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Concept: Cerebral hemorrhage

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Background Whether rapid lowering of elevated blood pressure would improve the outcome in patients with intracerebral hemorrhage is not known. Methods We randomly assigned 2839 patients who had had a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure to receive intensive treatment to lower their blood pressure (with a target systolic level of <140 mm Hg within 1 hour) or guideline-recommended treatment (with a target systolic level of <180 mm Hg) with the use of agents of the physician's choosing. The primary outcome was death or major disability, which was defined as a score of 3 to 6 on the modified Rankin scale (in which a score of 0 indicates no symptoms, a score of 5 indicates severe disability, and a score of 6 indicates death) at 90 days. A prespecified ordinal analysis of the modified Rankin score was also performed. The rate of serious adverse events was compared between the two groups. Results Among the 2794 participants for whom the primary outcome could be determined, 719 of 1382 participants (52.0%) receiving intensive treatment, as compared with 785 of 1412 (55.6%) receiving guideline-recommended treatment, had a primary outcome event (odds ratio with intensive treatment, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The ordinal analysis showed significantly lower modified Rankin scores with intensive treatment (odds ratio for greater disability, 0.87; 95% CI, 0.77 to 1.00; P=0.04). Mortality was 11.9% in the group receiving intensive treatment and 12.0% in the group receiving guideline-recommended treatment. Nonfatal serious adverse events occurred in 23.3% and 23.6% of the patients in the two groups, respectively. Conclusions In patients with intracerebral hemorrhage, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability. An ordinal analysis of modified Rankin scores indicated improved functional outcomes with intensive lowering of blood pressure. (Funded by the National Health and Medical Research Council of Australia; INTERACT2 ClinicalTrials.gov number, NCT00716079 .).

Concepts: Hypertension, Blood pressure, Modified Rankin Scale, Cerebral hemorrhage, Disability, Orthostatic hypotension, Barthel scale, Rehabilitation medicine

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Background Limited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral hemorrhage. Methods We randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm(3)) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3 to 15, with lower scores indicating worse condition) to a systolic blood-pressure target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment) in order to test the superiority of intensive reduction of systolic blood pressure to standard reduction; intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset. The primary outcome was death or disability (modified Rankin scale score of 4 to 6, on a scale ranging from 0 [no symptoms] to 6 [death]) at 3 months after randomization, as ascertained by an investigator who was unaware of the treatment assignments. Results Among 1000 participants with a mean (±SD) systolic blood pressure of 200.6±27.0 mm Hg at baseline, 500 were assigned to intensive treatment and 500 to standard treatment. The mean age of the patients was 61.9 years, and 56.2% were Asian. Enrollment was stopped because of futility after a prespecified interim analysis. The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard-treatment group (relative risk, 1.04; 95% confidence interval, 0.85 to 1.27; analysis was adjusted for age, initial GCS score, and presence or absence of intraventricular hemorrhage). Serious adverse events occurring within 72 hours after randomization that were considered by the site investigator to be related to treatment were reported in 1.6% of the patients in the intensive-treatment group and in 1.2% of those in the standard-treatment group. The rate of renal adverse events within 7 days after randomization was significantly higher in the intensive-treatment group than in the standard-treatment group (9.0% vs. 4.0%, P=0.002). Conclusions The treatment of participants with intracerebral hemorrhage to achieve a target systolic blood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg. (Funded by the National Institute of Neurological Disorders and Stroke and the National Cerebral and Cardiovascular Center; ATACH-2 ClinicalTrials.gov number, NCT01176565 .).

Concepts: Blood, Hypertension, Stroke, Blood pressure, Cerebral hemorrhage, Disability, Orthostatic hypotension, Glasgow Coma Scale

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Oral infectious diseases are epidemiologically associated with stroke. We previously showed that oral Streptococcus mutans with the cnm gene encoding a collagen-binding Cnm protein induced intracerebral hemorrhage (ICH) experimentally and was also associated with cerebral microbleeds (CMBs) in our population-based cohort study. We therefore investigated the roles of cnm-positive Streptococcus mutans in this single hospital-based, observational study that enrolled 100 acute stroke subjects. The cnm gene in Streptococcus mutans isolated from saliva was screened using PCR techniques and its collagen-binding activities examined. CMBs were evaluated on T2* gradient-recalled echo MRI. One subject withdrew informed consent and 99 subjects (63 males) were analyzed, consisting of 67 subjects with ischemic stroke, 5 with transient ischemic attack, and 27 with ICH. Eleven cases showed Streptococcus mutans strains positive for cnm. The presence of cnm-positive Streptococcus mutans was significantly associated with ICH [OR vs. ischemic stroke, 4.5; 95% CI, 1.17-19.1] and increased number of deep CMBs [median (IQR), 3 (2-9) vs. 0 (0-1), p = 0.0002]. In subjects positive for Streptococcus mutans, collagen binding activity was positively correlated with the number of deep CMBs (R(2) = 0.405; p < 0.0001). These results provide further evidence for the key role of oral health in stroke.

Concepts: Cohort study, Experimental design, Infectious disease, Informed consent, Stroke, Transient ischemic attack, Cerebral hemorrhage, Streptococcus mutans

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Shortly after intracerebral hemorrhage, neutrophils infiltrate the intracerebral hemorrhage-injured brain. Once within the brain, neutrophils degranulate, releasing destructive molecules that may exacerbate brain damage. However, neutrophils also release beneficial molecules, including iron-scavenging lactoferrin that may limit hematoma/iron-mediated brain injury after intracerebral hemorrhage. Here, we show that the immunoregulatory cytokine interleukin-27 is upregulated centrally and peripherally after intracerebral hemorrhage. Data from rodent models indicate that interleukin-27 modifies neutrophil maturation in the bone marrow, suppressing their production of pro-inflammatory/cytotoxic products while increasing their production of beneficial iron-scavenging molecules, including lactoferrin. Finally, interleukin-27 or lactoferrin administration results in reduced edema, enhanced hematoma clearance, and improved neurological outcomes in an animal model of intracerebral hemorrhage. These results suggest that interleukin-27/lactoferrin-mediated modulations of neutrophil function may represent a therapeutically viable concept for the modification of neutrophils toward a “beneficial” phenotype for the treatment of intracerebral hemorrhage.Neutrophils are important modulators of tissue damage after intracerebral hemorrhage (ICH), but how this function is regulated is not clear. Here, the authors show interleukin-27 promotes the tissue-protecting functions of neutrophils via, at least partly, the induction of lactoferrin to present a potential therapy for ICH.

Concepts: White blood cell, Medicine, Blood, Traumatic brain injury, Neurology, Cerebral hemorrhage, Neutrophil granulocyte, Lactoferrin

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Background-Large-scale prospective epidemiological data testing the association between physical activity (PA) and cerebrovascular diseases (CVDs) are scarce, particularly in Europe. The objective was to assess the risk of CVD according to PA levels in adults. METHODS: We included a total of 13 576 men and 19 416 women aged 29 to 69 years and participating in the European Prospective Investigation into Cancer and Nutrition cohort in Spain, recruited between 1992 and 1996 and followed-up until 2006 to ascertain incident CVD events. The validated European Prospective Investigation into Cancer and Nutrition PA questionnaire was used to assess metabolic equivalent × hours per week dedicated to different types of PA. Hazard ratios of CVD by PA levels were estimated using multivariate Cox regression. Extensive baseline data collected on diet, lifestyle habits, medical history, and anthropometry were available to adjust for. RESULTS: A total of 210 transient ischemic attacks and 442 stroke cases (80% ischemic, 10% hemorrhagic, 7% subarachnoid hemorrhage, and 3% mixed or unspecified) were registered after 12.3 years of mean follow-up. Recreational activity was inversely associated with risk of CVD in women but not in men. Women walking for ≥3.5 hours per week were at lower risk of stroke than those who did not engage in regular walking. No significant associations were found for other leisure time activities or vigorous PA with CVD in either sex. CONCLUSIONS: Recreational PA of moderate intensity was inversely associated with stroke incidence in women, whereas PA showed no effect on CVD risk in men. Increasing time dedicated to activities such as walking would be expected to help to reduce the stroke burden in women.

Concepts: Epidemiology, Nutrition, Obesity, Stroke, Subarachnoid hemorrhage, Cardiovascular system, Cerebral hemorrhage, Leisure

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Rates of acute intracerebral hemorrhage (ICH) increase in winter months but the magnitude of risk is unknown. We aimed to quantify the association of ambient temperature with the risk of ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) participants on an hourly timescale.

Concepts: Blood, Stroke, Bleeding, The Association, Subarachnoid hemorrhage, Cerebral hemorrhage, Winter, Coagulopathy

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Frequencies of cognitive impairment and dementia have not been assessed in spontaneous intracerebral hemorrhage (ICH). The objective of this study was to determine the frequencies and patterns of cognitive impairment and dementia in a cross-sectional study of consecutive patients hospitalized in a single university medical center.

Concepts: Hospital, Cross-sectional study, Cerebral hemorrhage, Cross-sectional analysis

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To determine whether calcium supplementation is associated with the development of dementia in women after a 5-year follow-up.

Concepts: Cerebral hemorrhage, Cerebrovascular disease

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Intracerebral hemorrhage (ICH) accounted for 9% to 27% of all strokes worldwide in the last decade, with high early case fatality and poor functional outcome. In view of recent randomized controlled trials (RCTs) of the management of ICH, the European Stroke Organisation (ESO) has updated its evidence-based guidelines for the management of ICH.

Concepts: Evidence-based medicine, Randomized controlled trial, Stroke, Cerebral hemorrhage, The Europeans

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Intravenous thrombolysis remains the mainstay treatment for acute ischemic stroke. One of the most feared complications of the treatment is thrombolysis-related symptomatic intracerebral hemorrhage (sICH), which occurs in nearly 6% of patients and carries close to 50% mortality. The treatment options for sICH are based on small case series and expert opinion, and the efficacy of recommended treatments is not well known.

Concepts: Stroke, Thrombosis, Pulmonary embolism, Cerebral hemorrhage, Tissue plasminogen activator, Thrombolysis, Plasmin