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Illustrative Teaching Case

Section Editors: Sophia Sundararajan, MD, PhD, and Shadi Yaghi, MD

Symptomatic Intracranial Atherosclerosis

With Impaired Distal Perfusion
A Case Study
Katarina Dakay, DO; Shadi Yaghi, MD

Case Description systolic and then 140 to 160 mm Hg systolic. Her examination
An 82-year-old woman with a history of hypertension pre- subsequently stabilized after 1 week with mild-to-moderate
sented to the emergency department with a 1-week history of global aphasia and severe right hemiparesis. Follow-up brain
3 episodes of word-finding difficulty and right arm weakness MRI RAPID showed improvement in the perfusion deficit
lasting for a few minutes each without any known triggers or (Figure 2), and she was discharged to a skilled nursing facility.
On discharge, her blood pressure goal was liberalized to nor-
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associated neurological symptoms.

On arrival, her blood pressure was 174/84 mm Hg. Her motension with a goal of ≤140 mm Hg systolic. The patient’s
general and neurological examination showed mild expres- recurrent symptoms were felt to be attributable to a pressure-
sive aphasia. Neuroimaging was immediately undertaken with dependent examination, often referred to as misery perfusion.
computerized tomographic angiogram of the brain and neck,
demonstrating high-grade proximal left M1 stenosis without Discussion
cervical artery stenosis (Figure 1). She then underwent mag- Intracranial atherosclerotic disease (ICAD) is an important
netic resonance imaging (MRI) of the brain with perfusion stroke mechanism, accounting for 9% to 17% of all strokes.1
imaging with rapid processing of perfusion and diffusion Certain demographic and clinical factors predispose to intra-
(RAPID), which demonstrated delayed perfusion in the left cranial atherosclerosis; the incidence seems to be the highest
middle cerebral artery territory and small left hemispheric in blacks and those of Asian descent, with whites having the
infarcts (Figure 2, top). She was started on aspirin, clopido- lowest incidence. Additionally, hypertension, diabetes melli-
grel, and high-intensity statin therapy and admitted to the tus, hyperlipidemia, and age are associated with the risk of
stroke unit. A transthoracic echocardiogram was unremark- developing ICAD. Angiography is considered the gold stan-
able, her glycosylated hemoglobin was 5.7%, and low-density dard for diagnosis of ICAD; however, noninvasive tests, such
lipoprotein was 131 mg/dL. Her stroke was attributed to intra- as computerized tomographic angiography, magnetic reso-
cranial atherosclerosis. She was discharged on dual antiplate- nance angiography, and transcranial Doppler ultrasound, are
let therapy and high-intensity statin therapy with persistent often used.1
mild expressive aphasia. ICAD can cause strokes by way of 3 mechanisms:
Two weeks after discharge, she represented with right artery-to-artery embolism, flow failure or hypoperfusion,
hemiplegia and severe near-global aphasia. Her blood pressure and branch-atheromatous disease; of these, artery-to-artery
was 130/82 mm Hg. Computerized tomographic angiogram of embolism seems to be the most common.2 Studies have
the head and neck was stable. A repeat brain MRI with RAPID shown a relatively high risk of recurrent cerebrovascular
showed expansion of infarcts to involve the left corona radiata events in patients with symptomatic ICAD. The SAMMPRIS
(Figure 2, bottom). Because of the large hypoperfused penum- study (Stenting Versus Aggressive Medical Management for
bra on MRI and suspected pressure-dependent examination, Preventing Recurrent Stroke in Intracranial Stenosis) showed
decision was made to augment cerebral blood flow, and she that the risk of recurrent events is ≈12% at 1 year and 20%
was placed on norepinephrine with a goal of systolic blood at 2 years from the initial event.3 However, the SAMMPRIS
pressure >180 mm Hg, which led to regaining of speech; how- trial excluded patients with worsening deficits during the 24
ever, her right hemiplegia persisted. She was then started on hours preceding stent placement. So it did not address the
oral midodrine and fludrocortisone, her home blood pressure subpopulation of patients with worsening neurological symp-
medications were held, and she was slowly weaned off nor- toms, despite medical therapy, such as our patient during her
epinephrine after 48 hours. During her hospital stay, her blood second admission. Other studies have shown that the highest
pressure goal was initially liberalized to 160 to 180 mm Hg risk of recurrence or worsening in patients with intracranial or

Received September 19, 2017; final revision received October 19, 2017; accepted October 20, 2017.
From the Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI.
Correspondence to Shadi Yaghi, MD, Department of Neurology, Warren Alpert Medical School of Brown University, 353 Eddy St, APC 530, Providence,
RI 02903. E-mail
(Stroke. 2018;49:e10-e13. DOI: 10.1161/STROKEAHA.117.019173.)
© 2017 American Heart Association, Inc.
Stroke is available at DOI: 10.1161/STROKEAHA.117.019173

Dakay and Yaghi   A Patient With a Left M1 Stenosis   e11

the clinical phenomenon of vasopressor-responsive flow

failure, there are no randomized clinical trials studying this
phenomenon.10 Given that pressure dependence is theoreti-
cally predicated on the presence of a penumbra, it is possible
that the widespread implementation of perfusion imaging
may help identify patients in whom a higher blood pressure
target may be beneficial. Induced hypertension, however, is
not an ideal treatment because the duration and blood pres-
sure target are widely variable among patients and there are
potential significant adverse events from prolonged use of
vasopressors. In the SAMMPRIS trial, blood pressure lower-
ing appeared to be safe and was included as part of the medi-
cal management arm.
Furthermore, patients with symptomatic ICAD and
unfavorable perfusion may benefit from revascularization
therapy beyond aggressive medical management alone. This
has already been suggested regarding treatment of extracra-
nial large-artery stenosis in a pooled analysis of completed
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randomized trials of carotid endarterectomy. In patients with

ICAD, the 2 prior randomized trials that assessed interven-
tions for intracranial atherosclerotic stenosis, SAMMPRIS3
and VISSIT (Vitesse Intracranial Stent Study on Ischemic
Figure 1. Computed tomographic angiogram demonstrates criti- Therapy),11 did not select patients based on perfusion status.
cal left proximal middle cerebral artery (M1) stenosis. In SAMMPRIS, the periprocedural complication rate was
≈15% in the first 30 days. Recently, results from the WEAVE
extracranial large-vessel atherosclerotic disease is in the first (Wingspan Stent System Post Market Surveillance Study) reg-
few days after the initial event.4,5 istry of symptomatic ICAD showed a relatively low risk of
Perfusion-based imaging has been recently used to aid periprocedural complications (≈5% at 30 days) with stenting
with acute stroke treatment decisions in patients with emer- when compared with the reported rates in the SAMMPRIS
gent proximal large-vessel anterior circulation intracranial study (NCT02034058). The authors attribute this to increased
occlusion. At our institution, we use RAPID—a software, operator experience with the device and perhaps because
which computes quantitative perfusion maps and can calcu- of a submaximal angioplasty alone strategy. Because of the
late the ratio of ischemic infarct on diffusion weighted imag- high recurrence risk in patients with symptomatic ICAD
ing to the hypoperfused penumbra.6 Recent data demonstrates and impaired perfusion, these patients may be a distinctive
the benefit from mechanical thrombectomy using perfusion- group in whom the safety of revascularization and reperfu-
based imaging selection with RAPID software beyond 6 hours sion against the risk of neurological deterioration in medically
from symptom onset.7 This may also be the case in patients treated patients may be studied.
with ICAD where there has been increased use of perfusion In addition to endovascular treatment, surgical revas-
imaging to predict stroke risk with a recent study showing an cularization by way of external carotid to internal carotid
increased risk of recurrent stroke in patients with impaired bypass through connecting the superficial temporal artery
distal blood flow.8 In addition to perfusion, 1 study demon- to the middle cerebral artery has been studied but failed to
strated that absent or poor collaterals portended a high risk of benefit patients with severe middle cerebral artery stenosis.12
stroke recurrence rate, whereas rapid filling of collateral ves- More recent studies have explored indirect bypass by way
sels was relatively protective against stroke recurrence.9 of encephaloduroarteriosynangiosis, wherein the superficial
To date, aggressive medical treatment with antiplate- temporal artery is transposed directly onto the brain, allow-
let agents, statins, and risk-factor modification remains the ing it to form collaterals. Preliminary studies of this proce-
treatment of choice for patients with symptomatic ICAD.1 dure in patients with moyamoya have been more promising
Aggressive medical treatment, however, may help stabilize than with atherosclerotic disease, where small prospective
atherosclerotic plaques and reduce the risk of embolization, trials have shown no benefit.13,14
but it is unlikely to significantly and acutely improve blood Our patient had minor neurological symptoms but had
flow to tissue at risk and prevent neurological deterioration. evidence of impaired distal blood flow on the initial brain
In fact, impaired distal blood flow detected by noninvasive MRI RAPID and exhibited neurological deterioration, despite
imaging has been shown to predict stroke risk in patients with aggressive medical treatment. Clinical trials investigating the
extracranial and ICAD, despite medical therapy.8 safety of reperfusion treatment in this patient population are
Hence, patients with symptomatic ICAD and impaired needed with an ultimate goal to reduce the risk of neurologi-
blood flow remain a therapeutically challenging subgroup. cal deterioration in patients with symptomatic ICAD causing
Although small trials and case reports have demonstrated impaired distal blood flow.
e12  Stroke  January 2018
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Figure 2. The patient’s sequential rapid processing of perfusion and diffusion (RAPID) magnetic resonance imaging (MRI) demonstrates
the evolution of the perfusion deficit. The top of the figure shows the initial RAPID MRI with punctate left hemispheric infarcts and
delayed perfusion in the left middle cerebral artery territory with 61-mL volume of brain tissue with T max >6-s delay. Middle of figure
shows second RAPID MRI with infarct expansion and 61-mL volume of brain tissue with T max >6-s delay. The bottom of the figure
shows the last RAPID MRI after blood pressure augmentation showing stable left hemispheric infarcts without areas of brain tissue with
T max >6-s delay. ADC indicates apparent diffusion coefficient.
Dakay and Yaghi   A Patient With a Left M1 Stenosis   e13

3. Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF, et
al; SAMMPRIS Trial Investigators. Stenting versus aggressive medical
TAKE-HOME POINTS therapy for intracranial arterial stenosis. N Engl J Med. 2011;365:993–
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• Intracranial atherosclerosis can cause stroke by 4. Yaghi S, Rostanski SK, Boehme AK, Martin-Schild S, Samai A, Silver
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5. Sangha RS, Naidech AM, Corado C, Ansari SA, Prabhakaran S.
atic intracranial atherosclerosis because of increased
Challenges in the medical management of symptomatic intracranial
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intracranial atherosclerosis. match analysis in acute stroke. J Magn Reson Imaging. 2010;32:1024–
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a threshold value. ing. J Neurol Sci. 2017;375:395–400. doi: 10.1016/j.jns.2017.02.044.
8. Amin-Hanjani S, Pandey DK, Rose-Finnell L, Du X, Richardson
• Pressure dependence can be demonstrated clinically
D, Thulborn KR, et al; Vertebrobasilar Flow Evaluation and Risk of
and is treated with augmentation of blood pressure Transient Ischemic Attack and Stroke Study Group. Effect of hemo-
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• Clinical trials investigating the safety of reperfusion lar occlusive disease. JAMA Neurol. 2016;73:178–185. doi: 10.1001/
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Disclosures Oberpfalzer M, Wakhloo A, et al; VISSIT Trial Investigators. Effect of
None. a balloon-expandable intracranial stent vs medical therapy on risk of
stroke in patients with symptomatic intracranial stenosis: the VISSIT
randomized clinical trial. JAMA. 2015;313:1240–1248. doi: 10.1001/
Acknowledgments jama.2015.1693.
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Symptomatic Intracranial Atherosclerosis With Impaired Distal Perfusion: A Case Study
Katarina Dakay and Shadi Yaghi

Stroke. 2018;49:e10-e13; originally published online November 22, 2017;

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doi: 10.1161/STROKEAHA.117.019173
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2017 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628

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