Case

Report

Recurrent Embolic Strokes AssociatedwithVertical AtlantoaxialSubluxation in a Patient with Rheumatoid Arthritis: A Case

Report and Review of Literature

Takuma Kuroki, MD,* Yuji Ueno, MD, PhD,* Ikuko Takeda, MD,*

Taiki Kambe, MD, PhD,* Kenya Nishioka, MD, PhD,* Hideki Shimura, MD, PhD,*

Masanori Itoh, MD, PhD,† Nobutaka Hattori, MD, PhD,‡ and Takao Urabe, MD, PhD*

From the *Department

Hospital, Chiba; †Depart

Urayasu Hospital, Chiba

University School of Med

Received April 27, 201

July 5, 2013.

Funding: None.

Address corresponden

Neurology, Juntendo Un

Urayasu, Chiba 279-0021

1052-3057/$ - see front

� 2013 by National Str

http://dx.doi.org/10.1

e676

We report a 78-year-old woman with rheumatoid arthritis who developed recurrent

embolic cerebellar strokes associated with vertical atlantoaxial subluxation (AAS).

On contrast angiography, the bilateral vertebral arteries (VAs) were occluded be-

tween the C1 and C2 levels, and the distal parts of bilateral VA were supplied by

the collateral circulations. Dynamic cerebral angiography and carotid duplex ultra-

sonography showed that blood flow was substantially decreased in the left VA and

left posterior inferior cerebellar artery on cervical anteflexion. It is suggested that

vertical AAS reduced the blood flow of collateral circulation in the left VA with

cervical anteflexion and might be a cause of recurrent ischemic stroke. Key Words:

Atlantoaxial subluxation—recurrent embolic stroke—angiography—carotid duplex

ultrasonography.

� 2013 by National Stroke Association

Introduction

Atlantoaxial subluxation (AAS), which is because of

destruction of the transverse ligament, with subsequent

laxity, occurs in patients with rheumatoid arthritis

(RA).1 AAS may cause severe neurological morbidity, in-

cluding paresthesia, cervical myelopathy, vertebrobasilar

insufficiency, and even sudden death because of brain-

stem and spinal cord compression.1-3 Transverse

of Neurology, Juntendo University Urayasu

ment of Neurosurgery, Juntendo University

; and ‡Department of Neurology, Juntendo

icine, Tokyo, Japan.

3; revision received June 20, 2013; accepted

ce to Yuji Ueno, MD, PhD, Department of

iversity Urayasu Hospital, 2-1-1 Tomioka,

, Japan. E-mail: yuji-u@juntendo.ac.jp.

matter

oke Association

016/j.jstrokecerebrovasdis.2013.07.010

Journal of Stroke and Cerebrovasc

ligament destruction may cause anterior or vertical

subluxation, at 5% and 1.4%, respectively.1

Disorders of cervical spine including AAS and cervical

spondylosis can cause cerebrovascular accident. Ischemic

stroke and symptomatic vertebrobasilar insufficiency not

infrequently occur during horizontal head rotation in

patients with cervical spine diseases because several ex-

trinsic structural changes of the cervical spine could tran-

siently obstruct the vertebral artery (VA) with head

motion.4-8

We report a case of recurrent embolic strokes in the cer-

ebellar hemispheres in a patient with vertical AAS. Based

on the presence of vertical AAS, dynamic carotid duplex

ultrasonography and cerebral angiography were per-

formed to evaluate for positional alteration of the verte-

brobasilar system with head motion.

Case Report

A 78-year-old woman with a 10-year history of RA

had a head injury after falling, and she then developed

ular Diseases, Vol. 22, No. 8 (November), 2013: pp e676-e681

RECURRENT EMBOLIC STROKES AND ATLANTOAXIAL SUBLUXATION e677

headache and vertigo for 2 weeks before admission.

She also had a medical history of tuberculosis and os-

teoporosis. Her family history included no cerebrovas-

cular diseases. She did not drink alcohol and did not

smoke. She suddenly developed dysarthria and was re-

ferred to our hospital. On admission, her blood pres-

sure was 124/64 mm Hg, and no carotid bruit or

abnormal heart sounds were heard. She had defor-

mities of the proximal and distal interphalangeal joints

of her hands. On neurological examination, she was

alert, but she had bilateral, horizontal gaze-paretic nys-

tagmus and slight dysarthria. Her muscle strengths

were normal. Dysmetria was found in both upper

limbs. The National Institutes of Health Stroke Scale

(NIHSS) score was 3 points. Diffusion-weighted imag-

ing showed multiple hyperintense lesions in the cere-

bellar hemispheres (Fig 1, A,B). MR angiography

showed reduced flow signals in vertebrobasilar arteries

(Fig 1, C). On 3-dimensional enhanced computed to-

mography, the left VA was occluded by dislodgment

between C1 and C2, and the right VA was occluded

at the same level and collaterally supplied by a branch

of the right thyrocervical trunk (Fig 1, D,E). There was

no evidence of arterial dissection, including intramural

hematoma, pearl and string signs, or barrel signs, in the

vertebrobasilar artery. We diagnosed her as having ver-

tical AAS based on cervical computed tomography and

magnetic resonance imaging (Fig 2, A-C). The patient

was treated with oral aspirin, intravenous edaravone

(a free radical scavenger), and glycerol soon after ad-

mission. On the third day of admission, she had a fever

of 39.0�C, and her blood pressure decreased to 60/

42 mm Hg. She became somnolent, and her dysarthria

and nystagmus worsened. She also showed left-sided

peripheral facial palsy, and dysmetria worsened in

left-sided limbs. Her NIHSS score was 10. Follow-up

diffusion-weighted imaging showed expansion of hy-

perintense lesions in the cerebellar hemispheres and

brainstem (Fig 2, B,C). Blood examinations revealed

a systemic inflammatory response: marked leukocytosis

with a left shift (white blood cells, 32,000/mL; neutro-

phils, 87%) and elevation of C-reactive protein

(17.6 mg/dL). The plasma D-dimer level was 2.88 mg/

mL. Escherichia coli was detected on blood cultures. Uri-

nalysis was normal. On transthoracic echocardiography,

left and right ventricular wall motions were normal, the

ejection fraction was 60%, and there was no evidence of

infectious endocarditis, including vegetations or de-

struction of valves. She was, therefore, diagnosed as

having early recurrent embolic stroke and septic shock.

Intravenous heparin was started, and an appropriate

antimicrobial agent and a vasopressor drug were given.

Moreover, she underwent cervical collar therapy ac-

cording to the previous case reports.8,9 On the

fifth day of admission, her temperature and blood

pressure were normalized. Her consciousness level

improved gradually, and her NIHSS score was 5.

Dynamic cervical spine X-ray and carotid duplex

ultrasonographic studies were performed (Fig 3A,B).

Doppler images showed an occluded flow pattern in

the left VA with cervical anteflexion, whereas the flow

pattern was normal in the mid-cervical position and

with cervical retroflexion (Fig 3, C,D). The flow pattern

was also normal on horizontal head rotation. Occluded

flow patterns in the right VA were found in any cervi-

cal positions. Cerebral angiography demonstrated that

the left VA was occluded between the C1 and C2 levels,

and the left vertebro-vertebral collateral circulation was

found in the mid-cervical position (Fig 3, E). On cervi-

cal anteflexion, blood flow was substantially decreased

in the left VA and posterior inferior cerebellar artery

(PICA) (Fig 3, F). The right VA could not be evaluated

because of anatomical problem. On the 18th day of ad-

mission, continuous heparin therapy was discontinued,

whereas oral aspirin therapy was continued. She has

had no further stroke recurrence.

Discussion

This case showed recurrent embolic strokes associated

with vertical AAS. She had chronic occlusion of the bilat-

eral VA, and the distal parts of bilateral VAwere supplied

by the collateral circulations.

On contrast angiography, the bilateral VAs were oc-

cluded between C1 and C2 levels. The distal part of

left VA was supplied by left proximal VA via vertebro-

vertebral anastomosis, and dynamic carotid duplex ul-

trasonography and cerebral angiography demonstrated

that blood flows of the left VA and PICA were substan-

tially reduced during cervical anteflexion. The distal

part of right VA was supplied by a branch of the right

thyrocervical trunk, and occluded flow patterns on dy-

namic carotid duplex ultrasonography in the right VA

were found in any cervical positions. In patients with

proximal vertebral artery occlusion, a variety of anasto-

motic flows including thyrocervical, deep cervical, occip-

ital, ascending pharyngeal, and anterior spinal arteries

compensate to the distal part of vertebral artery.10,11

Patients with RA for more than 20 years were reported

to have a high prevalence of VA stenosis or

occlusion.12 Although the present case had a 10-year his-

tory of RA, it is suggested that her bilateral VAs were

chronically occluded and collateral pathways were de-

veloped. There have been several case reports of symp-

tomatic vertebrobasilar insufficiency associated with

AAS in patients with RA.7,8,13 Intriguingly, those cases

showed transient positional occlusion of the VA during

horizontal head rotation.7,8 The present case had

chronic occlusion of the bilateral VA, and substantial

blood flow reduction in the left VA and PICA were

found during cervical anteflexion. Although the

association between reduction of vertebro-vertebral

Figure 1. (A and B) Representative diffusion-

weighted images at the time of the initial stroke,

showing multiple bilateral cerebellar infarcts.

(C) MR angiography showing decreased flow

signals of the vertebrobasilar arteries (yellow ar-

rowheads). (D and E) Three-dimensional en-

hanced computed tomography, showing that

the left VA is occluded by dislodgment between

C1 and C2 (D, yellow arrowheads) and the right

VA is occluded at the same level (E, yellow ar-

rowheads) and collaterally supplied by a branch

of the thyrocervical trunk (yellow arrows).

Abbreviations: C1, atlas; C2, axis; VA, vertebral

artery.

T. KUROKI ET AL.e678

Figure 2. (A and B) Sagittal (A) and axial (B)

images of cervical computed tomography show-

ing that the tip of the odontoid process is supe-

rior to McGregor line (dotted line), which

fulfills the diagnostic criteria of vertical atlan-

toaxial subluxation. (C) Sagittal image of cervi-

cal magnetic resonance imaging, showing the tip

of the odontoid process compressing the brain-

stem. (D and E) Representative diffusion-

weighted images at the time of the second stroke,

showing expansion of multiple bilateral cerebel-

lar infarcts.

RECURRENT EMBOLIC STROKES AND ATLANTOAXIAL SUBLUXATION e679

anastomotic flow and AAS with cervical anteflexion is

unknown, it is suggested that structural changes of the

cervical spine owing to vertical AAS reduced the left

vertebro-vertebral collateral circulation during cervical

anteflexion and, thereby, might cause recurrent embolic

strokes in the present case.

The present case had a head injury 2 weeks before

admission, which suggests that head injury might

have promoted mechanical stretching or compression

of the left occluded VA, thereby resulting in the initial

stroke. In addition, the hemodynamic state caused by

septic shock may have been associated with the recur-

rent attack. Recently, there has been growing interest

that impaired perfusion reserve might be more likely

to have stagnant flow that would increase the risk of

artery-to-artery embolism, and thus, this mechanism

might occur in the posterior circulation.14 These mech-

anisms might be involved in the pathogenesis of ische-

mic stroke associated with AAS. To the best of our

knowledge, there have been no cases with AAS in

whom the mechanisms of ischemic stroke were closely

investigated.

In conclusion, several mechanisms might have been

implicated in the pathogenesis of recurrent embolic

Figure 3. (A and B) X-ray images of cervical

spine with retroflexion (A) and anteflexion (B).

(C and D) Representative Doppler images of

carotid duplex ultrasonography of the left VA,

showing a normal flow pattern in the

mid-cervical position (C) and an occluded flow

pattern with cervical anteflexion (D). (E and

F) Cerebral angiography shows occlusion of the

left VA at the C1-C2 level (arrow) and collateral

circulation bridges the distal part of the left VA

(arrowheads) (E). On cervical anteflexion, blood

flow of the left VA and PICA is significantly

reduced (arrows) (F).

T. KUROKI ET AL.e680

strokes in the present case. In patients with cerebrovascu-

lar accidents associated with AAS, physicians should be

aware of the presence of chronic occlusion of the vertebral

artery, and dynamic carotid duplex ultrasonography and

cerebral angiography with cervical anteflexion may be

helpful to assess vertebrobasilar artery hemodynamics

and to prevent further stroke recurrence.

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