Shumei Man

Addition of Hyperacute MRI Aids in Patient Selection, Decreasing the Use of Endovascular Stroke Therapy

Background and Purpose— The failure of recent trials to show the effectiveness of acute endovascular stroke therapy (EST) may be because of inadequate patient selection. We implemented a protocol to perform pretreatment MRI on patients with large-vessel occlusion eligible for EST to aid in patient selection. Methods— We retrospectively identified patients with large-vessel occlusion considered for EST from January 2008 to August 2012. Patients before April 30, 2010, were selected based on computed tomography/computed tomography angiography (prehyperacute protocol), whereas patients on or after April 30, 2010, were selected based on computed tomography/computed tomography angiography and MRI (hyperacute MRI protocol). Demographic, clinical features, and outcomes were collected. Univariate and multivariate analyses were performed. Results— We identified 267 patients: 88 patients in prehyperacute MRI period and 179 in hyperacute MRI period. Fewer patients evaluated in the hyperacute MRI period received EST (85 of 88, 96.6% versus 92 of 179, 51.7%; P<0.05). The hyperacute-MRI group had a more favorable outcome of a modified Rankin scale 0 to 2 at 30 days as a group (6 of 66, 9.1% versus 33 of 140, 23.6%; P=0.01), and when taken for EST (6 of 63, 9.5% versus 17 of 71, 23.9%; P=0.03). On adjusted multivariate analysis, the EST in the hyperacute MRI period was associated with a more favorable outcome (odds ratio, 3.4; 95% confidence interval, 1.1–10.6; P=0.03) and reduced mortality rate (odds ratio, 0.16; 95% confidence interval, 0.03–0.37; P<0.001). Conclusions— Implementation of hyperacute MRI protocol decreases the number of endovascular stroke interventions by half. Further investigation of MRI use for patient selection is warranted.

Intracellular and circulating neuronal antinuclear antibodies in human epilepsy.

There are overwhelming data supporting the inflammatory origin of some epilepsies (e.g., Rasmussens encephalitis and limbic encephalitis). Inflammatory epilepsies with an autoimmune component are characterized by autoantibodies against membrane-bound, intracellular or secreted proteins (e.g., voltage gated potassium channels). Comparably, little is known regarding autoantibodies targeting nuclear antigen. We tested the hypothesis that in addition to known epilepsy-related autoantigens, the human brain tissue and serum from patients with epilepsy contain autoantibodies recognizing nuclear targets. We also determined the specific nuclear proteins acting as autoantigen in patients with epilepsy. Brain tissue samples were obtained from patients undergoing brain resections to treat refractory seizures, from the brain with arteriovenous malformations or from post-mortem multiple sclerosis brain. Patients with epilepsy had no known history of autoimmune disease and were not diagnosed with autoimmune epilepsy. Tissue was processed for immunohistochemical staining. We also obtained subcellular fractions to extract intracellular IgGs. After separating nuclear antibody-antigen complexes, the purified autoantigen was analyzed by mass spectrometry. Western blots using autoantigen or total histones were probed to detect the presence of antinuclear antibodies in the serum of patients with epilepsy. Additionally, HEp-2 assays and antinuclear antibody ELISA were used to detect the staining pattern and specific presence of antinuclear antibodies in the serum of patients with epilepsy. Brain regions from patients with epilepsy characterized by blood-brain barrier disruption (visualized by extravasated albumin) contained extravasated IgGs. Intracellular antibodies were found in epilepsy (n=13/13) but not in multiple sclerosis brain (n=4/4). In the brain from patients with epilepsy, neurons displayed higher levels of nuclear IgGs compared to glia. IgG colocalized with extravasated albumin. All subcellular fractions from brain resections of patients with epilepsy contained extravasated IgGs (n=10/10), but epileptogenic cortex, where seizures originated from, displayed the highest levels of chromatin-bound IgGs. In the nuclear IgG pool, anti-histone autoantibodies were identified by two independent immunodetection methods. HEp-2 assay and ELISA confirmed the presence of anti-histone (n=5/8) and anti-chromatin antibodies in the serum from patients with epilepsy. We developed a multi-step approach to unmask autoantigens in the brain and sera of patients with epilepsy. This approach revealed antigen-bound antinuclear antibodies in neurons and free antinuclear IgGs in the serum of patients with epilepsy. Conditions with blood-brain barrier disruption but not seizures, were characterized by extravasated but not chromatin-bound IgGs. Our results show that the pool of intracellular IgG in the brain of patients with epilepsy consists of nucleus-specific autoantibodies targeting chromatin and histones. Seizures may be the trigger of neuronal uptake of antinuclear antibodies.

Predictors of Infarct Growth after Endovascular Therapy for Acute Ischemic Stroke

BACKGROUND Intra-arterial (IA) thrombectomy for acute ischemic stroke has an excellent recanalization rate but variable outcomes. The core infarct also grows at a variable rate despite recanalization. We aim to study the factors that are associated with infarct growth after IA therapy. METHODS We reviewed the hyperacute ischemic stroke imaging database at Cleveland Clinic for those undergoing endovascular thrombectomy of anterior circulation from 2009 to 2012. Patients with both pretreatment and follow-up magnetic resonance imaging were included. Seventy-six patients were stratified into quartiles by infarct volume growth from initial to follow-up diffusion-weighted imaging (DWI) measure by a region of interest demarcation. RESULTS The median infarct growth of each quartile was .6 cm(3) (no-growth group), 13.8, 37, and 160.2 cm(3) (large-growth group). Pretreatment stroke severity was comparable among groups. Compared with the no-growth group, the large-growth group had larger initial infarct defined by computed tomography (CT) Alberta Stroke Program Early CT score (median 10 versus 8, P = .032) and DWI volume (mean 13.8 versus 29.2 cm(3), P = .034), lack of full collateral vessels on CT angiography (36.8% versus 0%, P = .003), and a lower recanalization rate (thrombolysis in cerebral infarction ≥2b, P = .044). The increase in infarct growth is associated with decrease in favorable outcomes defined by a modified Rankin Scale score of 0-2 at 30 days: 57.9%, 42.1%, 21.1%, and 5.3%, respectively (P < .001). DWI reversal was observed in 11 of 76 patients, translating to 82% favorable outcome. CONCLUSIONS Infarct evolution after endovascular thrombectomy is associated with an outcome. DWI reversal or no growth translated to a favorable outcome. Small initial ischemic core, good collateral support, and better recanalization grades predict the smaller infarct growth and favorable outcome after endovascular thrombectomy.

The Location of Pretreatment Hyperdense Middle Cerebral Artery Sign Predicts the Outcome of Intraarterial Thrombectomy for Acute Stroke

Intraarterial (IA) mechanical thrombectomy has an excellent recanalization rate but does not always correlate with good clinical outcomes. We aimed to investigate whether hyperdense middle cerebral artery sign (HMCAS) on preintervention nonenhanced CT (NECT) predicts IA therapy outcome for acute stroke.

Differences in Acute Ischemic Stroke Quality of Care and Outcomes by Primary Stroke Center Certification Organization

Background and Purpose— Primary stroke center (PSC) certification was established to identify hospitals providing evidence-based care for stroke patients. The numbers of PSCs certified by Joint Commission (JC), Healthcare Facilities Accreditation Program, Det Norske Veritas, and State-based agencies have significantly increased in the past decade. This study aimed to evaluate whether PSCs certified by different organizations have similar quality of care and in-hospital outcomes. Methods— The study population consisted of acute ischemic stroke patients who were admitted to PSCs participating in Get With The Guidelines-Stroke between January 1, 2010, and December 31, 2012. Measures of care quality and outcomes were compared among the 4 different PSC certifications. Results— A total of 477 297 acute ischemic stroke admissions were identified from 977 certified PSCs (73.8% JC, 3.7% Det Norske Veritas, 1.2% Healthcare Facilities Accreditation Program, and 21.3% State-based). Composite care quality was generally similar among the 4 groups of hospitals, although State-based PSCs underperformed JC PSCs in a few key measures, including intravenous tissue-type plasminogen activator use. The rates of tissue-type plasminogen activator use were higher in JC and Det Norske Veritas (9.0% and 9.8%) and lower in State and Healthcare Facilities Accreditation Program certified hospitals (7.1% and 5.9%) (P<0.0001). Door-to-needle times were significantly longer in Healthcare Facilities Accreditation Program hospitals. State PSCs had higher in-hospital risk-adjusted mortality (odds ratio 1.23, 95% confidence intervals 1.07–1.41) compared with JC PSCs. Conclusions— Among Get With The Guidelines-Stroke hospitals with PSC certification, acute ischemic stroke quality of care and outcomes may differ according to which organization provided certification. These findings may have important implications for further improving systems of care.

Stroke Legislation Impacts Distribution of Certified Stroke Centers in the United States

Background and Purpose— The number of certified primary stroke centers (PSCs) have increased dramatically during the past decade in the United States We aimed to understand the factors affecting PSC distribution in the United States, including the impact of state stroke legislation. Methods— PSCs certified by national organization or state until December 2013 were searched from available databases. The proportion of PSC among short-term general hospitals in each state was calculated and factors affecting its distribution were analyzed. Results— By the end of 2013, the proportion of PSC varied from 4% to 100% among the 50 states and District of Columbia. The 18 states that had legislation in designating stroke centers and regulating stroke triage had higher PSC percentages (median, 43%; range, 13%–100%) than the remaining states (median, 13%; range, 4%–75%; P<0.001). State stroke legislation, urbanization, state economic output, and larger hospital size independently increased the likelihood of a hospital to be stroke certified. From 2009 to 2013, states with stroke legislation had greater increase of PSC percentages when compared with the states without legislation (median increase, 16% versus 6%; P=0.0067). Among the 1505 stroke centers, 74% were certified by the Joint Commission, 20% by state, and 6% by other organizations. Stroke centers certified only by state were smaller in size by hospital bed count compared with those certified by the Joint Commission (P<0.001). Conclusions— State stroke legislation, a generalizable intervention, increased the number of certified stroke centers in the United States, potentially improving accessibility of standardized care for patients with acute ischemic stroke.

Impact of Stroke Center Certification on Mortality After Ischemic Stroke: The Medicare Cohort From 2009 to 2013

Background and Purpose— An increasing number of hospitals have been certified as primary stroke centers (PSCs). It remains unknown whether the action toward PSC certification has improved the outcome of stroke care. This study aimed to understand whether PSC certification reduced stroke mortality. Methods— We examined Medicare fee-for-service beneficiaries aged ≥65 years who were hospitalized between 2009 and 2013 for ischemic stroke. Hospitals were classified into 3 groups: new PSCs, the hospitals that received initial PSC certification between 2009 and 2013 (n=634); existing PSCs, the PSCs certified before 2009 (n=785); and non-SCs, the hospitals that have never been certified as PSCs (n=2640). Multivariate logistic regression and Cox proportional hazards model was used to compare the mortality among the 3 groups. Results— Existing PSCs were significantly larger than new PSCs as reflected by total number of beds and annual stroke admission (P<0.0001). Compared with existing PSCs, new PSCs had lower in-hospital (odds ratio, 0.862; 95% confidence interval [CI], 0.817–0.910) and 30-day mortality (hazard ratio [HR], 0.981; 95% CI, 0.968–0.993), after adjusting for patient demographics and comorbidities. Compared with non-SCs, new PSCs had lower adjusted in-hospital (odds ratio, 0.894; 95% CI, 0.848–0.943), 30-day (HR, 0.904; 95% CI, 0.892–0.917), and 1-year mortality (HR, 0.907; 95% CI, 0.898–0.915). Existing PSCs had lower adjusted 30-day (HR, 0.922; 95% CI, 0.911–0.933) and 1-year mortality (HR, 0.900; 95% CI, 0.892–0.907) than non-SCs. Conclusions— Obtaining stroke certification may reduce stroke mortality and overcome the disadvantage of being smaller hospitals. Further study of other outcome measures will be useful to improve stroke system of care.

Comparison of Acute Ischemic Stroke Care and Outcomes Between Comprehensive Stroke Centers and Primary Stroke Centers in the United States

Background: To improve stroke care, the Brain Attack Coalition recommended establishing primary stroke center (PSC) and comprehensive stroke center (CSC) certification. This study aimed to compare ischemic stroke care and in-hospital outcomes between CSCs and PSCs. Methods and Results: We analyzed patients with acute ischemic stroke who were hospitalized at stroke centers participating in Get With The Guidelines-Stroke from 2013 to 2015. Multivariable logistic regression models were generated to examine the association between stroke center certification (CSC versus PSC) and performances and outcomes. This study included 722 941 patients who were admitted to 134 CSCs and 1047 PSCs. Both CSCs and PSCs had good conformity to 7 performance measures and the summary defect-free care measure. Among emergency department admissions, CSCs had higher intravenous tPA (tissue-type plasminogen activator) and endovascular thrombectomy rates than PSCs (14.3% versus 10.3%, 4.1% versus 1.0%, respectively). Door to intravenous tPA time was shorter at CSCs (median, 52 versus 61 minutes; adjusted risk ratio, 0.92; 95% confidence interval, 0.89–0.95). More patients at CSCs had door to intravenous tPA time ⩽60 minutes (79.7% versus 65.1%; adjusted odds ratio, 1.48; 95% confidence interval, 1.25–1.75). For transferred patients, CSCs and PSCs had comparable overall performance in defect-free care, except higher endovascular thrombectomy therapy rates. The overall in-hospital mortality was higher at CSCs in both emergency department admissions (4.6% versus 3.8%; adjusted odds ratio, 1.14; 95% confidence interval, 1.01–1.29) and transferred patients (7.7% versus 6.8%; adjusted odds ratio, 1.17; 95% confidence interval, 1.05–1.32). In-hospital outcomes were comparable between CSCs and PSCs in patients who received intravenous tPA or endovascular thrombectomy. Conclusions: CSCs and PSCs achieved similar overall care quality for patients with acute ischemic stroke. CSCs exceeded PSCs in timely acute reperfusion therapy for emergency department admissions, whereas PSCs had lower risk-adjusted in-hospital mortality. This information may be important for acute stroke triage and targeted quality improvement.

Cost Analysis of the Addition of Hyperacute Magnetic Resonance Imaging for Selection of Patients for Endovascular Stroke Therapy

Background and Purpose: Patient selection is important to determine the best candidates for endovascular stroke therapy. In application of a hyperacute magnetic resonance imaging (MRI) protocol for patient selection, we have shown decreased utilization with improved outcomes. A cost analysis comparing the pre- and post-MRI protocol time periods was performed to determine if the previous findings translated into cost opportunities. Materials and Methods: We retrospectively identified individuals considered for endovascular stroke therapy from January 2008 to August 2012 who were ≤8 h from stroke symptoms onset. Patients prior to April 30, 2010 were selected based on results of the computed tomography/computed tomography angiography alone (pre-hyperacute), whereas patients after April 30, 2010 were selected based on results of MRI (post-hyperacute MRI). Demographic, outcome, and financial information was collected. Log-transformed average daily direct costs were regressed on time period. The regression model included demographic and clinical covariates as potential confounders. Multiple imputation was used to account for missing data. Results: We identified 267 patients in our database (88 patients in pre-hyperacute MRI period, 179 in hyperacute MRI protocol period). Patient length of stay was not significantly different in the hyperacute MRI protocol period as compared to the pre-hyperacute MRI period (10.6 vs. 9.9 days, p < 0.42). The median of average daily direct costs was reduced by 24.5% (95% confidence interval 14.1-33.7%, p < 0.001). Conclusions: Use of the hyperacute MRI protocol translated into reduced costs, in addition to reduced utilization and better outcomes. MRI selection of patients is an effective strategy, both for patients and hospital systems.