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Diabetes mellitus (DM) causes systemic vascular complications. Chronic hyperglycemia is a hallmark of DM and appears to be at least partially responsible for the vascular complications. In addition, hyperglycemia during acute tissue injury has been postulated to augment the injury. This review addresses the potential therapeutic benefits related to ischemic stroke from lowering hyperglycemia in two settings, in chronic hyperglycemia and during acute ischemic stroke.A recent efficacy trial to lower hyperglycemia during acute ischemic stroke showed no significant benefit overall as well as in patient subgroups. This finding helps to establish good clinical practice protocols for patients with acute ischemic stroke and hyperglycemia. Hyperglycemia appears to be a key mediator of the systemic vascular complications of DM. Despite current lack of evidence that lowering hyperglycemia during acute ischemic stroke improves functional outcome, unanswered questions remain in specific acute ischemic stroke settings that warrant additional research.

Background: Benefit from blood glucose (BG) control during acute ischemic stroke may depend on glycemic parameters. We evaluated for associations between the SHINE (Stroke Hyperglycemia Insulin Network Effort) randomized treatment group and the SHINE predefined 90-day functional outcome, within-patient subgroups defined by various glycemic parameters. Methods: The SHINE Trial randomized 1151 patients within 12 hours with acute ischemic stroke and hyperglycemia to standard (target BG 80–179 mg/dL) or intensive (target BG 80–130 mg/dL) BG control for 72 hours. We predefined 6 glycemic parameters: acute BG level, absence versus presence of diagnosed and undiagnosed diabetes, hemoglobin A1c, glycemic gap (acute BG–average daily hemoglobin A1c based BG), stress hyperglycemia ratio (acute BG/average daily hemoglobin A1c based BG), and BG variability (SD). Favorable functional outcome was defined by the SHINE Trial and based on the modified Rankin Scale score at 90 days, adjusted for stroke severity. We computed relative risks adjusted for baseline stroke severity and thrombolysis use. Results: Likelihood for favorable outcome was lowest among patients with undiagnosed diabetes compared to patients with true nondiabetes (adjusted relative risk, 0.42 [99% CI, 0.19–0.94]). We did not find any relationship between the favorable outcome rate and baseline BG or any of the glycemic parameters. No differences between SHINE treatment groups were identified among any of these patient subgroups. Conclusions: In this exploratory subgroup analysis, intensive versus standard insulin treatment of hyperglycemia in acute ischemic stroke patient subgroups, did not influence the 90-day functional outcomes, nor did we identify associations between these glycemic parameters and 90-day functional outcomes.

Background: Pharmacological and clinical evidence suggest that sulfonylurea (SU) medications may improve acute ischemic stroke (AIS) outcomes. The SHINE trial studied intensive vs standard blood sugar management in patients presenting with AIS and hyperglycemia. We investigated whether pre-existing SU use impacted functional outcomes in SHINE. Methods: SHINE data collection forms were reviewed to identify AIS patients taking SUs at the time of study enrollment. Our primary outcome compared the adjusted 90-day utility weighted modified Rankin Scale (UW-mRS) score in the SU and non-SU cohorts. The UW-mRS score was adjusted for age, baseline NIHSS, baseline glucose, and reperfusion therapy. Pre-specified analyses of the 90-day UW-mRS scores assessed for heterogeneity of SU effect across the following subgroups: age, stroke severity, reperfusion therapy, type of SU, and SHINE study arm. Results: In total, 1066 SHINE subjects with a final diagnosis of AIS were included (SU=248 [23.3%], non-SU=818 [76.7%]). Baseline demographics were generally similar (Table 1). Calculated 90-day mean UW-mRS score were higher in the non-SU group compared to the SU group: mean 0.617 ± 0.012 versus mean 0.566 ± 0.022 (Diff 0.051, 95% CI 0.001-0.1) without heterogeneity of treatment effect (Figure 1). Conclusion: Contrary to our hypothesis and published literature, our retrospective analysis of the SHINE trial demonstrated better functional outcomes in the non-SU cohort. This may be due to selection bias with inadequate controlling for baseline risk factors present in the SU cohort. Definitive prospective studies are required.

White matter pathologies are critically involved in the etiology of vascular cognitive impairment-dementia (VCID), Alzheimer's disease (AD), and Alzheimer's disease and related diseases (ADRD), and therefore need to be considered a treatable target ( Roseborough A, Hachinski V, Whitehead S. White matter degeneration - a treatable target? Roseborough et al. JAMA Neurol [Internet]. 2020 Apr 27;77(7):793-4, [1] . To help address this often-missed area of research, several workshops have been sponsored by the Leo and Anne Albert Charitable Trust since 2015, resulting in the incorporation of "The Albert Research Institute for White Matter and Cognition" in 2020. The first annual "Institute" meeting was held virtually on March 3-4, 2021. The Institute provides a forum and workspace for communication and support of the advancement of white matter science and research to better understand the evolution and prevention of dementia. It serves as a platform for young investigator development, to introduce new data and debate biology mechanisms and new ideas, and to encourage and support new research collaborations and directions to clarify how white matter changes, with other genetic and health risk factors, contribute to cognitive impairment. Similar to previous Albert Trust-sponsored workshops (Barone et al. in J Transl Med 14:1-14, [2]; Sorond et al. in GeroScience 42:81-96, [3]), established expert investigators were identified and invited to present. Opportunities to attend and present were also extended by invitation to talented research fellows and younger scientists. Also, updates on institute-funded research collaborations were provided and discussed. The summary that follows is a synopsis of topics and discussion covered in the workshop.

Decompressive craniectomy (DC) is an established optional treatment for malignant hemispheric infarction (MHI). We analyzed relevant clinical factors and computed tomography (CT) measurements in patients with DC for MHI to identify predictors of functional outcome 3-6 months after stroke.This study was performed at 2 comprehensive stroke centers. The inclusion criteria required DC for MHI, no additional intraoperative procedures (strokectomy or cerebral ventricular drain placement), and documented functional status 3-6 months after the stroke. We classified functional outcome as acceptable if the modified Rankin Scale score was5, or as unacceptable if it was 5 or 6 (bedbound and totally dependent on others or death). Multiple logistic regression analyzed relevant clinical factors and multiple perioperative CT measurements to identify predictors of acceptable functional outcome.Of 87 identified consecutive patients, 66 met the inclusion criteria. Acceptable functional outcome occurred in 35 of 66 (53%) patients. Likelihood of acceptable functional outcome decreased significantly with increasing age (OR 0.92, 95% CI 0.82-0.97, P = 0.004) and with increasing post-DC midline brain shift (OR 0.78, 95% CI 0.64-0.96, P = 0.016), and decreased non-significantly with left-sided stroke (OR 0.30, 95% CI 0.08-1.10, P = 0.069) and with increasing craniectomy barrier thickness (OR 0.92, 95% CI 0.85-1.01, P = 0.076).Patient age and the post-DC midline shift may be useful in prognosticating functional outcome after DC for MHI. Stroke side and craniectomy barrier thickness merit further ideally prospective outcome prediction testing.

Stroke constitutes the second leading cause of death and a major cause of disability worldwide. Stroke is normally classified as either ischemic or hemorrhagic stroke (HS) although 87% of cases belong to ischemic nature. Approximately 700,000 individuals suffer an ischemic stroke (IS) in the US each year. Recent evidence has denoted a rather pivotal role for defective macroautophagy/autophagy in the pathogenesis of IS. Cellular response to stroke includes autophagy as an adaptive mechanism that alleviates cellular stresses by removing long-lived or damaged organelles, protein aggregates, and surplus cellular components via the autophagosome-lysosomal degradation process. In this context, autophagy functions as an essential cellular process to maintain cellular homeostasis and organismal survival. However, unchecked or excessive induction of autophagy has been perceived to be detrimental and its contribution to neuronal cell death remains largely unknown. In this review, we will summarize the role of autophagy in IS, and discuss potential strategies, particularly, employment of natural compounds for IS treatment through manipulation of autophagy.

Decompressive craniectomy (DC) improves functional outcomes in selected patients with malignant hemispheric infarction (MHI), but variability in the surgical technique and occasional complications may be limiting the effectiveness of this procedure. Our aim was to evaluate predefined perioperative CT measurements for association with post-DC midline brain shift in patients with MHI.At two medical centers we identified 87 consecutive patients with MHI and DC between January 2007 and December 2019. We used our previously tested methods to measure the craniectomy surface area, extent of transcalvarial brain herniation, thickness of tissues overlying the craniectomy, diameter of the cerebral ventricle atrium contralateral to the stroke, extension of infarction beyond the craniectomy edges, and the pre and post-DC midline brain shifts. To avoid potential confounding from medical treatments and additional surgical procedures, we excluded patients with the first CT delayed30 hours post-DC, resection of infarcted brain, or insertion of an external ventricular drain during DC. The primary outcome in multiple linear regression analysis was the postoperative midline brain shift.We analyzed 72 qualified patients. The average midline brain shift decreased from 8.7 mm pre-DC to 5.4 post-DC. The only factors significantly associated with post-DC midline brain shift at the p0.01 level were preoperative midline shift (coefficient 0.32, standard error 0.10, p=0.002) and extent of transcalvarial brain herniation (coefficient -0.20, standard error 0.05, p0.001).In patients with MHI and DC, smaller post-DC midline shift is associated with smaller pre-DC midline brain shift and greater transcalvarial brain herniation. This knowledge may prove helpful in assessing DC candidacy and surgical success. Additional studies to enhance the surgical success of DC are warranted.

Background The modified Rankin Scale (mRS) is a key global outcome measure after stroke internationally. The latest English version of the simplified modified Rankin scale questionnaire (smRSq)(2011) is a reliable and valid tool in scoring the mRS after stroke. In order to use this tool in Chinese patients, we translated it into Chinese and tested its clinimetric properties. Methods The English version smRSq (2011) was translated into Chinese by a standard process. We recruited 300 consecutive hospitalized ischemic stroke patients in the department of neurology, Beijing Chaoyang Hospital. Six randomly paired raters scored the conventional mRS, the novel Chinese version smRSq (2011), the National Institutes of Health Stroke Scale (NIHSS), and the Barthel index (BI) in-person. Inter-rater reliability and validity were assessed. Results Among the 300 ischemic stroke patients, mean age was 64.9 ± 12.1 years, and 220 (73%) were male. For inter-rater reliability of the smRSq (2011), the percent agreement among the paired raters was 87%, the kappa (κ) was 0.84 (95% CI, 0.79–0.88), and the weighted kappa (κw) was 0.96 (95% CI, 0.95–0.98). The percent agreement between the smRSq (2011) scores and the conventional mRS scores was 55%, κ = 0.47 (95% CI, 0.40–0.54), and κw = 0.91 (95% CI, 0.89–0.93). In construct validity testing, the Spearman’s correlation coefficients comparing the smRSq (2011) scores with the NIHSS and the BI scores were 0.83 (P P Conclusions Our results show good to excellent clinimetric properties of the novel Chinese version smRSq (2011) in scoring the mRS in Chinese stroke patients. Further validation in other clinical settings, including in communities and by remote methods in China is warranted.

Background The slightly revised English version simplified modified Rankin scale questionnaire smRSq(2011) was shown to be reliable, valid, and useful in scoring the modified Rankin scale (mRS) after stroke. Our aim was to assess the inter-rater reliability and validity of a novel Chinese version smRSq(2011). Methods The English version smRSq(2011) was translated into Chinese by a standard process. We recruited 300 consecutive hospitalized ischemic stroke patients in the department of neurology, Beijing Chaoyang Hospital. Six randomly paired raters scored the conventional mRS, the novel Chinese version smRSq(2011), the National Institutes of Health Stroke Scale (NIHSS), and the Barthel index (BI) in-person. Inter-rater reliability and validity were assessed. Results Among the 300 ischemic stroke patients, mean age was 64.9±12.1 years, and 220 (73%) were male. For inter-rater reliability of the smRSq(2011), the percent agreement among the paired raters was 87%, the kappa (κ) was 0.84 (95% CI, 0.79-0.88), and the weighted kappa (κw) was 0.96 (95% CI, 0.95-0.98). The percent agreement between the smRSq(2011) scores by the first rater and the conventional mRS scores by the second rater in each pair was 55%, κ=0.47 (95% CI, 0.40-0.54), and κw=0.91 (95% CI, 0.89-0.93). In construct validity testing, the Spearman’s correlation coefficients comparing the smRSq(2011) scores by the first rater with the NIHSS and the BI scores by the second rater were 0.83 (P

Additional file 1: Figure S1. Slightly revised simplified modified Rankin Scale questionnaire (2011).

Additional file 2: Figure S2. The Chinese language smRSq(2011).

This important observation about the frequently reported prestroke modified Rankin Scale (mRS)1 is worthy of consideration. The mRS was not designed for use before brain injury.2,3 Scoring the mRS categories 0–2 requires a comparison between prestroke and poststroke functional states, which is not possible prestroke.

Objectives To test the reliability of three simplified measurements made after decompressive hemicraniectomy (DHC) for malignant hemispheric infarction on computed tomography (CT) scan. Patients and methods We defined new simple methods to measure the thickness of the soft tissues overlying the craniectomy defect and the extent of infarction beyond the anterior and posterior craniectomy edges on post-DHC CT. Multiple raters independently made the three new CT measurements in 49 patients from two institutions. The Intraclass Correlation Coefficient (ICC) compared the raters for interrater agreements (reliability). Results Between two raters at Augusta University Medical Center, each measuring 21 CT scans, the ICC coefficient point estimates were good to excellent (0.83 – 0.92). Among four raters at University of Virginia Medical Center, with three raters measuring each of 28 CT scans, the ICC coefficient point estimates were good to excellent (0.87 – 0.95). Conclusions The proposed simple methods to obtain three additional CT measurements after DHC in malignant hemispheric infarction have good to excellent reliability in two independent patient samples. The clinical usefulness of these measurements should be investigated.

Background: The slightly optimized English version simplified modified Rankin scale questionnaire smRSq(2011) was shown to be reliable, valid, and useful in scoring the modified Rankin scale (mRS) after stroke. Our aim was to assess the inter-rater reliability and validity of a novel Chinese version smRSq(2011). Methods: The English version smRSq(2011) was translated into Chinese by a standard process. We recruited 300 consecutive hospitalized ischemic stroke patients in the department of neurology, Beijing Chaoyang Hospital. Six randomly paired raters scored the conventional mRS, the novel Chinese version smRSq(2011), the National Institutes of Health Stroke Scale (NIHSS), and the Barthel index (BI) in-person. Inter-rater reliability and validity were assessed. Results: Among the 300 ischemic stroke patients, mean age was 64.9±12.1 years, and 220 (73%) were male. For inter-rater reliability of the smRSq(2011), the percent agreement among raters was 87%, the kappa (κ) was 0.84 (95% CI, 0.79-0.88), and the weighted kappa (κw) was 0.96 (95% CI, 0.95-0.98). The percent agreement between the conventional mRS and the smRSq(2011) was 63%, κ=0.57 (95% CI, 0.50-0.63) and κw=0.93 (95% CI, 0.91-0.95). In construct validity testing, the Spearman’s correlation coefficients comparing the smRSq(2011) to the NIHSS and the BI were 0.83 (P

BACKGROUND AND PURPOSE A standardized and validated method to measure brain shifts in malignant middle cerebral artery (MCA) stroke with decompressive hemicraniectomy (DHC) could facilitate clinical decision making, prognostication, and comparison of results between studies. METHODS We tested for reliability simplified methods to measure transcalvarial herniation, midline brain shift, and the contralateral cerebral ventricular atrium in malignant MCA stroke after DHC. Multiple raters measured brain shifts on post-DHC computed tomography (CT) scans with aligned and unaligned slice orientations in 25 patients. We compared the simplified measurements to previously reported more meticulous measurements. RESULTS The simplified measurements correlate well with the more meticulous measurements on both aligned and unaligned CTs (intraclass correlation coefficients .72-.89). CONCLUSIONS These simplified and expedient methods of measuring brain shifts in malignant MCA stroke after DHC correlate well with the more meticulous methods.

Introduction and purpose To facilitate modified Rankin scale (mRS) assessments, we developed and tested a smartphone/web application of the simplified mRS questionnaire (e-smRSq). The e-smRSq guides raters towards a final score according to the smRSq algorithm, and offers hints for scoring based on the conventional mRS concepts. Methods Initially, three experienced mRS certified raters prepared 30 vignettes of unstructured stroke patient interviews, and determined consensus reference scores. Using the e-smRSq, 16 raters of varied professional backgrounds without mRS training scored the mRS for 24 randomly selected vignettes. Subsequently, 5 certified and 5 uncertified raters using the e-smRSq scored 23 mRS certification vignettes developed and used in the Strategies to Innovate Emergency Care Clinical Trials Network-Neurological Emergencies Treatment Trials (SIREN-NETT). Cohen's and Fleiss's kappa (κ), weighted kappa (κw), and intra-class correlation (ICC) compared rater scores with reference scores and assessed interrater reliability. Results For the 16 initial raters using the e-smRSq with 24 vignettes, the κ (Fleiss) was 0.62 and ICC 0.87 (CI 0.80–0.93). Comparing raters’ scores with reference scores, Cohen's κ was 0.68 and κw 0.90. For the 10 subsequent raters using the e-smRSq on SIREN-NETT vignettes, κ (Fleiss) was 0.8 and ICC 0.95 (CI 0.91–0.97). Comparing all 10 raters scores with SIREN-NETT reference scores, Cohen's κ was 0.88 and κw 0.97. There was no significant difference between certified and uncertified raters. Conclusions The e-smRSq appears to have good reproducibility and validity metrics among both certified and non-certified mRS raters, possibly owing to its simplicity. Further testing in stroke patients in warranted.

Objective: Age-related cerebral white matter abnormalities, commonly termed leukoaraiosis (LA), are frequent manifestation of cerebral microvascular disease. Aging and hypertension are well linked to LA. We compared additional vascular risk factors and socioeconomic factors with LA severity in acute stroke patients. Methods: We analyzed 271 patients with acute ischemic or hemorrhagic stroke from a hospital registry. We collected clinical and socioeconomic data prospectively with a standardized questionnaire during acute stroke hospitalization. We scored LA severity on all available head computed tomography and magnetic resonance imaging (MRI) scans with the Wahlund LA scale. Mean response modeling analyzed for associations between LA severity and multiple potential predictors. Results: Among 238 patients with CT LA scores, ageing and history of hypertension emerged as independent predictors of LA severity in multivariable analysis. Among 186 patients with MRI LA scores, ageing and severe left ventricular hypertrophy emerged as independent predictors of LA severity in multivariable analysis. We did not find an independent significant association between LA severity and the other factors we tested. Conclusions: Our study confirms the association of LA severity with ageing, and with hypertension. However, other vascular and socioeconomic factors we tested were not independently associated with LA severity.

A standardized and validated method to measure brain shifts in malignant middle cerebral artery (MCA) stroke with decompressive hemicraniectomy (DHC) could facilitate clinical decision making, prognostication, and comparison of results between studies.We tested for reliability simplified methods to measure transcalvarial herniation, midline brain shift, and the contralateral cerebral ventricular atrium in malignant MCA stroke after DHC. Multiple raters measured brain shifts on post-DHC computed tomography (CT) scans with aligned and unaligned slice orientations in 25 patients. We compared the simplified measurements to previously reported more meticulous measurements.The simplified measurements correlate well with the more meticulous measurements on both aligned and unaligned CTs (intraclass correlation coefficients .72-.89).These simplified and expedient methods of measuring brain shifts in malignant MCA stroke after DHC correlate well with the more meticulous methods.

Despite effective treatments, hypertension remains uncontrolled in nearly half of the people with hypertension in the United States. Uncontrolled hypertension leads to end organ damage, such as left ventricular hypertrophy (LVH). To identify reasons for uncontrolled hypertension, we interviewed acute stroke patients with a history of hypertension and evaluated for LVH.Using a standardized questionnaire, we collected demographic, socioeconomic, and health-care data in 300 acute ischemic and hemorrhagic stroke patients in one hospital. We also collected relevant clinical data from medical records. We analyzed factors associated with echocardiographic LVH as a marker of uncontrolled hypertension in 190 acute stroke patients with a history of hypertension.Overall, 46% (88/190) of patients had LVH. In univariate analysis, lower household income and self-reported poor adherence to hypertension treatment were significantly associated with increased risk of LVH. In multiple logit modeling, only poor adherence to hypertension treatment remained significantly associated with LVH, odds ratio 1.77 (95% CI: 1.01-3.11), p0.05.In acute stroke patients, poor adherence to hypertension treatment is a significant independent predictor of LVH. A clear reason for poor adherence to treatment is elusive in a large proportion of these patients in our study. Further research is needed to identify and develop strategies to combat the key factors responsible for poor adherence to hypertension treatment.

Aims Hyperglycemia in type 2 diabetes mellitus (T2D) remains uncontrolled in approximately 50% of patients in the United States. Uncontrolled T2D is associated with various vascular complications, including stroke. We studied demographic and clinical factors association with pre-stroke glycemia, indicated by glycated hemoglobin (HbA1c), in acute stroke patients with T2D. Methods Using a questionnaire, we collected demographic, socioeconomic, and clinical information from 300 acute ischemic and hemorrhagic stroke patients in one hospital. We analyzed factors associated with HbA1c in patients with history of T2D. Results There were 111 patients with history of T2D and HbA1c measured on admission. In multivariable analyses factors associated with higher HbA1c were treatment with insulin (p = 0.05), history of hyperlipidemia (p = 0.01), and total cholesterol level (p = 0.02). Poor adherence to T2D treatment was associated with higher HbA1c levels (p = 0.006) only in a subgroup of patients with HbA1c ≥8%. Conclusion Insulin treatment and hyperlipidemia are associated with higher HbA1c levels in acute stroke patients with T2D. Poor adherence to diabetes treatment is associated with higher HbA1c levels only among patients with HbA1c ≥8%.

Rationale Patients with acute ischemic stroke and hyperglycemia have worse outcomes than those without hyperglycemia. Intensive glucose control during acute stroke is feasible and can be accomplished safely but has not been fully assessed for efficacy. Aims The Stroke Hyperglycemia Insulin Network Effort trial aims to determine the safety and efficacy of standard vs. intensive glucose control with insulin in hyperglycemic acute ischemic stroke patients. Design This is a randomized, blinded, multicenter, phase III trial of approximately 1400 hyperglycemic patients who receive either standard sliding scale subcutaneous insulin (blood glucose range 80–179 mg/dL, 4·44–9·93 mmol/L) or continuous intravenous insulin (target blood glucose 80–130 mg/dL, 4·44–7·21 mmol/L) for up to 72 h, starting within 12 h of stroke symptom onset. The acute treatment phase is single blind (for the patients), but the final outcome assessment is double blind. The study is powered to detect a 7% absolute difference in favorable outcome at 90 days. Study outcomes The primary outcome is a baseline severity adjusted 90-day modified Rankin Scale score, defined as 0, 0–1, or 0–2, if the baseline National Institutes of Health Stroke Scale score is 3–7, 8–14, or 15–22, respectively. The primary safety outcome is the rate of severe hypoglycemia (Discussion This trial will provide important novel information about preferred management of acute ischemic stroke patients with hyperglycemia. It will determine the potential benefits and risks of intensive glucose control during acute stroke.

Background A standardized, reliable, and practical method for measuring decompressive hemicraniectomy (DHC) defects and brain shifts in malignant middle cerebral artery (MCA) territory infarction is needed for reliable comparisons between computed tomography (CT) scans. Such a method could facilitate further studies on the effects of DHC. New method We describe and apply a method for measuring DHC defects and brain shifts on CT scans in 25 patients with malignant MCA territory infarction. Craniectomy area is adjusted for variations in head size, CT slice orientation is standardized, and the site of each measurement is defined. This method uses standard radiology platforms and volume-acquired helical CT scans. Results The measurements include a DHC size index (adjusted for variations in head size), midline brain shift (subfalcine), outward brain herniation (transcalvarial), and the diameter of the contralateral atrium of the lateral ventricle. Inter-rater agreement for these measurements in a sample of 15 subjects is excellent (correlation coefficients 0.90–0.98). Comparison with existing methods In contrast to previously reported methods, this method is tested in acute stroke patients, compensates for variability in head size, and includes a midline brain shift (subfalcine) and brain ventricular system measurements. Conclusions A practical method for measuring DHC size and brain shifts designed to be consistent between scans is proposed. This method should facilitate comparisons of measurements between serial scans, between patients, and perhaps between studies. This method could be useful in medical and surgical studies of brain herniations in malignant MCA territory infarction, and possibly other conditions.

Background and Purpose— Acute stroke clinical trials are conducted primarily at academic medical centers. As a result, patients living in rural areas are excluded from participation, results may not be generalizable to nonacademic settings, and studies may be slow to recruit subjects. Telemedicine can provide rural patients with emergency neurovascular consultation. We sought to determine whether telemedicine facilitates enrollment into acute stroke trials. Methods— We have an established rural “hub and spoke” telestroke network. From 2005 to 2009, we participated in 2 time-sensitive acute stroke trials: Factor Seven for Acute Hemorrhagic Stroke and Minocycline to Improve Neurological Outcome. Candidates for the 2 trials could be identified at either the hub or at the spokes, with patients presenting to the latter transferred to the hub for enrollment. We analyzed the times from symptom onset to consultation via telemedicine, arrival at the hub, and to initiation of a study drug to determine the impact of telemedicine on study enrollment. Results— Nineteen of 28 subjects enrolled in the 2 trials were identified initially at an outside facility via a telemedicine link. An additional 9 candidates identified by telemedicine could not be enrolled because of transportation time. Arrival at the hub was 127 minutes later (median, 207 [95% CI, 145 to 255] versus 80 [95% CI, 55 to 142]; P =0.0002), and study drug was started 74 minutes later (median, 298 [95% CI, 218 to 352] versus 225 [95% CI, 147 to 330]; P =0.05) for subjects who were identified via telemedicine and required transport to the hub compared with local subjects who presented directly to the hub. Conclusions— Telemedicine can enhance enrollment into time-sensitive acute stroke trials. However, transfer of subjects to the hub results in delays in study initiation for some and precludes enrollment for others similar to the weaknesses of “ship and drip” thrombolytic strategies. To save time, efforts are needed to enroll clinical trial subjects and begin the research drug at the remote site under telemedicine guidance.

Acute ischemic stroke (AIS) results from the occlusion of an artery and causes vascular and neuronal damage, both of which affect the extent of ischemic injury and stroke outcome. Despite extensive efforts, there is only one effective treatment for AIS. Given that up to 40% of the AIS patients present with admission hyperglycemia either as a result of diabetes or acute stress response, targets for neuronal and vascular protection under hyperglycemic conditions need to be better defined. Here, we review the impact of diabetes and acute hyperglycemia on experimental stroke with an emphasis on cerebrovasculature structure and function. The relevance to clinical evidence is also discussed.

A single optimal outcome measure in acute stroke has not been established. Changes in neurologic deficits might be useful outcome measures in acute stroke because they can measure within-subject changes on the entire spectrum of the scales starting at baseline.We tested the ability of percent National Institutes of Health Stroke Scale (NIHSS) score change (baseline-3 months) to predict the traditional functional outcomes in acute stroke (modified Rankin Scale [mRS], Barthel Index, Glasgow Outcome Scale, final NIHSS score). We analyzed data sets from two acute stroke clinical trials involving 44 clinical research centers throughout the United States and 1899 randomized patients.The percent NIHSS score change predicted functional outcomes very well, all areas under the curve of 0.90 or greater with all P values less than .001 in receiver operating characteristic analysis. In the National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator (rt-PA) Acute Stroke Trial, benefit from rt-PA was confirmed by a greater improvement on the NIHSS score than with placebo (67% v 50%, P.002). In moderate stroke severity (baseline NIHSS score 7-15) an improvement of at least 55% was the best predictor of functional independence at 3 months (mRSor= 2).This novel approach to the NIHSS score as an outcome measure in acute stroke appears to be an additional useful analytic and communication tool.

Objective: To assess the efficacy of carotid endarterectomy for stroke prevention in asymptomatic and symptomatic patients with internal carotid artery stenosis. Additional clinical scenarios, such as use of endarterectomy combined with cardiac surgery, are also reviewed. Methods: The authors selected nine important clinical questions. A systematic search was performed for articles from 1990 (the year of the last statement) until 2001. Additional articles from 2002 through 2004 were included using prespecified criteria. Two reviewers also screened for other relevant articles from 2002 to 2004. Case reports, review articles, technical studies, and single surgeon case series were excluded. Results: For several questions, high quality randomized clinical trials had been completed. Carotid endarterectomy reduces the stroke risk compared to medical therapy alone for patients with 70 to 99% symptomatic stenosis (16% absolute risk reduction at 5 years). There is a smaller benefit for patients with 50 to 69% symptomatic stenosis (absolute risk reduction 4.6% at 5 years). There is a small benefit for asymptomatic patients with 60 to 99% stenosis if the perioperative complication rate is low. Aspirin in a dose of 81 to 325 mg per day is preferred vs higher doses (650 to 1,300 mg per day) in patients undergoing endarterectomy. Conclusions: Evidence supports carotid endarterectomy for severe (70 to 99%) symptomatic stenosis (Level A). Endarterectomy is moderately useful for symptomatic patients with 50 to 69% stenosis (Level B) and not indicated for symptomatic patients with

Extracranial carotid artery disease can cause occipital infarction when the posterior cerebral artery originates from the carotid artery. To determine the prevalence of serious extracranial carotid artery stenosis (≥50%) and potential stroke mechanisms in patients with posterior cerebral artery territory occipital infarcts, we studied 24 consecutive patients with recent infarcts documented on computed tomography or magnetic resonance imaging. All patients presented with a homonymous visual field defect, and eight also had other cerebral dysfunctions. Eighteen patients had carotid studies: duplex ultrasound in 17 and arteriography in 1. Twenty patients had echocardiography. Presumed mechanisms of infarction were cardiac embolism in 10 patients (42%), hypercoagulability in 2 (8%), artery-to-artery embolism in 1 (4%), migraine in 1 (4%), multiple potential mechanisms (cardiac embolism, hypercoagulability, and migraine) in 1 (4%), and undetermined in the remaining 9 (38%). None of the patients had extracranial carotid artery stenosis ≥50%. Extracranial carotid artery disease appears to be a rare cause of occipital infarction. Our findings support conclusions reached in previous studies, that cardiac embolism is the principal cause of occipital infarction.

Diffusion and perfusion (MR) imaging modalities identify overlapping but not identical areas of tissue as lesion following a stroke. It is thought that the 'mismatch' between modalities may represent tissue that could be recovered with proper (thrombolytic) treatment. We have designed a tool for semi-automated segmentation of the images and calculation of the mismatch volume. We present results from software phantoms and clinical data. Phantom results show our mismatch volume calculations are unbiased at realistic noise levels. Clinical data show that raters using our tool are consistent, fast (15min per subject) and indistinguishable from an expert using manual segmentation.

Department of Neurology, Indiana University School of Medicine, 541 Clinical Drive, Room 292, Indianapolis, IN 46202-5111, USA Mayo Clinic, Rochester, MN, USA Cedars Sinai Medical Center, Los Angeles, CA, USA Medical College of Ohio, Toledo, OH, USA University of Illinois, Chicago, IL, USA Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 541 Clinical Drive, Room 292, Indianapolis, IN 46202-5111, USA

Objective To describe a case of recanalization of a basilar artery occlusion with intravenous (IV) tenecteplase. Case A 74-year-old man with a history of cardiomyopathy presented to an outside hospital with acute vertigo, dysarthria, gaze deviation, and ataxia. Computerized tomography arteriography demonstrated occlusion of the proximal basilar artery. IV tissue plasminogen activator was ordered; however, the patient received a cardiac dose of IV tenecteplase. The patient was transferred to our facility, whereby symptoms resolved, and repeat computerized tomography arteriography displayed recanalization of the basilar artery. Conclusions Tenecteplase has enhanced biochemical and pharmacokinetic properties that may be ideal for treatment of basilar artery occlusion and should be further investigated in a randomized clinical trial.

Background and Purpose— Through 2-way live video and audio communication, telestroke enhances urgent treatment of patients with acute stroke in emergency departments (EDs) without immediate access to on-site specialists. To assess for opportunities to shorten the door to thrombolysis time, we measured multiple time intervals in a telestroke system. Methods— We retrospectively analyzed 115 records of consecutive acute stroke patients treated with intravenous thrombolysis during a 20-month period via a statewide telestroke system in 17 EDs in Georgia. On the basis of times documented in the telestroke system, we calculated the time elapsed between the following events: ED arrival, telestroke patient registration, start of specialist consultation, head computed tomography, thrombolysis recommendation, and thrombolysis initiation. Results— The most conspicuous delay was from ED arrival to telestroke patient registration (median, 39 minutes; interquartile range, 21–56). Median time from ED arrival to thrombolysis initiation was 88 minutes, interquartile range 75 to 105. Thrombolysis was initiated within 60 minutes from ED arrival in 13% of patients. Conclusions— The greatest opportunity to expedite acute thrombolysis via telestroke is by shortening the time from ED arrival to telestroke patient registration.

Background Acute stroke size is one of the factors impacting functional outcome. To further validate the simplified modified Rankin Scale questionnaire (smRSq), we tested its correlation with stroke size. Methods We screened 60 ischemic stroke patients with acute brain images available for stroke volume measurement who were enrolled in 2 smRSq reliability studies. Inclusion criteria were acute ischemic stroke visible on computed tomography (CT) or magnetic resonance imaging (MRI) and the smRSq scored at least 3 months after stroke. We excluded patients with disabilities from a previous stroke. One investigator who was blinded to the functional outcomes measured stroke volumes with a specialized computer program (Analyze). We used MRI when both MRI and CT were available. We classified strokes into 2 size categories: lacunar type measuring ≤6.28 cm 3 , which corresponds to a cylinder with a maximum diameter and height of 2.00 cm, or strokes >6.28 cm 3 . The Spearman correlation analysis compared the smRSq between the lacunar type and the larger strokes. Results Thirty-two patients qualified for this analysis with a mean age of 59 ± 15 years, and 17 (53%) were men. Lacunar stroke volumes (n = 17) ranged from 0.03 to 4.58 cm 3 , and the larger stroke volumes (n = 15) ranged from 11.52 to 250.02 cm 3 . Lacunar strokes were associated with lower smRSq scores (median 1) than the larger strokes (median 4; r=0.68; R 2 = 0.46; P Conclusions Acute stroke size correlates well with the smRSq, supporting its validity in assessing functional outcome after stroke.

Stroke is a common problem in the United States and causes significant morbidity and mortality. In addition both the personal and economic costs of stroke are high. Chronic arterial hypertension is the most significant modifiable risk factor for stroke (ischemic and hemorrhagic), both because of it's high relative risk for stroke and also because of it's prevalence in the general population. In addition hypertension remains under-recognized and under-treated. Newer studies have demonstrated that more aggressive treatment of hypertension results in lower cardiovascular morbidity and mortality, including that due to stroke. Consequently, new definitions for hypertension and new recommendations for treatment have recently been published. Furthermore, certain conditions, such as stroke, have been determined to be a “compelling indication” for certain classes of antihypertension therapy. Chronic hypertension is an important cause of the vascular pathology which leads to stroke and intracerebral hemorrhage. Acute stroke and cerebral hemorrhage may also cause an acute rise in blood pressure. Treatment of elevated blood pressure during acute stroke must balance the theoretical risk of worsening the stroke due to reduced cerebral perfusion against the benefits of lowering blood pressure (reduced risk of hemorrhage, cerebral edema, and other end-organ damage). This has been made more challenging since the approval of thrombolytic therapy for acute ischemic stroke. Also, severely elevated blood pressure can also cause hypertensive encephalopathy which must be distinguished from stroke so that appropriate treatment can be instituted as quickly as possible.

Background and Purpose— The PROACT II study demonstrated a significant benefit from treatment with intra-arterial pro-urokinase (r-proUK) in patients with middle cerebral artery occlusion treated within 6 hours of stroke onset. The purpose of the current study was to examine baseline factors to determine predictors of good outcome and response to treatment. Methods— We selected from the baseline clinical, radiologic, and angiographic data variables that considered possibly related to outcome. A univariate analysis was performed to examine the association between these baseline factors and good outcome, defined as a modified Rankin scale score ≤2. A multivariate model then selected the most important variables independently influencing prognosis. A risk score for each patient was constructed on the basis of the patient’s individual values for each independent variable. Patients were stratified into risk quartiles based on their risk scores, and an odds ratio for each risk quartile was calculated. The treatment effects of each quartile were compared. Results— In the univariate analysis, screening National Institutes of Health stroke scale (NIHSS) score and age were strongly associated with good outcome. The multivariate model selected age, NIHSS score, and CT hypodensity as the most important prognostic variables. Dividing patients into quartiles based on risk scores achieved a uniform gradient of probability of good outcomes. A trend toward benefit of r-proUK treatment was seen in all risk quartiles, and no differential treatment effect was observed across risk groups. Conclusions— There was no evidence of differential effect of r-proUK across subgroups of patients stratified by risk.

Background and Purpose— Primary stroke centers (PSCs) are associated with greater rates of tissue plasminogen activator use and improved outcomes. The American Stroke Association has advocated for the preferential transport of stroke patients to PSCs. We investigated the impact of PSC certification on hospital stroke discharge patterns in Georgia communities with a choice between PSC and non-PSC. Methods— We analyzed data from the Georgia Discharge Data System before (2004) and after stroke certification (2009). Only Metropolitan Statistical Areas containing ≥1 PSC and ≥1 non-PSC were included in the analysis. We calculated the odds of acute stroke discharge from a PSC in 2009 compared with 2004. Results— In Georgia Metropolitan Statistical Areas with at least 1 PSC and 1 non-PSC hospital, the percent of patients discharged from a subsequently designated PSC increased from 50.2% to 56.6% between 2004 and 2009 (OR, 1.29; P Conclusions— Although there has been an overall increase in stroke discharges from PSCs, the impact of stroke certification on patient destination was small and inconsistent across the state suggesting that local factors influence the location of hospitalization.

Background: Hyperglycemia during acute ischemic stroke may augment brain injury, predispose to intracerebral hemorrhage (ICH), or both. Method: To analyze the relationship between admission glucose level and clinical outcomes from acute ischemic stroke, the authors performed multivariate regression analysis with the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) Stroke Trial data. Neurologic improvement was defined as improvement on the NIH Stroke Scale by 4 or more points from baseline to 3 months, or a final score of zero. Favorable outcome was defined as both Glasgow Outcome score of 1 and Barthel Index 95 to 100 at 3 months. Symptomatic ICH was defined as CT-documented hemorrhage temporally related to clinical deterioration within 36 hours of treatment. Potential confounding factors were controlled, including acute treatment (rt-PA or placebo), age, baseline NIH Stroke Scale score, history of diabetes mellitus, stroke subtype, and admission blood pressure. Results: There were 624 patients enrolled within 3 hours after stroke onset. As admission glucose increased, the odds for neurologic improvement decreased (odds ratio [OR] = 0.76 per 100 mg/dL increase in admission glucose, 95% CI 0.61 to 0.95, p = 0.01). The relation between admission glucose and favorable outcome depended on admission mean blood pressure (MBP): as admission MBP increased, the odds for favorable outcome related to increasing admission glucose levels progressively decreased ( p = 0.02). As admission glucose increased, the odds for symptomatic ICH also increased (OR = 1.75 per 100 mg/dL increase in admission glucose, 95% CI 1.11 to 2.78, p = 0.02). Admission glucose level was not associated with altered effectiveness of rt-PA. Conclusions: In patients with acute ischemic stroke, higher admission glucose levels are associated with significantly lower odds for desirable clinical outcomes and significantly higher odds for symptomatic ICH, regardless of rt-PA treatment. Whether this represents a cause and effect relationship remains to be determined.

The urgency of Code Stroke is founded on the rapidly evolving brain injury during acute cerebral infarction, and the time-sensitive effectiveness of thrombolytic therapy. Lay public and Emergency Medical Services awareness can lead to earlier arrival of acute stroke victims in Emergency Departments, increasing the chance of effective thrombolytic therapy. Specially established Stroke Teams at certified Stroke Centers are ideal for raising stroke awareness and optimizing acute therapy to improve outcomes. Stroke Teams ideally should include a diverse group of health care providers, supported by hospital administration, working in concert. Efficient evaluation of acute stroke victims includes urgent assessment with concomitant acquisition of a focused history, a focused physical examination, rapid neuroimaging, and pertinent blood tests. Based on these evaluations a decision can be made whether to recommend thrombolytic therapy. Additional acute therapies are aimed at preventing complications. Code stroke should swiftly transition from the Emergency Department to a specialized Stroke Unit for continued specialized care.

Background: Remote limb ischemic conditioning (RLIC) is a promising treatment for ischemic stroke. We have previously shown that RLIC increases cerebral blood flow, reduces infarct size, and improves outcome in a murine thromboembolic stroke model (Hoda N et al. Stroke. 2012; 43:2794). We hypothesized that RLIC will increase CBF in hypoperfused areas in acute stroke patients as detected by MRI Arterial Spin Labeling (ASL) Methods: Patients with an acute ischemic stroke within 14 days and with a persistent mismatch defined by a perfusion defect measured by ASL that was at least 20% larger than the area of infarction as measured by diffusion weighted imaging (DWI) were eligible. Patients underwent 4 cycles of blood pressure cuff inflation (x200 mm Hg) for 5 minutes and deflation for 5 minutes on the leg or arm, 1- 2 times per day. MRI ASL, DWI, and 3D T1-weighted Fast Spoiled Gradient-Echo (FSPGR) images were taken before and 60 minutes after the last cycle of RLIC to measure CBF. Two neuroradiologists analyzed the images. Results: After 3 of 4 RLIC sessions, the CBF improved and the mismatch decreased by at least 15%. In the one patient without a reduction in mismatch, the RLIC was performed on the arm and not the leg. Conclusions: 1.) RLIC increased CBF as measured by ASL in stroke patients with a persistent diffusion-perfusion mismatch. 2.) Since it can be repeated multiple times on the same patient, ASL may be a useful biomarker of the conditioning response in humans. 3.) Further work in a larger sample of patients is needed to define the optimal regimen of RLIC and to determine the utility of ASL as a biomarker.