Case Report

Unilateral Symptomatic Intracranial Arterial Stenosis and
Myopathy in an Adolescent with Graves Disease: A Case Report
of an High-resolution Magnetic Resonance Imaging Study
Jia Yin, MD,* Jiajia Zhu, MD,* Dongling Huang, MD,* Changzheng Shi, MD,†
Yuqing Guan, MD,* Liang Zhou, MD,* and Suyue Pan, MD, PhD*

Vascular and muscular involvements in Graves disease (GD) are rare. Here, we
report a case of a 17-year-old patient with unilateral symptomatic middle cerebral
artery stenosis concurrent with GD and myopathy. He presented with a 1-day history of acute severe right-sided hemiparesis and aphasia and a 3-week history of
high metabolic syndrome. The pathogenesis of the stenosis is most likely vasculitis
rather than atherosclerosis, based on contrast-enhanced high-resolution magnetic
resonance imaging showing concentric wall enhancement. We suggest that lipid
storage myopathy is secondary to GD, and it is likely mitochondrial dysfunction
or immune dysfunction induced by GD responsible for the myopathy and that magnetic resonance spectroscopy (MRS) is capable of establishing the diagnosis of
myopathy. Thus, MRS can be used for follow-up evaluations of the myopathy along
with the pathology biopsy. Key Words: Adolescent—infarction—middle cerebral
artery—Graves disease—muscular diseases—magnetic resonance imaging.
Ó 2015 by National Stroke Association

Graves disease (GD), a common autoimmune disorder
of the thyroid with genetic susceptibility, is mainly
induced by infection and trauma and often results in hyperthyroidism. During the past few years, an increasing

From the *Department of Neurology, Nanfang Hospital, Southern
Medical University, Guangzhou; and †Department of Radiology, First
Affiliated Hospital, Jinan University, Guangzhou, China.
Received July 22, 2014; revision received August 22, 2014; accepted
August 27, 2014.
J.Y. and J.Z. contributed equally to the present study.
The Natural Science Foundation of Guangdong Province, P.R.
China (Grant Nos. 8151051501000053).
The authors have no potential conflicts of interest.
Address correspondence to Suyue Pan, MD, PhD, Department of
Neurology, Nanfang Hospital, Southern Medical University, 1838th
of Guangzhou Avenue North, Guangzhou 510515, China. E-mail:
pan1965suyue@126.com.
1052-3057/$ - see front matter
Ó 2015 by National Stroke Association
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.08.030

number of case reports concerning hyperthyroidism,
together with intracranial arterial disease, cerebral infarction, or transient ischemic attack, have been published,
suggesting a growing interest in GD and vascular diseases.1-3 To the best of our knowledge, there has been
no report of a youth suffering from an ischemic stroke,
GD, and myopathy simultaneously. The present work is
likely the first case with these complicated issues and
provides an initial exploration of the potential etiology
and pathogenesis of the disease.

Case Report
A 17-year-old Asian boy without apparent vascular risk
factors initially presented with a 1-day history of acute severe right-sided hemiparesis and aphasia. Previously, the
patient had experienced bilateral lower extremity weakness early in the morning 3 times during March and April
2012, which was resolved in approximately 10 minutes
after receiving traditional Chinese medical treatment.

Journal of Stroke and Cerebrovascular Diseases, Vol. 24, No. 1 (January), 2015: pp e49-e52

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J. YIN ET AL.

Figure 1. (A) Multiple infarcts are observed in the distribution of the left middle cerebral artery (MCA) on magnetic resonance (MR) diffusion-weighted imaging. (B) MR angiography shows the obvious severe stenosis located at the M1 segment of the left MCA (arrow). (C) Coronal T1WI high-resolution magnetic
resonance imaging shows smooth, concentric wall thickening in the MCA at the onset of the attack (solid arrow). (D) Coronal T1WI with fat suppression demonstrates neither atherosclerosis plaques nor lipid storage existed in the vessel wall (solid arrow). (E) One year later, coronal Magnevist-enhanced T1WI demonstrates concentric wall enhancement (dotted arrow) and the expansion of the lesion (solid arrow) after treatment with methimazole, aspirin, and Lipitor. (F)
Sagittal contrast-enhanced T1WI shows concentric wall enhancement more clearly (dotted arrow).

The patient had been experiencing heat intolerance,
sweating, insomnia, and weight loss for 3 weeks. Except
for the symptoms listed previously, his prior medical history was unremarkable, and he has no history of inherited
disease. The physical examination revealed slight proptosis and a basal metabolic rate increase of .37. In the
neurologic examination, he showed mixed aphasia and
spastic paralysis. The patient scored 14 points on the National Institute of Health stroke scale. The initial laboratory examination showed hyperthyroidism (serum free
thyroxine, 42.25 pmol/L; free triiodothyronine, 13.706
pmol/L; and thyroid-stimulating hormone [TSH], 0.003
mIU/L), and the TSH receptor antibody and antithyroid
peroxidase antibody levels were also elevated (5.66
IU/L and 54.44 IU/mL, respectively). Ultrasound imaging of the thyroid displayed a thickened echo and heterogeneous distribution in both lobes. Routine magnetic
resonance imaging revealed a massive left middle cerebral artery (MCA) territory infarction, and time-of-flight
magnetic resonance angiography and angiography confirmed an identical severe stenosis of the left M1 segment
of approximately 1 cm in length (Fig 1, A,B). The vessel
wall images of high-resolution magnetic resonance imaging (HRMRI) with fat suppression delineated the stenotic
portion of the artery with smooth, concentric wall thickening and without lipid storage (Fig 1, C,D). The patient

was diagnosed with an acute cerebral infarction concurrent with GD. In addition to the traditional treatment
for the infarction, he received methimazole for the treatment of hyperthyroidism at that time. The patient recovered quickly, and his National Institute of Health stroke
scale score decreased to 0 after being hospitalized for a
month. Approximately 1 year later, a follow-up HRMRI
with black-blood contrast-enhancement T1-weighted
sequences showed the expansion of the lesion and concentric wall enhancement in the MCA wall (Fig 1, D,F),
despite almost normal clinical and serum examinations.
In addition, the patient’s initial imaging showed multiple
cortical necroses; as a result, we decided to perform a
muscle biopsy to determine whether mitochondrial encephalopathy was present. Surprisingly, a suspected diagnosis of lipid storage myopathy (LSM) was proposed.
Moreover, the findings from the magnetic resonance spectroscopy (MRS; Fig 2, A) were consistent with the muscle
biopsy (Fig 2, B,C). Interestingly, however, no abnormalities were observed in the blood tests (acylcarnitine
and amino acids), urine tests (organic acids), electromyography, and genetic detection tests (CPT2, CPT1A,
ACADVL, ETFDH, ETFA, ETFB, ACADS, ACADM,
SLC25A20, ABHD5, and SLC22A5). Our patient received
a repeat MRS examination in 2014, which showed that the
myopathy had significantly worsened (Fig 2, D).

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Figure 2. (A) Magnetic resonance spectroscopy showed the quantitative measurement of
lipids in 2013. (B) Hematoxylin-eosin–stained
paraffin section of the muscle biopsy showing
multiple small vacuoles inside parts of the muscle fibers. (C) The Oil Red O method shows that
the amount of red-stained droplets of lipids
among the muscle fibers is higher than normal.
(D) The quantitative measurement of lipids in
2014 was much higher than that in 2013 (A).
The first marked peak represents lipid content,
the second peak represents creatine, and the third
peak represents choline.

Discussion
To the best of our knowledge, this is the first case report
of an adolescent suffering from unilateral symptomatic
MCA stenosis, GD, and myopathy simultaneously. In
this case, 3T-HRMRI was performed twice, including at
the onset of the stroke and 1-year follow-up examinations,
to visualize the vessel wall pathology and differentiate
the etiology and pathogenesis. We inferred from the
HRMRI that neither atherosclerosis plaques nor lipid
storage existed in the vessel wall. Concentric wall enhancement and thickening suggested that the attack
could likely be attributed to vasculitis rather than atherosclerosis or other causes.4 We noted that only most of the
circle showed on Fig 1, F with contrast-enhancement in
the layer. The reason could be that a small part of the
vessel wall is not undergoing active period of vascular
inflammation all the time.
Hyperthyroidism has been confirmed to be closely
related to intracranial arterial stenosis.2,3 However, the
pathogenesis involved in this relationship has not been
elucidated, and several hypotheses have been proposed.
At first, sympathetic activity increases. Excessive thyroid hormones may augment the intracranial vascular
sensitivity to the sympathetic nervous system, leading
to pathologic changes in the vascular walls.5 Second, an
immune-mediated inflammatory mechanism may play
an important role in the pathogenesis of these diseases.6
There are only a few case reports in the literature of GD
occurring together with antiphospholipid antibody
syndrome, hyperthyroidism concurrent with Takayasu
arteritis, hyperthyroidism with giant cell arteritis,7,8 or
drug-induced vasculitis caused by antithyroid drugs9
that facilitate the development of pathologic blood ves-

sels. Third, the low hemodynamics induced by hyperthyroidism induces susceptibility to cerebral ischemic
events. High levels of thyroid hormone production are
thought to increase the cerebral metabolism and oxygen
consumption, gradually impairing cerebral perfusion.
Moreover, ischemic stroke is more likely to occur in
the case of intracranial arterial stenosis. In addition,
thyrotoxicosis-induced hypercoagulability may raise the
incidence of ischemic stroke.10 In our case, the cerebral
ischemic event occurred after heavy drinking and sweating. Indeed, we propose that low hemodynamics were
responsible for the cerebral ischemic event. In the literature, intracranial arterial stenosis in patients with GD
usually manifests as moyamoya syndrome, characterized
by progressive stenosis of the bilateral terminal portion of
the internal carotid artery.2 Shigeo et al2 reviewed 32
patients with GD and concurrent intracranial arterial
stenosis, including 28 cases of bilateral carotid artery terminuses stenosis and 3 cases of unilateral lesions. In addition, similar to a patient in another case report, our patient
completely recovered from his illness, but a follow-up
HRMRI showed no radiological improvement.11 Therefore, in our case, a reasonable hypothesis is that the clinical manifestation of intracranial arterial stenosis caused
by hyperthyroidism may be unilateral MCA stenosis in
the early stages, which may develop into a classic case
of moyamoya syndrome in a few years.2,12
As the disease progresses, the amount of intramuscular
lipids increase, and the mechanism underlying this drawback remains elusive. We consider that LSM is secondary
to GD because of the negative genetic tests of primary
LSM. Here, we propose 2 possible explanations for this
issue. One possibility is that mitochondrial dysfunction

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induced by hyperthyroidism may lead to secondary muscle carnitine deficiency.13-15 Evidences proved that a
decrease in muscle carnitine, but not in serum carnitine,
in hyperthyroidism potentially contributes to fatty
acid metabolism disorders, resulting in thyroid myopathy.16,17 The other possibility might be that the same
immune dysfunction mechanism induced by GD is
responsible for both intracranial arterial stenosis and
thyroid myopathy, because they continue to constantly
and gradually develop despite normalization of the T3,
T4, and TSH levels, with only the antibody against the
thyroid remaining elevated. This is similar to another 2
cases that LSM was secondary to Behcet disease18 and
that polymyositis was associated with GD.19 Therefore,
this case suggested that pathologic manifestations of
chronic hyperthyroidism myopathy might have been presented with pure intramuscular lipid deposition at disease onset.
Further research and follow-up evaluations are needed
to confirm our views. This case also illustrates the necessity of imaging technologies, such as HRMRI and MRS,
for patients with intracranial arterial stenosis or GD.

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