Reminder of important clinical lesson

Stroke in a young man: a late complication of
radiation therapy
Zhaozhi Jiang,1 Mitchell Elkind,2 Matthew Lucky,3 Zoltan Fekete4
1

Graduate Medical Education,
Orange Regional Medical
Center, Middletown, New York,
USA
2
Department of Neurology,
Vagelos College of Physicians
and Surgeons, Columbia
University, New York, New York,
USA
3
Graduate Medical Education,
Orange Regional Medical
Center, Middletown, New York,
USA
4
Crystal Run Healthcare, Rock
Hill, New York, USA
Correspondence to
Zhaozhi Jiang,
​zjiang@​student.​touro.​edu
Accepted 17 January 2019

Summary
This 37-year-old man presented with left sided facial
warmth and numbness associated with new suddenonset right hemiparesis. The patient first developed
sudden numbness of his left lip and warmth in left ear
which travelled to the rest of left face. His past medical
history was significant for hypertension, Hodgkin
lymphoma treated with radiation therapy at the age
of 10, and sleeve gastrectomy for obesity 1 year ago
complicated by bilateral ischaemic cerebral infarctions
with residual left hemiparesis. No acute infarcts were
found on MRI. Transesophageal echocardiography
revealed a complex atheroma near the sinotubular
junction in ascending aorta.

Background

Stroke is the fifth leading cause of death and the
leading cause of long-term disability in the USA.
Nearly, three-quarters of all strokes occur in people
over the age of 65. Stroke in young patients is relatively rare but increasing.1 One of the reasons for
stroke in the young can be a late complication of
radiation therapy used in treating cancers, such as
Hodgkin lymphoma.2 We describe a case of stroke
in a young survivor of Hodgkin lymphoma treated
with radiation therapy at the age of 10.

Case presentation

© BMJ Publishing Group
Limited 2019. Re-use
permitted under CC BY-NC. No
commercial re-use. See rights
and permissions. Published
by BMJ.
To cite: Jiang Z, Elkind M,
Lucky M, et al. BMJ Case
Rep 2019;12:e228029.
doi:10.1136/bcr-2018228029

A 37-year-old man presented with complaints of
left sided facial numbness and sensation of warmth
in left face associated with new right-sided hemiparesis. He was working at his computer when
he developed sudden numbness of his left lip and
simultaneous feelings of right sided weakness. He
then began to feel a sensation of warmness of his
left face, starting in the ear and travelling to the
rest of the face. On neurological examination, he
had right-sided and left-sided weakness, with no
changes in speech or mentation. The patient also
reported a rash on the abdomen and right elbow
for 1 week; he had been in urgent care and started
on a prednisone taper. He was also diagnosed with
colitis after left abdominal pain and was taking
ciprofloxacin and metronidazole.
The patient had a history of chronic essential hypertension, hypothyroidism and Hodgkin
lymphoma of left side of neck without metastasis at
the age of 10, which was treated with radiation of
neck and chest as well as splenectomy; and sleeve
gastrectomy complicated by bilateral ischaemic
strokes 1 year ago with residual left arm and leg

weakness. He had 180 lb weight loss after surgery.
Patient was on aspirin 81 mg daily and atorvastatin
40 mg daily since the stroke.

Investigations

On arrival, a head CT without contrast was
performed, which revealed three chronic infarcts
in the right MCA distribution and a chronic infarct
involving the left medial occipital cortex, with no
acute lesion.
Brain MRI revealed multiple wedge-shaped
transcortical areas of encephalomalacia and gliosis
bilaterally in the inferolateral right frontal lobe,
right posterior frontal lobe, right parietal lobe and
medial left occipital lobe, which correlates with his
previous CVA (figure 1). MRA of neck showed no
left internal carotid artery stenosis. ECG showed
normal sinus rhythm, normal intervals and no ST or
T wave changes. C
​ ontinuous telemetric​monitoring
​​
of the patient demonstrated normal sinus rhythm
throughout the hospitalisation​. Transthoracic​​echocardiography revealed mild aortic stenosis with
mitral valve calcification. Transoesophageal​​echocardiography (TEE) found a complex atheroma,
large, ulcerated and mobile, measuring 9-mm thickness near the sinotubular junction in ascending
aorta. Hypercoagulability evaluation, including
antiphospholipid antibodies, was negative.

Differential diagnosis

The exact cause of his stroke-like symptoms was
unclear. One possibility was cardiogenic ischaemic
stroke. Another possibility was hypercoagulable
state due to history of lymphoma. The third possibility was aortic stenosis secondary to radiation
therapy. Seizure and migraine were the other two
possibilities. SMART syndrome,3 4 which stands for
stroke-like migraine attacks after radiation therapy,
can also be a possible diagnosis but unlikely since
the patient had no headache, only received chest
radiation, no brain radiation therapy and the MRI
of the brain without and with contrast revealed old
chronic strokes and not SMART syndrome.

Treatment

The patient was given aspirin 325 mg and his symptoms resolved within a couple hours. The patient
started rivaroxaban and rosuvastatin for secondary
prevention of cardioembolic stroke after complex
aortic atheroma was found on TEE.

Outcome and follow-up

The patient was readmitted 2 months later with
identical complaints of left facial numbness. MRI of

Jiang Z, et al. BMJ Case Rep 2019;12:e228029. doi:10.1136/bcr-2018-228029

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Case report

Reminder of important clinical lesson

the brain again revealed no acute stroke. Patient was discharged
on aspirin 81 mg daily, rivaroxaban 20 mg daily and rosuvastatin
5 mg daily. Anticoagulation was subsequently stopped. Electroencephalogram was done to exclude seizures, and showed no
epileptiform abnormalities. He started levetiracetam to prevent
possible seizures.

Discussion

Young adults account for 10%–15% of all stroke cases. 5
Approximately 20%–30% of cerebral infarctions in a general
population are the result of a cardioembolic source, while
approximately 15%–20% of strokes are secondary to extracranial large vessel disease.6 Large-artery atherosclerosis has
been shown to be an infrequent cause of ischaemic stroke in
young adults, accounting for less than 10% of cases.5 Other
common reasons for stroke in young adults include small
vessel disease, hypercoagulability and miscellaneous other
causes. The most common risk factors include smoking,
dyslipidaemia and hypertension. 7 Other less common
causes of stroke in young adults include non-atherosclerotic
angiopathies, hematologic conditions, genetic diseases and
inflammatory and infectious conditions.5
Our patient was found to have a complex atheroma measuring
9-mm thickness near the sinotubular junction, which is possibly
a late complication of radiation. Other risk factors for atheroma
include smoking, hypercholesterolaemia, hypertension, obesity
and diabetes.
Aortic plaque 4 mm or larger is an independent risk factor
for ischaemic stroke. Stroke risk is greater for complex,
mobile plaques larger than 5 mm. 6 TEE is the preferred test
for diagnosis of aortic atherosclerosis. Although atherosclerosis can be seen in young patients, the clinical presentations are usually not seen until patients are older. Young
patients without conventional cardiac risk factors who
2

Jiang Z, et al. BMJ Case Rep 2019;12:e228029. doi:10.1136/bcr-2018-228029

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Figure 1 MRI of the brain.

received mediastinal irradiation for Hodgkin lymphoma
can present with coronary artery disease (CAD) in their
20s. 2
Radiation therapy, an essential method to treat Hodgkin
lymphoma, helped improved the overall prognosis, but can be
associated with serious complications. There is a 5- to 17-fold
greater risk of cerebrovascular events (stroke or transient ischaemic attack) in patients with head and neck cancer who are
treated with RT compared with matched non-RT treated
controls.8 A multi-institutional cohort study of more than 5-year
cancer survivors diagnosed between 1970 and 1986 showed
survivors of childhood Hodgkin disease are at increased risk of
stroke. The incidence of late-occurring stroke among HD survivors was 83.6 per 100 000 person-years, significantly higher
than expected range of 10–23 per 100 000 person-years in adults
aged 18–44 years in the general population.9 Another retrospective study showed among 415 Hodgkin lymphoma survivors
treated with radiation therapy, 42 patients (10.4%) developed
coronary artery disease at a median of 9 years after treatment,
30 patients (7.4%) developed carotid and/or subclavian artery
disease at a median of 17 years after treatment, and 25 patients
(6.2%) developed clinically significant valvular dysfunction at a
median of 22 years.10 However, there is no evidence of aortic
disease in the above studies.
Radiation-induced arterial injury may involve any arteries
exposed to radiation. We speculate that in our case, radiation therapy contributed to development of a complex aortic
atheroma. The exact mechanism of radiation therapy causing
aortic atheroma remains unclear. It is widely accepted that neck
and chest radiation can lead to carotid atherosclerosis and coronary atherosclerosis, thus increases the risk of stroke. The review
by Xu and Cao suggests endothelial dysfunction, injury and
occlusion of vasa vasorum and accelerated atherosclerosis be the
most likely cause of carotid stenosis.11 The review by Jaworski
et al reveals endothelial dysfunction is a precipitating factor in
the development of radiation induced cardiac disease.12 The
review by Darby et al suggests radiation induced coronary artery
disease results from intimal proliferation of myofibroblasts with
lipid-containing macrophages forming atherosclerotic plaques.2
Radiation induced aortic atheroma, as a process of aortic atherosclerosis, is likely caused by endothelial damage with plaque
formation, thus causes embolic stroke. The study by Stewart
et al suggests ionising radiation accelerates the development of
macrophage-rich and inflammatory atherosclerotic lesions in
ApoE−/− mice; lesions developed in the aortic roots of irradiated
mice were macrophage rich and lipid filled, whereas lesions in
non-irradiated mice were collagenous and only minimal macrophage infiltration.13
Management of cerebrovascular disease associated with radiation-induced vascular injury still needs further study. Evidencebased guidelines for the management of asymptomatic and
symptomatic (medium- and large-artery) radiation vasculopathy
are lacking.14
In patients who had a stroke with large-artery atherosclerosis
or small-vessel disease, antiplatelet drugs are recommended.
Acetylsalicylic acid (ASA) should be a first-choice antiplatelet
drug in secondary prevention.5 15 ASA in combination with
dipyridamole or clopidogrel monotherapy can also be used as
the first-line treatment.15 The combination of ASA and clopidogrel can reduce the risk of stroke in the first 90 days and does not
increase the risk haemorrhage.16
Thanks to Emmanuel Obeng Nketiah MD for doing and interpreting the TEE.

Reminder of important clinical lesson

►► Radiation therapy for lymphoma is often successful, and

therefore there are likely to be more and more lymphoma
survivors in the community. One of the possible complications
of chest radiation therapy may be vascular injury of the aorta
with consequent unstable mobile or ulcerated atheroma, as
in the case of our young patient.
►► One should consider this complication in young patients
who had a stroke with history of chest radiation, even when
remote.
►► Complex aortic atheroma may be a cause of stroke. The role
of early screening for aortic atheroma in patients with prior
chest radiation requires further study.
Contributors ZJ, ME and ZF contributed to the design of the case report. ZJ drafted
the manuscript. ME, ML and ZF revised the manuscript for important intellectual
content. ZF contributed to the final approval of the version to be published. ML
obtained the informed consent from the patient.
Funding The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Obtained.
Open access This is an open access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-commercially,
and license their derivative works on different terms, provided the original work
is properly cited and the use is non-commercial. See: http://​creativecommons.​org/​
licenses/​by-​nc/4​ .​0/

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