Characteristics of subarachnoid hemorrhage associated with COVID-19 infection: A systematic review and descriptive analysis.

OBJECTIVE: Subarachnoid hemorrhage (SAH) has been reported as a neurological manifestation in 0.1% of COVID-19 patients. This systematic review investigated the outcomes and predictive factors of SAH in patients with COVID-19. MATERIALS AND METHODS: An electronic literature search was conducted on PubMed, Embase, and Scopus from inception to 10th September 2021. Studies reporting SAH in COVID-19 patients were included. Demographic characteristics, risk factors for disease, severity of COVID-19, and mortality of SAH in COVID-19 patients were analyzed. Subgroup analyses stratified by COVID-19 severity and mortality were conducted. RESULTS: 17 case reports, 11 case series, and 2 retrospective cohort studies, with a total of 345 cases of SAH in COVID-19 patients, were included for analysis. Most published cases were reported in the US. Mean age was 55±18.4 years, and 162 patients (48.5%) were female. 242 patients (73.8%) had severe-to-critical COVID-19, 56.7% had aneurysmal SAH, 71.4% were on anticoagulation, and 10.8% underwent surgical treatment. 136 out of 333 patients (40.8%) died. Among patients with severe-to-critical COVID-19, 11 out of 18 (61.1%) died, and 8 out of 8 (100.0%) were non-aneurysmal SAH. CONCLUSIONS: SAH is a rare but morbid occurrence in COVID-19. The mortality rate of COVID-SAH patients was 40.8%, with a higher prevalence of severe-to-critical COVID-19 (100% versus 53.8%) and non-aneurysmal SAH (85.7% versus 44.6%) among COVID-SAH deaths. Given the changing landscape of COVID-19 variants, further studies investigating the association between COVID-19 and SAH may be warranted to identify the long-term effects of COVID-19.

Intravenous thrombolysis and endovascular thrombectomy for acute ischaemic stroke in patients with Moyamoya disease - a systematic review and meta-summary of case reports.

BACKGROUND AND AIMS: Patients with Moyamoya disease (MMD) can present with ischaemic or haemorrhagic stroke. There is no good evidence for treatment strategies in MMD-associated acute ischaemic stroke (AIS), particularly for treatments like intravenous thrombolysis (IVT) and endovascular thrombectomy (ET). As the intracranial vessels are friable in MMD, and the risk of bleeding is high, the use of IVT and ET is controversial. To clarify the safety and efficacy of IVT/ET in the treatment of MMD-associated AIS, we performed a systematic review and meta-summary to examine this issue. METHODS: A systematic search was performed from four electronic databases: PubMed (MEDLINE), Cochrane Library, EMBASE and Scopus, profiling data from inception till 21 November 2021, as well as, manually on Google Scholar. RESULTS: Ten case reports detailing 10 MMD patients presenting with AIS and undergoing IVT or ET, or both, were included in the analysis. The median National Institute of Health Stroke Scale score at presentation was 10 (Interquartile Range [IQR] = 6.0-16.5). IVT alone was instituted in 6 patients, primary ET was attempted in 2, and 2 had received bridging IVT with ET. Of the 4 patients who underwent ET, 2 patients achieved successful reperfusion (modified Thrombolysis In Cerebral Infarction scale [mTICI] ≥ 2b). In terms of functional outcomes, One patient achieved complete recovery (modified Rankin Scale 0), 4 patients attained improvement in neurological status, and 4 had no improvement, whilst functional outcome was unreported in 1 patient. No patient experienced symptomatic intracranial haemorrhage. CONCLUSIONS: In this systematic review and meta-summary, the utility of IVT and ET in MMD-associated AIS appears feasible in selected cases. Further larger cohort studies are required to evaluate these treatment approaches. HIGHLIGHTS: · AIS in MMD was typically managed with bypass surgery but not via thrombolysis or thrombectomy. · In this meta-summary, all patients treated with thrombolysis and/or thrombectomy survived and some experienced symptomatic and/or functional improvement. · Further larger cohort studies are necessary for investigating the role of thrombolysis and/or thrombectomy as treatment of AIS in MMD.

Effects of Sodium/Glucose Cotransporter Inhibitors on Atrial Fibrillation and Stroke: A Meta-Analysis.

OBJECTIVES: Recent clinical trials have shown the potential of sodium glucose cotransporter (SGLT) 2 inhibitors to reduce the risk of atrial fibrillation but not stroke. We conducted a systematic review and meta-analysis to clarify if SGLT2 or combined SGLT1/2 inhibitors affect the risk of atrial fibrillation and stroke in patients regardless of diabetic status. MATERIALS AND METHODS: Four electronic databases were searched on 21st November 2020 for studies evaluating outcomes of stroke and atrial fibrillation with SGLT2 or combined SGLT1/2 inhibitors in both diabetic and non-diabetic patients. Both random and fixed effect, pair-wise meta-analysis models were used to summarize the results of the studies. RESULTS: A total of 13 placebo-controlled, randomized-controlled trials were included. Eight trials comprising 35,702 patients were included in the analysis of atrial fibrillation outcomes and eight trials comprising 47,910 patients were included in the analysis of stroke outcomes. Patients on SGLT inhibitors, particularly SGLT2 inhibitors, had lower odds of atrial fibrillation (Peto odds ratio [95% confidence interval] = 0.76 [0.63-0.92]) compared to placebo. This effect remained significant with a follow-up duration longer than 1 year, in studies utilizing dapagliflozin, patients with type 2 diabetes mellitus, and patients with cardiovascular disease. No difference was observed in the odds of atrial fibrillation in patients with baseline heart failure. No effect was seen on the risk of stroke in patients taking SGLT inhibitors. CONCLUSIONS: SGLT2 inhibitors significantly reduced the odds of atrial fibrillation in diabetic patients. However, SGLT inhibitors did not significantly affect the risk of stroke.

Thrombectomy in Extensive Stroke May Not Be Beneficial and Is Associated With Increased Risk for Hemorrhage.

Background and Purpose: This study evaluates the benefit of endovascular treatment (EVT) for patients with extensive baseline stroke compared with best medical treatment. Methods: This retrospective, multicenter study compares EVT and best medical treatment for computed tomography (CT)­based selection of patients with extensive baseline infarcts (Alberta Stroke Program Early CT Score ≤5) attributed to anterior circulation stroke. Patients were selected from the German Stroke Registry and 3 tertiary stroke centers. Primary functional end points were rates of good (modified Rankin Scale score of ≤3) and very poor outcome (modified Rankin Scale score of ≥5) at 90 days. Secondary safety end point was the occurrence of symptomatic intracerebral hemorrhage. Angiographic outcome was evaluated with the modified Thrombolysis in Cerebral Infarction Scale. Results: After 1:1 pair matching, a total of 248 patients were compared by treatment arm. Good functional outcome was observed in 27.4% in the EVT group, and in 25% in the best medical treatment group (P=0.665). Advanced age (adjusted odds ratio, 1.08 [95% CI, 1.05­1.10], P<0.001) and symptomatic intracerebral hemorrhage (adjusted odds ratio, 6.35 [95% CI, 2.08­19.35], P<0.001) were independently associated with very poor outcome. Mortality (43.5% versus 28.9%, P=0.025) and symptomatic intracerebral hemorrhage (16.1% versus 5.6%, P=0.008) were significantly higher in the EVT group. The lowest rates of good functional outcome (≈15%) were observed in groups of failed and partial recanalization (modified Thrombolysis in Cerebral Infarction Scale score of 0/1­2a), whereas patients with complete recanalization (modified Thrombolysis in Cerebral Infarction Scale score of 3) with recanalization attempts ≤2 benefitted the most (modified Rankin Scale score of ≤3:42.3%, P=0.074) compared with best medical treatment. Conclusions: In daily clinical practice, EVT for CT­based selected patients with low Alberta Stroke Program Early CT Score anterior circulation stroke may not be beneficial and is associated with increased risk for hemorrhage and mortality, especially in the elderly. However, first- or second-pass complete recanalization seems to reveal a clinical benefit of EVT highlighting the vulnerability of the low Alberta Stroke Program Early CT Score subgroup. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.

Outcomes in young adults with acute ischemic stroke undergoing endovascular thrombectomy: A real-world multicenter experience.

Endovascular thrombectomy (EVT) is the standard of care for anterior circulation acute ischemic stroke (AIS) with large vessel occlusion (LVO). Young patients with AIS-LVO have distinctly different underlying stroke mechanisms and etiologies. Much is unknown about the safety and efficacy of EVT in this population of young AIS-LVO patients. All consecutive AIS-LVO patients aged 50 years and below were included in this multicenter cohort study. The primary outcome measured was functional recovery at 90 days, with modified Rankin Scale of 0-2 deemed as good functional outcome. A total of 275 AIS-LVO patients that underwent EVT from 10 tertiary centers in Germany, Sweden, Singapore, and Taiwan were included. Successful reperfusion was achieved in 85.1% (234/275). Good functional outcomes were achieved in 66.0% (182/275). Arterial dissection was the most prevalent stroke etiology (42/195, 21.5%). National Institutes of Health Stroke Scale (NIHSS) score at presentation was inversely related to good functional outcomes (aOR: 0.92, 95% CI: 0.88-0.96 per point increase, p < 0.001). Successful reperfusion (aOR: 3.22, 95% CI: 1.44-7.21, p = 0.005), higher ASPECTS (aOR: 1.21, 95% CI: 1.01-1.44, p = 0.036), and bridging intravenous thrombolysis (aOR: 2.37, 95% CI: 1.29-4.34, p = 0.005) independently predicted good functional outcomes. Successful reperfusion was inversely associated with in-hospital mortality (aOR: 0.14, 95% CI: 0.03-0.57, p = 0.006). History of hypertension strongly predicted in-hospital mortality (aOR: 4.59, 95% CI: 1.10-19.13, p = 0.036). While differences in functional outcomes exist across varying stroke aetiologies, high rates of successful reperfusion and good outcomes are generally achieved in young AIS-LVO patients undergoing EVT.

Predicting mortality, thrombus recurrence and persistence in patients with post-acute myocardial infarction left ventricular thrombus.

Left ventricular thrombus (LVT) is a common complication of acute myocardial infarction and is associated with morbidity from embolic complications. Predicting which patients will develop death or persistent LVT despite anticoagulation may help clinicians identify high-risk patients. We developed a random forest (RF) model that predicts death or persistent LVT and evaluated its performance. This was a single-center retrospective cohort study in an academic tertiary center. We included 244 patients with LVT in our study. Patients who did not receive anticoagulation (n = 8) or had unknown (n = 31) outcomes were excluded. The primary outcome was a composite outcome of death, recurrent LVT and persistent LVT. We selected a total of 31 predictors collected at the point of LVT diagnosis based on clinical relevance. We compared conventional regularized logistic regression with the RF algorithm. There were 156 patients who had resolution of LVT and 88 patients who experienced the composite outcome. The RF model achieved better performance and had an AUROC of 0.700 (95% CI 0.553-0.863) on a validation dataset. The most important predictors for the composite outcome were receiving a revascularization procedure, lower visual ejection fraction (EF), higher creatinine, global wall motion abnormality, higher prothrombin time, higher body mass index, higher activated partial thromboplastin time, older age, lower lymphocyte count and higher neutrophil count. The RF model accurately identified patients with post-AMI LVT who developed the composite outcome. Further studies are needed to validate its use in clinical practice.

An unusual presentation of Idiopathic hypereosinophilic syndrome.

Hypereosinophilic syndrome (HES) is a rare but life-threatening multi-organ disease which can be complicated by stroke, with devastating outcomes. Eosinophils can accumulate in multiple organs, most commonly involving the heart, skin, lungs, spleen, and liver. Neurological end-organ complications in hypereosinophilic syndrome are unusual and have been established to be of three types: brain infarction, encephalopathy and sensory polyneuropathy. We present a case where acute ischaemic stroke and encephalopathy are early manifestations of Idiopathic HES. It is important to consider HES as an aetiology for stroke and a high eosinophil count is an initial diagnostic clue. Early initiation of steroid therapy can potentially prevent disease progression.

Characterisation of acute ischemic stroke in patients with left ventricular thrombi after myocardial infarction.

Acute ischemic stroke (AIS) is a feared complication in post-acute myocardial infarction (AMI) patients who develop left ventricular (LV) thrombus. There is limited data available on the incidence of stroke in this population, and characterisation of stroke subtypes has not been previously reported. Our study aims to evaluate the incidence of AIS in post-AMI patients with LV thrombus and to characterise the pattern of stroke subtypes. We screened 5829 patients with echocardiogram reports containing the "thrombus" keyword from August 2006 to September 2017. AIS that occurred after LV thrombosis was captured and relevant clinical data was collected. We identified 289 post-AMI patients with acute LV thrombus formation. Mean age was 59.3 ± 13.4 years. AIS occurred in 34 patients (11.8%), median duration of 20.5 days (IQR = 5.5-671.8) after LV thrombosis. Despite initial thrombus resolution, nine (5.2%) encountered AIS subsequently. Cardioembolic stroke subtype was identified in 76.5% of AIS, whilst 14.7% was small vessel disease and 8.8% was of large artery atherosclerosis subtype. Presence of thrombus protrusion (HR 3.04, 95% CI 1.25-7.41, p = 0.01), failure of initial thrombus resolution (HR 3.03, 95% CI 1.23-7.45, p = 0.02) and thrombus recurrence (HR 4.20, 95% CI 1.46-12.11, p < 0.01) were significant independent predictors for stroke. Incidence of AIS in this Asian population of post-AMI patients with LV thrombus was 11.8%. Duration of anticoagulation may need to be individualised for patients with higher risk for stroke occurrence after LV thrombosis.

Order of Treatment Matters in Ischemic Stroke: Mechanical Thrombectomy First, Then Carotid Artery Stenting for Tandem Lesions of the Anterior Circulation.

BACKGROUND: One endovascular treatment option of acute ischemic stroke due to tandem occlusion (TO) comprises intracranial thrombectomy and acute extracranial carotid artery stenting (CAS). In this setting, the order of treatment may impact the clinical outcome in this stroke subtype. METHODS: Retrospective analysis was performed on data prospectively collected in 4 international stroke centers between 2013 and 2017. One hundred sixty-five patients with anterior TO were treated by endovascular therapy. Clinical and procedural data were evaluated. Favorable clinical outcome was defined as modified Rankin Scale (mRS) ≤2 at 90 days. Propensity score matching was performed for different treatment strategies. RESULTS: Patients' mean age was 65 ± 11 years and 118 were male (69%). The median admission National Institutes of Health Stroke Scale was 15 (interquartile range 8). In 59% of the patients (n = 101), the antegrade strategy (first stenting, then thrombectomy) was -performed, in 41% (n = 70) retrograde treatment (first thrombectomy, then stenting). Successful reperfusion (mTICI ≥2b) was achieved in 128 patients (75%). Fifty-nine patients (39%) showed a favorable clinical outcome after 90 days. After propensity score matching, data of 100 patients could be analyzed. Analysis revealed that the retrograde strategy yielded a significantly higher rate of successful reperfusion compared to the antegrade strategy (92 vs. 56%; p < 0.001). The rate of favorable clinical outcome after 90 days (mRS ≤2) was consistently higher (44 vs. 30%; p < 0.05) in the retrograde strategy group. CONCLUSION: Mechanical thrombectomy prior to acute CAS in TO is a predictive factor for favorable clinical outcome at 90 days.

Carotid Artery Stenosis Contralateral to Acute Tandem Occlusion: An Independent Predictor of Poor Clinical Outcome after Mechanical Thrombectomy with Concomitant Carotid Artery Stenting.

BACKGROUND AND PURPOSE: Cerebral ischemic strokes due to extra-/intracranial tandem occlusions (TO) of the anterior circulation are responsible for causing mechanical thrombectomy (MT). The impact of concomitant contralateral carotid stenosis (CCS) upon outcome remains unclear in this stroke subtype. METHODS: Retrospective analysis of prospectively collected data of 4 international stroke centers between 2011 and 2017. One hundred ninety-seven consecutive patients with anterior TO were treated with MT and acute carotid artery stenting (CAS). Clinical (including demographics and National Institutes of Health Stroke Scale [NIHSS]), imaging (including angiographic evaluation of CCS) and procedural data were evaluated. Favorable clinical outcome was defined as modified Rankin Scale (mRS) ≤2 at 90 days. RESULTS: In 186 out of 197 TO patients preinterventional CT angiography was available for analysis, thereof 49 patients (26%) presented with CCS. Median admission NIHSS and procedural timings did not differ between groups. Reperfusion was successful in 38 out of 49 patients (78%) vs. 113 out of 148 patients (76%) without CCS. In stark contrast, rate of favorable outcome at 90 days differed significantly between groups (22 vs. 44%; p < 0.05). The presence of CCS in TO was associated with an unfavorable clinical outcome independent of age and NIHSS in multivariate logistic regression (p < 0.05). Final infarct volume was significantly larger in CCS patients (100 ± 127 vs. 63 ± 77 cm3; p < 0.05). Neither all-cause mortality rates (25 vs. 17%) nor frequency of peri-interventional symptomatic intracranial hemorrhage differed between groups (7 vs. 6%). CONCLUSION: For patients with anterior TO undergoing MT with concomitant CAS the presence of CCS >50% is an independent predictor of poor clinical outcome. This most likely cause is due to poorer collateral flow to the affected tissue.

Prehospital stroke care in Singapore.

ABSTRACT: Due to the narrow window of opportunity for stroke therapeutics to be employed, effectiveness of stroke care systems is predicated on the efficiency of prehospital stroke systems. A robust prehospital stroke system of care that provides a rapid and well-coordinated response maximises favourable poststroke outcomes, but achieving this presents a unique set of challenges dependent on demographic and geographical circumstances. Set in the context of a highly urbanised first-world nation with a rising burden of stroke, Singapore's prehospital stroke system has evolved to reflect the environment in which it operates. This review aims to characterise the current state of prehospital stroke care in Singapore, covering prehospital aspects of the stroke survival chain from symptom onset till arrival at the emergency department. We identify areas for improvement and innovation, as well as provide insights into the possible future of prehospital stroke care in Singapore.

Comparing the Impact of Stenting vs. Medical Therapy for Intracranial Arterial Stenosis : A Systematic Review and One-stage and Two-stage Meta-Analysis of Randomized Clinical Trials.

PURPOSE: In the treatment of intracranial arterial stenosis (ICAS), controversies remain regarding the optimal treatment strategy. Our study aims to conduct an individual patient-level data meta-analysis of existing RCTs comparing PTAS versus best medical therapy and to identify differences in outcomes such as incidence of ischemic stroke or death. METHODS: Randomised controlled trials comparing the outcomes of stenting versus best medical therapy for patients who had symptomatic ICAS of >50%. Excluded studies included case reports, case series, reviews, observational studies,  letters or studies evaluating isolated angioplasty techniques without stenting. Data was extracted in accordance with PRISMA guidelines. RESULTS: 7 studies involving 1425 participants were included. There was an increased risk in the incidence of stroke and death within the first 30 days post-procedure for patients treated with PTAS over best medical therapy (RR = 2.22 [1.28-3.86], I²â€¯= 0%). Patients who underwent stenting also had a significantly higher risk of intracranial haemorrhage (RR = 12.66 [2.41-66.45], I²â€¯= 0%) and death (RR = 5.41 [1.20-24.28], I²â€¯= 0%).Under the shared frailty model, stenting when compared to medical therapy has a HR of 1.81 (95% CI:1.25-2.6) of stroke or death across 1 year. Under the parametric Royston-Parmar model, stenting has a significant decrease in the RMST(-0.83 months; 95% CI: -1.30-0.37). Stenting continued to show worse outcomes up to the 3 year mark with a HR of 1.60 (95% CI: 1.11-2.32). CONCLUSIONS AND RELEVANCE: There is an increased risk of peri- and post-procedural stroke and death over best medical therapy in patients with symptomatic ICAS who undergo PTAS. Further work is required to refine patient selection and mitigate peri-procedural risks.

Prognostication of Outcomes in Spontaneous Intracerebral Hemorrhage: A Propensity Score-Matched Analysis with Support Vector Machine.

OBJECTIVE: The role of surgery in spontaneous intracerebral hemorrhage (SICH) remains controversial. We aimed to use explainable machine learning (ML) combined with propensity-score matching to investigate the effects of surgery and identify subgroups of patients with SICH who may benefit from surgery in an interpretable fashion. METHODS: We conducted a retrospective study of a cohort of 282 patients aged ≥21 years with SICH. ML models were developed to separately predict for surgery and surgical evacuation. SHapley Additive exPlanations (SHAP) values were calculated to interpret the predictions made by ML models. Propensity-score matching was performed to estimate the effect of surgery and surgical evacuation on 90-day poor functional outcomes (PFO). RESULTS: Ninety-two patients (32.6%) underwent surgery, and 57 patients (20.2%) underwent surgical evacuation. A total of 177 patients (62.8%) had 90-day PFO. The support vector machine achieved a c-statistic of 0.915 when predicting 90-day PFO for patients who underwent surgery and a c-statistic of 0.981 for patients who underwent surgical evacuation. The SHAP scores for the top 5 features were Glasgow Coma Scale score (0.367), age (0.214), volume of hematoma (0.258), location of hematoma (0.195), and ventricular extension (0.164). Surgery, but not surgical evacuation of the hematoma, was significantly associated with improved mortality at 90-day follow-up (odds ratio, 0.26; 95% confidence interval, 0.10-0.67; P = 0.006). CONCLUSIONS: Explainable ML approaches could elucidate how ML models predict outcomes in SICH and identify subgroups of patients who respond to surgery. Future research in SICH should focus on an explainable ML-based approach that can identify subgroups of patients who may benefit functionally from surgical intervention.

Association of head and neck CT-derived sarcopenia with mortality and adverse outcomes: A systematic review.

BACKGROUND: There is growing interest in the association of CT-assessed sarcopenia with adverse outcomes in non-oncological settings. PURPOSE: The aim of this systematic review is to summarize existing literature on the prognostic implications of CT-assessed sarcopenia in non-oncological patients. MATERIALS AND METHODS: Three independent authors searched Medline/PubMed, Embase and Cochrane Library up to 30 December 2023 for observational studies that reported the presence of sarcopenia defined on CT head and neck in association with mortality estimates and other adverse outcomes, in non-oncological patients. The quality of included studies were assessed using the Quality of Prognostic Studies tool. RESULTS: Overall, 15 studies (3829 participants) were included. Nine studies were at low risk of bias, and six were at moderate risk of bias. Patient populations included those admitted for trauma or treatment of intracranial aneurysms, ischemic stroke, transient ischemic attack, and intracranial stenosis. Sarcopenia was associated with increased 30-day to 2-year mortality in inpatients and patients undergoing carotid endarterectomy or mechanical thrombectomy for acute ischemic stroke. Sarcopenia was also associated with poorer neurological and functional outcomes, increased likelihood of admission to long-term care facilities, and longer duration of hospital stays. The observed associations of sarcopenia with adverse outcomes remained similar across different imaging modalities and methods for quantifying sarcopenia. CONCLUSION: CT-assessed sarcopenia was associated with increased mortality and poorer outcomes across diverse patient populations. Measurement and early identification of sarcopenia in vulnerable patients allows for enhanced prognostication, and focused allocation of resources to mitigate adverse outcomes.

Migraine and atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Patients with migraines, particularly those with auras, may present with stroke. Atrial fibrillation is a known risk factor for stroke. With common pathophysiological factors between migraines and atrial fibrillation, we aimed to clarify the association between migraine and atrial fibrillation in this systematic review and meta-analysis. METHODS: A literature search was conducted in EMBASE, PubMed, Scopus and Cochrane electronic bibliographic databases from inception to 5 September 2022 with the following inclusion criteria: (a) cohort or cross-sectional studies; (b) studies that included only patients aged ≥18 years; and (c) studies that examined the association between atrial fibrillation and migraines. Exclusion criteria were case-control studies and the studies that included patients with previous diagnosis of atrial fibrillation or nonmigrainous headache. The Newcastle-Ottawa Scale was used to assess the quality of studies. RESULTS: Six studies were included, demonstrating a pooled prevalence of atrial fibrillation of 1.61% (95% confidence interval [CI] 0.51, 3.29) in migraine with aura and 1.32% (95% CI 0.17, 3.41) in migraine without aura. The overall prevalence of atrial fibrillation in migraine was 1.39% (95% CI 0.24, 3.46). CONCLUSION: In this systematic review and meta-analysis, the overall prevalence of atrial fibrillation in patients with migraine was low. Further studies are needed to clarify this relationship.

Bridging the Gap: Tailoring an Approach to Treatment in Febrile Infection-Related Epilepsy Syndrome.

Cytokine profiling before immunotherapy is increasingly prevalent in febrile infection-related epilepsy syndrome (FIRES). In this case, an 18-year-old man presented with first-onset seizure after a nonspecific febrile illness. He developed super-refractory status epilepticus requiring multiple antiseizure medications and general anesthetic infusions. He was treated with pulsed methylprednisolone and plasma exchange and started on ketogenic diet. Contrast-enhanced MRI brain revealed postictal changes. EEG findings showed multifocal ictal runs and generalized periodic epileptiform discharges. CSF analysis, autoantibody testing, and malignancy screening were unremarkable. Genetic testing revealed variants of uncertain significance in the CNKSR2 and OPN1LW genes. Initial serum and CSF cytokine analyses performed on days 6 and 21 revealed that interleukin (IL)-6, IL-1RA, monocyte chemoattractant protein-1, macrophage inflammatory protein 1ß, and interferon γ were elevated predominantly in the CNS, a profile consistent with cytokine release syndrome. Tofacitinib was initially trialed on day 30 of admission. There was no clinical improvement, and IL-6 continued to rise. Tocilizumab was given on day 51 with significant clinical and electrographic response. Anakinra was subsequently trialed from days 99 to 103 because clinical ictal activity re-emerged on weaning anesthetics but stopped because of poor response. Serial cytokine profiles showed improvement after 7 doses of tocilizumab. There was corresponding improved seizure control. This case illustrates how personalized immunomonitoring may be helpful in cases of FIRES, where proinflammatory cytokines are postulated to act in epileptogenesis. There is an emerging role for cytokine profiling and close collaboration with immunologists for the treatment of FIRES. The use of tocilizumab may be considered in patients with FIRES with upregulated IL-6.

Different dosing regimens of Tenecteplase in acute ischemic stroke: A network meta-analysis of the clinical evidence.

Introduction: Acute ischemic stroke remains the major cause of death and disability and conclusive evidence of Tenecteplase in treating stroke is lacking. Objective: To conduct a meta-analysis to determine whether Tenecteplase produces better outcomes than Alteplase and a network meta-analysis comparing the different dosing regimens of Tenecteplase. Methods: Searches were made in MEDLINE, CENTRAL, and ClinicalTrials.gov. The outcome measures are recanalization, early neurological improvement, functional outcomes at 90 days (modified Rankin Scale 0-1 and 0-2), intracranial hemorrhage, symptomatic intracranial hemorrhage, and mortality within 90 days from treatment. Results: Fourteen studies are included in the meta-analyses and 18 studies in the network meta-analyses. In the meta-analysis, Tenecteplase 0.25 mg/kg has significant results in early neurological improvement (OR = 2.35, and 95% CI = 1.16-4.72) and excellent functional outcome (OR = 1.20, and 95% CI = 1.02-1.42). In the network meta-analysis, Tenecteplase 0.25 mg/kg produces significant results in early neurological improvement (OR = 1.52 [95% CI = 1.13-2.05], p-value = 0.01), functional outcomes (mRS 0-1 and 0-2) (OR = 1.19 [95% CI = 1.03-1.37], p-value = 0.02; OR = 1.21 [95% CI = 1.05-1.39], p-value = 0.01; respectively) and mortality (OR = 0.78 [95% CI = 0.64-0.96], p-value = 0.02) whereas Tenecteplase 0.40 mg/kg increases the chances of symptomatic intracranial hemorrhage (OR = 2.35 [95% CI = 1.19-4.64], p-value = 0.01). Conclusion: While not conclusive, our study lends evidence to 0.25 mg/kg Tenecteplase dose for ischemic stroke treatment. Further randomized trials need to be done to validate this finding. Registration: International prospective register of systematic reviews (PROSPERO) - CRD42022339774URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=339774.

Role of plaque inflammation in symptomatic carotid stenosis.

Objective: Prior studies have shown that plaque inflammation on FDG-PET and the symptomatic carotid atheroma inflammation lumen-stenosis (SCAIL) score were associated with recurrent ischemic events, but the findings have thus far not been widely validated. Therefore, we aimed to validate the findings of prior studies. Methods: A single-center prospective cohort study that recruited patients with (1) recent TIA or ischemic stroke within the past 30 days, (2) ipsilateral carotid artery stenosis of ≥50%, and (3) were not considered for early carotid revascularization. The (1) maximum standardized uptake value (SUVmax) of the symptomatic carotid plaque, (2) the SCAIL score, and (3) stenosis severity of the symptomatic carotid artery were measured for all patients. The outcomes were (1) a 90-day ipsilateral ischemic stroke and (2) a 90-day ipsilateral symptomatic TIA or major adverse cardiovascular event (MACE). Results: Among the 131 patients included in the study, the commonest cardiovascular risk factor was hypertension (95 patients, 72.5%), followed by diabetes mellitus (77 patients, 58.8%) and being a current smoker (64 patients, 48.9%). The median (IQR) duration between the index cerebral ischemic event and recruitment to the study was 1 (0, 2.5) days. The median (IQR) duration between the index cerebral ischemic event and FDG-PET was 5 (4, 7) days. A total of 14 (10.7%) patients had a 90-day stroke, and 41 (31.3%) patients had a 90-day TIA or MACE. On comparison of the predictive performances of the SCAIL score and SUVmax, SUVmax was found to be superior to the SCAIL score for predicting both 90-day ipsilateral ischemic stroke (AUC: SCAIL = 0.79, SUVmax = 0.92; p < 0.001; 95% CI = 0.072, 0.229) and 90-day TIA or MACE (AUC: SCAIL = 0.76, SUVmax = 0.84; p = 0.009; 95% CI = 0.020, 0.143). Conclusion: Plaque inflammation as quantified on FDG-PET may serve as a reliable biomarker for risk stratification among patients with ECAD and recent TIA or ischemic stroke. Future studies should evaluate whether patients with significant plaque inflammation as quantified on FDG-PET benefit from carotid revascularization and/or anti-inflammatory therapy.

Revolutionizing the Management of Large-Core Ischaemic Strokes: Decoding the Success of Endovascular Therapy in the Recent Stroke Trials.

Endovascular therapy (EVT) has revolutionized the management of acute ischaemic strokes with large vessel occlusion, with emerging evidence suggesting its benefit also in large infarct core volume strokes. In the last two years, four randomised controlled trials have been published on this topic-RESCUE-Japan LIMIT, ANGEL-ASPECT, SELECT2 and TENSION, with overall results showing that EVT improves functional and neurological outcomes compared to medical management alone. This review aims to summarise the recent evidence presented by these four trials and highlight some of the limitations in our current understanding of this topic.