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Acute Ischemic Stroke Patterns in Infective and Nonbacterial Thrombotic Endocarditis: A Diffusion-Weighted Magnetic Resonance Imaging Study
Stroke Volume 33, Issue 51 May 2002

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Background and Purpose— Although infective endocarditis (IE) and nonbacterial thrombotic endocarditis (NBTE) are associated with cardioembolic stroke, differences in the nature of these conditions may result in differences in associated stroke patterns. We compared patterns of acute and recurrent ischemic stroke in IE and NBTE, using diffusion-weighted MRI (DWI).Methods— Using ICD-9 diagnostic codes and medical record review, we identified 362 patients (387 episodes) with IE and 14 patients with NBTE. Thirty-five patients (with 27 episodes of IE, 9 NBTE) who underwent 36 initial and 29 follow-up DWI scans were selected for this study. DWI lesion size, number, and location were compared between groups and correlated with stroke syndromes and endocarditis features.Results— DWI was abnormal in all but 2 patients. Four acute stroke patterns were identified: (1) single lesion, (2) territorial infarction, (3) disseminated punctate lesions, and (4) numerous small (<10 mm) and medium (10 to 30 mm) or large (>30 mm) lesions in multiple territories. All patients with NBTE exhibited pattern 4, whereas those with IE exhibited patterns 1, 2, 3, and 4 (6, 2, 8 and 9 episodes, respectively). Seventy-five percent of patients with pattern 3 exhibited the clinical syndrome of embolic encephalopathy. Vegetation size, valve, and organisms had no correlation with stroke patterns.Conclusion— DWI has utility in differentiating between IE and NBTE. Patients with NBTE uniformly have multiple, widely distributed, small and large strokes, whereas patients with IE exhibit a panoply of stroke patterns.
Incidence, Manifestations, and Predictors of Brain Infarcts Defined by Serial Cranial Magnetic Resonance Imaging in the Elderly: The Cardiovascular Health Study
- W.T. Longstreth,
- Corinne Dulberg,
- Teri A. Manolio,
- Michael R. Lewis,
- Norman J. Beauchamp,
- Daniel O’Leary,
- Jeff Carr and
- Curt D. Furberg
Stroke Volume 33, Issue 101 October 2002

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Background and Purpose— MRI-defined infarcts are common in the elderly. We sought to explore incidence, manifestations, and predictors of such infarcts.Methods— The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of 5888 people aged ≥65 years. Participants have had extensive baseline and follow-up evaluations; 1433 participants underwent 2 MRI scans separated by 5 years and had no infarcts on initial MRI.Results— On follow-up MRI, 254 participants (17.7%) had 1 or more infarcts. Most were single (75.6%), subcortical (79.9%), and small (3 to 20 mm in 87.0%). Only 11.4% of those with infarcts experienced a documented transient ischemic attack or stroke between the scans. Although participants were similar at initial MRI, those with MRI-defined infarcts on follow-up experienced greater decline than those without infarcts on the Modified Mini-Mental State Examination and Digit-Symbol Substitution test (both P<0.01). Severity of white matter changes on initial MRI was the strongest predictor of incident infarcts. When it was excluded from stepwise multivariable models, predictors were serum creatinine, age, and ankle-arm index.Conclusions— Incident MRI-defined infarcts commonly affect the elderly. Most are small, subcortical, and not associated with acute symptoms recognized as a transient ischemic attack or stroke. Nonetheless, they cannot be considered silent because of their association with subtle cognitive deficits. These covert infarcts are associated with white matter changes, which may share a common pathophysiology. Whether control of vascular risk factors, such as blood pressure, would reduce the risk of developing these infarcts and associated cognitive decline deserves further investigation.
Hyperbaric Oxygen Therapy in Acute Ischemic Stroke: Results of the Hyperbaric Oxygen in Acute Ischemic Stroke Trial Pilot Study
- Daniel E. Rusyniak,
- Mark A. Kirk,
- Jason D. May,
- Louise W. Kao,
- Edward J. Brizendine,
- Julie L. Welch,
- William H. Cordell and
- Robert J. Alonso
Stroke Volume 34, Issue 21 February 2003

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Background and Purpose— Hyperbaric oxygen therapy (HBO) has promise as a treatment for acute stroke. This study was conducted to evaluate the efficacy, safety, and feasibility of using HBO in acute ischemic stroke.Methods— We conducted a randomized, prospective, double-blind, sham-controlled pilot study of 33 patients presenting with acute ischemic stroke who did not receive thrombolytics over a 24-month period. Patients were randomized to treatment for 60 minutes in a monoplace hyperbaric chamber pressurized with 100% O₂ to 2.5-atm absolute (ATA) in the HBO group or 1.14 ATA in the sham group. Primary outcomes measured included percentage of patients with improvement at 24 hours (National Institutes of Health Stroke Scale [NIHSS]) and 90 days (NIHSS, Barthel Index, modified Rankin Scale, Glasgow Outcome Scale). Secondary measurements included complications of treatment and mortality at 90 days.Results— Baseline demographics were similar in both groups. There were no differences between the groups at 24 hours (P=0.44). At 3 months, however, a larger percentage of the sham patients had a good outcome defined by their stroke scores compared with the HBO group (NIHSS, 80% versus 31.3%; P=0.04; Barthel Index, 81.8% versus 50%; P=0.12; modified Rankin Scale, 81.8% versus 31.3%; P=0.02; Glasgow Outcome Scale, 90.9% versus 37.5%; P=0.01) with loss of statistical significance in a intent-to-treat analysis.Conclusions— Although our HBO protocol appears feasible and safe, it does not appear to be beneficial and may be harmful in patients with acute ischemic stroke.
MTHFR Gene Polymorphism as a Risk Factor for Silent Brain Infarcts and White Matter Lesions in the Japanese General Population: The NILS-LSA Study
- Katsuhiko Kohara,
- Michiko Fujisawa,
- Fujiko Ando,
- Yasuharu Tabara,
- Naoakira Niino,
- Tetsuro Miki and
- Hiroshi Shimokata
Stroke Volume 34, Issue 51 May 2003

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Background and Purpose— Silent brain infarcts (SBI) and white matter lesions are relatively common neuroimaging findings, especially in the elderly population. The genetic background for SBI and white matter lesions in a large Japanese general population was investigated.Methods— Subjects were recruited from participants in the National Institute for Longevity Sciences, Longitudinal Study of Aging. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T gene mutation and brain MRI examination were performed in 1721 subjects free of any history of stroke. SBI and white matter lesions were diagnosed from MRI findings.Results— Of 1721 MRI examinations, SBI was observed in 178 (10.3%). The prevalence of SBI and white matter lesions increased with age. The prevalence of SBI was significantly higher in subjects with the MTHFR TT genotype compared with the TC+CC genotype (14.6% versus 9.5%; 42 of 288 versus 136 of 1433; χ²=6.71; P=0.010). The stage of white matter lesions was not significantly different. In subjects ≥60 years of age (n=849), the prevalence of SBI was significantly higher in TT than TC+CC (27.7% versus 16.6%; 36 of 130 versus 119 of 719; χ²=9.16; P=0.002). The prevalence of moderately advanced white matter lesions was also significantly higher in TT than TC+CC (60.7% versus 49.0%; 79 of 130 versus 352 of 719; χ²=9.16; P=0.002). After correction for other risk factors, the MTHFR TT genotype was independently associated with SBI (odds ratio [OR], 1.72; 95% CI, 1.10 to 2.68; P=0.018) and moderately advanced white matter lesions (OR, 1.58; 95% CI, 1.07 to 2.33; P=0.02).Conclusions— These findings indicate that the MTHFR TT genotype is an independent risk factor for SBI and white matter lesions in the general Japanese population, especially in elderly subjects.
Soluble Thrombomodulin and Brain Infarction: Case-Control and Prospective Study
Stroke Volume 35, Issue 81 August 2004

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Background and Purpose— Increased soluble thrombomodulin (sTM) concentration has been associated with recurrent coronary events, whereas in one prospective study it predicted fewer first-ever coronary events. One study found no relationship between brain infarction (BI) and sTM levels. Among all subjects of the Étude du Profil Génétique de l’Infarctus Cérébral (GENIC) cohort and those free of previous vascular history, we investigated the relationship between sTM level and BI risk, and among cases, its relationship with BI prognosis.Methods— Patients with BI (n=492) were consecutively recruited from 12 centers. Hospital controls without a history of stroke (n=492) were individually matched for age, sex, and center. Blood samples were collected after hospitalization. Determination of sTM levels was centralized in a single laboratory.Results— Soluble TM concentration significantly increased with age and hypertensive status, but was similar in cases and controls. With analyses restricted to 278 pairs of subjects with no previous vascular history, sTM concentration >59.6 μg/L (second and third tertiles compared with the first) was associated with fewer first-ever BI (adjusted odds ratio of 0.56 (95% CI, 0.35 to 0.89; P=0.014). Among the cases, increased sTM concentration was associated with a higher death rate after a median follow-up of 5.2 (1.4 to 6.4) years. The adjusted hazard ratio per 1 SD of sTM concentration increase (34.2 μg/L) was 1.19 (95% CI, 1.02 to 1.39; P=0.028).Conclusions— Increased sTM concentration may be protective against BI in subjects with no previous vascular disease, whereas it may predict a fatal outcome in patients who have already had a BI. Consequently, sTM levels should be interpreted according to vascular history.
Mild to Moderate Atheromatous Disease of the Thoracic Aorta and New Ischemic Brain Lesions After Conventional Coronary Artery Bypass Graft Surgery
- George Djaiani,
- Ludwik Fedorko,
- Michael Borger,
- David Mikulis,
- Jo Carroll,
- Davy Cheng,
- Keyvan Karkouti,
- Scott Beattie and
- Jacek Karski
Stroke Volume 35, Issue 91 September 2004

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Background and Purpose— The presence of new ischemic brain infarcts, detected by diffusion-weighted magnetic resonance imaging (DW-MRI), have been reported in considerable number of patients after cardiac surgery. We sought to determine the role of proximal thoracic aortic atheroma in predicting embolic events and new ischemic brain lesions in patients undergoing conventional coronary revascularization surgery.Methods— Transesophageal echocardiography and epiaortic scanning was performed to assess the severity of aortic atherosclerosis in the ascending aorta and the aortic arch. Patients were allocated to either low-risk group, (intimal thickness ≤2mm), or high-risk group (intimal thickness >2mm). Transcranial Doppler was used to monitor the middle cerebral artery. DW-MRI was performed 3–7 days after surgery. The NEECHAM Confusion Scale was used for assessment and monitoring patient consciousness level.Results— Patients in the high-risk group were considerably older; 71±6 (n=38) versus 67±6 (n=72) years, P=0.004 and were more likely to have impaired left ventricular function. Confusion was present in 6 (16%) patients in the high-risk group and 5 (7%) patients in the low-risk group. Patients in the high-risk group had a three-fold increase in median embolic count, 223.5 versus 70.0, P=0.0003. DW-MRI detected brain lesions were only present in patients from high-risk group, 61.5 versus 0%, P<0.0001. There was significant correlation between the NEECHAM scores and embolic count in the high-risk group; r=0.63, P<0.001.Conclusions— The findings of this investigation suggest that mild to moderate atheromatous disease of the ascending aorta and the aortic arch (intimal thickness >2mm) is a major contributor to ischemic brain injury after cardiac surgery.
Microplasmin Reduces Ischemic Brain Damage and Improves Neurological Function in a Rat Stroke Model Monitored With MRI
- Yasuhiro Suzuki,
- Feng Chen,
- Yicheng Ni,
- Guy Marchal,
- Desire Collen and
- Nobuo Nagai
Stroke Volume 35, Issue 101 October 2004

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Background and Purpose— Microplasmin (μPli), a derivative of plasmin lacking the 5 “kringle” domains, was studied in a rat thrombotic stroke model with MRI monitoring.Methods— Brain ischemia was induced by middle cerebral artery (MCA) occlusion with photochemically induced thrombosis. Brain tissue damage was assessed at 1 hour and 24 hours after MCA occlusion by MRI and 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Neurological symptoms were scored at 24 hours. Animals with insufficient evidence of significant jeopardized brain tissue on perfusion-weighted imaging (PWI) at 1 hour were excluded before randomization. Included animals were randomized (blinded) to controls (solvent), 7.5 or 10 mg/kg μPli, administered as an intravenous bolus 90 minutes after MCA occlusion (n=8 per dose group).Results— μPli treatment reduced cerebral damage measured by TTC staining at 24 hours, from 250±69 mm³ (mean±SD) in controls to 150±30 and 170±62 mm³ with 7.5 and 10 mg/kg μPli, respectively; it reduced the expansion of the PWI positive area between 1 and 24 hours, and it reduced neurological deficits from a Bederson score of 7 (6 to 9) in controls to 4.5 (3 to 8) and 4 (3 to 6), with 7.5 and 10 mg/kg μPli, respectively (median and rangeP<0.05 for each dose versus controls for all parameters).Conclusions— Bolus intravenous μPli given 90 minutes after thrombotic MCA occlusion in rats reduces cerebral ischemic damage and improves neurological dysfunction, suggesting that μPli could be beneficial in ischemic stroke patients.
Anteromedian, Central, and Posterolateral Infarcts of the Thalamus: Three Variant Types
- Emmanuel Carrera,
- Patrik Michel and
- Julien Bogousslavsky
Stroke Volume 35, Issue 121 December 2004

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Background and Purpose— Thalamic infarcts have traditionally been classified into 4 territories: anterior, paramedian, inferolateral, and posterior. The purpose of this study was to review this classical versus variant distribution in patients with thalamic stroke.Methods— We reviewed all patients with a first clinical stroke included in the Lausanne Stroke Registry between 1990 and 2002. Among 71 patients with an acute stroke isolated to the thalamus confirmed by MRI, we selected all patients with lesions outside the classical territories and studied their clinical, etiological, and radiological features.Results— A total of 21 patients (30% of all thalamic stroke patients) showed infarction outside the classical territories, allowing us to delineate 3 variant distributions: (1) Anteromedian territory (9 patients [13%]) involving anterior and paramedian territories, with predominantly cognitive impairment, including executive dysfunction, anterograde amnesia, and aphasia in left-sided or bilateral lesions. The most frequent stroke mechanism was cardiac embolism. (2) Central territory (4 patients [6%]), with lesions on the central part of the thalamus, resulting in a variety of neurological and neuropsychological signs, reflecting the involvement of several adjacent structures. Microangiopathy was the most frequent etiology. (3) Posterolateral territory (8 patients [11%]), involving inferolateral and posterior territories, with hemihypesthesia as the most frequent manifestation, followed by hemiataxia, executive dysfunction, and aphasia in left-sided lesions. Artery-to-artery embolism and microangiopathy were the main stroke mechanisms.Conclusions— We describe 3 variant topographic patterns of thalamic infarction with distinct manifestations and etiologies. We postulate that these infarcts are the result of a variation in thalamic arterial supply or reflect borderzone ischemia.
Low-Molecular-Weight Heparins or Heparinoids Versus Standard Unfractionated Heparin for Acute Ischemic Stroke
- Graeme J. Hankey,
- P. Sandercock,
- C. Counsell and
- S.L. Stobbs
Stroke Volume 36, Issue 91 September 2005

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Neurogenesis in Rats After Focal Cerebral Ischemia is Enhanced by Indomethacin
- Benjamin D. Hoehn,
- Theo D. Palmer and
- Gary K. Steinberg
Stroke Volume 36, Issue 121 December 2005

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Background and Purpose— Newborn cells may participate in repair following ischemic brain injury, but their survival and function may be influenced by inflammation.Methods— We investigated the effects of indomethacin, a nonsteroidal antiinflammatory drug, on the fate of newborn cells following transient focal ischemia.Results— Bromodeoxyuridine (BrdU)-labeled cells, including migrating neuroblasts, were observed in the neighboring striatum and overlying cortex 1 day poststroke. The density of BrdU+ cells labeled with doublecortin, nestin, glial fibrillary acidic protein, or NG2 was increased at 14 and 28 days. Indomethacin increased BrdU+ cells of all lineages and reduced microglial/monocyte activation.Conclusion— Indomethacin enhanced the accumulation of newborn cells following stroke.
Does Hyperglycemia Contribute to Secondary Injury in Subarachnoid Hemorrhage?
- Jose I. Suarez
Stroke Volume 37, Issue 11 January 2006

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The Time Man Has Cometh to Brain: Tick … Death …. Tick … Death
- Steven R. Levine
Stroke Volume 37, Issue 11 January 2006

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Why Does Acute Hyperglycemia Worsen the Outcome of Transient Focal Cerebral Ischemia?: Role of Corticosteroids, Inflammation, and Protein O-Glycosylation
- Abraham Martín,
- Santiago Rojas,
- Ángel Chamorro,
- Carles Falcón,
- Núria Bargalló and
- Anna M. Planas
Stroke Volume 37, Issue 51 May 2006

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Background and Purpose— Hyperglycemia adversely affects the outcome of stroke. Global ischemia data support that the harmful effect of hyperglycemia is mediated by glucose-induced elevated plasma glucocorticoids. Here we sought to evaluate the negative effects of hyperglycemia on transient focal ischemia in the rat, and to test whether these could be prevented by inhibition of either corticosteroid production or neutrophil infiltration.Methods— Sprague-Dawley rats (n=217) were used. Ischemia was induced by 1 hour middle cerebral artery occlusion (n=196). Acute hyperglycemia was induced by IP injection of dextrose 30 minutes before ischemia. Neutrophil infiltration was blocked by neutropenia with vinblastine. Corticosterone synthesis was inhibited by chemical adrenalectomy with metyrapone. We measured MRI lesion and tissue infarct volumes, evaluated the neurological function, brain myeloperoxidase and matrix metalloproteinase-9 activities, and protein O-glycosylation.Results— Hyperglycemia significantly enhanced MRI diffusion-weighted imaging alterations, increased cortical, but not subcortical, infarct volume, worsened neurological score, and enhanced brain myeloperoxidase and matrix metalloproteinase-9 activities. Metyrapone did not prevent hyperglycemic brain damage despite successful reduction of plasma corticosterone. Yet, metyrapone tended to reduce cortical infarction and apparent diffusion coefficient lesion volume, indicating some negative contribution of corticosterone. Blocking neutrophil infiltration was also ineffective to prevent the harmful effect of hyperglycemia. A new finding was that O-linked glycosylation of cerebral proteins was increased under hyperglycemia.Conclusions— In transient middle cerebral artery occlusion, the hyperglycemia-exacerbated brain damage cannot be fully explained by the negative effects of plasma corticosteroids or neutrophil infiltration. The contribution of other intrinsic effects of high glucose, such as brain protein O-glycosylation, deserves further investigation.
Proportions of Stroke Subtypes Among Men and Women ≥40 Years of Age in an Urban Japanese City in 1992, 1997, and 2002
- Akihiko Kitamura,
- Yuko Nakagawa,
- Minoru Sato,
- Hiroyasu Iso,
- Shinichi Sato,
- Hironori Imano,
- Masahiko Kiyama,
- Takeo Okada,
- Hiroshi Okada,
- Minoru Iida and
- Takashi Shimamoto
Stroke Volume 37, Issue 61 June 2006

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Background and Purpose— Higher proportions of hemorrhagic stroke and lacunar infarction were reported in rural Japan compared with those in Western countries. We examined the relative proportions of stroke subtypes in an urban Japanese city where westernized lifestyles are more common than in rural areas.Methods— Stroke registration was performed in 1992, 1997, and 2002 for residents ≥40 years of age who were admitted with acute strokes to all of the 10 hospitals with ≥90 beds in Yao City, Osaka, Japan. Strokes were classified as intraparenchymal hemorrhage, subarachnoid hemorrhage, or ischemic strokes (embolic infarction, large-artery occlusive infarction, lacunar infarction, and unclassified thrombotic infarction) by criteria using computed tomography or MRI.Results— A total of 650 first-ever strokes were registered. The age-adjusted proportion of each stroke subtype was not significantly different among the 3 study periods in both men and women. Throughout the 3 periods, intraparenchymal hemorrhage, subarachnoid hemorrhage, and ischemic stroke accounted for 26%, 7%, and 65% in men, respectively. In women, the respective proportions were 29%, 21%, and 44%. The proportion of each subtype for total ischemic strokes was as follows: 51% to 61% lacunar infarction, 25% to 26% large-artery occlusive infarction, and 11% to 17% embolic infarction.Conclusions— Our study showed that hemorrhagic stroke represented a large proportion of all strokes, especially among women, and lacunar infarction was the most common subtype of ischemic stroke among both men and women in Yao City, which differed from findings in Western countries.
Lipoprotein(a) and Incident Ischemic Stroke: The Atherosclerosis Risk in Communities (ARIC) Study
- Tetsuya Ohira,
- Pamela J. Schreiner,
- Joel D. Morrisett,
- Lloyd E. Chambless,
- Wayne D. Rosamond and
- Aaron R. Folsom
Stroke Volume 37, Issue 61 June 2006

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Background and Purpose— Numerous case-control and cross-sectional studies have reported higher median lipoprotein(a) [Lp(a)] levels among stroke patients than controls, but existing prospective studies have not consistently shown an association. We sought to examine the relationship between plasma Lp(a) levels and the incidence of ischemic stroke among blacks and whites.Methods— Between 1987 and 1989, 14 221 men and women (3647 blacks and 10 574 whites) aged 45 to 64 years and free of clinical cardiovascular disease, took part in the first examination of the Atherosclerosis Risk in Communities (ARIC) study cohort. Lp(a) and other risk factors for cardiovascular disease were measured at baseline.Results— During the 13.5-year follow-up, 496 ischemic strokes occurred. Participants with Lp(a) ≥300 μg/mL had a 79% higher age, sex, and race-adjusted rate ratio (RR) of ischemic stroke than did those with Lp(a) levels <100 μg/mL. Compared with Lp(a) <100 μg/mL, the multivariate adjusted RRs for Lp(a) ≥300 μg/mL were 1.84 (95% CI, 1.05 to 3.07) in black women, 1.72 (95% CI, 0.86 to 3.48) in black men, 2.42 (95% CI, 1.30 to 4.53) in white women, and 1.18 (95% CI, 0.47 to 2.90) in white men. There was no significant increment in the RRs for 100 to 199 μg/mL and 200 to 299 μg/mL groups.Conclusions— A high Lp(a) concentration is associated with a higher incidence of ischemic stroke in blacks and white women, but not in white men.
Hyperbaric Oxygen Therapy for Acute Ischemic Stroke
- Graeme J. Hankey,
- Michael H. Bennett,
- Jason Wasiak,
- Christopher French,
- Peter Kranke and
- Alexander Schnabel
Stroke Volume 37, Issue 71 July 2006

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Risk Factors for Ischemic Stroke Subtypes: The Atherosclerosis Risk in Communities Study
- Tetsuya Ohira,
- Eyal Shahar,
- Lloyd E. Chambless,
- Wayne D. Rosamond,
- Thomas H. Mosley and
- Aaron R. Folsom
Stroke Volume 37, Issue 101 October 2006

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Background and Purpose— To evaluate risk factors for ischemic stroke by its subtypes may contribute to more effective prevention of ischemic stroke, but few prospective studies have characterized risk factors for specific subtypes of ischemic stroke.Methods— Between 1987 and 1989, 14 448 men and women aged 45 to 64 years and free of clinical stroke took part in the first examination of the Atherosclerosis Risk in Communities study. The incidence of stroke was ascertained from hospital surveillance records.Results— During an average follow-up of 13.4-years, 531 incident ischemic strokes occurred (105 lacunar, 326 nonlacunar, and 100 cardioembolic). Blacks had a 3-fold higher multivariate-adjusted risk ratio of lacunar stroke compared with whites. No racial difference in nonlacunar or cardioembolic strokes was found after adjusting for prevalent risk factors. In addition to traditional risk factors, nontraditional risk factors, such as waist-to-hip ratio, history of coronary heart disease, left ventricular hypertrophy, lipoprotein(a), and von Willebrand factor, were associated with increased risk for nonlacunar stroke, whereas lacunar stroke was related to only 1 nontraditional risk factor, white blood cell count. The population-attributable fraction (PAF) for hypertension was ≈35% for all ischemic stroke subtypes. The respective PAFs for diabetes and current smoking were 26.3% and 22.0% for lacunar versus 11.3% and 11.4% for nonlacunar stroke. The PAF for elevated von Willebrand factor was greater than that for current smoking for cardioembolic stroke.Conclusions— The impact of traditional and nontraditional risk factors other than hypertension on the incidence of ischemic stroke varied according to its subtype.
Cerebral Microbleeds Are Associated With Lacunar Stroke Defined Clinically and Radiologically, Independently of White Matter Lesions
- Joanna M. Wardlaw,
- Stephanie C. Lewis,
- Sarah L. Keir,
- Martin S. Dennis and
- Susan Shenkin
Stroke Volume 37, Issue 101 October 2006

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Background and Purpose— Associations among microbleeds, white matter lesions (WMLs), and small deep infarcts on imaging have been reported. Because many of these imaging infarcts were asymptomatic, the relationship of microbleeds to clinical lacunar stroke is unclear. An association between microbleeds and clinically defined lacunar stroke might suggest a common causal microangiopathy.Methods— Patients with lacunar, partial anterior circulation or posterior circulation stroke syndromes and older healthy subjects underwent MRI. Microhemorrhages, infarcts, hemorrhages, and WMLs were coded blind to clinical details. A final clinicoradiologic stroke subtype diagnosis was assigned.Results— Among 308 subjects (67 older healthy and 241 with stroke), 54 patients had microbleeds (17%). Microbleeds were twice as frequent in lacunar than cortical strokes (26% versus 13%, P=0.03) or healthy older subjects (9%) and associated with increasing WML scores (P<0.0001). Lacunar and cortical stroke subtypes and healthy older subjects had similar WML scores.Conclusions— Microbleeds are associated with lacunar stroke defined clinicoradiologically more than other stroke subtypes but not simply by association with WMLs. This suggests that microbleeds and lacunar stroke have a similar microvascular abnormality.
Candidate Gene Polymorphisms Do Not Differ Between Newborns With Stroke and Normal Controls
- Steven P. Miller,
- Yvonne W. Wu,
- Janet Lee,
- Edward J. Lammer,
- David M. Iovannisci,
- David V. Glidden,
- Sonia L. Bonifacio,
- Abigail Collins,
- Gary M. Shaw,
- A. James Barkovich and
- Donna M. Ferriero
Stroke Volume 37, Issue 111 November 2006

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Background and Purpose— Neonatal stroke is increasingly recognized with an estimated incidence of one in 4000 live births per year. Pathways involved in the pathophysiology of neonatal stroke are diverse and may include thrombosis and thrombolysis, vascular reactivity, and inflammation.Methods— We compared frequencies of polymorphisms in genes regulating thrombosis and thrombolysis, nitric oxide, cytokines, vascular tone, and cell adhesion in a hospital-based cohort of 59 newborns with stroke relative to a random sample of 437 California newborns.Results— Of the 31 polymorphisms evaluated, no variant allele was significantly more common than the reference allele in newborns with stroke than in the general population.Conclusions— Using a series of polymorphisms in pathways implicated in the etiology of stroke, newborns with stroke were not distinguished from a normal control group. Further studies are needed to determine the interaction of genetic polymorphisms with environmental risk factors in the pathogenesis of neonatal stroke.
Stroke-Induced Immunodepression: Experimental Evidence and Clinical Relevance
- Ulrich Dirnagl,
- Juliane Klehmet,
- Johann S. Braun,
- Hendrik Harms,
- Christian Meisel,
- Tjalf Ziemssen,
- Konstantin Prass and
- Andreas Meisel
Stroke Volume 38, Issue 21 February 2007

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Stroke affects the normally well-balanced interplay of the 2 supersystems: the nervous and the immune system. Recent research elucidated some of the involved signals and mechanisms and, importantly, was able to demonstrate that brain-immune interactions are highly relevant for functional outcome after stroke. Immunodepression after stroke increases the susceptibility to infection, the most relevant complication in stroke patients. However, immunodepression after stroke may also have beneficial effects, for example, by suppressing autoaggressive responses during lesion-induced exposure of central nervous system-specific antigens to the immune system. Thus, before immunomodulatory therapy can be applied to stroke patients, we need to understand better the interaction of brain and immune system after focal cerebral ischemia. Until then, anticipating an important consequence of stroke-induced immunodepression, bacterial infection, preventive antibiotic strategies have been proposed. In mouse experiments, preventive antibiotic treatment dramatically improves mortality and outcome. Results of clinical studies on this issue are contradictory at present, and larger trials are needed to settle the question whether (and which) stroke patients should be preventively treated. Nevertheless, clinical evidence is emerging demonstrating that stroke-induced immunodepression in humans not only exists, but has very similar features to those characterized in rodent experiments.

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