhage, intracerebral haemorrhage, and cerebral infarction—and reversible brain oedema.2, 7, 8, 33, 35 Chen and co-workers7, 24 used haemorrhage as an exclusion criterion in their
Cerebral angiography
To diagnose RCVS, direct (transfemoral) or indirect (CT or magnetic resonance) cerebral angiography is needed to show segmental narrowing and dilatation (string of beads) of one or more arteries (figure).2, 57 Calibre irregularities can affect the anterior and the posterior circulation, and are mostly bilateral and diffuse. The basilar artery, carotid siphon,3, 13 or external carotid artery can be affected.58 Narrowing of arteries is not fixed; a repeat angiogram after a few days might show
Ultrasonography
Cervical ultrasonography is normal except in cases of RCVS associated with cervical arterial dissection.5 Transcranial doppler ultrasonography can be useful in monitoring cerebral vasoconstriction.24, 64 Maximum mean flow velocities in the middle cerebral arteries might be normal during the first few days after onset of symptoms but then increase and peak (<2 m/s) about 3 weeks after headache onset.5, 24
Pathological investigations
Biopsy of the brain or temporal artery is not recommended for diagnosis of RCVS, and should be done only in cases in which cerebral angiitis is strongly suspected.13 In RCVS, arterial histology has been normal and active inflammation, vasculitis, and micro-thrombosis absent in brain biopsies and autopsies.6, 11, 13, 49, 60 However, in some cases interpretation of pathological samples can be difficult because prolonged, severe vasoconstriction can induce secondary inflammation.65
Diagnosis
Recurrent thunderclap headache for a few days immediately suggests RCVS, as does convexity subarachnoid haemorrhage. The disorder should also be suspected in patients with cryptogenic stroke, especially when the patient also has headache.2, 8, 33, 37, 66 RCVS with stroke but minimum or even absent headache probably can occur.34 The diagnostic criteria in panel 2 were proposed by experts1, 2 and modified on the basis of the results of the three large case series.7, 8, 9
Transcranial doppler and
Management
Management is guided by observational data and expert opinion. No randomised clinical trials of treatment for RCVS have been done, but early recognition of the syndrome is important so that symptoms can be managed effectively. Patients with consistent clinical and brain imaging features, no evidence for another cause of symptoms, and normal initial cerebral angiograms should be viewed as having possible or probable RCVS, and should receive the same symptomatic treatment as patients with visible
Prognosis
In most patients, headaches and angiographic abnormalities resolve within days or weeks. Long-term prognosis of RCVS is determined by the occurrence of stroke.8, 9 Most patients who have strokes gradually improve for several weeks, and few have residual deficits.2, 5, 7 Less than 5% develop life-threatening forms with several strokes and uncontrolled massive brain oedema.9, 23, 49, 60, 94, 95, 96, 97 The combined case fatality in the three largest studies7, 8, 9 was less than 1%. Intractable
Putative precipitants and associated disorders
Although RCVS can occur spontaneously, especially in middle-aged women,7, 24 at least half the cases occur after exposure to vasoactive drugs or post partum.2, 5, 6, 9, 12, 17, 18, 22, 28, 29, 30, 33, 34, 41, 48, 50, 52, 53, 59, 86, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107 Women are more susceptible to RCVS than are men, in whom exposure to several vasoactive drugs, and sometimes binging on cannabis and alcohol, is often required for the disorder to develop.5, 34 Panel 4 lists the
Postulated pathological mechanisms
Unpredictable and transient failure of regulation of cerebral arterial tone with sympathetic overactivity seems to have a role in the development of RCVS.2, 3 In susceptible people—eg, middle-aged women, who frequently present with RCVS without any known precipitant or trigger5—deregulation of vascular tone could result from spontaneous neuronal or vascular-driven discharge.3
A proposed anatomical explanation for both the vasoconstriction and the headache of RCVS is that cerebral arteries are
Conclusions and future directions
RCVS affects patients of all ages and has a female preponderance. The syndrome should be suspected in any patient who presents with recurrent thunderclap headaches or cryptogenic stroke, especially post partum or after the use of vasoactive drugs. Diagnosis is easy and an important step in the care of patients with RCVS. Despite the absence of a proven treatment, important steps should be taken during the acute phase—ie, removal of precipitants such as vasoactive substances, putting the patient
Search strategy and selection criteria
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