European Journal of Neurology 2008, 15: 306–308

doi:10.1111/j.1468-1331.2007.02025.x

SHORT COMMUNICATION

Bilateral cerebral hemispheric infarction associated with sildenafil citrate
(ViagraÒ) use
K.-K. Kima, D. G. Kima, Y. H. Kua, Y. J. Leeb, W.-C. Kima, O. J. Kima and H. S. Kima
Departments of aNeurology and bDepartment of Radiology, Pochon CHA University College of Medicine, Seongnam-si, Gyeunggi-do,
South Korea

Keywords:

cardioembolism, cerebral
infarction, sildenafil
Received 26 September 2006
Accepted 23 January 2007

Sildenafil citrate (ViagraÒ) is one of the frequently prescribed drugs for men with
erectile dysfunction. We describe a 52-year-old man with bilateral middle cerebral
artery (MCA) territory infarction after sildenafil use. He ingested 100 mg of sildenafil
and about 1 h later, he complained of chest discomfort, palpitation and dizziness
followed by mental obtundation, global aphasia and left hemiparesis. Brain magnetic
resonance imaging documented acute bilateral hemispheric infarction, and cerebral
angiography showed occluded bilateral MCA. Despite significant bilateral MCA
stenosis and cerebral infarction, systemic hypotension persisted for a day. We presume
that cerebral infarction was caused by cardioembolism with sildenafil use.

Introduction
Sildenafil citrate (ViagraÒ; Pfizer US Pharmaceutical
Group, New York, NY, USA) is the drug of choice for
most men with erectile dysfunction. Its main adverse
effects are headache, flushing, dyspepsia, nasal congestion, and visual disturbances to a mild degree [1]. In
both placebo-controlled and open-label studies, sildenafil was not associated with an increased risk of stroke
[2]. However, it should be prescribed with caution to
patients with persistent hypotension and patients who
have suffered a myocardial infarction, stroke, or lifethreatening arrhythmia within the last 6 months [3]. We
report a patient who had no past medical history of
cerebrovascular risk factors and presented with
bilateral hemispheric infarction shortly after sildenafil
use.

Case report
A 52-year-old, right-handed man presented with a
sudden onset of left hemiparesis and mental obtundation for 1 h. He had no previous medical history of
hypertension, diabetes, hyperlipidemia, cardiac disease,
or stroke. He smoked one pack of cigarettes per day for
the past 30 years, and drank socially. He had not taken
any medication for the last several months and he had
not been prescribed sildenafil before. According to his
spouse, he took 100 mg of sildenafil without achieving

Correspondence: Hyun Sook Kim, MD, Department of Neurology,
Pochon CHA University College of Medicine, Yatap-dong 351,
Bundang-gu, Seongnam-si, Gyeunggi-do, South Korea (tel.:
+ 82 31 780 5483; fax: + 82 31 780 5198;
e-mail: hskim626@cha.ac.kr).

306

an erection or participating in sexual intercourse. Then,
chest discomfort, palpitation, dizziness, and dull headache appeared 1 h after sildenafil use. A neurological
examination showed drowsy mental status, global
aphasia, gaze preference to the right side, and left
hemiparesis [Medical Research Council (MRC) scale
III in his left arm and leg]. Tendon reflexes were
hyperactive, but symmetric in all extremities without
pathological reflexes. Vital signs were stable, and his
heart rate was 105 beats/min with normal sinus rhythm.
But his blood pressure was around 90/60 mmHg for
initial 5 h. During this period, the lowest blood pressure
was 85/50 mmHg and the highest blood pressure was
100/60 mmHg.
Brain computerized tomography (CT) showed suspicious loss of gray–white matter interface in bitemporal regions. Transfemoral cerebral angiography was
started 5 h after the onset, and complete occlusion at
the superior division of the left middle cerebral artery
(MCA) and partial occlusion at the superior division of
the right MCA with thrombus were documented
(Fig. 1a and b). However, there was no carotid stenosis.
We infused 300 000 units of urokinase in the left MCA
(150 000 units were infused for 2 min first, followed by
three times of 50 000 units, each for 1 min with 5-min
interval), which was totally re-canalized. We also infused 100 000 units of urokinase in the right MCA (two
times of 50 000 units, each for 1 min with 5-min interval), which was partially re-canalized with good collateral circulation. The patient showed improvement of
left hemiparesis (up to MRC grade IV) immediately
after re-canalization. Because the blood pressure remained around 90/60 mmHg with vigorous iv fluid
replacement therapy, the patient was treated with
dopamine (5–10 lg/kg/min) after the thrombolytic
Ó 2008 The Author(s)
Journal compilation Ó 2008 EFNS

Cerebral infarctions by cardioembolism with sildenafil citrate use

(a)

(b)

(c)

(d)

307

normal global left ventricular (LV) systolic function
(ejection fraction = 73%). The transesophageal echocardiogram showed a small thrombus in the left atrial
appendage. The electrocardiogram at admission and at
12th hospital day, and 24 h holter monitoring resulted
in normal findings.
About 1 week later, motor weakness improved up to
MRC grade V and the patient could walk independently. Comprehensive function also recovered partially; however, motor aphasia and bulbar paralysis
persisted. His blood pressure has been checked between
120/80 and 140/90 mmHg up to the present.

Discussion

(e)

(f)

Figure 1 Cerebral angiography showed complete occlusion of
the superior division of the left middle cerebral artery (a, white
arrow) and partial occlusion of superior division of right middle
cerebral artery (b, whiter arrow). Brain MRI showed increased
signal intensities in bilateral middle cerebral artery territory on
T2-weighted image (c), and diffusion weighted image (d). After
thrombolysis, brain MRA showed re-canalized left (e) and right
(f) middle cerebral arteries.

procedure. His blood pressure was above 120/
80 mmHg and it could be maintained without
dopamine after 1 day. After 3 days, brain magnetic
resonance imaging (MRI) demonstrated bilateral MCA
territory infarction and hemorrhagic transformation at
right basal ganglia (Fig. 1c and d). And bilateral MCAs
were normal on brain magnetic resonance angiography
(Fig. 1e and f). The routine laboratory tests – including
the blood glucose level, thyroid functions, creatine
kinase (CK) and CK-myocardial band (MB) level,
Protein C and S, plasma homocysteine level, and
autoimmune screening tests were all within normal
range. Serum total cholesterol level was 263 mg/dl,
triglyceride was 300 mg/dl, and low-density lipoprotein
cholesterol was 175 mg/dl. The transthoracic echocardiogram showed normal sized cardiac chambers with

Sildenafil inhibits cyclic guanosine monophosphate
(cGMP)-specific phosphodiesterase type 5 (PDE5) and
increased cGMP promotes the effect of nitric oxide
(NO) [4]. Because relatively high levels of PDE5 are
found in the human corpus cavernosum and in vascular, visceral, and tracheal smooth muscles, NO causes
the vasodilatations not only in corpus cavernosum but
also in systemic vessels. This modest vasodilating
property produces an average decrease in blood pressure of 8.0/5.5 mmHg over the initial 24 h after a dose
of the drug and necessitates caution when prescribing
sildenafil to patients with cardiovascular disease [5,6].
Providentially, sildenafil citrate has much diminished
selectivity for cAMP-specific PDE isoform-3, which is
involved in regulating cardiac contractility [7]. Reported cardiovascular side effects in normal healthy
populations are typically minor and transient. However, acute myocardial infarction, sudden cardiac
death, symptomatic non-fatal ventricular arrhythmia,
transient cerebral ischemic attacks per se, and hemorrhagic stroke are clearly documented in patients
engaging in sexual exertion assisted with the use of
sildenafil [8,9]. It is proposed that pre-sildenafil treadmill tests assessing the presence of stress-induced
ischemia in patients with coronary artery disease can
guide the relative risk of cardiac ischemia during sexual
intercourse after sildenafil use [6].
Acute, symptomatic atrial fibrillation presenting with
dyspnea, palpitations, and dizziness was reported after
oral ingestion of sildenafil [5,10,11]. The mechanism of
atrial fibrillation induced by sildenafil is uncertain. One
explanation is that arterial vasodilatation induced by
the drug produces an increased pressure gradient over
the LV outflow tract, and previously existing cardiomyopathy are prone to producing the atrial fibrillation
[5]. Otherwise, atrial fibrillation may be secondarily
induced through increased sympathetic activity for
hypotension [10,11]. It was believed that cardiac
complications could occur in specific situations such as

Ó 2008 The Author(s)
Journal compilation Ó 2008 EFNS European Journal of Neurology 15, 306–308

308

K.-K. Kim et al.

sildenafil use accompanied with sexual activity or
among the patients with previous cardiovascular risk
factors [6,12]. However, there were patients with atrial
fibrillation without participating in sexual intercourse
[11] and in young healthy condition [10].
The etiology of vascular ischemia after sildenafil use
is still obscure. A few reports hypothesized that hypotension, cardioembolism or hypercoagulation were
responsible [9,13,14]. Although sildenafil has no direct
effects on platelet function, it modestly potentates the
inhibitory effect of the NO donor sodium nitroprusside
on ADP-induced platelet aggregation ex vivo. According to this mechanism of action, adverse bleeding episodes are the major concern [6], so, it is unlikely that
sildenafil induces a hypercoagulable state. Hypotension
and atrial fibrillation are relatively identified adverse
effects of sildenafil and there was a case with atrial
fibrillation and continuous hypotension induced by
sildenafil use [11]. Moreover, left atrial thrombus formation does occur in patients with acute atrial fibrillation less than a few days in duration [15]. In another
recent report, the proposed mechanism of stroke was
unidentified effect of sildenafil on the already damaged
blood vessel because of other disease like hypertension
or diabetes [16]. However, this hypothesis is discrepant
from that of our case, because our patient had no
causative diseases that damage the blood vessels.
The initial symptoms of our patient, such as chest
discomfort, palpitation, and dizziness were concordant
with the manifestations of cardiac arrhythmia. Additionally, this patient showed prominent hypotension for
a day. Sildenafil has a terminal half-life of about 4 h
and maximum observed plasma concentrations are
reached within 30–120 min (median 60 min) of oral
dosing in fasting state [2,3]. The onset of symptoms 1 h
after sildenafil ingestion is consistent with the time
range of maximal plasma concentration of the drug.
Transesophageal echocardiogram showed a thrombus
in the left atrial appendage, and cerebral angiography
showed thromboembolic occlusion in the bilateral
MCA. We suggest that transient arrhythmic cardioembolism induced by an excessive catecholamine
response to sildenafil-induced hypotension may be
the etiology.
Sildenafil is a widely used drug for men with erectile
dysfunction, but little is known about stroke risk in
patients who take sildenafil. And the mechanism(s) of
stroke after sildenafil use is still debatable. Because
sexual activity, sildenafil, drug interactions, or the patientÕs underlying cardiovascular disease can all be
implicated, it is more difficult to define the exact cause
for the mechanism of the adverse effect of sildenafil.
Our experience with the bilateral MCA territory
infarction associated with sildenafil use suggests that

sildenafil must be prescribed with caution for the patients without risk factors of vascular events. Further
studies regarding pathophysiology related to cerebral
infarction are needed.

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Ó 2008 The Author(s)
Journal compilation Ó 2008 EFNS European Journal of Neurology 15, 306–308