Incidence of white matter lesions in hospitalized COVID-19 patients: A meta-analysis.

OBJECTIVE: Novel coronavirus disease 2019 (COVID-19) has been found to be associated with encephalopathy and brain imaging abnormalities. The identification of incident white matter lesions, known to be associated with cerebral microcirculatory failure and cerebrovascular disease, in COVID-19 patients is of clinical and scientific interest. We performed a meta-analysis to investigate the incidence of white matter lesions (WMLs) in hospitalized COVID-19 patients. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for studies on brain imaging abnormalities in hospitalized COVID-19 patients. The terms used included "white matter lesions," "white matter hyperintensity," "COVID-19," "coronavirus," and "SARS-CoV-2." A random-effects meta-analysis was conducted to obtain a pooled estimate of WML prevalence in hospitalized COVID-19 patients. RESULTS: A total of 4 eligible studies involving 362 patients (144 with WMLs and 218 without) were included in the meta-analysis. We found the pooled estimate of WML prevalence to be 20% (ES 0.20; 95% CI 0.00-0.54; p = .03). CONCLUSIONS: The estimated pooled prevalence rate of WMLs was approximately 20% in hospitalized COVID-19 patients, albeit lower than the crude prevalence rate (39.8%).

Leukoaraiosis severity and post-reperfusion outcomes in acute ischaemic stroke: A meta-analysis.

OBJECTIVES: Severity of leukoaraiosis may mediate outcomes after reperfusion therapy in acute ischaemic stroke (AIS) patients. However, the level of the association remains poorly understood. We performed a meta-analysis to investigate the impact of leukoaraiosis severity on functional outcome, survival, haemorrhagic complications, and procedural success in AIS patients treated with intravenous thrombolysis and/or endovascular thrombectomy. MATERIALS AND METHODS: PubMed, EMBASE and the Cochrane library were searched for studies on leukoaraiosis in AIS receiving reperfusion therapy. A random-effects meta-analysis was conducted for post-reperfusion outcomes in AIS patients with absent-to-mild leukoaraiosis and moderate-to-severe leukoaraiosis. The strength of association between moderate-to-severe leukoaraiosis and poor outcomes was quantified using odds ratios (OR). RESULTS: A total of 15 eligible studies involving 6460 patients (1451 with moderate-to-severe leukoaraiosis and 5009 with absent-to-mild leukoaraiosis) were included in the meta-analysis. Moderate-to-severe leukoaraiosis was significantly associated with poor 90-day functional outcome (OR 3.16; 95% confidence interval (CI) 2.69-3.72; p < .0001), 90-day mortality (OR 3.11; 95% CI 2.27-4.26; p < .0001) and increased risk of symptomatic intracerebral haemorrhage (OR 1.69; 95% CI 1.24-2.32; p = .001) after reperfusion therapy. Overall, no significant association of leukoaraiosis severity with haemorrhagic transformation (HT) and angiographic recanalization status were observed. However, subgroup analysis revealed a significant association of WML severity with HT in patients receiving EVT. CONCLUSION: Leukoaraiosis is a useful prognostic biomarker in AIS. Patients with moderate-to-severe leukoaraiosis on baseline imaging are likely to have worse clinical and safety outcomes after reperfusion therapy.

Value of pre-intervention computed tomography perfusion imaging in the assessment of tissue outcome and long-term clinical prognosis in patients with anterior circulation acute ischemic stroke receiving reperfusion therapy: a systematic review.

BACKGROUND: Computed tomography perfusion (CTP) imaging has emerged as an important adjunct to the current armamentarium of acute ischemic stroke (AIS) workflow. However, its adoption in routine clinical practice is far from optimal. PURPOSE: To investigate the putative association of CTP imaging biomarkers in the assessment of prognosis in acute ischemic stroke. MATERIAL AND METHODS: We performed a systematic review of the literature using MEDLINE, EMBASE, and Cochrane Central Register of Clinical Trials focusing on CTP biomarkers, tissue-based and clinical-based patient outcomes. We included randomized controlled trials, prospective cohort studies, and case-controlled studies published from January 2005 to 28 August 2020. Two independent reviewers conducted the study appraisal, data extraction, and quality assessment of the studies. RESULTS: A total of 60 full-text studies were included in the final systematic review analysis. Increasing infarct core volume is associated with reduced odds of achieving functional independence (modified Rankin score 0-2) at 90 days and is correlated with the final infarct volume when reperfusion is achieved. CONCLUSION: CTP has value in assessing tissue perfusion status in the hyperacute stroke setting and the long-term clinical prognosis of patients with AIS receiving reperfusion therapy. However, the prognostic use of CTP requires optimization and further validation.

Emerging role of white matter lesions in cerebrovascular disease.

White matter lesions have been implicated in the setting of stroke, dementia, intracerebral haemorrhage, several other cerebrovascular conditions, migraine, various neuroimmunological diseases like multiple sclerosis, disorders of metabolism, mitochondrial diseases and others. While much is understood vis a vis neuroimmunological conditions, our knowledge of the pathophysiology of these lesions, and their role in, and implications to, management of cerebrovascular diseases or stroke, especially in the elderly, are limited. Several clinical assessment tools are available for delineating white matter lesions in clinical practice. However, their incorporation into clinical decision-making and specifically prognosis and management of patients is suboptimal for use in standards of care. This article sought to provide an overview of the current knowledge and recent advances on pathophysiology, as well as clinical and radiological assessment, of white matter lesions with a focus on its development, progression and clinical implications in cerebrovascular diseases. Key indications for clinical practice and recommendations on future areas of research are also discussed. Finally, a conceptual proposal on putative mechanisms underlying pathogenesis of white matter lesions in cerebrovascular disease has been presented. Understanding of pathophysiology of white matter lesions and how they mediate outcomes is important to develop therapeutic strategies.

Diagnostic and prognostic utility of computed tomography perfusion imaging in posterior circulation acute ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: Computed tomography perfusion (CTP) imaging could be useful in the diagnosis of posterior circulation stroke (PCS) and in identifying patients who are likely to experience favorable outcomes following reperfusion therapy. The current study sought to investigate the diagnostic and prognostic capability of CTP in acute ischemic PCS by performing a systematic review and meta-analysis. METHODS: Medline/PubMed and the Cochrane Library were searched using the terms: "posterior circulation", "CT perfusion", "acute stroke", and "reperfusion therapy". The following studies were included: (1) patients aged 18 years or above; (2) patients diagnosed with PCS; and (3) studies with good methodological design. Pooled sensitivity (SENS), specificity (SPEC), and area under the curve (AUC), computed using the summary receiver operating characteristic (SROC) curves, were used to determine diagnostic/prognostic capability. RESULTS: Out of 14 studies included, a meta-analysis investigating diagnostic accuracy of CTP was performed on nine studies. Meta-analysis demonstrated comparable diagnostic accuracy of CTP to non-contrast computed tomography (NCCT) (AUCCTP : 0.90 [95% CI 0.87-0.92] vs. AUCNCCT : 0.96 [95% CI 0.94-0.97]); however, with higher pooled sensitivity (SENSCTP : 72% [95% CI 57%-83%] vs. SENSNCCT : 25% [95% CI 17%-35%]) and lower specificity (SPECCTP : 90% [95% CI 83%-94%] vs. SPECNCCT : 96% [95% CI 95%-98%]) than NCCT. Meta-analysis to determine prognostic capability of CTP could not be performed. CONCLUSIONS: CTP has limited diagnostic utility in acute ischemic PCS, albeit with superior diagnostic sensitivity and inferior diagnostic specificity to NCCT. Further prospective trials are required to validate the prognostic capability of CTP-derived parameters in PCS.

In-hospital systems interventions in acute stroke reperfusion therapy: a meta-analysis.

OBJECTIVES: The value of in-hospital systems-based interventions in streamlining treatment delays associated with reperfusion therapy delivery in acute ischaemic stroke (AIS), in the emergency department (ED), is poorly understood. This systematic review and meta-analysis aimed to assess and quantify the value of in-hospital systems-based interventions in streamlining reperfusion therapy delivery following AIS. MATERIAL & METHODS: Articles from the following databases were retrieved: Medline, Embase and Cochrane Central Register of Controlled Trials. The primary endpoint was in-hospital time metrics between the intervention and control group. The secondary endpoint included the rate of good functional outcome at 90 days. RESULTS: 393 Systems intervention studies published after 2015 were screened, and 231 full articles were then read. In total, 35 studies with 35,815 patients were included in the final systematic review and 26 studies with 7,089 patients were used in the meta-analysis. The greatest time reductions from in-hospital system interventions were achieved in door-to-needle (DTN) time (SMD: -2.696, 95% CI: -2.976, -2.416, z = 3.03, p = 0.002). Systems interventions were also associated with a statistically significant improvement in mortality (RR: 0.25, 95% CI: 0.18, 0.38), rate of symptomatic intracerebral haemorrhage (RR: 0.07, 95% CI: 0.04, 0.1) and ≤60-minute reperfusion rates (RR: 0.63, 95% CI: 0.51, 0.79). CONCLUSIONS: The use of in-hospital workflow optimization is imperative to expedite reperfusion therapy delivery and improving patient outcomes. To reduce the morbidity and mortality of stroke globally, in-hospital workflow guidelines should be adhered to and incorporated including the optimal elements identified in this study.

Neutrophil-lymphocyte ratio in acute ischemic stroke: Immunopathology, management, and prognosis.

There is an ongoing need for accurate prognostic biomarkers in the milieu of acute ischemic stroke (AIS) receiving reperfusion therapy. Neutrophil-lymphocyte ratio (NLR) has been implicated in emergency medicine and acute stroke setting as an important biomarker in the prognosis of patients. However, there are ongoing questions around its accuracy and translation into clinical practice given suboptimal sensitivity and specificity results, as well as varying thresholds and lack of clarity around which NLR time points are most clinically indicative. This article provides a comprehensive overview of the role of NLR in AIS patients receiving reperfusion therapy and perspectives on areas of future research. NLR may be an important biomarker in risk stratifying patients in AIS to identify and select those who are more likely to benefit from reperfusion therapy. Appropriate clinical decision-making tools and models are required to harness the predictive value of NLR, which could be useful in identifying and monitoring high-risk patients to guide early treatment and achieve improved outcomes. Our understanding of the role of NLR in the immunopathogenesis of AIS is also suboptimal, which hinders the ability to translate this into clinical practice.

Impact of diabetes on clinical and safety outcomes in acute ischemic stroke patients receiving reperfusion therapy: A meta-analysis.

BACKGROUND: Patients with diabetes are known to have worse outcomes after an acute ischemic stroke (AIS) relative to those without diabetes. However, the impact of diabetes on the outcomes after the reperfusion therapy is poorly understood. OBJECTIVES: This study investigated prognostic accuracy of diabetes and its association with clinical and safety outcomes in AIS patients receiving intravenous thrombolysis (IVT), endovascular thrombectomy (EVT), or both. MATERIAL AND METHODS: Studies were identified from PubMed, Embase and Cochrane databases, using the following inclusion criteria: (a) AIS patients receiving reperfusion therapy, (b) age ≥ 18 years, (c) hemispheric stroke, and (d) the availability of comparative data between diabetic and nondiabetic groups and relevant poststroke outcomes. Random effects modelling was used to study the association of diabetes with functional outcome at discharge and at 90 days, mortality at 90 days, recanalization status, and postreperfusion safety outcomes, including rates of symptomatic intracerebral hemorrhage (sICH) and hemorrhagic transformation (HT). Forest plots of odds ratios (ORs) were generated. RESULTS: Of a total cohort of 82,764 patients who received reperfusion therapy, 16,877 had diabetes. Diabetes significantly increased the odds of poor functional outcome at discharge (OR 1.310; 95% confidence interval (95% CI): [1.091; 1.574]; p = 0.0037) and at 90 days (OR 1.487; 95% CI: [1.335; 1.656]; p < 0.00010), mortality at 90 days (OR 1.709; 95% CI: [1.633; 1.788]; p < 0.0001), sICH (OR 1.595; 95% CI: [1.301; 1.956]; p < 0.0001), and HT (OR 1.276; 95% CI: [1.055; 1.543]; p = 0.0118). CONCLUSION: Our meta-analysis demonstrates that diabetes is significantly associated with poor functional outcome, increased mortality and poor postprocedural safety outcomes, including sICH and HT.

Prognostic capacity of hyperdense middle cerebral artery sign in anterior circulation acute ischaemic stroke patients receiving reperfusion therapy: a systematic review and meta-analysis.

Pre-intervention CT imaging-based biomarkers, such as hyperdense middle cerebral artery sign (HMCAS) may have a role in acute ischaemic stroke prognostication. However, the clinical utility of HMCAS in settings of reperfusion therapy and the level of prognostic association is still unclear. This systematic review and meta-analysis investigated the association of HMCAS sign with clinical outcomes and its prognostic capacity in acute ischaemic stroke patients treated with reperfusion therapy. Prospective and retrospective studies from the following databases were retrieved from EMBASE, MEDLINE and Cochrane. Association of HMCAS with functional outcome, symptomatic intracerebral haemorrhage (sICH) and mortality were investigated. The random effect model was used to calculate the risk ratio (RR). Subgroup analyses were performed for subgroups of patients receiving thrombolysis (tPA), mechanical thrombectomy (EVT) and/or combined therapy (tPA + EVT). HMCAS significantly increased the rate of poor functional outcome by 1.43-fold in patients (RR 1.43; 95% CI 1.30-1.57; p < 0.0001) without any significant differences in sICH rates (RR 0.91; 95% CI 0.68-1.23; p = 0.546) and mortality (RR 1.34; 95% CI 0.72-2.51; p = 354) in patients with positive HMCAS as compared to negative HMCAS. In subgroup analyses, significant association between HMCAS and 90 days functional outcome was observed in patients receiving tPA (RR 1.53; 95% CI 1.40-1.67; p < 0.0001) or both therapies (RR 1.40; 95% CI 1.08-1.80; p = 0.010). This meta-analysis demonstrated that pre-treatment HMCAS increases risk of poor functional outcomes. However, its prognostic sensitivity and specificity in predicting long-term functional outcome, mortality and sICH after reperfusion therapy is poor.

COVID-19 and the cardiovascular system-current knowledge and future perspectives.

The current coronavirus disease 2019 (COVID-19) pandemic has had devastating impact on populations around the world. The high mortality rates in patients with COVID-19 has been attributed to the influence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), its causative viral agent, on several physiological systems in human body, including the respiratory, cardiovascular, and neurological systems. There is emerging evidence on propensity of this virus to attack cardiovascular system. However, various pathophysiological mechanisms by which SARS-CoV-2 interacts with cardiovascular system and leads to high morbidity and mortality, including cardiovascular complications, are poorly understood. This mini review aims to provide an update on the current knowledge and perspectives on areas of future research.

Digital subtraction angiography in cerebrovascular disease: current practice and perspectives on diagnosis, acute treatment and prognosis.

Digital Subtraction Angiography (DSA) is the gold-standard imaging modality in acute cerebrovascular diagnosis. The role of DSA has become increasingly prominent since the incorporation of endovascular therapy in standards of care for acute ischemic stroke. It is used in the assessment of cerebral vessel patency; however, the therapeutic role of DSA from a prognostic standpoint merits further investigation. The current paper provides an update on current practice on diagnostic, therapeutic and prognostic use of DSA in acute cerebrovascular diseases and various indications and perspectives that may apply, or limit its use, in ongoing surveillance or prognosis. Pre-clinical and clinical studies on the aspects, including but not limited to the morphology of cerebrovasculature in acute ischaemic stroke, are required to delineate and inform its prognostic role.

The association of transradial access and transfemoral access with procedural outcomes in acute ischemic stroke patients receiving endovascular thrombectomy: A meta-analysis.

OBJECTIVE: There is an ongoing debate regarding the benefits of using transradial access (TRA) over transfemoral access (TFA) in endovascular therapies including endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) patients. This study sought to investigate the association of TRA and TFA with procedural success, access-site complications, first-pass reperfusion (FPR), puncture-to-recanalisation (PTR) time and hemorrhagic transformation (HT) by performing a meta-analysis. MATERIALS AND METHODS: PubMed, EMBASE and Scopus were searched. Studies with patients aged ≥ 18 years and head-to-head TRA vs TFA comparisons were included. Random-effects modeling was performed to obtain summary effects and forest plots were plotted to study the association of TFA with access site complications, FPR, HT, PTR time and procedural success. RESULTS: Six studies encompassing 945 patients (347 TRA and 598 TFA) were included in the meta-analysis. Meta-analysis revealed that in AIS patients receiving EVT, TRA was significantly associated with a decreased risk of access-site complications (RR 0.17, 95% CI 0.05 0.54; p = 0.003, z = -2.957) and HT (RR 0.07, 95% CI 0.02 0.27; p < 0.0001, z = -3.8841). However, TRA was not significantly associated with procedural success (RR 0.96, 95% CI 0.90 1.01; p = 0.141, z = -1.473), FPR (RR 0.91, 95% CI 0.79 1.05; p = 0.194, z = -1.299) and PTR time (SMD -0.14, 95% CI -0.42 -0.14; p = 0.323, z = -0.989). CONCLUSION: Our meta-analysis demonstrated that TRA is a safe alternative to TFA, in AIS patients receiving EVT, with significantly decreased access-site complications and HT with TRA, albeit with comparable procedural success, FPR and PTR time to TFA. DATA AVAILABILITY STATEMENT: The original contributions presented in the study are included in the article/Supplementary information, further inquiries can be directed to the corresponding author.

Value of pre-intervention CT perfusion imaging in acute ischemic stroke prognosis.

Noninvasive imaging plays an important role in acute stroke towards diagnosis and ongoing management of patients. Systemic thrombolysis and endovascular thrombectomy (EVT) are proven treatments currently used in standards of care in acute stroke settings. The role of computed tomography angiography (CTA) in selecting patients with large vessel occlusion for EVT is well established. However, the value of CT perfusion (CTP) imaging in predicting outcomes after stroke remains ambiguous. This article critically evaluates the value of multimodal CT imaging in early diagnosis and prognosis of acute ischemic stroke with a focus on the role of CTP in delineating tissue characteristics, patient selection, and outcomes after reperfusion therapy. Insights on various technical and clinical considerations relevant to CTP applications in acute ischemic stroke, recommendations for existing workflow, and future areas of research are discussed.