Samir Belagaje

“Picture to Puncture” A Novel Time Metric to Enhance Outcomes in Patients Transferred for Endovascular Reperfusion in Acute Ischemic Stroke

Background— Comprehensive stroke centers allow for regionalization of subspecialty stroke care. Efficacy of endovascular treatments, however, may be limited by delays in patient transfer. Our goal was to identify where these delays occurred and to assess the impact of such delays on patient outcome. Methods and Results— This was a retrospective study evaluating patients treated with endovascular therapy from November 2010 to July 2012 at our institution. We compared patients transferred from outside hospitals with locally treated patients with respect to demographics, imaging, and treatment times. Good outcomes, as defined by 90-day modified Rankin Scale scores of 0 to 2, were analyzed by transfer status as well as time from initial computed tomography to groin puncture (“picture-to-puncture” time). A total of 193 patients were analyzed, with a mean age of 65.8±14.5 years and median National Institutes of Health Stroke Scale score of 19 (interquartile range, 15–23). More than two thirds of the patients (132 [68%]) were treated from referring facilities. Outside transfers were noted to have longer picture-to-puncture times (205 minutes [interquartile range, 162–274] versus 89 minutes [interquartile range, 70–119]; P 7: 50% versus 76%; P <0.001) and significantly worse clinical outcomes (29% versus 51%; P =0.003). In a logistic regression model, picture-to-puncture times were independently associated with good outcomes (odds ratio, 0.994; 95% confidence interval, 0.990–0.999; P =0.009). Conclusions— Delays in picture-to-puncture times for interhospital transfers reduce the probability of good outcomes among treated patients. Strategies to reduce such delays herald an opportunity for hospitals to improve patient outcomes. # Clinical Perspective {#article-title-29}Background— Comprehensive stroke centers allow for regionalization of subspecialty stroke care. Efficacy of endovascular treatments, however, may be limited by delays in patient transfer. Our goal was to identify where these delays occurred and to assess the impact of such delays on patient outcome. Methods and Results— This was a retrospective study evaluating patients treated with endovascular therapy from November 2010 to July 2012 at our institution. We compared patients transferred from outside hospitals with locally treated patients with respect to demographics, imaging, and treatment times. Good outcomes, as defined by 90-day modified Rankin Scale scores of 0 to 2, were analyzed by transfer status as well as time from initial computed tomography to groin puncture (“picture-to-puncture” time). A total of 193 patients were analyzed, with a mean age of 65.8±14.5 years and median National Institutes of Health Stroke Scale score of 19 (interquartile range, 15–23). More than two thirds of the patients (132 [68%]) were treated from referring facilities. Outside transfers were noted to have longer picture-to-puncture times (205 minutes [interquartile range, 162–274] versus 89 minutes [interquartile range, 70–119]; P<0.001), which was attributable to the delays in transfer. This corresponded to fewer patients with favorable Alberta Stroke Program Early CT Scores on preprocedural computed tomographic imaging (Alberta Stroke Program Early CT Scores >7: 50% versus 76%; P<0.001) and significantly worse clinical outcomes (29% versus 51%; P=0.003). In a logistic regression model, picture-to-puncture times were independently associated with good outcomes (odds ratio, 0.994; 95% confidence interval, 0.990–0.999; P=0.009). Conclusions— Delays in picture-to-puncture times for interhospital transfers reduce the probability of good outcomes among treated patients. Strategies to reduce such delays herald an opportunity for hospitals to improve patient outcomes.

Higher volume endovascular stroke centers have faster times to treatment, higher reperfusion rates and higher rates of good clinical outcomes

Background and purpose Technological advances have helped to improve the efficiency of treating patients with large vessel occlusion in acute ischemic stroke. Unfortunately, the sequence of events prior to reperfusion may lead to significant treatment delays. This study sought to determine if high-volume (HV) centers were efficient at delivery of endovascular treatment approaches. Methods A retrospective review was performed of nine centers to assess a series of time points from obtaining a CT scan to the end of the endovascular procedure. Demographic, radiographic and angiographic variables were assessed by multivariate analysis to determine if HV centers were more efficient at delivery of care. Results A total of 442 consecutive patients of mean age 66±14 years and median NIH Stroke Scale score of 18 were studied. HV centers were more likely to treat patients after intravenous administration of tissue plasminogen activator and those transferred from outside hospitals. After adjusting for appropriate variables, HV centers had significantly lower times from CT acquisition to groin puncture (OR 0.991, 95% CI 0.989 to 0.997, p=0.001) and total procedure times (OR 0.991, 95% CI 0.986 to 0.996, p=0.001). Additionally, patients treated at HV centers were more likely to have a good clinical outcome (OR 1.86, 95% CI 1.11 to 3.10, p<0.018) and successful reperfusion (OR 1.82, 95% CI 1.16 to 2.86, p<0.008). Conclusions Significant delays occur in treating patients with endovascular therapy in acute ischemic stroke, offering opportunities for improvements in systems of care. Ongoing prospective clinical trials can help to assess if HV centers are achieving better clinical outcomes and higher reperfusion rates.

Endovascular Reperfusion and Cooling in Cerebral Acute Ischemia (ReCCLAIM I)

Background The efficacy of hypothermia as a neuroprotectant has yet to be demonstrated in acute ischemic stroke. We conducted a phase I pilot study to assess the feasibility and safety of performing intravascular hypothermia after definitive intra-arterial reperfusion therapy (IAT). Methods ReCCLAIM (Reperfusion and Cooling in Cerebral Acute Ischemia) is a prospective single-arm open-label clinical trial conducted between May and August 2012 at Grady Memorial Hospital. Twenty patients with Alberta Stroke Program Early CT Score (ASPECTS) 5–7 and NIH Stroke Scale (NIHSS) score > 13 were enrolled and treated with intravascular cooling immediately after IAT. The incidence of pneumonia, deep vein thrombosis, cardiac arrhythmias and postoperative hemorrhages was documented for the entire length of stay. Secondary outcomes included blood–brain barrier (BBB) breakdown on gadolinium-enhanced MRIs and 90-day modified Rankin scores (mRS). Results The mean age, median NIHSS score and median final infarct volume were 59.7±14.6 years, 19 (IQR16–22) and 78 cm3 (IQR 16–107), respectively. The average time to the target temperature (33°C) was 64±50 min. Intracranial hemorrhages were found in three patients, of which one was symptomatic. Evidence of BBB breakdown was observed on 3 of 14 MRIs (21%). Six patients died due to withdrawal of care, whereas six patients (30%) achieved mRS of 0–2 at 90 days. In a binary logistical regression model comparing ReCCLAIM patients with 68 historical controls at our institution, hypothermia was protective against intracerebral hemorrhages (OR 0.09, 95% CI 0.02 to 0.56; p<0.01). Conclusions Hypothermia can be safely performed after definitive IAT in patients with large pretreatment core infarcts. A phase II study randomizing patients to hypothermia or normothermia is needed to properly assess the efficacy of hypothermia as a neuroprotectant for reperfusion injury. Trial registration number NCT01585597.

Comparison of Final Infarct Volumes in Patients Who Received Endovascular Therapy or Intravenous Thrombolysis for Acute Intracranial Large-Vessel Occlusions

IMPORTANCE Studies comparing the efficacy of intra-arterial therapy (IAT) and medical therapy in reducing final infarct volume (FIV) in intracranial large-vessel occlusions (ILVOs) are lacking. OBJECTIVES To assess whether patients with ILVOs who received IAT have smaller FIVs than patients who received either intravenous tissue plasminogen activator therapy (IVT) or no reperfusion therapy (NRT) and to determine a National Institutes of Health Stroke Scale (NIHSS) threshold score that identifies patients most likely to benefit from IAT. DESIGN Retrospective cohort study of patients with ILVOs between 2009 and 2011. SETTING Two large-volume stroke centers. PARTICIPANTS Adults with anterior circulation ILVOs who presented within 360 minutes from the time last seen as normal. Patients with isolated extracranial occlusions were not included. EXPOSURE Intra-arterial therapy, IVT, or NRT. MAIN OUTCOMES AND MEASURES Final infarct volumes, rates of acceptable outcome defined as a modified Rankin Scale score of 0 to 3 at hospital discharge, and NIHSS threshold scores. RESULTS A total of 203 consecutive patients with ILVOs were evaluated. Baseline characteristics were similar among the 3 groups. The median infarct volume was significantly smaller for the IAT group (42 cm3) than for the IVT group (109 cm3; P = .001) or the NRT group (110 cm3; P < .01). A higher magnitude of infarct volume reduction in more proximal occlusions was noted in the IAT group compared with the IVT and NRT groups combined: internal carotid artery terminus (75 vs 190 cm3; P < .001), M1 middle cerebral artery (39 vs 109 cm3; P = .004), and M2 middle cerebral artery (33 vs 59 cm3; P = .04) occlusions. Patients were stratified based on NIHSS score at presentation (8-13, 14-19, and ≥20). For patients with an NIHSS score of 14 or higher at presentation, IAT significantly reduced FIV (46 cm3 with IAT vs 149 cm3 with IVT or NRT; P < .001) compared with patients with an NIHSS score of 8 to 13 (22 cm3 with IAT vs 44 cm3 with IVT or NRT; P = .40). Patients with an NIHSS score of 14 or higher who received IAT appear to benefit most from IAT. CONCLUSIONS AND RELEVANCE Our data suggest a greater reduction of FIV with IAT compared with either IVT or NRT. Moreover, patients with an NIHSS score of 14 or higher may be the best candidates for endovascular reperfusion therapy.

ASPECTS decay during inter-facility transfer predicts patient outcomes in endovascular reperfusion for ischemic stroke: a unique assessment of dynamic physiologic change over time

Background Pretreatment Alberta Stroke Program Early CT Scores (ASPECTS) is associated with clinical outcomes. The rate of decline between subsequent images, however, may be more predictive of outcomes as it integrates time and physiology. Methods A cohort of patients transferred from six primary stroke centers and treated with intra-arterial therapy (IAT) was retrospectively studied. Absolute ASPECTS decay was defined as ((ASPECTS First CT—ASPECTS Second CT)/hours elapsed between images). A logistic regression model was performed to determine if the rate of ASPECTS decay predicted good outcomes at 90 days (modified Rankin Scale score of 0–2). Results 106 patients with a mean age of 66±14 years and a median National Institutes of Health Stroke Scale score of 19 (IQR 15–23) were analyzed. Median time between initial CT at the outside hospital to repeat CT at our facility was 2.7 h (IQR 2.0–3.6). Patients with good outcomes had lower rates of absolute ASPECTS decay compared with those who did not (0.14±0.23 score/h vs 0.49±0.39 score/h; p<0.001). In multivariable modeling, the absolute rate of ASPECTS decay (OR 0.043; 95% CI 0.004 to 0.471; p=0.01) was a stronger predictor of good patient outcome than static pretreatment ASPECTS obtained before IAT (OR 0.64; 95% CI 0.38 to 1.04; p=0.075). In practical terms, every 1 unit increase in ASPECTS decline per hour correlates with a 23-fold lower probability of a good outcome. Conclusions Patients with faster rates of ASPECTS decay during inter-facility transfers are associated with worse clinical outcomes. This value may reflect the rate of physiological infarct expansion and thus serve as a tool in patient selection for IAT.

Endovascular Treatment for Acute Ischemic Stroke in the Setting of Anticoagulation

Background and Purpose— Oral anticoagulation (OAC) plays a major role in atrial fibrillation stroke prevention but represents a contraindication to intravenous tissue-type plasminogen activator. Intra-arterial therapy remains a potential reperfusion strategy in these patients; however, supporting data are scarce. Methods— Retrospective analysis of prospectively collected consecutive intra-arterial therapies from October 2010 to March 2015 comparing OAC (vitamin-K antagonists and novel oral anticoagulants) versus normal hemostasis versus intravenous tissue-type plasminogen activator patients. Primary safety end point is parenchymal hematoma. Secondary safety end point is 90-day mortality. Efficacy end points are successful reperfusion (modified Thrombolysis in Cerebral Infarction, 2b-3) and good outcome (90-day modified Rankin Scale score of 0–2). Logistic regression for predictors of parenchymal hematoma was performed. Results— A total of 604 patients were qualified for the study. Baseline and outcomes variables were overall similar for vitamin-K antagonists (n=29) and novel oral anticoagulants (n=17) patients. When compared with normal hemostasis (n=265) and intravenous tissue-type plasminogen activator (n=297), OAC (n=46) patients were older and had more comorbidities. There were no statistically significant differences in the rates of parenchymal hematoma (8% versus 5%; P=0.42), 90-day modified Rankin Scale score of 0 to 2 (30% versus 40%; P=0.26), and 90-day mortality (32% versus 26%; P=0.46) among OAC and normal hemostasis patients. Similarly, there were no significant differences between OAC and intravenous tissue-type plasminogen activator patients in terms of parenchymal hematoma (8% versus 4%; P=0.16), 90-day modified Rankin Scale score of 0 to 2 (30% versus 43%; P=0.13), and 90-day mortality (32% versus 22%; P=0.18). The use of OAC was not associated with the occurrence of parenchymal hematoma on multivariate logistic regression analysis. Conclusions— Intra-arterial therapy seems to be safe in patients taking OACs; however, our study showed a nonsignificant increase in hemorrhage and mortality with a nonsignificant decrease in good outcomes in comparison with non-OAC patients. Although these nominal differences may have been related to older age and more comorbidities in the OAC group, larger studies are needed to confirm our findings given our limited sample size.

Endovascular Treatment for Patients With Acute Stroke Who Have a Large Ischemic Core and Large Mismatch Imaging Profile

Importance Endovascular therapy (ET) is typically not considered for patients with large baseline ischemic cores (irreversibly injured tissue). Computed tomographic perfusion (CTP) imaging may identify a subset of patients with large ischemic cores who remain at risk for significant infarct expansion and thus could still benefit from reperfusion to reduce their degree of disability. Objective To compare the outcomes of patients with large baseline ischemic cores on CTP undergoing ET with the outcomes of matched controls who had medical care alone. Design, Setting, and Participants A matched case-control study of patients with proximal occlusion after stroke (intracranial internal carotid artery and/or middle cerebral artery M1 and/or M2) on computed tomographic angiography and baseline ischemic core greater than 50 mL on CTP at a tertiary care center from May 1, 2011, through October 31, 2015. Patients receiving ET and controls receiving medical treatment alone were matched for age, baseline ischemic core volume on CTP, and glucose levels. Baseline characteristics and outcomes were compared. Main Outcomes and Measures The primary outcome measure was the shift in the degree of disability among the treatment and control groups as measured by the modified Rankin Scale (mRS) (with scores ranging from 0 [fully independent] to 6 [dead]) at 90 days. Results Fifty-six patients were matched across 2 equally distributed groups (mean [SD] age, 62.25 [13.92] years for cases and 58.32 [14.79] years for controls; male, 13 cases [46%] and 14 controls [50%]). Endovascular therapy was significantly associated with a favorable shift in the overall distribution of 90-day mRS scores (odds ratio, 2.56; 95% CI, 2.50-8.47; P = .04), higher rates of independent outcomes (90-day mRS scores of 0-2, 25% vs 0%; P = .04), and smaller final infarct volumes (mean [SD], 87 [77] vs 242 [120] mL; P < .001). One control (4%) and 2 treatment patients (7%) developed a parenchymal hematoma type 2 (P > .99). The rates of hemicraniectomy (2 [7%] vs 6 [21%]; P = .10) and 90-day mortality (7 [29%] vs 11 [48%]; P = .75) were numerically lower in the intervention arm. Sensitivity analysis for patients with a baseline ischemic core greater than 70 mL (12 pairs) revealed a significant reduction in final infarct volumes (mean [SD], 110 [65] vs 319 [147] mL; P < .001) but only a nonsignificant improvement in the overall distribution of mRS scores favoring the treatment group (P = .18). All 11 patients older than 75 years had poor outcomes (mRS score >3) at 90 days. Conclusions and Relevance In properly selected patients, ET appears to benefit patients with large core and large mismatch profiles. Future prospective studies are warranted.

Early Endovascular Treatment in Intravenous Tissue Plasminogen Activator–Ineligible Patients

Background and Purpose— Intravenous tissue-type plasminogen activator (tPA) treatment in acute stroke has many exclusion criteria. We aimed to assess the safety and efficacy of endovascular therapy (ET) in intravenous (IV) tPA-ineligible patients. Methods— Retrospective analysis of a prospectively collected database of consecutive patients treated with ET within 6 hours of stroke onset between September 2010 and April 2015. Patients treated with IV-tPA followed by ET were compared with those treated with ET alone because of IV-tPA ineligibility. Efficacy and safety end points included the rates of good outcome (90-day modified Rankin scale score ⩽2), successful reperfusion (modified Treatment in Cerebral Ischemia 2b-3), parenchymal hematoma (PH-1 and PH-2), and 90-day mortality. Univariate and logistic regression were performed to identify the predictors of outcomes. Results— A total of 422 patients were included. Two hundred and fifty-three (59%) patients received IV-tPA+ET, and 169 (41%), ET alone. Combined IV-tPA+ET patients were slightly younger (64.9±15.2 versus 67.9±14.9 years; P=0.05), more often males (56% versus 44%; P=0.01), and had less hypertension (70% versus 81%; P=0.02) and vertebrobasilar occlusions (3% versus 8%; P=0.02). The remaining baseline characteristics, including National Institutes of Health Stroke Scale score (20 [15–23] versus 19 [15–24]; P=0.85), Alberta Stroke Program Early CT Score (ASPECTS; 8 [7–9] versus 8 [7–9]; P=0.24), and stroke onset to puncture times (235±70 versus 240±81 minutes; P=0.27), were similar across both groups. There were no significant differences in the rates of modified Treatment in Cerebral Ischemia 2b-3 (83% versus 80%; P=0.52), 90-day modified Rankin scale score ⩽2 (45% versus 38%; P=0.21), or any PH (3% versus 5%; P=0.21). Unadjusted 90-day mortality was higher with ET alone (21% versus 34%; P<0.01); however, IV-tPA ineligibility was not associated with modified Treatment in Cerebral Ischemia 2b-3, any PH, good outcome, or 90-day mortality on logistic regression. Conclusions— IV-tPA-eligible and -ineligible patients seem to have similar outcomes after early ET.

Recent advances in stroke recovery and rehabilitation.

Stroke is the fourth leading cause of death in the United States, but remains a leading cause of disability. As more stroke victims survive with advanced acute care, effective strategies and interventions are required to optimize poststroke outcomes. In recent years, knowledge with respect to stroke recovery has expanded greatly through completion of preclinical and clinical trials. Emerging technology may provide further treatment options beyond the standard therapy and practices. In this article, the authors review recent advances in stroke recovery and rehabilitation, including the major determinants of poststroke recovery, challenges in translational stroke recovery research, and several emerging rehabilitation modalities such as noninvasive brain stimulation, brain-computer interface, biotherapeutics, and pharmacologic agents. Potential future directions in research are also addressed.

Disposition to home or acute rehabilitation is associated with a favorable clinical outcome in the SENTIS trial

Objective To explore the impact of stroke severity and discharge disposition on 90-day outcomes in US patients enrolled in the SENTIS trial. Methods SENTIS is a previously published prospective randomized controlled trial. We analyzed the demographic information, National Institutes of Health Stroke Scores (NIHSS) on day 4, discharge disposition and 90-day modified Rankin Score (mRS). Univariate models were constructed to determine the impact of discharge disposition on 90-day outcomes as well as the association of the day 4 NIHSS with outcomes. Results A total of 292 patients with a mean age of 65±14 years were analyzed. Discharge disposition was distributed as follows: 153 (52.1%) to an inpatient rehabilitation facility (IRF), 111 (38.0%) to home and 28 (9.6%) to a skilled nursing facility (SNF). Only 2 out of 28 patients (7.1%) discharged to a SNF achieved a 90-day mRS ≤2 compared with 60/153 (39.2%) in the IRF group (OR 8.39 (95% CI 1.92 to 36.64), p=0.0047). This association persisted after adjusting for age and admission NIHSS. Only 3 of 50 patients (6%) with a NIHSS of ≥14 at day 4 achieved a mRS 0–2 at day 90. Conclusions This analysis shows that discharge to an IRF is associated with better neurological outcomes than discharge to a SNF. Additionally, patients with a NIHSS of ≥14 at day 4 are unlikely to achieve independent function.