Differences in stroke clinical presentation among sexes.

INTRODUCTION: There are sex-based differences in stroke epidemiology, treatment, and outcomes. In this manuscript, we discuss the differences that exist in the clinical presentation of acute stroke among sexes. DISCUSSION: We present the differences in stroke presentation among sexes including age at the time of presentation, severity of stroke on presentation, and stroke type and location. We discuss the atypical clinical presentations, explore the radiographic findings on presentation (including location, infarct core volume, the impact of collateral circulation, hematoma location in intracranial hemorrhage), and discuss differences in time elapsed between symptom onset and management amongst sexes. CONCLUSION: Differences exist in stroke clinical presentation amongst sexes. These disparities have public health implications, and as they become better understood, impact awareness campaigns in both the public and healthcare communities.

Quantitative Time-of-Flight Head Magnetic Resonance Angiography of Cerebrovascular Disease.

BACKGROUND: Standard Cartesian time-of-flight (TOF) head magnetic resonance angiography (MRA) is routinely used to evaluate the intracranial arteries, but does not provide quantitative hemodynamic information that is useful for patient risk stratification as well as for monitoring treatment and tracking changes in blood flow over time. Quantitative TOF (qTOF) MRA represents a new and efficient method for simultaneous evaluating the intracranial arteries and quantifying blood flow velocity, but it has not yet been evaluated in patients with cerebrovascular disease. PURPOSE: To evaluate qTOF for simultaneously evaluating the intracranial arteries and quantifying intracranial blood flow velocity in patients with cerebrovascular disease, without the need for a phase contrast (PC) scan. STUDY TYPE: Prospective. SUBJECTS: Twenty-four patients (18 female, 6 male) with cerebrovascular disease. FIELD STRENGTH/SEQUENCES: Head MRA at 3 T using gradient-echo 3D qTOF, standard Cartesian TOF, and PC protocols. ASSESSMENT: Three independent readers assessed arterial image quality using a 4-point scale (1: non-diagnostic, 4: excellent) and artifact presence. Total and component flow velocities obtained with qTOF and PC were measured. STATISTICAL TESTS: Wilcoxon signed-rank tests, Gwet's AC2, intraclass correlation coefficients (ICC) for absolute agreement, Bland-Altman analyses, tests of equal proportions. P values <0.05 were considered statistically significant. RESULTS: Averaged across readers and compared to standard Cartesian TOF, qTOF significantly improved overall arterial image quality (3.8 ± 0.2 vs. 3.6 ± 0.5), image quality at locations of pathology (3.7 ± 0.5 vs. 3.4 ± 0.7), and increased the proportion of evaluations rated without artifacts (63.9% [46/72] vs. 37.5% [27/72]). qTOF significantly agreed with PC for total flow velocity (ICC = 0.71) and component flow velocity (ICC = 0.89). DATA CONCLUSION: qTOF angiography of the head matched or improved upon the image quality of standard Cartesian TOF, reduced image artifacts, and provided quantitative hemodynamic data, without the need for a PC scan. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Combined polygenic scores for ischemic stroke risk factors aid risk assessment of ischemic stroke.

BACKGROUND: Current risk assessment for ischemic stroke (IS) is limited to clinical variables. We hypothesize that polygenic scores (PGS) of IS (PGSIS) and IS-associated diseases such as atrial fibrillation (AF), venous thromboembolism (VTE), coronary artery disease (CAD), hypertension (HTN), and Type 2 diabetes (T2D) may improve the performance of IS risk assessment. METHODS: Incident IS was followed for 479,476 participants in the UK Biobank who did not have an IS diagnosis prior to the recruitment. Lifestyle variables (obesity, smoking and alcohol) at the time of study recruitment, clinical diagnoses of IS-associated diseases, PGSIS, and five PGSs for IS-associated diseases were tested using the Cox proportional-hazards model. Predictive performance was assessed using the C-statistic and net reclassification index (NRI). RESULTS: During a median average 12.5-year follow-up, 8374 subjects were diagnosed with IS. Known clinical variables (age, gender, clinical diagnoses of IS-associated diseases, obesity, and smoking) and PGSIS were all independently associated with IS (P < 0.001). In addition, PGSIS and each PGS for IS-associated diseases was also independently associated with IS (P < 0.001). Compared to the clinical model, a joint clinical/PGS model improved the C-statistic for predicting IS from 0.71 to 0.73 (P < 0.001) and significantly reclassified IS risk (NRI = 0.017, P < 0.001), and 6.48% of subjects were upgraded from low to high risk. CONCLUSIONS: Adding PGSs of IS and IS-associated diseases to known clinical risk factors statistically improved risk assessment for IS, demonstrating the supplementary value of inherited susceptibility measurement . However, its clinical utility is likely limited due to modest improvements in predictive values.

Validating Existing Scales for Identification of Acute Stroke in an Inpatient Setting.

Background and Purpose: A significant proportion of strokes occur while patients are hospitalized for other reasons. Numerous stroke scales have been developed and validated for use in pre-hospital and emergency department settings, and there is growing interest to adapt these scales for use in the inpatient setting. We aimed to validate existing stroke scales for inpatient stroke codes. Methods: We retrospectively reviewed charts from inpatient stroke code activations at an urban academic medical center from January 2016 through December 2018. Receiver operating characteristic analysis was performed for each specified stroke scale including NIHSS, FAST, BE-FAST, 2CAN, FABS, TeleStroke Mimic, and LAMS. We also used logistic regression to identify independent predictors of stroke and to derive a novel scale. Results: Of the 958 stroke code activations reviewed, 151 (15.8%) had a final diagnosis of ischemic or hemorrhagic stroke. The area under the curve (AUC) of existing scales varied from .465 (FABS score) to .563 (2CAN score). Four risk factors independently predicted stroke: (1) recent cardiovascular procedure, (2) platelet count less than 50 × 109 per liter, (3) gaze deviation, and (4) presence of unilateral leg weakness. Combining these 4 factors into a new score yielded an AUC of .653 (95% confidence interval [CI] .604-.702). Conclusion: This study suggests that currently available stroke scales may not be sufficient to differentiate strokes from mimics in the inpatient setting. Our data suggest that novel approaches may be required to help with diagnosis in this unique population.

Neurology of Systemic Disease: Selected Topics with a Focus on Women.

Sex differences exist within the neurologic complications of systemic disease. To promote new avenues for prevention and develop novel therapeutics, we highlight the role of sex in differential outcomes to infectious disease and cardiac arrest and educate the reader in paraneoplastic presentations that may herald underlying malignancies in women.

Acute Large Vessel Ischemic Stroke in Patients With COVID-19-Related Multisystem Inflammatory Syndrome.

BACKGROUND: Acute ischemic stroke (AIS) is rare in children, and diagnosis is often delayed. Neurological involvement may occur in multisystem inflammatory syndrome in children (MIS-C), but very few cases of AIS in patients with MIS-C have been reported. PATIENT DESCRIPTIONS: We two patients with AIS presenting with large vessel occlusive disease in previously healthy adolescents recently exposed to SARS-CoV-2 infection. RESULTS: Both patients were subsequently diagnosed with and treated for MIS-C. Here, we discuss the course of their treatments and clinical responses. CONCLUSION: Early recognition and diagnosis of AIS with large vessel occlusion in children with MIS-C is critical to make available all treatment options to improve clinical outcomes.

Stroke Center Designations, Neurointerventionalist Demand, and the Finances of Stroke Thrombectomy in the United States.

PURPOSE OF THE REVIEW: This article aims to provide an update on the designation of stroke centers, neurointerventionalist demand, and cost-effectiveness of stroke thrombectomy in the United States. RECENT FINDINGS: There are now more than 1,660 stroke centers certified by national accrediting bodies in the United States, 306 of which are designated as thrombectomy-capable or comprehensive stroke centers. Considering the amount of nationally certified centers and the number of patients with acute stroke eligible for thrombectomy, each center would be responsible for 64 to 104 thrombectomies per year. As a result, there is a growing demand placed on neurointerventionalists, who have the ability to alter the trajectory of large vessel occlusive strokes. Numbers needed to achieve functional independence after stroke thrombectomy at 90 days range from 3.2 to 7.4 patients in the early time window and 2.8 to 3.6 patients in the extended time window in appropriately selected candidates. With the low number needed to treat, in a variety of valued-based calculations and cost-effectiveness analyses, stroke thrombectomy has proved to be both clinically effective and cost-effective. SUMMARY: Advancements in the early recognition and treatment of stroke have been paralleled by a remodeling of health care systems to ensure best practices in a timely manner. Stroke center-accrediting bodies provide oversight to safeguard these standards. As successful trial data from high volume centers transform into real-world experience, we must continue to re-evaluate cost-effectiveness, strike a balance between sufficient case volumes to maintain clinical excellence vs the burden and burnout associated with call responsibilities, and improve access to care for all.

Acute Secondary Prevention of Ischemic Stroke: Overlooked No Longer.

Recent studies of interventions initiated acutely following onset of minor ischemic stroke or transient ischemic attack (TIA) have disclosed early stroke recurrence rates that are substantially higher than long-term recurrence rates and that can be reduced by acute antiplatelet treatment interventions. These observations, bolstered by analysis based on kinetic modeling of the time course of recurrence following initial events, suggest that acute stroke patients experience an underlying vulnerable state that quickly transitions to a more stable state. Some evidence also supports the benefits of early treatment with direct-acting oral anticoagulants in cardioembolic stroke and of continuation or early initiation of statin therapy in atherosclerotic stroke. Treatment of ischemic stroke should address the transient vulnerable state that follows the initial event, employing measures aiming to avert early recurrence of thromboembolism and to promote stabilization of vulnerable arterial plaque. These measures constitute acute secondary prevention following ischemic stroke.

Impact of Covid-19 on Stroke Code Activations, Process Metrics, and Diagnostic Error.

BACKGROUND AND PURPOSE: In a comprehensive stroke center, we analyzed the stroke code activations (SCA), assessed the impact of Covid-19, and the measures taken by the local government to lessen the spread of the disease. METHODS: We retrospectively reviewed SCA and classified them into 2 groups: pre-pandemic activations (February 15 to March 10) and Covid-19 pandemic activations (March 11 to April 30). The primary outcome was the ratio of true positive diagnoses of stroke relative to the total number of SCA in the 2 time periods. RESULTS: Among the 212 SCA, 83 (39.2%) were from the pre-pandemic period, whereas 129 (60.8%) were from the pandemic period, 147 (69.3%) in the Emergency Department (ED) versus 65 (30.7%) in the inpatient service. In the ED cohort, a rapid decrease in the number of SCA at the beginning of the pandemic was followed by a gradual increase to pre-pandemic levels and a significant increase in the number of true positive strokes over time (44.2% vs 61.1%, p = 0.037). An increase in door-to-CT time (p = 0.001) and an increase in the rate of diagnostic error in patients admitted from the ED (p = 0.016) were also seen. The in-hospital cohort had a sustained decrease in the number of SCA following the pandemic declaration, with no difference in the rate of true positive stroke. CONCLUSIONS: We observed a rapid decline and slow recovery in ED SCA with a shift toward increased true positive cases following the Covid-19 pandemic. Also, delays in obtaining CT and diagnostic error was increased, however, no difference in early clinical outcomes were seen between groups.

Two-State Kinetic Model of Rates of Stroke Recurrence in the POINT Study Population.

BACKGROUND AND PURPOSE: Following an acute ischemic stroke or transient ischemic attack, 2 rates of stroke recurrence are suggested by data from trials of acute secondary prevention treatments: a transient rapid rate followed by a persisting slower rate of stroke. METHODS: A kinetic model was constructed based on underlying vulnerable and stabilized states of patients following acute ischemic events related by fixed transition rates. Its predictions were fitted by nonlinear regression to the observed timing of outcome events in patients in the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke). RESULTS: The modeled survivor function produced a close fit to the observed data. The model's predicted kinetic rates suggest that, among subjects in the control group, the event rate was 100-fold higher in the vulnerable state than in the stabilized state. Active treatment halved this rapid rate and had little effect on event rates in the stabilized state. If at least one-tenth of the study population began in the vulnerable state, the rate of transition from the vulnerable to the stabilized state was still faster, with a half-life of only 1 to 2 days. CONCLUSIONS: Examination of kinetics of stroke occurrence, and of the rates associated with modeled state transitions, may provide insights into the underlying pathophysiological events that are targets for acute secondary prevention of stroke.

Early Determinants of Neurocritical Care Unit Length of Stay in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The present study considers patients with spontaneous intracerebral hemorrhage (ICH) admitted to the neurocritical care unit (NCCU) through the Emergency Department (ED). It aims to identify patient-specific clinical variables that can be assessed on presentation and that are associated with prolonged NCCU length of stay (LOS). METHODS: A cross-sectional, single-center, retrospective analysis of ICH patients directly admitted from the ED to the NCCU over an 8-year period was performed. Patients' demographics, clinical exam characteristics, serum laboratory values, intubation status, and neurosurgical procedures at presentation were recorded. Head computed tomography scans obtained on presentation were reviewed. LOS was calculated based on the number of midnights spent in the NCCU. Prolonged LOS was determined using a change point analysis, adopting the method of Taylor which utilizes CUMSUM charts and bootstrap analysis. A decision tree model was trained and validated to identify reliable variables associated with prolonged LOS. RESULTS: Two hundred and five patients with ICH were analyzed. Prolonged LOS was calculated to be a stay that exceeds 8 days; 68 patients (33%) had a prolonged LOS in NCCU. Median LOS did not differ between survivors and patients who died in hospital. Clinical variables explored through the decision tree model were intubation status, neurosurgical intervention (EVD, decompression or evacuation within 24 h from presentation), and components of the ICH score: age, GCS, hematoma volume, the presence of intraventricular hemorrhage (IVH), and infratentorial location. The model accuracy was 0.8 and AUC was 0.83 (95% CI 0.78-0.89). CONCLUSION: We propose an ICH-LOS model based on neurosurgical intervention, intubation status and GCS at presentation to predict prolonged LOS in the NCCU in patients with ICH. This simple clinical tool, if prospectively validated, could help with medical planning, contribute to patient care-directed conversations, assist in optimizing hospital resource utilization, and, more importantly, motivating patient-specific interventions aimed at optimizing outcomes and decreasing LOS.

Ipsilateral Nonstenotic Carotid Disease in Minor Ischemic Stroke: an Exploratory Analysis of The POINT Randomized Clinical Trial.

BACKGROUND AND AIM: Ipsilateral nonstenotic carotid disease is increasingly recognized as an etiology of ischemic stroke, however tailored treatment strategies are lacking. We aimed to examine clinical characteristics and treatment effects in patients with minor ischemic stroke associated with ipsilateral nonstenotic carotid disease in the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. METHODS: We performed an exploratory analysis of the interaction of the treatment effects of aspirin plus clopidogrel versus aspirin monotherapy, stratified by presence of ipsilateral nonstenotic carotid disease in patients with minor ischemic stroke in the POINT trial. RESULTS: For this exploratory analysis, 167 patients presenting with ischemic stroke and ipsilateral nonstenotic carotid disease, defined as 1%-49% carotid stenosis ipsilateral to the corresponding territory of ischemic stroke, and 833 patients no carotid disease were included. Compared to patients with no carotid disease, patients with ipsilateral nonstenotic carotid disease were older (68.5 ± 11.3 years versus 61.3 ± 12.8 years; P < 0.001), and had a higher prevalence of hypertension (76.6% versus 59.2%, P < 0.001), ischemic heart disease (13.8% versus 5.4%, P < 0.001), and tobacco use (past: 34.1% versus 25.2%, P = 0.005; present: 27.5% versus 22.8%, P = 0.005). 5.4% of patients with ipsilateral nonstenotic carotid disease had recurrent ischemic stroke within 14 days. Patients receiving dual antiplatelet therapy had a numerical reduction in recurrent ischemic stroke compared to patients receiving aspirin monotherapy, however the exploratory analysis was underpowered to detect a statistically significant difference in treatment effect (HR 0.50, 95% CI 0.18-1.40, P = 0.19). CONCLUSION: Patients with minor ischemic stroke and ipsilateral nonstenotic carotid disease had a high risk of early stroke recurrence in the POINT trial. Dual antiplatelet therapy provided a non-statistically significant reduction in recurrent ischemic stroke with no difference in safety outcomes compared to aspirin monotherapy. Further study is needed to determine if early and short duration dual antiplatelet therapy is beneficial for all patients with ipsilateral nonstenotic carotid disease.

BE-FAST: A Sensitive Screening Tool to Identify In-Hospital Acute Ischemic Stroke.

BACKGROUND: Development of acute ischemic stroke in hospitalized patients represents a significant proportion of all cerebral ischemia. Several prehospital stroke scales were developed to screen for acute ischemic stroke in the community. Despite the advent of inpatient stroke alert systems, there is a lack of validated screening tools for the inpatient population. This study aims to assess the validity of BE-FAST (Balance, Eyes, Face, Arm, Speech, Time) as a screening tool for acute ischemic stroke among inpatients. METHODS: We retrospectively analyzed all stroke alert activations at a single academic medical center between 2012 and 2016. We classified the triggering symptom as: focal neurologic deficit, aphasia, dysarthria, ataxia/vertigo/dizziness, alteration of consciousness, acute confusion, or headache. BE-FAST was applied retrospectively, and patients were classified as BE-FAST positive or negative. The final diagnosis was classified as acute ischemic stroke, transient ischemic attack , intracranial hemorrhage or noncerebrovascular diagnosis. RESULTS: Of 1965 stroke alerts, 489 were among inpatients. The mean age was 63 ± 16.1 years; 57% of patients were women (n = 1121). Acute ischemic stroke was diagnosed in 29% of all the activations (n = 567), transient ischemic attack in 12% (n = 232), intracranial hemorrhage in 8 % (n = 160) and noncerebrovascular in 51% (n = 1006). When comparing inpatient with community-onset stroke alerts, the sensitivity of BE-FAST for diagnosing acute ischemic stroke was 85% versus 94% (P = .005), with a specificity of 43% versus 23% (P < .001), respectively. However, when evaluating in-patients with an intact level of consciousness separately, BE-FAST sensitivity for diagnosing acute ischemic stroke was 92% compared to 94% in the community (P = .579). Among in-patients with acute ischemic stroke who were (1) candidates for reperfusion therapy and (2) diagnosed with acute large vessel occlusion, the sensitivity of BE-FAST was 83% and 94%, respectively. CONCLUSIONS: This is the first study to analyze the performance of BE-FAST among hospitalized patients evaluated through the inpatient stroke alert system. We found BE-FAST to be a very sensitive tool for screening for all in-hospital acute ischemic strokes, including inpatients that were candidates for acute reperfusion therapy.

Intracranial Hemorrhage in Hospitalized Patients: An Infrequently Studied Condition with High Mortality.

BACKGROUND: Intracranial hemorrhage (ICH) may occur in patients admitted to the hospital for unrelated medical conditions, resulting in prolonged hospitalization and worse prognosis. We aim to assess the clinical presentation and outcomes of in-hospital ICH compared to patients with ICH presenting from the community. METHODS: We conducted a retrospective analysis of all acute stroke alerts diagnosed with ICH in an urban academic hospital over a 4-year period. Demographics, clinical presentation, use of antithrombotic therapy, and presence of coagulopathy were recorded. ICH score and a sequential organ failure assessment score were calculated during the initial assessment. Initial head computed tomography was reviewed to determine ICH subtype, location, and volume of the hematoma. In-hospital mortality and discharge disposition were used as surrogate of clinical outcome. RESULTS: From the 1965 stroke alert cases analyzed over the studied years, 145 (7.4%) were diagnosed with ICH. Overall, the mean age was 62.9 ± 13.9 and 53.7% were women. Thirty-two patients (22%) developed ICH in the inpatient setting and 113 (78%) presented from the community. Systolic blood pressure at presentation was lower in the in-hospital group (p < 0.01). Inpatients who developed ICH were more likely than community ICH patients to be on combination of antiplatelet agents (21.9% vs. 5.3%, p < 0.05) or therapeutic heparinoids (21.9% vs. 0.9%, p < 0.01). Also, In-hospital ICH patients had a higher rate of spontaneous or iatrogenic coagulopathy (65.6% vs. 10.6%, p < 0.01) and thrombocytopenia (31.3% vs. 1.8%, p < 0.01). Lobar hemorrhages were more prevalent in the in-hospital group (82.6% vs. 39.1%, p < 0.01) and the mean hematoma volume was higher (40.9 ± 43.1 mL vs. 24.1 ± 30.4 mL; p < 0.02). Median ICH score in the in-hospital group was not statistically different from the emergency department group: 2 (IQR: 0-3) versus 1 (IQR: 0-3). When comparing patients with in-hospital ICH and those from the community, the short-term mortality was higher in the former group (81% vs. 31%, p < 0.01). The incidence of withdrawal of life-sustaining therapies as a proximate mechanism of death was higher, but not statistically significant, in the in-hospital group (86% vs. 61%). CONCLUSION: ICH is a critical complication in the inpatient setting, predominantly occurring in already ill patients with underlying spontaneous or iatrogenic coagulopathy. Large volume lobar intraparenchymal hemorrhage is a common radiographic finding. ICH is frequently a catastrophic event and powerfully weighs in with end-of-life discussion, resulting in high short-term mortality rate.

Mechanical Thrombectomy for Patients with In-Hospital Ischemic Stroke: A Case-Control Study.

BACKGROUND AND AIM: Patients with in-hospital acute ischemic stroke (AIS) have, in general, worse outcomes compared to those presenting from the community, partly attributed to the numerous contraindications to intravenous thrombolysis. We aimed to identify and analyze a group of patients with in-hospital AIS who remain suitable candidates for acute endovascular therapies. METHODS: A retrospective 6-year data analysis was conducted in patients evaluated through the in-hospital stroke alert protocol in a single tertiary care university hospital to identify those with in-hospital AIS due to acute intracranial large vessel occlusion (ILVO). Feasibility and safety of mechanical thrombectomy for in-hospital AIS was assessed in a case-control study comparing inpatients to those presenting from the community. RESULTS: From 1460 in-hospital stroke alert activations, 11% had a final diagnosis of AIS (n = 167). One hundred and two patients with in-hospital AIS had emergent intracranial vessel imaging and were included in our cohort. Acute ILVO was identified in 27 patients within this cohort. Patients were younger in the ILVO group and had more severe neurologic deficit on presentation. Compared to a matched (1:2) control group of patients presenting from the community, inpatients who underwent mechanical thrombectomy achieved equivalent technical success, safety, and clinical outcomes. CONCLUSIONS: The incidence of acute ILVO in patients with in-hospital AIS who underwent emergent vessel imaging is similar to the reported incidence of ILVO in patients presenting with community-onset AIS. Among patients with in-hospital AIS secondary to ILVO, mechanical thrombectomy is a feasible and safe therapy associated with favorable outcomes.

Incidence of Unreliable Automated Computed Tomography Perfusion Maps.

INTRODUCTION: Despite the increasing national adoption of automated computed tomography perfusion (CTP) to select thrombectomy patients 6 hours after last known well, reliability issues have been anecdotally reported. Unreliable diagnostic tests add time and confusion to a process that requires efficiency. Our study aims to critically assess an automated CTP program in a contemporary cohort of patients presenting with large vessel occlusion (LVO) in the extended time window by evaluating the rate of unreliable automated CTP maps and whether this influences clinical outcomes. METHODS: A retrospective review of consecutive thrombectomy candidates undergoing CTP imaging in the extended time window was performed. All automated CTP maps using RAPID software (iSchemaView, Menlo Park, CA) were assessed for reliability. Clinical outcomes were compared between patients with and without reliable RAPID reports. RESULTS: Ninety-nine consecutive thrombectomy candidates underwent automated CTP imaging from February 2017 to December 2018. Of these, 78 (79%) had LVO determined by CT angiographyand were included in the study population. Automated CTP maps were unreliable in 13% of cases as a result of motion artifact (n = 3) and contrast bolus flow issues (n = 7). Heart failure was more frequent in patients with unreliable studies. Clinical outcomes did not significantly differ between patients with and without unreliable studies. CONCLUSIONS: Thirteen percent of CTP maps generated by automated software were unreliable, with an increased frequency among patients with heart failure. Given the rate of unreliable automated CTP maps, further studies are warranted to not only establish the true necessity of currently available CTP software, but also more reliable methods to select patients for thrombectomy presenting in the extended time window.