Strokes Averted by Intravenous Thrombolysis: A Secondary Analysis of a Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

OBJECTIVE: This study was undertaken to examine averted stroke in optimized stroke systems. METHODS: This secondary analysis of a multicenter trial from 2014 to 2020 compared patients treated by mobile stroke unit (MSU) versus standard management. The analytical cohort consisted of participants with suspected stroke treated with intravenous thrombolysis. The main outcome was a tissue-defined averted stroke, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis and no acute infarction/hemorrhage on imaging. An additional outcome was stroke with early symptom resolution, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis. RESULTS: Among 1,009 patients with a median last known well to thrombolysis time of 87 minutes, 159 (16%) had tissue-defined averted stroke and 276 (27%) had stroke with early symptom resolution. Compared with standard management, MSU care was associated with more tissue-defined averted stroke (18% vs 11%, adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.13-2.98) and stroke with early symptom resolution (31% vs 21%, aOR = 1.74, 95% CI = 1.12-2.61). The relationships between thrombolysis treatment time and averted/early recovered stroke appeared nonlinear. Most models indicated increased odds for stroke with early symptom resolution but not tissue-defined averted stroke with earlier treatment. Additionally, younger age, female gender, hyperlipidemia, lower National Institutes of Health Stroke Scale, lower blood pressure, and no large vessel occlusion were associated with both tissue-defined averted stroke and stroke with early symptom resolution. INTERPRETATION: In optimized stroke systems, 1 in 4 patients treated with thrombolysis recovered within 24 hours and 1 in 6 had no demonstrable brain injury on imaging. ANN NEUROL 2024;95:347-361.

Effectiveness of Pfizer-BioNTech (BNT162b2) Vaccine Among Adolescents (Aged 12-15 Years): An Observational Study in Qatar.

In May 2021, Qatar launched the BNT162b2 COVID-19 vaccine campaign for adolescents aged 12 to 15 years across all 27 health centers. Our study assessed the safety and efficacy of the vaccine among vaccinated and nonvaccinated adolescents in Qatar. Using a retrospective observational study, we analyzed the medical records of 1956 adolescents who were severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive from June 17 to December 17, 2021. The mean age for the vaccinated group was 13.89 ± 0.93 years, and for the nonvaccinated group, it was 12.99 ± 0.93 years. In the vaccinated group, 46% were male (n = 185) compared with 53% in the nonvaccinated group (n = 827) and 54% were female in the vaccinated group (n = 217) versus 47% in the nonvaccinated group (n = 727). Our findings demonstrate satisfactory protection provided by the Pfizer-BioNTech COVID-19 vaccine, with only one fifth of the study population contracting SARS-CoV-2 infections after the double-dose regimen. These results highlight the importance of maximizing vaccination coverage and considering booster doses for adolescents to enhance protection.

Validation of the International Classification of Diseases, Tenth Revision Code for the National Institutes of Health Stroke Scale Score.

BACKGROUND: Administrative data can be useful for stroke research but have historically lacked data on stroke severity. Hospitals increasingly report the National Institutes of Health Stroke Scale (NIHSS) score using an International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code, but this code's validity remains unclear. METHODS: We examined the concordance of ICD-10 NIHSS scores versus NIHSS scores recorded in CAESAR (Cornell Acute Stroke Academic Registry). We included all patients with acute ischemic stroke from October 1, 2015, when US hospitals transitioned to ICD-10, through 2018, the latest year in our registry. The NIHSS score (range, 0-42) recorded in our registry served as the reference gold standard. ICD-10 NIHSS scores were derived from hospital discharge diagnosis code R29.7xx, with the latter 2 digits representing the NIHSS score. Multiple logistic regression was used to explore factors associated with availability of ICD-10 NIHSS scores. We used ANOVA to examine the proportion of variation (R2) in the true (registry) NIHSS score that was explained by the ICD-10 NIHSS score. RESULTS: Among 1357 patients, 395 (29.1%) had an ICD-10 NIHSS score recorded. This proportion increased from 0% in 2015 to 46.5% in 2018. In a logistic regression model, only higher registry NIHSS score (odds ratio per point, 1.05 [95% CI, 1.03-1.07]) and cardioembolic stroke (odds ratio, 1.4 [95% CI, 1.0-2.0]) were associated with availability of the ICD-10 NIHSS score. In an ANOVA model, the ICD-10 NIHSS score explained almost all the variation in the registry NIHSS score (R2=0.88). Fewer than 10% of patients had a large discordance (≥4 points) between their ICD-10 and registry NIHSS scores. CONCLUSIONS: When present, ICD-10 codes representing NIHSS scores had excellent agreement with NIHSS scores recorded in our stroke registry. However, ICD-10 NIHSS scores were often missing, especially in less severe strokes, limiting the reliability of these codes for risk adjustment.

Risk Stratification Models for Stroke in Patients Hospitalized with COVID-19 Infection.

OBJECTIVES: To derive models that identify patients with COVID-19 at high risk for stroke. MATERIALS AND METHODS: We used data from the AHA's Get With The Guidelines® COVID-19 Cardiovascular Disease Registry to generate models for predicting stroke risk among adults hospitalized with COVID-19 at 122 centers from March 2020-March 2021. To build our models, we used data on demographics, comorbidities, medications, and vital sign and laboratory values at admission. The outcome was a cerebrovascular event (stroke, TIA, or cerebral vein thrombosis). First, we used Cox regression with cross validation techniques to identify factors associated with the outcome in both univariable and multivariable analyses. Then, we assigned points for each variable based on corresponding coefficients to create a prediction score. Second, we used machine learning techniques to create risk estimators using all available covariates. RESULTS: Among 21,420 patients hospitalized with COVID-19, 312 (1.5%) had a cerebrovascular event. Using traditional Cox regression, we created/validated a COVID-19 stroke risk score with a C-statistic of 0.66 (95% CI, 0.60-0.72). The CANDLE score assigns 1 point each for prior cerebrovascular disease, afebrile temperature, no prior pulmonary disease, history of hypertension, leukocytosis, and elevated systolic blood pressure. CANDLE stratified risk of an acute cerebrovascular event according to low- (0-1: 0.2% risk), medium- (2-3: 1.1% risk), and high-risk (4-6: 2.1-3.0% risk) groups. Machine learning estimators had similar discriminatory performance as CANDLE: C-statistics, 0.63-0.69. CONCLUSIONS: We developed a practical clinical score, with similar performance to machine learning estimators, to help stratify stroke risk among patients hospitalized with COVID-19.

Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

BACKGROUND: Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied. METHODS: In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.5 hours after onset of acute stroke symptoms. The primary outcome was the score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes according to a patient value system, derived from scores on the modified Rankin scale of 0 to 6, with higher scores indicating more disability). The main analysis involved dichotomized scores on the utility-weighted modified Rankin scale (≥0.91 or <0.91, approximating scores on the modified Rankin scale of ≤1 or >1) at 90 days in patients eligible for t-PA. Analyses were also performed in all enrolled patients. RESULTS: We enrolled 1515 patients, of whom 1047 were eligible to receive t-PA; 617 received care by MSU and 430 by EMS. The median time from onset of stroke to administration of t-PA was 72 minutes in the MSU group and 108 minutes in the EMS group. Of patients eligible for t-PA, 97.1% in the MSU group received t-PA, as compared with 79.5% in the EMS group. The mean score on the utility-weighted modified Rankin scale at 90 days in patients eligible for t-PA was 0.72 in the MSU group and 0.66 in the EMS group (adjusted odds ratio for a score of ≥0.91, 2.43; 95% confidence interval [CI], 1.75 to 3.36; P<0.001). Among the patients eligible for t-PA, 55.0% in the MSU group and 44.4% in the EMS group had a score of 0 or 1 on the modified Rankin scale at 90 days. Among all enrolled patients, the mean score on the utility-weighted modified Rankin scale at discharge was 0.57 in the MSU group and 0.51 in the EMS group (adjusted odds ratio for a score of ≥0.91, 1.82; 95% CI, 1.39 to 2.37; P<0.001). Secondary clinical outcomes generally favored MSUs. Mortality at 90 days was 8.9% in the MSU group and 11.9% in the EMS group. CONCLUSIONS: In patients with acute stroke who were eligible for t-PA, utility-weighted disability outcomes at 90 days were better with MSUs than with EMS. (Funded by the Patient-Centered Outcomes Research Institute; BEST-MSU ClinicalTrials.gov number, NCT02190500.).

HaNDL Syndrome Presenting with Thunderclap Headache.

INTRODUCTION: Transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) is defined as a secondary, nonvascular headache disorder characterized by the findings described in its name. Patients with HaNDL syndrome typically present with gradual onset migrainous headaches of moderate to severe intensity with transient neurological symptoms. Case Report. We discuss a patient who presented with thunderclap headache, recent transient neurologic deficits, and was ultimately diagnosed with HaNDL after an extensive neurologic evaluation. CONCLUSION: Thunderclap headache has very rarely been described in patients with HaNDL. After excluding emergent and secondary causes, HaNDL should be considered in patients with thunderclap-quality headaches, particularly when there is a history of transient neurological symptoms.

Missed cerebrovascular events during prolonged sedation for COVID-19 pneumonia.

Cerebrovascular complications among critically ill patients with COVID-19 have yet to be fully characterized. In this retrospective case series from a single academic tertiary care referral center in New York City, we present 12 patients with ischemic or hemorrhagic strokes that were found on imaging after a period of prolonged sedation in the setting of COVID-19 pneumonia. This series demonstrates a pattern of cerebrovascular events clinically masked by deep sedation required for management of COVID-19 related acute respiratory distress syndrome (ARDS). Of the 12 patients included, 10 had ischemic stroke, 4 of which had hemorrhagic conversion, and 2 had primary intracerebral hemorrhage. Ten patients were on therapeutic anticoagulation prior to discovery of their stroke, and the remainder received intermediate dose anticoagulation (in a range between prophylactic and therapeutic levels). Additional studies are needed to further characterize the counterbalancing risks of ischemic and hemorrhagic stroke, as well as the optimal management of this patient population.

Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza.

IMPORTANCE: It is uncertain whether coronavirus disease 2019 (COVID-19) is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection. OBJECTIVE: To compare the rate of ischemic stroke between patients with COVID-19 and patients with influenza, a respiratory viral illness previously associated with stroke. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted at 2 academic hospitals in New York City, New York, and included adult patients with emergency department visits or hospitalizations with COVID-19 from March 4, 2020, through May 2, 2020. The comparison cohort included adults with emergency department visits or hospitalizations with influenza A/B from January 1, 2016, through May 31, 2018 (spanning moderate and severe influenza seasons). EXPOSURES: COVID-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 in the nasopharynx by polymerase chain reaction and laboratory-confirmed influenza A/B. MAIN OUTCOMES AND MEASURES: A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. We used logistic regression to compare the proportion of patients with COVID-19 with ischemic stroke vs the proportion among patients with influenza. RESULTS: Among 1916 patients with emergency department visits or hospitalizations with COVID-19, 31 (1.6%; 95% CI, 1.1%-2.3%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78 years); 18 (58%) were men. Stroke was the reason for hospital presentation in 8 cases (26%). In comparison, 3 of 1486 patients with influenza (0.2%; 95% CI, 0.0%-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3-25.2). The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission. CONCLUSIONS AND RELEVANCE: In this retrospective cohort study from 2 New York City academic hospitals, approximately 1.6% of adults with COVID-19 who visited the emergency department or were hospitalized experienced ischemic stroke, a higher rate of stroke compared with a cohort of patients with influenza. Additional studies are needed to confirm these findings and to investigate possible thrombotic mechanisms associated with COVID-19.

Risk of Ischemic Stroke in Patients with Covid-19 versus Patients with Influenza.

IMPORTANCE: Case series without control groups suggest that Covid-19 may cause ischemic stroke, but whether Covid-19 is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection is uncertain. OBJECTIVE: To compare the rate of ischemic stroke between patients with Covid-19 and patients with influenza, a respiratory viral illness previously linked to stroke. DESIGN: A retrospective cohort study. SETTING: Two academic hospitals in New York City. PARTICIPANTS: We included adult patients with emergency department visits or hospitalizations with Covid-19 from March 4, 2020 through May 2, 2020. Our comparison cohort included adult patients with emergency department visits or hospitalizations with influenza A or B from January 1, 2016 through May 31, 2018 (calendar years spanning moderate and severe influenza seasons). Exposures: Covid-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharynx by polymerase chain reaction, and laboratory-confirmed influenza A or B. Main Outcomes and Measures: A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, etiological mechanisms, and outcomes. We used logistic regression to compare the proportion of Covid-19 patients with ischemic stroke versus the proportion among patients with influenza. RESULTS: Among 2,132 patients with emergency department visits or hospitalizations with Covid-19, 31 patients (1.5%; 95% confidence interval [CI], 1.0%-2.1%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78) and 58% were men. Stroke was the reason for hospital presentation in 8 (26%) cases. For our comparison cohort, we identified 1,516 patients with influenza, of whom 0.2% (95% CI, 0.0-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was significantly higher with Covid-19 than with influenza infection (odds ratio, 7.5; 95% CI, 2.3-24.9). CONCLUSIONS AND RELEVANCE: Approximately 1.5% of patients with emergency department visits or hospitalizations with Covid-19 experienced ischemic stroke, a rate 7.5-fold higher than in patients with influenza. Future studies should investigate the thrombotic mechanisms in Covid-19 in order to determine optimal strategies to prevent disabling complications like ischemic stroke.

Mobile Stroke Units: Bringing Treatment to the Patient.

PURPOSE OF REVIEW: Mobile stroke units (MSUs) have revolutionized emergency stroke care by delivering pre-hospital thrombolysis faster than conventional ambulance transport and in-hospital treatment. This review discusses the history of MSUs technological development, current operations and research, cost-effectiveness, and future directions. RECENT FINDINGS: Multiple prospective and retrospective studies have shown that MSUs deliver acute ischemic stroke treatment with intravenous recombinant tissue plasminogen activator (IV r-tPA) approximately 30 min faster than conventional care. The 90-day modified Rankin Scores for patients who received IV r-tPA on the MSU compared to conventional care were not statistically different in the PHANTOM-S study. Two German studies suggest that the MSU model is cost-effective by reducing disability and improving adjusted quality-life years post-stroke. The ongoing BEST-MSU trial will be the first multicenter, randomized controlled study that will shed light on MSUs' impact on long-term neurologic outcomes and cost-effectiveness. MSUs are effective in reducing treatment times in acute ischemic stroke without increasing adverse events. MSUs could potentially improve treatment times in large vessel occlusion and intracranial hemorrhage. Further studies are needed to assess functional outcomes and cost-effectiveness. Clinical trials are ongoing internationally.

Geographic Analysis of Mobile Stroke Unit Treatment in a Dense Urban Area: The New York City METRONOME Registry.

Background Mobile stroke units (MSUs) reduce time to intravenous thrombolysis in acute ischemic stroke. Whether this advantage exists in densely populated urban areas with many proximate hospitals is unclear. Methods and Results We evaluated patients from the METRONOME (Metropolitan New York Mobile Stroke) registry with suspected acute ischemic stroke who were transported by a bi-institutional MSU operating in Manhattan, New York, from October 2016 to September 2017. The comparison group included patients transported to our hospitals via conventional ambulance for acute ischemic stroke during the same hours of MSU operation (Monday to Friday, 9 am to 5 pm). Our exposure was MSU care, and our primary outcome was dispatch-to-thrombolysis time. We estimated mean differences in the primary outcome between both groups, adjusting for clinical, demographic, and geographic factors, including numbers of nearby designated stroke centers and population density. We identified 66 patients treated or transported by MSU and 19 patients transported by conventional ambulance. Patients receiving MSU care had significantly shorter dispatch-to-thrombolysis time than patients receiving conventional care (mean: 61.2 versus 91.6 minutes; P=0.001). Compared with patients receiving conventional care, patients receiving MSU care were significantly more likely to be picked up closer to a higher mean number of designated stroke centers in a 2.0-mile radius (4.8 versus 2.7, P=0.002). In multivariable analysis, MSU care was associated with a mean decrease in dispatch-to-thrombolysis time of 29.7 minutes (95% CI, 6.9-52.5) compared with conventional care. Conclusions In a densely populated urban area with a high number of intermediary stroke centers, MSU care was associated with substantially quicker time to thrombolysis compared with conventional ambulance care.

Clinical Information Systems Integration in New York City's First Mobile Stroke Unit.

BACKGROUND: Mobile stroke units (MSUs) reduce time to thrombolytic therapy in acute ischemic stroke. These units are widely used, but the clinical information systems underlying MSU operations are understudied. OBJECTIVE: The first MSU on the East Coast of the United States was established at New York Presbyterian Hospital (NYP) in October 2016. We describe our program's 7-month pilot, focusing on the integration of our hospital's clinical information systems into our MSU to support patient care and research efforts. METHODS: NYP's MSU was staffed by two paramedics, one radiology technologist, and a vascular neurologist. The unit was equipped with four laptop computers and networking infrastructure enabling all staff to access the hospital intranet and clinical applications during operating hours. A telephone-based registration procedure registered patients from the field into our admit/discharge/transfer system, which interfaced with the institutional electronic health record (EHR). We developed and implemented a computerized physician order entry set in our EHR with prefilled values to permit quick ordering of medications, imaging, and laboratory testing. We also developed and implemented a structured clinician note to facilitate care documentation and clinical data extraction. RESULTS: Our MSU began operating on October 3, 2016. As of April 27, 2017, the MSU transported 49 patients, of whom 16 received tissue plasminogen activator (t-PA). Zero technical problems impacting patient care were reported around registration, order entry, or intranet access. Two onboard network failures occurred, resulting in computed tomography scanner malfunctions, although no patients became ineligible for time-sensitive treatment as a result. Thirteen (26.5%) clinical notes contained at least one incomplete time field. CONCLUSION: The main technical challenges encountered during the integration of our hospital's clinical information systems into our MSU were onboard network failures and incomplete clinical documentation. Future studies are necessary to determine whether such integrative efforts improve MSU care quality, and which enhancements to information systems will optimize clinical care and research efforts.

Modeling the Impact of Interhospital Transfer Network Design on Stroke Outcomes in a Large City.

BACKGROUND AND PURPOSE: We sought to model the effects of interhospital transfer network design on endovascular therapy eligibility and clinical outcomes of stroke because of large-vessel occlusion for the residents of a large city. METHODS: We modeled 3 transfer network designs for New York City. In model A, patients were transferred from spoke hospitals to the closest hub hospitals with endovascular capabilities irrespective of hospital affiliation. In model B, which was considered the base case, patients were transferred to the closest affiliated hub hospitals. In model C, patients were transferred to the closest affiliated hospitals, and transfer times were adjusted to reflect full implementation of streamlined transfer protocols. Using Monte Carlo methods, we simulated the distributions of endovascular therapy eligibility and good functional outcomes (modified Rankin Scale score, 0-2) in these models. RESULTS: In our models, 200 patients (interquartile range [IQR], 168-227) with a stroke amenable to endovascular therapy present to New York City spoke hospitals each year. Transferring patients to the closest hub hospital irrespective of affiliation (model A) resulted in 4 (IQR, 1-9) additional patients being eligible for endovascular therapy and an additional 1 (IQR, 0-2) patient achieving functional independence. Transferring patients only to affiliated hospitals while simulating full implementation of streamlined transfer protocols (model C) resulted in 17 (IQR, 3-41) additional patients being eligible for endovascular therapy and 3 (IQR, 1-8) additional patients achieving functional independence. CONCLUSIONS: Optimizing acute stroke transfer networks resulted in clinically small changes in population-level stroke outcomes in a dense, urban area.

Novel iron oxide microparticles used to render stone fragments paramagnetic: assessment of toxicity in a murine model.

PURPOSE: We developed novel peptide coated iron oxide supraparamagnetic microparticles that bind to calcium stones, allowing for extraction of these stones with magnetic tools. Urothelial and fibroblast cell lines show minimal to no toxicity when exposed to the particles. Before clinical evaluation, assessment of the in vivo systemic toxicity of the microparticles was required. This was studied in a murine model. MATERIALS AND METHODS: A total of 64 mice were exposed to different concentrations of microparticles (0.5, 1 or 5 mg/dl) intravesically or intravenously via the tail vein. Mice were sacrificed at different intervals (days 1, 3, 28 and 84). Representative samples from the brain, lung, heart, kidney and liver were evaluated histologically at each time point. The tissue distribution pattern of the particles and any degree of inflammation was noted by a clinical pathologist. Liver function tests were also performed at similar intervals. RESULTS: All mice survived until the assigned end point and appeared healthy after exposure to microparticles. In the bladder installation group no particles were seen in any organ regardless of the particle concentration instilled. In the intravenous instillation group there was tissue distribution in the liver and to a lesser extent in the lung. There was mild inflammation in the liver and lung, which was dose dependent. CONCLUSIONS: Novel iron oxide supraparamagnetic microparticles used to render stone fragments paramagnetic in the urinary collecting system did not appear to cross intact urothelial membranes. When introduced systemically, they led to minimal inflammatory changes, predominantly in the liver and lung. Additional long-term studies are required.

Tadalafil for prevention of renal dysfunction secondary to renal ischemia.

INTRODUCTION: Growing evidence suggests that phosphodiesterase-5 inhibitors may mitigate ischemia-related renal damage through multiple mechanisms. We evaluated the role of tadalafil in renal function preservation during experimentally induced ischemia/reperfusion injury (IRI) in a solitary kidney porcine model. MATERIALS AND METHODS: Ten adult female pigs underwent left laparoscopic nephrectomy followed by a 1 week recovery period. They were then randomized to tadalafil versus no treatment prior to cross-clamping the contralateral renal hilum for 90 minutes. The experimental group received 40 mg tadalafil in two equally divided doses, 12 hours before and just prior to surgery. Serum creatinine for each animal was obtained just prior to ischemia induction (D0) and at days 1, 3 and 7 following hilar occlusion. Median creatinine at each time point was compared between groups using the Kruskal-Wallis test. RESULTS: Median serum creatinine at D0 was significantly lower in the tadalafil group (after two doses of tadalafil) (123.8 µmol/L versus 168.0 µmol/L, p = 0.009). As expected, median creatinine for each group rose significantly on D1 (p = 0.04 for each). Median creatinines following hilar occlusion at D1, D3 and D7, however, were not significantly different between groups. CONCLUSIONS: In this porcine model, administration of perioperative tadalafil improves preoperative renal function, but it does not appear to mitigate ischemia/ reperfusion injury from hilar occlusion.