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Case Studies

Progressive Bilateral Vertebral Artery Dissection in a Case of
Osteogenesis Imperfecta
Yuji Kato, MD, PhD,* Harumitsu Nagoya, MD, PhD,* Tetsuya Abe, MD,*
Takeshi Hayashi, MD, PhD,* Masanori Yasuda, MD, PhD,† Akira Uchino, MD, PhD,‡
Norio Tanahashi, MD, PhD,* and Masaki Takao, MD, PhD*

A 32-year-old woman with osteogenesis imperfecta (OI) was admitted to the hospital because of a right-sided occipital headache and facial paresthesia. She was
diagnosed with lateral medullary syndrome due to right vertebral artery (VA) dissection. She was treated conservatively without antithrombotic therapy. She developed
subarachnoid hemorrhage because of contralateral VA dissection 18 days later. This
clinical course may reflect the underlying weakness of the vessel wall in OI. In
patients with OI, occlusion of a unilateral VA could cause dissection and subsequent rupture of the contralateral VA. Early surgical treatment for lesions of the
VA is required in such cases. Key Words: Osteogenesis imperfecta—bilateral vertebral
artery dissection—lateral medullary syndrome—subarachnoid hemorrhage.
© 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Introduction
Osteogenesis imperfecta (OI) is a heterogeneous and
inherited connective tissue disorder that is characterized
by excessive bone fragility.1 OI is caused by abnormalities of type I collagen, which is a major structural
component of vessel walls. Nevertheless, cerebrovascular complications have not been well analyzed in OI.2-7

From the *Department of Neurology and Cerebrovascular Medicine, Saitama Medical University International Medical Center, Hidaka,
Saitama, Japan; †Department of Pathology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan; and
‡Department of Diagnostic Radiology, Saitama Medical University
International Medical Center, Hidaka, Saitama, Japan.
Received October 29, 2016; revision received December 2, 2016;
accepted December 17, 2016.
Address correspondence to Yuji Kato, MD, PhD, Department of
Neurology and Cerebrovascular Medicine, Saitama Medical University
International Medical Center, 1397-1 Yamane, Hidaka, Saitama
350-1298, Japan. E-mail: yujik@saitama-med.ac.jp.
1052-3057/$ - see front matter
© 2017 National Stroke Association. Published by Elsevier Inc. All
rights reserved.
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.12.012

We present a case of progressive bilateral vertebral artery
(VA) dissection in a patient with OI.

Case Report
A 32-year-old woman developed a right-sided occipital headache and facial paresthesia. The patient had
clinically diagnosed OI (type 1) because of the presence
of bone fragility, blue-tinged sclerae, a family history, and
bone X-ray findings, including Wormian bone and low
bone density.1,8 She had a medical history of fractures of
the limbs (4 times), which were associated with minor
trauma since she was 4 years old. Her father and elder
brother also had a history of multiple fractures and were
clinically diagnosed with OI. The family history of the
patient suggested autosomal dominant transmission (Fig 1).
She had no risk factors, such as hypertension, dyslipidemia,
arrhythmia, or other cardiovascular diseases, or diabetes mellitus.
She was alert on admission and her height was 140 cm.
Her blood pressure was 127/76 mmHg and her heart rate
was 84 beats/minute. A neurological examination showed
right-sided blepharophimosis, miosis, and facial anhidrosis.

Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2016: pp ■■–■■

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Figure 3. Three-dimensional computed tomography angiography on admission shows occlusion in the right vertebral artery (A, arrow) and dilation
of the proximal basilar artery (A, B, arrowhead), although there appears
to be retrograde residual flow (B, arrow).
Figure 1. Abbreviated family pedigree. The square indicates a man and
the circle indicates a woman. Dark squares and circles indicate a history
of multiple fractures. An asterisk indicates the present case.

Rotatory nystagmus in the fast phase was directed toward
the left side. She had dysphagia resulting from soft palatal
paresis. The gag reflex had disappeared on the right side,
as well as dysmetria on the right side by finger-to-nose
testing, and ataxic gait.
Diffusion-weighted magnetic resonance (MR) imaging
on admission showed acute infarction at the right posterolateral medulla (Fig 2, A). T1-weighted MR imaging,
MR angiography, and partial maximum intensity projection

(MIP) images of the vertebrobasilar system showed thrombotic occlusion in the right VA and dilation of the proximal
basilar artery (BA) (Fig 2, B-D). An MR angiographic source
image showed a double lumen in the occluded right VA
(Fig 2, E). Basi-parallel anatomical scanning-MR imaging9
showed dilatation of the outer contour at the right VA
and proximal BA (Fig 2, F). Three-dimensional computed tomography angiography on admission showed
almost complete occlusion in the right VA and dilation
of the proximal BA (Fig 3, A), although there appeared
to be retrograde residual flow (Fig 3, B). Based on these
findings, we diagnosed lateral medullary syndrome due

Figure 2. Diffusion-weighted MR imaging (A) performed on admission shows hyperintensity in the
right posterolateral medulla (arrow). T1-weighted
MR imaging (B), MR angiography (C), and a partial
maximum intensity projection image of the
vertebrobasilar system (D) show occlusion of the
right VA with thrombus in the pseudolumen (arrowheads) and dilation of the proximal basilar artery
(BA) (arrow). MR angiographic source image (E)
shows a double lumen in the right occluded VA
(arrow). Basi-parallel anatomical scanning-MR
imaging (F) shows dilatation of the outer contour
at the right VA (arrowheads) and the proximal
BA (arrow). Abbreviations: MR, magnetic resonance; VA, vertebral artery.

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VA DISSECTION IN OSTEOGENESIS IMPERFECTA

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revealed diffuse subarachnoid hemorrhage (Fig 5). Despite
intensive treatment, she died on day 28.
An autopsy was performed 3 hours after death. According to the autopsy record, the brain showed severe
softening with massive subarachnoid hemorrhage, consistent with respiratory brain. Unfortunately, the major
cerebral arteries and brain stem were not appropriately
obtained. We analyzed multiple histological sections of
the brain from archival slides, but identifying the major
cerebral arteries, including the VAs, was difficult. Most
neurons in the cerebral cortex were atrophic and eosinophilic. Red blood cells were observed in the subarachnoid
space.

Discussion
Figure 4. MR angiography (A) and a partial maximum intensity projection (MIP) image of the vertebrobasilar system (B) on day 11 showing
left VA dissection with severe stenosis (string sign, arrows). MR angiography (C, arrowheads) and an MIP image of the vertebrobasilar system
(D, arrowheads) on day 18 show enlargement of the pseudolumen in the
left dissecting VA. Abbreviations: MR, magnetic resonance; VA, vertebral
artery.

to right VA dissection associated with proximal BA dissection. The patient was treated conservatively without
antithrombotic therapy because of an increased risk of
a dissected VA and BA rupture. Her blood pressure remained well controlled (<140/90 mmHg) without
antihypertensive agents during hospitalization. MR angiography and a partial MIP image of the vertebrobasilar
system on day 11 showed stenosis of the left VA, which
suggested newly developed dissection after admission
(Fig 4, A, B). However, the patient showed no neurological deterioration. MR angiography and a partial MIP
image of the vertebrobasilar system on day 18 showed
enlargement of the left dissecting VA (Fig 4, C, D). On
the 20th hospital day, she suddenly entered a coma and
was immediately intubated. Brain computed tomography

Figure 5. Brain computed tomography on day 20
shows diffuse subarachnoid hemorrhage.

In the present case, OI (type 1) was directly diagnosed based on clinical signs, symptoms, and a positive
family history, although we did not perform genetic
analysis.1,8 OI (type 1) results in an underproduction of
type I collagen, which is deposited on the surface of smooth
muscle cells or along elastin filaments in the cerebrovascular wall.10 In patients with OI and aortic dissection,
pathological examination of the resected aortic wall tissue
shows cystic medial degeneration.11 Therefore, type I collagen might play a role in the rigidity and elasticity of
the vascular wall.12,13
Although sporadic case reports have described cerebrovascular complications in adult patients with OI, it
is rare compared with other connective diseases. Particularly noteworthy are reports of cervicocephalic arterial
dissection, such as dissection of the VA or basilar artery,4,14
dissection of the carotid artery,3,5 bilateral dissection of
both internal carotid arteries and VAs,2 and subarachnoid hemorrhage due to a ruptured aneurysm.6 Vascular
dissection may be an important pathological condition
of OI, and may reflect the underlying weakness of the
vessel wall of OI.

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Contralateral VA dissection occurs after spontaneous
occlusion or occlusion therapy of ipsilateral VA
dissection.15-19 The clinical presentation of contralateral VA
dissection is variable and occlusive ischemia and aneurysm development are possible.15-19 In our case, the
mechanism of left VA dissection after occlusion of a dissecting right VA is unclear. Changes in hemodynamic stress
may contribute to this mechanism.15 In previous reports
of bilateral VA dissection, substantial elevation of arterial hemodynamic stress was indicated because the
contralateral VA became dilated after the unilateral VA
was occluded.16,17 Alternatively, unilateral VA dissection
may extend to the contralateral VA via the confluence
of bilateral VAs.18 In both mechanisms, vascular fragility in OI may have been a major factor in our case.
Conservative treatment was not effective for our patient.
In patients with OI, occlusion of a unilateral VA could cause
dissection and subsequent rupture of the contralateral VA.
Early surgical treatment, such as parent vessel sacrifice of
unilateral residual flow to prevent subsequent contralateral rupture and trapping of the dissected contralateral VA
with anastomosis, is required in such cases.

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