Karen C. Albright

Safety of tPA in stroke mimics and neuroimaging-negative cerebral ischemia

Background: Patients with acute neurologic symptoms may have other causes simulating ischemic stroke, called stroke mimics (SM), but they may also have averted strokes that do not appear as infarcts on neuroimaging, which we call neuroimaging-negative cerebral ischemia (NNCI). We determined the safety and outcome of IV thrombolysis within 3 hours of symptom onset in patients with SM and NNCI. Methods: Patients treated with IV tissue plasminogen activator (tPA) within 3 hours of symptom onset were identified from our stroke registry from June 2004 to October 2008. We collected admission NIH Stroke Scale (NIHSS) score, modified Rankin score (mRS), length of stay (LOS), symptomatic intracerebral hemorrhage (sICH), and discharge diagnosis. Results: Among 512 treated patients, 21% were found not to have an infarct on follow-up imaging. In the SM group (14%), average age was 55 years, median admission NIHSS was 7, median discharge NIHSS was 0, median LOS was 3 days, and there were no instances of sICH. The most common etiologies were seizure, complicated migraine, and conversion disorder. In the NNCI group (7%), average age was 61 years, median admission NIHSS was 7, median discharge NIHSS was 0, median LOS was 3 days, and there were no instances of sICH. Nearly all SM (87%) and NNCI (91%) patients were functionally independent on discharge (mRS 0–1). Conclusions: Our data support the safety of administering IV tissue plasminogen activator to patients with suspected acute cerebral ischemia within 3 hours of symptom onset, even when the diagnosis ultimately is found not to be stroke or imaging does not show an infarct.

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.

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.

ACCESS: Acute Cerebrovascular Care in Emergency Stroke Systems

OBJECTIVES Our primary objective was to determine the proportion of the population able to achieve acute cerebrovascular care in emergency stroke systems (ACCESS) in the United States. In addition, we examined how policy changes, including allowing ground ambulances to cross state lines and allowing air ambulances to transport patients from the prehospital setting to primary stroke centers (PSCs), would affect population access to stroke care. DESIGN Data were obtained via the US Census Bureau, The Joint Commission, and the Atlas and Database of Air Medical Services. Driving distances, ambulance driving speeds, and prehospital times were estimated using validated models and adjusted for population density. Access was determined by summing the population that could reach a PSC within the specified time intervals. SETTING/ PARTICIPANTS US population. MAIN OUTCOME MEASURES Thirty-, 45-, and 60-minute access by ground and air ambulance to PSCs. RESULTS Fewer than 1 in 4 Americans (22.3%) have access to a PSC within 30 minutes, less than half (43.2%) have access within 45 minutes, and just over half (55.4%) have access within 60 minutes. The use of air ambulances to deliver patients to PSCs would increase access from 22.3% to 26.0% for 30 minutes, 43.2% to 65.5% for 45 minutes, and from 55.4% to 79.3% for 60 minutes. The combination of prehospital regionalization and air ambulance transport of patients with acute stroke would reduce the 135.7 million Americans without 60-minute access to a PSC by half, to 62.9 million. CONCLUSIONS About half of the US population has timely access to a PSC. The use of air ambulances to triage patients with ischemic stroke to a PSC would increase the percentage of the US population with prompt access to stroke care. These data have implications for the ongoing design of the US stroke system.

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.

Geographic Access to Acute Stroke Care in the United States

Background and Purpose— Only 3% to 5% of patients with acute ischemic stroke receive intravenous recombinant tissue-type plasminogen activator (r-tPA) and <1% receive endovascular therapy. We describe access of the US population to all facilities that actually provide intravenous r-tPA or endovascular therapy for acute ischemic stroke. Methods— We used US demographic data and intravenous r-tPA and endovascular therapy rates in the 2011 US Medicare Provider and Analysis Review data set. International Classification of Diseases-Ninth Revision codes 433.xx, 434.xx and 436 identified acute ischemic stroke cases. International Classification of Diseases-Ninth Revision code 99.10 defined intravenous r-tPA treatment and International Classification of Diseases-Ninth Revision code 39.74 defined endovascular therapy. We estimated ambulance response times using arc-Geographic Information System’s network analyst and helicopter transport times using validated models. Population access to care was determined by summing the population contained within travel sheds that could reach capable hospitals within 60 and 120 minutes. Results— Of 370 351 acute ischemic stroke primary diagnosis discharges, 14 926 (4%) received intravenous r-tPA and 1889 (0.5%) had endovascular therapy. By ground, 81% of the US population had access to intravenous-capable hospitals within 60 minutes and 56% had access to endovascular-capable hospitals. By air, 97% had access to intravenous-capable hospitals within 60 minutes and 85% had access to endovascular hospitals. Within 120 minutes, 99% of the population had access to both intravenous and endovascular hospitals. Conclusions— More than half of the US population has geographic access to hospitals that actually deliver acute stroke care but treatment rates remain low. These data provide a national perspective on acute stroke care and should inform the planning and optimization of stroke systems in the United States.

Velocity Criteria for Intracranial Stenosis Revisited An International Multicenter Study of Transcranial Doppler and Digital Subtraction Angiography

Background and Purpose— Intracranial atherosclerotic disease is associated with a high risk of stroke recurrence. We aimed to determine accuracy of transcranial Doppler screening at laboratories that share the same standardized scanning protocol. Methods— Patients with symptoms of cerebral ischemia were prospectively studied. Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) criteria were used for identification of ≥50% stenosis. We determined velocity cutoffs for ≥70% stenosis on digital subtraction angiography by Warfarin–Aspirin Symptomatic Intracranial Disease criteria and evaluated novel stenotic/prestenotic ratio and low-velocity criteria. Results— A total of 102 patients with intracranial atherosclerotic disease (age 57±13 years; 72% men; median National Institutes of Health Stroke Scale 3, interquartile range 6) provided 690 transcranial Doppler/digital subtraction angiography vessel pairs. On digital subtraction angiography, ≥50% stenosis was found in 97 and ≥70% stenosis in 62 arteries. Predictive values for transcranial Doppler SONIA criteria were similar (P>0.9) between middle cerebral artery (sensitivity 78%, specificity 93%, positive predictive value 73%, negative predictive value 94%, and overall accuracy 90%) and vertebral artery/basilar artery (69%, 98%, 88%, 93%, and 92%). As a single velocity criterion, most sensitive mean flow velocity thresholds for ≥70% stenosis were: middle cerebral artery >120 cm/s (71%) and vertebral artery/basilar artery >110 cm/s (55%). Optimal combined criteria for ≥70% stenosis were: middle cerebral artery >120 cm/s, or stenotic/prestenotic ratio ≥3, or low velocity (sensitivity 91%, specificity 80%, receiver operating characteristic 0.858), and vertebral artery/basilar artery >110 cm/s or stenotic/prestenotic ratio ≥3 (60%, 95%, 0.769, respectively). Conclusions— At laboratories with a standardized scanning protocol, SONIA mean flow velocity criteria remain reliably predictive of ≥50% stenosis. Novel velocity/ratio criteria for ≥70% stenosis increased sensitivity and showed good agreement with invasive angiography.

Zero on the NIHSS Does NOT Equal the Absence of Stroke

STUDY OBJECTIVE The National Institutes of Health Stroke Scale (NIHSS) measures deficits caused by a stroke, but not all stroke signs are captured on the NIHSS. We determine the symptoms and stroke localization of patients with brain infarction and an NIHSS score of 0. METHODS We studied all patients who presented with acute neurologic symptoms to our stroke center from 2004 to 2008 and had persistent symptoms at the evaluation in the emergency department, an NIHSS score of 0, and an infarct on diffusion-weighted imaging. We characterized the symptoms, signs, lesion location, demographics, and stroke causes. RESULTS Twenty patients met inclusion criteria. Symptoms frequently experienced were headache, vertigo, and nausea. The posterior circulation was commonly infarcted in this group. Truncal ataxia was the most common neurologic sign. CONCLUSION Ischemic stroke may cause symptoms that are associated with no deficits on the NIHSS score.

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.