Aslam M. Khaja

Is Intra-Arterial Thrombolysis Safe After Full-Dose Intravenous Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke?

Background and Purpose— The optimal approach for acute ischemic stroke patients who do not respond to intravenous recombinant tissue plasminogen activator (IV rt-PA) is uncertain. This study evaluated the safety and response to intra-arterial thrombolytics (IATs) in patients unresponsive to full-dose IV rt-PA. Methods— A case series from a prospectively collected database on consecutive acute ischemic stroke patients treated with IATs after 0.9 mg/kg IV rt-PA during a 7-year interval was collected. Primary outcome measures included symptomatic intracranial hemorrhage and mortality. As indicators of response, secondary outcome measures were recanalization and discharge disposition. Results— Sixty-nine patients (mean±SD age, 60±13 years; range, 26 to 85 years; 55% male) with a median pretreatment National Institutes of Health Stroke Scale score of 18 (range, 6 to 39) were included. IV rt-PA was started at 124±32 minutes (median, 120 minutes) and IAT, at 288±57 minutes (median, 285 minutes). IATs consisted of reteplase (n=56), alteplase (n=7), and urokinase (n=6), with an average total dosage of 2.8 U, 8.6 mg, and 700 000 U, respectively. Symptomatic intracranial hemorrhage occurred in 4 of 69 (5.8%) patients; 3 cases were fatal. Recanalization was achieved in 50 (72.5%) and a favorable outcome (home or inpatient rehabilitation) in 38 (55%). Conclusions— IAT therapy after full-dose IV rt-PA in patients with persisting occlusion and/or lack of clinical improvement appears safe compared with IV rt-PA alone or low-dose IV rt-PA followed by IAT. A high rate of recanalization and favorable outcome can be achieved.

Intraventricular hemorrhage: Anatomic relationships and clinical implications

Background: Spontaneous intracerebral hemorrhage (ICH) is frequently associated with intraventricular hemorrhage (IVH), which is an independent predictor of poor outcome. The purpose of this study was to examine the relationship between ICH volume and anatomic location to IVH, and to determine if ICH decompression into the ventricle is truly beneficial. Methods: We retrospectively analyzed the CT scans and charts of all patients with ICH admitted to our stroke center over a 3-year period. Outcome data were collected using our prospective stroke registry. Results: We identified 406 patients with ICH. A total of 45% had IVH. Thalamic and caudate locations had the highest IVH frequency (69% and 100%). ICH volume and ICH location were predictors of IVH (p < 0.001). Within each location, decompression ranges (specific volume ranges where ventricular rupture tends to occur) were established. Patients with IVH were twice as likely to have a poor outcome (discharge modified Rankin scale of 4 to 6) (OR 2.25, p = 0.001) when compared to patients without IVH. Caudate location was associated with a good outcome despite 100% incidence of IVH. Spontaneous ventricular decompression was not associated with better outcome, regardless of parenchymal volume reduction (p = 0.72). Conclusions: Intraventricular hemorrhage (IVH) occurs in nearly half of patients with spontaneous intracerebral hemorrhage (ICH) and is related to ICH volume and location. IVH is likely to occur within the “decompression ranges” that take into account both ICH location and volume. Further, spontaneous ventricular decompression does not translate to better clinical outcome. This information may prove useful for future ICH trials, and to the clinician communicating with patients and families. GLOSSARY: ANOVA = analysis of variance; EVD = external ventricular drainage; HSD = honestly significant differences; ICC = interclass correlation coefficient; ICH = intracerebral hemorrhage; IVH = intraventricular hemorrhage; LOS = length of stay; mRS = modified Rankin Scale.

Established treatments for acute ischaemic stroke

This article reviews the recommended management of patients presenting to accident and emergency departments with acute ischaemic stroke, and focuses on thrombolysis. The review includes initial management, recommended clinical, laboratory, and radiographic examinations. Appropriate general medical care, consisting of monitoring of oxygenation, fever, blood pressure, and blood glucose concentrations are examined. Criteria for thrombolysis with intravenous recombinant tissue plasminogen activator (rt-PA) are discussed. Complications of rt-PA therapy, such as haemorrhagic transformation and angio-oedema, are reviewed. An approach to management of rt-PA complications is outlined. Only a small percentage of acute ischaemic stroke patients meet criteria for rt-PA; therefore, alternative acute treatment strategies are also discussed. Acute medical and neurological complications in stroke patients are analysed, along with recommendations for treatment.

Thrombus Burden Is Associated With Clinical Outcome After Intra-Arterial Therapy for Acute Ischemic Stroke

Background and Purpose— Studies have established a relation between recanalization and improved clinical outcome in acute ischemic stroke patients; however, intra-arterial clot size has not been routinely assessed. The aim of the study was to determine the impact of intra-arterial thrombus burden on intra-arterial treatment (IAT) and clinical outcome. Methods— A retrospective review of our IAT stroke database included procedure time, recanalization, symptomatic intracranial hemorrhage, poor outcome (modified Rankin Scale score ≥4 at discharge), and mortality. The modified Thrombolysis in Myocardial Infarction thrombus grade was dichotomized into grades 0 to 3 (no clot or moderate thrombus, <2 vessel diameters) versus grade 4 (large thrombus, >2 vessel diameters). Results— Data were collected on 135 patients with thrombus grading. The baseline median National Institutes of Health Stroke Scale score was higher in patients of grade 4 compared with grades 0 to 3 (19 vs 17, P=0.012). Grade 4 thrombi required longer (median, range) times for IAT (113, 37 to 415 minutes vs 74, 22 to 215 minutes, respectively; P<0.001) and higher rates of mechanical clot disruption (wire, angioplasty, snare, stent, or Merci retriever) compared with grades 0 to 3 (76% vs 53%, P=0.005). There were no differences in rates of symptomatic intracranial hemorrhage (6.6% vs 4.1%, P=0.701) or recanalization (50% vs 61%, P=0.216) in grade 4 versus grades 0 to 3. Multivariate analysis adjusted for age, baseline National Institutes of Health Stroke Scale score, and artery of involvement showed that grade 4 thrombi were independently associated with poor outcome (odds ratio=2.4; 95% CI, 1.06 to 5.57; P=0.036) and mortality (odds ratio=4.0; 95% CI, 1.2 to 13.2; P=0.023). Conclusions— High thrombus grade as measured by the modified Thrombolysis in Myocardial Infarction criteria may be a risk factor that contributes to poor clinical outcome.

Aggressive Blood Pressure–Lowering Treatment Before Intravenous Tissue Plasminogen Activator Therapy in Acute Ischemic Stroke

BACKGROUND Patients with acute ischemic stroke (AIS) commonly have elevated blood pressure (BP). Guidelines have recommended against treatment with intravenous tissue plasminogen activator (tPA) when aggressive measures such as continuous infusion with nicardipine hydrochloride are required to maintain BP lower than 185/110 mm Hg. We evaluated the effect of elevated BP and its management on clinical outcomes after tPA therapy in AIS. OBJECTIVES To evaluate safety and outcome in patients with AIS who require treatment to lower BP before tPA therapy and to compare safety and outcome in patients who received aggressive treatment with nicardipine with those who received labetalol hydrochloride before tPA. DESIGN Retrospective review of medical records for all patients who received intravenous tPA within 3 hours of AIS onset. SETTING Emergency department. Patients One hundred seventy-eight patients with AIS treated with tPA. MAIN OUTCOME MEASURES Occurrence of symptomatic intracerebral hemorrhage and neurologic deterioration. RESULTS Fifty patients required BP lowering before tPA therapy. Twenty-four of these patients (48%) received nicardipine either after labetalol or as first-line therapy. Patients requiring antihypertensive agents had higher baseline blood glucose concentrations, incidence of hypertension, and National Institutes of Health Stroke Scale scores. The rate of adverse events and of modified Rankin score at discharge were not significantly different in patients without BP-lowering treatment compared with patients given either labetalol or nicardipine before intravenous tPA therapy. CONCLUSIONS Blood pressure lowering before intravenous tPA therapy, even using aggressive measures, may not be associated with a higher rate of hemorrhage or poor outcome. Data suggest that patients with AIS requiring aggressive treatment to lower BP should not be excluded from receiving tPA therapy. A prospective study is needed to support these conclusions.

Is the drip-and-ship approach to delivering thrombolysis for acute ischemic stroke safe?

BACKGROUND The drip-and-ship method of treating stroke patients may increase the use of tissue plasminogen activator (t-PA) in community hospitals. OBJECTIVE The safety and early outcomes of patients treated with t-PA for acute ischemic stroke (AIS) by the drip-and-ship method were compared to patients directly treated at a stroke center. METHODS The charts of all patients who were treated with intravenous (i.v.) t-PA at outside hospitals under the remote guidance of our stroke team and were then transferred to our facility were reviewed. Baseline NIHSS (National Institutes of Health Stroke Scale) scores, onset-to-treatment (OTT), and arrival-to-treatment (ATT) times were abstracted. The rates of in-hospital mortality, symptomatic hemorrhage (sICH), early excellent outcome (modified Rankin Scale [mRS] ≤ 1), and early good outcome (discharge home or to inpatient rehabilitation) were determined. RESULTS One hundred sixteen patients met inclusion criteria. Eighty-four (72.4%) were treated within 3 h of symptom onset. The median estimated NIHSS score was 9.5 (range 3-27). The median OTT time was 150 min, and the median ATT was 85 min. These patients had an in-hospital mortality rate of 10.7% and sICH rate of 6%. Thirty percent of patients had an early excellent outcome and 75% were discharged to home or inpatient rehabilitation. When these outcome rates were compared with those observed in patients treated directly at our stroke center, there were no statistical differences. CONCLUSIONS In this small retrospective study, drip-and-ship management of delivering i.v. t-PA for AIS patients did not seem to compromise safety. However, a large prospective study comparing drip-and-ship management to routine care is needed to validate the safety of this approach to treatment.

Using Telemedicine to Facilitate Thrombolytic Therapy for Patients with Acute Stroke

BACKGROUND Recent stroke-care requirements state that all stroke patients should be screened for intravenous recombinant tissue plasminogen activator (rt-PA) and treated, if the appropriate inclusion and exclusion criteria are met. Two community hospitals 90-130 miles east of Houston deployed telemedicine (videoteleconferencing) to provide acute stroke consultative services. DEVELOPING A TELEMEDICINE CAPACITY: According to the Brain Attack Coalitions recommendations, neurosurgical services need to be accessible within two hours. Given their incomplete neurology coverage, the remote-site hospitals identified telemedicine as the best option, with the University of Texas Health Science Center at Houston stroke team as the provider of expertise. RESULTS In the 13 months preceding the telemedicine project (January 2003-March 2004), 2 (.8%) of 327 patients received rt-PA, compared with 14 (4.3%) of 328 patients during the telemedicine project (April 2004-May 2005), p < .001). Seven patients had > or = 4 points improvement in a stroke scale at 24 hours posttreatment. Three patients worsened during the 24-hour assessment. No intracerebral hemorrhages occurred. Door-to-needle median time was 85 minutes (range, 27-165 minutes). DISCUSSION Telemedicine facilitated thrombolytic therapy for acute stroke patients and is intended not to replace care provided by remote-site providers but rather to address a time- and spatially related emergency need.

Acute Ischemic Stroke Management: Administration of Thrombolytics, Neuroprotectants, and General Principles of Medical Management

The pathophysiology of acute ischemic stroke involves occlusion of a cerebral artery; therefore, cerebral reperfusion is the primary goal of acute treatment. This article discusses established and emerging therapies for acute ischemic stroke. In addition to thrombolysis, acute treatment with antiplatelet agents and other medications and neuroprotection are reviewed. The general medical management of acute ischemic stroke patients is also reviewed.

The Effect of Activated Factor VII for Intracerebral Hemorrhage Beyond 3 Hours Versus Within 3 Hours

Background and Purpose— Recombinant-activated factor VII (rFVIIa) is an investigational treatment for intracerebral hemorrhage (ICH). We have evaluated the drugs treatment effect based on time to treatment. Methods— ICH patients treated up to 4 hours from symptom onset were divided based on time to treatment: ≤3 hours (3H) and 3 to 4 hours (4H). Head CT was done at baseline and 24 hours. Outcome measures included: ICH growth at 24 hours, mortality, favorable outcome and discharge disposition. A cohort of nontreated matched ICH patients was used to asses the clinical efficacy. Results— Forty-six patients were treated with rFVIIa: 24 in the 3H group (range 70 to 180 minutes), 22 in the 4H group (range 181 to 300). One hundred and forty-eight patients formed the control group. Mean baseline ICH volume was 8.8 mL for 3H and 10.1 mL for 4H. Mean 24-hour volume was 9.3 mL for 3H (absolute increase 1.05 mL, relative increase 11.9%) and 11.5 mL for 4H (absolute increase 1.1 mL, relative increase 10.9%); P=0.47 is for the difference in relative increase. Mortality was 12.5% for 3H group, 13.6% for 4H, and 13.1% for the control. In the 3H group, 58.3% were discharged with a poor outcome, compared with 54.5% in 4H and 54.1% in the control. Thrombotic adverse events occurred in 11.1% of patients treated with rFVIIa. Conclusions— In our off-label with rFVIIa, we did not find evidence of a treatment effect based on time to treatment. Other criteria should be sought to identify patients who might benefit clinically from rFVIIa.

Diagnosis and Management of Ischemic Stroke

Until relatively recently, ischemic stroke management was a classic example of “diagnose and adios.” Care of patients presenting to the hospital or clinic with symptoms of stroke consisted of aspirin followed by rehabilitation, with few disease-specific strategies directed toward optimal treatment and outcomes. The past two decades have witnessed an explosion of research into ischemic stroke. We now have specific therapies and management strategies to reduce morbidity and mortality. This chapter will first discuss the identification of patients with ischemic stroke, followed by acute treatment, in-patient management, and secondary stroke prevention.