Elsevier

The Lancet Neurology

Volume 11, Issue 10, October 2012, Pages 906-917
The Lancet Neurology

Review
Reversible cerebral vasoconstriction syndrome

https://doi.org/10.1016/S1474-4422(12)70135-7Get rights and content

Summary

Recurrent thunderclap headaches, seizures, strokes, and non-aneurysmal subarachnoid haemorrhage can all reveal reversible cerebral vasoconstriction syndrome. This increasingly recognised syndrome is characterised by severe headaches, with or without other symptoms, and segmental constriction of cerebral arteries that resolves within 3 months. Reversible cerebral vasoconstriction syndrome is supposedly due to a transient disturbance in the control of cerebrovascular tone. More than half the cases occur post partum or after exposure to adrenergic or serotonergic drugs. Manifestations have a uniphasic course, and vary from pure cephalalgic forms to rare catastrophic forms associated with several haemorrhagic and ischaemic strokes, brain oedema, and death. Diagnosis can be hampered by the dynamic nature of clinicoradiological features. Stroke can occur a few days after initial normal imaging, and cerebral vasoconstriction is at a maximum on angiograms 2–3 weeks after clinical onset. The calcium channel blocker nimodipine seems to reduce thunderclap headaches within 48 h of administration, but has no proven effect on haemorrhagic and ischaemic complications.

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

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

References (139)

  • Y Ruzic et al.

    Intracerebral haemorrhage and postpartum cerebral angiopathy associated with the administration of sulprostone and norepinephrine

    Ann Fr Anesth Reanim

    (2012)
  • The international classification of headache disorders

    Cephalalgia

    (2004)
  • LH Calabrese et al.

    Narrative review: reversible cerebral vasoconstriction syndromes

    Ann Intern Med

    (2007)
  • DW Dodick et al.

    Nonaneurysmal thunderclap headache with diffuse, multifocal, segmental, and reversible vasospasm

    Cephalalgia

    (1999)
  • SP Chen et al.

    Recurrent primary thunderclap headache and benign CNS angiopathy: spectra of the same disorder?

    Neurology

    (2006)
  • A Ducros et al.

    The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome: a prospective series of 67 patients

    Brain

    (2007)
  • AB Singhal et al.

    Cerebral vasoconstriction and stroke after use of serotonergic drugs

    Neurology

    (2002)
  • SP Chen et al.

    Magnetic resonance angiography in reversible cerebral vasoconstriction syndromes

    Ann Neurol

    (2010)
  • A Ducros et al.

    Hemorrhagic manifestations of reversible cerebral vasoconstriction syndrome: frequency, features, and risk factors

    Stroke

    (2010)
  • AB Singhal et al.

    Reversible cerebral vasoconstriction syndromes: analysis of 139 cases

    Arch Neurol

    (2011)
  • BD Snyder et al.

    Isolated benign cerebral vasculitis

    Arch Neurol

    (1978)
  • M Serdaru et al.

    Isolated benign cerebral vasculitis or migrainous vasospasm?

    J Neurol Neurosurg Psychiatry

    (1984)
  • P Rousseaux et al.

    Acute benign cerebral angiopathy: 6 cases

    Presse Med

    (1983)
  • GK Call et al.

    Reversible cerebral segmental vasoconstriction

    Stroke

    (1988)
  • DA Nowak et al.

    Reversible segmental cerebral vasoconstriction (Call-Fleming syndrome): are calcium channel inhibitors a potential treatment option?

    Cephalalgia

    (2003)
  • M Razavi et al.

    CNS pseudovasculitis in a patient with pheochromocytoma

    Neurology

    (1999)
  • LH Calabrese et al.

    Benign angiopathy: a distinct subset of angiographically defined primary angiitis of the central nervous system

    J Rheumatol

    (1993)
  • RA Hajj-Ali et al.

    Benign angiopathy of the central nervous system: cohort of 16 patients with clinical course and long-term followup

    Arthritis Rheum

    (2002)
  • AB Singhal

    Postpartum angiopathy with reversible posterior leukoencephalopathy

    Arch Neurol

    (2004)
  • M Jackson et al.

    Migraine angiitis precipitated by sex headache and leading to watershed infarction

    Cephalalgia

    (1993)
  • SR Lu et al.

    Nimodipine for treatment of primary thunderclap headache

    Neurology

    (2004)
  • BB Worrall et al.

    Herbal energy drinks, phenylpropanoid compounds, and cerebral vasculopathy

    Neurology

    (2005)
  • N Marshall et al.

    MRA captures vasospasm in fatal migrainous infarction

    Headache

    (2007)
  • SP Chen et al.

    Transcranial color doppler study for reversible cerebral vasoconstriction syndromes

    Ann Neurol

    (2008)
  • A Kirton et al.

    A pediatric case of reversible segmental cerebral vasoconstriction

    Can J Neurol Sci

    (2006)
  • HY Liu et al.

    Three paediatric patients with reversible cerebral vasoconstriction syndromes

    Cephalalgia

    (2010)
  • SJ Wang et al.

    Bath-related thunderclap headache: a study of 21 consecutive patients

    Cephalalgia

    (2008)
  • BL Edlow et al.

    Reversible cerebral vasoconstriction syndrome associated with subarachnoid hemorrhage

    Neurocrit Care

    (2007)
  • CP Marder et al.

    Multimodal imaging of reversible cerebral vasoconstriction syndrome: a series of 6 cases

    AJNR Am J Neuroradiol

    (2012)
  • M Arnold et al.

    Postpartum cervicocephalic artery dissection

    Stroke

    (2008)
  • AB Singhal

    Cerebral vasoconstriction syndromes

    Top Stroke Rehabil

    (2004)
  • V Wolff et al.

    Cannabis use, ischemic stroke, and multifocal intracranial vasoconstriction: a prospective study in 48 consecutive young patients

    Stroke

    (2011)
  • SA Ansari et al.

    Reversible cerebral vasoconstriction syndromes presenting with subarachnoid hemorrhage: a case series

    J Neurointerv Surg

    (2011)
  • MR Ursell et al.

    Recurrent intracranial hemorrhage due to postpartum cerebral angiopathy: implications for management

    Stroke

    (1998)
  • C Spitzer et al.

    Non-traumatic cortical subarachnoid haemorrhage: diagnostic work-up and aetiological background

    Neuroradiology

    (2005)
  • RR Moustafa et al.

    Call-Fleming syndrome associated with subarachnoid haemorrhage: three new cases

    J Neurol Neurosurg Psychiatry

    (2008)
  • K Noda et al.

    Reversible cerebral vasoconstriction syndrome presenting as subarachnoid hemorrhage, reversible posterior leukoencephalopathy, and cerebral infarction

    Intern Med

    (2011)
  • M Soltanolkotabi et al.

    Spontaneous post-partum cervical carotid artery dissection in a patient with reversible cerebral vasoconstriction syndrome

    Interv Neuroradiol

    (2011)
  • S Yoshioka et al.

    A pediatric case of reversible cerebral vasoconstriction syndrome with cortical subarachnoid hemorrhage

    Brain Dev

    (2012)
  • SH Wong et al.

    Recurrent thunderclap headaches and multilobar intracerebral haemorrhages: two cases of reversible cerebral vasoconstriction syndrome (RCVS)

    Cephalalgia

    (2009)
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