Topical Review
Reversible Cerebral Vasoconstriction Syndrome
A Diagnostic Imaging Review
Tina M. Burton, MD; Cheryl D. Bushnell, MD, MHS
R eversible cerebral vasoconstriction syndrome (RCVS) is
used to describe a multitude of pathologies encompass-
ing the clinical terms Call-Fleming syndrome, thunderclap
headache (TCH) with reversible vasospasm, benign angiopa-
thy of the central nervous system, postpartum angiopathy,
migrainous vasospasm or migraine angiitis, drug-induced ce-
rebral arteritis or angiopathy, and sexual headache.1 RCVS is
diagnosed based on key clinical features of TCH (reaching
peak intensity within ≤1 minute) or severe recurrent head-
ache, cerebral vasoconstriction on imaging in at least 2 differ-
ent arteries and resolution of vasoconstriction by 3 months, in
the absence of primary angiitis of the central nervous system
(PACNS), or aneurysmal subarachnoid hemorrhage (SAH).
In a 2018 study comparing 110 patients with PACNS to 173
patients with RCVS, 70% of RCVS patients had a precipi-
tating factor. Factors listed from most to least common were
cannabis, selective serotonin reuptake inhibitors, nasal decon-
gestants, postpartum, binge alcohol consumption, steroids,
ergots, triptans, cocaine, nicotine patches, noradrenergic and
Downloaded from http://ahajournals.org by on February 23, 2021
selective serotonergic antidepressants, epinephrine, inter-
feron α, cyclosporine, and sulprostone.2 Other precipitants
for RCVS include direct vessel injury via dissection or sur-
gical manipulation, eclampsia, and strenuous physical/sexual
activity (Table 1).3–5 Patients with RCVS compared with
those with PACNS are more commonly women, have a his-
tory of migraine headache, and have a trigger of either vas-
oactive substances, or postpartum. Parenchymal imaging by
computed tomography (CT) or magnetic resonance imaging
(MRI) was abnormal in all PACNS patients and in only 31%
of RCVS patients.2
Although outcomes in RCVS are generally favorable,
complications of posterior reversible encephalopathy syn-
drome (PRES), seizure, hemorrhage, and brain infarction
can occur. When cerebral infarction is identified, important
alternative causes for similar patterns of cortical diffusion
restriction should be considered, including but not limited
to PACNS, inflammatory cerebral amyloid angiopathy, cere-
bral venous thrombosis, Creutzfeldt-Jakob disease, urea cycle
disorders, mitochondrial hypoxic-ischemic encephalopathy,
acute hepatic encephalopathy, leukodystrophy, infection,
Received March 5, 2019; final revision received May 14, 2019; accepted May 31, 2019.
From the Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, RI (T.M.B.); and Department of Neurology,
Wake Forest School of Medicine, Winston Salem, NC (C.D.B.).
Correspondence to Cheryl D. Bushnell, MD, MHS, Department of Neurology, Medical Center Blvd, Wake Forest University Health Sciences, Winston
Salem, NC 27157. Email cbushnel@wakehealth.edu
(Stroke. 2019;50:2253-2258. DOI: 10.1161/STROKEAHA.119.024416.)
© 2019 American Heart Association, Inc.
Stroke is available at https://www.ahajournals.org/journal/str
2253
abscess, and demyelinating disease. Clinical presentation, use
of intravenous contrast agents for imaging, serology and ce-
rebrospinal fluid (CSF) analysis can assist in differentiating
these entities.
Diagnostic imaging continues to advance, introducing
new strategies for identifying, characterizing, and monitoring
vasoconstrictive disease processes. With increasing aware-
ness, recognition of RCVS is growing; however, estimates of
the incidence range widely from 7% to 54%.1,5,6 This review
serves as a summary of current imaging modalities used in the
diagnosis and management of RCVS (Table 2).
Methods
Literature review was done via PubMed, without date limitations,
with the search terms: reversible cerebral vasoconstriction, RCVS,
Call-Fleming syndrome, TCH, benign angiopathy of the central
nervous system, postpartum angiopathy, migrainous vasospasm, mi-
graine angiitis, drug-induced cerebral arteritis or angiopathy, and
sexual headache. Articles were limited to those published in English
and were included if diagnostic imaging was a prominent feature of
the article. Publications with larger sample sizes and prospectively
collected data were selected preferentially to case reports/series and
retrospective chart reviews, which eliminated studies before 1989.
Diagnostic Imaging
There are multiple imaging modalities used in the diagnosis, monitor-
ing, and management of RCVS. Luminal and parenchymal biomark-
ers of RCVS have been established, whereas other imaging findings
bare associations in the context of the clinical diagnostic criteria
for RCVS. Vasoconstriction can be difficult to detect in very distal
branches and may be delayed up to a week, which can make the diag-
nosis by vessel imaging alone challenging.5 Many indirect biomark-
ers of cerebral vasoconstriction remain experimental and identify
changes in flow dynamics, metabolic demand, and cellular insults.
Selection of imaging modality is often based on diagnostic yield, ac-
cessibility, and safety profile, as outlined below.
Digital Subtraction Angiography
Cerebral catheter digital subtraction angiography (DSA) is considered
the gold standard in visualizing vasoconstriction and detecting abnor-
malities, especially in distal vessels with a sensitivity of 100% with
2-dimensional DSA (Figure, case example).7,8 DSA has additional ben-
efits of intervention with intraarterial injection of therapeutic agents
and ability to verify response.9,10 However, DSA is often deferred if
DOI: 10.1161/STROKEAHA.119.024416
 2254  Stroke  August 2019

Table 1.  RCVS Clinical Findings Table 2.  Imaging Modalities in RCVS

Clinical characteristics Modality Advantages Disadvantages

 Thunderclap headache/severe recurrent headache DSA Visualization of distal Complication risk
vessels
 Cerebral vasoconstriction in at least 2 different arteries
Dynamic study Contrast exposure
 Resolution of vasoconstriction by 3 mo
Intraarterial therapy Less accessible
Common precipitants
CTA Noninvasive Lower distal vessel
 Cannabis, binge alcohol consumption, cocaine
sensitivity
 Selective serotonin reuptake inhibitors, noradrenergic and selective
Accessible Contrast and radiation
serotonergic antidepressants, nasal decongestants, steroids, ergots,
exposure
triptans, nicotine patches, epinephrine, interferon alpha, cyclosporine,
sulprostone MRA Noninvasive Lower distal vessel
sensitivity
 Postpartum, vascular dissection, surgical manipulation
Relatively accessible (1.5T) MRI compatible devices only
Complications/associated imaging findings
±Gadolinium contrast
 Posterior reversible encephalopathy syndrome, convexity subarachnoid
exposure
hemorrhage, intracerebral hemorrhage, ischemic infarction, seizure
RCVS indicates reversible cerebral vasoconstriction syndrome. Less accessible at high
resolution (3T, 7T)
vasoconstriction is identified on noninvasive testing and the patient CE-FLAIR BBB breakdown found in MRI compatible devices only
is clinically stable or improving. DSA may be reserved as the defini- neurological complications
Contrast exposure
tive imaging modality when RCVS is strongly suspected or a patient of RCVS
worsens, and noninvasive methods have been unrevealing. Although
Relatively accessible (1.5T) Present in only 69% of 29
complications of DSA specific to RCVS patients have not yet been
clearly identified, general cerebrovascular complications include, but RCVS cases based on single-
are not limited to stroke, transient ischemic attack, arterial dissection, center study
and vessel perforation with or without subsequent SAH. In a single- TCD Safe Bone window dependent
center, prospectively collected database of 3636 patients undergoing
cerebral angiography (diagnostic only), from 2001 to 2007, there Cost-effective Isolated to carotid, vertebral,
were a total of 11 complications (0.3%). One patient (0.03%) had basilar, MCA, ACA, PCA flow
velocities
Downloaded from http://ahajournals.org by on February 23, 2021

an asymptomatic infarction identified on routine MRI, 5 arteries had

iatrogenic dissections (0.14%), and 5 patients had nonneurological lower sensitivity
complications of femoral abscess, femoral artery occlusion with leg
ischemia, dissection with pseudoaneurysm formation, and retroperi- Can also assess CVR Less accessible
toneal hemorrhage (0.14%). There was increased risk of complication MR Potential early biomarker MRI compatible devices only
in patients >65 years old.11 Another study used the National Inpatient perfusion when vasoconstriction is
Sample from 1999 to 2009 to analyze 424 105 primary cerebral angi- Contrast exposure
absent
ography discharges and found an embolic stroke complication rate of
3.84% and increased risk of this complication in patients >55 years May predict tissue at risk Less accessible
old.12 A more recent single-center study of 644 patients from 2011 ASL Potential early biomarker MRI compatible devices only
to 2014 undergoing cerebral angiography (diagnostic and therapeutic) perfusion when vasoconstriction is
for SAH, ischemic stroke, or intracranial lesion evaluation had a neu- absent
rological complication rate of 0.062%. The most common compli-
cation was groin hematoma in 1.55% of patients. Contrast-induced May predict tissue at risk Less accessible
nephropathy was identified in 6 of 120 patients screened (5%).13
No contrast exposure
Computed Tomography MR-VWI May help distinguish MRI compatible devices only
CT for brain parenchymal imaging and CT angiography (CTA) for RCVS from PACNS and
luminal imaging are often the first diagnostic images obtained in most Less accessible (3T)
intracranial atherosclerosis
emergency departments due to greater accessibility compared with
DSA and magnetic resonance angiography (MRA) and as part of the ACA indicates anterior cerebral arteries; ASL, arterial spin labeling; BBB,
emergent evaluation for SAH in patients with TCH. Compared with blood-brain barrier; CE-FLAIR, contrast-enhanced fluid-attenuated inversion
the gold standard, CTA and MRA both share a detection sensitivity of recovery; CTA, computed tomography angiography; CVR, cerebral vasomotor
≈80% in RCVS-related cerebral vasoconstriction.7,9,14 Although CTA reactivity; DSA, digital subtraction angiography; MCA, middle cerebral artery;
is faster and less prone to motion artifact, the risk of radiation expo- MR, magnetic resonance; MRA, magnetic resonance angiography; MRA,
sure and iodinated contrast may indicate preferential use of MRI and magnetic resonance angiography; MRI, magnetic resonance imaging; MR-VWI,
MRA. Based on the American College of Radiology expert opinion, in magnetic resonance vessel wall imaging; PACNS, primary angiitis of the central
emergent settings without other alternatives, if the benefit outweighs nervous system; PCA, posterior cerebral artery; RCVS, reversible cerebral
the risk of radiation and contrast dye, CTA may be considered, even in vasoconstriction syndrome; and TCD, transcranial Doppler.
select populations, such as pregnant and renal insufficiency patients.15
CT and CTA can effectively screen for nonaneurysmal cortical/
convexity SAH, an early parenchymal biomarker of RCVS when angiopathy, and cerebral venous thrombosis. Other nontraumatic
capture of vasoconstriction lags.16 Nontraumatic SAH in RCVS fol- SAH patterns not associated with RCVS are diffuse and perimes-
lows a characteristic pattern of focal cortical subarachnoid blood encephalic. Diffuse SAH is associated with aneurysms and vascular
in high convexity sulci. Other entities that must be considered in malformations. Perimesencephalic SAH is usually idiopathic but can
nontraumatic convexity SAH include PRES, cerebral amyloid be associated with vertebrobasilar aneurysm rupture, or more rarely
 Burton and Bushnell   RCVS: A Diagnostic Imaging Review   2255
Figure.  Digital subtraction angiogram of a 43-y-old woman with reversible cerebral vasoconstriction syndrome attributed to selective serotonin reuptake
inhibitors and pseudoephedrine use. A, Diffuse intracerebral vasoconstriction on initial angiogram, after 2 wk of headache then right hemiparesis and enceph-
alopathy. B, Resolution of vasoconstriction after 4 mo.
with acute dissection, vascular malformation, or cervicomedullary
junction tumor.17,18
Magnetic Resonance
When available, MRA and MRI are the luminal and parenchymal im-
aging modalities of choice, respectively. Gadolinium contrast agents
are typically unnecessary in the evaluation for RCVS; however, if
concern for an infectious or inflammatory process is on the differ-
ential, contrast may enhance diagnostic yield. MRA is noninvasive
compared with DSA and has similar sensitivity to CTA in detecting
cerebral vasospasm while sparing the patient radiation and contrast
exposure; however, addition of gadolinium can improve MRA quality.
MRA can also identify cervical arterial dissection, which has been as-
Downloaded from http://ahajournals.org by on February 23, 2021
sociated with RCVS.3 Additionally, patterns of luminal narrowing on
MRA may have prognostic value. In 1 study, the combination of M1
and P2 constriction showed the highest risk for development of PRES
and ischemic stroke in patients with RCVS (odds ratio, 11.6; 95% CI,
2.06–67.85; P=0.005).19
Presence of hyperintense vessels (HVs) on MRI fluid-attenu-
ated inversion recovery have been hypothesized to be a biomarker
for RCVS because they are a result of abnormal flow in small ves-
sels. They have been seen in disease processes that result in cere-
bral arterial occlusion, such as stroke, and pathology that results in
severe arterial stenosis, such as atherosclerosis and Moyamoya.20,21
In a study of 95 patients with RCVS, 22.1% had HVs with signifi-
cantly higher middle cerebral artery (MCA) and posterior cerebral
artery flow velocities and Lindegaard index on transcranial Doppler
(TCD), in addition to complications of PRES and ischemic stroke.22
Case reports have shown findings of HVs preceding detection of vas-
oconstriction.23,24 One report was of a 30-year-old woman present-
ing with severe, acute-onset headache, seizure, and bilateral vision
loss. She had distal HVs and normal MRA on early imaging and was
given nicardipine, phenytoin, and glycerol infusion with clinical im-
provement. MRI 7 days later showed HV resolution and MRA with
multifocal segmental stenoses of the basilar artery, posterior cerebral
arteries, and anterior cerebral arteries. Complete resolution was seen
on day 16 of MRA.23 HVs have been hypothesized to predate the
appearance of cerebral vasoconstriction on vessel imaging and may
be supportive of the centripetal propagation theory, which hypoth-
esizes that vasoconstriction starts at the smallest and most distal ves-
sels of a cerebrovascular bed and migrates more proximally to the
larger vessels supplying that territory.20,25
Although still experimental, the noninvasive method of using
MR–vessel wall imaging (VWI) may be helpful in distinguishing
between different pathologies that contribute to intracerebral vessel
constriction in RCVS, systemic vasculitis, PACNS, and atheroscle-
rotic disease. In a small study published in 2012, 3 of 7 patients
with segmental vasoconstriction diagnosed with RCVS had arte-
rial wall thickening with absent to minimal enhancement of vessel
walls compared with more pronounced enhancement due to other
pathologies (biopsy confirmed giant cell arteritis, biopsy-identified
sarcoidosis, central nervous system vasculitis by CSF, cocaine vas-
culopathy).26 Another study evaluated 118 lesions in 29 patients
using both T1 and T2 weighted VWI with and without contrast (21
intracranial atherosclerotic disease [ICAD], 4 RCVS, 4 PACNS). T2
hyperintensity was more commonly seen in ICAD compared with
RCVS and vasculitis. Wall thickness analysis on T1 imaging showed
that ICAD was more likely to have eccentric arterial wall thickening
compared with RCVS and vasculitis. On T1 postcontrast enhance-
ment, ICAD and vasculitis lesions showed higher intensity of con-
trast enhancement (grade 1 and 2) compared with RCVS (grade 0
and 1).27 Another study in Taiwan evaluated 48 RCVS patients with
T1-weighted pre and postintravenous gadolinium VWI. Marked en-
hancement was found in ≈10% of patients and mild enhancement
in ≈35%. Those with vessel wall enhancement had fewer headache
attacks, and vessel wall enhancement was persistent in ≈10% of
patients at up to 7 months.28 There is some evidence to suggest that
luminal imaging in conjunction with VWI can improve differentia-
tion of RCVS from other pathologies that cause nonocclusive cere-
brovascular stenosis, such as ICAD and vasculitis.27
MRI provides important information on brain parenchymal injury
and should be obtained in patients with suspected RCVS. Diffusion
restriction is often cortical and can be multifocal. Differential con-
siderations include, but are not limited to, Creutzfeldt-Jakob disease
(cortical ribboning, ±multifocal), inflammatory cerebral amyloid
angiopathy (lobar/cortical), cerebral venous thrombosis with infarc-
tion (multifocal, does not respect arterial boundaries), cerebral contu-
sion (frontotemporal predominance), herpes simplex virus (temporal
predominance), demyelinating disease (periventricular, ±multifocal),
abscess (contrast enhancing), toxoplasmosis (contrast enhancing),
carbon monoxide toxicity (deep and cortical), hypoxic-ischemic
injury (deep and cortical), ethylene glycol toxicity (cortical), hypo-
glycemia (cortical and deep), hyperammonemia (cortical and deep),
urea cycle disorders (cortical), mitochondrial hypoxic-ischemic en-
cephalopathy (cortical and deep), acute hepatic encephalopathy (cor-
tical and deep), and leukodystrophy (subcortical white matter).29
Absence of TCH and typical RCVS triggers would indicate the need
to broaden the differential diagnosis. Characteristic clinical presenta-
tions may guide further workup.
Blood-brain barrier (BBB) breakdown is another proposed
mechanism of RCVS, given the pathophysiological mechanisms
of sympathetic overactivity and dysregulation of cerebrovascular
tone. In a study of 29 definite RCVS patients, 69% had BBB break-
down on contrast-enhanced fluid-attenuated inversion recovery.
Neurological complications of PRES, infarct, focal neurological
deficit, seizure, and cortical SAH were only seen in patients with
BBB breakdown.30 Currently, the role of BBB imaging in RCVS
patients remains speculative.
 2256  Stroke  August 2019
Perfusion imaging may prove to be a useful approach in identi-
fying cerebral hypoperfusion secondary to cerebral vasoconstriction,
though evidence for its utility is currently limited to case reports.4,31
MR perfusion studies may be useful in initial stages, but timing and
frequency of serial imaging would be dependent on cumulative expo-
sure to gadolinium. Arterial spin labeling (ASL) MRI is a noninvasive
method of visualizing cerebral perfusion without the need for contrast
dye. In a case report, ASL was used to identify cerebral hypoperfu-
sion distal to regions of vasoconstriction on MRA with clinical and
radiographic improvement after treatment with verapamil. On day
16, there was significant improvement in cerebral perfusion on re-
peat ASL, with only minimal residual vasoconstriction on MRA.31
However, ASL has been shown to correlate best with time-to-peak
and may overestimate hypoperfusion when compared with dynamic
susceptibility contrast Tmax.32 Perfusion studies remain experimental
in the evaluation of RCVS.
Transcranial Doppler
Dynamic vessel imaging with TCD is abnormal in 69% to 81% of
RCVS cases.5,33 The sensitivity of TCD in detecting vasospasm is
currently based on data from aneurysmal SAH patients, and it is un-
clear whether these data should be applied to RCVS patients. In a
vessel-specific meta-analysis, TCD compared with DSA to assess va-
sospasm had an MCA sensitivity of 67% (95% CI, 48–87) based on
5 studies, and anterior cerebral artery sensitivity was 42% (95% CI,
11–72) based on 3 studies.8 TCD may also provide some prognostic
value. In a study of 32 patients, the risk of PRES or ischemic stroke
was higher with MCA mean flow velocity >120 m/s and MCA to
extracranial ICA ratio (Lindegaard index) >3.33 TCD, as a dynamic
and noninvasive diagnostic tool, provides a safe way to monitor for
response to pharmacological therapies and resolution of vasocon-
striction.34 TCD can also assess cerebral vasomotor reactivity, which
measures changes in arterial blood flow velocities in response to
carbon dioxide levels. Distal arterioles dilate when cerebral blood
flow is reduced; then when challenged by increased arterial carbon
Downloaded from http://ahajournals.org by on February 23, 2021
dioxide, their capacity for further dilation is reduced and thus a re-
duction in cerebral vasomotor reactivity. Breath Holding Index was
reduced in nearly all patients with RCVS, indicating a steal phe-
nomenon, which could explain watershed infarction patterns seen in
patients with RCVS.35
Longitudinal Monitoring
RCVS can be monitored over time using the luminal imaging modali-
ties as described above and would ideally compare the same modali-
ties for complications, recurrence, and resolution. However, repeat
imaging should prioritize diagnostic yield balanced with safety pro-
file, accessibility, and cost (Table 3). TCD is a low-cost and low-risk
option, but may not be available at many medical centers and has
lower sensitivity compared with other imaging modalities.8,36,37 In a
study of 77 patients, 8% had reversible vasoconstriction recurrence
over a median follow-up time of 25 months, all accompanied by clin-
ical symptoms of recurrent TCH.19
Discussion
The diagnosis of RCVS is based on clinical presentation,
trigger identification, reversible vasoconstriction in ≥2 ves-
sels, with serology and CSF analysis differentiating it from
vasculitis. Ideally, diagnostic imaging supports or refutes the
diagnosis of RCVS. However, despite advancements in im-
aging, some patients with suspected RCVS may never have
direct imaging evidence of vasoconstriction. Some may argue
that RCVS can be diagnosed on clinical symptoms alone, and
patients should be spared the costly and invasive methods
for an imaging diagnosis. Recently, a diagnostic score, the
RCVS2, was developed to improve accuracy in RCVS diag-
nosis. The score was defined by R (recurrent or single TCH,
positive predictor), C (carotid intracranial artery involvement,
Table 3.  RCVS Longitudinal/Follow-Up Imaging
Modality Sensitivity Considerations
Digital subtraction 100% Invasive, complication risk
angiography
Computed tomography 80% Radiation and contrast exposure
angiography
Magnetic resonance 80% Can be paired with parenchymal
angiography imaging
No contrast or radiation exposure
Transcranial Doppler 42%–67% Low sensitivity and vessel-
dependent
If identified, can be reliably
measured
RCVS indicates reversible cerebral vasoconstriction syndrome.
negative predictor), V (vasoconstrictive trigger, positive pre-
dictor), and S (sex and SAH, positive predictors) with scores
ranging from −2 to +10 and +10 being the highest likelihood of
RCVS diagnosis. It found that TCH and vasoconstrictive trig-
gers increased diagnostic yield. RCVS2 scores ≥5 were 90%
sensitive and 99% specific to RCVS as a diagnosis compared
with non-RCVS diagnoses, particularly PACNS.38 However,
patients with RCVS do not always present with TCH and have
been identified based on reversible angiographic findings and
exclusion of PACNS.39 Therefore, the combination of both
clinical history and diagnostic imaging remains crucial to not
only include a diagnosis of RCVS but also to exclude alterna-
tive diagnoses that require different treatment strategies.
Although outcomes in RCVS are generally favorable, ad-
verse events are not uncommon, including parenchymal in-
jury. When brain parenchymal imaging is abnormal, location
and distribution of injury can provide insight into other dif-
ferential diagnoses that should be entertained. When PRES
is identified, RCVS should be considered, but in the absence
of identifiable vasospasm, alternative causes of PRES should
be explored. Additionally, if nontraumatic SAH is identified,
the distribution pattern, vessel imaging, and MRI findings can
inform the diagnosis. When cortical diffusion restriction is
identified, workup should be guided by clinical presentation,
infarct distribution, and further diagnostic testing. Alternative
causes may include, but are not limited to, arterial or venous
stroke, infection, inflammatory conditions, toxic injury, and
metabolic derangements.
Many advancements in diagnostic imaging remain experi-
mental in the evaluation and management of RCVS, including
perfusion imaging, ASL, MR-VWI, and contrast-enhanced
fluid-attenuated inversion recovery for assessment of BBB
breakdown. Applications for these modalities are likely to
be most useful in patients who do not follow the typical be-
nign course of RCVS and may elucidate indicators of clinical
decline or chronic sequelae, such as development of chronic
headache syndromes, cognitive impairment, lasting neurolog-
ical deficits, or alternative diagnoses.
Longitudinal imaging in RCVS typically includes a
3-month luminal imaging evaluation to assess for reversal of
vasoconstriction; however, reversal can happen before this
time point, negating the need for 3-month imaging. Should
 Burton and Bushnell   RCVS: A Diagnostic Imaging Review   2257
vasoconstriction persist, further investigation for other vaso-
constrictive causes is warranted. MR-VWI may have utility in
determining alternative diagnoses for persistent vasoconstric-
tive disease processes. TCD is the safest method for follow-up
vessel imaging, and as long as vasoconstriction was identified
on the initial evaluation, this is a reasonable method of moni-
toring for recovery. In a TCD monitoring study of 15 patients
with RCVS, MCA flow velocities reached a mean peak of 163
cm/s between 3 and 4 weeks after their initial TCH, although
it is unclear if clinical improvement was directly correlated.36
This study suggested that serial imaging may be of benefit up
to 1 month after symptom onset with TCD; however, up to
30% of patients may be excluded from TCD sampling because
of inadequate temporal bone window.40
Currently, if RCVS is suspected in a patient with TCH
the following approach may be taken. CT and CTA brain are
emergently obtained. MRI and MRA may also be obtained
for further evaluation and identification of parenchymal
lesions to support or refute the diagnosis of RCVS. If vas-
oconstriction is not identified by either CTA or MRA, DSA
is obtained. If vasoconstriction is identified, TCD may be
performed to establish a baseline for further serial monitor-
ing. CSF and inflammatory and infectious labs are obtained.
If CSF and labs are unremarkable, RCVS diagnosis is sup-
ported. If the patient worsens, repeat imaging is performed
and may include CT, CTA, MRI, MRA, or TCD. Symptoms
may include new/worsening focal neurological deficit or
worsening headache. In the setting of a new focal neurolog-
ical deficit, it is worthwhile to consider MR or CT perfusion
Downloaded from http://ahajournals.org by on February 23, 2021
imaging to determine if there is tissue at risk or DSA if the
recurrent vasoconstriction may be amenable to intraarterial
therapies, such as local administration of calcium channel
blocker. Outpatient follow-up imaging with MRA, CTA, or
TCD may be performed after resolution of clinical symptoms
to confirm resolution of vasoconstriction or at 3 months if
vasoconstriction is not resolved in the subacute time frame.
If not resolved at 3 months, further diagnostic evaluation, in-
cluding MR-VWI, may be considered to identify other more
insidious or treatable disease processes.
A combination of established and experimental imaging
modalities may be used in the diagnosis and management
of patients that do not follow the typical benign RCVS clin-
ical course. Imaging modality selection should be based on
anticipated diagnostic and therapeutic benefit balanced by
patient-specific safety concerns. Ongoing studies of RCVS
focus on treatment,34 whereas new frontiers in RCVS iden-
tification and monitoring include the use of diagnostic
algorithms, such as RCVS2, combined with newer imaging
modalities such as perfusion imaging, ASL, VWI, contrast-
enhanced fluid-attenuated inversion recovery, and TCD with
vasomotor reactivity.
Disclosures
None.
References
1. Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB. Narrative re-
view: reversible cerebral vasoconstriction syndromes. Ann Intern Med.
2007;146:34–44.
2. de Boysson H, Parienti JJ, Mawet J, Arquizan C, Boulouis G, Burcin C,
et al. Primary angiitis of the CNS and reversible cerebral vasoconstric-
tion syndrome: a comparative study. Neurology. 2018;91:e1468–e1478.
doi: 10.1212/WNL.0000000000006367
3. Mawet J, Boukobza M, Franc J, Sarov M, Arnold M, Bousser MG, et al.
Reversible cerebral vasoconstriction syndrome and cervical artery dis-
section in 20 patients. Neurology. 2013;81:821–824. doi: 10.1212/WNL.
0b013e3182a2cbe2
4. Rosenbloom MH, Singhal AB. CT angiography and diffusion-perfu-
sion MR imaging in a patient with ipsilateral reversible cerebral vas-
oconstriction after carotid endarterectomy. AJNR Am J Neuroradiol.
2007;28:920–922.
5. Ducros A, Boukobza M, Porcher R, Sarov M, Valade D, Bousser MG. The
clinical and radiological spectrum of reversible cerebral vasoconstric-
tion syndrome. A prospective series of 67 patients. Brain. 2007;130(pt
12):3091–3101. doi: 10.1093/brain/awm256
6. Chen SP, Fuh JL, Lirng JF, Chang FC, Wang SJ. Recurrent primary
thunderclap headache and benign CNS angiopathy: spectra of the
same disorder? Neurology. 2006;67:2164–2169. doi: 10.1212/01.
wnl.0000249115.63436.6d
7. Ducros A, Bousser MG. Reversible cerebral vasoconstriction syndrome.
Pract Neurol. 2009;9:256–267. doi: 10.1136/jnnp.2009.187856
8. Mills JN, Mehta V, Russin J, Amar AP, Rajamohan A, Mack WJ.
Advanced imaging modalities in the detection of cerebral vasospasm.
Neurol Res Int. 2013;2013:415960. doi: 10.1155/2013/415960
9. Miller TR, Shivashankar R, Mossa-Basha M, Gandhi D. Reversible
cerebral vasoconstriction syndrome, part 2: diagnostic work-up, im-
aging evaluation, and differential diagnosis. AJNR Am J Neuroradiol.
2015;36:1580–1588. doi: 10.3174/ajnr.A4215
10. Kass-Hout T, Kass-Hout O, Sun CH, Kass-Hout T, Ramakrishnan P,
Nahab F, et al. A novel approach to diagnose reversible cerebral vasocon-
striction syndrome: a case series. J Stroke Cerebrovasc Dis. 2015;24:e31–
e37. doi: 10.1016/j.jstrokecerebrovasdis.2014.08.023
11. Fifi JT, Meyers PM, Lavine SD, Cox V, Silverberg L, Mangla S, et al.
Complications of modern diagnostic cerebral angiography in an ac-
ademic medical center. J Vasc Interv Radiol. 2009;20:442–447. doi:
10.1016/j.jvir.2009.01.012
12. Choudhri O, Schoen M, Mantha A, Feroze A, Ali R, Lawton MT,
et al. Increased risk for complications following diagnostic cere-
bral angiography in older patients: trends from the nationwide inpa-
tient sample (1999-2009). J Clin Neurosci. 2016;32:109–114. doi:
10.1016/j.jocn.2016.04.007
13. Shen J, Karki M, Jiang T, Zhao B. Complications associated with di-
agnostic cerebral angiography: a retrospective analysis of 644 consecu-
tive cerebral angiographic cases. Neurol India. 2018;66:1154–1158. doi:
10.4103/0028-3886.237018
14. Marder CP, Donohue MM, Weinstein JR, Fink KR. Multimodal
imaging of reversible cerebral vasoconstriction syndrome: a se-
ries of 6 cases. AJNR Am J Neuroradiol. 2012;33:1403–1410. doi:
10.3174/ajnr.A2964
15. ACR Manual On Contrast Media Version 10.3, Committee on Drugs
and Constrast Media, 2018. https://www.acr.org/-/media/ACR/Files/
Clinical-Resources/Contrast_Media.pdf. ISBN: 978-1-55903-012-0.
16. Yoon C, Jung S. Cerebral infarction and cortical subarachnoid hem-
orrhage preceded vascular contraction in reversible cerebral vasocon-
striction syndrome patient with hidden breast cancer. Ann Indian Acad
Neurol. 2018;21:220–222. doi: 10.4103/aian.AIAN_440_17
17. Ansari SA, Rath TJ, Gandhi D. Reversible cerebral vasoconstriction
syndromes presenting with subarachnoid hemorrhage: a case series. J
Neurointerv Surg. 2011;3:272–278. doi: 10.1136/jnis.2010.004242
18. Marder CP, Narla V, Fink JR, Tozer Fink KR. Subarachnoid hemor-
rhage: beyond aneurysms. AJR Am J Roentgenol. 2014;202:25–37. doi:
10.2214/AJR.12.9749
19. Chen SP, Fuh JL, Wang SJ, Chang FC, Lirng JF, Fang YC, et al.
Magnetic resonance angiography in reversible cerebral vasoconstriction
syndromes. Ann Neurol. 2010;67:648–656. doi: 10.1002/ana.21951
20. Chen SP, Wang SJ. Hyperintense vessels: an early MRI marker of revers-
ible cerebral vasoconstriction syndrome? Cephalalgia. 2014;34:1038–
1039. doi: 10.1177/0333102414529193
21. El Beltagi AH, El-Sheikh A, El-Saif R, Norbash A. Ivy sign in mildly
symptomatic β-thalassemia intermedia, with development of moyamoya
disease. Neuroradiol J. 2014;27:23–28. doi: 10.15274/NRJ-2014-10003
22. Chen SP, Fuh JL, Lirng JF, Wang SJ. Hyperintense vessels on flair im-
aging in reversible cerebral vasoconstriction syndrome. Cephalalgia.
2012;32:271–278. doi: 10.1177/0333102412437387
 2258  Stroke  August 2019
23. Kameda T, Namekawa M, Shimazaki H, Minakata D, Matsuura T,
Nakano I. Unique combination of hyperintense vessel sign on initial
FLAIR and delayed vasoconstriction on MRA in reversible cerebral
vasoconstriction syndrome: a case report. Cephalalgia. 2014;34:1093–
1096. doi: 10.1177/0333102414529197
24. Murase S, Gon Y, Watanabe A, Todo K, Kohara N, Mochizuki H,
et al. Isolated cortical vasogenic edema and hyperintense ves-
sel signs may be early features of reversible cerebral vasoconstric-
tion syndrome: case reports. Cephalalgia. 2018;38:1207–1210. doi:
10.1177/0333102417731779
25. Shimoda M, Oda S, Hirayama A, Imai M, Komatsu F, Hoshikawa K, et
al. Centripetal propagation of vasoconstriction at the time of headache
resolution in patients with reversible cerebral vasoconstriction syndrome.
AJNR Am J Neuroradiol. 2016;37:1594–1598. doi: 10.3174/ajnr.A4768
26. Mandell DM, Matouk CC, Farb RI, Krings T, Agid R, terBrugge K, et al.
Vessel wall MRI to differentiate between reversible cerebral vasoconstric-
tion syndrome and central nervous system vasculitis: preliminary results.
Stroke. 2012;43:860–862. doi: 10.1161/STROKEAHA.111.626184
27. Mossa-Basha M, Hwang WD, De Havenon A, Hippe D, Balu N, Becker
KJ, et al. Multicontrast high-resolution vessel wall magnetic resonance im-
aging and its value in differentiating intracranial vasculopathic processes.
Stroke. 2015;46:1567–1573. doi: 10.1161/STROKEAHA.115.009037
28. Chen CY, Chen SP, Fuh JL, Lirng JF, Chang FC, Wang YF, et al. Vascular
wall imaging in reversible cerebral vasoconstriction syndrome - a 3-T
contrast-enhanced MRI study. J Headache Pain. 2018;19:74. doi:
10.1186/s10194-018-0906-7
29. Finelli PF. Diagnostic approach to restricted-diffusion patterns on
MR imaging. Neurol Clin Pract. 2012;2:287–293. doi: 10.1212/CPJ.
0b013e318278bee1
30. Lee MJ, Cha J, Choi HA, Woo SY, Kim S, Wang SJ, et al. Blood-
brain barrier breakdown in reversible cerebral vasoconstriction syn-
drome: implications for pathophysiology and diagnosis. Ann Neurol.
2017;81:454–466. doi: 10.1002/ana.24891
31. Komatsu T, Kimura T, Yagishita A, Takahashi K, Koide R.
A case of reversible cerebral vasoconstriction syndrome presenting
with recurrent neurological deficits: evaluation using noninvasive arte-
rial spin labeling MRI. Clin Neurol Neurosurg. 2014;126:96–98. doi:
Downloaded from http://ahajournals.org by on February 23, 2021
10.1016/j.clineuro.2014.08.023
32. Nael K, Meshksar A, Liebeskind DS, Coull BM, Krupinski EA,
Villablanca JP. Quantitative analysis of hypoperfusion in acute stroke:
arterial spin labeling versus dynamic susceptibility contrast. Stroke.
2013;44:3090–3096. doi: 10.1161/STROKEAHA.113.002377
33. Chen SP, Fuh JL, Chang FC, Lirng JF, Shia BC, Wang SJ. Transcranial
color Doppler study for reversible cerebral vasoconstriction syndromes.
Ann Neurol. 2008;63:751–757. doi: 10.1002/ana.21384
34. Marsh EB, Ziai WC, Llinas RH. The Need for a rational approach to
vasoconstrictive syndromes: transcranial Doppler and calcium channel
blockade in reversible cerebral vasoconstriction syndrome. Case Rep
Neurol. 2016;8:161–171. doi: 10.1159/000447626
35. Topcuoglu MA, Chan ST, Silva GS, Smith EE, Kwong KK,
Singhal AB. Cerebral vasomotor reactivity in reversible cerebral
vasoconstriction syndrome. Cephalalgia. 2017;37:541–547. doi:
10.1177/0333102416650706
36. Levin JH, Benavides J, Caddick C, Laurie K, Wilterdink J, Yaghi S, et
al. Transcranial Doppler ultrasonography as a non-invasive tool for diag-
nosis and monitoring of reversible cerebral vasoconstriction syndrome.
R I Med J (2013). 2016;99:38–41.
37. Bogousslavsky J, Despland PA, Regli F, Dubuis PY. Postpartum ce-
rebral angiopathy: reversible vasoconstriction assessed by tran-
scranial Doppler ultrasounds. Eur Neurol. 1989;29:102–105. doi:
10.1159/000116388
38. Rocha EA, Topcuoglu MA, Silva GS, Singhal AB. RCVS2 score
and diagnostic approach for reversible cerebral vasoconstriction
syndrome. Neurology. 2019;92:e639–e647. doi: 10.1212/WNL.
0000000000006917
39. Singhal AB, Hajj-Ali RA, Topcuoglu MA, Fok J, Bena J, Yang D, et al.
Reversible cerebral vasoconstriction syndromes: analysis of 139 cases.
Arch Neurol. 2011;68:1005–1012. doi: 10.1001/archneurol.2011.68
40. Itoh T, Matsumoto M, Handa N, Maeda H, Hougaku H, Hashimoto
H, et al. Rate of successful recording of blood flow signals in the
middle cerebral artery using transcranial Doppler sonography. Stroke.
1993;24:1192–1195.
Key Words: angiography ◼ arteritis ◼ magnetic resonance imaging
◼ posterior reversible encephalopathy syndrome ◼ thunderclap headache
◼ vasoconstriction