Stroke

Delayed cerebral ischemia (DCI) accounts for a major part of the morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). MicroRNAs (miRNAs) are pathophysiologically involved in acute cerebral ischemia. This study compared miRNA profiles in cerebrospinal fluid from neurologically healthy patients, as well as SAH patients with and without subsequent development of DCI.

In a prospective case–control study of SAH patients treated with external ventricular drainage and neurologically healthy patients, miRNA profiles in cerebrospinal fluid were screened and validated using 2 different high-throughput real-time quantification polymerase chain reaction techniques. The occurrence of DCI was documented in patient charts and subsequently reviewed independently by 2 physicians.

MiRNA profiles from 27 SAH patients and 10 neurologically healthy patients passed quality control. In the validation, 66 miRNAs showed a relative increase in cerebrospinal fluid from SAH patients compared with neurologically healthy patients ( P <0.001); 2 (miR-21 and miR-221) showed a relative increase in SAH patients with DCI compared with those without ( P <0.05) in both the screening and validation.

SAH is associated with marked changes in the cerebrospinal fluid miRNA profile. These changes could be associated to the development of DCI.

URL: http://www.clinicaltrials.gov . Unique identifier: NCT01791257.

Background and Purpose— Tolerance to ischemic brain injury is induced by several preconditioning stimuli, including lipopolysaccharide (LPS). A small dose of LPS given systemically confers ischemic protection in the brain, a process that appears to involve activation of an inflammatory response before ischemia. We postulated that LPS preconditioning modulates the cellular inflammatory response after cerebral ischemia, resulting in neuroprotection.

Methods— Mice were treated with LPS (0.2 mg/kg) 48 hours before ischemia induced by transient middle cerebral artery occlusion (MCAO). The infarct was measured by 2,3,5-triphenyltetrazolium chloride staining. Microglia/macrophage responses after MCAO were assessed by immunofluorescence and flow cytometry. The effect of MCAO on white blood cells in the brain and peripheral circulation was measured by flow cytometry 48 hours after MCAO.

Results— LPS preconditioning induced significant neuroprotection against MCAO. Administration of low-dose LPS before MCAO prevented the cellular inflammatory response in the brain and blood. Specifically, LPS preconditioning suppressed neutrophil infiltration into the brain and microglia/macrophage activation in the ischemic hemisphere, which was paralleled by suppressed monocyte activation in the peripheral blood.

Conclusions— LPS preconditioning induces neuroprotection against ischemic brain injury in a mouse model of stroke. LPS preconditioning suppresses the cellular inflammatory response to ischemia in the brain and circulation. Diminished activation of cellular inflammatory responses that ordinarily exacerbate ischemic injury may contribute to neuroprotection induced by LPS preconditioning.

Perfusion-weighted imaging is used to select patients with acute ischemic stroke for intervention, but knowledge of cerebral perfusion can also inform the understanding of ischemic injury. Arterial spin labeling allows repeated measurement of absolute cerebral blood flow (CBF) without the need for exogenous contrast. The aim of this study was to explore the relationship between dynamic CBF and tissue outcome in the month after stroke onset.

Patients with nonlacunar ischemic stroke underwent ≤5 repeated magnetic resonance imaging scans at presentation, 2 hours, 1 day, 1 week, and 1 month. Imaging included vessel-encoded pseudocontinuous arterial spin labeling using multiple postlabeling delays to quantify CBF in gray matter regions of interest. Receiver–operator characteristic curves were used to predict tissue outcome using CBF. Repeatability was assessed in 6 healthy volunteers and compared with contralateral regions of patients. Diffusion-weighted and T2-weighted fluid attenuated inversion recovery imaging were used to define tissue outcome.

Forty patients were included. In contralateral regions of patients, there was significant variation of CBF between individuals, but not between scan times (mean±SD: 53±42 mL/100 g/min). Within ischemic regions, mean CBF was lowest in ischemic core (17±23 mL/100 g/min), followed by regions of early (21±26 mL/100 g/min) and late infarct growth (25±35 mL/100 g/min; ANOVA P <0.0001). Between patients, there was marked overlap in presenting and serial CBF values.

Knowledge of perfusion dynamics partially explained tissue fate. Factors such as metabolism and tissue susceptibility are also likely to influence tissue outcome.

Background and Purpose —This study examined the effectiveness of a slide/audio community education program aimed at increasing knowledge of stroke risk factors, stroke warning signs, and action needed when stroke warning signs occur. The program targets audiences at higher risk for stroke, especially individuals who are black or >50 years of age.

Methods —Subjects were 657 adults living in the community or in senior independent-living settings. The study examined the effectiveness of the program when presented alone and when accompanied by discussion (facilitation) led by a trained individual. Knowledge of stroke risk factors and warning signs was assessed using parallel pretests and posttests developed and validated specifically for the study.

Results —ANCOVA indicated that neither pretesting nor facilitation had a significant effect on posttest measures of knowledge. Paired t tests of groups receiving both the pretest and posttest demonstrated significant increase in knowledge (mean increase, 10.87%; P <0.001). ANCOVA indicated that these gains in knowledge were similar across subjects of different sex, race, age, and educational level. No significant differences could be ascribed to facilitation.

Conclusions —The data indicate that the slide/audio program is effective in increasing knowledge of stroke risk factors, warning signs, and necessary action in subjects of varying ages, races, and education. Pretesting and facilitation did not significantly affect the short-term acquisition of information. The slide/audio program appears to offer a short, easily used educational experience for diverse communities, whether as a stand-alone program or with facilitated discussion.

Several emerging stroke therapies require patients to be treated within several hours of symptom onset. Past studies have documented a significant delay between symptom onset and hospital presentation. As part of an experimental treatment study using tissue-type plasminogen activator, we began a multifaceted program of public and professional education to reduce the delay in presentation and referral of acute stroke patients.

The educational efforts focused on improving the recognition of stroke symptoms, the study enrollment criteria, and the need for rapid treatment of stroke patients. This program included 1) interviews on television and radio, 2) newspaper articles, 3) lectures to local and regional primary care and emergency department physicians, 4) mailings to several thousand local physicians, 5) having neurologists on-call for referrals 24 hrs/day, and 6) use of the Duke Life-Flight helicopter.

Since starting our program, 139 of 159 (86%) patients with cerebral infarction presented primarily to our were referred to our facility within 24 hours of symptom onset, compared with 70 of 187 (37%) before our educational efforts (p less than 0.00001). No significant change was seen in patients with intracerebral hemorrhage (23 of 30 +AD77%+BD within 24 hours after program, compared with 25 of 40 +AD63%+BD before educational efforts; p = 0.30).

These findings suggest that educational efforts aimed at the public and health professionals may increase recognition of stroke symptoms and reduce the delay in presentation and referral of stroke patients.

Background and Purpose We sought to determine knowledge at the time of symptom onset regarding the signs, symptoms, and risk factors of stroke in patients presenting to the emergency department with potential stroke.

Methods Patients admitted from the emergency department with possible stroke were identified prospectively. A standardized, structured interview with open-ended questions was performed within 48 hours of symptom onset to assess patients’ knowledge base concerning stroke signs, symptoms, and risk factors.

Results Of the 174 eligible patients, 163 patients were able to respond to the interview questions. Of these 163 patients, 39% (63) did not know a single sign or symptom of stroke. Unilateral weakness (26%) and numbness (22%) were the most frequently noted symptoms. Patients aged ≥65 years were less likely to know a sign or symptom of stroke than those aged <65 years (percentage not knowing a single sign or symptom, 47% versus 28%, P =.016). Similarly, 43% of patients did not know a single risk factor for stroke. The elderly were less likely to know a risk factor than their younger counterparts.

Conclusions Almost 40% of patients admitted with a possible stroke did not know the signs, symptoms, or risk factor of a stroke. Further public education is needed to increase awareness of the warning signs and risk factors of stroke.

Background and Purpose New treatments for acute stroke will likely have to be given soon after stroke onset. Little is known about stroke patients’ general knowledge about stroke, their interpretation of stroke symptoms, and how these factors influence the timing of their decision to seek medical attention.

Methods We interviewed consecutive stroke patients within 72 hours of stroke onset to define factors influencing time of arrival to the emergency department. Data recorded included demographic information, method of transportation, type of stroke symptoms, the patient’s interpretation of the symptoms, previous stroke, and knowledge of stroke warning signs. Stroke severity was measured with the Barthel Index. Early arrival was defined as within 3 hours of awareness of symptoms.

Results Sixty-seven patients were interviewed; 96% had an ischemic stroke and 4% a cerebral hemorrhage. Although 38% of patients professed to know the warning signs of stroke, only 25% correctly interpreted their symptoms. Patients with prior stroke were more likely to correctly interpret their symptoms (45% versus 16%; P =.03) but were not more likely to present early (19% versus 39%; P =.35). Eighty-six percent of patients presenting more than 3 hours after stroke onset thought that their symptoms were not serious. The 24% (n=16) of early arrivals were more likely to arrive by ambulance (81% versus 38%; P =.003) and had more severe strokes (Barthel Index score of 49 versus 72; P =.01) than late arrivals. Arrival by ambulance was independently associated with early arrival (odds ratio, 5.55; 95% confidence interval, 1.37 to 22.6).

Conclusions Approximately one quarter of stroke patients correctly interpret their symptoms as representing a stroke. This knowledge is not associated with early presentation to the emergency department. Ambulance transport is independently associated with early arrival at the emergency department. Even when patients know that they are having a stroke, most present late because they perceive their symptoms as “not serious.” Widespread public education of stroke-prone individuals may increase the proportion of patients eligible for new acute stroke treatments.

Background and Purpose —With the advent of time-dependent thrombolytic therapy for ischemic stroke, it has become increasingly important for stroke patients to arrive at the hospital quickly. This study investigates the association between the use of emergency medical services (EMS) and delay time among individuals with stroke symptoms and examines the predictors of EMS use.

Methods —The Second Delay in Accessing Stroke Healthcare Study (DASH II) was a prospective study of 617 individuals arriving at emergency departments in Denver, Colo, Chapel Hill, NC, and Greenville, SC, with stroke symptoms.

Results —EMS use was associated with decreased prehospital and in-hospital delay. Those who used EMS had a median prehospital delay time of 2.85 hours compared with 4.03 hours for those who did not use EMS ( P =0.002). Older individuals were more likely to use EMS (odds ratio [OR] 1.21 for each 5-year increase, 95% CI 1.14 to 1.29), as were individuals who expressed a high sense of urgency about their symptoms (OR 1.69, 95% CI 1.09 to 2.62). Knowledge of stroke symptoms was not associated with increased EMS use (OR 0.63, 95% CI 0.40 to 0.98). Patients were more likely to use EMS if someone other than the patient first identified that there was a problem (OR 2.35, 95% CI 1.61 to 3.44).

Conclusions —Interventions aimed at increasing EMS use among stroke patients need to stress the urgency of stroke symptoms and the importance of calling 911 and need to be broad-based, encompassing not only those at high risk for stroke but also their friends and family.

Background and Purpose— Homocysteine is an endothelial toxin and elevated levels have been associated with stroke risk. Stroke, particularly the small vessel disease (SVD) subtype, is increased in U.S. and UK black populations. In white populations elevated homocysteine has been associated with SVD, especially confluent leukoaraiosis, and may be acting through endothelial dysfunction. We determined the association between homocysteine and stroke subtypes, especially SVD, in a well-phenotyped UK cohort of black stroke patients compared to community controls.

Methods— Homocysteine, vitamin B12, folate levels, and renal function were measured in 457 black stroke patients recruited consecutively through the prospective South London Ethnicity and Stroke Study and 179 black community controls. All patients were subtyped using modified TOAST criteria. Leukoaraiosis in SVD patients was graded according to severity, and patients were additionally categorized on the basis of presence or absence of confluent leukoaraiosis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated.

Results— The highest homocysteine levels were seen in SVD patients compared to controls (16.2 [11.6] versus 11.8 [5.7] μmol/L, P <0.001) after adjusting for age, gender, vascular risk factors, vitamin levels, and renal function. Within SVD cases, highest homocysteine levels were found in lacunar infarction with confluent leukoaraiosis (19.6 [14.9] μmol/L) compared to lacunar infarction without leukoaraiosis (13.6 [7.1] μmol/L, P =0.001) and controls ( P <0.001). Homocysteine correlated with leukoaraiosis severity ( r =0.225, P <0.001).

Conclusions— In this well characterized UK black stroke population homocysteine levels were elevated and highest levels were found in lacunar stroke with leukoaraiosis.