Comparative safety of tenecteplase vs alteplase for acute ischemic stroke.

INTRODUCTION: Tenecteplase has been compared to alteplase in acute stroke randomized trials, with similar outcomes and safety measures, but higher doses of tenecteplase have been associated with higher hemorrhage rates in some studies. Limited data are available on the safety of tenecteplase outside of clinical trials. METHODS: We examined the safety measures of intracranial hemorrhage, angioedema, and serious extracranial adverse events in a 21-hospital integrated healthcare system that switched from alteplase (0.9 mg/kg, maximum dose 90 mg) to tenecteplase (0.25 mg/kg, maximum dose 25 mg) for acute ischemic stroke. RESULTS: Among 3,689 subjects, no significant differences were seen between tenecteplase and alteplase in the rate of intracranial hemorrhage (ICH), parenchymal hemorrhage, or volume of parenchymal hemorrhage. Symptomatic hemorrhage (sICH) was not different between the two agents: sICH by NINDS criteria was 2.0 % for alteplase vs 2.3 % for tenecteplase (P = 0.57), and sICH by SITS criteria was 0.8 % vs 1.1 % (P = 0.39). Adjusted logistic regression models also showed no differences between tenecteplase and alteplase: the odds ratio for tenecteplase (vs alteplase) modeling sICH by NINDS criteria was 0.9 (95 % CI 0.33 - 2.46, P = 0.83) and the odds ratio for tenecteplase modeling sICH by SITS criteria was 1.12 (95 % CI 0.25 - 5.07, P = 0.89). Rates of angioedema and serious extracranial adverse events were low and did not differ between tenecteplase and alteplase. Elapsed door-to-needle times showed a small improvement after the switch to tenecteplase (51.8 % treated in under 30 min with tenecteplase vs 43.5 % with alteplase, P < 0.001). CONCLUSION: In use outside of clinical trials, complication rates are similar between tenecteplase and alteplase. In the context of a stroke telemedicine program, the rates of hemorrhage observed with either agent were lower than expected based on prior trials and registry data. The more easily prepared tenecteplase was associated with a lower door-to-needle time.

Acute Stroke Presentation, Care, and Outcomes in Community Hospitals in Northern California During the COVID-19 Pandemic.

BACKGROUND AND PURPOSE: Shelter-in-place (SIP) orders implemented to mitigate severe acute respiratory syndrome coronavirus 2 spread may inadvertently discourage patient care-seeking behavior for critical conditions like acute ischemic stroke. We aimed to compare temporal trends in volume of acute stroke alerts, patient characteristics, telestroke care, and short-term outcomes pre- and post-SIP orders. METHODS: We conducted a cohort study in 21 stroke centers of an integrated healthcare system serving 4.4+ million members across Northern California. We included adult patients who presented with suspected acute stroke and were evaluated by telestroke between January 1, 2019, and May 9, 2020. SIP orders announced the week of March 15, 2020, created pre (January 1, 2019, to March 14, 2020) and post (March 15, 2020, to May 9, 2020) cohort for comparison. Main outcomes were stroke alert volumes and inpatient mortality for stroke. RESULTS: Stroke alert weekly volume post-SIP (mean, 98 [95% CI, 92-104]) decreased significantly compared with pre-SIP (mean, 132 [95% CI, 130-136]; P<0.001). Stroke discharges also dropped, in concordance with acute stroke alerts decrease. In total, 9120 patients were included: 8337 in pre- and 783 in post-SIP cohorts. There were no differences in patient demographics. Compared with pre-SIP, post-SIP patients had higher National Institutes of Health Stroke Scale scores (P=0.003), lower comorbidity score (P<0.001), and arrived more often by ambulance (P<0.001). Post-SIP, more patients had large vessel occlusions (P=0.03), and there were fewer stroke mimics (P=0.001). Discharge outcomes were similar for post-SIP and pre-SIP cohorts. CONCLUSIONS: In this cohort study, regional stroke alert and ischemic stroke discharge volumes decreased significantly in the early COVID-19 pandemic. Compared with pre-SIP, the post-SIP population showed no significant demographic differences but had lower comorbidity scores, more severe strokes, and more large vessel occlusions. The inpatient mortality was similar in both cohorts. Further studies are needed to understand the causes and implications of care avoidance to patients and healthcare systems.

Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment.

BACKGROUND AND PURPOSE: In large artery occlusion stroke, both intravenous (IV) tPA (tissue-type plasminogen activator) and endovascular stroke treatment (EST) are standard-of-care. It is unknown how often tPA causes distal embolization, in which a procedurally accessible large artery occlusion is converted to a more distal and potentially inaccessible occlusion. METHODS: We analyzed data from a decentralized stroke telemedicine program in an integrated healthcare delivery system covering 21 hospitals, with 2 high-volume EST centers. We captured all cases sent for EST and examined the relationship between IV tPA administration and the rate of distal embolization, the rate of target recanalization (modified Treatment in Cerebral Infarction scale 2b/3), clinical improvement before EST, and short-term and long-term clinical outcomes. RESULTS: Distal embolization before EST was quite common (63/314 [20.1%]) and occurred more often after IV tPA before EST (57/229 [24.9%]) than among those not receiving IV tPA (6/85 [7.1%]; P<0.001). Distal embolization was associated with an inability to attempt EST: after distal embolization, 26/63 (41.3%) could not have attempted EST because of the new clot location, while in cases without distal embolization, only 8/249 (3.2%) were unable to have attempted EST (P<0.001). Among patients who received IV tPA, 13/242 (5.4%) had sufficient symptom improvement that a catheter angiogram was not performed; 6/342 (2.5%) had improvement to within 2 points of their baseline NIHSS. At catheter angiogram, 2/229 (0.9%) of patients who had received tPA had complete recanalization without distal embolization. Both IV tPA and EST recanalization were associated with improved long-term outcome. CONCLUSIONS: IV tPA administration before EST for large artery occlusion is associated with distal embolization, which in turn may reduce the chance that EST can be attempted and recanalization achieved. At the same time, some IV tPA-treated patients show symptomatic improvement and complete recanalization. Because IV tPA is associated with both distal embolization and improved long-term clinical outcome, there is a need for prospective clinical trials testing the net benefit or harm of IV tPA before EST.

Cervical dystonia incidence and diagnostic delay in a multiethnic population.

BACKGROUND: Current cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is poorly characterized. OBJECTIVES: To determine CD incidence and characterize CD diagnostic delay within a large, multiethnic integrated health maintenance organization. METHODS: We identified incident CD cases using electronic medical records and multistage screening of more than 3 million Kaiser Permanente Northern California members from January 1, 2003, to December 31, 2007. A final diagnosis was made by movement disorders specialist consensus. Diagnostic delay was measured by questionnaire and health utilization data. Incidence rates were estimated assuming a Poisson distribution of cases and directly standardized to the 2000 U.S. census. Multivariate logistic regression models were employed to assess diagnoses and behaviors preceding CD compared with matched controls, adjusting for age, sex, and membership duration. RESULTS: CD incidence was 1.18/100,000 person-years (95% confidence interval [CI], 0.35-2.0; women, 1.81; men, 0.52) based on 200 cases over 15.4 million person-years. Incidence increased with age. Half of the CD patients interviewed reported diagnostic delay. Diagnoses more common in CD patients before the index date included essential tremor (odds ratio [OR] 68.1; 95% CI, 28.2-164.5), cervical disc disease (OR 3.83; 95% CI, 2.8-5.2), neck sprain/strain (OR 2.77; 95% CI, 1.99-3.62), anxiety (OR 2.24; 95% CI, 1.63-3.11) and depression (OR 1.94; 95% CI, 1.4-2.68). CONCLUSIONS: CD incidence is greater in women and increases with age. Diagnostic delay is common and associated with adverse effects. © 2019 International Parkinson and Movement Disorder Society.

Novel Telestroke Program Improves Thrombolysis for Acute Stroke Across 21 Hospitals of an Integrated Healthcare System.

BACKGROUND AND PURPOSE: Faster treatment with intravenous alteplase in acute ischemic stroke is associated with better outcomes. Starting in 2015, Kaiser Permanente Northern California redesigned its acute stroke workflow across all 21 Kaiser Permanente Northern California stroke centers to (1) follow a single standardized version of a modified Helsinki model and (2) have all emergency stroke cases managed by a dedicated telestroke neurologist. We examined the effect of Kaiser Permanente Northern California's Stroke EXpediting the PRrocess of Evaluating and Stopping Stroke program on door-to-needle (DTN) time, alteplase use, and symptomatic intracranial hemorrhage rates. METHODS: The program was introduced in a staggered fashion from September 2015 to January 2016. We compared DTN times for a seasonally adjusted 9-month period at each center before implementation to the corresponding 9-month calendar period from the start of implementation. The primary outcome was the DTN time for alteplase administration. Secondary outcomes included rate of alteplase administrations per month, symptomatic intracranial hemorrhage, and disposition at time of discharge. RESULTS: This study included 310 patients treated with alteplase in the pre-EXpediting the PRrocess of Evaluating and Stopping Stroke period and 557 patients treated with alteplase in the EXpediting the PRrocess of Evaluating and Stopping Stroke period. After implementation, alteplase administrations increased to 62/mo from 34/mo at baseline (P<0.001). Median DTN time decreased to 34 minutes after implementation from 53.5 minutes prior (P<0.001), and DTN time of <60 minutes was achieved in 87.1% versus 61.0% (P<0.001) of patients. DTN times <30 minutes were much more common in the Stroke EXpediting the PRrocess of Evaluating and Stopping Stroke period (40.8% versus 4.2% before implementation). There was no significant difference in symptomatic intracranial hemorrhage rates in the 2 periods (3.8% versus 2.2% before implementation; P=0.29). CONCLUSIONS: Introduction of a standardized modified Helsinki protocol across 21 hospitals using telestroke management was associated with increased alteplase administrations, significantly shorter DTN times, and no increase in adverse outcomes.

Outcome prediction in large vessel occlusion ischemic stroke with or without endovascular stroke treatment: THRIVE-EVT.

INTRODUCTION: The THRIVE score and the THRIVE-c calculation are validated ischemic stroke outcome prediction tools based on patient variables that are readily available at initial presentation. Randomized controlled trials (RCTs) have demonstrated the benefit of endovascular treatment (EVT) for many patients with large vessel occlusion (LVO), and pooled data from these trials allow for adaptation of the THRIVE-c calculation for use in shared clinical decision making regarding EVT. METHODS: To extend THRIVE-c for use in the context of EVT, we extracted data from the Virtual International Stroke Trials Archive (VISTA) from 7 RCTs of EVT. Models were built in a randomly selected development cohort using logistic regression that included the predictors from THRIVE-c: age, NIH Stroke Scale (NIHSS) score, presence of hypertension, diabetes mellitus, and/or atrial fibrillation, as well as randomization to EVT and, where available, the Alberta Stroke Program Early CT Score (ASPECTS). RESULTS: Good outcome was achieved in 366/787 (46.5%) of subjects randomized to EVT and in 236/795 (29.7%) of subjects randomized to control (P < 0.001), and the improvement in outcome with EVT was seen across age, NIHSS, and THRIVE-c good outcome prediction. Models to predict outcome using THRIVE elements (age, NIHSS, and comorbidities) together with EVT, with or without ASPECTS, had similar performance by ROC analysis in the development and validation cohorts (THRIVE-EVT ROC area under the curve (AUC) = 0.716 in development, 0.727 in validation, P = 0.30; THRIVE-EVT + ASPECTS ROC AUC = 0.718 in development, 0.735 in validation, P = 0.12). CONCLUSION: THRIVE-EVT may be used alongside the original THRIVE-c calculation to improve outcome probability estimation for patients with acute ischemic stroke, including patients with or without LVO, and to model the potential improvement in outcomes with EVT for an individual patient based on variables that are available at initial presentation. Online calculators for THRIVE-c estimation are available at www.thrivescore.org and www.mdcalc.com/thrive-score-for-stroke-outcome.

National Stroke Association recommendations for systems of care for transient ischemic attack.

Transient ischemic attacks (TIAs) are common and portend a high short-term risk of stroke. Evidence-based recommendations for the urgent evaluation and treatment of patients with TIA have been published. However, implementation of these recommendations reliably and consistently will require changes in the systems of care established for TIA. The National Stroke Association convened a multidisciplinary panel of experts to develop recommendations for the essential components of systems of care at hospitals to improve the quality of care provided to patients with TIA. The panel recommends that hospitals establish standardized protocols to assure rapid and complete evaluation and treatment for patients with TIA, with particular attention to urgency and close observation in patients at high risk of stroke.

Practice variation in neuroimaging to evaluate dizziness in the ED.

BACKGROUND: The appropriate role of neuroimaging to evaluate emergency department (ED) patients with dizziness is not established by guidelines or evidence. METHODS: We identified all adults with a triage complaint of dizziness who were evaluated at 20 EDs of a large Northern California integrated health care program in 2008. Using comprehensive medical records, we captured all head computed tomographies (CTs) or brain magnetic resonance images (MRIs) completed at presentation or within 2 days and all stroke diagnoses within 1 week. We assessed variation in neuroimaging use by site using a random-effects logistic model to account for differences in patient- (demographic and vascular risk factors) and site-level factors (volume, % patients with dizziness, and % patients with dizziness admitted) and linear regression to assess the relationship between neuroimaging rates and stroke diagnosis rates by site. RESULTS: Of 378 992 patients seen in 2008, 20 795 (5.5%) had at least one ED visit for dizziness. Overall, 5585 patients (26.9%) had a head CT and 652 (3.1%) had a brain MRI. Between 21.8% and 32.8% of ED patients with dizziness at each site had a head CT (P<.001). For brain MRI, the range was 0.8% to 6.2%-a nearly 8-fold variation (P<.001) that persisted after adjustment for patient- and site-level factors. Higher neuroimaging rates did not translate into higher stroke diagnoses rates, with 0.7% to 2.5% of patients with dizziness diagnosed with stroke by site. CONCLUSION: The use of neuroimaging for ED patients with dizziness varies substantially without an associated improvement in stroke diagnosis, which is identified only rarely.

Validation of the Stroke Prognostic Instrument-II in a large, modern, community-based cohort of ischemic stroke survivors.

BACKGROUND AND PURPOSE: The risk of recurrent stroke in the modern era of secondary stroke prevention is not well defined. Several prediction models, including the Stroke Prognostic Instrument-II (SPI-II), have been created to identify patients at highest risk, but their performance in modern populations has been infrequently tested. We aimed to assess the 1-year risk of recurrence after hospital discharge in a recent, large, community-based cohort of patients with ischemic stroke and to validate the SPI-II prediction model in this cohort. METHODS: From 2004 through 2006, 5575 patients with acute ischemic stroke were prospectively identified and followed for recurrent events. Kaplan-Meier statistics were used to analyze the cumulative incidence of recurrent ischemic stroke. Harrell c-statistic was calculated to determine the performance of SPI-II in predicting stroke or death at 1 year, and the log-rank test was used to compare the differences among low-, middle-, and high-risk groups. RESULTS: Among 5575 patients with ischemic stroke, recurrence was observed in 221 during the subsequent year. Kaplan-Meier estimates of cumulative rates of recurrent stroke were 2.5%, 3.6%, and 4.8% at 3, 6, and 12 months, respectively. Rates of stroke or death for SPI-II in the low-, middle-, and high-risk groups were 8.2%, 24.5%, and 35.6%, respectively (trend, P=0.001). The c-statistic for SPI-II was 0.62 (95% CI, 0.61-0.64). CONCLUSIONS: The modern 1-year rate of recurrent stroke after hospital discharge is low but still substantial at 4.8%. SPI-II is a modestly effective tool in identifying patients with ischemic stroke at highest risk of developing recurrence or death.

Standardized discharge orders after stroke: results of the quality improvement in stroke prevention (QUISP) cluster randomized trial.

OBJECTIVE: Proven strategies to reduce risk of stroke recurrence are under-utilized. We sought to evaluate the impact of standardized stroke discharge orders on treatment practices in a cluster-randomized trial. METHODS: The Quality Improvement in Stroke Prevention (QUISP) trial randomized 12 hospitals to continue usual care or to receive assistance in the development and implementation of standardized stroke discharge orders. All patients with ischemic stroke were identified during a 12-month period prior to implementation and for 12 months afterward, and were followed for 6 months after discharge. The primary outcome was optimal treatment at 6 months, defined as taking a statin, having blood pressure <140/90mmHg, and receiving anticoagulation if atrial fibrillation was diagnosed. The primary analysis treated the hospital as the unit of analysis, comparing optimal treatment rates-adjusted for race, age, dementia, atrial fibrillation, and history of bleeding-between intervention and non-intervention hospitals using a paired t test. RESULTS: In the primary analysis with hospital as the unit of analysis, the odds of optimal treatment was not significantly increased at intervention compared to non-intervention hospitals (odds ratio, 1.39; 95% confidence interval, 0.71-2.76; p = 0.27). However, in analyses conducted at the level of the individual patients (N = 3,361), rates of optimal treatment increased from 37% to 45% in the intervention hospitals (p = 0.001) and did not change significantly in the non-intervention hospitals (39% to 40%; p = 0.27). INTERPRETATION: Implementation of standardized discharge orders after stroke was associated with increased rates of optimal secondary prevention; this improvement was not significant in the primary analysis at the hospital level.

Potential accuracy of prehospital NIHSS-based triage for selection of candidates for acute endovascular stroke therapy.

OBJECTIVE: Whether patients with acute stroke and large vessel occlusion (LVO) benefit from prehospital identification and diversion by emergency medical services (EMS) to an endovascular stroke therapy (EST)-capable center is controversial. We sought to estimate the accuracy of field-based identification of potential EST candidates in a hypothetical best-of-all-worlds situation. METHODS: In Kaiser Permanente Northern California, all acute stroke patients arriving at its 21 stroke centers between 7:00 am and midnight from January 2016 to December 2019 were evaluated by teleneurologists on arrival. Initial National Institutes of Health Stroke Scale (NIHSS) score, presence of LVO, and referral for EST were obtained from standardized teleneurology notes. Factors associated with LVO were evaluated using generalized estimating equations accounting for clustering by facility. RESULTS: Among 13,377 patients brought in by EMS with potential stroke, 7168 (53.6%) were not candidates for acute stroke interventions. Of the remaining 6089 cases, 2,573 (42.3%) had an NIHSS score >10, the cutoff with a higher association for LVO. Only 703 patients (27.3% with NIHSS score >10) were ultimately diagnosed with LVO and referred for EST. Across all NIHSS scores, only 884 (6.6%) suspected acute stroke patients had LVO and EST referral. CONCLUSIONS: Even if field-based tools were as accurate as NIHSS scoring and predictions by stroke neurologists, only about 1 in 4 acute stroke patients diverted to EST-capable centers would benefit by receiving EST. Depending on geography and stroke center performance on door-to-needle time, many systems may be better served by focusing on expediting evaluation, treatment with intravenous thrombolysis, and transfer to EST-capable centers.

Gender differences in treatment of severe carotid stenosis after transient ischemic attack.

BACKGROUND AND PURPOSE: Gender differences in carotid endarterectomy (CEA) rates after transient ischemic attack are not well studied, although some reports suggest that eligible men are more likely to have CEA than women after stroke. METHODS: We retrospectively identified all patients diagnosed with transient ischemic attack and >or=70% carotid stenosis on ultrasound in 2003 to 2004 from 19 emergency departments. Medical records were abstracted for clinical data; 90-day follow-up events, including stroke, cardiovascular events, or death; CEA within 6 months; and postoperative 30-day outcomes. We assessed gender as a predictor of CEA and its complications adjusting for demographic and clinical variables as well as time to CEA between groups. RESULTS: Of 299 patients identified, 47% were women. Women were older with higher presenting systolic blood pressure and less likely to smoke or to have coronary artery disease or diabetes. Fewer women (36.4%) had CEA than men (53.8%; P=0.004). Reasons for withholding surgical treatment were similar in women and men, and there were no differences in follow-up stroke, cardiovascular event, postoperative complications, or death. Time to CEA was also significantly delayed in women. CONCLUSIONS: Women with severe carotid stenosis and recent transient ischemic attack are less likely to undergo CEA than men, and surgeries are more delayed.

Race-ethnicity on blood pressure control after ischemic stroke: a prospective cohort study.

Disparities in health care access and socioeconomic status (SES) have been associated with racial-ethnic differences in blood pressure (BP) control. We examined post-ischemic stroke BP in a multiethnic cohort with good health care access. We included all hypertensive patients (n = 2972) from a randomized quality improvement trial on secondary stroke prevention, conducted in 14 Kaiser Permanente hospitals in Northern California from 2004-2006 (QUISP). Average age 73.2 ± 12.2 years; 52% female, 66% non-Hispanic white, 14% African-American, 11% Asian, 8% Hispanic, and 1% other. Demographics, diagnoses, health care utilization, BP measurements, and medications were obtained as part of routine care. We used random effects logistic regression models to examine race as a predictor of blood pressure control (<140/90 mm Hg) at 6 months post-discharge, adjusted for SES, age, gender, dementia, antihypertensive therapy, and attendance at follow-up visits. At 6 months, BP was controlled in 52.7% of blacks compared to 61.4% of whites (OR = 0.63, 95% CI, 0.48-0.82, P = .001). Black race remained independently associated with poorer BP control in adjusted analysis, although blacks were as likely to attend post-discharge visits, and more likely to be on any antihypertensive therapy than whites. Greater difficulty in controlling BP and lifestyle differences may account for this difference.

Massive CNS monocytic infiltration at autopsy in an alemtuzumab-treated patient with NMO.

OBJECTIVES: To describe the clinical course and neuropathology at autopsy of a patient with neuromyelitis optica (NMO) treated with alemtuzumab. METHODS: Case report. RESULTS: A 61-year-old woman with aquaporin-4 immunoglobulin G antibody seropositive NMO had 10 clinical relapses in 4 years despite treatment with multiple immunosuppressive therapies. Alemtuzumab was administered and was redosed 15 months later. For the first 19 months after the initial alemtuzumab infusion, the patient did not experience discrete clinical relapses or have evidence of abnormally enhancing lesions on brain or spinal cord MRI. However, she experienced insidiously progressive nausea, vomiting, and vision loss, and her brain MRI revealed marked extension of cortical, subcortical, and brainstem T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities. She died 20 months after the initial alemtuzumab infusion. Acute, subacute, and chronic demyelinating lesions were found at autopsy. Many of the lesions showed marked macrophage infiltration with a paucity of lymphocytes. CONCLUSIONS: Following alemtuzumab treatment, there appeared to be ongoing innate immune activation associated with tissue destruction that correlated with nonenhancing T2/FLAIR hyperintensities on MRI. We interpret the cessation of clinical relapses, absence of contrast-enhancing lesions, and scarcity of lymphocytes at autopsy to be indicative of suppression of adaptive immunity by alemtuzumab. This case illustrates that progressive worsening in NMO can occur as a consequence of tissue injury associated with monocytic infiltration. This observation may be relevant to multiple sclerosis (MS) as well as NMO and might explain why in previous studies of secondary progressive MS alemtuzumab did not seem to inhibit disability progression despite a dramatic decline in contrast-enhancing lesions.