Stroke Telemedicine for Arizona Rural Residents, the Legacy Telestroke Study.

Background: Efficacy of telemedicine for stroke was first established by the Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC) trials in California and Arizona. Following these randomized controlled trials, the Stroke Telemedicine for Arizona Rural Residents (STARR) network was the first telestroke network to be established in Arizona. It consisted of a 7 spoke 1 hub telestroke system, and it was designed to serve rural, remote, or neurologically underserved communities. Objective: The objective of STARR was to establish a multicenter state-wide telestroke research network to determine the feasibility of prospective collection, recording, and regularly analysis of telestroke patient consultations and care data for the purposes of establishing quality measures, improvement, and benchmarking against other national and international telestroke programs. Methods: The STARR trial was open to enrollment for 29 months from 2008 to 2011. Mayo Clinic Hospital, Phoenix, Arizona served as the hub primary stroke center and its vascular neurologists provided emergency telestroke consultations to seven participating rural, remote, or underserved spoke community hospitals in Arizona. Eligibility criteria for activation of a telestroke alert and study enrollment were established. Consecutive patients exhibiting symptoms and signs of acute stroke within a 12 h window were enrolled, assessed, and treated by telemedicine. The state government sponsor, Arizona Department of Health Services' research grant covered the cost of acquisition, maintenance, and service of the selected telemedicine equipment as well as the professional telestroke services provided. The study deployed multiple telemedicine video cart systems, picture archive and communications systems software, and call management solutions. The STARR protocol was reviewed and approved by Mayo Clinic IRB, which served as the central IRB of record for all the participating hospitals, and the trial was registered at ClinicalTrials.gov. Results: The telestroke hotline was activated 537 times, and ultimately 443 subjects met criteria and consented to participate. The STARR successfully established a multicenter state-wide telestroke research network. The STARR developed a feasible and pragmatic approach to the prospective collection, storage, and analysis of telestroke patient consultations and care data for the purposes of establishing quality measures and tracking improvement. STARR benchmarked well against other national and international telestroke programs. STARR helped set the foundation for multiple regional and state telestroke networks and ultimately evolved into a national telestroke network. Conclusions: Multiple small and rurally located community hospitals and health systems can successfully collaborate with a more centrally located larger hospital center through telemedicine technologies to develop a coordinated approach to the assessment, diagnosis, and emergency treatment of patients manifesting symptoms and signs of an acute stroke syndrome. This model may serve well the needs of patients presenting with other time-sensitive medical emergencies.Clinical Trial Registration number: NCT00829361.

Stroke Mortality Outcomes in Uganda.

BACKGROUND AND PURPOSE: Stroke outcome data in Uganda is lacking. The objective of this study was to capture 30-day mortality outcomes in patients presenting with acute and subacute stroke to Mbarara Regional Referral Hospital (MRRH) in Uganda. METHODS: A prospective study enrolling consecutive adults presenting to MRRH with abrupt onset of focal neurologic deficits suspicious for stroke, from August 2014 to March 2015. All patients had head computed tomography (CT) confirmation of ischemic or hemorrhagic stroke. Data was collected on mortality, morbidity, risk factors, and imaging characteristics. RESULTS: Investigators screened 134 potential subjects and enrolled 108 patients. Sixty-two percent had ischemic and 38% hemorrhagic stroke. The mean age of all patients was 62.5 (SD 17.4), and 52% were female. More patients had hypertension in the hemorrhagic stroke group than in the ischemic stroke group (53% vs. 32%, p = 0.0376). Thirty-day mortality was 38.1% (p = 0.0472), and significant risk factors were National Institutes of Health Stroke Scale (NIHSS) score, female sex, anemia, and HIV infection. A one unit increase of the NIHSS on admission increased the risk of death at 30 days by 6%. Patients with hemorrhagic stroke had statistically higher NIHSS scores (p = 0.0408) on admission compared to patients with ischemic stroke, and also had statistically higher Modified Rankin Scale (mRS) scores at discharge (p = 0.0063), and mRS score change from baseline (p = 0.04). CONCLUSIONS: Our study highlights an overall 30-day stroke mortality of 38.1% in southwestern Uganda, and identifies NIHSS at admission, female sex, anemia, and HIV infection as predictors of mortality.

Aqueous extract of Sedum oxypetalum induces mineralization and osteogenic differentiation by human Periodontal Ligament-Derived cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant Sedum oxypetalum Kunth (Crassulaceae), locally known as Jiote or in general Siempreviva (always alive) has been traditionally used by people of the Mexican community of Tenango del Valle as a home remedy to treat periodontal diseases, inducing teeth strengthening. Consequently, the aim of this work was to investigate its capacity directed to mineralized tissues regeneration. MATERIALS AND METHODS: The aerial parts of the plant were processed and its aqueous extract (AE) was chemically characterized. The AE and its components sedoheptulose and syngenite were tested for either osteogenic differentiation or mineral-nucleation induction respectively. RESULTS: The AE and one of its components (sedoheptulose) were shown to promote the proliferation and/or osteogenic differentiation by Human Periodontal Ligament-Derived Cells (hPDLs), while inducing the mineralization process. The AE also promoted the nucleation of octacalcium phosphate and its component syngenite, the hydroxyapatite crystals formation in vitro. CONCLUSION: The findings reported herein support the traditional use of S. oxypetalum due to its potential capacity to promote the regeneration of mineralized tissues.

Retinal Microvascular Abnormalities as Surrogate Markers of Cerebrovascular Ischemic Disease: A Meta-Analysis.

BACKGROUND: To determine the predictive value of retinal microvascular abnormalities for cerebrovascular ischemic diseases (CVDs), we aimed to investigate the quantitative association between retinal microvascular changes and CVD subcategories: white matter hyperintensities (WMHIs), lacunar infarcts (LIs), and cerebral infarctions (CIs). METHODS: Using Meta-analyses Of Observational Studies in Epidemiology guidelines, we searched 6 databases through September 2016 for studies evaluating the linkage between retinal microvascular abnormalities and WMHI, and LI and CI. Studies were included if they reported odds ratios (ORs) and 95% confidence intervals or raw patient level data (that were computed into ORs). Unadjusted and vascular risk-factor adjusted ORs were pooled into meta-analysis using DerSimonian Laird random effects model. Study quality and dissemination biases were assessed and integrated. RESULTS: From 24,444 search-identified records, 28 prospective studies encompassing 56,379 patients were eligible for the meta-analysis. After vascular risk-factor adjustment, focal arteriolar narrowing was associated with WMHI (OR, 1.24 [1.01-1.79]), LI (OR, 1.77 [1.14-2.74]), and CI (OR, 1.75 [1.14-2.69]). Venular dilation was associated with LI (OR, 1.46 [1.10-1.93]), and retinal hemorrhages with WMHI (OR, 2.23 [1.34-3.70]). Any retinopathy exhibited significant association with CI (OR, 1.96 [1.65-2.50]). Heterogeneity was significant (I2>50%) for all syntheses except retinal hemorrhages and WMHI, and retinopathy and CI (I2=0 ⋅ 0%). Associations remained significant after adjustments for quality and publication bias. CONCLUSIONS: We found the most significant association between retinal hemorrhages and WMHI. Focal arteriolar narrowing and retinopathy predicted CVD subtypes after risk-factor adjustment, suggesting that features different than traditional vascular risk factors, are involved in CVD pathophysiology.

Is Intravenous Thrombolysis Safe and Effective in Central Retinal Artery Occlusion? A Critically Appraised Topic.

BACKGROUND: Central retinal artery occlusion (CRAO) is a neurological and ophthalmologic emergency associated with poor visual recovery. There is a dilemma regarding the appropriate treatment, as formal guidelines are lacking. Despite being considered an ocular equivalent of cerebral infarction, the time window of intravenous (IV) thrombolysis administration for maximum efficacy and safety in CRAO remains uncertain. OBJECTIVE: To critically assess the current evidence regarding the safety and effectiveness of IV thrombolysis in the treatment of patients with CRAO. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, and content experts in the fields of vascular neurology and ophthalmology. RESULTS: A recent patient-level meta-analysis was selected for critical appraisal. The study compared the visual recovery rates after IV thrombolysis in CRAO against the natural history of this illness and conservative therapies (ocular massage, anterior chamber paracentesis, and/or hemodilution). Time to thrombolytic therapy administration had a significant impact on visual recovery in CRAO (P<0.001). IV thrombolysis within the first 4.5 hours after symptom onset resulted in recovery of vision in 50.0% of the patients [95% confidence interval (CI), 32.4%-67.6%]. The rate of visual recovery was nearly 3 times higher than in the natural history cohort [odds ratio, 4.7 (95% CI, 2.3-9.6); P<0.001], with a 32.3% absolute risk reduction and a number needed to treat of 4.0 (95% CI, 2.6-6.6). There was no significant difference in the recovery rate after thrombolysis compared with the natural history cohort for those patients treated after 4.5 hours. No major hemorrhages occurred after alteplase administration in this meta-analysis. CONCLUSIONS: IV thrombolysis in CRAO seems to be safe and effective within the first 4.5 hours of symptom onset. A clinical decision based on this meta-analysis alone cannot be made due to several limitations. A randomized controlled clinical trial of early IV alteplase administration in CRAO is necessary to provide evidence-based therapeutic guidance.

CHA2DS2-VASc Score: A Predictor of Thromboembolic Events and Mortality in Patients With an Implantable Monitoring Device Without Atrial Fibrillation.

OBJECTIVE: To determine if the CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, sex category) predicts thromboembolism and death in patients without atrial fibrillation in a population with implantable cardiac monitoring devices. PATIENTS AND METHODS: A retrospective review utilizing the Rochester Epidemiology Project research infrastructure was conducted to evaluate the CHA2DS2-VASc tool as a predictor of mortality and ischemic stroke, transient ischemic attack, or systemic embolism in patients without atrial fibrillation. An implantable device was required in the inclusion criteria to discern the absence of atrial fibrillation. The study period was January 1, 2004, through March 7, 2016. RESULTS: The study population (N=1606) had a mean (SD) age of 69.8 (12.6) years and median follow-up of 4.8 years (range, 0-12 years; quartile 1, 2.6 years and quartile 3, 8.1 years). The number of thromboembolic and mortality events stratified by CHA2DS2-VASc score groupings of 0 to 2 (399 patients), 3 to 5 (756 patients), and 6 to 9 (451 patients) were 12 (3.0%), 109 (14.4%), and 123 (27.3%) and 22 (5.5%), 205 (27.1%), and 214 (47.4%), respectively. The CHA2DS2-VASc score predicted thromboembolism and death. The hazard ratios (HRs) for thromboembolic events for CHA2DS2-VASc scores 3 to 5 and 6 to 9 were 4.84 (95% CI, 2.66-8.80) and 10.53 (95% CI, 5.77-19.21) (reference group, scores 0-2). The HRs for death for the corresponding score categories were 4.45 (95% CI, 2.86-6.91) and 8.18 (95% CI, 5.23-12.78). The CHA2DS2-VASc score also predicted development of atrial fibrillation, for which the HRs for scores 3 to 5 and 6 to 9 were 1.51 (95% CI, 1.13-2.00) and 2.17 (95% CI, 1.60-2.95). CONCLUSION: The CHA2DS2-VASc tool predicts thromboembolic events and overall mortality in patients without atrial fibrillation who have implantable devices.

Improving Blood Pressure Management and Disease Severity Documentation in Patients With Acute Intracerebral Hemorrhage.

OBJECTIVE: To ensure prime blood pressure management and intracerebral hemorrhage (ICH) score documentation within 6 hours of arrival and/or before any intervention in patients admitted to Mayo Clinic Hospital with acute ICH. PATIENTS AND METHODS: A quality improvement initiative was conducted between September 29, 2015, and May 30, 2017, following the Define-Measure-Analyze-Improve-Control methodology. Our prespecified goals for the first 8 months postintervention were that at least 80% of patients with ICH will have systolic blood pressure (SBP) control as per guideline-based recommendations (SBP ≤140 mm Hg) and at least 80% will have ICH score documented within 6 hours postadmission. Neurovascular stakeholders' feedback was included in the process development. Practice gaps and their leading causes were identified and served rational interventions' planning. Education and admission order-set modifications were chosen as intervention methods. RESULTS: At 4 (first measurement, n=13) and 8 months (second measurement, n=15) postintervention, 92.3% and 100% of patients with ICH, respectively, reached the target SBP, compared with 50% in the preintervention group (comparison group, n=26); 84.6% and 85.7% of the patient population had the ICH score documented at the first and second outcome measurement, respectively, compared with 42.3% in the preintervention group. Stakeholders reported good satisfaction with the novel applications. Sustainability plans and future directions were established. CONCLUSION: Effective education methods enhance the introduction of guideline-based clinical practices. This quality improvement project has the potential to impact patient outcomes, staff efficiency, and stroke centers' maintenance of certification and quality care recognition. This initiative warrants implementation at hospitals across all Mayo Clinic campuses and nationwide.

Management of Postthrombolysis Hemorrhagic and Orolingual Angioedema Complications.

Intravenous recombinant tissue plasminogen activator was first approved for the treatment of acute ischemic stroke in the United States in 1996. Thrombolytic therapy has been proven to be effective in acute ischemic stroke treatment and shown to improve long-term functional outcomes. Its use is associated with an increased risk of symptomatic intracerebral hemorrhage as well as orolingual angioedema. Our goal is to outline the management strategies for these postthrombolysis complications.

Evaluation of the diuretic activity in two Mexican medicinal species: Selaginella nothohybrida and Selaginella lepidophylla and its effects with ciclooxigenases inhibitors.

ETHNOPHARMACOLOGICAL RELEVANCE: Doradilla is a plant that has a long history in the Mexican traditional system of medicine for gall and renal stones, diuresis, stomach and liver inflammation among other diseases. Major components isolated from these plants include biflavonoids as amentoflavone (1), robustaflavone (2) and (S)-2,3-dihydrorobustaflavone (3) and the carbohydrate trehalose (4). The aim of this study was to evaluate the diuretic effect of the decoction of Selaginella nothohybrida Valdespino and Selaginella lepidophylla (Hook & Grev) Spring (Selaginellaceae), and compounds 1-4. We also explored the probable mode of action comparing the effects when using nonspecific and specific COX׳s inhibitors. MATERIALS AND METHODS: Three biflavonoids (1-3) were isolated from the ethyl acetate extraction of the aqueous decoction and the carbohydrate trehalose (4) from the aqueous phase. The structures of all compounds were elucidated by spectroscopic methods and comparisons were made against published data. The diuretic activity was assessed in mice by oral administration of the decoctions in doses of 1000 and 2000mg/kg and biflavonoids 1-3 and trehalose (4) in a dose range of 10mg/kg using furosemide as a standard drug. Inhibitors of COX׳s such as acetyl salicylic acid, sodium naproxen, indomethacin and Celebrex were also assayed to analyze the involvement of renal prostaglandins in diuresis. Water excretion rate, pH, density, conductivity, and contents of Na(+) and K(+) were measured in the urine of mice. RESULTS: Decoction of Selaginella lepidophylla showed lower effect in the urine output at doses of 1000 and 2000mg/kg, while decoction of Selaginella nothohybrida produced an increase at 2000mg/kg (P<0.05). Urinary electrolytes excretion was also affected by this last extract and pure compounds: decoction diminished urinary excretion of sodium and potassium ions, so as compounds 1 and 4; compounds 2 and 3 observed just a natriuretic effect. Pretreated mice with COX׳s inhibitors and then with test compounds 1, 2, 4 and decoction showed inhibition of diuresis in all cases exception for treatment with trehalose (4); natriuretic effect was observed in all cases except for biflavonoid robustaflavone (2) which behaved as the reference compound furosemide. Selaginella nothohybrida decoction behaved similarly to COX-2 inhibitor Celebrex (8), inhibiting diuresis. CONCLUSIONS: Selaginella nothohybrida presents a moderate diuretic effect, which appears to be in partly mediated by the presence of biflavonoids and trehalose. Renal prostaglandins may be involved in the mechanism of diuresis. The present results provide a quantitative basis explaining the traditional folk medicine use of Selaginella nothohybrida as a diuretic agent by Mexican population.

Robotic telepresence versus standardly supervised stroke alert team assessments.

BACKGROUND: Telemedicine has created access to emergency stroke care for patients in all communities, regardless of geography. We hypothesized that there is no difference in speed of assessment between vascular neurologist (VN) robotic telepresence and standard VN-supervised stroke alert patients in a metropolitan primary stroke center. MATERIALS AND METHODS: A retrospective stroke alert database was used to identify all robotic telepresence and standardly supervised stroke alert patient assessments at a primary stroke center emergency department from 2009 to 2012. The primary outcome measure was the duration of assessment from stroke alert activation to treatment or downgrade. RESULTS: The sample size was 196 subjects. The mean duration of time from stroke alert activation to initiation of intravenous (IV) thrombolytic treatment or downgrade was 8.6 min longer in the robotic group than in the standard group (p=0.03). Among the subgroup of acute ischemic stroke patients treated with IV thrombolysis, the mean duration of time from activation to treatment was 18 min longer in the robotic group than in the standard group (p=0.01). Safety outcomes including thrombolysis protocol violations (0% versus 1%), post-thrombolysis symptomatic intracranial hemorrhagic complications (3% versus 1%), and death during hospitalization (8% versus 6%) were low in the robotic group and not significantly different from that in the standard group. CONCLUSIONS: Standard VN-supervised acute stroke team assessments were swifter than those supervised by robotic telepresence. Safety outcomes of robotic telepresence-supervised stroke alerts were excellent, and this modality may be preferred in circumstances when a VN is not immediately available on-site.

New anticoagulants (dabigatran, apixaban, rivaroxaban) for stroke prevention in atrial fibrillation.

New oral anticoagulants have been found to be as efficacious as warfarin and safer in terms of intracranial bleeding. All patients with nonvalvular atrial fibrillation should receive antithrombotic therapy for stroke prevention. For those at low risk, antiplatelet therapy is probably sufficient. For those at intermediate or high risk, anticoagulation is superior to antiplatelet therapy. Four oral anticoagulants are currently approved for stroke and systemic embolism prevention in atrial fibrillation: warfarin, dabigatran, rivaroxaban, and apixaban. Management of bleeding complications while on the new agents remains an area of concern and management is based on anecdotal experience and observational studies.

Smartphone teleradiology application is successfully incorporated into a telestroke network environment.

BACKGROUND AND PURPOSE: ResolutionMD mobile application runs on a Smartphone and affords vascular neurologists access to radiological images of patients with stroke from remote sites in the context of a telemedicine evaluation. Although reliability studies using this technology have been conducted in a controlled environment, this study is the first to incorporate it into a real-world hub and spoke telestroke network. The study objective was to assess the level of agreement of brain CT scan interpretation in a telestroke network between hub vascular neurologists using ResolutionMD, spoke radiologists using a Picture Archiving and Communications System, and independent adjudicators. METHODS: Fifty-three patients with stroke at the spoke hospital consented to receive a telemedicine consultation and participate in a registry. Each CT was evaluated by a hub vascular neurologist, a spoke radiologist, and by blinded telestroke adjudicators, and agreement over clinically important radiological features was calculated. RESULTS: Agreement (κ and 95% CI) between hub vascular neurologists using ResolutionMD and (1) the spoke radiologist; and (2) independent adjudicators, respectively, were: identification of intracranial hemorrhage 1.0 (0.92-1.0), 1.0 (0.93-1.0), neoplasm 1.0 (0.92-1.0), 1.0 (0.93-1.0), any radiological contraindication to thrombolysis 1.0 (0.92-1.0), 0.85 (0.65-1.0), early ischemic changes 0.62 (0.28-0.96), 0.58 (0.30-0.86), and hyperdense artery sign 0.40 (0.01-0.80), 0.44 (0.06-0.81). CONCLUSIONS: CT head interpretations of telestroke network patients by vascular neurologists using ResolutionMD on Smartphones were in excellent agreement with interpretations by spoke radiologists using a Picture Archiving and Communications System and those of independent telestroke adjudicators using a desktop viewer. CLINICAL TRIAL REGISTRATION INFORMATION: www.clinicaltrials.gov unique identifier NCT00829361.

CT interpretation in a telestroke network: agreement among a spoke radiologist, hub vascular neurologist, and hub neuroradiologist.

BACKGROUND AND PURPOSE: The American Stroke Association guidelines emphasized the need for further high-quality studies that assess agreement by radiologists and nonradiologists engaged in emergency telestroke assessments and decision-making. Therefore, the objective of this study was to determine the level of agreement of baseline brain CT scan interpretations of patients with acute stroke presenting to telestroke spoke hospitals between central reading committee neuroradiologists and each of 2 groups, spoke hospital radiologists and hub hospital vascular neurologists (telestrokologists). METHODS: The Stroke Team Remote Evaluation Using a Digital Observation Camera Arizona trial was a prospective, urban single-hub, rural 2-spoke, randomized, blinded, controlled trial of a 2-way, site-independent, audiovisual telemedicine and teleradiology system designed for remote evaluation of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis. In the telemedicine arm, the subjects' CT scans were interpreted by the hub telestrokologist and in the telephone arm by the spoke radiologist. All subjects' CT scans were subsequently interpreted centrally, independently, and blindly by 2 hub neuroradiologists. The primary CT outcome was determination of a CT-based contraindication to thrombolytic treatment. Kappa statistics and exact agreement rates were used to analyze interobserver agreement. RESULTS: Fifty-four subjects underwent random assignment. The overall agreement for the presence of radiological contraindications to thrombolysis was excellent (0.91) and did not differ substantially between the hub telestrokologist to neuroradiologist and spoke radiologist to neuroradiologist (0.92 and 0.89, respectively). CONCLUSIONS: In the context of a telestroke network designed to assess patients with acute stroke syndromes, agreement over the presence or absence of radiological contraindications to thrombolysis was excellent whether the comparisons were between a telestrokologist and neuroradiologist or between spoke radiologist and neuroradiologist. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00623350.

Is dabigatran cost effective compared with warfarin for stroke prevention in atrial fibrillation? A critically appraised topic.

BACKGROUND: Warfarin has provided protection against cardioembolic stroke in the setting of nonvalvular atrial fibrillation (NVAF) for the past 60 years. Dabigatran, the first oral direct thrombin inhibitor to be approved in the United States, promises to provide the same or better stroke protection with reduced risk of intracranial hemorrhage. However, it remains to be seen whether grand-scale adoption of dabigatran will be cost effective. OBJECTIVE: To critically assess current evidence regarding the cost effectiveness of dabigatran for preventing stroke in patients with NVAF compared with warfarin. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular neurology. RESULTS: A cost-effectiveness analysis (CEA) that followed a hypothetical cohort of NVAF patients 65 years of age or older and CHADS2≥1 over their lifetime comparing dabigatran with adjusted-dose warfarin was reviewed. Assuming a willingness to pay a threshold of $50,000 per quality-adjusted life year (QALY), base case results favored high-dose (150 mg bid) dabigatran as a cost-effective alternative to warfarin. Sensitivity analysis asserted that the cost effectiveness of dabigatran improved if it could be obtained for ≤$13/d or if it was used in populations with high risk of stroke or intracranial hemorrhage. CONCLUSIONS: Dabigatran 150 mg bid ($12,286 per QALY) is a cost-effective alternative to International Normalized Ratio-adjusted warfarin for the prevention of ischemic stroke in patients 65 years of age or older with NVAF.

Intracranial hemorrhage: diagnosis and management.

Intracranial hemorrhage (ICH) is defined as bleeding within the intracranial vault and has several subtypes depending on the anatomic location of bleeding. ICH is diagnosed through history, physical examination, and, most commonly, noncontrast CT examination of the brain, which discloses the anatomic bleeding location. Trauma is a common cause. In the absence of trauma, spontaneous intraparenchymal hemorrhage is a common cause associated with hypertension when found in the deep locations such as the basal ganglia, pons, or caudate nucleus. This article addresses the diagnosis and general management of ICH and discusses specialized management for select ICH subtypes.

Safety and efficacy of ultrasound-enhanced thrombolysis in the treatment of acute middle cerebral artery infarction: a critically appraised topic.

BACKGROUND: Despite appropriate therapy with intravenous (IV) tissue plasminogen activator (tPA), a significant proportion of patients with acute middle cerebral artery (MCA) infarction continue to suffer residual disability or death. The therapeutic use of transcranial Doppler ultrasonography (TCD) concomitantly with IV tPA is speculated to increase recanalization rates and improve clinical outcomes in patients with acute MCA stroke. OBJECTIVE: To critically appraise the evidence concerning the safety and efficacy of the simultaneous delivery of IV tPA and continuous TCD monitoring as an acute therapy in patients with MCA territory infarction. METHODS: The objective was addressed through the development of a structured, critically appraised topic. This incorporated a clinical scenario, background information, a structured question, literature search strategy, results, critical appraisal, clinical bottom line, and expert commentary from vascular neurology. RESULTS: In a multicenter phase II randomized controlled study, 126 patients with acute MCA stroke were randomized to receive treatment with IV tPA and continuous TCD monitoring or placebo monitoring. Complete recanalization or dramatic clinical recovery within 2 hours after the administration of a tPA bolus occurred in 31 patients in the target group (49%), as compared with 19 patients in the control group (30%); P=0.03. At 3 months, of the patients eligible for follow-up, 22 of 53 (42%) in the target group and 14 of 49 (29%) in the control group had favorable outcomes; P=0.20. Four symptomatic intracerebral hemorrhages were noted in each group. CONCLUSIONS: Therapeutic use of continuous TCD monitoring concomitantly with IV tPA increases recanalization rates in patients with acute MCA stroke relative to treatment with IV tPA alone without increasing the complication of intracerebral hemorrhage.

Statins and intracerebral hemorrhage: collaborative systematic review and meta-analysis.

BACKGROUND: A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. METHODS AND RESULTS: We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10; 95% confidence interval, 0.86-1.41), cohort studies (risk ratio, 0.94; 95% confidence interval, 0.81-1.10), or case-control studies (risk ratio, 0.60; 95% confidence interval, 0.41-0.88). Substantial statistical heterogeneity was evident for the case-control studies (I(2)=66%, P=0.01), but not for the cohort studies (I(2)=0%, P=0.48) or randomized trials (I(2)=30%, P=0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. CONCLUSIONS: We found no evidence that statins were associated with intracerebral hemorrhage; if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs.