Glucose Control and Risk of Symptomatic Intracerebral Hemorrhage Following Thrombolysis for Acute Ischemic Stroke: A SHINE Trial Analysis.

BACKGROUND AND OBJECTIVES: Baseline hyperglycemia is associated with worse outcomes in acute ischemic stroke (AIS), including higher risk of symptomatic intracerebral hemorrhage (sICH) following treatment with thrombolysis. Prospective data are lacking to inform management of post-thrombolysis hyperglycemia. In a prespecified analysis from the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial of hyperglycemic stroke management, we hypothesized that post-thrombolysis hyperglycemia is associated with a higher risk of sICH. METHODS: Hyperglycemic AIS patients <12 hours onset were randomized to intensive insulin (target range 80-130 mg/dL) vs standard sliding scale (80-179 mg/dL) over a 72-hour period, stratified by treatment with thrombolysis. Three board-certified vascular neurologists independently reviewed all sICH events occurring within 7 days, defined by neurologic deterioration of ≥4 points on the NIH Stroke Scale (NIHSS). Associations between blood glucose control and sICH were analyzed using logistic regression accounting for NIHSS, age, systolic blood pressure, onset to thrombolysis time, and endovascular therapy (odds ratios [OR], 95% CI). Additional analysis compared patients in a high-risk group (age older than 60 years and NIHSS ≥8) vs all others. Categorical variables and outcomes were compared using the χ2 test (p < 0.05). RESULTS: Of 1151 SHINE participants, 725 (63%) received thrombolysis (median age 65 years, 46% women, 29% Black, 18% Hispanic). The median NIHSS was 7, baseline blood glucose was 187 (interquartile range 153-247) mg/dL, and 80% were diabetic. Onset to thrombolysis time was 2.2 hours (1.6-2.9). Post-thrombolysis sICH occurred in 3.6% (3.0% intensive vs 4.3% standard glucose control, OR 1.10, 0.60-2.01, p = 0.697). In the first 12 hours, every 10 mg/dL higher glucose increased the odds of sICH (OR 1.08, 1.03-1.14, p = 0.004), and a greater proportion of glucose measures in the normal range (80-130 mg/dL) decreased the odds of sICH (0.89, 0.80-0.99, p = 0.030). These associations were strongest in the high-risk group (age older than 60 years and NIHSS ≥8). DISCUSSION: In this prespecified analysis from the SHINE trial, intensive insulin therapy was not associated with a reduced risk of post-thrombolysis sICH compared with standard sliding scale. However, early post-thrombolysis hyperglycemia was associated with a higher risk of sICH overall, particularly in older patients with more severe strokes. Further prospective research is warranted to address the risk of sICH in hyperglycemic stroke patients undergoing endovascular therapy. TRIAL REGISTRATION INFORMATION: NCT01369069.

Serum Uric Acid and Serum Lipid Levels in Patients with Acute Ischemic Stroke Admitted in Mymensingh Medical College Hospital.

Stroke is the second-leading cause of death and also a leading cause of combined death and disability. In Bangladesh, stroke prevalence is 11.39 per 1000 population, but highest prevalence of stroke is 14.71 per 1000 population in the Mymensingh division. Hyperuricemia has been reported as an independent risk factor for stroke in different studies and a significant association between serum uric acid and dyslipidemia has also been stated. On the contrary, some studies suggest that uric acid has a neuroprotective role. This cross-sectional study was completed in the Medicine Department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh from March 2021 to January 2023. In this cross-sectional study, 352 adult acute ischemic stroke patients were included from the Medicine Department of Mymensingh Medical College Hospital. Serum uric acid and fasting serum lipid levels were measured within 48 hours of admission. The mean age ±SD of the respondents was 61.9±12.8 years. Hyperuricemia was found among 18.2% of respondents, whose mean ±SD serum uric acid was 5.7±1.9 mg/dl. Dyslipidemia was present in 88.4% of patients. The mean ±SD of the National Institutes of Health Stroke Scale (NIHSS) score was 12.0±5.9. Most of the patients (65.6%) were suffering from moderate stroke, followed by moderate to severe stroke (15.1%), severe stroke (10.8%) and minor stroke (8.5%). After multiple linear regressions, the independent variables age, gender, serum uric acid and total cholesterol were found to be significant predictors of the NIHSS score of the respondents. In conclusion, the majority of acute ischemic stroke patients have an association with dyslipidemia, but only around one-fifth of patients have hyperuricemia. There is a significant association of high serum uric acid and high serum total cholesterol with stroke severity (NIHSS score). But low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and, triglycerides have no association with stroke severity.

Time­dependent changes in blood cells, NIHSS and mRS according to reperfusion treatment type in stroke patients who developed hemorrhagic complication.

Hemorrhagic complications may be seen following reperfusion therapy with rtPA and/or thrombectomy after acute ischemic stroke (AIS). Neutrophils, lymphocytes, and platelets have important roles in the inflammatory and immune responses that develop in these patients. We investigated time­dependent changes in blood cells, NIHSS and mRS values according to type of reperfusion therapy in AIS patients who developed cerebral hemorrhage. In AIS patients who underwent rtPA and/or thrombectomy and developed cerebral hemorrhage within the first 24 hours after treatment, leukocyte, neutrophil, lymphocyte, platelet counts and their ratios were recorded on admission, 1st, 3rd, and 7th days. NIHSS values on admission, 3rd days and mRS values on admission, discharge, and the 3rd month were recorded. These values were compared according to the type of reperfusion therapy. Out of 436 AIS patients, rtPA was applied in 50.5%, thrombectomy in 28.2%, and rtPA+thrombectomy in 21.3%. Hemorrhage developed in 25.5% of the patients. Patients treated with thrombectomy had a greater rate of cerebral hemorrhage. Pre­stroke mRS values were lower in all therapy types than mRS scores at discharge and the 3rd month. The NIHSS scores did not differ significantly in 3 days. Depending on the type of reperfusion treatment, there are a few time­dependent significant changes observed in the blood cell counts and ratios. In conclusion, there is a relation between the type of reperfusion therapy and the time­dependent changes in blood cells and ratios as well as mRS scores among AIS patients who have undergone rtPA and/or thrombectomy and developed cerebral hemorrhage.

ADAMTS13 deficiency exacerbates neuroinflammation by targeting matrix metalloproteinase-9 in ischemic brain injury.

Our design aimed to explore the potential involvement of matrix metalloproteinase-9 (MMP-9) in the inflammatory response associated with acute ischemic stroke (AIS). We also aimed to preliminarily examine the potential impact of a disintegrin-like and metalloprotease with thrombospondin type I repeats-13 (ADAMTS13) on MMP-9 in AIS. We conducted oxygen-glucose deprivation models of microglia cells and mice models of AIS with middle cerebral artery occlusion (MCAO). We assessed the expression pattern of MMP-9 with western blotting (WB) and real-time quantitative PCR both in vivo and in vitro. MMP-9 downregulation was achieved by using ACE inhibitors such as trandolapril. For the MCAO model, we used ADAMTS13-deficient mice. We then evaluated the related neurological function scores, cerebral edema and infarct volume. The levels of inflammation-related proteins, such as COX2 and iNOS, were assessed using WB, and the expression of inflammatory cytokines was measured via enzyme-linked immuno sorbent assay in vivo. Our findings indicated that MMP-9 was up-regulated while ADAMTS13 was down-regulated in the MCAO model. Knockdown of MMP-9 reduced both inflammation and ischemic brain injury. ADAMTS13 prevented brain damage, improved neurological function and decreased the inflammation response in mice AIS models. Additionally, ADAMTS13 alleviated MMP-9-induced neuroinflammation in vivo. It showed that ADAMTS13 deficiency exacerbated ischemic brain injury through an MMP-9-dependent inflammatory mechanism. Therefore, the ADAMTS13-MMP-9 axis could have therapeutic potential for the treatment of AIS.

Differential DNA methylation associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a systematic review.

Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.

Targeting brain-peripheral immune responses for secondary brain injury after ischemic and hemorrhagic stroke.

The notion that the central nervous system is an immunologically immune-exempt organ has changed over the past two decades, with increasing evidence of strong links and interactions between the central nervous system and the peripheral immune system, both in the healthy state and after ischemic and hemorrhagic stroke. Although primary injury after stroke is certainly important, the limited therapeutic efficacy, poor neurological prognosis and high mortality have led researchers to realize that secondary injury and damage may also play important roles in influencing long-term neurological prognosis and mortality and that the neuroinflammatory process in secondary injury is one of the most important influences on disease progression. Here, we summarize the interactions of the central nervous system with the peripheral immune system after ischemic and hemorrhagic stroke, in particular, how the central nervous system activates and recruits peripheral immune components, and we review recent advances in corresponding therapeutic approaches and clinical studies, emphasizing the importance of the role of the peripheral immune system in ischemic and hemorrhagic stroke.

Leukocyte counts and ratios as potential predictors of large vessel occlusion in acute ischemic stroke: A retrospective cohort study.

Leukocyte counts and ratios are independent biomarkers to determine the severity and prognosis of acute ischemic stroke (AIS). In AIS, the connection between leukocytes and large vessel occlusion (LVO) is uncertain. This study aims to determine the relationship between the existence of LVO and leukocyte counts and ratios on admission to AIS. Patients were retrospectively evaluated within six hours of AIS starting between January 2019 and April 2023. On admission, blood specimens were collected, and leukocyte subtype counts were promptly analyzed. Computed tomography or digital subtraction angiography were utilized to verify the existence of LVO. Regression analysis and receiver operating characteristic (ROC) curves were employed to investigate the connections between the counts and ratios of leukocytes and the existence of LVO, as well as the discriminatory ability of these variables in predicting LVO. Total white blood cell (WBC) count, neutrophil count, and neutrophil-to-lymphocyte ratio (NLR) were substantially higher in the LVO existence group compared to the LVO absence group, whereas the ratio of eosinophils to neutrophils (ENR × 102) was lower (P < .001, respectively). Significant associations were observed between total WBC counts, neutrophil counts, NLR, and ENR × 102 and the existence of LVO (P < .001, respectively). Total WBC counts, neutrophil counts, NLR, and ENR × 102 had respective areas under the curves (AUC) of 0.730, 0.748, 0.704, and 0.680 for identifying LVO. Our results show that in AIS patients, the existence of LVO is independently associated with elevated total WBC and neutrophil counts, high NLR, and low ENR × 102 levels. Neutrophil and total WBC counts, as well as NLR and levels of ENR × 102, may serve as potential biomarkers for predicting LVO. Neuroinflammation, based on the existence of LVO, should be given particular attention in future investigations.

Personalised stroke evaluation and management: tailoring individualised patient care for hereditary haemorrhagic telangiectasia.

SummaryHereditary haemorrhagic telangiectasia (HHT) has an estimated prevalence of 1 in 5000-8000 individuals globally with pulmonary arteriovenous malformations (PAVMs) affecting approximately 15%-50% of HHT patients. Ischaemic stroke is a known complication of PAVMs that affects ≤30% of patients with PAVMs. Studies have shown that patients with PAVMs have ischaemic stroke a decade earlier than routine stroke. The predominant mechanism of ischaemic stroke in HHT patients is paradoxical embolism due to PAVMs, but most HHT-related PAVMs are asymptomatic. Additionally, HHT is often underdiagnosed in patients and poses a challenge to physicians due to its rarity. We present a case of a patient with ischaemic stroke who was subsequently diagnosed with HHT and found to have a PAVM on further evaluation. This case highlights the importance of using an individualised patient-centred stroke evaluation and screening for PAVMs in patients who had a stroke with possible or suspected HHT and definite HHT.

CT Imaging Computed Tomography/Computed Tomography Angiography/Perfusion in Acute Ischemic Stroke and Vasospasm.

Computed tomography (CT), CT angiography (CTA), and CT perfusion (CTP) play crucial roles in the comprehensive evaluation and management of acute ischemic stroke, aneurysmal subarachnoid hemorrhage (SAH), and vasospasm. CTP provides functional data about cerebral blood flow, allowing radiologists, neurointerventionalists, and stroke neurologists to more accurately delineate the volume of core infarct and ischemic penumbra allowing for patient-specific treatment decisions to be made. CTA and CTP are used in tandem to evaluate for vasospasm associated with aneurysmal SAH and can help provide an insight into the physiologic impact of angiographic vasospasm, better triaging patients for medical and interventional treatment.

MR Imaging Techniques for Acute Ischemic Stroke and Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage.

Acute ischemic stroke (AIS) is a leading cause of death and disability worldwide, and its prevalence is expected to increase with global population aging and the burgeoning obesity epidemic. Clinical care for AIS has evolved during the past 3 decades, and it comprises of 3 major tenants: (1) timely recanalization of occluded vessels with intravenous thrombolysis or endovascular thrombectomy, (2) prompt initiation of antithrombotic agents to prevent stroke recurrences, and (3) poststroke supportive care and rehabilitation. In this article, we summarize commonly used MR sequences for AIS and DCI and highlight their clinical applications.

Post-stroke arrhythmia could be a potential predictor for post-stroke depression.

Post-stroke depression (PSD) is regarded as the consequence of multiple contributors involving the process of cognition, mood and autonomic system, with the specific mechanism unclear yet. As a common type of stroke-heart syndromes, post-stroke arrhythmia shared some common pathogenesis with PSD. We presumed that post-stroke arrhythmia might be an early distinguishable marker for the presence of PSD and aimed to verity their association in this study. Patients with first-ever ischemic stroke were enrolled. The presence of post-stroke ectopic arrhythmia and the symptoms of arrhythmia were recorded with anti-arrhythmia drugs prescribed when necessary. Patients were followed up 3 months later to identify their presence and severity of PSD using Hamilton Depression Scale (HAMD) and also presence and severity of arrhythmia. Characteristics including the prevalence of various types of arrhythmias were compared between PSD and non-PSD groups. The HAMD scores were compared between patients with and without arrhythmia in PSD group. Logistic regression was used to identify the independent predictor of PSD. Patients with PSD had higher prevalence of post-stroke arrhythmia especially newly-detected arrhythmia, symptomatic arrhythmia and poor-controlled arrhythmia. In PSD group, patients of post-stroke arrhythmia had higher scores of HAMD than those without arrhythmia. Presence of newly-detected, symptomatic and poor-controlled arrhythmias were independent predictor of PSD. post-stroke arrhythmia especially newly-detected arrhythmia and symptomatic arrhythmia could be an early predictor of PSD. Successful control of arrhythmia was associated with reduced prevalence and severity of PSD.

The Relationship Between Composite Inflammatory Ratios and Complications of Massive Ischaemic Stroke.

OBJECTIVE: To investigate the relationship between complications of massive cerebral infarction (MCI) and composite inflammatory ratios. STUDY DESIGN: A case-control study. Place and Duration of the Study: Department of Neurology, Affiliated Hospital of Putian University, Putian, China, from January 2019 to November 2021. METHODOLOGY: Eighty-two patients with MCI underwent blood tests within 24 hours of admission. Complications such as cerebral herniation, haemorrhage transformation (HT), and stroke-associated pneumonia (SAP) were evaluated based on imaging examinations. The prognosis was assessed using the modified Rankin Scale score (mRS) at discharge. RESULTS: Among the 82 patients, the cerebral herniation group had higher levels of systemic immune inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) compared to the non-cerebral herniation group. MCI patients who developed HT had higher levels of SII, NLR, mean platelet volume/platelet (MPV/PLT), and platelet-to-lymphocyte ratio (PLR). The SAP group had higher levels of MPV/PLT and NLR compared to the non-SAP group. The poor prognosis group had higher SII and NLR levels but a lower lymphocyte-to-monocyte ratio (LMR) compared to the good prognosis group. CONCLUSION: NLR showed high accuracy in predicting complications and the short-term prognosis of MCI. SII was linked to cerebral herniation, HT, and the short-term prognosis of MCI. MPV/PLT was found to be related to SAP and HT caused by MCI. LMR may act as a protective factor for the short-term prognosis of MCI. KEY WORDS: Massive cerebral infarction, Neutrophil-to-lymphocyte ratio, Systemic immune inflammation index, Prognosis.

Unconsciousness as the main nonfocal symptom of anterior circulation transient ischemic attack: A case report.

RATIONALE: Unconsciousness is a nonfocal symptom of transient ischemic attack (TIA) that is frequently observed in patients with vertebrobasilar artery stenosis or occlusion. Conversely, loss of consciousness due to anterior circulation involvement (e.g., middle cerebral artery [MCA]) is a rare occurrence in TIA. PATIENT CONCERNS: This report describes a rare case in a 59-year-old woman who experienced recurrent episodes of altered consciousness because of the occlusion or stenosis of her MCAs. DIAGNOSES: The diagnosis of the case was updated from TIA to acute cerebral infarction, finally. Following initial loss of consciousness, cranial magnetic resonance imaging (MRI) did not reveal any evidence of acute cerebral infarction. However, following the second and third episodes of unconsciousness, the MRI revealed multiple new acute cerebral infarcts affecting both the cerebral hemispheres. Further evaluation through digital subtraction angiography disclosed complete occlusion of the left MCA and severe stenosis of the right MCA. INTERVENTIONS: Early in her illness, the patient was treated with vasodilators, aspirin and atorvastatin. Finally, 2 stents in her right and left MCAs were placed respectively, followed by treatment with aspirin, clopidogrel, and double-dosed atorvastatin calcium. Meanwhile, the patient focused on avoiding conditions which may lead to dehydration in her daily life routine. OUTCOMES: The episodes of unconsciousness of this patient were completely resolved. During the 1-year postoperative follow-up, the patient remained clinically stable without any symptoms of unconsciousness, limb numbness or weakness, or dizziness. LESSONS: These findings suggested that hypoperfusion in the bilateral cerebral hemispheres played a pivotal role in precipitating the patient episodes of unconsciousness. This case underscores the possibility that occlusion or severe stenosis in both MCAs can contribute to recurrent episodes of unconsciousness due to hypoperfusion. Moreover, it emphasizes the association between these episodes of unconsciousness and an increased risk of subsequent ischemic stroke.

Remote Ischemic Conditioning With Medical Management or Reperfusion Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Remote ischemic conditioning (RIC) is a low-cost, accessible, and noninvasive neuroprotective treatment strategy, but its efficacy and safety in acute ischemic stroke are controversial. With the publication of several randomized controlled trials (RCTs) and the recent results of the RESIST trial, it may be possible to identify the patient population that may (or may not) benefit from RIC. This systematic review and meta-analysis aims to evaluate the effectiveness and safety of RIC in patients with ischemic stroke receiving different treatments by pooling data of all randomized controlled studies to date. METHODS: We searched the PubMed, Embase, Cochrane, Elsevier, and Web of Science databases to obtain articles in all languages from inception until May 25, 2023. The primary outcome was the modified Rankin Scale (mRS) score at the specified endpoint time in the trial. The secondary outcomes were change in NIH Stroke Scale (NIHSS) and recurrence of stroke events. The safety outcomes were cardiovascular events, cerebral hemorrhage, and mortality. The quality of articles was evaluated through the Cochrane risk assessment tool. This study was registered in PROSPERO (CRD42023430073). RESULTS: There were 7,657 patients from 22 RCTs included. Compared with the control group, patients who received RIC did not have improved mRS functional outcomes, regardless of whether they received medical management, reperfusion therapy with intravenous thrombolysis (IVT), or mechanical thrombectomy (MT). In the medical management group, patients who received RIC had decreased incidence of stroke recurrence (risk ratio 0.63, 95% CI 0.43-0.92, p = 0.02) and lower follow-up NIHSS score by 1.72 points compared with the control group (p < 0.00001). There was no increased risk of adverse events including death or cerebral hemorrhage in the IVT or medical management group. DISCUSSION: In patients with ischemic stroke who are not eligible for reperfusion therapy, RIC did not affect mRS functional outcomes but significantly improved the NIHSS score at the follow-up endpoint and reduced stroke recurrence, without increasing the risk of cerebral hemorrhage or death. In patients who received IVT or MT, the benefit of RIC was not observed.

Duration of Remote Ischemic Conditioning and Outcome in Acute Ischemic Stroke.

BACKGROUND: Remote ischemic conditioning has been found to be effective in improving functional outcomes in acute ischemic stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to determine whether long-term remote ischemic conditioning duration after stroke onset is associated with better clinical outcomes in ischemic stroke. METHODS AND RESULTS: Patients from the full analysis set were included in this secondary analysis. The primary outcome was the proportion of patients with an excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. Among the 1776 patients, there were 55 patients in the 1 to 7 days remote ischemic conditioning group, 345 in the 8 to 10 days group, 412 in the 11 to 13 days group, 51 in the 14 to 16 days group, and 913 in the control group. Compared with the control group, a significantly higher proportion of excellent functional outcomes at 90 days was found in the 11 to 13 days remote ischemic conditioning group (adjusted absolute difference, 9.1% [95% CI, 3.7%-14.5%]; P =0.001), which was attenuated in the other groups (adjusted absolute difference in the 8-10 days group, 2.0% [95% CI, -4.0% to 8.0%]; P=0.51; adjusted absolute difference in the 14-16 days group, 7.4% [95% CI, -5.8% to 20.5%]; P=0.27), but compared to the control group, there was lower proportion of excellent functional outcomes in the 1 to 7 days group (adjusted absolute difference, -14.4% [95% CI, -27.8% to 0.0%]; P=0.05). CONCLUSIONS: Among patients with acute moderate ischemic stroke, a higher likelihood of excellent clinical outcome was found in patients with longer duration of remote ischemic conditioning.

Trajectories of stroke severity and functional outcomes after endovascular treatment in ischemic stroke: A post hoc analysis of a randomized controlled trial.

BACKGROUND: The trajectory of early neurological changes in patients with acute ischemic stroke has been understudied. This study aimed to investigate the association between longitudinal trajectories of stroke severity and 90-day functional outcomes in patients with acute ischemic stroke receiving endovascular treatment. METHODS: We enrolled patients from a prospective, multicenter, randomized controlled trial. The stroke severity was assessed with the National Institute of Health Stroke Scale at the pre-procedure, 24 hours, and seven days after the procedure. Group-based trajectory modeling (GBTM) was used to identify trajectories of stroke severity. Multivariable logistic regression was performed to explore the association between stroke severity markers and 90-day functional outcomes. RESULTS: Of 218 enrolled patients, 127 (58.3%) had poor functional outcomes at 90 days. We identified three trajectories of stroke severity in the GBTM: stable symptom (38.1%), symptom deterioration (17.0%), and symptom improvement (44.9%). In multivariable analyses, trajectories of stroke severity were associated with an increased risk of poor functional outcomes (symptom improvement versus symptom deterioration: odds ratio, 0.007; 95% confidence interval, 0.001-0.040; P <0.001). Reclassification indexes revealed that trajectories of stroke severity would increase the predictive ability for poor functional outcomes at 90 days. CONCLUSION: After endovascular treatment, patients would follow one of three distinct trajectories of stroke severity. Symptom deterioration trajectory was associated with an increased risk of poor functional outcomes at 90 days. TRIAL REGISTRATION NUMBER: NCT04973332.

Baseline Uric Acid Levels and Intravenous Thrombolysis Outcomes in Patients With Acute Ischemic Stroke: A Prospective Cohort Study.

BACKGROUND: The study aimed to investigate the relationship between uric acid (UA) levels and functional outcomes at 3 months in patients with acute ischemic stroke (AIS) who underwent intravenous thrombolysis (IVT). METHODS AND RESULTS: This prospective cohort study included 1001 consecutive patients with AIS who underwent IVT. The correlation between UA levels and post-IVT AIS outcomes was examined. Any nonlinear relationship was assessed using a restricted cubic spline function. The nonlinear P value for the association of UA levels with favorable (modified Rankin Scale [mRS] score ≤2) and excellent (mRS score ≤1) outcomes at 3 months post-IVT were <0.001 and 0.001, respectively. However, for patients with and without hyperuricemia, no evident nonlinear relationship was observed between UA levels and favorable 3-month post-IVT outcomes, with nonlinear P values of 0.299 and 0.207, respectively. The corresponding interaction analysis yielded a P value of 0.001, indicating significant heterogeneity. Similar results were obtained for excellent outcomes at 3 months post-IVT. In the hyperuricemia group, increased UA levels by 50 µmol/L reduced the odds of a favorable 3-month post-AIS outcome (odds ratio [OR], 0.75 [95% CI, 0.57-0.97]). Conversely, in the nonhyperuricemia group, a similar UA increase was linked to higher favorable outcome odds (OR, 1.31 [95% CI, 1.15-1.50]). CONCLUSIONS: An inverted U-shaped nonlinear relationship was observed between UA levels and favorable and excellent outcomes at 3 months in patients with AIS who underwent IVT. Higher UA levels predict favorable outcomes in patients without hyperuricemia but unfavorable outcomes in those with hyperuricemia.

Prevalence and impact of SARS-CoV-2 infection among patients with acute ischaemic stroke: a nationwide register-based cohort study in Denmark.

OBJECTIVES: An increased risk of stroke has been reported among patients with COVID-19 caused by SARS-CoV-2. We aimed to investigate the nationwide prevalence of SARS-CoV-2 among patients with acute ischaemic stroke and to study the impact on stroke severity, quality of care and mortality on an individual patient level. DESIGN: This was a nationwide register-based cohort study. SETTING: We used data from several Danish registers which were linked at an individual patient level using the unique civil registration number assigned to all Danish citizens. Patients were identified from the Danish Stroke Registry and information on SARS-CoV-2 infection status was collected from the Danish National COVID-19 Registry. Concurrent SARS-CoV-2 infection was defined as a positive PCR test within 31 days prior to, and 1 day after, stroke admission. Information on comorbidity was collected from the Danish National Patient Registry and information on vital status was collected from the Danish Civil Registration System. PARTICIPANTS: A total of 11 502 patients admitted with acute ischaemic stroke from 10 March 2020 to 31 May 2021 were included in the study. RESULTS: Among the included patients, the majority (84.6%) were tested for SARS-CoV-2, but only 68 had a positive test. These patients were more prone to have atrial fibrillation and were more often treated with reperfusion therapy. They had a significantly increased risk of severe stroke (adjusted relative risk (aRR) 1.93, 95% CI: 1.22 to 3.04) and a significantly increased 30-day mortality risk (aRR 2.29, 95% CI: 1.19 to 4.39). There was no difference in the proportion of patients fulfilling relevant performance measures on quality of care. CONCLUSION: In this nationwide study, only 0.6% of patients with acute ischaemic stroke were tested positive for a concurrent SARS-CoV-2 infection. The patients with SARS-CoV-2 presented with more severe strokes.