Case Report

Intracranial and extracranial multiple
arterial dissecting aneurysms in
rheumatoid arthritis: A case report

Interventional Neuroradiology
1–7
! The Author(s) 2020
Article reuse guidelines:
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DOI: 10.1177/1591019920965359
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Ken Uekawa1,2 , Yasuyuki Kaku1 , Toshihiro Amadatsu1,2,
Hiroaki Matsuzaki2, Yuki Ohmori1, Takayuki Kawano3, Shinya Hirata4,
Tomomi Yamaguchi5,6,7, Tomoki Kosho5,6,7 and Akitake Mukasa1

Abstract
Objective: We describe a case of intracranial and extracranial multiple arterial dissecting aneurysms in rheumatoid arthritis (RA).
Case Presentation: A 29-year-old man with a medical history of RA since 18 years of age was admitted to our hospital for
vomiting, dysarthria, and conscious disturbance. At 23, he underwent ligation of the left internal carotid artery (ICA) with
superficial temporal artery to middle cerebral artery anastomosis because of acute infarct of the left hemisphere caused by
arterial dissection of the left ICA. During the current admission, computed tomography (CT) revealed subarachnoid hemorrhage, and digital subtraction angiography (DSA) demonstrated dissecting aneurysms of the left intracranial vertebral
artery (VA) and right extracranial VA. We diagnosed him with a ruptured dissecting aneurysm of the left intracranial VA and
performed endovascular parent artery occlusion on the left VA. For the right unruptured VA aneurysm, we performed coil
embolization simultaneously. At 2 weeks after the endovascular treatment, follow-up DSA revealed that multiple de novo
dissecting aneurysms developed on the origin of the left VA and left and right internal thoracic arteries. Those aneurysms
were treated with coil embolization. Other remaining aneurysms on the left thyrocervical trunk, right transverse cervical
artery, and both common iliac arteries were treated by conservative therapy. While continuing medical treatment for RA, the
patient recovered and was discharged to a rehabilitation hospital.
Conclusion: Considering that RA-induced vasculitis can be a potential risk of vascular complications including multiple arterial
dissections, physicians should carefully perform endovascular interventional procedures for patients with long-term RA.
Keywords
Intracranial and extracranial multiple arterial dissecting aneurysms, rheumatoid arthritis, de novo dissecting aneurysm,
endovascular treatment, TNF-a antagonist
Received 1 July 2020; accepted 14 September 2020

Introduction
Rheumatoid arthritis (RA) is an inflammatory disorder that primarily affects the joints, and in the progressive phase, it can damage systemic organs, including
the blood vessels. The systemic inflammation accelerates vascular complications in RA.1 However, multiple
arterial dissections associated with RA are poorly
understood. Herein, we describe a rare case of intracranial and extracranial multiple arterial dissecting
aneurysms in a patient with long-term RA.

Case presentation
Medical history
A 29-year-old man had a medical history of RA since
18 years of age, and he has been taking methotrexate
and prednisolone. His paternal aunt had RA. When
he was 23 years old, he developed sudden onset right

1
Department of Neurosurgery, Kumamoto University Hospital, Kumamoto,
Japan
2
Department of Cerebrovascular Medicine & Surgery, Division of
Neurosurgery, Saiseikai Kumamoto Hospital, Kumamoto, Japan
3
Department of Neurosurgery, Kurume University School of Medicine,
Fukuoka, Japan
4
Department of Rheumatology, Kumamoto University Hospital,
Kumamoto, Japan
5
Department of Medical Genetics, Shinshu University School of Medicine,
Nagano, Japan
6
Center for Medical Genetics, Shinshu University Hospital, Nagano, Japan
7
Division of Clinical Sequence, Shinshu University School of Medicine,
Nagano, Japan

Corresponding author:
Ken Uekawa, Department of Neurosurgery, Kumamoto University
Hospital, Kumamoto, Japan.
Email: kenuekawa@gmail.com

2
hemiparesis. Magnetic resonance imaging (MRI) and
diffusion-weighted imaging demonstrated acute
infarct of the watershed area of the left-middle-toanterior cerebral artery territories (Figure 1(a)).
Digital subtraction angiography (DSA) was conducted, and left common carotid artery (CCA) angiography revealed severe stenosis of the origin of the
left internal carotid artery (ICA) caused by arterial
dissection (Figure 1(b) and (c)). We assumed that
the mechanism of the infarct was the hemodynamic
stroke or subsequent embolic strokes caused by
thrombosis formation due to the arterial dissection.
To prevent the recurrence of cerebral infarction, antiplatelet therapy with aspirin was started, and the
patient underwent ligation of the origin of the left
ICA with superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis. Postoperative
DSA confirmed that the ligation of the left ICA was
complete (Figure 1(d)), cross flow from the right ICA
to the left hemisphere through the anterior communicating artery existed (Figure 1(e)), and STA-MCA
anastomosis was patent (Figure 1(f)). He was discharged home with slight right hemiparesis remaining. He continued to take methotrexate and

Interventional Neuroradiology 0(0)
prednisolone. He started infliximab, a chimeric monoclonal antibody against tumor necrosis factor-alpha
(TNF-a) because of exacerbation of RA, and continued this treatment for 5 years. Two months before the
recent emergency hospital admission, infliximab was
switched to golimumab, another TNF-a antagonist.

Current admission
When the patient was 29 years of age, he was admitted to the emergency department because of sudden
headache, vomiting, and conscious disturbance. Head
computed tomography (CT) revealed a subarachnoid
hemorrhage (SAH) on the basal cistern and prepontine cistern (Figure 2(a)). His Glasgow Coma Scale
score was 13 (eyes, 3; verbal, 4; motor, 6), and the
neurological severity of the SAH was determined as
Hunt and Kosnik grade 3 and World Federation of
Neurosurgical Societies grade III. CT angiography
indicated the existence of a dissecting aneurysm of
the left vertebral artery (VA). We conducted endovascular embolization with the patient under general
anesthesia on the next day of onset. We confirmed
that the endovascular access route was intact,

Figure 1. (a) MRI diffusion-weighted image demonstrates acute infarct of the watershed area of the left middle to anterior cerebral artery
territories. (b, c) Frontal views of left CCA angiography (b) and 3D angiography (c) reveal severe stenosis of the origin of the left ICA
caused by arterial dissection (white arrow). (d, e, f) On postoperative DSA, frontal view of left CCA angiography (d) shows complete
ligation of the left ICA (black arrow). (e) Frontal view of right ICA angiography shows the existence of cross flow from the right ICA to the
left hemisphere through the anterior communicating artery. (f) Lateral view of the ECA angiography shows patency of the STA-MCA
anastomosis (double bypass) (black arrowhead).
MRI: magnetic resonance imaging; CCA: common carotid artery; ICA: internal carotid artery; DSA: digital subtraction angiography; ECA:
external carotid artery; STA-MCA: superficial temporal artery to middle cerebral artery.

Uekawa et al.

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Figure 2. (a) CT image on admission reveals a diffuse SAH on the basal cistern and prepontine cistern, and an especially thick hematoma
exists on the left pontocerebellar cistern. (b–d) Pre-treatment DSA shows that the access route is intact, and there is no dissecting
aneurysm of both femoral arteries (b), the right carotid artery and right subclavian artery, (c) and left VA and left subclavian artery (d).
Although the representative images are relatively faint in (b–d), when the series of images on the angiography are seen, we were able to
confirm that there is no aneurysm on the branches. (e) Angiography of both Vas demonstrates a dissecting aneurysm on the left side of
the intracranial VA, which is suspected to be a ruptured aneurysm (black arrow), and another dissecting aneurysm of the right extracranial VA (V3-V4 portion), which is suspected to be unruptured (black arrowhead). (f and g) After endovascular treatment, right VA
angiography shows that PAO with coil embolization of the left VA dissecting aneurysm (black arrow in f and white arrow in g) and coil
embolization of the right VA dissecting aneurysm (black arrowhead in f and white arrowhead in g) are completed.
CT: computed tomography; SAH: subarachnoid hemorrhage; DSA: digital subtraction angiography; VA: vertebral artery; PAO: parent artery
occlusion.

including both femoral arteries (Figure 2(b)), the right
subclavian artery (Figure 2(c)), and left subclavian
artery (Figure 2(d)). Angiography of both VAs demonstrated a dissecting aneurysm of the left intracranial VA, which was presumed to be the source of the
SAH, and a dissecting aneurysm of the right extracranial VA (V3-V4 portion), which was considered to be
unruptured (Figure 2(e)). We diagnosed the patient
with SAH due to a ruptured dissecting aneurysm of
the left intracranial VA. In order to prevent rehemorrhage, we decided to perform endovascular
parent artery occlusion (PAO) with coil embolization
of the left VA dissecting aneurysm (Figure 2(f) and
(g)). In addition, we treated the unruptured right VA
dissecting aneurysm with coil embolization simultaneously (Figure 2(f) and (g)), considering that PAO
of the left VA could increase the risk of rupture of the
right VA dissecting aneurysm due to the increase in
the alternated blood flow stress on the right VA.
At 2 weeks after the first session of endovascular
treatment, follow-up DSA revealed multiple de novo
dissecting aneurysms in the cervicothoracic portion,
including on the right internal thoracic artery (RITA)

(Figure 3(a)), proximal part of the left VA, and left
internal thoracic artery (LITA) (Figure 3(b)). We performed aortography to confirm the overall image of
multiple dissecting aneurysms in the cervicothoracic
portion, and aortic dissection was not observed
(Figure 3(c)). Considering the risk of aneurismal rupture, we treated these de novo dissecting aneurysms
with coil embolization (Figure 3(d) and (e)). When
we finished embolization, we noticed that other multiple dissecting aneurysms remained on the origin of
the right transverse cervical artery bifurcated from the
thyrocervical trunk (Figure 3(d)) and on the origin of
the left thyrocervical trunk and costocervical trunk
(Figure 3(e)). Immediately before removing the
sheath introducer from the left femoral artery, arterial
dissections of both common iliac arteries were
observed (Figure 3(f)). Those de novo aneurysms
had not been seen during the initial endovascular
treatment (Figure 2(b) to (d)). Because we considered
that the damage to the fragile artery due to RAinduced vasculitis during catheterization may be a
potential cause of the formation of the multiple dissecting aneurysms, we treated the patient with

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Figure 3. (a–c) Follow-up DSA at 2 weeks after the first session of endovascular treatment reveals multiple de novo dissecting aneurysms
in the cervicothoracic portion. (a) Right subclavian artery angiography shows dissecting aneurysms of RITA (black arrow) and the origin of
the right transverse cervical artery (black arrowhead). (b) Left subclavian artery angiography shows dissecting aneurysms on the proximal
part (V1 portion) of the left VA (black arrow), LITA (white arrow), origin of left thyrocervical trunk (black arrowhead), and costocervical
cervical trunk (white arrowhead). (c) Aortography shows an overall image of the arteries and aneurysms in the cervicothoracic portion. (d
and e) Complete occlusions with coil embolization of the dissecting aneurysms of RITA (black arrow in d), the left VA (black arrow in e),
and LITA (white arrow in e) are confirmed. Other multiple dissecting aneurysms remain on the origin of the right transverse cervical
artery (black arrowhead in D), origin of the left thyrocervical trunk (black arrowhead in e), and costocervical cervical trunk (white
arrowhead in E). (f) Arterial dissections of both common iliac arteries (black arrows) are revealed by DSA immediately before removing
the sheath introducer inserted through the left femoral artery.
DSA: digital subtraction angiography; RITA: right internal thoracic artery; VA: vertebral artery; LITA: left internal thoracic artery.

conservative therapy, which included the continuation of medical treatment for RA.
We consulted with staff in the Department of
Rheumatology, and reconfirmed the diagnosis of
RA based on the findings of polyarthritis, ulnar
drift deformity, radiography, and highly elevated
level of the anti-cyclic citrullinated peptide antibody.
There were no apparent features of hereditary connective tissue disorders, such as Marfan syndrome or
Ehlers-Danlos syndrome (EDS). No pathogenic variants were detected through a next-generation
sequencing-based custom panel analysis comprising
17 causative genes for hereditary connective
tissue disorders (ADAMTS2, B4GALT7, CHST14,
COL1A1, COL1A2, COL3A1, COL5A1, COL5A2,
FBN1, FBN2, FKBP14, PLOD1, SLC39A13,
TGFBR1, TGFBR2, TNXB, ZNF469) using
genomic DNA extracted from peripheral blood and
an Ion PGM (Thermo Fisher Scientific, Carlsbad,
CA, USA).2

Outcome
The patient recovered within a month after the second
endovascular treatment and was discharged to a rehabilitation hospital to continue medical treatment for
RA (methotrexate and low-dose prednisolone and
golimumab). Five years after the endovascular treatment, the patient’s condition was ameliorated with no
significant finding of recurrence of vascular complication including arterial dissection, and follow-up CT
angiography showed no significant change in the
remaining multiple aneurysms (Figure 4(a)) or both
common iliac arteries (Figure 4(b)).

Discussion
It has been suggested that patients with RA who have
persistently high levels of inflammation are at greater
risk of developing cardiovascular diseases and systemic vascular complications.1 Rheumatoid vasculitis
(RV) is an inflammatory disease that affects blood

Uekawa et al.

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Figure 4. (a and b) Follow-up CT angiography at 5 years after endovascular treatment shows no significant change of the cervicothoracic
multiple aneurysms (a) or both common iliac arteries (white arrowheads in b).
CT: computed tomography.

vessels directly in patients with RA.3 RV has a heterogeneous clinical presentation that includes skin
disorders, neuropathy, eye symptoms, and systemic
inflammation.4 RV is usually seen in patients with
long-standing, severe, seropositive, and often uncontrolled RA. RV typically causes severe injury to the
affected blood vessels and most frequently involves
small vessels, but it may also involve medium and
large vessels.3 With regard to the large vessels affected
by RV, rheumatoid aortitis is reported to be a rare
feature of severe RA.5 As for medium vasculitis, cerebral rheumatoid vasculitis (CRV) has been reported
as an infrequent complication in RA, and the
characteristic feature of CRV is cerebral parenchymal
vasculitis in both cerebral hemispheres.6 However,
RA-related arterial dissection of large vessels in the
intracranial or cervicothoracic part, like in our case, is
poorly reported.
The disease activity of RA could be associated with
the vascular damage and induce the dissecting aneurysms. We are not able to confirm the patient’s previous detailed RA disease activity because he was
treated for RA in another hospital before the onset
of SAH. The C-reactive protein was 0.77 mg/dL on
the current admission due to SAH, and other components of disease activity score such as disease activity
score-28 (DAS28), clinical disease activity index
(CDAI), or simplified disease activity index (SDAI)
were not measured. Since the biological disease modifying anti-rheumatic drugs were switched from infliximab to golimumab for enhancement of RA
treatment two months before the onset of SAH, we
assume that the disease activity of RA might be high
or moderate.
TNF-a inhibitors, such as infliximab or golimumab, have been reported to carry a potential risk of
inducing RV, although this idea is still controversial.3
A case report described a rapidly fatal mycotic

aneurysm of the ICA that ruptured in a patient with
RA who was taking a TNF-a inhibitor.7 In our case,
systemic infection, bacteremia, or fungemia was not
seen, and it was not assumed that those aneurysms
were caused by infection. Moreover, some studies
reported that rheumatoid cervical spine disease can
cause a VA dissection in patients with RA. 8,9 In
our case, however, findings of cervical spine disease,
such as osteophytes, were not seen on radiography.
Therefore, we assumed that the state and bioactive
condition of RA or RV could affect the formation
of multiple arterial dissections and that the medications including the biologics (TNF-a inhibitors) may
affect the healing or even deterioration of the multiple
dissections.
Except for RA- or RV-related cases, the onset of
cervical artery dissections has generally been associated with major head and neck trauma as well as with
minor trauma secondary to a wide range of insults.
Instead of major trauma, spontaneous cases are considered to be caused by intrinsic factors that weaken
the arterial wall, including hereditary connective
tissue disorders, infection, hyperhomocysteinemia,
migraine, hypertension, fibromuscular dysplasia, atherosclerosis, and low levels of a1-antitrypsin.10
Representative hereditary connective tissue disorders
exhibiting systemic arterial dissection are Marfan syndrome caused by pathogenic variants in FBN111 and
vascular EDS caused by pathogenic variants in
COL3A1.2 The present patient showed no apparent
features of hereditary connective tissue disorders, and
he was found to have no pathogenic variants in relevant genes through next-generation-based genetic
screening. A case of multiple spontaneous cervical
artery dissections occurring after ruptured intracranial aneurysm embolization was reported, and the
author discussed the effect of head extension during
embolization as the prevailing factor in multiple

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artery dissections.12 In our case, the patient’s head
and neck were not extended during endovascular
embolization. In addition, other connective tissue disorders that overlap with RA associated with vasculitis
(such as systemic lupus erythematosus, Sjogren syndrome) or tuberculosis have not been diagnosed previously by physical examination and from laboratory
findings including autoantibody screening. Because
our patient had no other related condition including
connective tissue disorders, except for RA, we assume
that RV may affect and accelerate the formation of
multiple arterial dissecting aneurysms. To evaluate
the arterial wall inflammation, the utility of vesselwall MRI imaging is reported.13 We did not perform
the vessel-wall MRI imaging on this patient, but it
could be useful to better investigate similar cases
in future.
In terms of the indication for diagnostic angiography and endovascular treatment, because of the fragile nature of connective tissue, some connective tissue
disorders, such as vascular EDS, are often accompanied by neurovascular complications secondary to
vessel dissection or aneurysm.14 In patients with vascular EDS, some articles have reported postendovascular treatment intracranial hemorrhage15 or
abdominal bleeding14 due to an unknown cause located at the remote area from puncture or catheterization, i.e., “remote vascular catastrophes.” Patients
with long-term RA are at greater risk of developing
cardiovascular disease,1 and they occasionally undergo diagnostic angiography and percutaneous coronary intervention for cardiovascular disease, but the
arterial dissections after the endovascular procedure
are rare. In this case, considering the localization of
the de novo dissecting aneurysms on the branches of
subclavian arteries bilaterally, we assume that during
the first procedure the guidewire could have been
inserted in the branches. Hence, the guidewire and
catheter navigation in the predisposed condition of
long-term RA could have induced dissections in
those branches two weeks after the endovascular procedure performed bilaterally on the vertebral arteries.
Although the risk of arterial dissection may not be so
great in patients with RA, considering that RV can
induce arterial fragility, RA may be a potential cause
of de novo multiple dissecting aneurysms after endovascular treatment. Physicians should consider these
potential hazards when there is a need to conduct an
endovascular procedure in patients who are suspected
to have vasculitis due to long-term RA.

Conclusions
We reported a rare case of intracranial and extracranial multiple arterial dissecting aneurysms in RA.
When performing endovascular procedures in
patients with long-term RA, damage to the fragile

Interventional Neuroradiology 0(0)
artery during catheterization can be a potential
cause of multiple arterial dissecting aneurysms.
Thus, physicians should consider the potential vascular risk of RA and carefully perform endovascular
procedures in patients with long-term RA.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of
this article.

Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.

ORCID iDs
Ken Uekawa
https://orcid.org/0000-0001-8952-7009
Yasuyuki Kaku
https://orcid.org/0000-0002-0202-858X

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