ARTICLE IN PRESS

Case Studies

Ischemic Stroke Secondary to Paradoxical Embolism Through a
Pulmonary Arteriovenous Malformation: Case Report and
Review of the Literature
Ryan Cappa, MD,* Jeanette Du, BS,† Joseph F. Carrera, MD,‡
Jimmy V. Berthaud, MD, MPH,§ and Andrew M. Southerland, MD, MSc‡

Paradoxical embolism due to isolated pulmonary arteriovenous malformation (AVM)
is an uncommon cause of ischemic stroke, with the majority occurring in patients who have not yet been diagnosed with their malformation. We report a
32-year-old man who presented with an abrupt onset of right facial weakness and
expressive aphasia. Brain magnetic resonance imaging revealed an acute infarct
in the left middle cerebral artery territory and chronic infarcts in the bilateral cerebellar hemispheres. A cardioembolic mechanism was initially considered in the
setting of perimyocarditis diagnosed a few months earlier. Transthoracic and
transesophageal echocardiograms revealed high volume right to left shunting, but
no septal defects. A pulmonary AVM was confirmed with computed tomography angiography and fistualization was successfully treated with embolization.
This report highlights a case of undiagnosed pulmonary AVM leading to recurrent paradoxical emboli to the brain. We review the epidemiology, pathophysiology,
and management of pulmonary AVMs in relation to stroke risk.

Case Report
A 32-year-old right-handed man was admitted after experiencing sudden onset right facial weakness and language
disturbance. He described a 15-minute episode of blurred
vision, right-sided facial weakness, slurred speech, and
inability to read with intact comprehension of the number
system. Past medical history included hypertension,
hyperlipidemia, tobacco use, and epilepsy on phenytoin.
From the *University of Virginia Health System Charlottesville,
Charlottesville, Virginia; †University of Virginia School of Medicine,
Charlottesville, Virginia; ‡University of Virginia Health System, Charlottesville, Virginia; and §University of Virginia, Charlottesville, Virginia.
Received December 15, 2017; revision received January 16, 2018;
accepted February 9, 2018.
Address correspondence to Ryan Cappa, University of Virginia
Health System Charlottesville, VA. E-mail: rncappa@virginia.edu.
1052-3057/$ - see front matter
© 2018 National Stroke Association. Published by Elsevier Inc. All
rights reserved.
https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.02.015

He was hospitalized 2.5 months prior for perimyocarditis
with hypokinesis of the apex noted on cardiac magnetic
resonance imaging (MRI). Family history was significant for cardiovascular disease and myocardial infarctions
at early ages.
Upon arrival to the emergency department the patient
was asymptomatic. Given his history was concerning for
stroke, a brain MRI and magnetic resonance angiogram
of the head and neck were performed. MRI revealed an
acute infarct in the left middle cerebellar artery territory, and small chronic cerebellar infarcts. Magnetic resonance
angiogram showed thrombus within the distal left middle
cerebral artery branches, and an attenuated right posterior
cerebral artery in the P3 and P4 segments. His symptoms
returned while in the emergency department and his exam
revealed horizontal nystagmus, dysarthria, right lower facial
palsy, and generalized hyperreflexia. His National Institutes of Health Stroke Scale score was 4.
A cardioembolic mechanism was considered given the
presence of infarcts of varying ages in multiple vascular

Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2018: pp ■■–■■

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Figure 1. Computed tomography of pulmonary arteriovenous malformation (white arrow).

territories, and prior diagnosis of apical cardiac hypokinesis. Transthoracic echocardiogram to assess for persistence
of the previous cardiac findings as a possible contributor
to thromboembolism revealed high volume right-to-left
shunting. A transesophageal echocardiogram with bubble
study revealed no atrial septal defect or patent foramen
ovale. A high volume shunt was again visualized, with
late appearance of saline bubbles in the left heart demonstrating a shunt of grade of 2 or greater and suggesting
a hepatopulmonary source. No thrombus was visualized. A follow-up pulmonary computed tomography (CT)
angiogram confirmed a 3.1 by 1.8 cm pulmonary arteriovenous malformation (PAVM) in the left lower lobe
(Fig 1). The feeding artery to the AVM measured 5 mm.
The AVM was successfully embolized with an Amplatzer
4 plug of the left lower lobe (Figs 2, 3). Further clarification
of the patient’s history revealed that he had experienced
1-2 nocturnal episodes of epistaxis annually. At discharge,
he was referred to genetics for evaluation of Hereditary
Hemorrhagic Telangiectasia and tested positive for the activin
A receptor type II-like 1 (ACVRL1) pathogenic variant.

Discussion
Paradoxical embolization is a recognized cause of ischemic stroke that occurs when thrombotic or bacterial emboli
of venous origin occlude arteries of various organs, including the brain, after bypassing the filtering system of
the pulmonary capillaries and traveling to the arterial circulation via an abnormal channel.1 While most paradoxical
emboli are likely attributed to patent foramen ovales,
PAVMs are another less common source of right-to-left
shunting contributing to risk of stroke in the young.2 Once
considered rare by autopsy studies, population-wide
thoracic CT screenings estimates a PAVM prevalence of
1 in 2630.3 Up to 80% of PAVMs occur in patients with
hereditary hemorrhagic telangiectasia (HHT).4 Genetic

Figure 2. Arteriogram showing pulmonary arteriovenous malformation
(white arrow) prior to plug.

Figure 3. Arteriogram of pulmonary arteriovenous malformation site after
plug (white arrow).

testing for HHT in our patient revealed the ACVRL1
variant, 1 of the 2 most common variants associated with
HHT.5 ACVRL1 is a transforming growth factor receptor expressed on actively proliferating endothelial cells,
and is associated with an autosomal dominant inheritance pattern.6 HHT as a mechanism for our patient’s longstanding epilepsy was considered, but felt to be unlikely
given his chronic infarcts were subcortical.
The majority of patients with PAVMs remain asymptomatic over the course of their lifetime, but about 30%
of patients have complications related to the central nervous
system including seizure, migraine, brain abscess, transient
ischemic attack, and ischemic stroke.2 The risk of paradoxical
embolization may depend on PAVM perfusion. A “3 mm

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PULMONARY AVMS IN RELATION TO STROKE RISK

rule” for the feeding artery luminal diameter is no longer
considered a standard for clinical significance, but is still
commonly used as a threshold guideline for PAVM embolization in practice.7 Higher shunt grade on transthoracic
contrast echocardiography (TTCE) predicts PAVM size on
CT, and may be a more reliable indicator for necessity of
embolization. Shunt grades 2 and 3 were associated with
an odds ratio of 4.78 and 10.4 respectively for the development of stroke, TIA, or abscess, compared with grade
1 shunts that had no enhanced risk.8 Thus, PAVMs causing
grade 1 shunts are unlikely to result in ischemic strokes
and are too small for embolization, whereas most grade
2 or 3 shunts on TTCE are CT-evident and feasible for
embolization. Our patient had a shunt of grade 2 or greater,
and underwent catheter embolization on the basis of both
perfusion and clinical significance.
Observational studies suggest that at least 25% of untreated patients with PAVM will suffer an ischemic stroke,
thus it is important to diagnose and definitively treat malformations amenable to endovascular therapy.9 Vascular
plugs are now preferred over coiling as the preferred method
of embolization due to advantages that reduce procedure time, radiation exposure, and risk of occluding vessels
supplying healthy lung.10 After successful occlusion of
feeding arteries, the PAVM no longer recruits vascular
supply from nearby arteries.11 Remodeling leads to PAVM
regression with return of former feeding and draining
vessels to normal size, and risk of ischemic stroke is reduced
following therapy.11 Recanalization after embolization is
described, however reported rates in the literature vary.5
Local excision, lobectomy, or pneumonectomy is reserved for patients who are not candidates for embolization.12
Finally, the risk of neurologic complications in HHT
patients warrants frequent follow up after embolization, as PAVMs may recur or evolve in size over time.13
In patients with treated PAVMs, TTCE can be falsely positive and should no longer be used for follow up screening,
and current guidelines recommend repeating pulmonary CT scans 6-12 months after embolization and then
every 3 years thereafter.5 For patients with grade 1 or 2
shunts and no treatable PAVM on CT, transthoracic
echocardiogram every 5 years may be advised.8 For patients who have already suffered from ischemic stroke
due to PAVM and do not undergo embolization, longterm anti-coagulation may be considered for secondary
prevention, although supportive evidence is lacking.14

Conclusion
This case highlights the need to consider PAVM in the
differential diagnosis for cryptogenic stroke, particularly

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in young persons with evidence of right to left shunting on cardiac imaging. Embolization is the definitive
treatment for clinically significant PAVMs or those with
high risk shunting physiology. Current guidelines suggest
that patients with treated PAVMs receive follow-up imaging
at 3-year intervals.

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