Reversible cerebral vasoconstriction syndromes

Aneesh B Singhal MD (Dr. Singhal of Harvard Medical School received consutling fees from Biogen, Dock Technologies, and Medicolegal for consulting, owns stock in Biogen, and receives research support from Boehringer Ingelheim.)
Steven R Levine MD, editor. (Dr. Levine of the SUNY Health Science Center at Brooklyn has received honorariums from Genentech for service on a scientific advisory committee and a research grant from Genentech as a principal investigator.)
Originally released December 16, 2003; last updated August 25, 2015; expires August 25, 2018

This article includes discussion of reversible cerebral vasoconstriction syndromes, benign angiopathy of the central nervous system, benign cerebral vasculitis, Call syndrome, Call-Fleming syndrome, cerebral pseudovasculitis, cerebral Raynaud phenomenon, migraine angiitis, migrainous vasospasm, postpartum angiopathy, RCVS, reversible angiitis, and reversible cerebral angiopathy. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Reversible cerebral vasoconstriction syndromes are characterized by recurrent, severe “thunderclap” headaches and multifocal cerebral arterial narrowing and dilatation, often complicated by ischemic or hemorrhagic strokes or reversible brain edema. Reversible cerebral vasoconstriction syndromes affect young individuals, mostly women, and have been associated with diverse conditions such as pregnancy, migraine, vasoconstrictive drug use, pheochromocytoma, and neurosurgical procedures. Until recently, reversible cerebral vasoconstriction syndromes were considered rare and were frequently misdiagnosed as primary angiitis of the CNS because of overlapping clinical-angiographic features. With the publication of comprehensive review articles and large case series and the advent of relatively noninvasive diagnostic tests such as CT-angiography and MR-angiography, reversible cerebral vasoconstriction syndromes are being recognized and diagnosed more frequently. In this article, the author provides a comprehensive overview of reversible cerebral vasoconstriction syndromes.

Key points

 

• Reversible cerebral vasoconstriction syndromes (RCVS) are an instantly recognizable. They have distinct clinical, laboratory, imaging, and angiographic features that allow easy diagnosis and distinction from mimics such as cerebral vasculitis and ruptured brain aneurysms.

 

• Most patients present with recurrent thunderclap headaches. Ischemic stroke, brain hemorrhage, and cerebral edema can develop in approximately 35% to 40% of patients within the first 1 to 3 weeks, but approximately 95% of patients have benign 3-month outcomes with little or no residual neurologic deficits.

 

• Because the natural history of reversible cerebral vasoconstriction syndrome is spontaneous resolution within a few weeks, simple observation with liberal pain control and avoidance of physical exertion is usually adequate. Calcium-channel blockers may reduce the intensity of headaches. Glucocorticoids should be avoided. Intraarterial vasodilator therapy should be reserved for the rare patient with unrelenting clinical progression.

Historical note and terminology

Angiographic narrowing of intracerebral arteries usually results from pathological conditions such as atherosclerosis, inflammatory vasculitis, infectious arteritis, and fibromuscular dysplasia. Reversible cerebral arterial vasoconstriction has been considered a rare phenomenon, except when associated with aneurysmal subarachnoid hemorrhage (“vasospasm”). However, over the last 6 decades, numerous case reports have documented reversible multifocal cerebral vasoconstriction on serial angiography in patients without aneurysmal subarachnoid hemorrhage and without evidence for infection or inflammation. Descriptions of this phenomenon date back to the 1960s (Armstrong and Hayes 1961; Buckle 1964; Rascol 1979). Reversible cerebral vasoconstriction has been associated with diverse conditions including the postpartum state, use of vasoconstrictive drugs, migraine, thunderclap headache, other primary headaches, cerebral trauma, and hypertensive encephalopathy, among others (Table 1).

Table 1. Precipitating Factors Associated with Cerebral Vasoconstriction Syndromes

(A) Pregnancy and puerperium

Early puerperium, late pregnancy, eclampsia, pre-eclampsia, delayed post-partum eclampsia

(B) Exposure to drugs
and blood products

Phenylpropanolamine, pseudoephedrine, phenylephrine, epinephrine, ergotamine tartrate, methylergonovine, bromocriptine, hydroxycut, lisuride, selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenaline reuptake inhibitors (SNRIs), sumatriptan and other triptans, isometheptene, indomethacin, etoricoxib, cocaine, ecstasy, amphetamine derivatives, marijuana, lysergic acid diethylamide, tacrolimus (FK-506), cyclophosphamide, erythropoietin, intravenous immune globulin (IVIg), interferon alpha, nicotine patches, red blood cell transfusions, licorice, oral contraceptive pills, hormonal agents

(C) Miscellaneous

Hypercalcemia, porphyria, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, pheochromocytoma, bronchial carcinoid tumor, unruptured saccular cerebral aneurysm, head trauma, spinal subdural hematoma, post-carotid endarterectomy, neurosurgical procedures, carotid glomus tumor, tonsillectomy, neck surgery, high altitude

(D) Idiopathic

No identifiable precipitating factor.

Associated with headache disorders such as migraine, primary thunderclap headache, benign exertional headache, benign sexual headache, primary cough headache

Given the diversity of the associated conditions, patients with these syndromes have been described in the literature using variable nosology. For example, “migrainous vasospasm” (Serdaru et al 1984) or “migraine angiitis” (Jackson et al 1993) for patients with prior migraine; “postpartum angiopathy” (Rascol 1979; Bogousslavsky et al 1989; Raroque et al 1993) when associated with pregnancy or puerperium; and “drug-induced vasculitis” (Kaye and Fainstat 1987) when associated with drug exposure. At the 1987 Boston Stroke Society meeting, Marie Fleming presented 2 patients with reversible cerebral vasoconstriction. The following year Drs. Call, Fleming, C Miller Fisher, and others described these patients and several additional personal cases in a series titled “Reversible Cerebral Segmental Vasoconstriction” (Call et al 1988). Over the past decade, Singhal and others have recognized that despite the wide range of associated conditions and varied nosology, these patients have an easily recognizable clinical-imaging syndrome characterized by severe headaches and reversible cerebral angiographic abnormalities, often complicated by seizures and ischemic or hemorrhagic stokes. Consequently, these syndromes are now collectively referred to as “reversible cerebral vasoconstriction syndromes” (RCVS) (Singhal et al 2001; Singhal 2004; Singhal and Bernstein 2005; Calabrese et al 2007; Ducros et al 2007; Chen et al 2008; Ducros et al 2010; Singhal et al 2011; Ducros 2012; Yancy et al 2013; Singhal 2014). It is conceivable that individual entities still have some unique features.

Historically, patients with reversible cerebral vasoconstriction syndromes have been misinterpreted as having primary angiitis of the central nervous system due to overlapping clinical-imaging features such as headache, stroke, and angiographic abnormalities (Snyder and McClelland 1978; Bettoni et al 1984; van Calenbergh et al 1986). Before the recent recognition of reversible cerebral vasoconstriction syndromes, primary angiitis of the central nervous system had become recognized and accepted as a devastating and potentially fatal inflammatory condition that warranted aggressive treatment with immunosuppressive agents (Calabrese et al 1997). Segmental narrowing of intracranial arteries was believed to be the “typical” angiographic feature of PACNS. Among patients with PACNS, there emerged a subset of patients who had an unusually benign clinical course and prompt resolution of angiographic abnormalities without prolonged immunosuppressive therapy. Calabrese and colleagues classified these patients as “benign angiopathy of the CNS” (BACNS) and noted that they were usually diagnosed solely on the basis of angiographic abnormalities, without supporting evidence for inflammation on tests like CSF examination or brain biopsy (Calabrese et al 1993). Their group has analyzed the clinical characteristics and long-term outcomes of BACNS and concluded that it is probably a vasoconstrictive rather than a vasculitic condition (Hajj-Ali et al 2002). Severe and prolonged vasoconstriction can induce secondary inflammation, making the distinction between vasculitis and vasoconstriction extremely difficult in some cases (Calado et al 2004).

The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.

If you are a subscriber, please log in.

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.

If you have never registered before, click Learn More about MedLink Neurology  or view available Service Plans.