□ CASE REPORT □

Medullary Hemorrhagic Infarction after Radiation
for Nasopharyngeal Carcinoma
Jian-Ren Liu 1, Jian Huang 2, Min Zhang 3, Qi-Chun Wei 4, Ying Song 5,
Jian-Zheng Huang 6, Mei-Ping Ding 7 and Ping-Juan Jia 8

Abstract
Head and neck irradiation may lead to accelerated atherosclerosis over several years. Delayed stroke has
been described after head and neck irradiation administered for a number of conditions. However, brain stem
stroke has only rarely been associated with irradiation. We report a patient with medullary hemorrhagic infarction 6 years after radiotherapy for nasopharyngeal carcinoma. A 42-year-old normotensive Chinese male
had rapid onset of vertigo, diplopia, ataxia, dysphagia, hypophonic dysarthria, hemiparesis, and respiratory
distress. Cranial MR imaging 2 days after symptom onset showed medullary infarction, and cranial MR imaging 5 days after symptom onset showed medullary hemorrhage. He needed ventilatory support and died of
bacterial pneumonia 1 month later. Other risk factors for stroke were absent. Hemorrhagic infarction in this
patient was likely associated with the radiotherapy. Radiotherapy is the first choice of treatment for nasopharyngeal carcinoma, however, it may induce fatal medullary hemorrhagic infarction.
Key words: medullary hemorrhagic infarction, nasopharyngeal carcinoma, radiotherapy, radioencephalopathy, magnetic resonance imaging, diffusion weighted imaging
(DOI: 10.2169/internalmedicine.46.6279)

Introduction

Case Report

The incidence of nasopharyngeal carcinoma is more common among Chinese in southern China and Southeast Asia.
The principal treatment for nasopharyngeal carcinoma is radiotherapy, even though it can cause late delayed neurological complications in 13% of treated patients, and can damage the brainstem and cervical cord in about 2% of patients
(1-3). However, radiation-associated brain stem stroke has
rarely been reported. Herein we report a Chinese man who
had medullary hemorrhagic infarction 6 years after radiotherapy for nasopharyngeal carcinoma.

A 42-year-old Chinese man was admitted for rapid onset
of vertigo, diplopia, ataxia, dysphagia, hypophonic dysarthria, right hemiparesis and respiratory distress. Six years
previously, the patient had been diagnosed as suffering from
nasopharyngeal carcinoma. The histological finding was low
differentiated squamous cell carcinoma. The patient received
a radiation dose of 70 Gy in 7 weeks to the nasopharynx
and adjacent structure, a further 60 Gy was administered to
the soft tissue of the neck. The radiotherapy was delivered
by linear accelerator (6 MV photon), once a day, five times
per week. Bilateral opposing faciocervical fields to cover the
nasopharynx and upper neck lymphatics in one volume,
matched with one lower neck lymphatics were used (38 Gy/

１

Department of Neurology, Second Affiliated Hospital, College of Medicine, Zhejiang University, China, ２ Department of Oncology, Second Affiliated Hospital, College of Medicine, Zhejiang University, China, ３ Department of Oncology, Armed Police Hospital of Hangzhou, Hangzhou, ４
Department of Radiation Oncology, Second Affiliated Hospital, College of Medicine, Zhejiang University, China, ５ College of Medicine, Zhejiang University, China, ６ Department of Neurology, Second Affiliated Hospital, College of Medicine, Zhejiang University, China, ７ Department of
Neurology, Second Affilitated Hospital, College of Medicine, Zhejiang University, China and ８ Department of Neurology, Shangyu People’s
Hospital, China
Received for publication October 2, 2006; Accepted for publication January 9, 2007
Correspondence to Prof. Mei-Ping Ding, dingmeiping2006@zj.com

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DOI: 10.2169/internalmedicine.46.6279

margin of the brain stem received a dose of 60 Gy, while
the center of the area where the hemorrhagic infarction did
occur got a dose about 40 Gy. No neurotoxic radiosensitizer
and no concurrent chemotherapy were used during radiotherapy. He was followed up every year and no clinical abnormality was found until he experienced bilateral progressive sensori-neural hearing loss 3 years previously (the left
one was much more severe than the right). He had no history of stroke, coronary heart disease, arrhythmia, cardiomyopathy, hypertension, diabetes, peripheral atherosclerotic
b）
a）
disease, nor any other disorders.
On admission he was afebrile, with blood pressure of
120/84 mmHg, heart rate of 84 beats per minute, and respiratory rate of 25 breaths per minute. He was alert, and had
multidirectional crassitude nystagmus, a peripheral left facial
palsy, dysarthria and dysphagia, bilateral hypoglossal palsy,
right hemiparesis, right limbs hypesthesia, and dysmetria
and dysdiadochokinesia of the bilateral limbs. The muscle
strength of his right and left extremities was 4/5 and 5-/5,
d）
c）
respectively; the right plantar response was extensor and the
left was flexor. His respiration was shallow.
Cranial computed tomography on the first day of symptom onset showed no abnormality (Fig. 1a, 1b). Cranial MR
imaging 2 days after symptom onset in local hospital
showed medullary infarction (Fig. 1c, 1d, 1e, 1f). Cranial
MR imaging 5 and 7 days after symptom onset in our hospital showed a hemorrhagic lesion in the medullary region
(Fig. 2a, 2b, 2c, 2d) and three small radio-encephalopathic
lesions in the pons. The hemorrhagic lesion showed hyperintensity on T1-weighted MR imaging, heterogeneous intensity on T2-weighted MR imaging, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping. Those radio-encephalopathic lesions showed hypoinf）
e）
tensity in T1-weighted MR imaging and showed hyperintensity in T2-weighted MR imaging, DWI and ADC mapping
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and there was no evidence of carcinoma recurrence. He was
hy
pe
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A mo
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diagnosed with radiation-associated medullary hemorrhagic
f
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.
]
infarction and pontine radio-encephalopathy, and was treated
with Tab prednisone (60 mg per day). He had not received
any anti-coagulation or anti-platelet drugs.
One week after admission his breathing became more
19F/DT), then the split-field technique was used with two
pre-auricular fields (22 Gy/11F/DT) and one pre-nasal field shallow, and he gradually lost consciousness. His breathing
(10 Gy/5F/DT) for the nasopharynx, matched with an ante- required assistance of a respirator. However, one month after
rior cervical field for the neck lymphatics. The patient was the acute onset of the symptoms, he died of bacterial pneutreated with conventional radiotherapy, no dose volume his- monia.
togram (DVH) was available at that time. Therefore, fields
were reconstructed based on MRI data of this patient to get
an idea of the dose distribution of brain stem. The anterior
612

DOI: 10.2169/internalmedicine.46.6279

a）

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Discussion
Treatment of nasopharyngeal carcinoma is difficult because of the characteristic propensity of the tumour for extensive invasion and its anatomical proximity to critical
structures. Although the optimum dose schedule has yet to
be determined, it is agreed that doses below 60 Gy at conventional fractionation of 2 Gy daily are inadequate for tu-

mor eradication. Thus, all normal tissues within the target
volume will be exposed to a potentially damaging dose.
Neural structures adjacent to the base of the skull, including
temporal lobes and the brain stem, are particularly vulnerable (1-3). Radiation-induced brain stem encephalopathy and
cervical spinal cord myelopathy are the most serious sequelae, the reported incidence ranges from 0.2% to 18%,
with a median of 2% (1-3). However, brain stem stroke after
radiation in nasopharyngeal carcinoma has rarely been reported.
Herein we report a case of fatal medullary hemorrhagic
infarction 6 years after radiotherapy for nasopharyngeal carcinoma. He eventually died of respiratory distress and pulmonary infection. The first cranial MR imaging showed medullary infarction, and the second MR imaging 3 and 5 days
after the first cranial MR imaging showed medullary hemorrhage in the same position. Therefore, the diagnosis of medullary hemorrhagic infarction was considered. Medullary
hemorrhagic infarction in this patient was likely associated
with radiotherapy for the following reasons: 1) The brain
stem was located in the radiation field, there were radionecrotic lesions adjacent to the hematoma and the patient
had left progressive sensori-neural hearing loss three years
after radiotherapy, which implied the brain stem and cranial

613

DOI: 10.2169/internalmedicine.46.6279

and neck and stroke has been demonstrated retrospectively
by Haynes et al (6). Of their 413 patients, 20 had strokes
occurring between 2 and 146 months after radiotherapy. The
5-year actuarial rate of stroke was 12%, which corresponded
to a relative risk of 2.09 (P=.0007) compared with the
population-based “expected” data. Median radiation therapy
dose was 64 Gy; there was no correlation between radiation
therapy dose and stroke risk. Carotid artery stenosis is a late
complication that is shown to be consistently related to rab）
diotherapy for nasopharyngeal carcinoma (7, 8), however,
a）
vertebral artery stenosis or brain stem infarction induced by
Fi
g
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)Sa
g
i
t
t
a
lbr
a
i
ns
t
e
ma
ndc
e
r
v
i
c
a
lc
o
r
de
nha
nc
e
d irradiation for nasopharyngeal carcinoma was rarely reported
T1
we
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e
dMR i
ma
g
i
ng7da
y
sa
f
t
e
rs
y
mpt
o
mo
ns
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ts
ho
w- (9-11). Although conventional cerebral angiography or MR
e
dame
dul
l
a
r
yhe
mo
r
r
ha
g
i
cl
e
s
i
o
nwi
t
ho
ute
nha
nc
e
me
nt
.b) angiography was not done for the present patient, transcraAx
i
a
lc
r
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ni
a
le
nha
nc
e
dT1
we
i
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ma
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- nial Doppler of our patient did not show any abnormality.
t
e
rs
y
mpt
o
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ns
e
ts
ho
we
dame
dul
l
a
r
yhe
mo
r
r
ha
g
i
cl
e
s
i
o
n Thus, there might not be any significant stenotic lesions in
wi
t
ho
ute
nha
nc
e
me
nt
.
the carotid or vertebral arteries. From our experience, vertebral artery commonly compensates the severely stenotic carotid arteries induced by radiotherapy for nasopharyngeal
nerves had sustained irradiation injury. 2) The hemorrhagic carcinoma. Therefore, we presumed that the hemorrhagic ininfarction in this patient was not caused by vascular malfor- farction in the present patient was caused by irradiationmation because cerebral hemorrhagic infarction seldom hap- induced vasculopathy of the small arteries supplying the mepens in vascular malformation. Lack of any flow void in the dulla oblongata.
Irradiation-induced stroke which is commonly ischemic,
medullary parenchyma did not support the existence of other
kinds of vascular malformation, such as arteriovenous mal- delayed cerebral hemorrhage or hemorrhagic infarction
formation, capillary malformations, and developmental ve- caused by irradiation has only rarely been reported (12-15)
nous anormaly. Cranial MR imaging of this patient did not The present case was the first case to have medullary hemshow the distinct feature of cavernous malformation, i.e., a orrhagic infarction following irradiation for nasopharyngeal
reticulated core of mixed signal intensity with a surrounding carcinoma. Irradiation-induced vasculopathy might have the
rim of decreased signal intensity representing hemosiderin potential to cause hemorrhage or hemorrhagic transformafrom previous hemorrhaging. Lack of abnormalities in the tion. The hemorrhagic transformation was not induced by
cranial CT and the first cranial T1-weighted MR imaging in anti-coagulant or anti-platelet drugs, because the patient had
the medullary region further helped to exclude the diagnosis not received such drugs. He did not have a history of heart
of cavernous malformation. 3) The patient had no clinical or disease or peripheral atherosclerotic artery disease, and there
pathological evidence of relapse of nasopharyngeal carci- was no evidence to show that he had embolic infarction
noma. Cranial MR imaging also excluded the possibility of which had transformed to hemorrhagic infarction.
In conclusion, radiotherapy for nasopharyngeal carcinoma
tumor-induced hemorrhagic infarction. 4) The patient did
might induce fatal medullary hemorrhagic infarction. The
not have common risk factors or a family history of stroke.
Accelerated atherosclerosis is a well-recognized complica- brain stem is the key area to be protected during radiothertion of irradiation (4, 5). An association between high-dose apy for these patients.
cervical irradiation for squamous cell carcinoma of the head

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