Ischemic stroke in COVID-19 patients: Mechanisms, treatment, and outcomes in a consecutive Swiss Stroke Registry analysis

BACKGROUND: Most case series of patients with ischemic stroke (IS) and COVID-19 are limited to selected centers or lack 3-month outcomes. The aim of this study was to describe the frequency, clinical and radiological features, and 3-month outcomes of patients with IS and COVID-19 in a nationwide stroke registry. METHODS: From the Swiss Stroke Registry (SSR), we included all consecutive IS patients ≥18 years admitted to Swiss Stroke Centers or Stroke Units during the first wave of COVID-19 (25 February to 8 June 2020). We compared baseline features, etiology, and 3-month outcome of SARS-CoV-2 polymerase chain reaction-positive (PCR+) IS patients to SARS-CoV-2 PCR- and/or asymptomatic non-tested IS patients. RESULTS: Of the 2341 IS patients registered in the SSR during the study period, 36 (1.5%) had confirmed COVID-19 infection, of which 33 were within 1 month before or after stroke onset. In multivariate analysis, COVID+ patients had more lesions in multiple vascular territories (OR 2.35, 95% CI 1.08-5.14, p = 0.032) and fewer cryptogenic strokes (OR 0.37, 95% CI 0.14-0.99, p = 0.049). COVID-19 was judged the likely principal cause of stroke in 8 patients (24%), a contributing/triggering factor in 12 (36%), and likely not contributing to stroke in 13 patients (40%). There was a strong trend towards worse functional outcome in COVID+ patients after propensity score (PS) adjustment for age, stroke severity, and revascularization treatments (PS-adjusted common OR for shift towards higher modified Rankin Scale (mRS) = 1.85, 95% CI 0.96-3.58, p = 0.07). CONCLUSIONS: In this nationwide analysis of consecutive ischemic strokes, concomitant COVID-19 was relatively rare. COVID+ patients more often had multi-territory stroke and less often cryptogenic stroke, and their 3-month functional outcome tended to be worse

Prevalence and time course of post-stroke pain: A multicenter prospective hospital-based study

OBJECTIVE: Pain prevalence data for patients at various stages after stroke. DESIGN: Repeated cross-sectional, observational epidemiological study. SETTING: Hospital-based multicenter study. SUBJECTS: Four hundred forty-three prospectively enrolled stroke survivors. METHODS: All patients underwent bedside clinical examination. The different types of post-stroke pain (central post-stroke pain, musculoskeletal pains, shoulder pain, spasticity-related pain, and headache) were diagnosed with widely accepted criteria during the acute, subacute, and chronic stroke stages. Differences among the three stages were analyzed with χ(2)-tests. RESULTS: The mean overall prevalence of pain was 29.56% (14.06% in the acute, 42.73% in the subacute, and 31.90% in the chronic post-stroke stage). Time course differed significantly according to the various pain types (P < 0.001). The prevalence of musculoskeletal and shoulder pain was higher in the subacute and chronic than in the acute stages after stroke; the prevalence of spasticity-related pain peaked in the chronic stage. Conversely, headache manifested in the acute post-stroke stage. The prevalence of central post-stroke pain was higher in the subacute and chronic than in the acute post-stroke stage. Fewer than 25% of the patients with central post-stroke pain received drug treatment. CONCLUSIONS: Pain after stroke is more frequent in the subacute and chronic phase than in the acute phase, but it is still largely undertreated

Endovascular therapy versus no endovascular therapy in patients receiving best medical management for acute isolated occlusion of the posterior cerebral artery : A systematic review and meta-analysis

Background and purpose Endovascular therapy (EVT) is increasingly reported for treatment of isolated posterior cerebral artery (PCA) occlusions although its clinical benefit remains uncertain. This study-level meta-analysis investigated the functional outcomes and safety of EVT and best medical management (BMM) compared to BMM alone for treatment of PCA occlusion stroke. Methods We conducted a literature search in PubMed, Web of Science and Embase for studies in patients with isolated PCA occlusion stroke treated with EVT + BMM or BMM including intravenous thrombolysis. There were no randomized trials and all studies were retrospective. The primary outcome was modified Rankin Scale score of 0-2 at 3 months, while safety outcomes included mortality rate and incidence of symptomatic intracranial hemorrhage (sICH). Results Twelve studies with a total of 679 patients were included in the meta-analysis: 338 patients with EVT + BMM and 341 patients receiving BMM alone. Good functional outcome at 3 months was achieved in 58.0% (95% confidence interval [CI] 43.83-70.95) of patients receiving EVT + BMM and 48.1% (95% CI 40.35-55.92) of patients who received BMM alone, with respective mortality rates of 12.6% (95% CI 7.30-20.93) and 12.3% (95% CI 8.64-17.33). sICH occurred in 4.2% (95% CI 2.47-7.03) of patients treated with EVT + BMM and 3.2% (95% CI 1.75-5.92) of patients treated with BMM alone. Comparative analyses were performed on studies that included both treatments and these demonstrated no significant differences. Conclusions Our results demonstrate that EVT represents a safe treatment for patients with isolated PCA occlusion stroke. There were no differences in clinical or safety outcomes between treatments, supporting randomization of future patients into distal vessel occlusion trials.Peer reviewe

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation.

The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes. This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months. Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p &lt; 0.001; quantile regression: β -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51). Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42-53

Thrombolysis in stroke patients with elevated inflammatory markers.

OBJECTIVE To investigate the prognostic value of white blood cell count (WBC) on functional outcome, mortality and bleeding risk in stroke patients treated with intravenous thrombolysis (IVT). METHODS In this prospective multicenter study from the TRISP registry, we assessed the association between WBC on admission and 3-month poor outcome (modified Rankin Scale 3-6), mortality and occurrence of symptomatic intracranial hemorrhage (sICH; ECASS-II-criteria) in IVT-treated stroke patients. WBC was used as continuous and categorical variable distinguishing leukocytosis (WBC > 10 × 109/l) and leukopenia (WBC  10 mg/l) on outcomes. RESULTS Of 10,813 IVT-treated patients, 2527 had leukocytosis, 112 leukopenia and 8174 normal WBC. Increasing WBC (by 1 × 109/l) predicted poor outcome (ORadjusted 1.04[1.02-1.06]) but not mortality and sICH. Leukocytosis was independently associated with poor outcome (ORadjusted 1.48[1.29-1.69]) and mortality (ORadjusted 1.60[1.35-1.89]) but not with sICH (ORadjusted 1.17[0.94-1.45]). Leukopenia did not predict any outcome. In a subgroup, combined leukocytosis and elevated CRP had the strongest association with poor outcome (ORadjusted 2.26[1.76-2.91]) and mortality (ORadjusted 2.43[1.86-3.16]) when compared to combined normal WBC and CRP. CONCLUSION In IVT-treated patients, leukocytosis independently predicted poor functional outcome and death. Bleeding complications after IVT were not independently associated with leukocytosis

Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce. METHODS We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019). RESULTS We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI], 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031). CONCLUSIONS Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage

Insights from thrombi retrieved in stroke due to large vessel occlusion

The recent advances of endovascular procedures to treat stroke due to large cerebral vessel occlusion have made it possible to analyze the retrieved thrombus material. Analysis of cerebral thrombi is emerging as a relevant opportunity to complement the diagnostic workup of etiology, to develop new lytic approaches and to optimize the acute treatment of stroke due to large vessel occlusion. Nonetheless, retrieved thrombi are frequently discarded since their informative potential is often neglected and standards are missing. This review provides an overview of the current knowledge and expanding research relating to thrombus composition analysis in large vessel occlusions. We first discuss the heterogeneity of thrombogenic factors that underlie the thrombotic formation in stroke and its implications to identify stroke etiology and thrombus age. Further, we show that understanding structural characteristics of thrombus is pivotal for the development of new-targeted lytic therapies as well as to improve, through thrombus modeling, the development of thrombectomy devices. Finally, we discuss the on-going attempts to identify a signature of thrombus composition indirectly through imaging and peripheral blood biomarkers, which might in future assist treatment decision-making as well as secondary prevention. Thrombus analysis might contribute to the advancement and optimization of personalized stroke treatments

The risk of stroke recurrence in patients with atrial fibrillation and reduced ejection fraction.

Atrial fibrillation (AF) and congestive heart failure often coexist due to their shared risk factors leading to potential worse outcome, particularly cerebrovascular events. The aims of this study were to calculate the rates of ischemic and severe bleeding events in ischemic stroke patients having both AF and reduced ejection fraction (rEF) (⩽40%), compared to ischemic stroke patients with AF but without rEF. We performed a retrospective analysis that drew data from prospective studies. The primary outcome was the composite of either ischemic (stroke or systemic embolism), or hemorrhagic events (symptomatic intracranial bleeding and severe extracranial bleeding). The cohort for this analysis comprised 3477 patients with ischemic stroke and AF, of which, 643 (18.3%) had also rEF. After a mean follow-up of 7.5 ± 9.1 months, 375 (10.8%) patients had 382 recorded outcome events, for an annual rate of 18.0%. While the number of primary outcome events in patients with rEF was 86 (13.4%), compared to 289 (10.2%) for the patients without rEF; on multivariable analysis rEF was not associated with the primary outcome (OR 1.25; 95% CI 0.84-1.88). At the end of follow-up, 321 (49.9%) patients with rEF were deceased or disabled (mRS ⩾3), compared with 1145 (40.4%) of those without rEF; on multivariable analysis, rEF was correlated with mortality or disability (OR 1.35; 95% CI 1.03-1.77). In patients with ischemic stroke and AF, the presence of rEF was not associated with the composite outcome of ischemic or hemorrhagic events over short-term follow-up but was associated with increased mortality or disability

Embolic Stroke of Undetermined Source and Patent Foramen Ovale Risk of Paradoxical Embolism Score Validation and Atrial Fibrillation Prediction

Background and Purpose: The Risk of Paradoxical Embolism (RoPE) score stratifies patients with stroke according to the probability of having a patent foramen ovale (PFO), which (through Bayes theorem and simple assumptions) can be used to estimate the probability that a PFO is pathogenic in a given subgroup of patients with specific features (ie, a given RoPE score value): a higher PFO prevalence corresponds to a higher probability that a PFO is pathogenic. Among alternative mechanisms in embolic stroke of undetermined source (ESUS), the actual stroke cause may be covert atrial fibrillation. We aimed to validate the RoPE score in a large ESUS population and investigate the rate of stroke recurrence and new incident atrial fibrillation during follow-up according to PFO status and RoPE score. Methods: We pooled data of consecutive patients with ESUS from 3 prospective stroke registries. We assessed RoPE score’s calibration and discrimination for the presence of PFO (and consequently for the probability that it is pathogenic). Multivariate logistic regression analysis was performed to identify factors associated with PFO. Results: Among 455 patients with ESUS (median age 59 years), 184 (40%) had PFO. The RoPE score’s area under the receiver operating characteristic curve was 0.75. In addition to RoPE score variables, absence of left ventricular hypertrophy, absence of atherosclerosis, and infratentorial lesions were independently associated with PFO. In patients with PFO and RoPE 7 to 10, PFO and RoPE 0 to 6, and without PFO, new incident atrial fibrillation rate was 3.1%, 20.5%, and 31.8%, respectively (log-rank test=6.28, P=0.04). Stroke recurrences in patients with likely pathogenic PFO were not statistically different from other patients. Conclusions: This multicenter study validates the RoPE score to predict the presence/absence of PFO in patients with ESUS, which strongly suggests that RoPE score is helpful in identifying patients with ESUS with pathogenic versus incidental PFOs. Left ventricular hypertrophy, atherosclerosis, and infratentorial stroke may further improve the score. Low RoPE scores were associated with more incidental atrial fibrillation during 10-year follow-up

ASPECTS-based selection for late endovascular treatment: a retrospective two-site cohort study.

IntroductionThe DAWN trial demonstrated the effectiveness of late endovascular treatment (EVT) in acute ischemic stroke (AIS) patients selected on the basis of a clinical-core mismatch. We explored in a real-world sample of EVT patients if a clinical-ASPECTS (Alberta Stroke Program Early CT Score) mismatch was associated with an outcome benefit after late EVT. MethodsWe retrospectively analysed all consecutive AIS patients admitted 6-24 hours after last proof of good health in two stroke centres, with initial National Institutes of Health Stroke Scale (NIHSS) â¥10 and an internal carotid artery or M1 occlusion. We defined clinical-ASPECTS mismatch as NIHSSâ¥10 and ASPECTSâ¥7, or NIHSSâ¥20 and ASPECTSâ¥5. We assessed the interaction between clinical-ASPECTS mismatch positive and negative patients and late EVT, using ordinal shift analysis of the 3-month modified Rankin Scale and adjusting for multiple confounders.ResultsThe included 337 patients had a median age of 73 years (IQR=61-82), admission NIHSS of 18 (15-22) and baseline ASPECTS of 7 (5-9). Out of 196 (58.2%) patients showing clinical-ASPECTS mismatch, 146 (74.5%) underwent late EVT. Among 141 (41.8%) mismatch negative patients, late EVT was performed in 72 (51.1%) patients. In the adjusted analysis, late EVT was significantly associated with a better outcome in the presence of clinical-ASPECTS mismatch (adjusted Odd Ratio, aOR=2.83; 95% confidence interval, CI: 1.48-5.58) but not in its absence (aOR=1.32; 95%CI: 0.61-2.84). The p-value for the interaction term between clinical-ASPECTS mismatch and late EVT was 0.073. ConclusionsIn our retrospective two-site analysis, late EVT seemed effective in the presence of a clinical-ASPECTS mismatch, but not in its absence. If confirmed in randomized trials, this finding could support the use of an ASPECTS-based selection for late EVT decisions, obviating the need for advanced imaging