Case Report
Paradoxical Brain Embolism Associated with Kimura Disease Mimics Watershed Infarction Yasutaka Tanaka, MD, PhD, Yuji Ueno, MD, PhD, Yoshiaki Shimada, MD, Kazuo Yamashiro, MD, PhD, Ryota Tanaka, MD, PhD, Takao Urabe, MD, PhD, and Nobutaka Hattori, MD, PhD
Kimura disease (KD) is an uncommon chronic inflammatory disease presenting as subcutaneous lymphadenopathy with eosinophilia. To date, only a single case of brain embolism caused by fibroblastic endocarditis associated with KD has been reported. Watershed infarction was seen in patients with episodes of severe hypotension or cardiac surgery. We here report a young case of KD who developed ischemic stroke and showed multiple small infarcts in the border zones between the territories of major cerebral arteries, mimicking watershed infarction. Transesophageal echocardiography revealed patent foramen ovale and atrial septal aneurysm. Concurrently, deep venous thrombus in the femoral vein was found on duplex ultrasonography. Our case supports the notion that paradoxical brain embolism associated with KD can cause multiple small embolisms and mimic watershed infarction. Key Words: Stroke—paradoxical brain embolism—Kimura disease— watershed infarction—patent foramen ovale. Ó 2015 by National Stroke Association
Kimura disease (KD) is an uncommon chronic inflammatory disorder of unknown etiology presenting as subcutaneous lymphadenopathy of the head and neck associated with eosinophilia and increased serum levels of immunoglobulin E.1
Case Report A 36-year-old Japanese man who had been diagnosed with KD at 17 years visited our hospital with loss of con-
From the Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. Received August 25, 2014; revision received September 15, 2014; accepted September 17, 2014. The authors declare that they have no competing interests. Address correspondence to Yuji Ueno, MD, PhD, Department of Neurology, Juntendo University School of Medicine, Hongo, 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.09.018
centration accompanied by numbness of the right hand. Physical examination revealed subcutaneous masses in the right neck and right groin. The patient was alert but apathetic. Cognitive function was not disturbed. He showed right-sided motor weakness and sensory disturbance. Positive results were obtained for the Babinski reflex on the right side. Diffusion-weighted imaging showed disseminated small brain infarcts in bilateral cerebral and cerebellar cortices (Fig 1, A). Laboratory data showed eosinophilia: leukocyte count, 15,700/mL with 56.0% eosinophils and serum immunoglobulin E, 45,322 IU/mL. D-dimer level was 5.7 mg/mL and thrombin– antithrombin III complex level was 6.2 ng/mL. Transesophageal echocardiography revealed patent foramen ovale on the contrast study, together with atrial septal aneurysm (Fig 1, B). Mural thrombus was detected in the right femoral vein on duplex ultrasonography (Fig 1, C). Paradoxical brain embolism associated with KD was diagnosed,2 and anticoagulant therapy with heparin followed by warfarin was started. Betamethasone was
Journal of Stroke and Cerebrovascular Diseases, Vol. 24, No. 2 (February), 2015: pp e55-e57
e55
Y. TANAKA ET AL.
e56
The present case showed a specific infarct pattern of multiple small infarcts in the border zones between the territories of the anterior and middle cerebral arteries and middle and posterior cerebral arteries, indicating watershed infarctions. Watershed infarction has typically been found in patients with episodes of severe hypotension, cardiopulmonary arrest, or cardiac surgery.5,6 Although our patient had not experienced such conditions, deep venous thrombosis passing through the patent foramen ovale could enter multiple small cerebral arteries and thereby cause multiple brain embolisms mimicking watershed infarction. Hypereosinophilia can induce a hypercoagulable state via tissue factor exposure, eosinophil peroxidase production, direct toxic effects on endothelial cells and CD40 ligand expression, which might have been the mechanism underlying deep venous thrombosis in this case.7-10 Alternatively, thrombus might have been produced locally by stagnant venous flow because of the right groin lymphadenopathy. This represents the first known report of KD showing multiple watershed infarction caused by paradoxical brain embolism. Acknowledgments: Written informed consent was obtained from the patients for publication of this case report and the accompanying images. Y.T., Y.U., Y.S., K.Y., and R.T. were responsible for acquisition of data. Y.T., Y.U., and Y.S. were responsible for analysis and interpretation of data. Y.T., Y.U., T.U., and N.H. were responsible for drafting of the article. Y.U., T.U., and N.H. were responsible for critical revision of the article for important intellectual content.
References Figure 1. Magnetic resonance, transesophageal echocardiographic, and duplex ultrasound images. (A) Representative axial diffusion-weighted images show disseminated hyperintense signals in the watershed areas of the bilateral middle, anterior, and posterior cerebral arteries, and cerebellar hemispheres. (B) Transesophageal echocardiographic images show the atrial septal aneurysm protruding from the midline of the atrial septum to the left atrium (arrow) and the right-to-left atrial shunt on the contrast study (arrowheads) throughout the cardiac cycle. (C) Mural thrombus is found in the right femoral vein on duplex ultrasonography (arrowheads).
started at 2 mg/day for treatment for KD. The patient experienced no further stroke episodes.
Discussion KD is frequently complicated by nephrotic syndrome, eosinophilic endocarditis, cardiac valvular disease, and peripheral vein vasculitis.1,3 However, only a single case of brain embolism caused by fibroblastic endocarditis has been reported.4
1. Chen H, Thompson LD, Aguilera NS, et al. Kimura disease: a clinicopathologic study of 21 cases. Am J Surg Pathol 2004;28:505-513. 2. Ueno Y, Iguchi Y, Inoue T, et al. Paradoxical brain embolism may not be uncommon-prospective study in acute ischemic stroke. J Neurol 2007;254:763-766. 3. Danis R, Ozmen S, Akin D, et al. Thrombosis of temporal artery and renal vein in Kimura-disease-related nephrotic syndrome. J Thromb Thrombolysis 2009;27:115-118. 4. Barge S, Bouchachi A, Bechara C, et al. Eosinophilia with stroke in a Chinese patient: Kimura’s disease complicated with fibroblastic endocarditis, first report. Am J Hematol 2008;83:432. 5. Torvik A. The pathogenesis of watershed infarcts in the brain. Stroke 1984;15:221-223. 6. Gottesman RF, Sherman PM, Grega MA, et al. Watershed strokes after cardiac surgery: diagnosis, etiology, and outcome. Stroke 2006;37:2306-2311. 7. Moosbauer C, Morgenstern E, Cuvelier SL, et al. Eosinophils are a major intravascular location for tissue factor storage and exposure. Blood 2007; 109:995-1002.
KD MIMICS WATERSHED INFARCTION 8. Slungaard A, Vercellotti GM, Walker G, et al. Tumor necrosis factor alpha/cachectin stimulates eosinophil oxidant production and toxicity towards human endothelium. J Exp Med 1990;171:2025-2041. 9. Wang JG, Mahmud SA, Thompson JA, et al. The principal eosinophil peroxidase product, HOSCN, is a uniquely
e57 potent phagocyte oxidant inducer of endothelial cell tissue factor activity: a potential mechanism for thrombosis in eosinophilic inflammatory states. Blood 2006;107:558-565. 10. Gauchat JF, Henchoz S, Fattah D, et al. CD40 ligand is functionally expressed on human eosinophils. Eur J Immunol 1995;25:863-865.
Paradoxical Brain Embolism Associated with Kimura Disease Mimics Watershed Infarction Yasutaka Tanaka, MD, PhD, Yuji Ueno, MD, PhD, Yoshiaki Shimada, MD, Kazuo Yamashiro, MD, PhD, Ryota Tanaka, MD, PhD, Takao Urabe, MD, PhD, and Nobutaka Hattori, MD, PhD
Kimura disease (KD) is an uncommon chronic inflammatory disease presenting as subcutaneous lymphadenopathy with eosinophilia. To date, only a single case of brain embolism caused by fibroblastic endocarditis associated with KD has been reported. Watershed infarction was seen in patients with episodes of severe hypotension or cardiac surgery. We here report a young case of KD who developed ischemic stroke and showed multiple small infarcts in the border zones between the territories of major cerebral arteries, mimicking watershed infarction. Transesophageal echocardiography revealed patent foramen ovale and atrial septal aneurysm. Concurrently, deep venous thrombus in the femoral vein was found on duplex ultrasonography. Our case supports the notion that paradoxical brain embolism associated with KD can cause multiple small embolisms and mimic watershed infarction. Key Words: Stroke—paradoxical brain embolism—Kimura disease— watershed infarction—patent foramen ovale. Ó 2015 by National Stroke Association
Kimura disease (KD) is an uncommon chronic inflammatory disorder of unknown etiology presenting as subcutaneous lymphadenopathy of the head and neck associated with eosinophilia and increased serum levels of immunoglobulin E.1
Case Report A 36-year-old Japanese man who had been diagnosed with KD at 17 years visited our hospital with loss of con-
From the Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. Received August 25, 2014; revision received September 15, 2014; accepted September 17, 2014. The authors declare that they have no competing interests. Address correspondence to Yuji Ueno, MD, PhD, Department of Neurology, Juntendo University School of Medicine, Hongo, 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.09.018
centration accompanied by numbness of the right hand. Physical examination revealed subcutaneous masses in the right neck and right groin. The patient was alert but apathetic. Cognitive function was not disturbed. He showed right-sided motor weakness and sensory disturbance. Positive results were obtained for the Babinski reflex on the right side. Diffusion-weighted imaging showed disseminated small brain infarcts in bilateral cerebral and cerebellar cortices (Fig 1, A). Laboratory data showed eosinophilia: leukocyte count, 15,700/mL with 56.0% eosinophils and serum immunoglobulin E, 45,322 IU/mL. D-dimer level was 5.7 mg/mL and thrombin– antithrombin III complex level was 6.2 ng/mL. Transesophageal echocardiography revealed patent foramen ovale on the contrast study, together with atrial septal aneurysm (Fig 1, B). Mural thrombus was detected in the right femoral vein on duplex ultrasonography (Fig 1, C). Paradoxical brain embolism associated with KD was diagnosed,2 and anticoagulant therapy with heparin followed by warfarin was started. Betamethasone was
Journal of Stroke and Cerebrovascular Diseases, Vol. 24, No. 2 (February), 2015: pp e55-e57
e55
Y. TANAKA ET AL.
e56
The present case showed a specific infarct pattern of multiple small infarcts in the border zones between the territories of the anterior and middle cerebral arteries and middle and posterior cerebral arteries, indicating watershed infarctions. Watershed infarction has typically been found in patients with episodes of severe hypotension, cardiopulmonary arrest, or cardiac surgery.5,6 Although our patient had not experienced such conditions, deep venous thrombosis passing through the patent foramen ovale could enter multiple small cerebral arteries and thereby cause multiple brain embolisms mimicking watershed infarction. Hypereosinophilia can induce a hypercoagulable state via tissue factor exposure, eosinophil peroxidase production, direct toxic effects on endothelial cells and CD40 ligand expression, which might have been the mechanism underlying deep venous thrombosis in this case.7-10 Alternatively, thrombus might have been produced locally by stagnant venous flow because of the right groin lymphadenopathy. This represents the first known report of KD showing multiple watershed infarction caused by paradoxical brain embolism. Acknowledgments: Written informed consent was obtained from the patients for publication of this case report and the accompanying images. Y.T., Y.U., Y.S., K.Y., and R.T. were responsible for acquisition of data. Y.T., Y.U., and Y.S. were responsible for analysis and interpretation of data. Y.T., Y.U., T.U., and N.H. were responsible for drafting of the article. Y.U., T.U., and N.H. were responsible for critical revision of the article for important intellectual content.
References Figure 1. Magnetic resonance, transesophageal echocardiographic, and duplex ultrasound images. (A) Representative axial diffusion-weighted images show disseminated hyperintense signals in the watershed areas of the bilateral middle, anterior, and posterior cerebral arteries, and cerebellar hemispheres. (B) Transesophageal echocardiographic images show the atrial septal aneurysm protruding from the midline of the atrial septum to the left atrium (arrow) and the right-to-left atrial shunt on the contrast study (arrowheads) throughout the cardiac cycle. (C) Mural thrombus is found in the right femoral vein on duplex ultrasonography (arrowheads).
started at 2 mg/day for treatment for KD. The patient experienced no further stroke episodes.
Discussion KD is frequently complicated by nephrotic syndrome, eosinophilic endocarditis, cardiac valvular disease, and peripheral vein vasculitis.1,3 However, only a single case of brain embolism caused by fibroblastic endocarditis has been reported.4
1. Chen H, Thompson LD, Aguilera NS, et al. Kimura disease: a clinicopathologic study of 21 cases. Am J Surg Pathol 2004;28:505-513. 2. Ueno Y, Iguchi Y, Inoue T, et al. Paradoxical brain embolism may not be uncommon-prospective study in acute ischemic stroke. J Neurol 2007;254:763-766. 3. Danis R, Ozmen S, Akin D, et al. Thrombosis of temporal artery and renal vein in Kimura-disease-related nephrotic syndrome. J Thromb Thrombolysis 2009;27:115-118. 4. Barge S, Bouchachi A, Bechara C, et al. Eosinophilia with stroke in a Chinese patient: Kimura’s disease complicated with fibroblastic endocarditis, first report. Am J Hematol 2008;83:432. 5. Torvik A. The pathogenesis of watershed infarcts in the brain. Stroke 1984;15:221-223. 6. Gottesman RF, Sherman PM, Grega MA, et al. Watershed strokes after cardiac surgery: diagnosis, etiology, and outcome. Stroke 2006;37:2306-2311. 7. Moosbauer C, Morgenstern E, Cuvelier SL, et al. Eosinophils are a major intravascular location for tissue factor storage and exposure. Blood 2007; 109:995-1002.
KD MIMICS WATERSHED INFARCTION 8. Slungaard A, Vercellotti GM, Walker G, et al. Tumor necrosis factor alpha/cachectin stimulates eosinophil oxidant production and toxicity towards human endothelium. J Exp Med 1990;171:2025-2041. 9. Wang JG, Mahmud SA, Thompson JA, et al. The principal eosinophil peroxidase product, HOSCN, is a uniquely
e57 potent phagocyte oxidant inducer of endothelial cell tissue factor activity: a potential mechanism for thrombosis in eosinophilic inflammatory states. Blood 2006;107:558-565. 10. Gauchat JF, Henchoz S, Fattah D, et al. CD40 ligand is functionally expressed on human eosinophils. Eur J Immunol 1995;25:863-865.
