2252 Case Reports / Journal of Clinical Neuroscience 21 (2014) 2252–2254

O. tsutsugamushi antibodies (1:80) and level of protein (88.1 mg/dL),
but white blood cells were absent.
A nerve conduction study demonstrated reduced sensory nerve
action potentials and absent H-reflexes. After the diagnosis of MFS,
intravenous Ig was administered for 5 days, and his symptoms
gradually improved.
3. Discussion
ulid mites. The neurological complications of scrub typhus can lead
to meningoencephalitis, vasculitic neuropathy, and cerebral
infarction. Cases of GBS related to O. tsutsugamushi manifesting
as respiratory failure, polyneuropathy, and cerebral infarction have
been reported [5]. However, to the best of our knowledge, cases of
MFS related to O. tsutsugamushi have not been reported. This case
suggests that O. tsutsugamushi infection should be considered
when identifying antecedent pathogens in patients with MFS.

We describe a patient with MFS following O. tsutsugamushi Conflicts of Interest/Disclosures

infection, which to our knowledge has not been reported in the lit-
erature. MFS is a variant of GBS and has a higher reported inci-
dence in Asian populations. Areflexia, ophthalmoplegia, and
ataxia are the clinical characteristics of MFS and anti-ganglioside
IgG antibodies are detected in serum [1,3].
Well-known inciting pathogens are C. jejuni, Mycoplasma pneu-
moniae, Haemophilus influenzae, Epstein-Barr virus, cytomegalovi-
rus, varicella zoster virus, human immunodeficiency virus, and
Helicobacter pylori. However, large prospective serological studies
have revealed that the infective agents remain unknown in the
majority of cases [2]. There are also many case reports of rare caus-
ative pathogens such as enterovirus, dengue virus, Coxiella burnetii,
and Pasteurella multocida.
One study reported an elevation up to 89% of anti-GQ1b
antibodies in MFS patients. These antibodies are known to cause
ophthalmoplegia by blocking neuromuscular transmission in
oculomotor muscles. However, anti-GQ1b antibodies are not
always present in MFS, and many cases remain antibody negative.
Reduced sensory nerve action potentials and absent H-reflexes, as
in our patient, are the most consistent electrophysiological find-
ings in MFS [4].
O. tsutsugamushi is a cause of an acute febrile zoonosis, scrub
typhus, and is transmitted to humans by the bite of larval trombic-
The authors declare that they have no financial or other
conflicts of interest in relation to this research and its publication.
Acknowledgements
This study was partially supported by a Grant from the Korea
Healthcare technology R & D project, Ministry of Health and Wel-
fare, Republic of Korea (HI10C2020).
References
[1] Fisher CM. An unusual variant of acute idiopathic polyneuritis (syndrome of
ophthalmoplegia, ataxia and areflexia). N Engl J Med 1956;255:57–65.
[2] Koga M, Gilbert M, Li J, et al. Antecedent infections in Fisher syndrome: a
common pathogenesis of molecular mimicry. Neurology 2005;64:1605–11.
[3] Chiba A, Kusunoki S, Obata H, et al. Serum anti-GQ1b IgG antibody is
associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré
syndrome: clinical and immunohistochemical studies. Neurology 1993;43:
1911–7.
[4] Arányi Z, Kovács T, Sipos I, et al. Miller Fisher syndrome: brief overview and
update with a focus on electrophysiological findings. Eur J Neurol
2012;19:15–20.
[5] Ju IN, Lee JW, Cho SY, et al. Two cases of scrub typhus presenting with Guillain-
Barré syndrome with respiratory failure. Korean J Intern Med 2011;26:474–6.

http://dx.doi.org/10.1016/j.jocn.2014.04.027

Giant cell polymyositis associated with myasthenia gravis and thymoma

Lin Jie a,1, Lu Jun a,1, Zhao Chongbo a, Qiao Kai b, Zhu Wenhua a, Yue Dongyue a, Luo Sushan a, Wang Yin c,
Fang Wentao d,⇑, Lu Jiahong a
a
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
b
Department of Neurophysiology, Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China
c
Department of Neuropathology, Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China
d
Department of Thoracic Surgery, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, 241 W Huaihai Road, Shanghai, China

a r t i c l e i n f o a b s t r a c t

Article history: We report a case of a 40-year-old woman who developed generalized muscle weakness over a period of
Received 24 September 2013 2 months. Physical examination revealed palpable masses in her arms and hands. Serum creatine kinase
Accepted 23 April 2014 levels were elevated. Electromyography showed myopathic changes and 3 Hz repetitive nerve stimula-
tion revealed a decremental pattern on repetitive nerve stimulation. Muscle MRI demonstrated increased
signal intensity in the biceps brachii on T1-weighted images. Chest CT scan showed a mediastinal mass
Keywords: suggestive of thymoma. Muscle biopsy revealed giant cell polymyositis. The patient was treated with
Giant cell polymyositis
cholinesterase inhibitors and corticosteroids with improvement of strength, and subsequently under-
Muscle MRI
Myasthenia gravis
went thymectomy followed by radiotherapy.
Thymoma Ó 2014 Elsevier Ltd. All rights reserved.

⇑ Corresponding author. Tel.: +86 21 5288 8155; fax: +86 21 6248 3421.
E-mail address: fudan78@hotmail.com (W. Fang).
1
These authors have contributed equally to the manuscript.
1. Introduction
Giant cell polymyositis associated with myasthenia gravis
(MG) and thymoma are exceptionally rare. In 1944, Giordano and

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 Case Reports / Journal of Clinical Neuroscience 21 (2014) 2252–2254 2253

Haymondo reported the first autopsied case with MG, thymoma,
giant cell polymyositis and myocarditis [1]. In 1969, Burke
reported a case of sudden death due to similar disease [2]. To our
knowledge, previously reported cases of giant cell myocarditis or
myositis associated with thymoma and MG were almost all diag-
nosed on autopsy [3–7]. We report a patient who presented with
weakness due to a combination of MG and giant cell polymyositis
diagnosed by muscle biopsy.
2. Case report
A 40-year-old woman presented to our hospital with a 2 month
history of limb swelling and stiffness. The swelling began in her left
foot and ankle, and gradually extended proximally. A month later
she noticed the development of nodules within the muscle of her
right arm and thenar muscles of both hands. The patient then
developed generalized muscle tenderness and weakness followed
by bilateral ptosis, dysphagia and fatigue. Injection of neostigmine
resulted in significant improvement of her weakness.
Physical examination revealed mild edema in both feet and
ankles, contractures at the elbows and knees, and subcutaneous
nodules in the right arm and hands. No lymph node enlargement
or skin rash was found. Neurological examination showed slight
bilateral ptosis, nasal speech, and moderate proximal muscle
weakness. Tendon reflexes and the remainder of the neurological
findings were normal.
Serum creatine kinase level was elevated at 2865 U/L (normal
38–174 U/L) and serum acetylcholine receptors antibodies were
positive (6.27 nmol/L; normal <0.45 nmol/L). Troponin T was
0.425 ng/ml (normal 0.013–0.025 ng/ml), and C-reactive protein
and erythrocyte sedimentation rate were elevated, at 66.8 mg/L
(normal <6.8 mg/L) and 48 mm/hour (normal 620 mm/hour),
respectively. Antinuclear antibodies were positive 1:100 (normal
is negative); perinuclear anti-neutrophil cytoplasmic antibodies
were also positive. Myositis-associated antibodies, including Mi-
2, Ku, PM-Scl, Jo-1, PL-7, PL-12, Ro-52, and signal recognition par-
ticle were negative.
The electrocardiogram and echocardiogram were both normal.
Needle electromyogram demonstrated active myopathic units in
limb muscles. Three Hz repetitive nerve stimulation of the axillary,
accessory and median nerves showed a 26–36% decrement sugges-
tive of a defect of neuromuscular transmission.
MRI of the limbs revealed multifocal high signal intensity in
several muscles (the right biceps, flexor carpi ulnaris, flexor carpi
radialis and brachioradialis; bilateral adductor magnus, rectus
femoris, hamstring and gastrocnemius) on short T1-weighted
inversion recovery images (Fig. 1). A large paraspinal mass was
incidentally found by MRI (Fig. 2A). To further characterize this
mass, a chest CT scan was performed and this revealed a large mass
in the anterior mediastinum, extending into the right pleural cavity
(Fig. 2B).
Muscle biopsy of the right biceps brachii showed muscle fiber
size variability, necrotic and regenerating muscle fibers and an
inflammatory exudate consisting of lymphocytes and macrophages
(Fig. 3). There were numerous giant cells of myogenous type,
including foreign-body giant cells, Langhans giant cells and Touton
giant cells. Inflammatory cells stained positive for CD68, CD3,
CD45, CD138 and CD20 and infiltrative lymphocytes were positive
for CD8.
The patient was treated with steroid therapy and significantly
improved, with resolution of the right arm muscle nodules and
gradual reduction of serum creatine kinase. Thymectomy was
performed and histological examination revealed epithelial
thymoma (B3 by the World Health Organization classification).
The patient remains on oral prednisone and is in a stable condition.
3. Discussion
MG is an autoimmune disease of the neuromuscular junction
leading to fluctuating muscle weakness and fatigability. Thymoma

Fig. 1. T1-weighted axial MRI of muscle revealed patchy abnormal signal in the thighs (A) and calves (B).

Fig. 2. T1-weighted coronal MRI revealed abnormal signal in the right arm and a paravertebral mass was noted (A). Axial CT scan showed an anterior mediastinal mass and a
large posterior mass in the right pleural cavity (B).

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2254 Case Reports / Journal of Clinical Neuroscience 21 (2014) 2252–2254
Fig. 3. Hematoxylin and eosin staining (original magnification  400) of the muscle showed giant cells, including Touton giant cell (A, D), foreign-body giant cell (B) and
Langhans giant cell (C). (This figure is available in colour at http://www.sciencedirect.com/.)
is present in 10–15% of all MG patients [5]. Other autoimmune
diseases, including rheumatoid arthritis, idiopathic systemic lupus
erythematosus, and vasculitis, have been reported in association
with MG. However, there are very few reports of combined giant
cell polymyositis, MG and thymoma.
Giant cells can be classified into several morphological variants.
The origin of giant cells in giant cell polymyositis with MG and thy-
moma is primarily foreign-body giant cell and Langhans giant cell
[7]. Foreign-body giant cells contain many nuclei that are arranged
in a diffuse manner throughout the cytoplasm. In comparison, Lan-
ghans giant cells are located in the periphery surrounding the Golgi
complex and other organelles. Touton giant cells are also found in
the disease, but they are rare.
Most similar cases reported in the literature were diagnosed on
autopsy. Our patient was diagnosed by muscle biopsy. Soft tissue
and musculature changes in idiopathic myositis include edema
within and around muscles, muscle calcification as well as fatty
infiltration of muscle [8]. Sonography shows increased muscle ech-
ogenicity. In addition, fascia and septa become obscure with alter-
ation of the normal striated (on longitudinal scans) and patchy (on
transverse scans) architecture [9].
To our knowledge there are no reports regarding the MRI fea-
tures of giant cell polymyositis in the literature. In this patient,
we found patchy abnormal signal within the short head of the
biceps brachii, and proximal muscles of the upper and lower limbs.
Moreover, the signal changes were more prominent around the
periphery of the muscle fibers compared to signal changes within
muscle fibers, suggesting that the inflammatory changes mainly
focused on around the musculature. This is different from
idiopathic polymyositis and more similar to focal myositis. This
suggests that giant cell polymyositis might be an independent
inflammatory muscle disease.
Giant cell myocarditis is a lethal disease, leading to heart fail-
ure, cardiac arrhythmia and sudden death [10]. It is occasionally
http://dx.doi.org/10.1016/j.jocn.2014.04.027
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For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
accompanied by giant cell polymyositis associated with MG and
thymoma and should be considered in the context of a patient with
features of both MG and myositis. Such patients require evaluation
for cardiac involvement and long-term follow-up for late myocar-
dial damage.
Conflicts of Interest/Disclosures
The authors declare that they have no financial or other con-
flicts of interest in relation to this research and its publication.
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necropsy findings. Am J Clin Pathol 1944;14:253–65.
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with thymoma and myasthenia gravis. Arch Pathol 1969;88:359–66.
[3] Watanabe M, Suzuki H, Ara T, et al. Relapsing polychondritis complicated by
giant cell myocarditis and myositis. Intern Med 2013;52:1397–402.
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cardiogenic shock: an unusual presentation of malignant thymoma. Cardiol
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[6] Sato H, Iwasaki E, Nogawa S, et al. A patient with giant cell myocarditis and
myositis associated with thymoma and myasthenia gravis. Rinsho Shinkeigaku
2003;43:496–9.
[7] Kon T, Mori F, Tanji K, et al. Giant cell polymyositis and myocarditis associated
with myasthenia gravis and hymoma. Neuropathology 2013;33:281–7.
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[9] Cantwell C, Ryan M, O’Connell M, et al. A comparison of inflammatory
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[10] Morrissey RP, Rana JS, Luthringer DJ, et al. Case of fulminant giant-cell
myocarditis associated with polymyositis, treated with a biventricular assist
device and subsequent heart transplantation. Heart Lung 2011;40:340–5.