High-Resolution Magnetic Resonance Imaging Findings of Reversible Cerebral
Vasoconstriction Syndrome associated with Severe
Anemia: A Case Report
중증 빈혈과 관련된 가역적 뇌혈관 수축 증후군의 고해상도 자기공명영상 소견: 증례 보고
Yongsang Kim, MD1 , Ra Gyoung Yoon, MD1* , Ji Ye Lee, MD2 , Jong-Moo Park, MD3
Departments of 1Radiology, 3Neurology, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, Korea
2Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Ischemic stroke is one of the manifestations of reversible cerebral vasoconstriction syndrome (RCVS). Many precipitants and associated disorders of RCVS have been suggested. However, few case reports have indicated an association between anemia and RCVS. Here, we report a case of a 66-year-old female with severe iron deficiency anemia (IDA), who presented with isch- emic stroke and cerebral vasoconstriction, which gradually improved with conservative treat- ment. High-resolution vessel wall magnetic resonance imaging findings and reversibility sug- gested the possibility of RCVS. In patients with RCVS and ischemic stroke, IDA should be considered. Prompt management should be delivered to prevent disease progression and re- currence.
Index terms Cerebrovascular Disorders; Vasoconstriction; Stroke;
Magnetic Resonance Imaging; Anemia
INTRODUCTION
Reversible cerebral vasoconstriction syndrome (RCVS) is a heterogeneous clinical syn-
Received February 18, 2020 Revised April 24, 2020 Accepted May 7, 2020
*Corresponding author Ra Gyoung Yoon, MD Department of Radiology, Nowon Eulji Medical Center, Eulji University
College of Medicine,
68 Hangeulbiseok-ro, Nowon-gu, Seoul 01830, Korea.
Tel 82-2-970-8551 Fax 82-2-970-8346 E-mail [email protected] This is an Open Access article distributed under the terms of the Creative Commons Attribu- tion Non-Commercial License (https://creativecommons.org/
licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduc- tion in any medium, provided the original work is properly cited.
ORCID iDs Yongsang Kim https://
orcid.org/0000-0002-1636-1105 Ra Gyoung Yoon
https://
orcid.org/0000-0003-3203-921X Ji Ye Lee
https://
orcid.org/0000-0002-3929-6254 Jong-Moo Park
https://
orcid.org/0000-0002-4199-3024
drome characterized by severe headache and multifocal segmental stenosis of the intracra- nial arteries, which resolves within 3 months (1). Unpredictable and transient failure of regu- lation of the cerebral arterial tone with sympathetic overactivity is thought to be the pathological mechanism of RCVS, and ischemic stroke is one of the major complications of RCVS (2). Although RCVS can occur spontaneously, previous studies have reported many pu- tative precipitants of RCVS, including various drugs and diseases. Among them, only a few case reports have reported an association between anemia and RCVS (3, 4). Herein, we report a case of a woman with acute ischemic stroke associated with RCVS that was considered to be caused by severe iron deficiency anemia (IDA) with high resolution vessel wall (HRVW) mag- netic resonance imaging (MRI) findings.
CASE REPORT
A 66-year-old woman presented to the emergency department of our institution with the sudden onset of dysarthria that occurred an hour before the visit. The last normal time was 5 hours ago. She did not have any medical history of cardiovascular disease, diabetes mellitus, neurological or hematological disorders. Her vital signs were within the normal ranges. How- ever, neurological examination revealed right sided weakness (grade 2) and dysarthria. The pa- tient’s National Institutes of Health Stroke Scale (NIHSS) was 4 points at the time of the emer- gency room visit.
Laboratory testing showed a low hemoglobin level (1.9 g/dL), low mean corpuscular volume, low mean corpuscular hemoglobin, low serum ferritin level, which were consistent with se- vere IDA. The possibility of hemolytic anemia was ruled out according to peripheral blood morphology.
Diffusion-weighted image (DWI) MRI revealed multifocal acute infarctions in the left fron- tal, temporal, and parietal lobes at the left middle cerebral artery (MCA) territory. Additional- ly, time-of-flight (TOF) magnetic resonance angiography (MRA) revealed multifocal segmen- tal stenosis in the right distal internal carotid artery, A1 segment of the right anterior cerebral artery, M2 segment of the right MCA, and M1 segments of the bilateral MCAs (Fig. 1). The dif- ferential diagnoses included moyamoya disease, vasculitis, and atherosclerotic stenosis. She was admitted to the stroke unit and was managed with aspirin. After then, the patient’s NIHSS improved to 1 point. Due to her improved clinical condition, endovascular treatment was not considered. Systemic examinations, including computed tomography of the chest and abdo- men, esophagogastroduodenoscopy, colonoscopy, and bone marrow biopsy, were performed simultaneously to investigate the cause of the severe IDA, and they revealed negative findings.
Laboratory test results for autoimmune antibodies were not remarkable.
After 5 days of transfusion and conservative management, her hemoglobin level improved to 9.8 g/dL without deterioration of neurological deficit. Subsequent HRVW MRI was performed for the further evaluation of vascular pathology. On follow-up MRA, the severe stenosis of the bilateral M1 segments improved, with residual mild stenosis in the proximal portion of the M1 segments. On HRVW MRI, the stenosed segments showed mild concentric wall thickening with- out contrast enhancement (Fig. 1B). Because the clinical symptoms were mild, additional treat-
Follow-up MRA performed 4 months after the initial attack showed normal intracranial ar- teries, and there was no recurrence of ischemic stroke (Fig. 1A).
DISCUSSION
Headache is the main symptom of RCVS; however, transient sensory or motor deficits are present in slightly more than 8–43% of patients (2). Previous cohort studies reported that ce- rebral infarction was present in about 6–39% of RCVS patients (5, 6). The pathophysiology of
Fig. 1. MRI of reversible cerebral vasoconstriction syndrome in a 66-year-old woman.
A. Initial MRI of reversible cerebral vasoconstriction syndrome in a 66-year-old woman. DWI, ADC map, and FLAIR show recent infarctions (ar- rows) in the left internal carotid artery internal borderzone and middle cerebral artery territory. Perfusion map (rCBV, rCBF) demonstrates in- crease of rCBV and decreased rCBF of left frontal to parietal lobe. Initial time-of-flight MRA shows the multifocal segmental stenosis in the in- tracranial arteries. Follow-up MRA after 5 days of transfusion shows mild improvement with mild residual focal stenosis in the bilateral proximal M1 segments. Follow-up MRA performed after 4 months shows normalization of the previously stenosed segments of the bilateral middle cerebral arteries.
ADC = apparent diffusion coefficient, DWI = diffusion-weighted imaging, FLAIR = fluid attenuation inversion recovery images, MRA = magnetic resonance angiography, MRI = magnetic resonance imaging, rCBF = relative cerebral blood flow, rCBV = relative cerebral blood volume
A
ischemic lesions in RCVS is thought to be related to either transformation of vasogenic edema into cytotoxic edema in patients with posterior reversible encephalopathy syndrome (PRES) or severe vasospasm of medium and large arteries. Furthermore, because of the frequent asso- ciation between PRES and RCVS, it is possible that endothelial dysfunction has a role in both disorders (2).
Traditionally, direct or indirect angiography is needed to diagnose RCVS, which involves mul- tifocal segmental narrowing and dilatation of one or more arteries (2). A diagnosis of RCVS can only be confirmed when the reversibility of vasoconstriction is assessed. Twelve weeks from the onset of symptoms has been proposed as a cutoff, and the reversal should be complete or at least substantial (1, 7). However, it is difficult to differentiate between RCVS and cerebral vas- culitis until the resolution of vasoconstriction, because both can involve medium to small ar- teries. As steroids might worsen the clinical course of RCVS (5), accurate differential diagnosis Fig. 1. MRI of reversible cerebral vasoconstriction syndrome in a 66-year-old woman.
B. Sagittal high-resolution MRI shows mild concentric wall thickening without contrast enhancement (arrows) at the right A1 segment, right M1 segment, right distal ICA and left M1 segment.
ICA = internal carotid artery, MRI = magnetic resonance imaging, T1CE = contrast-enhanced T1-weighted images, T2WI = T2-weighted images
B
Right A1 - T2WI
Right distal ICA - T2WI
Right A1 - T1CE
Right distal ICA - T1CE
Right M1 - T2WI
Left M1 - T2WI
Right M1 - T1CE
Left M1 - T1CE
HRVW MRI, previous reports demonstrated that less, diffuse, uniform, and continuous wall thickening with or without mild enhancement; a short interval to restoration; and a high rate of resolution were helpful imaging features to differentiate RCVS from CNS vasculitis (8). As our patient showed mild concentric wall thickening without contrast enhancement on HRVW MRI, we were able to make a diagnosis of RCVS with confidence. The pathology of transient vasoconstriction without arterial inflammation in RCVS might be consistent with weak or no enhancement on HRVW MRI.
RCVS can occur spontaneously, without an obvious underlying cause, or it can be secondary to an identifiable trigger (up to 60% of cases) (5, 7, 9). A diverse group of possible exogenous triggers for secondary RCVS has been proposed. Among them, an association between IDA and RCVS has been proposed in few case reports (3, 4). Microcytic blood cells in IDA patients have altered deformability, which cause a decrease in the oxygen-carrying capacity of red blood cells might cause anemic hypoxia and compensatory cerebral vasodilatation. This increased blood flow might cause increased cerebrovascular resistance and endothelial damage. As tran- sient regulation failure of the cerebral arterial tone with sympathetic overactivity appears to have a role in the development of RCVS (2), IDA might induce an increased sympathetic tone through sympathetic reflex decompensation and cause subsequent RCVS.
Interestingly, ischemic stroke was accompanied to RCVS in our patient. According to the pre- vious reports, IDA has been proposed as a possible precipitating factor of stroke (9). Thrombo- cytosis and anemic hypoxia might play roles in the development of ischemic stroke among pa- tients with IDA. Moreover, microcytic blood cells cause increased blood viscosity and might increase the risk of thrombosis (9). Consequently, it might be assumed that the ischemic stroke is attributed to the overlap of RCVS and underlying IDA because this patient was very vulner- able to ischemic stroke due to her underlying condition.
Typical angiographic findings of RCVS had been reported as multiple areas of smooth or ta- pered arterial narrowing followed by segments of normal-caliber or distended arteries (5). How- ever, MRA showed abrupt severe stenosis in our patient, rather than typical findings in previ- ous reports. This finding might be related to an increase in blood viscosity due to severe IDA.
A previous report suggested that increased viscosity causes a decrease in blood flow (10), which can contribute to excessive saturation of arterial spins on TOF-MRA. For this reason, the de- gree of stenosis could be exaggerated than the exact on TOF-MRA.
In conclusion, we reported a case involving RCVS, probably associated with severe anemia.
In our case, HRVW MRI allowed accurate diagnosis of RCVS. In patients with ischemic stroke and RCVS, severe anemia should be considered as an underlying cause, and prompt diagnos- tic and therapeutic strategies should be adopted. Because of the unclear pathophysiological association between severe anemia and RCVS, further studies are needed to validate the pro- posed mechanisms.
Author Contributions
Conceptualization, Y.R.G., K.Y., L.J.Y.; data curation, Y.R.G., K.Y., L.J.Y.; formal analysis, Y.R.G., K.Y., L.J.Y.; investigation, all authors; project administration, Y.R.G., K.Y., L.J.Y.; resources, all authors; su- pervision, Y.R.G., L.J.Y.; visualization, Y.R.G., K.Y., L.J.Y.; writing—original draft, Y.R.G., K.Y., L.J.Y.; and writing—review & editing, Y.R.G., K.Y.
Conflicts of Interest
The authors have no potential conflicts of interest to disclose.
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중증 빈혈과 관련된 가역적 뇌혈관 수축 증후군의 고해상도 자기공명영상 소견: 증례 보고
김용상1 · 윤라경1* · 이지예2 · 박종무3
가역적 뇌혈관 수축 증후군은 허혈성 뇌졸중을 야기할 수 있으며 다양한 질환이 원인이 된다.
하지만 빈혈과 가역적 뇌혈관 수축 증후군의 연관성을 나타내는 사례 보고는 거의 없다. 이에 저자들은 보존적 치료로 호전된 66세 여성의 허혈성 뇌졸중과 뇌혈관 수축을 동반한 중증 철 결핍빈혈의 사례를 보고하고자 한다. 고해상도 혈관벽 자기공명영상 소견 및 뇌혈관 협착의 가역성을 토대로 가역적 뇌혈관 수축 증후군을 진단할 수 있었다. 가역적 뇌혈관 수축 증후 군 및 허혈성 뇌졸중을 가진 환자에서 철결핍빈혈은 하나의 원인으로 고려되어야 하며 즉각 적인 처치를 통해 질병의 진행 및 재발을 방지해야 한다.
을지대학교 의과대학 노원을지대학교병원 1영상의학과, 3신경과,
