Stroke caused by an inflammatory thrombus: a case report
© The Author(s). 2017
Received: 3 November 2016
Accepted: 9 February 2017
Published: 16 February 2017
Stroke is the leading cause of mortality and disability worldwide. Several definite risk factors have been identified for stroke, although infectious factors might also contribute to stroke episodes through increased susceptibility or direct induction.
A 46-year-old Chinese male initially presented with fever, headache, and impaired memory and developed disturbance of consciousness after admission. A clinical diagnosis of Staphylococcus aureus sepsis, massive cerebral infarction and haemorrhagic transformation (left internal carotid arterial system, inflammatory thrombus) were made based on brain radiography, blood culture and postoperative pathological examinations. These symptoms improved following antibiotic therapy with vancomycin and conventional treatments for stroke.
For stroke patients without traditional cerebrovascular risk factors but with signs of infection, infectious causes should be considered.
KeywordsStroke Infection Staphylococcus aureus Inflammatory thrombus Haemorrhagic transformation
Stroke is the leading cause of mortality and disability worldwide , and several definite risk factors have been identified for stroke. As shown by the INTERSTROKE study, approximately 90% of stroke episodes are associated with hypertension, smoking, heart disease, diabetes and six additional risk factors . However, infectious factors might also contribute to stroke episodes through increased susceptibility or direct induction . In this paper, one case admitted to our hospital due to stroke induced by Staphylococcus aureus sepsis is described with the purpose of increasing clinicians’ understanding of infectious stroke.
As an emergency diagnosis, massive cerebral infarction (probable atherosclerosis of the left internal carotid artery system) was considered, and intracranial infection could not be excluded; appropriate treatments included aspirin for anti-platelet aggregation, atorvastatin for lipid regulation and plaque stabilization, and cefuroxime and acyclovir for anti-infection.
The patient described herein was middle-aged and healthy; although no stroke risk factors were identified, a rapid onset of disease was observed. After admission, the brain CT suggested cerebral infarction, subsequently followed by haemorrhagic transformation. After craniotomy, the pathological examination indicated that the cerebral infarction was induced by inflammatory thrombosis. Additionally, the patient also experienced fever, shortness of breath and unconsciousness. Laboratory examinations suggested abnormal elevations of haematological variables, CRP, PCT and D-dimer. Staphylococcus aureus was indicated by blood culture. This condition responded well to vancomycin treatment. Therefore, the sepsis was considered to be induced by Staphylococcus aureus infection.
Although there were definite risk factors for stroke, all episodes of this disease could not be fully explained by the factors currently identified. Indeed, many patients who develop stroke do not have any risk factors, and no definite aetiologies are identified for approximately one-third of stroke cases. As shown by several studies, there might be a correlation between systemic infection and episodes of stroke . Indeed, relevant case–control studies have confirmed this correlation between systemic infection and stroke. In patients with stroke, the odds ratio of a precursor infection was in the range of 2–14.5 [5–10].
A wide range of pathogens has been found to be associated with an elevation of stroke risk, including viruses, bacteria, fungi and parasites. The most investigated pathogens include Helicobacter pylori, Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Epstein-Barr virus (EBV), herpes simplex virus (HSV)-1, HSV-2 and cytomegalovirus [3, 11].
Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections . Staphylococcus aureus bacteraemia (SAB) is associated with a short-term increased risk of stroke, and the risk can persist for up to 180 days. The risk factors for stroke after SAB include old age, prior arterial thromboembolic events, atrial flutter/fibrillation, hypertension and endocarditis .
The mechanism of stroke induced by infection remains incompletely understood, although stimulation of the inflammatory response is considered to be the main driver for stroke [14–16]. Pathogens may directly invade the vascular wall during the course of infection, concomitant with an increase in smooth muscle cell proliferation or inflammatory cytokine production. Additionally, regions far away from the primary infected loci might also be affected, and this secondary impairment might also lead to damage of the arterial wall. Furthermore, the inflammatory response induced by infection could stimulate enhancement of platelet aggregation and dysfunction of vasodilation . It has been described that blood levels of high-sensitivity CRP (HS-CRP) may be considered an independent predictor for ischemic stroke, although the exact correlation remains unclear [17, 18].
Based on the current patient’s medical history, physical examination, and laboratory, radiology and pathological examinations, the aetiology of stroke was considered to be embolic stroke and subsequent haemorrhagic transformation as a result of migration of the septic emboli induced by systematic Staphylococcus aureus infection to the left internal carotid artery system. Staphylococcus aureus is a common pathogen of acute infective endocarditis, and infective endocarditis has been identified as an important cause of cardioembolic stroke [19–21]. However, two TTE examinations showed no abnormal findings. A diagnosis of infective endocarditis was still possible for this case because one major and one minor criterion of the modified Duke criteria were met . Further cardiac evaluation, such as a transoesophageal echocardiography (TEE), should have been considered. Unfortunately, due to the serious condition of the patient and the unavailability of bedside TEE in our hospital, TEE was not performed in this case.
Additionally, post-operational pathological findings suggested inflammatory changes of brain tissues, consistent with purulent thrombosis. However, a culture of brain tissue was not obtained because of the poor communication between the emergency physicians and neurosurgeons during such an urgent situation. If the same strain were identified between this culture and the blood culture, the aetiological diagnosis of this case would be further confirmed.
Appropriate aetiological judgment is critical for the treatment of stroke. In clinical practice, the possibility of stroke induced by infective factors should be considered with caution for patients with no traditional risk factors of stroke and infective signs. For these patients, an appropriate regimen should be determined based on targeted anti-infective therapies in addition to traditional treatments for stroke. Additionally, similar to traditional risk factors, preventive interventions against some infections might also contribute to decreasing the incidence of stroke in some cases.
Glasgow coma scale
Human immunodeficiency virus
High-sensitivity C-reactive protein
Herpes simplex virus
Magnetic resonance imaging
Staphylococcus aureus bacteraemia
Toxoplasmosis other infections, rubella, cytomegalovirus, and herpes simplex virus
White blood cell
The authors would like to thank Dr. Jun-Mei Wang, a neuropathologist at the Laboratory of Pathology, Beijing Institute of Neurosurgery, China, for her valuable advice on interpreting the pathological findings.
No funding was obtained.
Availability of data and materials
The datasets supporting the conclusions of this article are included within the article and its additional files.
KS examined the patient and drafted the manuscript. WG participated in the design of the case report and helped to draft the manuscript. Both authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Ethics approval and consent to participate
This case report involves a patient. The case report complies with the Helsinki Declaration, and approval was obtained from the ethics committee of Beijing Tiantan Hospital.
The authors report no disclosures related to this manuscript.
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- Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2197–223.View ArticlePubMedGoogle Scholar
- O'Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, et al. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case–control study. Lancet. 2016;388:761–75.View ArticlePubMedGoogle Scholar
- Fugate JE, Lyons JL, Thakur KT, Smith BR, Hedley-whyte ET, Mateen FJ. Infectious causes of stroke. Lancet Infect Dis. 2014;14:869–80.View ArticlePubMedGoogle Scholar
- Grau AJ, Urbanek C, Palm F. Common infections and the risk of stroke. Nat Rev Neurol. 2010;6:681–94.View ArticlePubMedGoogle Scholar
- Grau AJ, Buggle F, Heindl S, Steichen-Wiehn C, Banerjee T, Maiwald M, et al. Recent infection as a risk factor for cerebrovascular ischemia. Stroke. 1995;26:373–9.View ArticlePubMedGoogle Scholar
- Bova IY, Bornstein NM, Korczyn AD. Acute infection as a risk factor for ischemic stroke. Stroke. 1996;27:2204–6.View ArticlePubMedGoogle Scholar
- Syrjänen J, Valtonen V, Livanainen M, Kaste M, Huttunen JK. Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients. BMJ (Clin Res Ed). 1988;296:1156–60.View ArticleGoogle Scholar
- Clayton TC, Thompson M, Meade TW. Recent respiratory infection and risk of cardiovascular disease: case–control study through a general practice database. Eur Heart J. 2008;29:96–103.View ArticlePubMedGoogle Scholar
- Nencini P, Sarti C, Innocenti R, Pracucci G, Inzitari D. Acute inflammatory events and ischemic stroke subtypes. Cerebrovasc Dis. 2003;15:215–21.View ArticlePubMedGoogle Scholar
- Paganini-Hill A, Lozano E, Fischberg G, Barreto MP, Rajamani K, Ameriso SF, et al. Infection and risk of ischemic stroke: differences among stroke subtypes. Stroke. 2003;34:452–7.View ArticlePubMedGoogle Scholar
- Miller E, Elkind MS. Infection and Stroke: an Update on Recent Progress. Curr Neurol Neurosci Rep. 2016;16:1–10.View ArticleGoogle Scholar
- Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler Jr VG. Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management. Clin Microbiol Rev. 2015;28:603–61.View ArticlePubMedPubMed CentralGoogle Scholar
- Mejer N, Gotland N, Uhre ML, Westh H, Schonheyder HC, Petersen A, et al. Increased risk of arterial thromboembolic events after Staphylococcus aureus bacteremia: A matched cohort study. J Infect. 2015;71:167–78.View ArticlePubMedGoogle Scholar
- Elkind MS, Ramakrishnan P, Moon YP, Bodenalbala B, Liu K, Rundek T, et al. Infectious burden and risk of stroke: the northern Manhattan study. Arch Neurol. 2010;67:33–8.View ArticlePubMedGoogle Scholar
- Epstein SE, Zhou YF, Zhu J. Infection and atherosclerosis: emerging mechanistic paradigms. Circulation. 1999;100:e20–8.View ArticlePubMedGoogle Scholar
- Lindsberg PJ, Grau AJ. Inflammation and infections as risk factors for ischemic stroke. Stroke. 2003;34:2518–32.View ArticlePubMedGoogle Scholar
- Elkind MS. Inflammatory mechanisms of stroke. Stroke. 2010;41:S3–8.View ArticlePubMedPubMed CentralGoogle Scholar
- DA E, Lowe GD, Thompson S, Collins R, Danesh J, Nissinen A, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375:132–40.View ArticleGoogle Scholar
- Dickerman SA, Abrutyn E, Barsic B, Bouza E, Cecchi E, Moreno A, et al. The relationship between the initiation of antimicrobial therapy and the incidence of stroke in infective endocarditis: an analysis from the ICE Prospective Cohort Study (ICE-PCS). Am Heart J. 2007;154:1086–94.View ArticlePubMedGoogle Scholar
- Duval X. lung B, Klein I, Brochet E, Thabut G, Arnoult F, 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.View ArticlePubMedGoogle Scholar
- Chow FC, Marra CM, Cho TA. Cerebrovascular disease in central nervous system infections. Semin Neurol. 2011;31:286–306.View ArticlePubMedGoogle Scholar
- Hoen B, Duval X. Infective endocarditis. N Engl J Med. 2013;368:1425–33.View ArticlePubMedGoogle Scholar