Mobile Stroke Units in Acute Ischemic Stroke: A Comprehensive Systematic Review and Meta-Analysis of 5 "T Letter" Domains.

Intravenous thrombolysis (IVT) may be administered to stroke patients requiring immediate treatment more quickly than emergency medical services if certain conditions are met. These conditions include the presence of mobile stroke units (MSUs) with on-site treatment teams and a computed tomography scanner. We compared clinical outcomes of MSU conventional therapy by emergency medical services through a systematic review and meta-analysis. We searched key electronic databases from inception till September 2021. The primary outcomes were mortality at 7 and 90 days. The secondary outcomes included the modified Rankin Scale score at 90 days, alarm to IVT or intra-arterial recanalization, and time from symptom onset or last known well to thrombolysis. We included 19 controlled trials and cohort studies to conduct our final analysis. Our comparison revealed that 90-day mortality significantly decreased in the MSU group compared with the conventional care group [risk ratio = 0.82; 95% confidence interval (CI), 0.71-0.95], while there was no significant difference at 7 days (risk ratio = 0.89; 95% CI, 0.69-1.15). MSU achieved greater functional independence (modified Rankin Scale = 0-2) at 90 days (risk ratio = 1.08; 95% CI, 1.01-1.16). MSU was associated with shorter alarm to IVT or intra-arterial recanalization time (mean difference = -29.69; 95% CI, -34.46 to -24.92), treating patients in an earlier time window, as shown through symptom onset or last known well to thrombolysis (mean difference = -36.79; 95% CI, -47.48 to -26.10). MSU-treated patients had a lower rate of 90-day mortality and better 90-day functional outcomes by earlier initiation of IVT compared with conventional care.

Endovascular thrombectomy for treatment of isolated posterior cerebral artery occlusion: a real-world analysis of hospitalizations in the United States.

BACKGROUND: Despite renewed interest and recently demonstrated efficacy for endovascular thrombectomy (EVT) for treatment of acute ischemic stroke (AIS) of the posterior circulation, to date, no randomized clinical trials have been conducted to evaluate EVT for isolated occlusions of the posterior cerebral artery (IPCA). METHODS: Hospitalizations for adult patients with primary admission diagnoses of IPCA occlusion were identified in the National Inpatient Sample registry during the period of 2016-2020. The study exposure was treatment with EVT, and primary clinical endpoints included favorable functional outcome (defined as discharge disposition to home without services, previously shown to have high concordance with modified Rankin scale scores 0-2), in-hospital mortality, and any intracranial hemorrhage (ICH). Inverse probability of treatment weighting (IPTW) was performed to balance baseline clinical characteristics between those receiving EVT or medical management (MM). RESULTS: This analysis identified 34,880 IPCA occlusion hospitalizations, 730 (2.1%) of which documented treatment with EVT. Following IPTW adjustment, EVT was associated with favorable outcome in IPCA patients presenting with mild deficits (M-D) (NIHSS < 6) [adjusted odds ratio (aOR) 2.36, 95% confidence interval (CI) 2.27, 2.45; p < 0.001] and in those presenting with moderate-to-severe deficits (M-S-D) (NIHSS 6-42) (aOR 2.00, 95% CI 1.86, 2.15; p < 0.001). Mortality rates did not differ among those with M-S-D [EVT 4.8% vs. MM 4.7%, p = 0.742], while ICH rates were lower. CONCLUSION: Retrospective analysis of a large administrative registry in the Unites States demonstrates an association of EVT with favorable outcomes following IPCA occlusion, without concomitant risk of hemorrhagic transformation or mortality.

Review of Cerebral Collateral Circulation and Insight into Cardiovascular Strategies to Limit Collateral Damage in Ischemic Stroke.

Cerebral collateral circulation is a dynamic and adaptive process by which alternative vascular pathways supply perfusion to ischemic brain tissue in the event of an arterial occlusion. This complicated network of blood vessels that acts as a natural bypass plays a pivotal role in stroke pathophysiology and has become a key area of study given its significance in stroke treatment and patient outcomes. In this review, we will study the factors influencing the formation, recruitment, and endurance of collateral vessels; discuss imaging modalities for quantitative and qualitative assessment of this network; explore the role of collaterals in stroke management; and highlight several cardiovascular strategies to minimize damage to collaterals and optimize stroke outcomes.

Effect of chronic antiplatelet therapy on clinical outcomes of endovascular thrombectomy for treatment of acute ischemic stroke.

OBJECTIVE: The objective of this study was to investigate the prognostic significance of chronic antiplatelet therapy (APT) usage in acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT). Long-term APT may enhance recanalization but may also predispose patients to an increased risk of hemorrhagic transformation. METHODS: Weighted hospitalizations for anterior-circulation AIS treated with EVT were identified in a large United States claims-based registry. Baseline clinical characteristics and outcomes were compared between patients with and without chronic APT usage prior to admission. Multivariable logistic regression analysis was performed to assess adjusted associations between APT and study endpoints. RESULTS: This analysis identified 36,560 patients, of whom 8170 (22.3%) were on a chronic APT regimen prior to admission. These patients were older and demonstrated a higher burden of comorbid disease, but had similar stroke severity on presentation in comparison with those not on APT. On unadjusted analysis, patients with prior APT demonstrated higher rates of favorable outcomes (24.3% vs 21.5%, p < 0.001), lower rates of mortality (7.0% vs 10.1%, p < 0.001), and lower rates of any intracranial hemorrhage (ICH; 20.3% vs 24.2%, p < 0.001), but no difference in rates of symptomatic ICH (sICH). Following multivariable adjustment for baseline clinical characteristics including age, acute stroke severity, and comorbidity burden, prior APT was associated with favorable outcome (adjusted odds ratio [aOR] 1.21, 95% CI 1.17-1.24, p < 0.001) and a lower likelihood of mortality (aOR 0.73, 95% CI 0.70-0.77, p < 0.001), without an increased likelihood of ICH (any ICH aOR 0.84, 95% CI 0.81-0.87, p < 0.001; sICH aOR 0.92, 95% CI 0.82-1.03, p = 0.131). CONCLUSIONS: Retrospective evaluation of patients with AIS treated with EVT using registry-based data demonstrated an association of prior APT usage with favorable outcomes, without an increased risk of hemorrhagic transformation.

Aneurysmal Subarachnoid Hemorrhage and Cardiac Related Fatality: Who Dies and Why?

Medical complications are a notable source of in-hospital death following aneurysmal subarachnoid hemorrhage (aSAH). However, there is a paucity of literature examining medical complications on a national scale. This study uses a national dataset to analyze the incidence rates, case fatality rates, and risk factors for in-hospital complications and mortality following aSAH. We found that the most common complications in aSAH patients (N = 170, 869) were hydrocephalus (29.3%) and hyponatremia (17.3%). Cardiac arrest was the most common cardiac complication (3.2%) and was associated with the highest case fatality rate overall (82%). Patients with cardiac arrest also had the highest odds of in-hospital mortality [odds ratio (OR), 22.92; 95% confidence interval (CI), 19.24-27.30; P < 0.0001], followed by patients with cardiogenic shock (OR, 2.96; 95% CI, 2.146-4.07; P < 0.0001). Advanced age and National Inpatient Sample-SAH Severity Score were found to be associated with an increased risk of in-hospital mortality (OR, 1.03; 95% CI, 1.03-1.03; P < 0.0001 and OR, 1.70; 95% CI, 1.65-1.75; P < 0.0001, respectively). Renal and cardiac complications are significant factors to consider in aSAH management, with cardiac arrest being the strongest indicator of case fatality and in-hospital mortality. Further research is needed to characterize factors that have contributed to the decreasing trend in case fatality rates identified for certain complications.

Intravenous thrombolysis plus mechanical thrombectomy versus mechanical thrombectomy alone for acute ischemic stroke: A systematic review and updated meta-analysis of clinical trials.

BACKGROUND: Mechanical thrombectomy (MT) is the gold standard treatment for large vessel occlusion (LVO). A vital factor that might influence MT outcomes is the use of intravenous thrombolysis (IVT). A few clinical trials in this domain thus far have not yielded consistent outcomes. We conducted this meta-analysis to synthesize collective evidence in this regard. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines were followed, and we performed a comprehensive literature search of four databases (PubMed, Scopus, Web of Science, Cochrane CENTRAL). For outcomes constituting continuous data, the mean difference (MD) and its standard deviation (SD) were pooled. For outcomes constituting dichotomous data, the frequency of events and the total number of patients were pooled as the risk ratio (RR). RESULTS: Seven clinical trials with a total of 2317 patients are included in this meta-analysis. Six trials are randomized, and one trial was nonrandomized. No significant differences were found between MT plus IVT and MT alone in successful recanalization (RR 1.04, 95% Confidence Interval (CI) [0.92 to 1.17], P = 0.53), 90-day functional independence (RR 1.03, 95% CI [0.90 to 1.19], P = 0.65), symptomatic intracranial hemorrhage (sICH) (RR 1.22, 95% CI [0.84 to 1.75], P = 0.30), or mortality (RR 0.94, 95% CI [0.76 to 1.18], P = 0.61). CONCLUSION: The current evidence does not favor either MT plus IVT or MT alone for LVO except for the procedural time. More trials are needed in this regard, and certain factors should be considered when comparing the two approaches.

Trajectories of Neurologic Recovery 12 Months After Hospitalization for COVID-19: A Prospective Longitudinal Study.

BACKGROUND AND OBJECTIVE: Little is known about trajectories of recovery 12 months after hospitalization for severe COVID-19. METHODS: We conducted a prospective, longitudinal cohort study of patients with and without neurologic complications during index hospitalization for COVID-19 from March 10, 2020, to May 20, 2020. Phone follow-up batteries were performed at 6 and 12 months after COVID-19 onset. The primary 12-month outcome was the modified Rankin Scale (mRS) score comparing patients with or without neurologic complications using multivariable ordinal analysis. Secondary outcomes included activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA), and Quality of Life in Neurologic Disorders (Neuro-QoL) batteries for anxiety, depression, fatigue, and sleep. Changes in outcome scores from 6 to 12 months were compared using nonparametric paired-samples sign test. RESULTS: Twelve-month follow-up was completed in 242 patients (median age 65 years, 64% male, 34% intubated during hospitalization) and 174 completed both 6- and 12-month follow-up. At 12 months, 197/227 (87%) had ≥1 abnormal metric: mRS >0 (75%), Barthel Index <100 (64%), t-MoCA ≤18 (50%), high anxiety (7%), depression (4%), fatigue (9%), or poor sleep (10%). Twelve-month mRS scores did not differ significantly among those with (n = 113) or without (n = 129) neurologic complications during hospitalization after adjusting for age, sex, race, pre-COVID-19 mRS, and intubation status (adjusted OR 1.4, 95% CI 0.8-2.5), although those with neurologic complications had higher fatigue scores (T score 47 vs 44; p = 0.037). Significant improvements in outcome trajectories from 6 to 12 months were observed in t-MoCA scores (56% improved, median difference 1 point; p = 0.002) and Neuro-QoL anxiety scores (45% improved; p = 0.003). Nonsignificant improvements occurred in fatigue, sleep, and depression scores in 48%, 48%, and 38% of patients, respectively. Barthel Index and mRS scores remained unchanged between 6 and 12 months in >50% of patients. DISCUSSION: At 12 months after hospitalization for severe COVID-19, 87% of patients had ongoing abnormalities in functional, cognitive, or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurologic complications during index hospitalization. However, significant improvements in cognitive (t-MoCA) and anxiety (Neuro-QoL) scores occurred in 56% and 45% of patients, respectively, between 6 and 12 months. These results may not be generalizable to those with mild or moderate COVID-19.

The critically ill brain after cardiac arrest.

Cardiac arrest can cause hypoxic-anoxic ischemic brain injury due to signaling cascades that lead to damaged cell membranes and vital cellular organelles, resulting in cell death in the setting of low or no oxygen. Some brain areas are more prone to damage than others, so patients with hypoxic-anoxic ischemic brain injury present with several outcomes, including reduced level of consciousness or alertness, memory deficits, uncoordinated movements, and seizures. Some patients may have mild deficits, while others may have such severe injury that it can progress to brain death. High-quality cardiopulmonary resuscitation is a proven technique to improve outcome after cardiac arrest, although morbidity and mortality remain high. Induced hypothermia, which involves artificially cooling the body immediately after cardiac arrest, may reduce injury to the brain and improve morbidity and mortality. Neuroprognostication after cardiac arrest is challenging and requires a multimodal approach involving clinical neurologic examinations, brain imaging, electrical studies to assess brain activity, and biomarkers to predict outcome.

A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications.

BACKGROUND: Little is known regarding long-term outcomes of patients hospitalized with COVID-19. METHODS: We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. RESULTS: Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N = 196 neurological patients and N = 186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 1.98, 95%CI 1.23-3.48, P = 0.02), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P = 0.01) and were less likely to return to work than controls (41% versus 64%, P = 0.04). Cognitive and Neuro-QOL metrics were similar between groups. CONCLUSIONS: Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.

Cerebral Venous Sinus Thrombosis in the COVID-19 Pandemic.

BACKGROUND: Recent studies have noted concern for increased thromboembolic events in the setting of Coronavirus Disease 2019 (COVID-19). Cerebral venous sinus thrombosis (CVST) is a form of thromboembolism that has been observed as a neuro-ophthalmologic complication of COVID-19. METHODS: Review of the scientific literature. RESULTS: In this article, we report an overview of CVST epidemiology, clinical presentation, diagnostics, disease pathophysiology, and management in the setting of COVID-19. CONCLUSION: CVST is an uncommon thromboembolic event with variable phenotypes and multiple etiologies. Neurologic complications can be severe, including significant visual deficits and death. Current observations suggest that the risk of CVST may be profoundly impacted by this novel COVID-19 pandemic, thus prompting increased attention to disease presentation, pathogenesis, and management.

Modafinil in Recovery after Stroke (MIRAS): A Retrospective Study.

BACKGROUND AND PURPOSE: Acute rehabilitation is known to enhance stroke recovery. However, poststroke lethargy and fatigue can hinder participation in rehabilitation therapies. We hypothesized that in patients with moderate to severe stroke complicated by poststroke fatigue and lethargy early stimulant therapy with modafinil increases favorable discharge disposition defined as transfer to acute inpatient rehabilitation or home. METHODS: We retrospectively reviewed a cohort of patients with acute stroke admitted to the stroke service over a 3-year period. All patients 18 years or older with confirmed ischemic or hemorrhagic stroke, an NIHSS greater than or equal to 5 and documentation of fatigue/lethargy in clinical documentation were included. We compared patients that were treated with modafinil 50-200 mg to those managed with standard care. The primary outcome measure was discharge disposition. Secondary outcome was 90 day modified Rankin score (mRS). Statistical significance was determined using chi-square test for association and logistic regression models. Logistic regression models were derived in 2 ways with both raw data and an adjusted model that accounted for age, sex, and NIHSS score to account for the lack of randomization. RESULTS: This study included 199 stroke patients (145 ischemic, 54 hemorrhagic). Seventy-two (36.2%) were treated with modafinil and 129 (64.8%) were discharged to acute inpatient rehabilitation, while none were recommended for discharge home. Median NIHSS for modafinil patients was 13.5 versus 11 for standard care patients (P = .059). In adjusted models, modafinil was associated with higher odds of favorable discharge disposition (OR 2.00, 95% CI 1.01-3.95). Favorable outcome at 90 days defined as mRS less than or equal to 2 occurred more frequently with modafinil (5.6% versus 3.3%) but this did not achieve statistical significance (P > .1). These results occurred despite the modafinil group requiring longer ICU stays and having more in-hospital complications such as infections and need for percutaneous gastrostomy tubes. The benefit of modafinil was seen across all subgroups except those with severe stroke (NIHSS ≥ 15). There were no significant adverse events associated with modafinil administration. CONCLUSIONS: Modafinil use in acute in-hospital stroke patients with moderate stroke complicated by lethargy and fatigue was associated with improved discharge disposition. Randomized controlled trials are needed to further study the safety, efficacy, and long-term effects of modafinil in this patient population.

Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance.

BACKGROUND: Non-ischemic fibrosis (NIF) on cardiac magnetic resonance (CMR) has been linked to poor prognosis, but its association with adverse right ventricular (RV) remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress. METHODS AND RESULTS: The population comprised patients with RV dysfunction (EF<50%) undergoing CMR and transthoracic echo within a 14 day (5 ± 3) interval. Cardiac structure, function, and NIF were assessed on CMR. Pulmonary artery systolic pressure (PASP) was measured on echo. 118 patients with RV dysfunction were studied, among whom 47% had NIF. Patients with NIF had lower RVEF (34 ± 10 vs. 39 ± 9%; p = 0.01) but similar LVEF (40 ± 21 vs. 39 ± 18%; p = 0.7) and LV volumes (p = NS). RV wall stress was higher with NIF (17 ± 7 vs. 12 ± 6 kPa; p < 0.001) corresponding to increased RV end-systolic volume (143 ± 79 vs. 110 ± 36 ml; p = 0.006), myocardial mass (60 ± 21 vs. 53 ± 17 gm; p = 0.04), and PASP (52 ± 18 vs. 41 ± 18 mmHg; p = 0.001). NIF was associated with increased wall stress among subgroups with isolated RV (p = 0.005) and both RV and LV dysfunction (p = 0.003). In multivariable analysis, NIF was independently associated with RV volume (OR = 1.17 per 10 ml, [CI 1.04-1.32]; p = 0.01) and PASP (OR = 1.43 per 10 mmHg, [1.14-1.81]; p = 0.002) but not RV mass (OR = 0.91 per 10 gm, [0.69-1.20]; p = 0.5) [model χ2 = 21; p<0.001]. NIF prevalence was higher in relation to PA pressure and RV dilation and was > 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001). CONCLUSION: Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling.

Echocardiographic Algorithm for Post-Myocardial Infarction LV Thrombus: A Gatekeeper for Thrombus Evaluation by Delayed Enhancement CMR.

OBJECTIVES: The goal of this study was to determine the prevalence of post-myocardial infarction (MI) left ventricular (LV) thrombus in the current era and to develop an effective algorithm (predicated on echocardiography [echo]) to discern patients warranting further testing for thrombus via delayed enhancement (DE) cardiac magnetic resonance (CMR). BACKGROUND: LV thrombus affects post-MI management. DE-CMR provides thrombus tissue characterization and is a well-validated but an impractical screening modality for all patients after an MI. METHODS: A same-day echo and CMR were performed according to a tailored protocol, which entailed uniform echo contrast (irrespective of image quality) and dedicated DE-CMR for thrombus tissue characterization. RESULTS: A total of 201 patients were studied; 8% had thrombus according to DE-CMR. All thrombi were apically located; 94% of thrombi occurred in the context of a left anterior descending (LAD) infarct-related artery. Although patients with thrombus had more prolonged chest pain and larger MI (p ≤ 0.01), only 18% had aneurysm on echo (cine-CMR 24%). Noncontrast (35%) and contrast (64%) echo yielded limited sensitivity for thrombus on DE-CMR. Thrombus was associated with stepwise increments in basal → apical contractile dysfunction on echo and quantitative cine-CMR; the echo-measured apical wall motion score was higher among patients with thrombus (p < 0.001) and paralleled cine-CMR decrements in apical ejection fraction and peak ejection rates (both p < 0.005). Thrombus-associated decrements in apical contractile dysfunction were significant even among patients with LAD infarction (p < 0.05). The echo-based apical wall motion score improved overall performance (area under the curve 0.89 ± 0.44) for thrombus compared with ejection fraction (area under the curve 0.80 ± 0.61; p = 0.01). Apical wall motion partitions would have enabled all patients with LV thrombus to be appropriately referred for DE-CMR testing (100% sensitivity and negative predictive value), while avoiding further testing in more than one-half (56% to 63%) of patients. CONCLUSIONS: LV thrombus remains common, especially after LAD MI, and can occur even in the absence of aneurysm. Although DE-CMR yielded improved overall thrombus detection, apical wall motion on a noncontrast echocardiogram can be an effective stratification tool to identify patients in whom DE-CMR thrombus assessment is most warranted. (Diagnostic Utility of Contrast Echocardiography for Detection of LV Thrombi Post ST Elevation Myocardial Infarction; NCT00539045).

Secretome identification of immune cell factors mediating metastatic cell homing.

Metastatic cell homing is a complex process mediated in part by diffusible factors secreted from immune cells found at a pre-metastatic niche. We report on connecting secretomics and TRanscriptional Activity CEll aRray (TRACER) data to identify functional paracrine interactions between immune cells and metastatic cells as novel mediators of homing. Metastatic breast cancer mouse models were used to generate a diseased splenocyte conditioned media (D-SCM) containing immune cell secreted factors. MDA-MB-231 metastatic cell activity including cell invasion, migration, transendothelial migration, and proliferation were increased in D-SCM relative to control media. Our D-SCM secretome analysis yielded 144 secreted factor candidates that contribute to increased metastatic cell activity. The functional mediators of homing were identified using MetaCore software to determine interactions between the immune cell secretome and the TRACER-identified active transcription factors within metastatic cells. Among the 5 candidate homing factors identified, haptoglobin was selected and validated in vitro and in vivo as a key mediator of homing. Our studies demonstrate a novel systems biology approach to identify functional signaling factors associated with a cellular phenotype, which provides an enabling tool that complements large-scale protein identification provided by proteomics.