Hen Hallevi

Thrombolytic Therapy for Patients Who Wake-Up With Stroke

Background and Purpose— Approximately 25% of ischemic stroke patients awaken with their deficits. The last-seen-normal time is defined as the time the patient went to sleep, which places these patients outside the window for thrombolysis. The purpose of this study was to describe our center’s experience with off-label, compassionate thrombolysis for wake-up stroke (WUS) patients. Methods— A retrospective review of our database identified 3 groups of ischemic stroke patients: (1) WUS treated with thrombolysis; (2) nontreated WUS; and (3) 0- to 3-hour intravenous tissue plasminogen activator-treated patients. Safety and clinical outcome measures were symptomatic intracerebral hemorrhage, excellent outcome (discharge modified Rankin score, 0–1), favorable outcome (modified Rankin score, 0–2), and mortality. Outcome measures were controlled for baseline NIHSS using logistic regression. Results— Forty-six thrombolysed and 34 nonthrombolysed WUS patients were identified. Sixty-one percent (28/46) of the treated WUS patients underwent intravenous thrombolysis alone whereas 30% (14/46) were given only intra-arterial thrombolysis. Four patients received both intravenous and intra-arterial thrombolysis (9%). Two symptomatic intracerebral hemorrhages occurred in treated WUS (4.3%). Controlling for NIHSS imbalance, treated WUS had higher rates of excellent (14% vs 6%; P=0.06) and favorable outcome (28% vs 13%; P=0.006), but higher mortality (15% vs 0%) compared to nontreated WUS. A second comparison controlling for baseline NIHSS between treated WUS and 174 intravenous tissue plasminogen activator patients treated within 3 hours of symptoms showed no significant differences in safety and clinical outcomes. Conclusion— Thrombolysis may be safe in WUS patients. Our center’s experience supports considering a prospective, randomized trial to assess the safety and outcome of thrombolysis for this specific patient population.

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.

Can comprehensive stroke centers erase the 'weekend effect'?

Background: Prior epidemiological work has shown higher mortality in ischemic stroke patients admitted on weekends, which has been termed the ‘weekend effect’. Our aim was to assess stroke patient outcomes in order to determine the significance of the ‘weekend effect’ at 2 comprehensive stroke centers. Methods: Consecutive stroke patients were identified using prospective databases. Patients were categorized into 4 groups: intracerebral hemorrhage (ICH group), ischemic strokes not treated with IV t-PA (intravenous tissue plasminogen activator; IS group), acute ischemic strokes treated with IV t-PA (AIS-TPA group), and transient ischemic attack (TIA group). Weekend admission was defined as the period from Friday, 17:01, to Monday, 08:59. Patients treated beyond the 3-hour window, receiving intra-arterial therapy, or enrolled in nonobservational clinical trials were excluded. Patient demographics, NIHSS scores, and admission glucose levels were examined. Adverse events, poor functional outcome (modified Rankin scale, mRS, 3–6), and mortality were compared. Results: A total of 2,211 patients were included (1,407 site 1, 804 site 2). Thirty-six percent (800/2,211) arrived on a weekend. No significant differences were found in the ICH, IS, AIS-TPA, or TIA groups with respect to the rate of symptomatic ICH, mRS on discharge, discharge disposition, 90-day mRS, or 90-day mortality when comparing weekend and weekday groups. Using multivariate logistic regression to adjust for site, age, admission NIHSS, and blood glucose, weekend admission was not a significant independent predictive factor for in-hospital mortality in all strokes (OR = 1.10, 95% CI 0.74–1.63, p = 0.631). Conclusions: Our results suggest that comprehensive stroke centers (CSC) may ameliorate the ‘weekend effect’ in stroke patients. These results may be due to 24/7 availability of stroke specialists, advanced neuroimaging, or ongoing training and surveillance of specialized nursing care available at CSC. While encouraging, these results require confirmation in prospective studies.

The Spot Sign in Intracerebral Hemorrhage: The Importance of Looking for Contrast Extravasation

Background: The ‘spot sign’ is a bright spot on computerized tomography angiography (CTA) source images predictive of hematoma growth. Contrast extravasation (CE) is seen on routine head CT following CTA as pooling of contrast within the hematoma. Our aim was to re-evaluate the predictive value of both the spot sign and CE and measure the reliability of scoring them. Methods: Consecutive cases of spontaneous intracerebral hemorrhage (ICH) presenting within 4 h. The presence of a ‘spot’ and CE, ICH and intraventricular hemorrhage volume at baseline and on follow-up scans were assessed. Clinical outcome was captured using the modified Rankin Scale on hospital discharge. Results: We identified 28 patients with a mean age of 56.8 years, median ICH volume of 19 ml, and median NIH Stroke Scale score on admission of 17.5. 11/27 (40.7%) had a positive spot and 13/22 (59.1%) had CE. Interrater reliability was 0.812 (95% CI 0.57–0.91, p < 0.001) for the spot sign and 0.952 (95% CI 0.89–0.98, p < 0.001) for CE. ICH volume increased in 16/28 (57.1%) patients. Both the spot sign and CE were associated with ICH growth (p < 0.001) and poor outcome (p < 0.001). Conclusions: In ICH patients, the presence of the spot sign or CE is highly correlated with early ICH growth. In our experience, CE is a more sensitive predictor of ICH growth with a better negative predictive value than the spot sign; CE is more consistently identified even by experienced clinicians. Postcontrast CT should be done routinely after CTA in patients presenting with ICH within 4 h. Patients who are CE-positive may be candidates for hemostatic therapies or early surgical intervention.

Identifying Patients at High Risk for Poor Outcome After Intra-Arterial Therapy for Acute Ischemic Stroke

BACKGROUND AND PURPOSE Intra-arterial recanalization therapy (IAT) is increasingly used for acute stroke. Despite high rates of recanalization, the outcome is variable. We attempted to identify predictors of outcome that will enable better patient selection for IAT. METHODS All patients who underwent IAT at the University of Texas Houston Stroke Center were reviewed. Poor outcome was defined as modified Rankin Scale score 4 to 6 on hospital discharge. Findings were validated in an independent data set of 175 patients from the University of California at Los Angeles Stroke Center. RESULTS One hundred ninety patients were identified. Mean age was 62 years and median baseline National Institutes of Health Stroke Scale score was 0.18. Recanalization rate was 75%, symptomatic hemorrhage rate was 6%, and poor outcome rate was 66%. Variables associated with poor outcome were: age, baseline National Institutes of Health Stroke Scale, admission glucose, diabetes, heart disease, previous stroke, and the absence of mismatch on the pretreatment MRI. Logistic regression identified 3 variables independently associated with poor outcome: age (P=0.049; OR, 1.028), National Institutes of Health Stroke Scale (P=0.013; OR, 1.084), and admission glucose (P=0.031; OR, 1.011). Using these data, we devised the Houston IAT score: 1 point for age >75 years; 1 for National Institutes of Health Stroke Scale score >18, and 1 point for glucose >150 mg/dL (range, 0 to 3 mg/dL). The percentage of poor outcome by Houston IAT score was: score of 0, 44%; 1, 67%; 2, 97%; and 3, 100%. Recanalization rates were similar across the scores (P=0.4). Applying Houston IAT to the external cohort showed comparable trends in outcome and nearly identical rates in the Houston IAT therapy 3 tier. CONCLUSIONS The Houston IAT score estimates the chances of poor outcome after IAT, even with recanalization. It may be useful in comparing cohorts of patients and when assessing the results of clinical trials.

The IVH Score: A novel tool for estimating intraventricular hemorrhage volume: Clinical and research implications

Objective:Intraventricular extension of intracerebral hemorrhage (IVH) is an independent predictor of poor outcome. IVH volume may be important in outcome prediction and management; however, it is difficult to measure routinely. Design and Patients:We reviewed the charts and computed tomographies of a cohort of consecutive patients with IVH. The cohort was divided into two groups: index and validation by random sampling. IVH and intracerebral hemorrhage (ICH) volume were measured manually in all patients. IVH was also graded using a simple classification system termed IVH score (IVHS). Clinical outcome was determined by the modified Rankin Scale (mRS) at discharge and in-hospital death. Poor outcome was defined as mRS 4–6. Main Results:One hundred seventy-five patients were analyzed, 92 in the index group and 83 in the validation group. Exponential regression yielded the following formula for estimating IVH volume (mL): eÎVHS/5 (R2 = .75, p < 0.001). The IVH estimation formula was then verified in the validation group (R2 = .8, p < 0.001). The following correlations with mRS were obtained: IVH volume R = .305; ICH volume R = .468; total volume {lsqb;TV{rsqb; R = .571 (p < 0.001 for all three correlations). Partial correlation of TV with mRS controlling for ICH volume yielded R = .3 for TV (p < 0.001). Logistic regression model comparing ICH and TV association with poor outcome yielded the following: ICH odds ratio = 5.2, 95% confidence interval 2.3–11.6, p < 0.001; TV odds ratio = 41.6, 95% confidence interval 9.6–180.6, p < 0.001. Substituting TV for ICH volume in the ICH score resulted in a significant increase in the specificity from 64% to 87% for predicting mortality. Conclusions:IVHS enables clinicians to rapidly estimate IVH volume. The addition of IVH to ICH volume increases its predictive power for poor outcome and mortality significantly. IVHS and TV may be used in clinical practice and clinical trials of patients with ICH.

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.

Combined Neuroprotective Modalities Coupled with Thrombolysis in Acute Ischemic Stroke: A Pilot Study of Caffeinol and Mild Hypothermia

BACKGROUND Both caffeinol and hypothermia are neuroprotective in preclinical models of transient middle cerebral artery occlusion. We tested whether combining caffeinol and hypothermia with tissue plasminogen activator (t-PA) in patients with acute stroke is safe and feasible. METHODS Twenty patients with acute ischemic stroke were treated with caffeinol (caffeine 8-9 mg/kg + ethanol 0.4 g/kg intravenously [IV] x 2 hours, started by 4 hours after symptom onset) and hypothermia (started by 5 hours and continued for 24 hours [target temperature 33-35 degrees C] followed by 12 hours of rewarming). IV t-PA was given to eligible patients. Meperidine and buspirone were used to suppress shivering. RESULTS All patients received caffeinol, and most reached target blood levels. Cooling was attempted in 18 patients via endovascular (n = 8) or surface (n = 10) approaches. Two patients were not cooled due to catheter or machine failure. Thirteen patients reached target temperature; average time from symptom onset was 9 hours and 43 minutes. The last 5 hypothermia patients received surface cooling with iced saline induction and larger doses of meperidine; all patients reached target temperature, on average within 2 hours and 30 minutes from induction and 6 hours and 21 minutes from symptom onset. Three patients died: one from symptomatic hemorrhage, one from malignant cerebral edema, and one from unrelated medical complications. No adverse events were attributed to caffeinol. One patient had reduced respiratory drive due to meperidine, requiring BiPAP. DISCUSSION Combining caffeinol with hypothermia in patients with acute stroke given IV t-PA is feasible. A prospective placebo-controlled randomized study is needed to further assess safety and to test the efficacy of caffeinol, hypothermia, or both.

Intracerebral Hemorrhage in Cocaine Users

Background and Purpose— Cocaine is a cause of intracerebral hemorrhage (ICH), but there are no large studies that have characterized the location, pathology, and outcome of patients with cocaine-associated ICH. Methods— We performed a retrospective analysis of all patients admitted to our stroke service from 2004 to 2007 who had nontraumatic ICH and urine drug screens positive for cocaine and compared them with similar patients who had negative drug screens for cocaine. Results— We identified 45 patients with cocaine-associated ICH and 105 patients with cocaine-negative ICH. There were no significant differences in age or gender, but there was a significantly higher incidence of black patients in the cocaine-positive group. Cocaine-associated ICH patients had higher admission blood pressures, significantly more subcortical hemorrhages, and higher rates of intraventricular hemorrhage compared to patients with cocaine-negative ICH. Cocaine-positive patients had worse functional outcome, defined as modified Rankin Scale score >3 at the time of discharge (OR, 4.90; 95% CI, 2.19–10.97), and were less likely to be discharged home or to inpatient rehabilitation. Patients with cocaine-associated ICH were nearly 3-times more likely to die during their acute hospitalization when compared to cocaine-negative patients. Conclusion— Recent cocaine ingestion is associated with hemorrhages that occur more frequently in subcortical locations, have a higher risk of intraventricular hemorrhage, and have a poor prognosis compared to patients with cocaine-negative, spontaneous ICH.

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.