(Stroke. 1995;26:373-379.)
© 1995 American Heart Association, Inc.
Articles |
Recent Infection as a Risk Factor for Cerebrovascular Ischemia
From the Departments of Neurology (A.J.G., F.B., S.H., C.S.-W., T.B., W.H.), Microbiology (M.M., M.R., H.S.), and Medicine (W.F.), University of Heidelberg; and the Department of Epidemiology, German Cancer Research Center (H.B.), Heidelberg, Germany.
Correspondence to Armin J. Grau, MD, Neurologische Universitätsklinik Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
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Abstract |
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Background and Purpose Previous infection is discussed as a risk factor for ischemic stroke in children and younger adults. We tested the hypothesis that the role of recent infection in cerebrovascular ischemia is not restricted to younger patients and investigated which infections are mainly relevant in this respect.
Methods We performed a case-control study with 197 patients aged 18 to 80 years with acute cerebrovascular ischemia and 197 randomly selected control subjects matched for sex, age, and area of residence.
Results Infection within 1 week before ictus or examination was
significantly more common among patients (38 of 197) than control
subjects (10 of 197; odds ratio [OR], 4.5; 95% confidence interval
[CI], 2.1 to 9.7). Patients more often had febrile and subfebrile
infections (
37.5°C) than control subjects (29 of 197 versus 5 of
197; OR, 7.0; 95% CI, 2.5 to 20). Respiratory tract infections were
most common in both groups. Bacterial infections dominated among
patients but not among control subjects. Infection increased the risk
for cerebrovascular ischemia in all age groups; this reached
significance for patients aged 51 to 60 and 61 to 70 years. The profile
of vascular risk factors was similar in patients with and patients
without previous infection. Infection remained a significant risk
factor when previous stroke, hypertension, diabetes mellitus, coronary
heart disease, and current smoking were included as covariates in a
logistic model (OR, 4.6; 95% CI, 1.9 to 11.3).
Conclusions Recent infection, primarily of bacterial origin, may be a risk factor for cerebrovascular ischemia in older as well as younger patients.
Key Words: cerebral ischemia • infection • risk factor
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Predictive indexes for cerebrovascular ischemia are imperfect, suggesting that there may be risk factors that are not yet commonly recognized. A lack of risk factors or causative diseases can be observed among younger patients in particular, although not exclusively. Furthermore, the question arises regarding why patients with risk factors or diseases that predispose them to stroke suffer from cerebrovascular ischemia at a particular time. A carotid stenosis or a cardiac arrhythmia may have been unchanged for a long period before causing a cerebral infarct.
Recent infection may be a hitherto underestimated risk factor for cerebrovascular ischemia. A positive association between the death rate of cardiovascular diseases and epidemics of respiratory infections has been observed.1 The increased rate of infection during winter months appears to be partly responsible for the winter peak of deaths from cardiovascular diseases in England and Wales.2 Several authors have discussed infection as a causative factor for ischemic stroke in children and young adults.3 4 5 6 7 8 9 10 11 A case-control study with patients aged younger than 50 years indicated that recent infection is an important and independent risk factor for ischemic stroke in Finland.12 During a study of leukocyte function in acute stroke excluding subjects with infection,13 we noted a high prevalence of recent infection among patients of all ages in southern California, an observation supported by the report of Ameriso and coworkers.14 Because an investigation including older patients was still lacking, we designed a case-control study to determine whether previous infection is an independent risk factor for cerebral ischemia in adult patients aged 80 years or younger living in a small area in southwest Germany. In particular, we addressed the following questions: Is an association of stroke and recent infection restricted to younger age groups? What kind of infection and which temporal relationship between infection and cerebral ischemia are mainly relevant?
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Subjects and Methods |
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Between October 1991 and October 1992 we studied patients between 18 and 80 years of age with persistent or transient cerebral ischemia who are inhabitants of the city of Heidelberg or two neighboring counties. The study included patients who were examined in the emergency unit of the Neurology Department of the University of Heidelberg. Almost all younger patients and many of the older patients living in this area are referred to our emergency unit for primary diagnostic and therapeutic procedures after stroke. All patients received a computed tomographic (CT) scan, and the diagnosis of cerebrovascular ischemia was in all cases made by experienced neurologists who were not involved in the study. We excluded patients with a cerebral hemorrhage and patients in whom there was still uncertainty about the diagnosis.
During 1 year we included 197 patients (83 women and 114 men; mean±SD age, 63.1±10.9 years; range, 22 to 80 years) in the study. The staff nurses of the emergency unit were asked to inform a member of the study team by a long-distance paging system on arrival of a patient with a suspected stroke. After neurological and technical examinations, approximately 75% of all acute stroke patients seen in our emergency unit are referred to other hospitals. We could not include all patients seen during this year because in some instances the stay in the emergency unit was very short, comprising only a neurological examination and a CT scan. The design of this study did not allow a potentially disadvantageous delay of the patients' transfer to other hospitals when a member of our study group had not yet arrived. In other instances we were not informed or were informed too late about the arrival of a patient, or technical problems with the paging system occurred. In addition, it was not possible to enter patients who were already in the process of being transferred to other hospitals. In total we entered approximately 67% of the eligible patients into the study. We took particular care to avoid any selection bias in patient identification. In stroke patients, questions and tests regarding previous or present infections were not part of the regular evaluation done by the staff of the emergency unit, and this did not change during the study.
We examined 119 of the patients within 24 hours, 59 during the second day, and 19 between the third and the sixth day after the onset of symptoms. The diagnosis of ischemic stroke was made in 177 patients either by a positive CT scan on first or repeated examination (n=140) or by clinical symptoms lasting more than 24 hours (n=37). In 20 patients the neurological deficit lasted less than 24 hours, and no acute ischemic lesion could be detected, at least on an early CT scan.
The control subjects were randomly selected from the population of the above area and matched with patients for sex, age (±2 years), and area of residence (maximally 10 km distant from the patient's village or city). In accordance with the German law for the protection of personal data and after permission by the local authorities of all 81 communities in the above area, we obtained a random sample from the official register of all inhabitants containing name, sex, date of birth, and address. Within 1 week after the examination of a patient, we selected two matching control subjects from this sample and asked them to participate in the study, first by a letter and a few days later by telephone. Only the first cooperative person was entered into the study. In cases in which both persons declined to participate, we selected a second pair of potential control subjects. Thus, a case-control study matched one to one was performed. In 104 cases the first person asked and in 43 cases the second person asked agreed to participate. In 50 patients additional volunteers had to be asked to find a control subject. The response rate was approximately 61%. Because of difficulties in finding cooperative control subjects for older patients, we reduced the upper age limit to 75 years during the last 4 months of the study. The average time interval between the examination of a patient and his respective control was 27 days. There were no exclusion criteria for the control group. Because medical and economic considerations should not be factors in a denial to participate, we offered a small financial incentive for control subjects to come to the hospital or to be visited at home. As a result, 70 of 197 control subjects were visited at home. In cases in which the control subjects were not willing to participate, we tried to determine the reasons. To our knowledge, none of the subjects asked refused for medical reasons; lack of time and interest were the most common explanations.
We evaluated the medical history of all patients and control subjects
with use of an extensive standardized questionnaire focusing on signs
of potential infection during the last 4 weeks and any previous
infections. Other questions were directed to prior vascular diseases
and their risk factors, noninfective inflammatory diseases,
malignancies, smoking and alcohol habits, and use of oral
contraceptives and other medication. We interviewed the relatives of
patients with disturbed consciousness or aphasia; patients were not
excluded when information was lacking but rather qualified as not
having had a previous infection. All patients and control subjects
received a detailed physical examination by one of the study members,
including an oral measurement of body temperature. A urine sample and a
sample of venous blood for biochemical and antimicrobial analysis
were taken from all patients and control subjects. For a second
analysis of antimicrobial antibodies, the blood collection was
repeated 10 to 18 days after the first investigation. Antimicrobial
serum analysis was performed with established methods and included
common bacteria and viruses for which serological methods were
available (Table 1
). In cases of suspicious or
pathological findings, additional cultural or radiological
investigations were done. The human subjects committee of the
University Hospital in Heidelberg approved the protocol of this
study.
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We diagnosed an infection if at least one typical symptom was present in combination with fever (>38.0°C), subfebrile temperature (37.5°C to 37.9°C), or a corresponding serological or cultural finding that indicated an acute infection. An additional diagnostic criterion for an infection was a combination of at least two symptoms typical of a local infection (eg, cough and purulent sputum). Combinations of signs and symptoms that may have been caused by diseases other than infection (eg, by an allergy) were not accepted. Symptoms of infection had to have started before cerebral ischemia to be acknowledged. In cases of technical and serological findings that demonstrated an acute infection in asymptomatic subjects, we diagnosed a subclinical infection.
For statistical analysis we used a conditional logistic analysis.15 Variables for the final logistic model were selected in order of their probability values in univariate analysis. Odds ratio (OR) estimates and 95% confidence intervals (CI) are given in all analyses. We used the statistical software package SAS for the analyses.
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Results |
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Infection was significantly more common among patients than control subjects both within 4 weeks and within 1 week before cerebral ischemia or examination (P<.001) (Table 2
).
Because the period 1 week before cerebral ischemia or examination
accounted for most of the differences between groups, in the following
paragraphs we will focus on this time interval. Infection during the
preceding week was a significant risk factor in both men and women.
Patients with infection reported or still had elevated body temperature
more often than control subjects with infection. The OR of suffering
from cerebral ischemia in association with febrile or subfebrile
infection was even higher than with infection in total (Table 2). Among
the 20 patients with rapidly reversible symptoms and no detectable
lesion on CT scan, 5 had an infection within 1 week before ischemia
(OR, 4.0; 95% CI, 0.45 to 35.8).
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Infection in patients had started up to 4 weeks before stroke; in most cases (31 of 38), however, symptoms had begun within 1 week. Among the 38 patients with an infection during the preceding week, 31 still had at least one sign or symptom of the infection on admission. In all cases the history clearly indicated that infection preceded cerebral ischemia. Fourteen of the 38 patients had consulted a physician because of their infection.
The above analysis only included subjects whose history and/or
findings satisfied our criteria for certified infection (Table 3). The history made an infection within 1 week likely
in 13 additional patients (6.6%) and 4 additional control subjects
(2.0%). The risk of suffering from cerebral ischemia in association
with a certified or a probable infection was in the same range as for
proven infection alone (OR, 4.6; 95% CI, 2.3 to 9.1). In 9 patients
(5.1%) and 15 control subjects (7.6%), serological data (6 patients,
9 control subjects) or urine analysis (3 patients, 6 control
subjects) revealed subclinical infection. Therefore, subclinical
infection was not correlated with an increased risk for cerebrovascular
ischemia.
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Respiratory tract, gastrointestinal, and urinary tract infections were
all more frequent among patients than among control subjects (Table 4). None of our patients or control subjects had
endocarditis, bacterial or tuberculous meningitis, active Lyme
borreliosis, or syphilis. Respiratory tract infections dominated in
both groups. However, infections more often involved lower parts of the
respiratory tract in patients than in control subjects and thus were
often more severe in the patients' group (Table 4). The diagnosis
"upper respiratory tract infection" comprises infections such as
sinusitis, otitis, tonsillitis, or laryngitis, but often more than one
organ appeared to be involved. In the 7 patients with pneumonia, a
chest x-ray confirmed the diagnosis in 6 cases; the remaining patient
had fever, and auscultation indicated consolidation.
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Bacterial infections dominated among patients but not among control
subjects with an infection during the preceding week (Table 4
).
Bacterial infections significantly increased the risk for
cerebrovascular ischemia (OR, 5.75; 95% CI, 2.0 to 16.9;
P<.002). Viral infections were also more common among
patients than control subjects; however, they did not represent
a significant risk factor for cerebrovascular ischemia (OR, 2.25; 95%
CI, 0.69 to 7.3). In the absence of serological findings, we suspected
viral infections in cases of upper respiratory infection without
evidence of bacterial participation. Several different bacteria and
viruses could be identified in patients (Table 5). Among
the 12 patients with bacterial infection without identification of
causative organisms (Table 4), 6 suffered from purulent bronchitis, 3
had pneumonia on chest x-ray typical of a bacterial origin, and 3
showed significant bacteriuria. Three of the 38 patients and 3 of the
10 control subjects with infection within 1 week had received
antibiotic therapy before ictus or examination; 2 of these patients and
2 of these control subjects had bacterial infection according to our
classification.
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Infection increased the risk for cerebrovascular ischemia in all age
groups (Table 6). This reached significance for subjects
aged 51 to 60 and 61 to 70 years. The highest prevalence of infection
within 1 week before cerebral ischemia was found in patients younger
than 51 years and in those aged 51 to 60 years. However, significance
was missed for patients younger than 51 years, a finding which is
probably due to the low number of subjects (n=24) and the relatively
high prevalence of infection among the respective control subjects.
Both groups were not different with respect to socioeconomic status
when subjects were divided into three classes according to their
profession. In 45 pairs control subjects were in a higher class than
patients, and in 31 pairs patients were in a higher class than control
subjects (P=NS by 
2 test).
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Both patients and control subjects were also investigated for the
presence of established or suspected risk factors for and diseases
presumably associated with cerebrovascular ischemia. In a univariate
analysis hypertension, diabetes mellitus, coronary heart disease,
previous cerebral ischemia, and a familial history of stroke were shown
to be significant risk factors. In contrast, current smoking failed to
be significant, and hypercholesterolemia did not have any predictive
value for cerebrovascular ischemia (Table 7). With
respect to hypertension, diabetes mellitus, current smoking, coronary
heart disease, and previous cerebrovascular ischemia, the risk factor
profile was similar in patients with and in patients without preceding
infection (Table 8). In addition, 13% of the patients
with infection (5 of 38) and 13% of the patients without infection (21
of 159) did not have any of these five risk factors. Only
hypercholesterolemia was significantly less common among patients with
than among those without preceding infection. More patients than
control subjects reported having had two or more episodes of purulent
bronchitis, and this difference almost reached significance (Table 7).
Other chronic or recurrent infections did not occur more often among
patients than among control subjects (data not shown).
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To investigate whether infection is a risk factor independent of other
confounding factors, a conditional logistic regression analysis for
matched pairs was performed. In both sexes combined and in men but not
in women, previous infection was a significant risk factor when
hypertension, diabetes mellitus, current smoking, coronary heart
disease, and previous cerebral ischemia were included as covariates in
the logistic model (Table 9). The estimated ORs were
similar to the results in univariate analysis (Table 7). In an
additional step we investigated whether ORs are age dependent by
including appropriate interaction terms into the model. We found that
the OR for diabetes mellitus significantly decreases with increasing
age. For the other factors given in Table 9 we could not detect
significant differences. Infection appears to have a slightly stronger
effect in younger subjects; however, definite conclusions cannot be
drawn.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Our results indicate that infection during the preceding week is a risk factor for cerebrovascular ischemia. Infection increased the risk in all age groups; analyzing all subjects together, the effect of infection remained significant when we controlled for other risk factors for stroke. Infections among patients were mainly of bacterial origin and were most commonly located in the respiratory tract.
It was a particular interest of this study to investigate whether previous infection represents a risk factor for stroke exclusively in younger patients. Because mainly young and middle-aged patients are admitted to the University Hospital in Heidelberg, we also included patients who were only seen in our emergency department and were referred to hospitals in the vicinity after primary care. Therefore, we could not investigate patients consecutively. However, we took particular care to avoid any selection bias in patients, and the incidence of infection among our patients was lower than in previous reports,12 14 suggesting that we did not overestimate the association of infection and cerebral ischemia. Because persons with multiple illnesses are more likely to seek medical help, it could be expected that transient ischemic attack or minor stroke patients with concomitant infection may be overrepresented in a hospital-based study. Patients or their relatives rarely mentioned previous infections spontaneously; thus, we have no indication that infection may have directly influenced the decision to come to the hospital.
We randomly selected our control subjects from the general population and tried to minimize the influence of local and seasonal variations of infections. Therefore, we matched patients and control subjects for the area of residence and investigated control subjects as soon as possible after investigation of the respective patient. Both groups did not significantly differ with respect to the prestige of the subjects' profession, indicating that the different prevalence of infection is probably not caused by differences in socioeconomic status. Choosing control subjects from the community may lead to a selection of healthier individuals in general than the case subjects because infected people are less likely to participate in any study than people without infection at the time of the study. Being aware of this potential bias, we offered to visit the persons at home and tried to determine the reasons in cases of refusal. Subjects unwilling to participate almost exclusively mentioned lack of time and interest as an explanation; the question of whether medical reasons determined their unwillingness to take part in the study was denied in all cases in which people commented on their motivation. Therefore, there is no indication that the refusals in the control group caused any considerable bias. Selecting hospitalized nonstroke patients as a control group may have the advantage of a higher participation rate. On the other hand, it may not allow matching case patients and control subjects for the area of residence, and in such a control group, the rate of infection will most likely be higher than in the general population. Analyzing both hospitalized and community control subjects could be a reasonable procedure in future studies.
The low rate of prior infection in the control group yielded wide confidence limits and unstable estimates, which were a limitation of our study. However, our sample size still provides sufficient power for detecting a high risk of cerebrovascular ischemia in association with infection. We found that infections within 1 week before ictus in particular (and to a nonsignificant extent, those 2 to 4 weeks before ictus) increase the risk for cerebrovascular ischemia. The prevalence of infection was relatively smaller during the 2 to 4 preceding weeks than within the 1 week before ischemia or examination not only among patients but also in the control group, perhaps because people might not have remembered events that occurred up to 4 weeks ago. In addition, our strict criteria for acknowledging an infection may have caused a higher rate of exclusions among more antecedent infections. Most of the patients still showed signs or symptoms of their infection on admission to the hospital; this supports a rather close temporal relationship between infection and cerebral ischemia. The infections began before the cerebral ictus but were generally still active when cerebral ischemia occurred.
The infections among our patients were mainly of bacterial origin and were most commonly located in the respiratory tract, in accordance with previous results.12 14 16 A significant association of respiratory infection with the onset of myocardial infarction has also been reported recently.17 We found several different causative organisms, which indicates that cerebrovascular ischemia is not related to infection by one particular bacterium or by one group of bacterial organisms. Several case reports describe an association between cerebral ischemia and Mycoplasma infections7 8 11 18 ; we did not detect an infection with Mycoplasma pneumoniae among our patients. Viral infections that preceded the stroke were not associated with an increased risk for cerebral ischemia in this study. In single cases, however, the preceding viral infection may still have played a role in the pathogenesis of stroke.3 9 Although many patients had only minor infections, the infectious diseases were more often severe and more often accompanied by fever among patients than among control subjects.
In the past the association between infection and cerebral ischemia was mainly considered to be a relevant phenomenon in children and younger adults. Our results indicate that the importance of acute infection as a risk factor for cerebral ischemia is not restricted to young and middle-aged patients. Hypertension, diabetes mellitus, coronary heart disease, previous stroke or transient ischemic attack, and a positive family history of stroke were significant predictors for cerebrovascular ischemia in our study, in accordance with previous reports.19 20 21 22 23 24 25 Current smoking failed to be a significant risk factor in univariate analysis; it was significant, however, in our conditional logistic model. Previous results concerning smoking as a risk factor for cerebral ischemia are equivocal.21 22 25 26 27 In agreement with most other reports, increased serum cholesterol was not a risk factor for cerebral ischemia.21 25 28 Some of the vascular risk factors, such as diabetes mellitus, smoking, or previous disabling stroke, alter the susceptibility to infection. Therefore, the increased prevalence of infection among patients with cerebral ischemia may be caused by those underlying risk factors. The multivariate analysis, however, identified infection as an independent risk factor in both sexes together and in men but not in women.
The profile of predictors for cerebrovascular ischemia was similar in patients with and in patients without preceding infection. Therefore, infection appears to temporarily increase the risk for cerebral ischemia in patients with a preexisting increased risk and acts mainly as a trigger factor for ischemic stroke. In single cases (for example, in children and younger adults), when no other risk factors or causative diseases are present, infection may also be the main cause for cerebral arterial thrombosis. Control subjects with bacterial infection had received treatment with antibiotics relatively more often than patients with bacterial infection. Further investigations are needed to determine whether early treatment with antibiotics can prevent cerebral ischemic accidents in patients with vascular risk factors and acute bacterial infection.
The mechanisms linking infection and cerebral ischemia are still
largely undetermined. In endocarditis, emboli from infected heart
valves can cause ischemic stroke,29 and in bacterial,
including tuberculous, meningitis, cerebral vasculitis can lead to
ischemic stroke30 ; after herpes zoster of the neck and
face, a local necrotizing arteritis can occur and can cause cerebral
ischemia.31 However, these conditions were not present
in our patients. Inflammatory mechanisms that accompany infection can
stimulate coagulation by several pathways. These include the expression
of thromboplastin by monocytes and macrophages,32
increased serum levels of tumor necrosis factor-
and other
cytokines33 34 that may alter coagulant function of the
endothelium, the inhibition of the protein C/protein S anticoagulant
system,35 36 and increased levels of clotting factors such
as fibrinogen.2 In patients with infection-associated
cerebral infarction, Ameriso and coworkers14 detected
increased fibrin generation, increased cardiolipin immunoreactivity,
and hyperfibrinogenemia compared with stroke patients without
infections. This indicates a link between ischemic stroke, infection,
and a procoagulant state. Further investigations are required to
clarify the mechanisms linking acute infection and cerebral
ischemia.
We conclude that an infection during the preceding week may be a significant risk factor for cerebral ischemia in older as well as younger patients, although the effect of this factor may be more pronounced in younger subjects. Among patients with vascular risk factors, infection may act as a trigger factor and appears to temporarily increase the risk for cerebrovascular ischemia. Further studies that use different methodical approaches are desirable to confirm these results and to obtain more precise estimates regarding previous infection as a risk factor for cerebrovascular ischemia.
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Acknowledgments |
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We gratefully acknowledge the financial support provided by Boehringer Mannheim Inc for the purchase of the random sample from the official register of all inhabitants of the investigated area. We wish to thank the staff of the emergency unit in the Neurology Department of the University of Heidelberg for their helpful assistance in patient identification.
Received August 12, 1994; revision received November 25, 1994; accepted December 13, 1994.
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 B. W. McColl, N. J. Rothwell, and S. M. Allan Systemic Inflammatory Stimulus Potentiates the Acute Phase and CXC Chemokine Responses to Experimental Stroke and Exacerbates Brain Damage via Interleukin-1- and Neutrophil-Dependent Mechanisms J. Neurosci., April 18, 2007; 27(16): 4403 - 4412. [Abstract] [Full Text] [PDF]
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 Z. T. Bloomgarden Third Annual World Congress on the Insulin Resistance Syndrome: Atherothrombotic disease Diabetes Care, August 1, 2006; 29(8): 1973 - 1980. [Full Text] [PDF]
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 B.A. Taylor, G.H. Tofler, H.M.R. Carey, M.-C. Morel-Kopp, S. Philcox, T.R. Carter, M.J. Elliott, A.D. Kull, C. Ward, and K. Schenck Full-mouth Tooth Extraction Lowers Systemic Inflammatory and Thrombotic Markers of Cardiovascular Risk Journal of Dental Research, January 1, 2006; 85(1): 74 - 78. [Abstract] [Full Text] [PDF]
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 A. Razmara, D. N. Krause, and S. P. Duckles Testosterone augments endotoxin-mediated cerebrovascular inflammation in male rats Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1843 - H1850. [Abstract] [Full Text] [PDF]
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 E. Kazanci, K. K. Oguz, A. Gurgey, and M. Topcu Streptococcus oralis as a Risk Factor for Middle Cerebral Artery Thrombosis J Child Neurol, July 1, 2005; 20(7): 611 - 613. [Abstract] [PDF]
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 J.A. Zeller, A. Lenz, C.C. Eschenfelder, P. Zunker, and G. Deuschl Platelet-Leukocyte Interaction and Platelet Activation in Acute Stroke With and Without Preceding Infection Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1519 - 1523. [Abstract] [Full Text] [PDF]
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A. J. Grau, B. Fischer, C. Barth, P. Ling, C. Lichy, and F. Buggle Influenza Vaccination Is Associated With a Reduced Risk of Stroke Stroke, July 1, 2005; 36(7): 1501 - 1506. [Abstract] [Full Text] [PDF]
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 J. H. Meurman, M. Sanz, and S.-J. Janket ORAL HEALTH, ATHEROSCLEROSIS, AND CARDIOVASCULAR DISEASE Critical Reviews in Oral Biology & Medicine, November 1, 2004; 15(6): 403 - 413. [Abstract] [Full Text] [PDF]
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A. J. Grau, A. W. Boddy, D. A. Dukovic, F. Buggle, C. Lichy, T. Brandt, W. Hacke, and for the CAPRIE Investigators Leukocyte Count as an Independent Predictor of Recurrent Ischemic Events Stroke, May 1, 2004; 35(5): 1147 - 1152. [Abstract] [Full Text] [PDF]
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P. J. Lindsberg and A. J. Grau Inflammation and Infections as Risk Factors for Ischemic Stroke Stroke, October 1, 2003; 34(10): 2518 - 2532. [Abstract] [Full Text] [PDF]
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D. Acalovschi, T. Wiest, M. Hartmann, M. Farahmi, U. Mansmann, G. U. Auffarth, A. J. Grau, F. R. Green, C. Grond-Ginsbach, and M. Schwaninger Multiple Levels of Regulation of the Interleukin-6 System in Stroke Stroke, August 1, 2003; 34(8): 1864 - 1869. [Abstract] [Full Text] [PDF]
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B. Guillon, K. Berthet, L. Benslamia, M. Bertrand, M.-G. Bousser, and C. Tzourio Infection and the Risk of Spontaneous Cervical Artery Dissection: A Case-Control Study Stroke, July 1, 2003; 34 (7): e79 - e81. [Abstract] [Full Text] [PDF]
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A. Paganini-Hill, E. Lozano, G. Fischberg, M. Perez Barreto, K. Rajamani, S.F. Ameriso, P.N.R. Heseltine, and M. Fisher Infection and Risk of Ischemic Stroke: Differences Among Stroke Subtypes Stroke, February 1, 2003; 34(2): 452 - 457. [Abstract] [Full Text] [PDF]
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P. B. Gorelick Stroke Prevention Therapy Beyond Antithrombotics: Unifying Mechanisms in Ischemic Stroke Pathogenesis and Implications for Therapy: An Invited Review Stroke, March 1, 2002; 33(3): 862 - 875. [Abstract] [Full Text] [PDF]
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A. J. Grau, C. Weimar, F. Buggle, A. Heinrich, M. Goertler, S. Neumaier, J. Glahn, T. Brandt, W. Hacke, and H.-C. Diener Risk Factors, Outcome, and Treatment in Subtypes of Ischemic Stroke: The German Stroke Data Bank Stroke, November 1, 2001; 32(11): 2559 - 2566. [Abstract] [Full Text] [PDF]
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T. A. Kent, V. M. Soukup, and R. H. Fabian Heterogeneity Affecting Outcome From Acute Stroke Therapy: Making Reperfusion Worse Stroke, October 1, 2001; 32(10): 2318 - 2327. [Abstract] [Full Text] [PDF]
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M. Di Napoli, F. Papa, and V. Bocola C-Reactive Protein in Ischemic Stroke : An Independent Prognostic Factor Stroke, April 1, 2001; 32(4): 917 - 924. [Abstract] [Full Text] [PDF]
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V. L. Feigin, C. S. Anderson, N. E. Anderson, J. B. Broad, M. J. Pledger, and R. Bonita Is There a Temporal Pattern in the Occurrence of Subarachnoid Hemorrhage in the Southern Hemisphere? : Pooled Data From 3 Large, Population-Based Incidence Studies in Australasia, 1981 to 1997 Stroke, March 1, 2001; 32(3): 613 - 619. [Abstract] [Full Text] [PDF]
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N. Vila, J. Castillo, A. Davalos, and A. Chamorro Proinflammatory Cytokines and Early Neurological Worsening in Ischemic Stroke Stroke, October 1, 2000; 31(10): 2325 - 2329. [Abstract] [Full Text] [PDF]
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D. J. Lanska and R. J. Kryscio Risk Factors for Peripartum and Postpartum Stroke and Intracranial Venous Thrombosis Stroke, June 1, 2000; 31(6): 1274 - 1282. [Abstract] [Full Text] [PDF]
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 A. J. Grau, T. Brandt, F. Buggle, E. Orberk, J. Mytilineos, E. Werle, C. Conradt, M. Krause, R. Winter, and W. Hacke Association of Cervical Artery Dissection With Recent Infection Arch Neurol, July 1, 1999; 56(7): 851 - 856. [Abstract] [Full Text] [PDF]
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K. W. Muir, C. J. Weir, W. Alwan, I. B. Squire, and K. R. Lees C-Reactive Protein and Outcome After Ischemic Stroke Stroke, May 1, 1999; 30(5): 981 - 985. [Abstract] [Full Text] [PDF]
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 D. J. Lanska and R. G. Hoffmann Seasonal variation in stroke mortality rates Neurology, March 1, 1999; 52(5): 984 - 984. [Abstract] [Full Text]
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L. Pantoni, C. Sarti, and D. Inzitari Cytokines and Cell Adhesion Molecules in Cerebral Ischemia : Experimental Bases and Therapeutic Perspectives Arterioscler. Thromb. Vasc. Biol., April 1, 1998; 18(4): 503 - 513. [Abstract] [Full Text] [PDF]
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R. L. Sacco, R. Gan, B. Boden-Albala, I-F. Lin, D. E. Kargman, W. A. Hauser, S. Shea, and M. C. Paik Leisure-Time Physical Activity and Ischemic Stroke Risk : The Northern Manhattan Stroke Study Stroke, February 1, 1998; 29(2): 380 - 387. [Abstract] [Full Text] [PDF]
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 H. S Markus and M. A Mendall Helicobacter pylori infection: a risk factor for ischaemic cerebrovascular disease and carotid atheroma J. Neurol. Neurosurg. Psychiatry, January 1, 1998; 64(1): 104 - 107. [Abstract] [Full Text]
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A. Armengou, A. Davalos, J. M. Fernandez-Real, and J. Castillo Serum Ferritin Concentrations Are Not Modified in the Acute Phase of Ischemic Stroke Stroke, January 1, 1998; 29(1): 258 - 260. [Full Text]
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A. J. Grau, F. Buggle, C. Ziegler, W. Schwarz, J. Meuser, A.-J. Tasman, A. Buhler, C. Med, C. Benesch, H. Becher, et al. Association Between Acute Cerebrovascular Ischemia and Chronic and Recurrent Infection Stroke, September 1, 1997; 28(9): 1724 - 1729. [Abstract] [Full Text]
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 J. K. Grether and K. B. Nelson Maternal Infection and Cerebral Palsy in Infants of Normal Birth Weight JAMA, July 16, 1997; 278(3): 207 - 211. [Abstract] [PDF]
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I.Y. Bova, N.M. Bornstein, and A.D. Korczyn Acute Infection as a Risk Factor for Ischemic Stroke Stroke, December 1, 1996; 27(12): 2204 - 2206. [Abstract] [Full Text]
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M. L.J. Wimmer, R. Sandmann-Strupp, P. Saikku, and R. L. Haberl Association of Chlamydial Infection With Cerebrovascular Disease Stroke, December 1, 1996; 27(12): 2207 - 2210. [Abstract] [Full Text]
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R. F. Macko, S. F. Ameriso, R. Barndt, W. Clough, J. M. Weiner, and M. Fisher Precipitants of Brain Infarction: Roles of Preceding Infection/Inflammation and Recent Psychological Stress Stroke, November 1, 1996; 27(11): 1999 - 2004. [Abstract] [Full Text]
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R. F. Macko, S. F. Ameriso, A. Gruber, J. H. Griffin, J. A. Fernandez, R. Barndt, F. P. Quismorio, J. M. Weiner, and M. Fisher Impairments of the Protein C System and Fibrinolysis in Infection-Associated Stroke Stroke, November 1, 1996; 27(11): 2005 - 2011. [Abstract] [Full Text]
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A. J. Grau, F. Buggle, C. Steichen-Wiehn, S. Heindl, T. Banerjee, R. Seitz, R. Winter, M. Forsting, E. Werle, C. Bode, et al. Clinical and Biochemical Analysis in Infection-Associated Stroke Stroke, September 1, 1995; 26(9): 1520 - 1526. [Abstract] [Full Text]
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