Sonothrombolysis for Ischemic Stroke.

Stroke is a major cause of death and disability globally, with ischemic stroke being the predominant mechanism. While spontaneous recanalization may occur, significant neuronal injury would have occurred in the interim. Intravenous thrombolysis administered within the first 4.5 h after stroke onset and endovascular thrombectomy within 24 h in patients with a salvageable penumbra improves functional independence. Ultrasound has been shown in both in vivo and in vitro models to enhance clot lysis, even more-so in the presence of thrombolytic agents. The use of transcranial Doppler and transcranial color-coded Doppler ultrasound in acute IS has been reported in case series, case-controlled studies, and clinical trials. While ultrasound at a frequency of 300 kHz increases the risk of intracranial hemorrhage, the 2 MHz range ultrasound aids thrombolysis and improves recanalization without significantly increasing the risk of symptomatic intracranial hemorrhage. Despite this, functional independence was not increased in clinical trials, nor was a benefit shown with the adjunctive use of microbubbles or microspheres. Nonetheless, newer technologies such as endovascular ultrasound, endovascular delivery of microbubbles, and thrombolytic-filled microbubbles await clinical trials. More evidence is needed before sonothrombolysis can be routinely used in the hyperacute management of ischemic stroke.

Left Ventricular Diastolic Dysfunction Is Associated with Poor Functional Outcomes after Endovascular Thrombectomy.

INTRODUCTION: With the advent of endovascular thrombectomy (ET), patients with acute ischaemic strokes (AIS) with large vessel occlusion (LVO) have seen vast improvements in treatment outcomes. Left ventricular diastolic dysfunction (LVDD) has been shown to herald poorer prognosis in conditions such as myocardial infarction. However, whether LVDD is related to functional recovery and outcomes in ischaemic stroke remains unclear. We studied LVDD for possible relation with clinical outcomes in patients with LVO AIS who underwent ET. METHODS: We studied a retrospective cohort of 261 LVO AIS patients who had undergone ET at a single comprehensive stroke centre and correlated LVDD to short-term mortality (in-hospital death) as well as good functional recovery defined as modified Rankin Scale of 0-2 at 3 months. RESULTS: The study population had a mean age of 65-years-old and were predominantly male (54.8%). All of the patients underwent ET with 206 (78.9%) achieving successful reperfusion. Despite this, 25 (9.6%) patients demised during the hospital admission and 149 (57.1%) did not have good function recovery at 3 months. LVDD was present in 82 (31.4%) patients and this finding indicated poorer outcomes in terms of functional recovery at 3 months (OR 2.18, 95% CI 1.04-4.54, p = 0.038) but was not associated with increased in-hospital mortality (OR 2.18, 95% CI 0.60-7.99, p = 0.240) after adjusting for various confounders. CONCLUSION: In addition to conventional echocardiographic indices such as left ventricular ejection fraction, LVDD may portend poorer outcomes after ET, and this relationship should be investigated further.

Dual Antiplatelet Therapy for the Acute Management and Long-term Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack, An Updated Review.

To improve the efficacy over antiplatelet monotherapy, dual antiplatelet therapy (DAPT) has been increasingly adopted in the management of non-cardioembolic stroke. For minor ischemic stroke and high-risk transient ischemic attack, the aspirin-clopidogrel combination is now recommended for acute short-term treatment, whereas aspirin-ticagrelor combination may be considered in selected patients, especially those with resistance to clopidogrel. For long-term stroke prevention, aspirin-dipyridamole combination has been used as an alternative to antiplatelet monotherapy, and aspirin or clopidogrel combined with cilostazole may be prescribed for added protection in high-risk patients. In this paper, we review the development of DAPT from a historical perspective and describe the findings from major clinical trials published up until the end of 2023. Using the 2021 American Heart Association guideline for secondary stroke prevention as a basis for our recommendations, we further discuss areas of controversy and more recent developments to provide an updated review for clinicians to consider in their daily practice.

Enhanced external counter pulsation therapy in patients with symptomatic and severe intracranial steno-occlusive disease: a randomized clinical trial protocol.

Intracranial stenosis is prevalent among Asians and constitutes a common cause of cerebral ischemia. While the best medical therapy carries stroke recurrence rates in excess of 10% per year, trials with intracranial stenting have been associated with unacceptable peri-procedural ischemic events. Cerebral ischemic events are strongly related to the severity of intracranial stenosis, which is high in patients with severe intracranial stenosis with poor vasodilatory reserve. Enhanced External Counter Pulsation (EECP) therapy is known to improve myocardial perfusion by facilitating the development of collateral blood vessels in the heart. In this randomized clinical trial, we evaluate whether EECP therapy may be useful in patients with severe stenosis of intracranial internal carotid (ICA) or middle cerebral artery (MCA). The review of literature, methods of evaluation, status of currently used therapeutic approaches, and trial protocol have been presented. Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03921827.

Risk of Liver Fibrosis Is Associated with More Severe Strokes, Increased Complications with Thrombolysis, and Mortality.

The Fibrosis (FIB)-4 index is an established non-invasive test to detect liver fibrosis. Liver fibrosis is postulated to be one of the predictors of the risk of symptomatic Intracranial Haemorrhage (SICH) after intravenous tissue plasminogen activator (IV tPA) therapy, the mainstay of treatment following acute ischemic stroke (AIS). However, SICH is a feared complication of thrombolytic therapy. We aimed to evaluate the association of FIB-4 with outcomes of AIS after IV tPA. Consecutive AIS patients receiving IV tPA from 2006 to 2018 at a single stroke centre were studied in a retrospective cohort study. Multivariable adjusted logistic regression was performed to assess associations of FIB-4 with outcomes. The primary outcome was SICH, and secondary outcomes included functional independence (mRS of 0−2) and mortality measured at 90 days. Among 887 patients (median age: 67 (IQR: 57−77)), 342 had FIB-4 < 1.3 and 161 had FIB-4 > 2.67. A greater proportion of moderate to severe strokes (NIHSS ≥10) occurred in the FIB-4 > 2.67 group (n = 142, 88.8%) compared to the FIB-4 < 1.3 group (n = 208, 61.2%). Amongst the different stroke subtypes, median FIB-4 was highest in cardioembolic stroke (CES) compared to the 3 other non-CES stroke subtypes (1.90 (IQR: 1.41−2.69)). Following IV tPA, having FIB-4 > 2.67 was associated with an increased rate of SICH (adjusted OR: 4.09, 95% CI: 1.04−16.16, p = 0.045) and increased mortality (adjusted OR 3.05, 95% CI: 1.28−7.26, p = 0.012). Advanced liver fibrosis was associated with an increased rate of SICH and increased 90-day mortality after IV tPA. The FIB-4 score may be useful for prognostication after IV tPA.

Potential Embolic Sources in Embolic Stroke of Undetermined Source Patients with Patent Foramen Ovale.

INTRODUCTION: A patent foramen ovale (PFO) may coexist with other potential embolic sources (PESs) in patients with embolic stroke of undetermined source (ESUS), leading to difficulty in attributing the stroke to either the PFO or other PESs. We aimed to investigate the prevalence and predictors of concomitant PESs in ESUS patients with PFOs. METHODS: A retrospective cohort study was conducted in a tertiary stroke centre. Consecutive patients with ESUS and a concomitant PFO admitted between 2012 and 2021 were included in the study. Baseline characteristics and investigations as a part of stroke workup including echocardiographic and neuroimaging data were collected. PESs were adjudicated by 2 independent neurologists after reviewing the relevant workup. RESULTS: Out of 1,487 ESUS patients, a total of 309 patients who had a concomitant PFO with mean age of 48.8 ± 13.2 years were identified during the study period. The median Risk of Paradoxical Embolism (RoPE) score for the study cohort was 6 (IQR 5-7.5). Of the 309 patients, 154 (49.8%) only had PFO, 105 (34.0%) patients had 1 other PES, 34 (11.0%) had 2 PES, and 16 (5.2%) had 3 or more PES. The most common PESs were atrial cardiopathy (23.9%), left ventricular dysfunction (22.0%), and cardiac valve disease (12.9%). The presence of additional PESs was associated with age ≥60 years (p < 0.001), RoPE score ≤6 (p ≤0.001), and the presence of comorbidities including diabetes mellitus (p = 0.004), hypertension (p≤ 0.001), and ischaemic heart disease (p = 0.011). CONCLUSION: A large proportion of ESUS patients with PFOs had concomitant PESs. The presence of concomitant PESs was associated with older age and a lower RoPE score. Further, large cohort studies are warranted to investigate the significance of the PES and their overlap with PFOs in ESUS.

The use of colchicine as an anti-inflammatory agent for stroke prevention in patients with coronary artery disease: a systematic review and meta-analysis.

OBJECTIVE: The primary objective is to evaluate the use of colchicine as an anti-inflammatory agent for stroke prevention in patients with coronary artery disease. BACKGROUND: There has been a rising number of randomized controlled trials conducted in patients with coronary artery disease on the use of colchicine in reducing cardiovascular complications. Recent publications suggest colchicine reduces the risk of stroke and other cardiovascular events. METHODS: We performed a systematic review of known trials in the current literature to characterize the clinical characteristics and outcomes of colchicine treatment in patients with coronary artery disease. A literature search was performed in PubMed, Embase and SCOPUS using a suitable keyword search strategy from inception to 4 June 2021. All studies evaluating cardiovascular outcomes of colchicine treatment in patients with coronary artery disease were included. RESULTS: The systemic review included 5 randomized controlled trials assessing a total of 11,790 patients. Majority of studies used a colchicine dosing regimen of 0.5 mg once daily, with the median follow-up duration ranging from 6 to 36 months. Meta-analytic estimates for stroke incidence highlighted a statistically significant benefit for patients that were administered colchicine compared to placebo (OR 0.47, 95% CI 0.27-0.81, p = 0.006), and a non-significant benefit for myocardial infarction. There was no significant association between colchicine treatment and the adverse effects of gastrointestinal symptoms and myopathy/myalgia. CONCLUSIONS: The use of colchicine reduces the risk of stroke in patients with a history of coronary artery disease, without a significant increase in gastrointestinal and myopathy/myalgia adverse effects.

Effect of frailty on outcomes of endovascular treatment for acute ischaemic stroke in older patients.

BACKGROUND: frailty has been shown to be a better predictor of clinical outcomes than age alone across many diseases. Few studies have examined the relationship between frailty, stroke and stroke interventions such as endovascular thrombectomy (EVT). OBJECTIVE: we aimed to investigate the impact of frailty measured by clinical frailty scale (CFS) on clinical outcomes after EVT for acute ischemic stroke (AIS) in older patients ≥70 years. METHODS: in this retrospective cohort study, we included all consecutive AIS patients age ≥ 70 years receiving EVT at a single comprehensive stroke centre. Patients with CFS of 1-3 were defined as not frail, and CFS > 3 was defined as frail. The primary outcome was modified Rankin Score (mRS) at 90 days. The secondary outcomes included duration of hospitalisation, in-hospital mortality, carer requirement, successful reperfusion, symptomatic intracranial haemorrhage and haemorrhagic transformation. RESULTS: a total of 198 patients were included. The mean age was 78.1 years and 52.0% were female. Frail patients were older, more likely to be female, had more co-morbidities. CFS was significantly associated with poor functional outcome after adjustment for age, NIHSS and time to intervention (adjusted odds ratio [aOR] 1.54, 95% confidence interval [CI] 1.04-2.28, P = 0.032). There was trend towards higher mortality rate in frail patients (frail: 18.3%; non-frail: 9.6%; P = 0.080). There were no significant differences in other secondary outcomes except increased carer requirement post discharge in frail patients (frail: 91.6%; non-frail: 72.8%; P = 0.002). CONCLUSIONS: frailty was associated with poorer functional outcome at 90 days post-EVT in patients ≥ 70 years.

Association of triglyceride-glucose index with clinical outcomes in patients with acute ischemic stroke receiving intravenous thrombolysis.

Intravenous tissue plasminogen activator (tPA) remains the cornerstone of recanalization therapy for acute ischemic stroke (AIS), albeit with varying degrees of response. The triglyceride-glucose (TyG) index is a novel marker of insulin resistance, but association with outcomes among AIS patients who have received tPA has not been well elucidated. We studied 698 patients with AIS who received tPA from 2006 to 2018 in a comprehensive stroke centre. TyG index was calculated using the formula: ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. TyG index was significantly lower in patients that survived at 90-days than those who died (8.61 [Interquartile Range: 8.27-8.99] vs 8.76 [interquartile range: 8.39-9.40], p = 0.007). In multivariate analysis, TyG index was significantly associated with 90-day mortality (OR: 2.12, 95% CI: 1.39-3.23, p = 0.001), poor functional outcome (OR: 1.41 95% CI: 1.05-1.90, p = 0.022), and negatively associated with early neurological improvement (ENI) (OR: 0.68, 95% CI: 0.52-0.89, p = 0.004). There was no association between TyG index and symptomatic intracranial hemorrhage. 'High TyG' (defined by TyG index ≥ 9.15) was associated with mortality, poor functional outcomes and no ENI. In conclusion, the TyG index, a measure of insulin resistance, was significantly associated with poorer clinical outcomes in AIS patients who received tPA.

Bridging Thrombolysis versus Direct Mechanical Thrombectomy in Stroke Due to Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT. METHODS: This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0-3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH). RESULTS: Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not as Comorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013). CONCLUSIONS: Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.

Preprocedural Imaging : A Review of Different Radiological Factors Affecting the Outcome of Thrombectomy.

BACKGROUND: Endovascular treatment (EVT) has strong evidence for its effectiveness in treatment of acute ischemic stroke (AIS); however, up to half of the patients who undergo EVT still do not have good functional outcomes. Various prethrombectomy radiological factors have been shown to be associated with good clinical outcomes and may be the key to better functional outcomes, reduced complications, and reduced mortality. In this paper, we reviewed the current literature on these imaging parameters so they can be employed to better estimate the probability of procedural success, therefore allowing for more effective preprocedural planning of EVT strategies. We reviewed articles in the literature related to imaging factors which have been shown to be associated with EVT success. The factors which are reviewed in this paper included: anatomical factors such as 1) the type of aortic arch and its characteristics, 2) the characteristics of the thrombus such as length, clot burden, permeability, location, 3) the middle cerebral artery features including the tortuosity and underlying intracranial stenosis, 4) perfusion scans estimating the volume of infarct and the penumbra and 5) the effect of collaterals on the procedure. The prognostic effect of each factor on the successful outcome of EVT is described. The identification of preprocedural thrombectomy imaging factors can help to improve the chances of recanalization, functional outcomes, and mortality. It allows the interventionist to make time-sensitive decisions in the treatment of acute ischemic stroke.

Association of Global Cardiac Calcification with Atrial Fibrillation and Recurrent Stroke in Patients with Embolic Stroke of Undetermined Source.

BACKGROUND: Calcium deposits in the heart have been associated with cardiovascular events, mortality, stroke, and atrial fibrillation (AF). However, there is no accepted standard method for scoring cardiac calcifications. Existing methods have also not been validated for the assessment of patients with embolic stroke of undetermined source (ESUS). The aim of this study was to evaluate the association of various cardiac calcification scores with new-onset AF and stroke recurrence in a cohort of patients with ESUS. METHODS: In this study, 181 consecutive patients with stroke diagnosed with ESUS were identified and evaluated. They were followed for new-onset AF and ischemic stroke recurrence for a median duration of 2.1 years. Various echocardiographic cardiac calcification scores were assessed on transthoracic echocardiography performed during the evaluation of ESUS and subsequently assessed for their relation to AF detection and recurrent stroke. The echocardiographic calcium scores assessed were the (1) global cardiac calcium score (GCCS), (2) echocardiographic calcium score (eCS), (3) echocardiographic calcification score, (4) echocardiographic composite cardiac calcium score, and (5) total heart calcification score. Only two of these scoring schemes, GCCS and eCS, quantified the cardiac calcium burden. RESULTS: Higher calcium scores as measured by GCCS and eCS were found to be significantly associated with subsequent AF detection as well as recurrent ischemic stroke in patients with ESUS. The association with recurrent stroke remained significant even after adjustment for comorbidities and AF. CONCLUSIONS: Higher cardiac calcification measured using the GCCS and eCS is independently associated with AF detection and recurrent ischemic stroke in patients with ESUS, and these scores can be useful markers for further risk stratification in patients with ESUS.

Intra-Arterial Adjunctive Medications for Acute Ischemic Stroke During Mechanical Thrombectomy: A Meta-Analysis.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke with large vessel occlusion, the role of intra-arterial adjunctive medications (IAMs), such as urokinase, tPA (tissue-type plasminogen activator), or glycoprotein IIb/IIIa inhibitors, during mechanical thrombectomy (MT) has not been clearly established. We aim to evaluate the efficacy and safety of concomitant or rescue IAM for acute ischemic stroke with large vessel occlusion patients undergoing MT. METHODS: We searched Medline, Embase, and Cochrane Stroke Group Trials Register databases from inception until March 13, 2020. We analyzed all studies with patients diagnosed with acute ischemic stroke with large vessel occlusion in the anterior or posterior circulation that provided data for the two treatment arms, (1) MT+IAM and (2) MT only, and also reported on at least one of the following efficacy outcomes, recanalization and 90-day modified Rankin Scale, or safety outcomes, symptomatic intracranial hemorrhage and 90-day mortality. Data were collated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Sixteen nonrandomized observational studies with a total of 4581 patients were analyzed. MT only was performed in 3233 (70.6%) patients, while 1348 (29.4%) patients were treated with both MT and IAM. As compared with patients treated with MT alone, patients treated with combination therapy (MT+IAM) had a higher likelihood of achieving good functional outcome (risk ratio, 1.13 [95% CI, 1.03-1.24]) and a lower risk of 90-day mortality (risk ratio, 0.82 [95% CI, 0.72-0.94]). There was no significant difference in successful recanalization (risk ratio, 1.02 [95% CI, 0.99-1.06]) and symptomatic intracranial hemorrhage between the two groups (risk ratio, 1.13 [95% CI, 0.87-1.46]). CONCLUSIONS: In acute ischemic stroke with large vessel occlusion, the use of IAM together with MT may achieve better functional outcomes and lower mortality rates. Randomized controlled trials are warranted to establish the safety and efficacy of IAM as adjunctive treatment to MT.

Predicting Clinical Outcomes in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy with Machine Learning : A Systematic Review and Meta-analysis.

PURPOSE: Conventional predictive models are based on a combination of clinical and neuroimaging parameters using traditional statistical approaches. Emerging studies have shown that the machine learning (ML) prediction models with multiple pretreatment clinical variables have the potential to accurately prognosticate the outcomes in acute ischemic stroke (AIS) patients undergoing thrombectomy, and hence identify patients suitable for thrombectomy. This article summarizes the published studies on ML models in large vessel occlusion AIS patients undergoing thrombectomy. METHODS: We searched electronic databases including PubMed from 1 January 2000 up to 14 October 2019 for studies that evaluated ML algorithms for the prediction of outcomes in stroke patients undergoing thrombectomy. We then used random-effects bivariate meta-analysis models to summarize the studies. RESULTS: We retained a total of five studies that evaluated ML (4 support vector machine, 1 decision tree model) with a combined cohort of 802 patients. The prevalence of good functional outcome defined by 90-day mRS of 0-2 when available. Random effects model demonstrated that the AUC was 0.846 (95% confidence interval, CI 0.686-0.902). A pooled diagnostic odds ratio of 12.6 was computed. The pooled sensitivity and specificity were 0.795 (95% CI 0.651-0.889) and 0.780 (95% CI 0.634-0.879), respectively. CONCLUSION: ML may be useful as an adjunct to clinical assessment to predict functional outcomes in AIS patients undergoing thrombectomy, and hence identify suitable patients for treatment. Further studies validating ML models in large multicenter cohorts are necessary to explore this further.

Association of Electrocardiographic P-Wave Markers and Atrial Fibrillation in Embolic Stroke of Undetermined Source.

BACKGROUND: Several P-wave indices are thought to represent underlying atrial remodeling and have been associated with ischaemic stroke even in the absence of atrial fibrillation (AF). However, the utility of these P-wave indices in predicting outcomes in patients with embolic stroke of undetermined source (ESUS) has not been studied. The aim of this study is to examine these different P-wave indices towards predicting new-onset AF and stroke recurrence in a cohort of patients with ESUS, thereby demonstrating the value of these electrocardiographic markers for stroke risk stratification. METHODS: Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF and ischaemic stroke recurrence. The various P-wave indices, namely, the P-terminal force in the precordial lead V1 (PTFV1), P-wave duration, P-wave dispersion, interatrial blocks, and P-wave axis, were assessed on the initial electrocardiogram on presentation and studied for their relation to eventual AF detection and recurrent stroke. RESULTS: 181 ischaemic stroke patients with ESUS were recruited and followed up for a median duration of 2.1 years. An abnormal PTFV1 was associated with occult AF detection but not with recurrent ischaemic strokes. No significant association was observed between the other P-wave indices with either occult AF or stroke recurrence. CONCLUSION: PTFV1 is associated with AF detection but not recurrent strokes in ESUS patients and can be a useful electrocardiographic marker for further risk stratification in ESUS patients.

Characterization and Functional Assessment of Endothelial Progenitor Cells in Ischemic Stroke Patients.

Endothelial dysfunction has been implicated in atherosclerosis, ischemic heart disease, and stroke. Endothelial progenitor cells (EPCs), found in the bone marrow and peripheral blood as rare cell population, demonstrated a high proliferation and differentiation capacity. Understanding how such diseases influence the quantity and functionality of EPCs is essential for the development of novel therapies. This study aims to investigate the factors that affect the quantity and functionality of circulating EPCs in stroke patients and healthy controls. Blood samples were collected once from healthy donors (n = 30) and up to 3 times (within 7 days (baseline), 3 and 12 months post-stroke) from stroke patients (n = 207). EPC subpopulations were isolated with flow cytometry for characterization. The Matrigel tubular formation assay was performed as a measure of functionality. An increased amount of circulating EPCs was observed in stroke patients over 45 years when compared to age-matched healthy individuals. EPCs showed a rising trend in stroke patients over the 12-month post-stroke period, reaching statistical significance at 12 months post-stroke. Isolated CD34+KDR+ cells from stroke patients showed impairment in tubular formation capability when compared to cells from healthy donors. The quantity and vasculogenic function of circulating EPCs in peripheral blood have been effectively evaluated in stroke patients and healthy control donors in this study. Age and stroke are found to be 2 influencing factors on the angiogenic capacity. It is suggested that the increase in EPC number is triggered by the recovery response following ischemic stroke. Graphical abstract.

COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature.

Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain. We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients. A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020. All studies reporting AIS occurrence in COVID-19 patients were included. A total of 39 studies comprising 135 patients were studied. The pooled incidence of AIS in COVID-19 patients from observational studies was 1.2% (54/4466) with a mean age of 63.4 ± 13.1 years. The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8. Laboratory investigations revealed an elevated mean D-dimer (9.2 ± 14.8 mg/L) and fibrinogen (5.8 ± 2.0 g/L). Antiphospholipid antibodies were detected in a significant number of cases. The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62.1%, 64/103), followed by multiple vascular territory (26.2%, 27/103). A high mortality rate was reported (38.0%, 49/129). We report the pooled incidence of AIS in COVID-19 patients to be 1.2%, with a high mortality rate. Elevated D-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis.

Impact of the COVID-19 pandemic on hyperacute stroke treatment: experience from a comprehensive stroke centre in Singapore.

The Coronavirus disease 2019 (COVID-19) pandemic is rapidly evolving and affecting healthcare systems across the world. Singapore has escalated its alert level to Disease Outbreak Response System Condition (DORSCON) Orange, signifying severe disease with community spread. We aimed to study the overall volume of AIS cases and the delivery of hyperacute stroke services during DORSCON Orange. This was a single-centre, observational cohort study performed at a comprehensive stroke centre responsible for AIS cases in the western region of Singapore, as well as providing care for COVID-19 patients. All AIS patients reviewed as an acute stroke activation in the Emergency Department (ED) from November 2019 to April 2020 were included. System processes timings, treatment and clinical outcome variables were collected. We studied 350 AIS activation patients admitted through the ED, 206 (58.9%) pre- and 144 during DORSCON Orange. Across the study period, number of stroke activations showed significant decline (p = 0.004, 95% CI 6.513 to - 2.287), as the number of COVID-19 cases increased exponentially, whilst proportion of activations receiving acute recanalization therapy remained stable (p = 0.519, 95% CI - 1.605 to 2.702). Amongst AIS patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 h (-4 versus -4, p = 0.685) were largely similar between the pre- and during DORSCON orange periods. The number of stroke activations decreased while the proportion receiving acute recanalization therapy remained stable in the current COVID-19 pandemic in Singapore.