Takayasu Arteritls: A Treatable
Cause of Stroke in Infancy
Michael H . K o h r m a n , M D a n d P e t e r R. H u t t e n l o c h e r , M D
Takayasu disease is an artetids of unknown etiology
involving the aorta and its major branches. Untreated,
75% of patients die within two years. A 6-month-old
black female presented with a tight focal seizure, a
flaccid right hemiparesis, decreased pulses in the right
arm, a large left fmntoparietal hypodense area on
computed tomography, and an elevated erythrocyte
sedimentation rate. Cerebral angiography demonstrated irregular dilatation of both carotid arteries and
narrowing of the left middle cerebral artery. Aneurysm
of the right sinus of Valsalva, dilatation of the aortic
root, narrowing of the origins of both carotid arteries,
and beading of the descending aorta were demonstrated by cardiac angiography. The patient was treated
with prednisone (2 mg/kg/day) and azathioptine
(1 mg/kg/day). There was gradual return of the
erythrocyte sedimentation rate to normal over the
ensuing 3-10 months, resolution of the hemiparesis,
and acquisition of normal developmental milestones.
Digital subtraction angiography revealed improvement
in the appearance of the descending aorta and of the
common carotid arteries with the disappearance of the
arterial wall irregularities. Early diagnosis and vigorous
immunosuppression may improve outcome in this rare
and often fatal vascular disease in childhood.
Kohrman MH, Huttenlocher PR. Takayasu arteritis: A
treatable cause of stroke in infancy. Pediatr Neurol
1986;2:154-8.
Introduction
Takayasu or nonspecific aortitis, first described by
Savory in 1856 [1], and Kussmaul in 1872 [2], affects
the aorta and its larger branches. Cerebrovascular
involvement is uncommon with stroke, reported only in
5-10% of patients [3-5]. The pulmonary arteries also
may be involved [6]. The disease has been known by
many terms including pulseless disease, young female
arteritis, idiopathic aortitis, reverse coarctation syndrome, and Martorell syndrome. Takayasu in 1908
described the ocular manifestations as consisting of
wreath-like anastomosis surrounding the optic disk [7].
The most common signs are hypertension, absent
pulses, and vascular bruits [3]. Although it occurs
world-wide, the disease is most commonly found in
From the Departments of Pediatrics and Neurology; University of
Chicago, Pritzker School of Medicine ;.Chicago, Illinois.
Presented in part at the Fourteenth Annual Child Neurology Society
Meeting; Memphis, TN; October, 1985.

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India,Japan, China, and Southeast Asia [8]. The age of
onset in most patients is between 15-20 years [4]. There
is a female to male predominance of 9 to 1 [4]. Rarely
have patients under 2 years of age been reported [9-11].
Two of these patients had rapidly fatal courses. Immunosuppression with steroids has greatly improved
patient outcome in adults. Prior to the use of steroids,
75% of adult patients died in the first 2 years after
diagnosis [12]. We present a 14-month-old black
female infant who had a stroke at age 5 months and
who improved after immunosuppressive therapy.

Case Report
This black female child was well until the age of 5 months when she
experienced 3 days of fever, diarrhea, vomiting, and irritability. Her
appetite decreased, and she was reported to have had neck stiffness
and inability to support her head. On the day of admission she had a
focal motor seizure with transient apnea, followed by paresis of the
right arm and leg. During the next 24 hours she had several further
brief convulsions and worsening of the hemiparesis. She remained
alert interictally. She was born at term, by normal spontaneous
vaginal delivery, of an 18-year-old primiparous mother. Birth weight
was 2,900 grams. There had been no difficulty with the pregnancy or
neonatal period. The family history was unremarkable.
Her head circumference was 40.2 cm (2nd percentile), weight 6.1
kg (10th percentile), length 63 cm (50th percentile), temperature
37.9 °C, pulse 118, respirations 18, and blood pressure 119/89 mm
Hg. Her pupils were 3 mm and reactive; the optic fundi were
unremarkable. Extraocular movements were intact. Facial movements
were symmetric. Gag reflex was present and the tongue was in the
midline. She had a flaccid right hemiparesis. Her deep tendon
reflexes were hyperactive accompanied by a few beats of right ankle
clonus. Her plantar response was flexor bilaterally. The left axillary
pulse was diminished.
The hemoglobin was 8.8 gm/dl, hematocrit 26.8%, white cell
count 5,700/mm3 (5% bands, 50% neutrophils, 36% lymphocytes,
19% monocytes). Platelet count was 668,000/mm3. Hemoglobin
electrophoretic pattern was normal. Erythrocyte sedimentation rate
(ESR) was 75 mm/hr. Serum electrolytes were normal. Glucose was 88
mg/dl. Cerebrospinal fluid (CSF) contained 1 RBC/mm 3 and 3
WBC/mm3. The CSF protein was 34 mg/dl and the glucose was 31
mg/dl. Urine amino acids were normal. Rheumatoid factor was 1:40
(normal <80), C-reactive protein was 12.2 mg/dl (normal <0.6
mg/dl) and anti-nuclear antibody was 50. Her total hemolytic
complement was 175 U (normal: 182-320 U), C4 immuno-adherence
was 2,000 U (normal: 3,000-3,000 U), Catecholamines and VMA
were normal. Plasma renin activity was 10.17 ng/ml/hr (normal: 4.613 ng/ml/hr). Her PPD test was negative.
A large left frontoparietal unenhanced hypodense area was
demonstrated by computed tomography (CT) (Fig 1). Cerebral
angiography revealed marked vascular changes, including ectasia of
the left carotid body, peculiar segmental constrictions in the proximal
Communications should be addressed to:
Dr. Huttenlocher; Department of Pediatrics, Section of Pediatric
Neurology; The University of Chicago; Box 228, 5841 South
Maryland Avenue; Chicago, IL 60637.
Received February 24, 1986; accepted March 25, 1986.

Figure 1.

CT scan demonstrates a left frontoparietal hypodensity.

intracranial branches of the left middle cerebral artery, and sudden
termination of the proximal anterior cerebral artery and several of its
smaller branches (Fig 2). Cardiac ultrasound studies and cardiac
catheterization documented an aneurysm of the sinus of Valsalva,
dilatation of the aortic root, narrowing of the origins of both carotid
arteries, and a beaded appearance of the descending aorta (Fig 3,4).
Ultrasound study of the kidneys was noncontributory. Ultrasound
study of the aorta revealed a dilated thoraco-abdominal aorta and a
questionable narrowing of the celiac axis. Electroencephalogram
(EEG) was unremarkable.
She was treated initially with dexamethasone (1 mg/kg/day) (Fig
5) which was replaced by prednisone (2 mg/kg/day). Her ESR fell to
38 m m / h r but then rose gradually to 73 m m / h r . Azathioprine (1
mg/kg/day) was added concurrently with a fall in the ESR to 5
m m / h r over the next 2 months. Digital subtraction venous
angiogram perfomed after 3 months of immunosuppression (Fig 6)
demonstrated continued dilatation of the aortic arch, a normal
descending aorta, slight dilatation of the common carotid arteries
with no abnormality of the arterial walls, and occlusion of the right
vertebral artery (not visualized on previous studies). EEG revealed a
mild asymmetry of sleep spindles that indicated left hemisphere
dysfunction. Ultrasound of the aorta demonstrated a normal aorta
and celiac axis. In general, the follow-up angiographic study
demonstrated striking improvement compared to the initial findings.
At 14 months of age her head circumference was 43 cm (2nd
percentile), weight 7.9 kg (3rd percentile) and height 72 cm (7th
percentile). She used several words meaningfully and responded to
her name. She cruised around furniture. Her right hand was kept
fisted, but she used it to grasp objects and transferred objects from
her left to her right hand. She had full extension at the elbow and
wrist but slight limitation of supination on the right. She tended to
keep the left leg externally rotated when cruising and took steps with
minimal assistance. Her reflexes were normal and symmetric but her
right Babinski response was extensor. After gradually discontinuing
azathioprine, the ESR rose to 37 m m / h r . Currently she is being
treated with prednisone (2 mg/kg/day) and azathioprine (1
mg/kg/day).

Discussion
Takayasu arteritis rarely is recognized in infancy
[9-11]. Considering the widespread arterial changes of
this disease, stroke is remarkably uncommon in all age

Figure 2. Cerebral angiogram (left carotid injection) demonstrates
ectasia at the level of the carotid body, narrowing of the distal
internal carotid artery, and lack of filling o f the anterior cerebral
artery.

Figure 3. Cardiac catheterization with a left ventricular injection
reveals dilatation of the aortic root, aneurysm of the sinus of Valsalva,
and dilatation at the origins of the left carotid and ngbt subclavian
arteries.

Kohrman and Huttenlocher: Takayasu Arteritis in Infancy

155

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Figure 4. Cardiac catheterization with a left ventticular inleettbn
demonstrates the beaded appearance of the descending aorta and
multiple ectasiasof the right subclavian artery.

groups. Lupi-Herrera et al. [3], reported in a study of
107 patients, that 7% had hemiplegia, 1% had
paraplegia, 57% had headache, and 15 % had syncope.
Cupps and Fauci [4] reported stroke in 7 % and syncope
in 51%. Tech et al. [5], in a study of 48 patients,
described hemiplegia in 10%, headache in 19%,
blurred vision in 4 %, optic atrophy in 1%, and ptosis
in 1%. In a recent study of 32 North American
patients, 1 patient had hemiparesis as the result of
stroke, 2 patients had seizures, 3 patients had diplopia
secondary to cerebrovascular insufficiency, and 2
patients had episodes of amaurosis [8]. The etiology of
stroke appears to be thrombus formation or embolus
from distal large vessels. No neurologic signs were
reported in 7 patients with cardiac valvular involvement [13].
Constitutional symptoms in older patients include
weight loss (22%), fever (18%), and asthenia (56%)
[3]. Cardiovascular signs and symptoms include
hypertension (78%), intermittent claudication (29%),
pulse deficit (46%), and vascular bruits (94%) [3].
Elevation of ESR occurs in 83% of patients and
C-reactive protein in 23 %. The blood urea nitrogen is
elevated in 16 %, while the creatinine is elevated in 4 %
[3]. Rheumatoid factor is positive in 4%. Serum
3,-globulin is increased in 34% and proteinuria occurs
in 28% [3]. In this series from Mexico, 48% of patients
had a history of active tuberculosis [3].
Features of Takayasu arteritis overlap those features
of granulomatous arteritis and sclerosing arteritis [8].
The granulomatous features correspond to the active
phase of the disease, with inflammation confined to the
media and adventitia [8]. The cellular infiltrate consists
predominantly of lymphocytes, plasma cells, and
histiocytes [8]. The sclerosing arteritis signifies the
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l~'gure5. ESR is documented tbrougbout the courseof therapy. (A)
Dexametbasone 0.5 mg/kg/day; (B) Predgisone 2 mg/kg/day
begun; (C) Azat/a'oprine 1 mg /kg /day added; (D) Otitis mea~'a; (E)
Digital subtraction angiogram andprednisone taper begun; (F) Otitis
media; (G) Azathioprine 0.8 mg/kg/day and prednisone 1.25
mg/kg/day; (H) Herpangina, prednisone 2 mg/kg/day, and
azatbioprine 1.0 mg /kg /day.

chronic phase of the disease [8] which is characterized
by bland fibrous intimal hyperplasia, medial
degeneration, and adventitial fibrosis [8], Disruption of
the elastic lamina, thrombus formation, and aneurysm
formation occur in the chronic phase of the disease, The
arterial involvement is divided into four types [3]: type
1 (Shimizu-Sano) involves the ascending aorta and its
major branches; type 2 0edmoto) involves the abdominal aorta and renal arteries; type 3 (Inada)

Figure 6. Digital subtraction angiogram with an inferior vena cava
injection demonstrates the normM appeara~*xeof the origins of ske
leJ9carotidand right subclavian arteriesand lumen of tbe descending
aorta.

combines the features of types 1 and 2, and; type 4
(Lupi-Herrera) involves the pulmonary arteries. Our
patient appears to have type 1.
The etiology of Takayasu arteritis is unknown. There
is a strong association with previous exposure to
tuberculosis. Tuberculin sensitivity has been
demonstrated in 81-100% of patients studied [14].
Between 21-70% of patients have had active tuberculosis [14]. The general incidence of active tuberculosis
in these populations ranges from 0.028-0.309% and
the prevalence from 1.5-4.2 %. Rabbits inoculated with
M. tuberculosis in the subadventitia of the aorta
showed changes similar to those of Takayasu arteritis
[3]. One pair of twins, born to parents who were first
cousins, was reported to be concordant for Takayasu
arteritis [15]. HLA and blood types of the twins were
identical to the father's. A number of families were
reported with involvement in two generations and also
families with two affected siblings [15]. However, no
consistent HLA association was reported in Japan,
Mexico, or the United States [8].
Therapy of stroke in infancy is available for only a few
causes, including Takayasu arteritis. It should be
distinguished from other forms of focal vasculitis [4],
traumatic injury to the carotid artery [16], moyamoya
disease [17], sickle cell cerebrovascular disease [18], and
embolic occlusion from cardiac thrombi [19]. ESR
measurement and ultrasound examination of the heart
and great vessels are simple screening tests which help
to differentiate Takayasu arteritis from these other
conditions, as does the finding of arterial hypertension.
Characteristic changes in the large vessels are readily
demonstrable by digital subtraction angiography.
Four cases of stroke in Takayasu arteritis have been
described in the pediatric population. A 9-month-old
female presented with seizures, fever, nystagmus,
bulbar signs, and a right hemiparesis. Her ESR was 90
mm/hr, and CSF was normal initially but the protein
content rose to 100 mg/dl. Angiography revealed
lesions in both common carotid, the left subclavian,
and the superior mesenteric arteries, as well as in the
descending aorta. The patient died 7 weeks after onset
of symptoms despite steroid therapy [10]. Three older
children, ages 6-10 years, were reported [20-22], two
with fatal outcomes. Takayasu arteritis without
cerebrovascular involvement was described in two
infants [9,11]. One child presented with an abdominal
mass and vomiting at 7 months, and had rapidly
progressive heart failure. Autopsy demonstrated an
aneurysm of the right common iliac artery and an
iliocaval fistula [9]. The other child presented at 6
months of age with failure-to-thrive and excessive
sweating. At 8 months of age the child had fever,
hypertension, renal failure, and elevated ESR (94
mm/hr).
Angiography indicated severe aortic,
mesenteric, and renal artery involvement. Both kidneys
were reimplanted and the child is doing well 41/2 years
later, without use of immunosuppressive drugs [11].

This case appears to be an example of restricted involvement (type 2 disease) which may have a better
prognosis.
Prior to steroid therapy, 75 % of patients died within
2 years of diagnosis [12]. Steroid therapy clearly
decreases the signs of systemic inflammation in adult
patients with Takayasu arteritis [4,8,12,23]. Adult
5-year survival rate with steroid therapy is 94% [8].
Although it has been suggested that steroid therapy
alone is sufficient for most patients with Takayasu
arteritis, there has been no controlled trial of the effects
of steroids or cytotoxic drugs [4,8]. Steroid therapy
alone did not reduce the ESR to normal levels in our
patient. Among 29 patients treated with corticosteroids
alone, 16 had an ESR initially greater than 40 mm/hr;
in only 5 of the 16 did the ESR fall to the normal range
after treatment [23]. Of the 29 patients, 18 had positive
clinical responses to therapy. The addition of
azathioprine resulted in the ESR returning to normal in
our patient, accompanied by improvement of the
vascular lesions as demonstrated by angiography.
Although the disease now may have a low mortality in
adults because of corticosteroid therapy, incomplete
response to steroids appears to be a reasonable criterion
for the use of more vigorous immunosuppression,
especially in infants with a rapidly progressive form of
the disease.
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