Rare disease

Case report

Takayasu arteritis presenting as embolic stroke
Kristina Field, Laila Gharzai, Kaye Bardeloza, Bruce Houghton
Department of Internal
Medicine, Creighton University
School of Medicine, Omaha,
Nebraska, USA
Correspondence to
Dr Bruce Houghton,
​bruce.​houghton@​alegent.​org
Accepted 18 August 2017

Summary
A 52-year-old Caucasian woman presented to the
emergency department with symptoms of acute
ischaemic stroke (right-side weakness, confusion and
aphasia) that resolved completely after administration
of tissue plasminogen activator. During stroke work-up,
she was found to have an enhancing infiltrate of the
aorta at the level of the take-off of the great vessels,
most consistent with early Takayasu arteritis. After being
discharged home on steroids and dual antiplatelet
therapy, she returned 2 days later with re-presentation
of weakness and aphasia. Further work-up revealed two
intraluminal clots in the left common carotid and left
internal carotid arteries that had not been discovered
during previous testing. This case illustrates the need
to screen for sources of embolic stroke in patients
with Takayasu arteritis, especially those with recurring
symptoms.

Background

Takayasu arteritis (TA) is a rare granulomatous
vasculitis of large and medium arteries typically
affecting the aorta, subclavian and carotid arteries.
The incidence of TA worldwide is only 1–2 per
million people, predominantly affecting Asians and
women in their 20s.1 The signs and symptoms of
TA are due to both systemic inflammation as well as
local damage to the vasculature. The presentation
of TA can be quite variable, ranging from diminished pulses to ischaemic stroke. While stroke is
a rare presenting symptom of TA, it can occur in
5%–17% of patients with TA.2–4 Ischaemic strokes
can be either occlusive, from external compression of arteries, or embolic, from stasis caused by
poor flow through stenotic areas. Guidelines for
the work-up of TA are unclear as it is such a rare

To cite: Field K, Gharzai L,
Bardeloza K, et al. BMJ Case
Rep Published Online First:
[please include Day Month
Year]. doi:10.1136/bcr-2017220001

Figure 1 Axial CT angiography of the neck
demonstrating occlusion of the left common carotid
artery.

disease; here we present a case of TA where the
source of emboli causing ischaemic stroke was not
discovered during initial work-up.

Case presentation
A 52-year-old woman presented to the emergency
department with less than 1 hour of sudden onset of
weakness, mild confusion and complete aphasia. On
physical exam, her stroke manifestations included
aphasia, mild confusion, weakness and right-sided
pronator drift. During admission, a blood pressure
difference between the arms was found, with the
right arm 115/73 and left arm 99/62. There were no
appreciable carotid bruits and pulses were palpable
in all four extremities. CT of the head showed a
hyperdense middle cerebral artery (MCA) sign
involving the distal M1 segment of the left MCA
with questionable extension into an M2 branch. CT
angiography (CTA) of the head showed asymmetry
of the distal internal carotid arteries, left smaller
than the right, and an abrupt occlusion of the distal
M1 branch of the left MCA artery. Later, MRI of
the brain showed an acute infarct involving the
left temporal insular and peri-insular region. The
patient’s symptoms resolved completely an hour
after tissue plasminogen activator (tPA) administration.
Due to the patient’s age and lack of significant
risk factors for stroke,5 work-up was carried further.
The asymmetry of the distal internal carotid arteries
seen on the CTA of the head prompted a CTA of
the neck. This revealed soft tissue thickening with
inflammatory stranding involving the proximal
aortic arch with extension into the great vessels
and involvement of the carotid system, concerning
for an inflammatory vasculitis. Additionally, severe
stenosis was present with near-occlusion of the left
common carotid artery. Additional areas of inflammatory changes and wall thickening involving the
mid and distal left common carotid artery extending
into the left internal and external carotid arteries
were also observed (figure 1). Echocardiogram was
normal. CTA of the chest showed an enhancing
infiltrative mass around the proximal great vessels
and aortic arch at the level of the great vessel takeoffs, measuring approximately 8 mm in thickness,
most consistent with early TA (figure 2 and 3). At
this time no further imaging was pursued due to
the radiologically apparent disease on CTA of the
chest and neck (sensitivity and specificity for the
diagnosis of TA are 95% and 100%, respectively1).
Rheumatological screening showed sedimentation
rate of 36 mm/hour, C reactive protein (CRP) of
12 mg/L and positive antinuclear antibody.

Field K, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2017-220001

1

Rare disease

Figure 2 Axial CT angiography of the chest demonstrating an
enhancing infiltrative mass around the aortic arch.
A diagnosis of TA was made based on the difference in blood
pressure, elevated erythrocyte sedimentation rate (ESR) and
characteristic radiographical findings involving the aorta and
common carotid.6 The patient was released on high-dose daily
prednisone, aspirin and clopidogrel. Unfortunately, she re-presented 2 days after discharge complaining of similar symptoms,
namely aphasia, right-side leg weakness and leg cramping. At this
time, tPA administration was not pursued due to recent administration during previous admission, in accordance with standard
guidelines.7 Symptoms resolved without further intervention.
MRI revealed interval extension of infarct in the left subinsular
and insular region, with a new infarct in the inferior insular

Figure 4 Interventional radiology (IR) cerebral angiogram obtained
at second admission, demonstrating the left common carotid and two
intraluminal clots.
cortex and in the periatrial white matter on the left. Further
work-up at this admission included an interventional radiology
cerebral angiogram with catheter placement in the internal
carotid. Conventional angiography revealed severe left common
carotid artery stenosis at origin, resulting in stasis of blood and
leading to the development of a large positional thrombus of
the left common carotid artery. A second large intraluminal
thrombus was found in the proximal left internal carotid artery
(figure 4). Perfusion of the left internal carotid artery above
the level of this thrombus showed distinct delay. At this time
vascular surgery was consulted for possible thrombectomy. This
was deferred due to concern related to the friability of the vessel
in the setting of severe inflammation. Thrombophilia work-up
returned negative, and the clots were felt to be due to arterial
stasis secondary to compression of the vessels from vasculitis. At
this time, clopidogrel was discontinued. The patient was therapeutically anticoagulated with warfarin. Aspirin was continued.
Methotrexate was added for further management of the arteritis
and in hopes of being able to reduce the dose of prednisone once
inflammation was better controlled.

Differential diagnosis

Figure 3 Coronal CT angiography of the chest demonstrating an
enhancing infiltrative mass around the proximal great vessels, aortic
arch, at the level of the great vessel take-offs approximately 8 mm thick,
most consistent with Takayasu arteritis.
2

TA is a difficult disease to diagnose given that it is relatively rare
and the differential diagnosis is wide; the differential diagnosis
for causes of ischaemic stroke is narrower but can be equally
difficult to diagnose.
The differential diagnosis for TA includes other large-vessel
vasculitides such as giant cell arteritis (GCA), systemic lupus
erythematosus, syphilis, tuberculosis and Kawasaki disease,
and congenital connective tissue disorders such as Marfan’s
syndrome, as well as several other disorders and pathologies.
These can be difficult to distinguish from TA and are typically
differentiated by epidemiological characteristics, complications
and appearance on imaging.1 8 Angiography is considered the
gold standard diagnostic imaging for TA with a sensitivity and
specificity of 100%. CT is considered to be a reliable alternative
Field K, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2017-220001

Rare disease
to angiography. However, neither of these two tests offer much
clinical utility in evaluating the early disease processes associated
with TA. Positron emission tomography (PET) scan is considered
to be the most sensitive test for detecting early inflammatory
stigmata of TA. PET scan offers some additional benefits in being
able to evaluate disease recurrence and response to treatment.1
PET scan was not used in our patient during initial work-up as
it was not felt to add any further information in light of characteristic lesions on CTA.
The aetiology of ischaemic stroke in TA is occlusive or
embolic, from compression of arteries or from clot formation. Guidelines for the work-up of ischaemic stroke in TA
are unclear. In our case, we initially attributed the patient’s
stroke symptoms to occlusion—the symptoms resolved with
tPA administration, and the aetiology was felt to be related
to compression of arteries from the underlying vasculitis.
Pursuing further work-up was deferred until the patient re-presented with similar stroke symptoms. At this point, interventional radiology (IR)-guided catheter placement revealed the
presence of two large intraluminal thrombi that were likely the
source of emboli.
The wide differential underscores the difficulty in arriving
at the diagnosis of TA, especially if the patient does not fit the
typical demographics. In our case, the characteristic imaging
findings of large-vessel aortitis and the suspicion of the diagnosing radiologist helped to narrow the differential. Once the
carotid thrombi were discovered, these were felt to be the most
likely aetiology of the patient’s stroke and treated accordingly.

Treatment
There are no meta-analyses available for the treatment of TA,
but expert consensus and a few clinical trials outline the treatment strategies used today. Treatment can be pharmacological
or surgical, with pharmacological therapy being the predominant modality in one survey (75.2% pharmacological vs 13.3%
surgical9).
Pharmacological therapy aims at controlling the dysregulated
inflammatory process in TA. Corticosteroids are the mainstay
of treatment. Adjuvant immunosuppressants are often added
with higher, difficult-to-control levels of inflammation, as well
as when attempts to taper steroid therapy are made.4 Highdose corticosteroids (1 mg/kg/day) are used initially to treat TA.
Weaning steroids has proven to be difficult in patients with TA.
Immunosuppressants such as cyclophosphamide, azathioprine,
methotrexate and mycophenolate can be used when attempting
to taper steroid therapy. With the initiation of immunosuppression, the disease takes a stable course in the majority of
patients.10 Biological agents such as anti-tumour necrosis factor
therapy, infliximab and etanercept also have a role in steroid
dose reduction and control of inflammation.1
Surgical interventions are less commonly employed and
include endovascular surgery and surgical revascularisation.
Surgical intervention is aimed at reducing complications that
can reduce life expectancy, namely stroke, myocardial infarction, renal failure and aneurysmal rupture. Although a seemingly good option for treatment, restenosis after transluminal
angioplasty and stent-graft placement occur in up to two-thirds
of patients and are only recommended in certain cases. Indications for surgery include severe renovascular stenosis, severe
myocardial ischaemia, extreme claudication, critical cerebral
ischaemia or stenosis of three or more cerebral vessels, severe
aortic stenosis, thoracic or abdominal aneurysms >5 cm with a
tendency to rupture, and severe aortic coarctation.1
Field K, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2017-220001

In those patients who have thrombus formation secondary to
stenosis, appropriate administration of anticoagulation therapy
is necessary. In patients with embolic stroke without TA, shortterm anticoagulation (3–6 months) is used for acute symptomatic
occlusion.11 12 To the best of the authors’ knowledge, no guidelines on how to approach anticoagulation for thrombus formation in TA exist. The thrombus formation can be presumed to be
provoked by the state of inflammation from TA; however, the
risk of further clot formation from ongoing inflammation will be
dependent on disease control and will need to be tailored to each
individual patient. Thus in these cases, the typical short course of
anticoagulation may not be sufficient.

Outcome
After the patient was discharged, she returned for follow-up with
rheumatology 6 weeks later with no other stroke events. She was
stable with methotrexate 15 mg weekly, prednisone 60 mg daily,
folate and warfarin. Her international normalised ratio remained
therapeutic with subsequent testing demonstrating decrease in
CRP and ESR to within normal limits. At this point, the patient
elected to move care to a different hospital system and was lost
to follow-up.

Discussion
TA is a rare large-vessel systemic vascular arteritis usually
affecting the aorta and the main branches.1 2 The pathogenesis
of TA continues to remain largely unknown. Neither inflammatory markers nor clinical exam is reliable in determining disease
course or response to treatment. As such imaging remains an
essential part of disease monitoring. Due to the significant
sequelae associated with TA, early diagnosis and treatment are
important for reducing the overall morbidity and mortality of
the disease. TA has a wide differential and can be particularly
difficult to diagnosis. There are two distinct phases of TA, active
inflammatory phase and late chronic phase. The early active
phase is characterised by general symptoms such as malaise,
fever, night sweats, arthralgias, headaches and rashes. During the
late chronic phase, vessel involvement is apparent. Those in the
late chronic phase tend to experience more specific symptoms
including but not limited to renovascular hypertension, acute
mesenteric ischaemia, retinopathy, amaurosis fugax, transient
ischaemic attacks and strokes.1 In a single-institution study, 13%
of 45 patients with TA initially presented with stroke.13 Emboli
arise from involved vessels due to thickening, stenosis, dilation
and/or aneurysmal formation .
Overall incidence of stroke in this subset of patients has been
cited anywhere from 10% to 20%14; stroke as initial manifestation is even more rare.15–17 In a single-institution retrospective
study, the prevalence of stroke in patients already diagnosed
with TA was 15%.2 Other than embolism, occlusive lesions from
stenosis, hypertension and cerebral hypoflow are all possible
aetiologies. The rarity of the disease in the setting of this atypical presentation can cause delay of diagnosis.15 Ultimately
when patients with neurological deficit present in the setting of
systemic symptoms, TA should rise in the differential.10 16
Although our patient had low suspicion for TA based on physical exam and lack of systemic symptoms of inflammation, the
diagnosis was ultimately made due to her signs and symptoms
of unequal blood pressures in both arms, limb claudication and
abnormal imaging. She had another stroke 2 days after discharge
and was placed on anticoagulation therapy after discovery of
intraluminal thrombi. Although biopsy and thrombectomy were
initially considered, neither was pursued due to the limited
3

Rare disease
utility of biopsy1 and because of concern about the friability of
the left common carotid with any surgical manipulation.
There are case reports in the literature of TA presenting with
ischaemic stroke,3 14 18 but identifying embolic stroke is rare
and not well-described.19 Specific guidelines for evaluating for
thrombi in areas of stenosis do not exist. This case demonstrates
the need for maintaining a high suspicion for embolism as the
aetiology for ischaemic stroke, especially in those patients who
re-present with stroke symptoms. The discovery of two intraluminal thrombi in this patient led to the initiation of anticoagulation, and the patient suffered from no additional stroke
events after adequate anticoagulation. Initial discovery of the
thrombi during our patient’s first admission may have prevented
the second stroke and progression of ischaemia; however, as no
guidelines exist, investigation of thrombi in areas of stenosis was
not thought to be cost-effective in management during work-up
for our patient. The rarity of this presentation underscores the
difficulty of knowing when to pursue further testing. We suggest
considering the patient’s degree of stenosis and using this as a
guide to the risk of thrombosis; in our patient, near-complete
occlusion led to arterial stasis. Further description of such cases
in the literature is needed to develop guidelines for distinguishing
emboli as the cause of ischaemic stroke in TA.

Learning points
►► Cryptogenic stroke in young patients should

include Takayasu arteritis in the differential.

►► High suspicion for embolism as source of ischaemic stroke in

new diagnosis of Takayasu arteritis must be maintained.

►► Prompt initiation of anticoagulation therapy for those

with Takayasu arteritis and thrombi is necessary to prevent
embolic stroke.

Contributors KF was instrumental in the conception and design, acquisition of
data or analysis, and interpretation of data; drafting the article or revising it critically
for important intellectual content; and final approval of the version published. LG
was instrumental in the conception and design, acquisition of data or analysis,
and interpretation of data; drafting the article or revising it critically for important
intellectual content; and final approval of the version published. KB was instrumental
in the conception and design, acquisition of data, or analysis and interpretation
of data; drafting the article; and final approval of the version published. . BH was
instrumental in the conception and design, acquisition of data, or analysis and

interpretation of data; drafting the article or revising it critically for important
intellectual content; and final approval of the version published. All authors agree to
be accountable for the article and to ensure that all questions regarding the accuracy
or integrity of the article are investigated and resolved.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article)
2017. All rights reserved. No commercial use is permitted unless otherwise expressly
granted.

References

1	Serra R, Butrico L, Fugetto F, et al. Updates in Pathophysiology, Diagnosis and
Management of Takayasu Arteritis. Ann Vasc Surg 2016;35:210–25.
2 de Paula LE, Alverne AR, Shinjo SK. Clinical and vascular features of Takayasu arteritis
at the time of ischemic stroke. Acta Reumatol Port 2013;38:248–51.
3 Humayun MA, Masood A, Waseem T, et al. An unusual cause of stroke in a young
female. Am J Emerg Med 2014;32:685.e3–685.e5.
4 Kerr GS, Hallahan CW, Giordano J, et al. Takayasu arteritis. Ann Intern Med
1994;120:919–29.
5	Saver JL. Cryptogenic Stroke. N Engl J Med Overseas Ed 2016;374:2065–74.
6	Sharma BK, Jain S, Suri S, et al. Diagnostic criteria for Takayasu arteritis. Int J Cardiol
1996;54:S141–S147.
7 Jauch EC, Saver JL, Adams HP, et al. Guidelines for the Early management of Patients
with Acute Ischemic Stroke. Stroke 2013;44:870–947.
8 Johnston SL, Lock RJ, Gompels MM. Takayasu arteritis: a review. J Clin Pathol
2002;55:481–6.
9	Ogino H, Matsuda H, Minatoya K, et al. Overview of late outcome of medical and
surgical treatment for Takayasu arteritis. Circulation 2008;118:2738–47.
10	Ringleb PA, Strittmatter EI, Loewer M, et al. Overview of late outcome of medical and
surgical treatment for Takayasu arteritis. Circulation 2008;118:2738–47.
11 Barnett HJ, Peerless SJ, Kaufmann JC. "Stump" on internal carotid artery--a source for
further cerebral embolic ischemia. Stroke 1978;9:448–56.
12 Barnett HJ. Delayed cerebral ischemic episodes distal to occlusion of major cerebral
arteries. Neurology 1978;28:769–74.
13 Ureten K, Oztürk MA, Onat AM, et al. Takayasu’s arteritis: results of a university
hospital of 45 patients in Turkey. Int J Cardiol 2004;96:259–64.
14 Maeda Y, Taguchi H, Kudo T, et al. Takayasu arteritis and ischaemic stroke. QJM
2016;109:45–6.
15	Pereira VC, de Freitas CC, Luvizutto GJ, et al. Stroke as the First Clinical Manifestation
of Takayasu’s Arteritis. Case Rep Neurol 2014;6:271–4.
16	Sikaroodi H, Motamedi M, Kahnooji H, et al. Stroke as the first manifestation of
Takayasu arteritis. Acta Neurol Belg 2007;107:18–21.
17 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice. 4th edn.
Philadelphia: Elsevier, 2004.
18	Park KC, Kim JH, Yoon SS, et al. Takayasu’s disease presenting with atherothrombotic
ischaemic stroke. Neurol Sci 2008;29:363–6.
19 Kato Y, Dembo T, Takeda H, et al. Stroke as a manifestation of Takayasu’s arteritis likely
due to distal carotid stump embolism. Intern Med 2010;49:695–9.

Copyright 2017 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit
http://group.bmj.com/group/rights-licensing/permissions.
BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission.
Become a Fellow of BMJ Case Reports today and you can:
►► Submit as many cases as you like
►► Enjoy fast sympathetic peer review and rapid publication of accepted articles
►► Access all the published articles
►► Re-use any of the published material for personal use and teaching without further permission
For information on Institutional Fellowships contact consortiasales@bmjgroup.com
Visit casereports.bmj.com for more articles like this and to become a Fellow

4

Field K, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2017-220001