Journal of Clinical Neuroscience xxx (2014) xxx–xxx

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Journal of Clinical Neuroscience
journal homepage: www.elsevier.com/locate/jocn

Case Report

A male Fabry disease patient treated with intravenous thrombolysis
for acute ischemic stroke
Jukka T. Saarinen a,⇑, Niko Sillanpää b, Ilkka Kantola c
a

Department of Neurology, Vaasa Central Hospital, 65100 Vaasa, Finland
Medical Imaging Center, Tampere University Hospital, Tampere, Finland
c
Department of Internal Medicine, Turku University Hospital, Turku, Finland
b

a r t i c l e

i n f o

Article history:
Received 3 April 2014
Accepted 26 July 2014
Available online xxxx
Keywords:
Acute ischemic stroke
CT angiography
Fabry disease
Intracranial haemorrhage
Intravenous thrombolytic therapy
R227X mutation
Telestroke

a b s t r a c t
The use of intravenous thrombolytic therapy for acute ischemic stroke is associated with improved outcomes. Fabry disease is an X-linked glycosphingolipid storage disease with vascular endothelial deposits.
Affected males with the classic phenotype develop renal, cardiac, and cerebrovascular disease and die
prematurely. However, Fabry disease is rare in young men with first ischemic stroke of undetermined
cause. We report a 38-year-old man with acute aphasia and a left M2 segment of the middle cerebral
artery thrombus with no recanalization who was finally diagnosed with Fabry disease after left ventricular hypertrophy of undetermined cause had been identified. A gene test revealed a R227X mutation typical of Fabry disease with the classical phenotype. To our knowledge our patient is the first reported male
Fabry patient who was given intravenous thrombolytic therapy and the first reported Fabry patient who
received intravenous thrombolytic therapy between 3 and 4.5 hours of the symptom onset. Despite
favorable prognostic indicators on admission imaging, our patient suffered a significant stroke and had
an unfavorable clinical outcome. Fortunately, the episode was not complicated by intracranial hemorrhage. Further studies are needed to evaluate the efficacy and safety of intravenous thrombolytic therapy
in treating patients with Fabry disease and acute ischemic stroke.
Ó 2014 Elsevier Ltd. All rights reserved.

1. Introduction
The use of intravenous thrombolytic therapy (IVT) for acute
ischemic stroke is associated with improved outcomes for a broad
spectrum of patients who can be treated within 3 hours of symptom onset and for a more selective spectrum of patients who can
be treated between 3 and 4.5 hours of symptom onset. Treatment
with IVT is also associated with increased rates of intracranial
hemorrhage, which may be fatal [1].
Fabry disease is an X-linked glycosphingolipid storage disease
with vascular endothelial deposits due to deficient a-galactosidase
A activity. Affected males with the classic phenotype develop renal,
cardiac, and cerebrovascular disease and die prematurely. However, Fabry disease is rare in young men with a first ischemic
stroke of undetermined cause [2].
2. Case report
In April 2013, a 38-year-old man with acute aphasia was admitted to the Vaasa Central Hospital in the western part of Finland as a
⇑ Corresponding author.
E-mail address: jukka.saarinen@vshp.fi (J.T. Saarinen).

candidate for IVT. According to his patient records, 5 years earlier
he visited a urologist due to atypical abdominal pain. In 2010, he
visited the emergency department due to prolonged respiratory
inflammation and complained of suffering from severe muscle pain
during fever. The following year he developed progressive leg
edema of unknown cause. In 2012, he was admitted to the cardiologic department due to thoracic pain and inferolateral T-wave
inversions in an electrocardiogram. Coronary artery angiography
was performed but no sign of coronary artery disease was found.
However, aspirin monotherapy was recommended. Echocardiography showed left ventricular hypertrophy (LVH) which was thought
to be caused by hypertension and the patient continued to use
blood pressure (BP) lowering medication.
In April 2013, no acute ischemic changes were visible on admission CT imaging and his Alberta Stroke Program Early CT Score
(ASPECTS) was 10 (Fig. 1). However, on the right frontal hemisphere there were multiple chronic lacunar infarcts in the white
matter (Fig. 1A). On cranial CT angiography (CTA) an M2 segment
of the middle cerebral artery thrombus was visualized on the left
side (Fig. 1B). The ASPECTS of the CTA source images was 10 and
collateral circulation was rated as good (collateral score of 2).
Despite the patient’s young age atherosclerotic changes were
already discernible in the proximal intracranial vessels both in

http://dx.doi.org/10.1016/j.jocn.2014.07.021
0967-5868/Ó 2014 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Saarinen JT et al. A male Fabry disease patient treated with intravenous thrombolysis for acute ischemic stroke. J Clin
Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.07.021

2

Case Report / Journal of Clinical Neuroscience xxx (2014) xxx–xxx

Fig. 1. Admission (A–C) and day 1 follow-up (D) imaging. (A) Axial CT scan showing small chronic lacunar ischemic lesions in the right frontal white matter (white arrows).
(B) The site of occlusion can be seen in a left proximal M2 branch (black arrow) on angiography. (C) Axial CT scan showing no acute ischemic changes whereas in (D) a
subacute infarction is evident (white arrows) on the same level axial slice the following day.

the anterior and posterior circulation. Following a telestroke consultation IVT was administered 3 hours and 10 minutes after
symptom onset. National Institutes of Health Stroke Scale score
was four due to aphasia and BP at the time of bolus of the thrombolytic agent (alteplase) was 134/71 mmHg. The patient received
90 mg (0.9 mg/kg) of alteplase over 1 hour.
The following day no neurologic improvement had taken place.
CT imaging showed a subacute infarction (ASPECTS 6) in the left
temporoparietal region corresponding to the vascular territory of
the occluded M2 segment vessel (Fig. 1D). Hemorrhagic transformation was not observed. The patient was under continuous bedside electrocardiogram monitoring and no paroxysmal atrial
fibrillation was detected. Cervical arteries were intact according
to CTA but the occluded left M2 branch had not recanalized. Echocardiography did not reveal any sources of embolism but LVH was
again noted. The attending neurologist realized that the patient’s
previous diagnosis of hypertension was probably false because
documents from the patient́s occupational health care showed that
a 24 hour ambulatory BP monitoring period had been normal.
Ischemic stroke and LVH of undetermined cause led to a suspicion
of Fabry disease. A remarkable deficiency of a-galactosidase A
activity in leukocytes was demonstrated and finally a gene test
revealed a R227X mutation typical of Fabry disease with classical
phenotype [3]. At the 3 month follow-up, his modified Rankin scale
score was three due to moderate disability caused by aphasia.
Starting from December 2013, the patient has been on enzyme
replacement therapy with a-galactosidase A. At the time of writing
neither recurrent stroke nor renal dysfunction had occurred.

3. Discussion
Our patient is the first case of diagnosed Fabry disease in the
Vaasa Hospital District which has approximately 170,000 inhabitants. Despite having had some typical features of Fabry disease,
diagnosis was delayed until the patient had a severe cerebrovascular manifestation. According to data from the Fabry Registry, 6.9%
of male Fabry patients at a median age of 39 years and 4.3% of
female Fabry patients at a median age of 46 years experience
strokes. Hemorrhagic strokes are more common in Fabry males
(16.9%) than females (6.8%) [4]. In the literature, one case report
of a female Fabry patient who received IVT 3 hours after symptom
onset was found [5]. To our knowledge our patient is the first
reported male Fabry patient who was given IVT and the first
reported Fabry patient who received IVT between 3 and 4.5 hours
of symptom onset. Despite favorable prognostic indicators on
admission imaging scans and IVT, our patient suffered a significant
stroke and had an unfavorable clinical outcome. Fortunately, the
episode was not complicated by intracranial hemorrhage. Further
studies are needed to evaluate the efficacy and safety of IVT in
treating patients with Fabry disease and acute ischemic stroke.

Conflicts of Interest/Disclosures
Dr. Saarinen has received speaker honoraria from Boehringer
Ingelheim and funding for travel from Genzyme. Dr. Kantola is an
advisory board member of Boehringer Ingelheim, and has received

Please cite this article in press as: Saarinen JT et al. A male Fabry disease patient treated with intravenous thrombolysis for acute ischemic stroke. J Clin
Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.07.021

Case Report / Journal of Clinical Neuroscience xxx (2014) xxx–xxx

speaker honoraria and funding for travel from Genzyme and Shire.
Dr Sillanpää declares no financial or other conflicts of interest in
relation to this research and its publication.

References
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patients with acute ischemic stroke: a guideline for healthcare professionals
from the American Heart Association/American Stroke Association. Stroke
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[2] Wozniak MA, Kittner SJ, Tuhrim S, et al. Frequency of unrecognized Fabry
disease among young European–American and African–American men with
first ischemic stroke. Stroke 2010;41:78–81.
[3] Eng CM, Resnick-Silverman LA, Niehaus DJ, et al. Nature and frequency of
mutations in the alpha-galactosidase A gene that cause Fabry disease. Am J
Hum Genet 1993;53:1186–97.
[4] Sims K, Politei J, Banikazemi M, et al. Stroke in Fabry disease frequently occurs
before diagnosis and in the absence of other clinical events: natural history data
from the Fabry Registry. Stroke 2009;40:788–94.
[5] Zenone T, Chan V. Young woman with recurrent ischemic strokes diagnosed as
Fabry disease: lessons learned from a case report. Clin Neurol Neurosurg
2011;113:586–8.

Please cite this article in press as: Saarinen JT et al. A male Fabry disease patient treated with intravenous thrombolysis for acute ischemic stroke. J Clin
Neurosci (2014), http://dx.doi.org/10.1016/j.jocn.2014.07.021