Recombinant Tissue Plasminogen Activator Treatment Research Articles

Thrombolysis on Ischemic Stroke Patients with Decreased Level of Consciousness within 4.5 h

Few reports concerned on recombinant tissue plasminogen activator (rt-PA) treatment in stroke patients with decreased consciousness. This study assesses the efficacy and safety of intravenous rt-PA administration within 4.5 h in stroke patients with decreased consciousness. A total of 136 stroke patients with decreased consciousness, who received or not rt-PA intravenously within 4.5 h after stroke onset from Jiangsu province of China from 2009 to 2012, were reviewed retrospectively. Glasgow Coma Scale (GCS), National Institute of Health Stroke Scale (NIHSS), intracranial hemorrhage rate, and mortality were used to determine patient outcome when discharged. A 3-month outcome was calculated by modified Rankin Scale (mRS) with score 0 to 1 considered favorable outcome. Baseline characteristics of two groups were similar. When discharged, no significant differences were observed regarding NIHSS score (P = 0.994) or GCS score (P = 0.591) between groups. After 3 months, 22.8% patients in rt-PA group had favorable outcome as compared with 7.5% patients in control group (P = 0.014). Treatment with rt-PA did not significantly increase incidence of hemorrhage (P = 0.494) or mortality (P = 0.169). Intravenous rt-PA administration within 4.5 h after onset of symptoms benefited stroke patients with abnormal consciousness.

Abstracts for Canadian Stroke Conference

Specogna, AV; Patten, SB; Hill, MD; University of Calgary, Calgary, AB Background: Previous studies have examined predictors of treatment costs after Spontaneous Intracerebral Hemorrhage (ICH) in various countries and healthcare systems. Currently however, there is no clear understanding of which factors are associated with cost in any Canadian setting and thus no way of understanding how to plan ICH healthcare spending. Methods: We used a retrospective case series study design and adjusted linear regression to investigate if an association existed between the total cost of ICH hospital care in a Canadian health centre and age (years), gender (female vs. male), Charlson Comorbidity Index (0 vs. ≥1), in-hospital mortality (alive vs. dead), and having surgery (no vs. yes). Economic, treatment, and patient data were obtained from administrative sources. Total inflation-adjusted hospital cost per discharge was estimated in Canadian Dollars and log transformed for all analyses. Results: Analyses were performed using 987 consecutive ICH discharges from 1999 to 2008. The total cost of ICH hospital care was highly variable (mean cost per discharge=$25,613.96±$36,116.33; min $446.81 to max $326,275.10). Older age (β=–0.0057; 95% CI: –0.0103 to –0.0011) and death in hospital (β=–0.4859; 95% CI: –0.6357 to –0.3342) were significantly associated with lower total hospital cost per discharge. Whereas Charlson Comorbidity Index of ≥1 (β=0.6489; 95% CI: 0.5063 to 0.7916) and having surgery (β=1.3552; 95% CI: 1.1893 to 1.5210) were significantly associated with higher total hospital cost per discharge. Gender was not significantly associated with cost (β=0.0727; 95% CI: –0.0679 to 0.2134). Conclusions: To our knowledge this is the first study to examine predictors of ICH treatment costs in Canada. In a Canadian health centre, ICH treatment costs were significantly associated with patient age, level of comorbidity, in-hospital mortality, and surgical treatment. This study provides evidence that it may be reasonable to consider …

Thrombolysis Outcomes among Obese and Overweight Stroke Patients: An Age- and National Institutes of Health Stroke Scale–matched Comparison

Whether obese and overweight stroke patients respond differently to intravenous thrombolysis is unclear. The purpose of this study is to determine the influence of obesity and risk components of metabolic syndrome to stroke recovery in patients undergoing intravenous thrombolysis. Outcomes after recombinant tissue plasminogen activator treatment were compared between obese (body mass index [BMI] >30 kg/m(2)), overweight (BMI 25-30 kg/m(2)), and normal weight (BMI <25 kg/m(2)) patients. The association between BMI, risk components of the metabolic syndrome, and dose of recombinant tissue plasminogen activator per kilogram of body weight to stroke outcomes were assessed in a multivariable model. A total of 169 patients (mean age 75 years; baseline National Institutes of Health Stroke Scale score 11) were included. No differences in the frequency of symptomatic intracranial hemorrhage and poor functional recovery were observed among obese, overweight, and normal weight patients. A linear trend toward worse stroke recovery was observed in patients with a greater number of metabolic risk components (P for trend .043). By contrast, there were no significant associations between the number of risk components of metabolic syndrome with respect to symptomatic intracranial hemorrhage. Using stepwise regression analyses, age, baseline stroke severity, and the number of risk components of the metabolic syndrome accounted for 52% variation in functional recovery after intravenous thrombolysis. Acute stroke outcomes do not differ between obese and overweight patients undergoing intravenous thrombolysis. The number of metabolic risk components contributes more significantly to functional recovery following intravenous thrombolysis.

Abstract 62: Thrombolysis with Intravenous Recombinant Tissue Plasminogen Activator 3 to 4.5 h After Acute Ischemic Stroke In China

Background and Purpose_ Extending the time window is an important strategy in maximizing thrombolytic therapy in stroke patients. ECASS III had examined a 3 to 4.5h time window and showed a benefit to treated patients. However, little is known about safety and efficacy of intravenous recombinant tissue plasminogen activator(rtPA) treatment in the 3 to 4.5 h time window of acute ischemic stroke in chinese people. Methods_ We analyzed data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China(TIMS-China)- a prospective, multicentric cohort study of intravenous alteplase treatment with patient enrollment from 67 centres across China. Patients who were fully compliant with Chinese product characteristics criteria of alteplase except for the time window and within 4.5 h after symptom onset were included. The symptomatic intracranial hemorrhage, mortality and 90-day outcome of patients treated between 3 and 4.5 h and within 3 h of symptom onset were compared. Results_ A total of 574 patients were included. 165 patients received alteplase between 3 and 4.5 h of symptom onset and 409 patients received altepase within 3 h. In the 3-4.5h cohort, treatment was started at a median of 80 min later after symptom onset (220 min versus 140 min, p&lt;0.0001). After adjustment for the baseline variables including age, sex, past history, aspirin treatment at stroke onset, baseline NIHSS, et al, there were no significant differences between the 3-4.5h cohort and the within 3h cohort for any outcome measure-rate of symptomatic intracranial haemorrhage(2.42% versus 1.47%, p=0.70); mortality(5.70% versus 6.33%, p=0.52); and independence(70.25% versus 64.56%, p=0.15). Conclusion_ Our study suggests that intravenous rtPA treatment also remains safe and effective for chinese people between 3 and 4.5 h of symptom onset after acute ischemic stroke.

Abstract 156: Impact Of Obesity And Metabolic Syndrome In Stroke Patients Undergoing Intravenous Thrombolysis

Background: The influence of high body mass index (BMI) in acute stroke patients treated with intravenous thrombolysis has not been extensively studied. Previous studies have observed an “obesity paradox” among stroke patients, where better outcomes were observed among overweight and obese patients. The purpose of this study is to determine the influence of obesity and risk components of metabolic syndrome to stroke recovery in patients undergoing intravenous recombinant tissue plasminogen activator (rtPA) treatment. Methods: Patients with acute ischemic stroke who received intravenous rtPA within three-hour from symptom onset at St. Marys Hospital, Mayo Clinic, Rochester, between April 2006 and January 2011, were included in this study. Information on vascular risk factors, stroke severity, and baseline hemodynamic and laboratory indices, were collected. Study outcomes, consisting symptomatic intracerebral hemorrhage (sICH) and poor functional recovery (modified Rankin scale &gt;2), were compared between obese (body mass index, BMI &gt;30 kg/m 2 ), overweight (BMI 25-30 kg/m 2 ) and normal weight (BMI &lt;25 kg/m 2 ) patients. The association between BMI, risk components of the metabolic syndrome and dose of rtPA per kg body weight to stroke outcomes were assessed in a multivariable model. Results: A total of 158 patients (mean age, 75 years; baseline NIHSS, 11), frequency-matched by age and baseline stroke severity, were included in this study. No differences in the frequency of SICH and poor functional recovery were observed among obese, overweight and normal weight patients, before and after adjusting for their baseline characteristics. A linear trend towards worse stroke recovery was observed in patients with a greater number of metabolic risk components (p-trend=0.043). By contrast, there were no significant associations between the number of risk components of metabolic syndrome with respect to sICH. Using stepwise regression analyses, age, baseline stroke severity and the number of risk components of the metabolic syndrome accounted for 52% variation in functional recovery following rtPA treatment. Conclusions: Acute stroke outcomes do not differ between obese and overweight patients. The presence of metabolic risk factors contributes significantly to functional outcomes following rtPA treatment. These results suggest that decreasing the prevalence of metabolic syndrome in the community could reduce the societal burden of stroke-related disability.

Use of tissue plasminogen activator to treat intracardiac thrombosis in extremely low-birth-weight infants

Intracardiac thrombosis is a life-threatening complication of extreme prematurity. We describe the use of tissue plasminogen activator to treat intracardiac thrombosis in extremely low-birth-weight preterm infants. Case series, literature review, and practice guideline for recombinant tissue plasminogen activator treatment of intracardiac thrombosis in extremely low-birth-weight preterm infants. Neonatal intensive care. Four extremely low-birth-weight preterm infants coincidentally diagnosed with intracardiac thrombosis during neonatal intensive care. Recombinant tissue plasminogen activator in a starting dose of 20 μg/kg/hr, increasing to 200-400 μg/kg/hr, infused for 2-6 days. Thrombolytic therapy with recombinant tissue plasminogen activator helped achieve rapid clot resolution in all infants and none had any major hemorrhagic complication associated with treatment. Tissue plasminogen activator may safely be used to treat intracardiac thrombosis in extremely low-birth-weight preterm infants. Close monitoring of therapy is imperative. Further data are required to confirm the safety of tissue plasminogen activator in preterm infants.

α-linolenic omega-3 fatty acid for stroke protection: from brain preconditioning paradigm to nutrition

Stroke is the third leading cause of death, due to its high incidence, the severity of the insult, and lack of treatment options. The only therapeutic is restoration of cerebral blood flow achieved by recombinant tissue plasminogen activator treatment, but only approximately 5% of patients receive it. In addition, therapeutics aimed at achieving neuroprotection by blocking the ischemic cascade, as identified in numerous preclinical studies, failed in clinical trials. This failure in translation from experimental models to clinical trials led to a re-evaluation of properties which would constitute the ‘‘best-in class’’ therapeutics to be used against stroke. Given that neuroprotection appears ineffective per se, an emerging direction is to identify therapies, probably combinatorial in nature, which protect the whole neurovascular unit and target timedependent neurotoxic mechanisms. Molecules that activate complex cellular signaling cascades that render the brain resistant to subsequent ischemia, known as preconditioners, offer a novel perspective in stroke protection. Preconditioning elicits complex endogenous neuroprotective responses that act by pleiotropic mechanisms to block death pathways, promote survival pathways and increase resistance. In addition to chemical preconditioners, natural/endogenous compounds such as adenosine, glutamate, lysophospholipids, and omega-3 polyunsaturated fatty acids have been demonstrated to be excellent preconditioners. Consequently, a major new concept in preconditioning to combat stroke is introduced, which is preconditioning achieved through supplementation of an essential item in diet or as a nutraceutical. Several epidemiologic studies suggested a beneficial effect of a seafood/omega-3-enriched diet in cerebral diseases, but the omega-3-induced protective mechanisms are still poorly identified. This review highlights how α-linolenic acid (ALA), the omega-3 polyunsaturated fatty acid precursor, protects the brain from in vivo and in vitro models of stroke, thus potentially fulfilling the goal of identifying the ‘‘best-in class’’ therapeutics against stroke. Also described is the surprising pleiotric nature of ALA in protecting neurons, vasodilating brain arteries and stimulating neuroplasticity. Importantly, feasibility of delivery has been demonstrated, since ALA supplementation can be achieved through modification of the daily diet, for which prevention of stroke-induced mortality and cerebral damage has been confirmed. Therefore evaluating ALA as an interesting preconditioner against stroke represents a novel and extremely relevant concept in the context of nutraceutical and functional food development.

Expedited Computed Tomography Perfusion and Angiography in Acute Ischemic Stroke: A Feasibility Study

BackgroundAcute ischemic stroke diagnosis and treatment are among the most challenging in Emergency Medicine. Perfusion computed tomography (CTP) can increase the sensitivity for detecting ischemic stroke and, especially with the addition of CT angiography (CTA), improve decision-making regarding thrombolytic therapy compared to non-contrast computed tomography (NCCT) alone. However, because acute stroke protocols do not generally include procedures for multimodal imaging, they are not commonly performed. In addition, there is concern that additional studies could delay or preclude therapy in patients otherwise eligible for thrombolytic therapy. ObjectivesTo demonstrate the feasibility of perfusion CTP and CTA in addition to NCCT of the brain in the emergency assessment of patients with acute ischemic stroke. Methods: Starting January 2008, multimodal (CTP and CTA) imaging was added to NCCT in the Emergency Department (ED) initial assessment of patients with stroke of ≤ 5 h duration. Over the subsequent 9 months, we measured the time from ED arrival to imaging and to recombinant tissue plasminogen activator (rt-PA) treatment and compared these times to patients evaluated with CT alone. ResultsFrom January to October 2008, 95 patients had CTP and CTA studies in addition to NCCT for acute ischemic stroke. There were no differences between the average time to CT study or to rt-PA treatment between patients evaluated with multimodal CT imaging and patients assessed with NCCT alone. ConclusionsCombining CTP and CTA with NCCT is feasible and does not adversely increase the time to CT imaging or rt-PA treatment in patients with acute ischemic stroke.

Rapid revascularization reverses cerebral and myocardial ischemia arising from aortic dissection

Thrombolytic therapy is relatively contraindicated in aortic dissection (AD)–related cerebral and myocardial ischemia for high risk of bleeding. We report a 52-year-old woman experiencing acute cerebral and myocardial ischemia arising from AD. Intravenous recombinant tissue plasminogen activator treatment was held immediately when carotid duplex revealed common carotid artery dissection and chest computed tomography confirmed the existence of type A AD. Emergent surgery completely reversed her neurologic deficit and myocardial injury. We suggest that carotid duplex could be a useful tool to detect AD-related stroke before thrombolytic therapy and would not delay the timing for treatment.

Prevalence, Predictors and Prognosis of Post-Stroke Hyperglycaemia in Acute Stroke Trials: Individual Patient Data Pooled Analysis from the Virtual International Stroke Trials Archive (VISTA)

Background: Post-stroke hyperglycaemia (PSH) is associated with higher mortality and dependence, but further data on predictors of PSH and its evolution over time are required. We examined the prevalence, predictors, and prognosis of acute PSH using data from well-characterised clinical trials in the VISTA database. Methods: Data were extracted for individual participants enrolled <24 h after stroke with ≧1 blood glucose readings documented. PSH was defined as glucose >7.0 mmol/l. Outcome measures were: (1) prevalence of PSH; (2) predictors of PSH by binary logistic regression; (3) mortality, and (4) favourable functional outcome [modified Rankin Scale (mRS) score <2] at day 90. Results: For 2,649 subjects treated at a median 5.5 h after admission, PSH was present in 1,126 (42.6%, 95% CI 40.7–44.5) on admission and within the first 48 h in 1,421 (53.7%, 95% CI 51.8–55.6). PSH developed between 24 and 48 h in 19.4% (95% CI 17.5–21.4) of initially normoglycaemic subjects. Admission and 48-hour PSH were predicted predominantly by a history of diabetes (for admission PSH: OR 7.40, 95% CI 5.60–9.79) and less clearly by stroke severity. Favourable outcome (mRS <2) at day 90 was less likely with PSH within the first 48 h, advanced age, and higher NIHSS score, and more likely with recombinant tissue plasminogen activator treatment. Conclusions: Over 40% of ischaemic stroke patients are hyperglycaemic on admission, and 20% of those who are initially normoglycaemic develop hyperglycaemia within 48 h. Diabetes is the strongest predictor of acute hyperglycaemia. Hyperglycaemia within the first 48 h is independently associated with higher mortality and poorer functional outcome, with an absolute increase of 12.9%.

Intravitreal recombinant tissue plasminogen activator without and with additional gas injection in patients with submacular haemorrhage associated with age‐related macular degeneration

To compare intravitreal recombinant tissue plasminogen activator (rt-PA) treatment with and without gas injection in patients with submacular haemorrhage associated with age-related macular degeneration. We conducted a retrospective, non-randomized comparative case study of 110 eyes from 76 women and 34 men (mean age 78.1 ± 6.9 years). Evaluations of the data were performed for baseline visit (t1), and visits 1-3 weeks (t2), 3 months (t3) and 6 months after (t4). The patients were classified according to gas treatment into group A (without gas, n = 46) and group B (with gas, n = 64) and according to rt-PA-dosage into group A1 and B1 (50 μg), group A2 and B2 (100 μg), and group A3 and B3 (200 μg). At t4, the patients in group A had a median increase of 0.4 logMAR, and those in group B had a decrease of 0.1 logMAR (p = 0.183). The best corrected visual acuity (BCVA) remained stable or increased in 55% and 62% of patients in groups A and B, respectively (p = 0.151), in 50% and 68% of patients in groups A1 and B1, respectively (p = 0.620), in 40% and 100% of patients in groups A2 and B2, respectively (p = 0.250), and in 75% and 63% of patients in groups A3 and B3, respectively (p = 0.463). Complications were observed in 13.6% of patients. Best results were obtained in patients treated with 50 and 100 μg of rt-PA and in those cases BCVA development was more beneficial if additional gas was injected.

Patient-Level and Hospital-Level Determinants of the Quality of Acute Stroke Care

Quality of care may be influenced by patient and hospital factors. Our goal was to use multilevel modeling to identify patient-level and hospital-level determinants of the quality of acute stroke care in a stroke registry. During 2001 to 2002, data were collected for 4897 ischemic stroke and TIA admissions at 96 hospitals from 4 prototypes of the Paul Coverdell National Acute Stroke Registry. Duration of data collection varied between prototypes (range, 2-6 months). Compliance with 8 performance measures (recombinant tissue plasminogen activator treatment, antithrombotics < 24 hours, deep venous thrombosis prophylaxis, lipid testing, dysphagia screening, discharge antithrombotics, discharge anticoagulants, smoking cessation) was summarized in a composite opportunity score defined as the proportion of all needed care given. Multilevel linear regression analyses with hospital specified as a random effect were conducted. The average hospital composite score was 0.627. Hospitals accounted for a significant amount of variability (intraclass correlation = 0.18). Bed size was the only significant hospital-level variable; the mean composite score was 11% lower in small hospitals (≤ 145 beds) compared with large hospitals (≥ 500 beds). Significant patient-level variables included age, race, ambulatory status documentation, and neurologist involvement. However, these factors explained < 2.0% of the variability in care at the patient level. Multilevel modeling of registry data can help identify the relative importance of hospital-level and patient-level factors. Hospital-level factors accounted for 18% of total variation in the quality of care. Although the majority of variability in care occurred at the patient level, the model was able to explain only a small proportion.

Response to Letter by Chan

Response: We appreciate the comments by Chan concerning our article entitled “Outcomes of Thrombolytic Therapy for Acute Ischemic Stroke in Chinese: The Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) Study.”1 We agree that the rate of patients receiving recombinant tissue plasminogen activator treatment is important. However, we do not agree with Chan’s statement that the main key …

VIDEO MICROSCOPE RECORDING OF THE DYNAMIC COURSE OF THROMBOSIS AND THROMBOLYSIS OF THE RETINAL VEIN IN RABBITS

The purpose of this study was to investigate the dynamic course of experimental thrombosis and thrombolysis of the retinal veins. Dynamic changes in the blood flow in the retinal veins were documented on a digital recorder through a microscope-mounted video camera and were analyzed on a monitor by video playback. Photochemical thrombus formation was induced by intravenous injection of 30% Rose Bengal followed by endoillumination of individual branch retinal veins of the eyes of 20 anesthetized pigmented rabbits. Subsequently, 10 rabbits were treated with an infusion in an ear vein of 3 mg/kg recombinant tissue plasminogen activator, whereas 10 control rabbits were administered with similar volumes of normal saline solution. Occlusion and recanalization were confirmed histologically and assessed by video microscopy. At the site exposed to light, photochemical injury resulted in the formation of a white thrombus, stagnation of blood flow, and subsequent complete venous occlusion in 20 rabbits. In this study, of the 10 animals in the recombinant tissue plasminogen activator treatment group, 9 (90%) showed evident thrombolysis, whereas none of the control group animals showed evident thrombolysis. The video showed that the massive thrombus disrupted into nonuniform fragments, which were quickly washed away by the blood flow, and the circulation was reestablished with no recurrence of secondary obstruction. In vivo data suggest that video microscopy may provide a visual approach for observing the dynamic changes occurring during experimental thrombus formation and lysis by the early administration of recombinant tissue plasminogen activator; this approach may assist in future investigation of thrombus research of ocular fundus.

Quality of Care and Outcomes in Patients With Diabetes Hospitalized With Ischemic Stroke

Diabetes is a common comorbid disease in stroke patients and has a strong influence on stroke-related outcomes, including stroke recurrence. We sought to examine the quality of care and in-hospital outcomes in patients with diabetes in the Get With the Guidelines-Stroke (GWTG-Stroke) program. Data were obtained from 415 926 ischemic stroke patients from 1070 United States hospitals that participated in GWTG-Stroke between 2003 and 2008. We analyzed the relationships between diabetes and quality of care, in-hospital mortality, and discharge home using multivariable logistic regression. There were 130 817 (31%) ischemic stroke patients with diabetes. Quality of care received by patients with and without diabetes was similar except for intravenous recombinant tissue plasminogen activator (rt-PA) and cholesterol treatment. Fifty-four percent of patients with diabetes who arrived within 2 hours of onset received rt-PA compared to 60.8% of patients without diabetes (adjusted odds ratio [aOR], 0.83; 95% CI, 0.79-0.88). Almost 80% of patients with diabetes were discharged on cholesterol treatment compared to 71% of patients without diabetes (aOR, 1.40; 95% CI, 1.37-1.44). Diabetes patients were less likely to be discharged home (aOR, 0.80; 95% CI, 0.78-0.81) and had a higher risk of in-hospital death (aOR, 1.12; 95% CI, 1.08-1.15). Quality of care among patients with and without diabetes was similar except for rt-PA and cholesterol treatment. Diabetes was associated with worse stroke-related outcomes. Greater quality-improvement efforts to increase the use of rt-PA and other secondary prevention treatments in patients with diabetes are warranted.

Cost-Effectiveness of Patient Selection Using Penumbral-Based MRI for Intravenous Thrombolysis

Better selection of patients for intravenous recombinant tissue plasminogen activator (IV tPA) treatment may improve clinical outcomes. We examined the cost-effectiveness of adding penumbral-based MRI to usual computed tomography (CT)-based methods to identify patients for IV tPA treatment. A decision-analytic model estimated the lifetime costs and outcomes associated with penumbral-based MRI selection in a patient population similar to that enrolled in the IV tPA clinical trials. Inputs were obtained from published literature, clinical trial data, claims databases, and expert opinion. Outcomes included cost per life-year saved and cost per quality-adjusted life-year (QALY) gained. Costs and outcomes were discounted at 3% annually. Sensitivity analyses were conducted. The addition of penumbral-based MRI selection increased total cost by $103 over the patient's remaining lifetime. Penumbral-based MRI selection resulted in favorable outcomes (modified Rankin Scale <or=1) more often than CT-based selection (36.66% versus 35.06%) with an incremental cost per life year of $1840 and an incremental cost per QALY of $1004. Multivariate sensitivity analysis predicted cost-effectiveness (<or=$50,000 per QALY) in 99.7% of simulation runs. Selecting ischemic stroke patients for IV tPA treatment using penumbral-based MRI after routine CT may increase overall acute care costs, but the benefit is large enough to make this highly cost-effective. This economic analysis lends further support to the consideration of a paradigm shift in acute stroke evaluation.

Safety and Efficacy of MRI-Based Selection for Recombinant Tissue Plasminogen Activator Treatment: Responder Analysis of Outcome in the 3-Hour Time Window

Introduction: The use of MRI may alter the target population for intravenous recombinant tissue plasminogen activator (rtPA) treatment relative to conventional CT. If selection changes, it remains crucial to demonstrate safety and efficacy of rtPA for the overall population, as well as in subpopulations hypothesized to benefit from MRI. Materials and Methods: Clinical outcome and incidence of symptomatic intracerebral hemorrhage (ICH) was recorded in 112 consecutive patients treated with intravenous rtPA (0–3 h) with MRI as first-choice imaging modality. According to the responder analysis, favorable outcome was separately defined for mild (NIHSS <8; n = 51), moderate (NIHSS 8–14; n = 30) and severe (NIHSS >14; n = 31) stroke. Results: Eighty-three patients were treated with rtPA after MRI, and 29 after CT. Adjusted for baseline severity, 42% of all patients had a favorable outcome, compared to 37% in NINDS. Among patients with severe stroke, MR-selected patients showed a good outcome in 52% of patients compared to 29% in NINDS (p < 0.05). Symptomatic ICH occurred in 2 patients (1.9 %), and 7 patients died during hospitalization (6.3%). Conclusion: MRI-based rtPA is safe and time-efficient. Outcome data compares well with NINDS data. Diagnostic information obtained from multimodal MRI may affect the target group. Our data support the hypothesized benefit of MRI in patients with severe stroke.

Cosmic Implications of NXY-059

The SAINT studies on NXY-0591,2 have reinvigorated debate over the momentous issues of neuroprotection and the development of novel stroke therapeutics. Some may argue there is little new ground that NXY-059 has unearthed and, in fact, the clinical trials merely confirm that as a strategy, neuroprotection has not been shown to be effective. Editorials in high-profile journals have sent out the clarion call to terminate research on neuroprotection given decades of work, which has uniformly led to failure after failure in clinical studies.3 These sentiments are premature and ignore studies showing that hypothermia improves outcome in patients after cardiac arrest, a major cause of global cerebral ischemia.4,5 Proof for the neuroprotection concept has therefore already been established. Despite decades of neutral clinical trials, there still remains optimism among the stroke academic community. A majority of university-affiliated stroke neurologists in the United States in a recent survey still believe neuroprotection is a viable therapeutic strategy, although admittedly, that survey was conducted between the SAINT I and SAINT II publications.6 However, the question whether neuroprotection will ever work in stroke has been overshadowed by the larger issue of whether animal studies, which serve as the foundation for the development of stroke therapeutics, are even relevant to our patients with acute stroke. In the discussion section of the SAINT II article, the authors write, “it is possible that the animal models of acute focal infarction are not relevant to the patient population; they certainly are insufficient to guarantee a positive clinical-trial result.” Have all prior neuroprotective agents failed in clinical studies because rodent stroke is not relevant to human stroke? This is a key question. Substantial reductions in infarct size in rodents with stroke treated with various types of purported neuroprotective agents would seem to support this view. There …

Upgraded Acute Stroke Care Including Thrombolysis Is Associated with Reduced Length of Hospital Stay among Non-Stroke Patients

Background: Implementing thrombolytic therapy in a stroke unit (SU) profoundly affects the resources available to all patients admitted for suspected acute stroke. We examined the benefits of an acute stroke service to non-stroke patients in terms of length of hospitalization, and estimated the economic impact in terms of derived costs. Methods: We performed a historical follow-up study of 792 non-stroke patients admitted to our SU for suspected stroke before, during and after implementing thrombolysis as part of our service. Data on demographic and clinical characteristics, including imaging data and final diagnoses, and length of stay (LOS) were collected prospectively. Multivariate logistic regression analysis was performed to identify variables associated with LOS. Results: Median LOS for non-stroke patients in the SU decreased from 43.8 h (interquartile range, 19–96) to 23.5 h (16–44) after implementing thrombolytic therapy. Total hospital LOS for non-stroke patients decreased from 52.7 (22–147) to 28.7 (21–124) h during the same period. Initial magnetic resonance imaging was associated with shorter LOS in the SU. The derived cost reductions from shorter LOS reduced the costs of implementing recombinant tissue plasminogen activator treatment. Conclusions: Stroke care reorganization following the introduction of thrombolytic treatment was associated with a 50% reduction in LOS for non-stroke patients admitted to the SU. Reduced LOS in the SU for non-stroke patients could further add to the cost-effectiveness of thrombolytic treatment.

Salvage of a congested DIEAP flap with subcutaneous recombinant tissue plasminogen activator treatment

Thrombolytic agents are frequently employed in the treatment of thrombosis in combination with early surgical exploration and management. Recombinant tissue plasminogen activator is a second generation thrombolytic agent, which acts specifically at the site of the haemostatic clot with minimal side effects. In this paper, we present a case with venous congestion of the deep inferior epigastric artery perforator (DIEAP) flap, despite a patent anastomosis, in which we achieved a successful outcome with subcutaneous recombinant tissue plasminogen activator treatment.