Case Report Streptococcus Agalactiae Infective Endocarditis with Multiple Cerebral Hemorrhages: A Case Report Wakoh Takahashi, MD, Shizuka Netsu, MD, Chikage Kijima, MD, Yusuke Moriya, MD, Yukari Shirasugi, MD, Shunya Takizawa, MD From the Department of Neurology, Tokai University School of Medicine, Kanagawa, Japan (WT,CK,YM,ST); Department of Clinical Practice, Tokai University Hospital, Tokyo, Japan (SN); and Department of Hematology, Tokai University School of Medicine, Kanagawa, Japan (YS).
Keywords: Infective endocarditis, microbleeds, cerebral hemorrhage, Streptococcus agalactiae. Acceptance: Received January 9, 2014, and in revised form May 15, 2014. Accepted for publication June 1, 2014. Correspondence: Address correspondence to Wakoh Takahashi, MD, Department of Neurology, Tokai University School of Medicine, Shimokasuya143, Isehara, Kanagawa 259–1143, Japan. E-mail: [email protected] J Neuroimaging 2014;00:1-3. DOI: 10.1111/jon.12157
Introduction Infective endocarditis (IE) often affects multiple organs, including the central nervous system. Neurological complications observed in 20-35% of patients with IE1–4 include cerebral embolism, transient ischemic attack, cerebral hemorrhage, meningitis, encephalopathy, and brain abscess.1,3,4 Recently, we experienced a patient with Streptococcus agalactiae IE complicated by aplastic anemia. The patient had multiple cerebral hemorrhages on computed tomography (CT), in addition to microhemorrhages on magnetic resonance imaging (MRI). Since S. agalactiae IE is a rare clinical entity,3,5,6 the profile of hemorrhagic complications in S. agalactiae IE is not well known. In this study, we report the characteristics of the cerebral complications accompanying IE in a patient with aplastic anemia.
Case Report The patient was a 40-year-old man who was diagnosed with aplastic anemia in a general hospital at 30 years of age. In midDecember 2012, he presented with fever, shortness of breath, and swelling in the lower limbs. At the end of December, he noticed mildly blurred vision bilaterally, and his visual acuity rapidly deteriorated to blindness the following day. He was admitted to our hospital at the beginning of January 2013 to evaluate severe headache and altered consciousness. On admission, his blood pressure was 112/57 mmHg and pulse was 96 beats per minute with a regular rhythm. Body
temperature was 38.3 ˚C, and a second degree systolic heart murmur was heard. No subcutaneous bleeding or skin eruption was observed. Conjunctival hemorrhages were observed bilaterally. On neurological examination, he was drowsy and found to be blind, with a pupil size of 4.5 mm bilaterally and no light reflexes. Muscle strength in the upper and lower extremities was mildly weak bilaterally, but no hyperreflexia or pathological reflexes in the extremities were observed. He exhibited nuchal rigidity, and Kernig’s sign was positive. On laboratory examination, hemoglobin concentration was 7.1 g/dl, leukocyte count was 2,300 cells/µl, and platelet count was 1,000 plt/µl. Fibrin degradation product (FDP) was to 26.2 µg/dl. Serum C-reactive protein was elevated to 12.80 mg/dl. On initial CT performed on admission, multiple hemorrhages were found in the cerebral white matter bilaterally (Fig 1A), and numerous low signal intensities suggesting microhemorrhages in the cortical or subcortical regions were detected on gradient-echo T2*-weighted sequences (Fig 1B). Diffusionweighted images (DWI) showed no high signal lesions suggestive of acute cerebral ischemia (Fig 1C). None of the lesions detected were apparent on gadolinium-enhanced T1 -weighted images (Fig 1D). No abnormalities of the intra-cranial arteries, including cerebral aneurysms, were detected on magnetic resonance angiography (MRA). Echocardiography performed on hospital day 4 revealed an area of vegetation 4 mm in length in the mitral annular ring and moderate mitral regurgitation. The patient was diagnosed with IE based on clinical characteristics
Copyright
◦ 2014 by the American Society of Neuroimaging C
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Fig 1. CT and MR images on admission. Multiple hemorrhages in the cerebral white matter bilaterally on CT (A, upper left), and numerous low signal intensities in the cortical and subcortical regions on gradient-echo T2*-weighted sequences (B, upper right). DWI does not show acute cerebral infarction (C, lower left). None of the detected lesions are apparent on gadolinium-enhanced T1-weighted images (D, lower right). and echocardiographic findings. His blindness was diagnosed as severe endophthalmitis with detached retinas, complicated by IE. Intravenous administration of ceftriaxone and vancomycin had been empirically started on hospital day 1. On hospital day 2, phacoemulsification with aspiration and vitrectomy were performed bilaterally. The weakness in the upper and lower extremities accompanying consciousness disturbance improved on hospital day 3. S. agalactiae was detected from both cultures of blood and vitreous humor on hospital day 7. On day 43, echocardiography did not detect the valvular vegetation, and mitral regurgitation had improved. On day 60, CT demonstrated the cerebral hematomas had markedly improved (Fig 2A), but multiple low signal intensities suggesting old microhemorrhages persisted on the T2*-weighted MR images on day 81 (Fig 2B). After receiving continuous cyclosporin, anti-lymphocyte globulin, granulocyte colony-stimulating factor, and platelet transfusions, he was discharged on day 116.
Discussion The patient’s condition, which corresponded to definite IE, fulfilled one major criterion (cardiac echo finding) and three minor criteria (fever, vascular phenomena, and positive blood
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culture) of the Duke-Li criteria.7 On admission, he presented with consciousness disturbance and weakness in the upper and lower extremities. However, these symptoms, as well as fever, rapidly improved after starting antibiotics. These symptoms might therefore have been induced by meningitis or encephalopathy of IE, rather than the intracerebral hemorrhages. Cerebral hemorrhagic complications are less frequent than their ischemic counterparts, despite cerebral embolism being the most frequent neurological complication.1–3 Previous investigations have reported asymptomatic cerebrovascular lesions appearing on MRI markedly more frequently than clinical neurological complications.2,4,8–10 Above all, cerebral hypointense lesions detected on T2*-weighted images were frequently observed, as were ischemic lesions on MRI.8–10 These lesions have been interpreted as microbleeds, mycotic aneurysms, or bacterial clots.11 In this study, numerous hypointense masses on T2*-weighted images were found mainly in the cerebral gray and white matter. We presumed that they might reflect mainly cerebral microbleeds rather than hemorrhagic infarction or a brain abscess because they were not apparent on DWI or gadolinium-enhanced T1-weighted images. Cerebral aneurysm was not seen on MRA, though the sensitivity of MRA for mycotic aneurysm is somewhat
Fig 2. Follow-up CT and gradient-echo T2*-weighted images. Hematomas show marked adsorption on CT on hospital day 60 (A, left), and multiple low signal intensity lesions are still apparent on T2*-weighted MR images on day 81 (B, right). less than that of conventional cerebral angiography;12 thus, some of the hypointense lesions, particularly those in the cortical regions, in this case might reflect mycotic aneurysms. Our patient had not only punctate hypointense masses on T2*-weighted images, but also multiple intraparenchymal hematomas on CT. Among the neurological complications in IE, ischemic events are significantly correlated with Staphylococcus aureus infection1–3 and the size of valve vegetation.1–3,10 In contrast, the relationship between hemorrhagic complications and causal microorganisms remains uncertain. A multicenter observational study reported that prior anticoagulant use might be significantly associated with the presence of hemorrhagic cerebral complications on CT in IE.3 Our patient had severe thrombocytopenia due to aplastic anemia. Thus, it is speculated that the severe thrombocytopenia might be associated with the appearance of numerous cerebral hemorrhages and might have contributed to inhibition of ischemic complications. The coexistence of cerebral microbleeds and intraparenchymal hematomas in our patient might be supported by the findings that cerebral microbleeds on T2*-weighted images rapidly increase under bleeding-favorable conditions such as cardiac surgery13 or because they are predictive of future intracranial hemorrhage in IE.14 In conclusion, neurological complications in IE vary with the severity of IE, causal microorganisms, and underlying disease. In cases of IE, accompanying thrombocytopenia might increase the risk for hemorrhagic complications, and gradient-echo T2*-weighted sequences appear to be useful for detecting asymptomatic cerebral complications, especially microbleeds.
References 1. Heiro M, Nikoskelainen J, Engblom E, et al. Neurologic menifestations of infective endocarditis. A 17-year experience in a teaching hospital in Finland. Arch Intern Med 2000;160:27812787.
2. Snygg-Martin U, Gustafsson L, Rosengren L, et al. Cerebrovascular complications in patients with left-sided infective endocarditis are common: a prospective study using magnetic resonance imaging and neurochemical brain damage markers. Clin Infect Dis 2008;47:23-30. 3. García-Cabrera E, Fernández-Hidalgo N, Almirante B, et al. Neurological complications of infective endocarditis: risk factors, outcome, and impact of cardiac surgery: a multicenter observational study. Circulation 2013;127:2272-2284. 4. Hoen B, Duval X. Infective endocarditis. N Engl J Med 2013;368:1425-1433. 5. Sambola A, Miro JM, Tornos MP, et al. Streptococcus agalactiae infective endocarditis: analysis of 30 cases and review of the literature, 1962–1998. Clin Infect Dis 2002;34:1576-1584. 6. Rollan ´ MJ, San Roman ´ JA, Vilacosta I, et al. Clinical profile of Streptococcus agalactiae native valve endocarditis. Am Heart J 2003;146:1095-1098. 7. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infec Dis 2000;30:633-637. 8. Klein I, Ing B, Labreuche J, et al. Cerebral microbleeds are frequent in infective endocarditis. A case-controle study. Stroke 2009;40:3461-3465. 9. Duval X, Iung B, Klein I, et al. Effect of early cerebral magnetic resonance imaging on clinical decisions in infective endocarditis. A prospective study. Ann Intern Med 2010;152:497-504. 10. Iung B, Tubiana S, Klein I, et al. Determinants of cerebral lesions in endocarditis on systematic cerebral magnetic resonance imaging: a prospective study Stroke 2013;44:3056-3062. 11. Bertorini TE, Laster RE Jr, Thompson BF, et al. Magnetic resonance imaging of the brain in bacterial endocarditis. Arch Intern Med 1989;149:815-817. 12. Matsuda T, Kiyose H, Yamashita M, et al. A case of multiple mycotic intracranial aneurysms presenting with subdural hematoma. No Shinkei Geka 2002;30:73-78. 13. Jeon AB, Lee JW, Kim AJ, et al. New cerebral lesions on T2*weighted gradient-echo imaging after cardiac valve surgery. Cerebrovasc Dis 2010;30:194-199. 14. Okazaki S, Sakaguchi M, Hyun BH, et al. Cerebral microbleeds predict impending intracranial hemorrhage in infective endocarditis. Cerebrovasc Dis 2011;32:483-488.
Takahashi et al: Streptococcus Agalactiae Infective Endocarditis
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Keywords: Infective endocarditis, microbleeds, cerebral hemorrhage, Streptococcus agalactiae. Acceptance: Received January 9, 2014, and in revised form May 15, 2014. Accepted for publication June 1, 2014. Correspondence: Address correspondence to Wakoh Takahashi, MD, Department of Neurology, Tokai University School of Medicine, Shimokasuya143, Isehara, Kanagawa 259–1143, Japan. E-mail: [email protected] J Neuroimaging 2014;00:1-3. DOI: 10.1111/jon.12157
Introduction Infective endocarditis (IE) often affects multiple organs, including the central nervous system. Neurological complications observed in 20-35% of patients with IE1–4 include cerebral embolism, transient ischemic attack, cerebral hemorrhage, meningitis, encephalopathy, and brain abscess.1,3,4 Recently, we experienced a patient with Streptococcus agalactiae IE complicated by aplastic anemia. The patient had multiple cerebral hemorrhages on computed tomography (CT), in addition to microhemorrhages on magnetic resonance imaging (MRI). Since S. agalactiae IE is a rare clinical entity,3,5,6 the profile of hemorrhagic complications in S. agalactiae IE is not well known. In this study, we report the characteristics of the cerebral complications accompanying IE in a patient with aplastic anemia.
Case Report The patient was a 40-year-old man who was diagnosed with aplastic anemia in a general hospital at 30 years of age. In midDecember 2012, he presented with fever, shortness of breath, and swelling in the lower limbs. At the end of December, he noticed mildly blurred vision bilaterally, and his visual acuity rapidly deteriorated to blindness the following day. He was admitted to our hospital at the beginning of January 2013 to evaluate severe headache and altered consciousness. On admission, his blood pressure was 112/57 mmHg and pulse was 96 beats per minute with a regular rhythm. Body
temperature was 38.3 ˚C, and a second degree systolic heart murmur was heard. No subcutaneous bleeding or skin eruption was observed. Conjunctival hemorrhages were observed bilaterally. On neurological examination, he was drowsy and found to be blind, with a pupil size of 4.5 mm bilaterally and no light reflexes. Muscle strength in the upper and lower extremities was mildly weak bilaterally, but no hyperreflexia or pathological reflexes in the extremities were observed. He exhibited nuchal rigidity, and Kernig’s sign was positive. On laboratory examination, hemoglobin concentration was 7.1 g/dl, leukocyte count was 2,300 cells/µl, and platelet count was 1,000 plt/µl. Fibrin degradation product (FDP) was to 26.2 µg/dl. Serum C-reactive protein was elevated to 12.80 mg/dl. On initial CT performed on admission, multiple hemorrhages were found in the cerebral white matter bilaterally (Fig 1A), and numerous low signal intensities suggesting microhemorrhages in the cortical or subcortical regions were detected on gradient-echo T2*-weighted sequences (Fig 1B). Diffusionweighted images (DWI) showed no high signal lesions suggestive of acute cerebral ischemia (Fig 1C). None of the lesions detected were apparent on gadolinium-enhanced T1 -weighted images (Fig 1D). No abnormalities of the intra-cranial arteries, including cerebral aneurysms, were detected on magnetic resonance angiography (MRA). Echocardiography performed on hospital day 4 revealed an area of vegetation 4 mm in length in the mitral annular ring and moderate mitral regurgitation. The patient was diagnosed with IE based on clinical characteristics
Copyright
◦ 2014 by the American Society of Neuroimaging C
1
Fig 1. CT and MR images on admission. Multiple hemorrhages in the cerebral white matter bilaterally on CT (A, upper left), and numerous low signal intensities in the cortical and subcortical regions on gradient-echo T2*-weighted sequences (B, upper right). DWI does not show acute cerebral infarction (C, lower left). None of the detected lesions are apparent on gadolinium-enhanced T1-weighted images (D, lower right). and echocardiographic findings. His blindness was diagnosed as severe endophthalmitis with detached retinas, complicated by IE. Intravenous administration of ceftriaxone and vancomycin had been empirically started on hospital day 1. On hospital day 2, phacoemulsification with aspiration and vitrectomy were performed bilaterally. The weakness in the upper and lower extremities accompanying consciousness disturbance improved on hospital day 3. S. agalactiae was detected from both cultures of blood and vitreous humor on hospital day 7. On day 43, echocardiography did not detect the valvular vegetation, and mitral regurgitation had improved. On day 60, CT demonstrated the cerebral hematomas had markedly improved (Fig 2A), but multiple low signal intensities suggesting old microhemorrhages persisted on the T2*-weighted MR images on day 81 (Fig 2B). After receiving continuous cyclosporin, anti-lymphocyte globulin, granulocyte colony-stimulating factor, and platelet transfusions, he was discharged on day 116.
Discussion The patient’s condition, which corresponded to definite IE, fulfilled one major criterion (cardiac echo finding) and three minor criteria (fever, vascular phenomena, and positive blood
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Journal of Neuroimaging Vol 00 No 0 xxx 2014
culture) of the Duke-Li criteria.7 On admission, he presented with consciousness disturbance and weakness in the upper and lower extremities. However, these symptoms, as well as fever, rapidly improved after starting antibiotics. These symptoms might therefore have been induced by meningitis or encephalopathy of IE, rather than the intracerebral hemorrhages. Cerebral hemorrhagic complications are less frequent than their ischemic counterparts, despite cerebral embolism being the most frequent neurological complication.1–3 Previous investigations have reported asymptomatic cerebrovascular lesions appearing on MRI markedly more frequently than clinical neurological complications.2,4,8–10 Above all, cerebral hypointense lesions detected on T2*-weighted images were frequently observed, as were ischemic lesions on MRI.8–10 These lesions have been interpreted as microbleeds, mycotic aneurysms, or bacterial clots.11 In this study, numerous hypointense masses on T2*-weighted images were found mainly in the cerebral gray and white matter. We presumed that they might reflect mainly cerebral microbleeds rather than hemorrhagic infarction or a brain abscess because they were not apparent on DWI or gadolinium-enhanced T1-weighted images. Cerebral aneurysm was not seen on MRA, though the sensitivity of MRA for mycotic aneurysm is somewhat
Fig 2. Follow-up CT and gradient-echo T2*-weighted images. Hematomas show marked adsorption on CT on hospital day 60 (A, left), and multiple low signal intensity lesions are still apparent on T2*-weighted MR images on day 81 (B, right). less than that of conventional cerebral angiography;12 thus, some of the hypointense lesions, particularly those in the cortical regions, in this case might reflect mycotic aneurysms. Our patient had not only punctate hypointense masses on T2*-weighted images, but also multiple intraparenchymal hematomas on CT. Among the neurological complications in IE, ischemic events are significantly correlated with Staphylococcus aureus infection1–3 and the size of valve vegetation.1–3,10 In contrast, the relationship between hemorrhagic complications and causal microorganisms remains uncertain. A multicenter observational study reported that prior anticoagulant use might be significantly associated with the presence of hemorrhagic cerebral complications on CT in IE.3 Our patient had severe thrombocytopenia due to aplastic anemia. Thus, it is speculated that the severe thrombocytopenia might be associated with the appearance of numerous cerebral hemorrhages and might have contributed to inhibition of ischemic complications. The coexistence of cerebral microbleeds and intraparenchymal hematomas in our patient might be supported by the findings that cerebral microbleeds on T2*-weighted images rapidly increase under bleeding-favorable conditions such as cardiac surgery13 or because they are predictive of future intracranial hemorrhage in IE.14 In conclusion, neurological complications in IE vary with the severity of IE, causal microorganisms, and underlying disease. In cases of IE, accompanying thrombocytopenia might increase the risk for hemorrhagic complications, and gradient-echo T2*-weighted sequences appear to be useful for detecting asymptomatic cerebral complications, especially microbleeds.
References 1. Heiro M, Nikoskelainen J, Engblom E, et al. Neurologic menifestations of infective endocarditis. A 17-year experience in a teaching hospital in Finland. Arch Intern Med 2000;160:27812787.
2. Snygg-Martin U, Gustafsson L, Rosengren L, et al. Cerebrovascular complications in patients with left-sided infective endocarditis are common: a prospective study using magnetic resonance imaging and neurochemical brain damage markers. Clin Infect Dis 2008;47:23-30. 3. García-Cabrera E, Fernández-Hidalgo N, Almirante B, et al. Neurological complications of infective endocarditis: risk factors, outcome, and impact of cardiac surgery: a multicenter observational study. Circulation 2013;127:2272-2284. 4. Hoen B, Duval X. Infective endocarditis. N Engl J Med 2013;368:1425-1433. 5. Sambola A, Miro JM, Tornos MP, et al. Streptococcus agalactiae infective endocarditis: analysis of 30 cases and review of the literature, 1962–1998. Clin Infect Dis 2002;34:1576-1584. 6. Rollan ´ MJ, San Roman ´ JA, Vilacosta I, et al. Clinical profile of Streptococcus agalactiae native valve endocarditis. Am Heart J 2003;146:1095-1098. 7. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infec Dis 2000;30:633-637. 8. Klein I, Ing B, Labreuche J, et al. Cerebral microbleeds are frequent in infective endocarditis. A case-controle study. Stroke 2009;40:3461-3465. 9. Duval X, Iung B, Klein I, et al. Effect of early cerebral magnetic resonance imaging on clinical decisions in infective endocarditis. A prospective study. Ann Intern Med 2010;152:497-504. 10. Iung B, Tubiana S, Klein I, et al. Determinants of cerebral lesions in endocarditis on systematic cerebral magnetic resonance imaging: a prospective study Stroke 2013;44:3056-3062. 11. Bertorini TE, Laster RE Jr, Thompson BF, et al. Magnetic resonance imaging of the brain in bacterial endocarditis. Arch Intern Med 1989;149:815-817. 12. Matsuda T, Kiyose H, Yamashita M, et al. A case of multiple mycotic intracranial aneurysms presenting with subdural hematoma. No Shinkei Geka 2002;30:73-78. 13. Jeon AB, Lee JW, Kim AJ, et al. New cerebral lesions on T2*weighted gradient-echo imaging after cardiac valve surgery. Cerebrovasc Dis 2010;30:194-199. 14. Okazaki S, Sakaguchi M, Hyun BH, et al. Cerebral microbleeds predict impending intracranial hemorrhage in infective endocarditis. Cerebrovasc Dis 2011;32:483-488.
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