Cerebral Microbleeds in Critically Ill Patients with Respiratory Failure or Sepsis: A Scoping Review.

BACKGROUND: Cerebral microbleeds (CMBs) have been described in critically ill patients with respiratory failure, acute respiratory distress syndrome (ARDS), or sepsis. This scoping review aimed to systematically summarize existing literature on critical illness-associated CMBs. METHODS: Studies reporting on adults admitted to the intensive care unit for respiratory failure, ARDS, or sepsis with evidence of CMBs on magnetic resonance imaging were included for review following a systematic search across five databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science) and a two-stage screening process. Studies were excluded if patients' CMBs were clearly explained by another process of neurological injury. RESULTS: Forty-eight studies reporting on 216 critically ill patients (mean age 57.9, 18.4% female) with CMBs were included. Of 216, 197 (91.2%) patients developed respiratory failure or ARDS, five (2.3%) patients developed sepsis, and 14 (6.5%) patients developed both respiratory failure and sepsis. Of 211 patients with respiratory failure, 160 (75.8%) patients had coronavirus disease 2019. The prevalence of CMBs among critically ill patients with respiratory failure or ARDS was 30.0% (111 of 370 patients in cohort studies). The corpus callosum and juxtacortical area were the most frequently involved sites for CMBs (64.8% and 41.7% of all 216 patients, respectively). Functional outcomes were only reported in 48 patients, among whom 31 (64.6%) were independent at discharge, four (8.3%) were dependent at discharge, and 13 (27.1%) did not survive until discharge. Cognitive outcomes were only reported in 11 of 216 patients (5.1%), all of whom showed cognitive deficits (nine patients with executive dysfunction and two patients with memory deficits). CONCLUSIONS: Cerebral microbleeds are commonly reported in patients with critical illness due to respiratory failure, ARDS, or sepsis. CMBs had a predilection for the corpus callosum and juxtacortical area, which may be specific to critical illness-associated CMBs. Functional and cognitive outcomes of these lesions are largely unknown.

Patient's understanding of and satisfaction with acute stroke treatment.

OBJECTIVE: We aimed to assess patient and surrogate understanding of and satisfaction with communication regarding acute stroke treatments of intravenous thrombolysis (IVT) and endovascular therapy (EVT). METHODS: In this single health-system prospective observational study, patients or their surrogates were interviewed within 72 h of acute stroke therapy. Respondent's satisfaction and self-reported understanding were rated on a Likert scale. Responses to open-ended questions were evaluated for recall of purpose and risks of treatment. RESULTS: Of 56 completed interviews (24 patients and 32 surrogates), 33 patients received IVT alone, 11 IVT and EVT, 12 EVT alone. Forty participants (71%) reported being extremely satisfied with their acute stroke care, 46 (82%) reported no difficulty understanding the purpose of treatment, while 36 (64%) reported no difficulty understanding risks. Two or more risks were verbalized by 8 (24%) participants for IVT, 2 (17%) for EVT, and 7 (64%) for both IVT and EVT. Brain bleeding was the most recalled risk for IVT and "lack of benefit" for EVT. CONCLUSIONS: Majority of the participants were extremely satisfied and reported no difficulty understanding purpose and risks of acute stroke treatment, however only 30% were able to verbalize two or more risks associated with the treatment.

Trends in Stroke Thrombolysis Care Metrics and Outcomes by Race and Ethnicity, 2003-2021.

Importance: Understanding is needed of racial and ethnic-specific trends in care quality and outcomes associated with the US nationwide quality initiative Target: Stroke (TS) in targeting thrombolysis treatment for acute ischemic stroke. Objective: To examine whether the TS quality initiative was associated with improvement in thrombolysis metrics and outcomes across racial and ethnic groups. Design, Setting, and Participants: This retrospective cohort study included patients who presented within 4.5 hours of ischemic stroke onset at hospitals participating in the Get With The Guidelines-Stroke initiative from January 1, 2003, to December 31, 2021. The data analysis was performed between December 15, 2022, and November 27, 2023. Exposures: TS phases I (2010-2013), II (2014-2018), and III (2019-2021). Main Outcomes and Measures: The primary outcomes were thrombolysis rates and time metrics. Patient function and mortality were secondary outcomes. Results: Analyses included 1 189 234 patients, of whom 1 053 539 arrived to the hospital within 4.5 hours. The cohort included 50.4% female and 49.6% male patients and 2.8% Asian [median (IQR) age, 72 (61-82) years], 15.2% Black [median (IQR) age, 64 (54-75) years], 7.3% Hispanic [median (IQR) age, 68 (56-79) years], and 74.1% White [median (IQR) age, 75 (63-84) years] patients). Unadjusted thrombolysis rates increased in both the pre-TS (2003-2009) and TS periods in all racial and ethnic groups from 10% to 15% in 2003 to 43% to 46% in 2021, but disparities were observed in adjusted analyses and persisted in TS phase III, with Asian, Black, and Hispanic patients having significantly lower odds of receiving thrombolysis than White patients (adjusted odds ratio, 0.85 [95% CI, 0.81-0.90], 0.76 [95% CI, 0.74-0.78], and 0.86 [95% CI, 0.83-0.89], respectively). Door-to-needle (DTN) times improved in all racial and ethnic groups during TS, with DTN times of 60 minutes or less increasing from 26% to 28% in 2009 to 66% to 72% in 2021. However, in adjusted analyses, racial and ethnic disparities emerged. During TS phase III, compared with White patients, Asian, Black, and Hispanic patients had significantly lower odds of receiving thrombolysis with a DTN time of 60 minutes or less compared with White patients (risk-adjusted odds ratios, 0.91 [95% CI, 0.84-0.98], 0.78 [95% CI, 0.75-0.81], and 0.87 [95% CI, 0.83-0.92], respectively). During TS, clinical outcomes improved for all racial and ethnic groups from pre-TS, with TS phase III showing higher odds of ambulation at discharge among Asian, Black, Hispanic, and White patients. Asian, Black, and Hispanic patients were less likely to present within 4.5 hours. Conclusions and Relevance: In this cohort study of patients with ischemic stroke, the TS quality initiative was associated with improvement in thrombolysis frequency, timeliness, and outcomes for all racial and ethnic groups. However, disparities persisted, indicating a need for further interventions.

Structural Brain Injury on Brain Magnetic Resonance Imaging in Acute Respiratory Distress Syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is an acute inflammatory respiratory failure condition that may be associated with brain injury. We aimed to describe the types of structural brain injuries detected by brain magnetic resonance imaging (MRI) among patients with ARDS. METHODS: We retrospectively reviewed and collected data on brain injuries as detected by brain MRI during index hospitalization of all patients with ARDS at a single tertiary center in the United States from January 2010 to October 2018 (pre-COVID era). Structural brain injuries were classified as cerebral ischemia (ischemic infarct and hypoxic-ischemic brain injury) or cerebral hemorrhage (intraparenchymal hemorrhage, cerebral microbleeds, subarachnoid hemorrhage, and subdural hematoma). Descriptive statistics were conducted. RESULTS: Of the 678 patients with ARDS, 66 (9.7%) underwent brain MRI during their ARDS illness. The most common indication for brain MRI was encephalopathy (45.4%), and the median time from hospital admission to MRI was 10 days (interquartile range 4-17). Of 66 patients, 29 (44%) had MRI evidence of brain injury, including cerebral ischemia in 33% (22 of 66) and cerebral hemorrhage in 21% (14 of 66). Among those with cerebral ischemia, common findings were bilateral globus pallidus infarcts (n = 7, 32%), multifocal infarcts (n = 5, 23%), and diffuse hypoxic-ischemic brain injury (n = 3, 14%). Of those with cerebral hemorrhage, common findings were cerebral microbleeds (n = 12, 86%) and intraparenchymal hemorrhage (n = 2, 14%). Patients with ARDS with cerebral hemorrhage had significantly greater use of rescue therapies, including prone positioning (28.6% vs. 5.8%, p = 0.03), inhaled vasodilator (35.7% vs. 11.5%, p = 0.046), and recruitment maneuver (14.3% vs. 0%, p = 0.04). CONCLUSIONS: Structural brain injury was not uncommon among selected patients with ARDS who underwent brain MRI. The majority of brain injuries seen were bilateral globus pallidus infarcts and cerebral microbleeds.

Epidemiology of ischemic stroke and hemorrhagic stroke in venoarterial extracorporeal membrane oxygenation.

BACKGROUND: While venoarterial extracorporeal membrane oxygenation (V-A ECMO) provides lifesaving support for cardiopulmonary failure, complications may increase mortality, with few studies focusing on ischemic/hemorrhagic stroke. We aimed to determine the trends and associations of stroke incidence and mortality, and their risk factors, including the effects of annual case volumes of ECMO centers. METHODS: Retrospective analysis was performed on the Extracorporeal Life Support Organization (ELSO) registry, including adult V-A ECMO patients from 534 international centers between 2012 and 2021, excluding extracorporeal cardiopulmonary resuscitation. Temporal trend analyses were performed for stroke incidence and mortality. Univariate testing, multivariable regression, and survival analysis were used to evaluate the associations of stroke, 90-day mortality, and impact of annual center volume. RESULTS: Of 33,041 patients, 20,297 had mortality data, and 12,327 were included in the logistic regression. Between 2012 and 2021, ischemic stroke incidence increased (p < 0.0001), hemorrhagic stroke incidence remained stable, and overall 90-day mortality declined (p < 0.0001). Higher 24-h PaO2 and greater decrease between pre-ECMO PaCO2 and post-cannulation 24-h PaCO2 were associated with greater ischemic stroke incidence, while annual case volume was not. Ischemic/hemorrhagic strokes were associated with increased 90-day mortality (both p < 0.0001), while higher annual case volume was associated with lower 90-day mortality (p = 0.001). Hazard of death was highest in the first several days of V-A ECMO. CONCLUSION: In V-A ECMO patients between 2012 and 2021, 90-day mortality decreased, while ischemic stroke incidence increased. ELSO centers with higher annual case volumes had lower mortality, but were not associated with ischemic/hemorrhagic stroke incidence. Both ischemic/hemorrhagic strokes were associated with increased mortality.

The prevalence of radiological cerebral amyloid angiopathy-related inflammation in patients with cerebral amyloid angiopathy.

OBJECTIVES: Cerebral amyloid angiopathy (CAA) related inflammation (CAA-RI) is an autoimmune inflammatory condition occurring in patients with CAA. We aimed to determine the prevalence of radiological CAA-RI amongst patients with CAA and to describe their presenting clinical features. METHODS: We performed a retrospective review of electronic medical records across multiple centers within a single healthcare network. Patients who met radiological modified Boston 2.0 criteria for CAA and had white matter hyperintensity (WMH) were included. Scans were analyzed by a vascular neurologist and confirmed by a neuroradiologist blinded to clinical information for meeting criteria for possible or probable radiographic CAA-RI. RESULTS: Out of 1100 patients reviewed, 511 patients met radiological modified Boston criteria for CAA and 193 patients had WMH on MRI. A total of 55 (28.5 % of those with CAA and WMH, and 10.8 % of all CAA with or without WMH) patients had MRI brain imaging suggestive of possible or probable radiographic CAA-RI. The diagnosis of CAA-RI was reported in only 10 (18.2 %) patients initially while 20 (36.4 %) were diagnosed up to 74 months later (median 0, IQR 0-9 months). At the time of earliest probable CAA-RI findings on imaging, the most common concurrent findings were cognitive impairment (74.5 %), macro-hemorrhages (52.7 %), headache (30.9 %), seizures (14.5 %), and ischemic infarcts (14.5 %). Only 18 (32.7 %) patients were treated with immunosuppression. CONCLUSIONS: The prevalence of radiographic CAA-RI was high, and most cases were unrecognized and untreated. Further studies are needed to assess if earlier detection and treatment of radiologic CAA-RI may halt disease progression and prevent cognitive decline in these patients.

Cerebral microbleeds in acute respiratory distress syndrome.

BACKGROUND: Cerebral microbleeds (CMB) have been observed in patients with critical illness. We sought to examine the frequency of CMB in patients with acute respiratory distress syndrome (ARDS) and association with neurologic complications including acute cerebral ischemia and seizures. METHODS: A retrospective review of patients with ARDS from January 2010 to October 2018 was performed. Patients with brain MRIs with susceptibility weighted imaging or gradient echo sequences were included. We compared neurologic complications and intensive care unit outcomes between patients with and without CMB. Cerebral small vessel disease (CSVD) was defined as the presence of CMB, lacunar infarcts, enlarged perivascular spaces, and white matter hyperintensities. RESULTS: Of 678 patients with ARDS, 61 met inclusion criteria. Median age was 54 years (IQR 42-63) and 28 were males. Of 12 (20%) with CMB, 10 had lobar CMB. Four patients had CMB in the corpus callosum, all involving the splenium. Neurologic complications were more common in those with CMB including acute cerebral ischemia (41.7% versus 10.2%, p=0.008) and seizures (33.3% versus 8.2%, p=0.021). ARDS rescue therapies were more commonly used in patients with CMB (p=0.005). There was no difference in hospital mortality (41.7% versus 34.7%, p=0.652). Patients with CMB did not have a higher CSVD score than those without CMB when accounting for the presence of CMB (median=1 versus 0, p=0.891). CONCLUSION: CMB were present in twenty percent of patients with ARDS who had MRI and were more commonly seen in patients requiring ARDS rescue therapies.

The early impact of COVID-19 pandemic on mobile stroke unit care delivery: A worldwide survey.

OBJECTIVE: To report COVID -19 pandemic impact on mobile stroke units (MSUs) a world-wide survey of MSU programs. METHODS: Contact information of MSU program was obtained through the Pre-hospital Stroke Treatment Organization. Anonymous electronic questionnaire was developed and sent through the email to one representative of each program on May 15, 2020. RESULTS: Of 26 programs queried, 20 responded and completed survey based on the data or personal impression. Eighteen programs were in the regions with pandemic lockdown. Six either suspended or reduced MSU availability at some point. The reasons given for change in availability were as follows: decreased personnel availability (5 programs), risk of exposure (5 programs), and financial concerns (1 program). Staff availability was a concern among 8 programs. MSU activations were reported to be unchanged by 10 programs, but 9 programs experienced decline in activation, 1 program had more activations. Sixteen programs reported change in MSU protocol including introduction of screening questionnaire, PPE, reducing patient contact, and cleaning protocols. Nine reported that the crew was under greater stress. Only 2 respondents felt that the pandemic delayed stroke care on MSU and the remainder did not. CONCLUSION: Overall Stroke care delivery had no major disruptions despite COVID 19 pandemic posed challenges to MSU Operations.

Epidemiology of Ischemic Stroke and Hemorrhagic Stroke in Venoarterial Extracorporeal Membrane Oxygenation.

Background: While venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides lifesaving support for cardiopulmonary failure, complications may arise that increase mortality, with few studies focusing on ischemic/hemorrhagic stroke. We aimed to determine the trends of stroke incidence and mortality, associations with each other, and associations with total case volume at each Extracorporeal Life Support Organization (ELSO) center. Methods: Retrospective analysis of ELSO registry, including adult VA-ECMO patients from 534 international centers between 2012-2021, excluding extracorporeal cardiopulmonary resuscitation. Cochran-Armitage test and Poisson regression were used for trend analysis of stroke incidence and mortality. Kaplan-Meier curves, hazard functions, and multivariable logistic regression were used to study the impact of stroke on 90-day mortality. Results: Of 33,041 patients (median age = 58 years, female = 32%), 4% developed ischemic stroke, and 2% developed hemorrhagic stroke. Ischemic stroke incidence increased (×1.21/year, p < 0.0001), while hemorrhagic stroke incidence remained stable, and overall 90-day mortality declined (1.78%/year, p < 0.0001). Ischemic/hemorrhagic strokes were associated with increased overall 90-day mortality (OR = 3.29, 3.99 respectively, both p < 0.0001) after controlling for pre-selected covariates, including age, pre/post-cannulation lab values, ECMO duration, center volume, and on-ECMO complications. Total center volume was associated positively with ischemic/hemorrhagic stroke incidences (OR = 1.039, 1.053 per-additional-100-cases respectively, both p = 0.022), but inversely with 90-day mortality (OR = 0.909 per-additional-100-cases, p < 0.0001). Hazard of death was highest in the first several days of VA-ECMO. Conclusion: In VA-ECMO patients, while the reported ischemic stroke incidence steadily increased over time, 90-day mortality decreased. ELSO centers with higher case volumes reported greater stroke incidence, but lower mortality. Both ischemic/hemorrhagic strokes were associated with increased mortality.

Central Nervous System Vasculitis: Primary Angiitis of the Central Nervous System and Central Nervous System Manifestations of Systemic Vasculitis.

Central nervous system vasculitis (CNSV) is a group of disorders leading to inflammatory vasculopathy within the brain, spinal cord, and leptomeninges. CNSV is divided into primary angiitis of the central nervous system (PACNS) and secondary CNSV based on the underlying etiology. PACNS is a rare inflammatory disorder with poorly understood pathophysiology and heterogeneous and highly variable clinical features. The diagnosis depends on a combination of clinical and laboratory variables, multimodal imaging, and histopathological examination as well as exclusion of mimics. Several systemic vasculitides, infectious etiologies and connective tissue disorders have been shown to cause secondary CNSV and require prompt recognition.

Outcomes of heart transplant recipients with prior left ventricular assist device associated stroke.

BACKGROUND: Left ventricular assist devices (LVADs) improve survival in patients with end-stage heart failure but are associated with ischemic stroke and intracranial hemorrhage (ICH). The impact of LVAD-associated stroke on transplant candidacy and outcomes has not been characterized. METHODS: Adult patients undergoing LVAD implantation at Cleveland Clinic between 2004 to 2021 were reviewed and patients who developed ischemic stroke or ICH were identified. Post-transplant survival analysis was performed between patients with LVAD-associated stroke vs. without. RESULTS: 917 patients had an LVAD implantation of whom 244 (median age 57, 79% male) underwent subsequent transplant including 25 with prior LVAD-associated stroke. The 1- and 2-year survival after transplant in patients with LVAD-associated stroke were 100% and 95% respectively, compared with 92% and 90% in patients without stroke (p=0.156; p=0.323) Similarly, there was no difference in stroke incidence at 1- and 2 years after transplant between patients with LVAD-associated stroke (4% and 5%) and those without prior stroke (5% and 6%, p = 0.884; p=0.744). CONCLUSIONS: In this single-center retrospective study, patients with LVAD-associated stroke were significantly less likely to undergo heart transplant, but those who underwent heart transplant had similar post-transplant outcomes as patients without history of LVAD-associated stroke. Given the similar outcomes seen in this population, history of LVAD-associated stroke should not be viewed as an absolute contraindication to subsequent heart transplant.

Quantitative CTA vascular calcification, atherosclerosis burden, and stroke mechanism in patients with ischemic stroke.

BACKGROUND: Vascular calcification is recognized as the advanced stage of atherosclerosis burden. We hypothesized that vascular calcium quantification in CT angiography (CTA) would be helpful to differentiate large artery atherosclerosis (LAA) from other stroke etiology in patients with ischemic stroke. METHODS: We studied 375 acute ischemic stroke patients (200 males, mean age 69.9 years) who underwent complete CTA images of the aortic arch, neck, and head. The automatic artery and calcification segmentation method measured calcification volumes in the intracranial internal carotid artery (ICA), cervical carotid artery, and aortic arch using deep-learning U-net model and region-grow algorithms. We investigated the correlations and patterns of vascular calcification in the different vessel beds among stroke etiology by age category (young: <65 years, intermediate: 65-74 years, older ≥75 years). RESULTS: Ninety-five (25.3%) were diagnosed with LAA according to TOAST criteria. Median calcification volumes were higher by increasing the age category in each vessel bed. One-way ANOVA with Bonferroni correction showed calcification volumes in all vessel beds were significantly higher in LAA compared with other stroke subtypes in the younger subgroup. Calcification volumes were independently associated with LAA in intracranial ICA (OR; 2.89, 95% CI 1.56-5.34, P = .001), cervical carotid artery (OR; 3.40, 95% CI 1.94-5.94, P < .001) and aorta (OR; 1.69, 95%CI 1.01-2.80, P = .044) in younger subsets. By contrast, the intermediate and older subsets did not show a significant relationship between calcification volumes and stroke subtypes. CONCLUSION: Atherosclerosis calcium volumes in major vessels were significantly higher in LAA compared to non-LAA stroke in younger age.

Shorter Door-to-Needle Times Are Associated With Better Outcomes After Intravenous Thrombolytic Therapy and Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND: Existing data and clinical trials could not determine whether faster intravenous thrombolytic therapy (IVT) translates into better long-term functional outcomes after acute ischemic stroke among those treated with endovascular thrombectomy (EVT). Patient-level national data can provide the required large population to study the associations between earlier IVT, versus later, with longitudinal functional outcomes and mortality in patients receiving IVT+EVT combined treatment. METHODS: This cohort study included older US patients (age ≥65 years) who received IVT within 4.5 hours or EVT within 7 hours after acute ischemic stroke using the linked 2015 to 2018 Get With The Guidelines-Stroke and Medicare database (38 913 treated with IVT only and 3946 with IVT+EVT). Primary outcome was home time, a patient-prioritized functional outcome. Secondary outcomes included all-cause mortality in 1 year. Multivariate logistic regression and Cox proportional hazards models were used to evaluate the associations between door-to-needle (DTN) times and outcomes. RESULTS: Among patients treated with IVT+EVT, after adjusting for patient and hospital factors, including onset-to-EVT times, each 15-minute increase in DTN times for IVT was associated with significantly higher odds of zero home time in a year (never discharged to home) (adjusted odds ratio, 1.12 [95% CI, 1.06-1.19]), less home time among those discharged to home (adjusted odds ratio, 0.93 per 1% of 365 days [95% CI, 0.89-0.98]), and higher all-cause mortality (adjusted hazard ratio, 1.07 [95% CI, 1.02-1.11]). These associations were also statistically significant among patients treated with IVT but at a modest degree (adjusted odds ratio, 1.04 for zero home time, 0.96 per 1% home time for those discharged to home, and adjusted hazard ratio 1.03 for mortality). In the secondary analysis where the IVT+EVT group was compared with 3704 patients treated with EVT only, shorter DTN times (≤60, 45, and 30 minutes) achieved incrementally more home time in a year, and more modified Rankin Scale 0 to 2 at discharge (22.3%, 23.4%, and 25.0%, respectively) versus EVT only (16.4%, P<0.001 for each). The benefit dissipated with DTN>60 minutes. CONCLUSIONS: Among older patients with stroke treated with either IVT only or IVT+EVT, shorter DTN times are associated with better long-term functional outcomes and lower mortality. These findings support further efforts to accelerate thrombolytic administration in all eligible patients, including EVT candidates.

Clinical characteristics, brain magnetic resonance imaging findings and diagnostic approach of the primary central nervous system vasculitis according to angiographic classification.

OBJECTIVES: To determine the diagnostic accuracy for high-resolution vessel wall image (HR-VWI) and brain biopsy according to angiographical classification in patients with primary central nervous system vasculitis (PCNSV). METHODS: We extracted the patients with PCNSV who underwent the complete brain MRI protocol and cerebral vascular image from Cleveland Clinic prospective CNS vasculopathy Bioregistry. The large-medium vessel variant (LMVV) was defined as patients with cerebral vasculature indicating vasculitis in proximal or middle arterial segments, whereas vessel involvements in smaller distal branches or normal angiography were considered as the small vessel variant (SVV). We compared clinical demographics, magnetic resonance imaging (MRI) findings, and diagnostic approaches between two variants. RESULTS: In this case-control study that included 34 PCNSV patients, the LMVV group comprised a total of 11 patients (32.4%), and 23 patients (67.6%) were classified as the SVV group. The LMVV had more strong/concentric vessel wall enhancement on HR-VWI (LMVV: 90% (9/10) vs. SVV: 7.1% (1/14), p<0.001). By contrast, meningeal/parenchymal contrast enhancement lesion was more frequently observed in the SVV group (p=0.006). The majority of SVV was diagnosed by brain biopsy (SVV: 78.3% vs. LMVV: 30.8%, p=0.022). The diagnostic accuracy of the brain biopsy was 100% (18/18) in SVV and 57.1% (4/7) in LMVV, respectively (p=0.015). CONCLUSIONS: Diagnostic approach for PCNSV differs concerning the affected vessel size. HR-VWI is a useful imaging modality for the diagnosis of LMVV. Brain biopsy remains the gold standard for proving PCNSV with SVV but is still positive in almost one-third of LMVV.

National Trends, Risk Factors, and Outcomes of Acute In-Hospital Stroke Following Lung Transplantation in the United States: Analysis of the United Network for Organ Sharing Registry.

BACKGROUND: Lung transplantation (LTx) is the definitive treatment for end-stage lung failure. However, there have been no large, long-term studies on the impact of acute in-hospital stroke in this population. RESEARCH QUESTION: What are the trends, risk factors, and outcomes of acute stroke in patients undergoing LTx in the United States? STUDY DESIGN AND METHODS: We identified adult first-time isolated LTx recipients from the United Network for Organ Sharing database, which comprehensively captures every transplant in the United States, between May 2005 and December 2020. Stroke was defined as occurring at any time after LTx but prior to discharge. Multivariable logistic regression with stepwise feature elimination was used to identify risk factors for stroke. Freedom from death in patients with a stroke vs those without a stroke was evaluated with Kaplan-Meier analysis. Cox proportional hazards analysis was used to identify predictors of death at 24 months. RESULTS: Of 28,564 patients (median age, 60 years; 60% male), 653 (2.3%) experienced an acute in-hospital stroke after LTx. Median follow-up was 1.2 (stroke) and 3.0 (non-stroke) years. Annual incidence of stroke increased (1.5% in 2005 to 2.4% in 2020; P for trend = .007), as did lung allocation score and utilization of post-LTx extracorporeal membrane oxygenation (P = .01 and P < .001, respectively). Compared with those without stroke, patients with stroke had lower survival at 1 month (84% vs 98%), 12 months (61% vs 88%), and 24 months (52% vs 80%) (log-rank test, P < .001 for all). In Cox analysis, acute stroke conferred a high hazard of mortality (hazard ratio, 3.01; 95% CI, 2.67-3.41). Post-LTx extracorporeal membrane oxygenation was the strongest risk factor for stroke (adjusted OR, 2.98; 95% CI, 2.19-4.06). INTERPRETATION: Acute in-hospital stroke post-LTx has been increasing over time and is associated with markedly worse short- and long-term survival. As increasingly sicker patients undergo LTx as well as experience stroke, further research on stroke characteristics, prevention, and management strategies is warranted.

Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.

BACKGROUND AND OBJECTIVES: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). METHODS: We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations. DISCUSSION: There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. TRIAL REGISTRATION INFORMATION: This study is registered under NCT04934020.

MRI of Cerebrovascular Injury Associated With COVID-19 and Non-COVID-19 Acute Respiratory Distress Syndrome: A Matched Case-Control Study.

OBJECTIVES: Cerebrovascular injury associated with COVID-19 has been recognized, but the mechanisms remain uncertain. Acute respiratory distress syndrome (ARDS) is a severe pulmonary injury, which is associated with both ischemic and hemorrhagic stroke. It remains unclear if cerebrovascular injuries associated with severe COVID-19 are unique to COVID-19 or a consequence of severe respiratory disease or its treatment. The frequency and patterns of cerebrovascular injury on brain MRI were compared among patients with COVID-19 ARDS and non-COVID-19 ARDS. DESIGN: A case-control study. SETTING: A tertiary academic hospital system. PATIENTS: Adult patients (>18 yr) with COVID-19 ARDS (March 2020 to July 2021) and non-COVID-19 ARDS (January 2010-October 2018) who underwent brain MRI during their index hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebrovascular injury on MRI included cerebral ischemia (ischemic infarct or hypoxic ischemic brain injury) and intracranial hemorrhage (intraparenchymal, subarachnoid, or subdural, and cerebral microbleed [CMB]).Twenty-six patients with COVID-19 ARDS and sixty-six patients with non-COVID ARDS underwent brain MRI during the index hospitalization, resulting in 23 age- and sex-matched pairs. The frequency of overall cerebrovascular injury (57% vs 61%), cerebral ischemia (35% vs 43%), intracranial hemorrhage (43% vs 48%), and CMB (52% vs 41%) between COVID-19 ARDS and non-COVID-19 ARDS patients was similar (all p values >0.05). However, four of 26 patients (15%) with COVID-19 and no patients with non-COVID-19 ARDS had disseminated leukoencephalopathy with underlying CMBs, an imaging pattern that has previously been reported in patients with COVID-19. CONCLUSIONS: In a case-control study of selected ARDS patients with brain MRI, the frequencies of ischemic and hemorrhagic cerebrovascular injuries were similar between COVID-19 versus non-COVID-19 ARDS patients. However, the MRI pattern of disseminated hemorrhagic leukoencephalopathy was unique to the COVID-19 ARDS patients in this cohort.

Cerebral embolic protection and severity of stroke following transcatheter aortic valve replacement.

BACKGROUND: The cerebral embolic protection (CEP) device captures embolic debris during transcatheter aortic valve replacement (TAVR). However, the impact of CEP on stroke severity following TAVR remains unclear. Therefore, we aimed to examine whether CEP was associated with reduced severity of stroke following TAVR. METHODS: This was a retrospective cohort study of 2839 consecutive patients (mean age: 79.2 ± 9.5 years, females: 41.5%) who underwent transfemoral TAVR at our institution between 2013 and 2020. We categorized patients into Sentinel CEP users and nonusers. Neuroimaging data were reviewed and the final diagnosis of a cerebrovascular event was adjudicated by a neurologist blinded to the CEP use or nonuse. We compared the incidence and severity (assessed by the National Institutes of Health Stroke Scale [NIHSS]) of stroke through 72 h post-TAVR or discharge between the two groups using stabilized inverse probability of treatment weighting (IPTW) of propensity scores. RESULTS: Of the eligible patients, 1802 (63.5%) received CEP during TAVR and 1037 (36.5%) did not. After adjustment for patient characteristics by stabilized IPTW, the rate of overall stroke was numerically lower in CEP users than in CEP nonusers, but the difference did not reach statistical significance (0.49% vs. 1.18%, p = 0.064). However, CEP users had significantly lower rates of moderate-or-severe stroke (NIHSS ≥ 6: 0.11% vs. 0.69%, p = 0.013) and severe stroke (NIHSS ≥ 15: 0% vs. 0.29%, p = 0.046). Stroke following CEP use (n = 8), compared with stroke following CEP nonuse (n = 15), tended to carry a lower NIHSS (median [IQR], 4.0 [2.0-7.0] vs. 7.0 [4.5-19.0], p = 0.087). Four (26.7%) out of 15 patients with stroke following CEP nonuse died within 30 days, with no death after stroke following CEP use. CONCLUSIONS: CEP use may be associated with attenuated severity of stroke despite no significant difference in overall stroke incidence compared with CEP nonuse. This finding is considered hypothesis-generating and needs to be confirmed in large prospective studies.