doi: 10.2169/internalmedicine.5099-20
Intern Med 59: 3089-3092, 2020
http://internmed.jp

【 CASE REPORT 】

Cerebral Infarction and Myalgia in a 75-year-old Man
with Eosinophilic Granulomatosis with Polyangiitis
Yuki Ueta 1, Yuki Akiba 1, Jun Yamazaki 1, Yoshihiko Okubo 2, Takeshi Taguchi 1,
Hiroo Terashi 2, Yukiko K. Hayashi 3 and Hitoshi Aizawa 2

Abstract:
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare condition of systemic vasculitis of small to
medium-sized blood vessels. We herein report the case of a 75-year-old man who presented with hemiplegia
on his right side due to cerebral infarction following myalgia and a high fever. He had no history of asthma
or allergic rhinitis. He was diagnosed with EGPA based on the presence of eosinophilia, sinusitis suggested
by magnetic resonance imaging, and muscle pathology. His hemiplegia improved rapidly after corticosteroid
therapy. This case suggests that EGPA should be a differential diagnosis of cerebral infarction with myalgia
and eosinophilia.
Key words: eosinophilic granulomatosis with polyangiitis (EGPA), Churg-Strauss syndrome, cerebral
infarction, myalgia, muscle biopsy, corticosteroid therapy
(Intern Med 59: 3089-3092, 2020)
(DOI: 10.2169/internalmedicine.5099-20)

Introduction
Eosinophilic granulomatosis with polyangiitis (EGPA,
also known as Churg-Strauss syndrome) is a systemic necrotizing vasculitis of small- to medium-sized vessels with
extravascular eosinophilic infiltration (1, 2). EGPA is clinically characterized by asthma, a history of allergy, neuropathy, pulmonary infiltrates, and abnormalities of paranasal sinuses (2). Remission induction therapy for EGPA includes
corticosteroids with immunosuppressant drugs, such as cyclophosphamide and rituximab (3, 4). However, without the
characteristic features, a diagnosis of EGPA is difficult.
We herein report a patient with cerebral infarction following myalgia and a high fever due to EGPA, which was suggested by a muscle biopsy. His clinical symptoms improved
rapidly after corticosteroid therapy.

Case Report
A 75-year-old man who was undergoing treatment for hyperlipidemia and hypertension complained of a high-grade

fever and myalgia in the limb girdle muscles for the past 10
days. He had a history of esophageal and colon cancer.
There was no history of asthma or allergic rhinitis. He was
admitted four days after his first visit to our hospital.
An initial physical examination revealed the following: his
blood pressure was 112/74 mmHg, pulse rate 108 beats per
minute, and body temperature 38.4℃. He had no skin
rashes or enlargement of cervical lymph nodes. A neurological examination revealed muscle weakness of Medical Research Council (MRC) Muscle scale grade 4 in the bilateral
deltoid and iliopsoas muscles with myalgia. There were no
additional physical or neurological abnormalities.
The level of serum creatine kinase was 632 IU/L. The peripheral blood leukocyte count was 20,100/μL with eosinophilia (8,744/μL; 43.5% leukocytes). The serum levels of Creactive protein (CRP) and IgE were 7.35 mg/dL and 2,240
IU/L, respectively. The electrolyte levels and renal function
were within the normal ranges. The plasma level of D-dimer
was 0.87 μg/mL. The patient was negative for perinuclear
anti-neutrophil cytoplasmic antibodies, and no hematological
malignancies were suggested from the bone marrow or cytogenetic testing. Cytogenetic testing excluded the presence of

１

Department of Neurology, Tokyo Medical University Hachioji Medical Center, Japan, ２ Department of Neurology, Tokyo Medical University, Japan and ３ Department of Pathophysiology, Tokyo Medical University, Japan
Received: April 16, 2020; Accepted: June 21, 2020; Advance Publication by J-STAGE: August 4, 2020
Correspondence to Dr. Yuki Ueta, yukiueta@tokyo-med.ac.jp

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Figure 1. Short-tau inversion recovery magnetic resonance
imaging of the bilateral thigh muscles. A) A coronal image reveals high-signal lesions scattered in the bilateral thigh muscles. B) An axial image reveals high-signal lesions in the right
vastus lateralis (arrow).

deletions in the chromosome 4q12 region and translocations
involving the PDGFRA or FGFR1 genes, both of which
have been reported in patients with myeloid or lymphoid
neoplasms with eosinophilia.
Computed tomography showed no sign of pulmonary infiltration. Short-tau inversion recovery (STIR) magnetic
resonance imaging (MRI) revealed high signal lesions scattered in the bilateral thigh muscles (Fig. 1A), including the
right vastus lateralis (Fig. 1B). Nerve conduction studies
were normal for the right median, ulnar, fibular, tibial, and
sural nerves. Electromyography of the left iliopsoas muscle
revealed low-amplitude motor unit potentials with normal
recruitment and no spontaneous activity.
Four days after admission, hemiplegia appeared suddenly
on the patient’s right side. His muscle strength was grade 2
in the right arm and grade 1 in the right leg based on the
MRC scale. His tendon reflexes slightly increased in the
right extremities, with indifferent plantar reflexes in the bilateral feet. Laboratory tests revealed elevated CRP (11.3
mg/dL) and D-dimer (3.05 μg/mL) levels. Brain diffusionweighted imaging (DWI)-MRI revealed a fresh infarction in
the left posterior limb of the internal capsule (Fig. 2A) with
a decreased apparent diffusion coefficient (ADC) value.
Fluid-attenuated inversion recovery (FLAIR) MRI revealed a
hyperintense lesion in the left posterior limb of the internal

Figure 2. Changes in magnetic resonance imaging (MRI) of the brain. The upper and lower panels
show diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI, respectively. A) On day 4 after hospital admission, DWI reveals a fresh infarct in the left posterior limb
of the internal capsule (yellow arrow). FLAIR MRI reveals a high-signal lesion in the left posterior
limb of the internal capsule and the white matter around the anterior horn of the right lateral ventricle (white arrow). The signal intensity of the lesion in the left posterior limb of the internal capsule
on the FLAIR MRI is weak (yellow dotted arrow). B) Six days after starting oral corticosteroid therapy, DWI and FLAIR MRI show that the high-signal lesion in the left posterior limb of the internal
capsule is clearer than on the first MRI scan. C) Ten months after starting oral corticosteroid therapy, the originally high-signal lesion in the left posterior limb of the internal capsule is barely detectable.
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Figure 3. Frozen tissue sections from the muscle biopsy of the right vastus lateralis stained with
Hematoxylin and Eosin staining. A) Many degenerating fibers and grouped small fibers are observed.
B) Inflammation and obstruction of a blood vessel in the muscle specimen (arrow). C) One extravascular granuloma is observed (arrow). D) Eosinophils are scattered within fibrous tissues (arrow).
Bar: 50 μm

capsule and the white matter around the anterior horn of the
right lateral ventricle (Fig. 2A). In addition, T2-weighted
MRI revealed mucosal thickening in the ethmoid and bilateral maxillary sinuses, which suggested the presence of sinusitis. No stenoses or occlusions were observed in the
cervicocephalic arteries using magnetic resonance angiography or carotid ultrasound. Electrocardiography and transthoracic echocardiography findings were normal. The patient
was treated with aspirin (100 mg/day), cilostazol (200 mg/
day), and edaravone (60 mg/day); however, the patient’s
right hemiplegia worsened.
On day 6 after admission, oral corticosteroid therapy
(prednisone at 1 mg/kg/day) was begun, resulting in a dramatic improvement of right hemiplegia, muscle weakness,
and myalgia within a few days. Six days after starting oral
corticosteroid therapy, DWI and FLAIR MRI of the brain
revealed a subacute lesion in the left posterior limb of the
internal capsule (Fig. 2B) with a normal ADC value. T2weighted MRI revealed an improvement of the mucosal
thickening in the paranasal sinuses. STIR MRI on day 15
revealed that the lesions scattered in the bilateral thigh muscles still showed a high signal.
A muscle biopsy from the patient’s right vastus lateralis
was performed on day 30 (Fig. 3). Frozen sections that were

stained with Hematoxylin and Eosin showed many degenerating, pale-colored fibers and grouped smaller-sized fibers
(Fig. 3A). Multiple mononuclear cell infiltrates were observed around and inside small-sized blood vessels, but not
around the non-necrotic fibers (Fig. 3B). There was one extravascular granuloma (Fig. 3C), and eosinophils were scattered within interstitial fibrous tissues (Fig. 3D). There was
no cellular infiltration within the fascia. These results were
consistent with EGPA.
The patient’s muscle weakness improved to grade 5 in his
left side and grade 4 in his right side based on the MRC
scale 5 days after starting corticosteroid therapy. The leukocytosis with eosinophilia and elevated CRP and D-dimer
levels were also improved. The patient was prescribed prednisone at 0.4 mg/kg/day and discharged on day 49. On DWI
and FLAIR MRI at 10 months after starting oral corticosteroid therapy, the previously observed high-signal lesion in
the left posterior limb of the internal capsule was barely detectable (Fig. 2C).

Discussion
EGPA is a rare form of vasculitis, and its prevalence in
Japan is 17.8 per million adults. The median age at the on-

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set is 59.7 (range, 49.8-70.4) years old, and more than 64%
of the patients are women (5). We reported a 75-year-old
man who presented with myalgia and cerebral infarction due
to EGPA, which was suggested by a muscle biopsy. His
clinical symptoms improved rapidly after corticosteroid therapy.
Neurological complications are common in EGPA, but
cerebral infarction is much less frequent than neuropathy,
being observed in 3-10% of patients with EGPA (6-8). The
mechanism underlying cerebral infarction due to EGPA is
uncertain; however, an autopsy case of EGPA reported that
cerebral infarction was due to cerebral vasculitis with infiltration of eosinophils and embolism from a cardiac thrombus (9). Granule proteins, such as eosinophilic cationic protein, major basic protein, or eosinophil-derived neurotoxin,
can lead to hypercoagulability and damaged cells (10-12).
Although our patient’s D-dimer level was elevated at the onset of cerebral infarction, the rapidly improved hemiplegia
observed after corticosteroid therapy suggested the presence
of cerebral vasculitis. Our patient presented with cerebral infarction without peripheral neuropathy. Some previous case
reports have described ischemic stroke without peripheral
neuropathy in patients with EGPA (13, 14). However, the
difference in the mechanisms of vasculitis between the central nervous system and peripheral nerve in EGPA is uncertain.
Of note, the patient reported here had presented with a
high fever, myalgia with weakness of proximal limb muscles, and eosinophilia when he visited our clinic, all of
which are common symptoms of EGPA (7, 15). EGPA was
also suggested from a muscle biopsy that revealed necrotizing vasculitis, scattered eosinophils, and extravascular granuloma. A previous report stated that a muscle biopsy demonstrated definite and probable vasculitis in 18% and 35% of
patients with systemic vasculitic neuropathy, respectively (16). As the early diagnosis of EGPA is important but
difficult, a muscle biopsy may be helpful for patients who
present with some of the major clinical manifestations of
EGPA together with myalgia or muscle weakness.
In conclusion, EGPA should be considered in the differential diagnosis of cerebral infarction in patients with myalgia and eosinophilia. A muscle biopsy may aid in the diagnosis in such patients. An early diagnosis and prompt administration of corticosteroids or other immunosuppressant
drugs may improve the prognosis of cerebral infarction in
EGPA.
Written informed consent was obtained from the patient for
the publication of the case history and the accompanying images.

Measures for Intractable Diseases from the Ministry of Health
Labour and Welfare and by an Intramural Research Grant (29-4)
for Neurological and Psychiatric Disorders of National Center of
Neurology and Psychiatry.

References
1. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International
Chapel Hill Consensus Conference Nomenclature of Vasculitides.
Arthritis Rheum 65: 1-11, 2012.
2. Masi AT, Hunder GG, Lie JT, et al. The American College of
Rheumatology 1990 criteria for the classification of Churg-Strauss
syndrome (allergic granulomatosis and angiitis). Arthritis Rheum
33: 1094-1100, 1990.
3. Ntatsaki E, Carruthers D, Chakravarty K, et al. BSR and BHPR
guideline for the management of adults with ANCA-associated
vasculitis. Rheumatology (Oxford) 53: 2309-2306, 2014.
4. Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis.
Ann Rheum Dis 75: 1583-1594, 2016.
5. Saku A, Furuta S, Hiraguri M, et al. Longterm outcomes of 188
Japanese patients with eosinophilic granulomatosis with polyangiitis. J Rheumatol 45: 1159-1166, 2018.
6. Sehgal M, Swanson JW, DeRemee RA, Colby TV. Neurologic
manifestations of Churg-Strauss syndrome. Mayo Clin Proc 70:
337-341, 1995.
7. Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, Casassus
P. Churg-Strauss syndrome. Clinical study and long-term followup of 96 patients. Medicine (Baltimore) 78: 26-37, 1999.
8. Wolf J, Bergner R, Mutallib S, Buggle F, Grau AJ. Neurologic
complications of Churg-Strauss syndrome-a prospective monocentric study. Eur J Neurol 17: 582-588, 2010.
9. Hira K, Shimura H, Kamata R, et al. Multiple cerebral infarction
diagnosed as eosinophilic granulomatosis with polyangiitis by
autopsy. BMC Neurol 19: 288, 2019.
10. Fattahi P, Sheriff F, Narayanan NS, Greer DM, Schindler J.
Thrombolysis for acute stroke in patients with vasculitis: case report and literature discussion. Clin Neurol Neurosurg 115: 351353, 2013.
11. Gleich GJ, Frigas E, Loegering DA, Wassom DL, Steinmuller D.
Cytotoxic properties of the eosinophil major basic protein. J Immunol 123: 2925-2927, 1979.
12. Durack DT, Sumi SM, Klebanoff SJ. Neurotoxicity of human
eosinophils. Proc Natl Acad Sci USA 76: 1443-1447, 1979.
13. Kang DW, Kim DE, Yoon BW, Seo JW, Roh JK. Delayed diagnosis: recurrent cerebral infarction associated with Churg-Strauss
syndrome. Cerebrovasc Dis 12: 280-281, 2001.
14. Cheng MJ, Huang PH, Liao PW, Chen JT, Chiang TR. Multiple
cerebral and cerebellar infarcts as the first clinical manifestation in
a patient with Churg-Strauss syndrome: case report and literature
review. Acta Neurol Taiwan 21: 169-175, 2012.
15. Lanham JG, Elkon KB, Pusey CD, Hughes GR. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the ChurgStrauss syndrome. Medicine (Baltimore) 63: 65-81, 1984.
16. Bennett DLH, Groves M, Blake J, et al. The use of nerve and
muscle biopsy in the diagnosis of vasculitis: a 5 year retrospective
study. J Neurol Neurosurg Psychiatry 79: 1376-1381, 2008.

The authors state that they have no Conflict of Interest (COI).
Financial Support
Dr. Hayashi was supported by the grant for Research on

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Ⓒ 2020 The Japanese Society of Internal Medicine
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