Morgan S. Campbell

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.

Yield and Accuracy of Urgent Combined Carotid/Transcranial Ultrasound Testing in Acute Cerebral Ischemia

Background and Purpose— We routinely perform an urgent bedside neurovascular ultrasound examination (NVUE) with carotid/vertebral duplex and transcranial Doppler (TCD) in patients with acute cerebral ischemia. We aimed to determine the yield and accuracy of NVUE to identify lesions amenable for interventional treatment (LAITs). Methods— NVUE was performed with portable carotid duplex and TCD using standardized fast-track (<15 minutes) insonation protocols. Digital subtraction angiography (DSA) was the gold standard for identifying LAIT. These lesions were defined as proximal intra- or extracranial occlusions, near-occlusions, ≥50% stenoses or thrombus in the symptomatic artery. Results— One hundred and fifty patients (70 women, mean age 66±15 years) underwent NVUE at median 128 minutes after symptom onset. Fifty-four patients (36%) received intravenous or intra-arterial thrombolysis (median National Institutes of Health Stroke Scale (NIHSS) score 14, range 4 to 29; 81% had NIHSS ≥10 points). NVUE demonstrated LAITs in 98% of patients eligible for thrombolysis, 76% of acute stroke patients ineligible for thrombolysis (n=63), and 42% in patients with transient ischemic attack (n=33), P<0.001. Urgent DSA was performed in 30 patients on average 230 minutes after NVUE. Compared with DSA, NVUE predicted LAIT presence with 100% sensitivity and 100% specificity, although individual accuracy parameters for TCD and carotid duplex specific to occlusion location ranged 75% to 96% because of the presence of tandem lesions and 10% rate of no temporal windows. Conclusions— Bedside neurovascular ultrasound examination, combining carotid/vertebral duplex with TCD yields a substantial proportion of LAITs in excellent agreement with urgent DSA.

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.

Analysis of Emboli during Carotid Stenting with Distal Protection Device

Background: The newly developed multi-frequency transcranial Doppler (TCD) is able to differentiate gaseous from solid emboli. Our goal was to apply this technology to initially characterize emboli detected during carotid stenting with distal protection. Methods: Patients undergoing carotid angiography and stenting were monitored with 2–2.5 MHz TCD (Embo-Dop, DWL) over the middle cerebral artery unilateral to stent deployment. Sonographers insured optimal signal recordings during the procedures. Automated emboli detection and classification software (MultiXLab version 2.0) was applied for offline count and analysis. Monitoring using the Filter Wire EX (Boston Scientific) and ACCUNET system (Guidant Corporation) was performed. Results: A total of 9,649 embolic signals were detected during 11 angiographic and 10 stenting procedures. An observer confirmed the signals using the International Consensus definition. Automated software classified these events into 5,900 gaseous and 3,749 solid emboli. During contrast injections without the protection device, 1,013 emboli were detected with 28% of these being solid. With deployment of the distal protection device, 8,636 emboli were found with 40% being solid (p < 0.001). During stenting and angioplasty with the protection device, 7,395 emboli with 42% solids were detected (p < 0.001). Finally injection of contrast after the procedure, with the protection device still deployed, yielded 1,241 emboli with 31% solids (NS). Only 1 patient developed transient hemiparesthesia during ballooning that reduced the flow velocity to zero for 14 s. Neither gaseous nor solid emboli resulted in a mean flow velocity decrease or clinical symptoms. Conclusions: Microembolization frequently occurs during stenting even with deployment of the distal protection device. More solid emboli are seen during manipulations associated with lesion crossing. Although novel TCD methods yield a high frequency of embolic signals, further validation of this technique to determine the true nature, size, and number of emboli is needed.

Postpartum cerebral angiopathy: atypical features and treatment with intracranial balloon angioplasty.

Postpartum cerebral angiopathy (PCA) is an uncommon cause of ischemic and hemorrhagic stroke in young women. It is usually clinically benign and not relapsing. We describe a patient with nonhemorrhagic PCA who had an atypical progressive neurological deficit from bilateral hemisphere watershed ischemia despite treatment with aggressive medical therapy and intracranial balloon angioplasty.

Emergency endovascular treatment of cerebral sinus thrombosis with a rheolytic catheter device.

Severe thrombosis of the superior sagittal, transverse, and straight sinuses developed in a 53‐year‐old woman. This resulted in extensive multifocal hemorrhagic venous infarction and severe intracranial hypertension refractory to intensive management. Endovascular therapy using a rheolytic catheter device in combination with a small amount of fibrinolytic agent led to rapid normalization of the intracranial pressure, allowing optimization of the cerebral perfusion pressures and was followed by steady, albeit protracted, clinical improvement. The patient not only survived but also left the hospital with minimal neurologic deficit. The rheolytic catheter endovascular treatment is, in the opinion of the authors, the treatment of choice for patients with life‐threatening cerebral sinus thrombosis.

Sex Disparity in Stroke Quality of Care in a Community-Based Study

BACKGROUND Studies have suggested that women may receive lower stroke quality of care (QOC) than men, although population-based studies at nonacademic centers are limited. We investigated sex disparities in stroke QOC in the Brain Attack Surveillance in Corpus Christi Project. METHODS All ischemic stroke patients admitted to 1 of 6 Nueces County nonacademic hospitals between February 2009 and June 2012 were prospectively identified. Data regarding compliance with 7 performance measures (PMs) were extracted from the medical records. Two overall quality metrics were calculated: a composite score of QOC representing the number of achieved PMs over all patient-appropriate PMs, and a binary measure of defect-free care. Multivariable models with generalized estimating equations assessed the association between sex and individual PMs and between sex and overall quality metrics. RESULTS A total of 757 patients (51.6% female) were included in our analysis. After adjustment, women were less likely to receive deep vein thrombosis prophylaxis at 48 hours (relative risk [RR] = .945; 95% CI, .896-.996), an antithrombotic by 48 hours (RR = .952; 95% CI, .939-.965), and to be discharged on an antithrombotic (RR = .953; 95% CI, .925-.982). Women had a lower composite score (mean difference -.030, 95% CI -.057 to -.003) and were less likely to receive defect-free care than men (RR = .914; 95% CI, .843-.991). CONCLUSIONS Women had lower overall stroke QOC than men, although absolute differences in most individual PMs were small. Further investigation into the factors contributing to the sex disparity in guideline-concordant stroke care should be pursued.

Stroke Performance Measures Do Not Predict Functional Outcome

Background and Purpose: Poststroke functional outcome is critical to stroke survivors. We sought to determine whether adherence to current stroke performance measures is associated with better functional outcome 90 days after an ischemic stroke. Methods: Utilizing the Brain Attack Surveillance in Corpus Christi cohort, we examined adherence to 7 ischemic stroke performance measures from February 2009 to June 2012. Adherence to the measures was analyzed in aggregate using a binary defect-free score and an opportunity score, representing the proportion of eligible measures met. The opportunity score ranges from 0 to 1, with values closer to 1 implying better adherence. Functional outcome, defined by an activities of daily living and instrumental activities of daily living (ADL/IADL) score (range 1-4, higher scores worse), was ascertained at 90 days poststroke. Tobit regression models were fitted to examine the associations between the performance measures and functional outcome, adjusting for demographic and clinical characteristics, including stroke severity. Results: There were 565 patients with ischemic stroke included in the analysis. The median ADL/IADL score was 2.32 (interquartile range [IQR]: 1.41-3.41). The median opportunity score was 1 (IQR: 0.8-1), and 58.4% of the patients received defect-free care. After adjustment, the opportunity score (P = .67) and defect-free care (P = .92) were not associated with functional outcome. Conclusion: In this population, adherence to a composite of current stroke performance measures was not associated with poststroke functional outcome after adjustment for other factors. Performance measures that are associated with improved functional outcome should be developed and incorporated into stroke quality measures.

Emerging temporal trends in tissue plasminogen activator use: Results from the BASIC project.

Objective: To explore temporal trends in tissue plasminogen activator (tPA) administration for acute ischemic stroke (AIS) in a biethnic community without an academic medical center and variation in trends by age, sex, ethnicity, and stroke severity. Methods: Cases of AIS were identified from 7 hospitals in the Brain Attack Surveillance in Corpus Christi (BASIC) project, a population-based surveillance study between January 1, 2000, and June 30, 2012. tPA, demographics, and stroke severity as assessed by the NIH Stroke Scale (NIHSS) were ascertained from medical records. Temporal trends were explored using generalized estimating equations, and adjustment made for age, sex, ethnicity, and NIHSS. Interaction terms were included to test for effect modification. Results: There were 5,277 AIS cases identified from 4,589 unique individuals. tPA use was steady at 2% and began increasing in 2006, reaching 11% in subsequent years. Stroke severity modified temporal trends (p = 0.003) such that cases in the highest severity quartile (NIHSS > 8) had larger increases in tPA use than those in lower severity quartiles. Although ethnicity did not modify the temporal trend, Mexican Americans (MAs) were less likely to receive tPA than non-Hispanic whites (NHWs) due to emerging ethnic differences in later years. Conclusions: Dramatic increases in tPA use were apparent in this community without an academic medical center. Primary stroke center certification likely contributed to this rise. Results suggest that increases in tPA use were greater in higher severity patients compared to lower severity patients, and a gap between MAs and NHWs in tPA administration may be emerging.