Anticoagulation Versus Antiplatelets in Spontaneous Cervical Artery Dissection: A Systematic Review and Meta-Analysis.

BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P=0.02; I2=0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P=0.03, I2=0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

Statin treatment intensity and cerebral vasomotor reactivity response in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Cerebral vasomotor reactivity (VMR) is vital for regulating brain blood flow and maintaining neurological function. Impaired cerebral VMR is linked to a higher risk of stroke and poor post-stroke outcomes. This study explores the relationship between statin treatment intensity and VMR in patients with ischemic stroke. METHODS: Seventy-four consecutive patients (mean age 69.3 years, 59.4% male) with recent ischemic stroke were included. VMR levels were assessed 4 weeks after the index stroke using transcranial Doppler, measuring the breath-holding index (BHI) as an indicator of the percentage increase in middle cerebral artery blood flow (higher BHI signifies higher VMR). Multistep multivariable regression models, adjusted for demographic and cerebrovascular risk factors, were employed to examine the association between statin intensity treatment and BHI levels. RESULTS: Forty-one patients (55%) received high-intensity statins. Patients receiving high-intensity statins exhibited a mean BHI of 0.85, whereas those on low-intensity statins had a mean BHI of 0.67 (mean difference 0.18, 95% confidence interval: 0.13-0.22, p-value<.001). This significant difference persisted in the fully adjusted model (adjusted mean values: 0.84 vs. 0.68, p-value: .008). No significant differences were observed in BHI values within patient groups on high-intensity or low-intensity statin therapy (all p-values>.05). Furthermore, no significant association was found between baseline low-density lipoprotein (LDL) levels and BHI. CONCLUSIONS: High-intensity statin treatment post-ischemic stroke is linked to elevated VMR independent of demographic and clinical characteristics, including baseline LDL level. Further research is needed to explore statin therapy's impact on preserving brain vascular function beyond lipid-lowering effects.

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Thrombolysis for central retinal artery occlusion: An individual participant-level meta-analysis.

BACKGROUND: Whether thrombolysis improves outcomes in non-arteritic central retinal artery occlusion (naCRAO) is uncertain. We aimed to evaluate the rate of visual recovery after intra-venous thrombolysis (IVT) or intra-arterial thrombolysis (IAT) administration of tissue plasminogen activator (tPA) or urokinase among patients with naCRAO and explore the parameters affecting the final visual acuity (VA). AIM: We systematically searched six databases. Logarithm of the minimum angle of resolution (logMAR) and VA of ⩾20/100 were used to quantify visual recovery. To explore the role of other factors on visual recovery, we defined two models for studies with aggregated data (designs 1 and 2) and 16 models for individual participant data (IPD, models 1-16). SUMMARY OF REVIEW: We included data from 771 patients out of 72 publications in nine languages. Visual improvement for ⩾0.3 logMAR was reported in 74.3% of patients who received IVT-tPA within 4.5 h (CI: 60.9-86.0%; unadjusted rate: 73.2%) and 60.0% of those who received IAT-tPA within 24 h (CI: 49.1-70.5%; unadjusted rate: 59.6%). VA of ⩾20/100 was observed among 39.0% of patients after IVT-tPA within 4.5 h and 21.9% of those with IAT-tPA within 24 h. IPD models highlighted the association between improved visual outcomes and VA at presentation, at least 2 weeks follow-up before reporting the final VA, antiplatelet therapy, and shorter symptom onset to thrombolysis window. CONCLUSION: Early thrombolytic therapy with tPA is associated with enhanced visual recovery in naCRAO. Future studies should refine the optimum time window for thrombolysis in naCRAO.

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study.

BACKGROUND: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. METHODS: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. FINDINGS: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9%) patients had a stroke-123(79%) ischaemic stroke, 27(17%) intracerebral/subarachnoid hemorrhage, and 6(4%) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5% among all centres in all countries, and 0.7% among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95% CI:1.1-3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95% CI:1.4-4.7, p = 0.006) were predictive of stroke. INTERPRETATION: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5%(pooled risk: 0.9%). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. FUNDING: None.

Timing of Recanalization and Functional Recovery in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Although onset-to-treatment time is associated with early clinical recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (tPA), the effect of the timing of tPA-induced recanalization on functional outcomes remains debatable. METHODS: We conducted a multicenter, prospective observational cohort study to determine whether early (within 1-hour from tPA-bolus) complete or partial recanalization assessed during 2-hour real-time transcranial Doppler monitoring is associated with improved outcomes in patients with proximal occlusions. Outcome events included dramatic clinical recovery (DCR) within 2 and 24-hours from tPA-bolus, 3-month mortality, favorable functional outcome (FFO) and functional independence (FI) defined as modified Rankin Scale (mRS) scores of 0-1 and 0-2 respectively. RESULTS: We enrolled 480 AIS patients (mean age 66±15 years, 60% men, baseline National Institutes of Health Stroke Scale score 15). Patients with early recanalization (53%) had significantly (P<0.001) higher rates of DCR at 2-hour (54% vs. 10%) and 24-hour (63% vs. 22%), 3-month FFO (67% vs. 28%) and FI (81% vs. 39%). Three-month mortality rates (6% vs. 17%) and distribution of 3-month mRS scores were significantly lower in the early recanalization group. After adjusting for potential confounders, early recanalization was independently associated with higher odds of 3-month FFO (odds ratio [OR], 6.19; 95% confidence interval [CI], 3.88 to 9.88) and lower likelihood of 3-month mortality (OR, 0.34; 95% CI, 0.17 to 0.67). Onset to treatment time correlated to the elapsed time between tPA-bolus and recanalization (unstandardized linear regression coefficient, 0.13; 95% CI, 0.06 to 0.19). CONCLUSIONS: Earlier tPA treatment after stroke onset is associated with faster tPA-induced recanalization. Earlier onset-to-recanalization time. RESULTS: in improved functional recovery and survival in AIS patients with proximal intracranial occlusions.

Epidemiology of Intracranial and Extracranial Large Artery Stenosis in a Population-Based Study of Stroke in the Middle East.

BACKGROUND: Intracranial large-artery disease (LAD) is a predominant vascular lesion found in patients with stroke of Asian, African, and Hispanic origin, whereas extracranial LAD is more prevalent among Caucasians. These patterns are not well-established in the Middle East. We aimed to characterize the incidence, risk factors, and long-term outcome of LAD strokes in a Middle-Eastern population. METHODS: The Mashhad Stroke Incidence Study is a community-based study that prospectively ascertained all cases of stroke among the 450,229 inhabitants of Mashhad, Iran between 2006 and 2007. Ischemic strokes were classified according to the TOAST criteria. Duplex-ultrasonography (98.6%), MR-angiography (8.3%), CT-angiography (11%), and digital-subtraction angiography (9.7%) were performed to identify involvements. Vessels were considered stenotic when the lumen was occluded by >50%. RESULTS: We identified 72 cases (15.99 per 100,000) of incident LAD strokes (mean age 67.6 ± 11.7). Overall, 77% had extracranial LAD (58% male, mean age 69.8 ± 10.3; 50 [89%] carotid vs. 6 [11%] vertebral artery), and the remaining 23% (56% male, mean age 60.2 ± 13.4; 69% anterior-circulation stenosis) had intracranial LAD strokes. We were unable to detect differences in case-fatality between extracranial (1-year: 28.6%; 5-year: 59.8%) and intracranial diseases (1-year: 18.8%; 5-year: 36.8%; log-rank; p = 0.1). CONCLUSION: Extracranial carotid stenosis represents the majority of LAD strokes in this population. Thus, public health strategies may best be developed in such a way that they are targeted toward the risk factors that contribute to extracranial stenosis.

Acute management of stroke in Iran: Obstacles and solutions.

Background: Stroke is among the leading causes of mortality and permanent disability in the world. Iran is located in the stroke belt and has a high age-adjusted stroke incidence rate. In this multistep prospective qualitative study, we aimed at investigating the status and challenges of stroke management in Iran and explore possible solutions. Methods: In the first and second phase, we attempted to define the status of stroke management in Iran by searching the relevant literature and conducting semi-structured interviews with health-care providers in thirteen hospitals located in seven large cities in Iran. In the third phase, we tried to recommend possible solutions based on international standards and experience, as well as interviews with stroke experts in Iran and the United States. Results: Little public awareness of stroke symptoms and its urgency, low prioritization for stroke management, and an inadequate number of stroke-ready hospitals are some of the major obstacles toward timely treatment of stroke in Iran. Every hospital in our pool except two hospitals had guideline-based algorithms for the administration of intravenous thrombolysis. However, there was no single call activation system for stroke alert. Data from some of the centers showed that hospital arrival of stroke patients to final decision-making took 116-160 minutes. Although there were four endovascular programs in our target areas, there was no center with 24-hour coverage. Conclusion: There are many challenges as well as potentials for improvement of stroke care in Iran. Improving public knowledge of stroke and establishing an organized and comprehensive stroke program in the hospitals will improve acute stroke management in Iran. The Iranian ministry of health should define and advocate the establishment of stroke centers, track the rate of death and disability from stroke, introduce pathways to improve the quality of stroke care through national data monitoring systems, and eliminate disparities in stroke care.

Safety of Intravenous Thrombolysis among Stroke Patients Taking New Oral Anticoagulants--Case Series and Systematic Review of Reported Cases.

BACKGROUND: Current guidelines do not recommend the administration of intravenous tissue plasminogen activator (IV-tPA) to patients with acute ischemic stroke (AIS) who take new oral anticoagulants (NOACs). We present a multicenter case series of IV-tPA use while the patients are on NOACs, as well as a systematic review of the literature. METHODS: We reviewed the medical records of consecutive patients on NOACs who received IV-tPA for symptoms of AIS at four participating stroke centers in the United States and Europe. Safety endpoints were post-thrombolysis symptomatic intracranial hemorrhage (sICH) or other serious systemic bleeding. RESULTS: Between October 2010 and October 2014, 6 patients received IV-tPA for possible AIS while taking dabigatran. None of the patients had sICH or any other hemorrhagic complication. Literature review resulted in a total of 26 patients receiving IV-tPA while on NOACs (dabigatran: 15, rivaroxaban: 10, apixaban: 1). Among them, two patients experienced sICH and died. None of the patients experienced major extracranial hemorrhage; however, minor and asymptomatic hemorrhagic complications were described in 7 patients. Pooled analysis indicates an sICH rate of 6.45% (95% CI by the adjusted Wald method: .8-21.7%). The mean interval between the last dose of NOAC and IV thrombolysis was 12 ± 7.8 [4-28.3] hours. CONCLUSIONS: Although the safety of IV-tPA cannot be definitively confirmed in a small series, consideration of stroke severity and management of hemorrhage risk with general precautions with post-tPA management protocols can justify treatment in the absence of coagulopathy.

Gaps and hurdles deter against following stroke guidelines for thrombolytic therapy in Iran: exploring the problem.

BACKGROUND: Insufficient information is available on the barriers that explain low rates of thrombolytic therapy for acute ischemic stroke (AIS) in developing countries compared with rates in developed societies. By the present study, we aimed to assess the implementation of thrombolytic therapy in the northeast of Iran to explore the gaps and hurdles against thrombolysis as the generally accepted treatment for AIS. METHODS: In a 1-year cohort study among AIS patients admitted to the second largest tertiary neurologic referral center in Iran, those who met the prespecified selection criteria were treated with intravenous recombinant tissue plasminogen activator (rtPA). RESULTS: Among 1,144 patients admitted with AIS, only 14 (1.2%) were treated with rtPA. The mean onset-to-needle and door-to-needle times were 172 and 58 minutes, respectively; 980 (85.6%) patients were initially excluded from the study because of late arrival. Additionally, 60 patients in total were omitted because of either their high age (3.7%) or passing the gold standard time limit for rtPA therapy after preliminary evaluations (1.6%), and 90 more patients (7.9%) were considered not suitable for thrombolysis because of the severity of the symptoms or the higher risk of bleeding on rtPA. CONCLUSIONS: Access to thrombolytic therapy for AIS in Iran is less than in most developed countries but comparable with other developing countries. Awareness campaigns are needed to minimize barriers and improve access to thrombolysis and specialized stroke care in Iran.

Investigating the utility of previously developed prediction scores in acute ischemic stroke patients in the stroke belt.

BACKGROUND: To assess the utility of previously developed scoring systems, we compared SEDAN, named after the components of the score (baseline blood Sugar, Early infarct signs and (hyper) Dense cerebral artery sign on admission computed tomography scan, Age, and National Institutes of Health Stroke Scale on admission), Totaled Health Risks in Vascular Events (THRIVE), Houston Intra-arterial Therapy (HIAT), and HIAT-2 scoring systems among patients receiving systemic (intravenous [IV] tissue plasminogen activator [tPA]) and endovascular (intra-arterial [IA]) treatments. METHODS: We retrospectively reviewed all IV tPA and IA patients presenting to our center from 2008-2011. The scores were assessed in patients who were treated with IV tPA only, IA only, and a combination of IV tPA and IA (IV-IA). We tested the ability of THRIVE to predict discharge modified Rankin scale (mRS) 3-6, HIAT and HIAT-2 discharge mRS 4-6, and SEDAN symptomatic intracerebral hemorrhage (sICH). RESULTS: Of the 366 patients who were included in this study, 243 had IV tPA only, 89 had IA only, and 34 had IV-IA. THRIVE was predictive of mRS 3-6 in the IV-IA (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.30-2.91) and the IV group (OR, 1.71; 95% CI, 1.43-2.04), but not in the IA group. HIAT was predictive of mRS 4-6 in the IA (OR, 3.55; 95% CI, 1.65-7.25), IV (OR, 3.47; 95% CI, 2.26-5.33), and IV-IA group (OR, 6.48; 95% CI, 1.41-29.71). HIAT-2 was predictive of mRS 4-6 in the IA (OR, 1.39; 95% CI, 1.03-1.87) and IV group (OR, 1.36; 95% CI, 1.18-1.57), but not in the IV-IA group. SEDAN was not predictive of sICH in the IA or the IV-IA group, but was predictive in the IV group (OR, 1.54; 95% CI, 1.01-2.36). CONCLUSIONS: Our study demonstrated that although highly predictive of outcome in the original study design treatment groups, prediction scores may not generalize to all patient samples, highlighting the importance of validating prediction scores in diverse samples.

Can STOP Trial Velocity Criteria Be Applied to Iranian Children with Sickle Cell Disease?

BACKGROUND AND PURPOSE: Sickle cell disease (SCD) is strongly linked to stroke across all haplotypes in the pediatric population. Transcranial Doppler (TCD) ultrasound is known to identify the highest risk group in African-Americans who need to receive and stay on blood transfusions, but it is unclear if the same flow velocity cut-offs can be applied to the Iranian population. We aimed to evaluate baseline TCD findings in Iranian children with SCD and no prior strokes. METHODS: Children with genetically confirmed SCD (Arabian haplotype, homozygote) and without SCD (controls) were prospectively recruited from pediatric outpatient clinic over a period of 9 months. We performed TCD in both groups to determine flow velocities in the middle cerebral (MCA) and terminal internal carotid arteries (TICA). RESULTS: Of 74 screened children, 60 met the inclusion/exclusion criteria (62% female; mean age 10±4 years). Baseline characteristics did not differ between the cases and controls, except hemoglobin (Hb) which was significantly lower in the SCD group (P<0.001). The right MCA TAMM (Time Averaged Maximum Mean) was significantly higher than in controls (125+5.52 cm/s vs. 92.5+1.63 cm/s, P<0.001). Left MCA did not show differences. The TICA TAMM was also different between cases and controls (P<0.05). CONCLUSIONS: Among Iranian children with asymptomatic SCD and without receiving recent transfusion TCD velocities are higher as compared to healthy controls but appear much lower than those observed in STOP (Stroke Prevention Trial in Sickle Cell Anemia) studies. We hypothesize that some children at high risk may be present with velocities lower than 170-200 cm/s thresholds. A prospective validation of ethnicity-specific prognostic criteria is warranted.

N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities.

BACKGROUND: There is an expanding field of research investigating the benefits of medicines with multiple mechanisms of action across neurological disorders. N-acetylcysteine (NAC), widely known as an antidote to acetaminophen overdose, is now emerging as treatment of vascular and nonvascular neurological disorders. NAC as a precursor to the antioxidant glutathione modulates glutamatergic, neurotrophic, and inflammatory pathways. AIM AND DISCUSSION: Most NAC studies up to date have been carried out in animal models of various neurological disorders with only a few studies completed in humans. In psychiatry, NAC has been tested in over 20 clinical trials as an adjunctive treatment; however, this topic is beyond the scope of this review. Herein, we discuss NAC molecular, intracellular, and systemic effects, focusing on its potential applications in neurodegenerative diseases including spinocerebellar ataxia, Parkinson's disease, tardive dyskinesia, myoclonus epilepsy of the Unverricht-Lundbor type as well as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. CONCLUSION: Finally, we review the potential applications of NAC to facilitate recovery after traumatic brain injury, cerebral ischemia, and in treatment of cerebrovascular vasospasm after subarachnoid hemorrhage.

A randomized trial to assess the long-term safety of NeuroAiD among Caucasian patients with acute ischemic stroke.

OBJECTIVE: To assess the long-term (up to 6 months) safety profile of a 3-month regimen of NeuroAiD for acute ischemic stroke. METHODS: A total of 190 patients with acute ischemic stroke were identified for eligibility in a randomized, double-blind, placebo-controlled clinical trial, of which 150 patients allocated to either receiving NeuroAiD (80 cases) or placebo (70 cases) were analyzed after dropouts due to absence of baseline data, early death, or noncompliance. Both groups received treatment for three months and followed up for another three months after the completion of the treatment. Occurrence of clinical adverse events and laboratory parameters were assessed at 1 month, 3 months (while under treatment) and 6 months (3 months after the completion of treatment). Statistical comparisons between groups were performed using chi-square test or t-test whenever appropriate. RESULTS: The two groups had comparable baseline characteristics. Mild nausea was more commonly reported in patients taking NeuroAid compared with placebo (P=0.01), of which 9 out of 10 were observed only during the first month of treatment. However, none of the adverse events reported were considered severe or required discontinuation of the study drug. There was no significant change observed in mean arterial blood pressure, haemoglobin, renal and liver laboratory parameters during treatment with NeuroAid and up to 3 months after completion of a 3-month regimen. CONCLUSION: NeuroAiD is safe and does not affect hematologic, hepatic, and renal functions during and long after completion of treatment.

Safety of intravenous tissue plasminogen activator administration with computed tomography evidence of prior infarction.

BACKGROUND: Prior stroke within 3 months excludes patients from thrombolysis; however, patients may have computed tomography (CT) evidence of prior infarct, often of unknown time of origin. We aimed to determine if the presence of a previous infarct on pretreatment CT is a predictor of hemorrhagic complications and functional outcomes after the administration of intravenous (IV) tissue plasminogen activator (tPA). METHODS: We retrospectively analyzed consecutive patients treated with IV tPA at our institution from 2009-2011. Pretreatment CTs were reviewed for evidence of any prior infarct. Further review determined if any hemorrhagic transformation (HT) or symptomatic intracerebral hemorrhage (sICH) were present on repeat CT or magnetic resonance imaging. Outcomes included sICH, any HT, poor functional outcome (modified Rankin Scale score of 4-6), and discharge disposition. RESULTS: Of 212 IV tPA-treated patients, 84 (40%) had evidence of prior infarct on pretreatment CT. Patients with prior infarcts on CT were older (median age, 72 versus 65 years; P=.001) and had higher pretreatment National Institutes of Health Stroke Scale scores (median, 10 versus 7; P=.023). Patients with prior infarcts on CT did not experience more sICH (4% versus 2%; P=.221) or any HT (18% versus 14%; P=.471). These patients did have a higher frequency of poor functional outcome at discharge (82% versus 50%; P<.001) and were less often discharged to home or inpatient rehabilitation center (61% versus 73%; P=.065). CONCLUSIONS: Visualization of prior infarcts on pretreatment CT did not predict an increased risk of sICH in our study and should not be viewed as a reason to withhold systemic tPA treatment after clinically evident strokes within 3 months were excluded.

Predictors of systemic inflammatory response syndrome in ischemic stroke undergoing systemic thrombolysis with intravenous tissue plasminogen activator.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is an inflammatory process associated with poor outcomes in acute ischemic stroke (AIS) patients. However, no study to date has investigated predictors of SIRS in AIS patients treated with intravenous (IV) tissue plasminogen activator (tPA). METHODS: Consecutive patients were retrospectively reviewed for evidence of SIRS during their acute hospitalization. SIRS was defined as the presence of 2 or more of the following: (1) body temperature less than 36°C or greater than 38°C, (2) heart rate greater than 90, (3) respiratory rate greater than 20, or (4) white blood cell count less than 4000/mm or greater than 12,000/mm or more than 10% bands for more than 24 hours. Those diagnosed with an infection were excluded. A scoring system was created to predict SIRS based on patient characteristics available at the time of admission. Logistic regression was used to evaluate potential predictors of SIRS using a sensitivity cutoff of ≥65% or area under the curve of .6 or more. RESULTS: Of 212 patients, 44 had evidence of SIRS (21%). Patients with SIRS were more likely to be black (61% versus 54%; P = .011), have lower median total cholesterol at baseline (143 versus 167 mg/dL; P = .0207), and have history of previous stroke (51% versus 35%; P = .0810). Ranging from 0 to 6, the SIRS prediction score consists of African American (2 points), history of hypertension (1 point), history of previous stroke (1 point), and admission total cholesterol less than 200 (2 points). Patients with an SIRS score of 4 or more were 3 times as likely to develop SIRS when compared with patients with a score of ≤3 (odds ratio = 2.815, 95% confidence interval 1.43-5.56, P = .0029). CONCLUSIONS: In our sample of IV tPA-treated AIS patients, clinical and laboratory characteristics available on presentation were able to identify patients likely to develop SIRS during their acute hospitalization. Validation is required in other populations. If validated, this score could assist providers in predicting who will develop SIRS after treatment with IV tPA.

Racial disparities in early mortality in 1,134 young patients with acute stroke.

We sought to investigate potential racial disparities in early outcomes of young individuals with stroke in an international multicenter study. We evaluated consecutive patients with first-ever acute stroke aged 18-45 years from prospective databases involving 12 tertiary-care stroke centers in North America (n = 2), Europe (n = 6), and Asia (n = 4). Demographics, vascular risk factors, stroke subtypes, pre-stroke functional status, stroke severity, blood pressure parameters, and serum glucose at hospital admission were documented. The outcome events of interest were 30-day mortality and 30-day favorable functional outcome (FFO) defined as modified-Rankin Scale score of 0-1. A total of 1,134 young adults (mean age 37.4 ± 7.0 years; 58.8 % men; 48.6 % Whites, 23.9 % Blacks, and 27.5 % Asians; median baseline National Institutes of Health Stroke Scale score 6 points, interquartile range 2-13) were included in the analyses. The 30-day stroke mortality and FFO rates differed (p < 0.001) across races. After adjusting for potential confounders, race was independently associated with 30-day mortality (p = 0.026) and 30-day FFO (p = 0.035). Blacks had a fourfold higher odds of 30-day stroke mortality in comparison to Asians (OR 4.00; 95 % CI 1.38-11.59; p = 0.011). Whites also had an increased likelihood of 30-day stroke mortality in comparison to Asians (OR 3.59; 95 % CI 1.28-10.03; p = 0.015). Blacks had a lower odds of 30-day FFO in comparison to Whites (OR 0.57; 95 % CI 0.35-0.91; p = 0.018). Racial disparities in early outcomes following first-ever stroke in young individuals appear to be independent of other known outcome predictor variables. Whites appear to have higher likelihood of 30-day FFO and Asians have lower odds of 30-day stroke mortality.

Safety of protocol violations in acute stroke tPA administration.

BACKGROUND: Intravenous (IV) tissue plasminogen activator remains the only approved therapy for acute ischemic stroke (AIS) in the United States; however, less than 10% of patients receive treatment. This is partially because of the large number of contraindications, narrow treatment window, and physician reluctance to deviate from these criteria. METHODS: We retrospectively analyzed consecutive patients who received IV thrombolysis at our stroke center for National Institute of Neurological Disorders and Stroke (NINDS) protocol violations and rates of symptomatic intracerebral hemorrhage (sICH). Other outcome variables included systemic hemorrhage, modified Rankin Scale at discharge, and discharge disposition. RESULTS: A total of 212 patients were identified in our stroke registry between 2009 and 2011 and included in the analysis. Protocol violations occurred in 76 patients (36%). The most common violations were thrombolysis beyond 3 hours (26%), aggressive blood pressure management (15%), elevated prothrombin time (PT) or partial thromboplastin time (PTT) (6.6%), minor or resolving deficits (4.2%), unclear time of onset (3.9%), and stroke within 3 months (3%). There were no significant differences in any of the safety outcomes or discharge disposition between patients with or without protocol violations. Controlling for age, National Institutes of Health Stroke Scale on admission, and glucose on admission, there was no significant increase in sICH (odds ratio: 3.8; 95% confidence interval: .37-38.72) in the patients who had protocol violations. CONCLUSIONS: Despite more than one third of patients receiving thrombolysis with protocol violations, overall rates of hemorrhage remained low and did not differ from those who did not have violations. Our data support the need to expand access to thrombolysis in AIS patients.