Safety of acute internal carotid artery stenting during endovascular thrombectomy in patients with acute ischemic stroke: a retrospective analysis of the OPTIMISE registry.

BACKGROUND: The optimal management of tandem carotid lesions during endovascular thrombectomy (EVT) remains uncertain. The safety and efficacy of acute carotid artery stenting (aCAS) are debated, including safety concerns such as procedural complications and symptomatic intracerebral hemorrhage (sICH). We aimed to assess aCAS safety among EVT-treated patients using a large Canadian registry. METHODS: We retrospectively analyzed the OPTIMISE registry and compared adult patients undergoing EVT and aCAS versus EVT only. The primary outcome was a composite of in-hospital death, long-term care facility destination at discharge, sICH, or any EVT-related procedural complications. Secondary outcomes included individual components of the primary outcome, EVT workflow times, final modified Thrombolysis in Cerebral Ischemia score and 90-day modified Rankin Scale score. Statistical significance was evaluated by a multivariate logistic regression model. RESULTS: 4205 patients were included (330 with EVT-aCAS and 3875 with EVT-only). Both groups were similar with regard to baseline National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score and use of IV thrombolysis, but differed in age (EVT-aCAS group 67.2±12.1 years vs EVT-only group 71.3±14.1 years, P<0.001), proportion of women (28.2% vs 53.3%, P<0.001), and occlusion location (internal carotid artery terminus 44% vs 16%, P<0.001). The EVT-aCAS group showed a non-significant increase in odds of composite safety outcomes (adjusted OR 1.35 (95% CI 0.97 to 1.84), P=0.06) with a significantly higher proportion of procedural complications (10.0% vs 6.2%, P=0.002). CONCLUSION: In a large national registry, EVT-aCAS was associated with a higher proportion of unfavorable safety outcomes, driven by more frequent procedural complications. Further research is needed to clarify the role of aCAS in tandem occlusion stroke.

Risk of major adverse cardiovascular events and stroke associated with treatment with GLP-1 or the dual GIP/GLP-1 receptor agonist tirzepatide for type 2 diabetes: A systematic review and meta-analysis.

INTRODUCTION: Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the first-in-class, dual glucose-dependent-insulinotropic-polypeptide GIP/GLP-1 RA approved for T2DM. PATIENTS AND METHODS: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). RESULTS: Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; p < 0.01; I2 = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; p < 0.01; I2 = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; p < 0.01; I2 = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; p < 0.01; I2 = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; p < 0.01; I2 = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; p = 0.105; I2 = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; p < 0.01; I2 = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; p = 0.792; I2 = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction. DISCUSSION AND CONCLUSION: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention.

European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke.

A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We addressed acute treatment (including progressive lacunar stroke) and secondary prevention in lacunar ischaemic stroke, and prioritised the interventions of thrombolysis, antiplatelet drugs, blood pressure lowering, lipid lowering, lifestyle, and other interventions and their potential effects on the clinical outcomes recurrent stroke, dependency, major adverse cardiovascular events, death, cognitive decline, mobility, gait, or mood disorders. We systematically reviewed the literature, assessed the evidence and where feasible formulated evidence-based recommendations, and expert concensus statements. We found little direct evidence, mostly of low quality. We recommend that patients with suspected acute lacunar ischaemic stroke receive intravenous alteplase, antiplatelet drugs and avoid blood pressure lowering according to current acute ischaemic stroke guidelines. For secondary prevention, we recommend single antiplatelet treatment long-term, blood pressure control, and lipid lowering according to current guidelines. We recommend smoking cessation, regular exercise, other healthy lifestyle modifications, and avoid obesity for general health benefits. We cannot make any recommendation concerning progressive stroke or other drugs. Large randomised controlled trials with clinically important endpoints, including cognitive endpoints, are a priority for lacunar ischaemic stroke.

Antithrombotic regimen in emergent carotid stenting for acute ischemic stroke due to tandem occlusion: a meta-analysis of aggregate data.

BACKGROUND: The periprocedural antithrombotic regimen might affect the risk-benefit profile of emergent carotid artery stenting (eCAS) in patients with acute ischemic stroke (AIS) due to tandem lesions, especially after intravenous thrombolysis. We conducted a systematic review and meta-analysis to evaluate the safety and efficacy of antithrombotics following eCAS. METHODS: We followed PRISMA guidelines and searched MEDLINE, Embase, and Scopus from January 1, 2004 to November 30, 2022 for studies evaluating eCAS in tandem occlusion. The primary endpoint was 90-day good functional outcome. Secondary outcomes were symptomatic intracerebral hemorrhage, in-stent thrombosis, delayed stent thrombosis, and successful recanalization. Meta-analysis of proportions and meta-analysis of odds ratios were implemented. RESULTS: 34 studies with 1658 patients were included. We found that the use of no antiplatelets (noAPT), single antiplatelet (SAPT), dual antiplatelets (DAPT), or glycoprotein IIb/IIIa inhibitors (GPI) yielded similar rates of good functional outcomes, with a marginal benefit of GPI over SAPT (OR 1.88, 95% CI 1.05 to 3.35, Pheterogeneity=0.31). Sensitivity analysis and meta-regression excluded a significant impact of intravenous thrombolysis and Alberta Stroke Program Early CT Score (ASPECTS). We observed no increase in symptomatic intracerebral hemorrhage (sICH) with DAPT or GPI compared with noAPT or SAPT. We also found similar rates of delayed stent thrombosis across groups, with acute in-stent thrombosis showing marginal, non-significant benefits from GPI and DAPT over SAPT and noAPT. CONCLUSIONS: In AIS due to tandem occlusion, the periprocedural antithrombotic regimen of eCAS seems to have a marginal effect on good functional outcome. Overall, high intensity antithrombotic therapy may provide a marginal benefit on good functional outcome and carotid stent patency without a significant increase in risk of sICH.

Clinical, Neuroimaging, and Genetic Markers in Cerebral Amyloid Angiopathy-Related Inflammation: A Systematic Review and Meta-Analysis.

BACKGROUND: There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy-related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri. METHODS: A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings. Subgroup analyses were performed based on (1) prospective or retrospective study design and (2) CAA-ri diagnosis with or without available biopsy. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using Cochran-Q and I2-statistics. RESULTS: We identified 4 prospective and 17 retrospective cohort studies comprising 378 patients with CAA-ri (mean age, 71.5 years; women, 52%). The pooled prevalence rates were as follows: cognitive decline at presentation 70% ([95% CI, 54%-84%]; I2=82%), focal neurological deficits 55% ([95% CI, 40%-70%]; I2=82%), encephalopathy 54% ([95% CI, 39%-68%]; I2=43%), seizures 37% ([95% CI, 27%-49%]; I2=65%), headache 31% ([95% CI, 22%-42%]; I2=58%), T2/fluid-attenuated inversion recovery-hyperintense white matter lesions 98% ([95% CI, 93%-100%]; I2=44%), lobar cerebral microbleeds 96% ([95% CI, 92%-99%]; I2=25%), gadolinium enhancing lesions 54% ([95% CI, 42%-66%]; I2=62%), cortical superficial siderosis 51% ([95% CI, 34%-68%]; I2=77%) and lobar macrohemorrhage 40% ([95% CI, 11%-73%]; I2=88%). The prevalence rate of the ApoE (Apolipoprotein E) ε4/ε4 genotype was 34% ([95% CI, 17%-53%]; I2=76%). Subgroup analyses demonstrated no differences in these prevalence rates based on study design and diagnostic strategy. CONCLUSIONS: Cognitive decline was the most common clinical feature. Hyperintense T2/fluid-attenuated inversion recovery white matter lesions and lobar cerebral microbleeds were by far the most prevalent neuroimaging findings. Thirty-four percent of patients with CAA-ri have homozygous ApoE ε4/ε4 genotype and scarce data exist regarding the cerebrospinal fluid biomarkers and its significance in these patients.

Cerebral Venous Sinus Thrombosis and Thrombotic Events After Vector-Based COVID-19 Vaccines: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: There is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes. METHODS: We performed a systematic review and meta-analysis of clinical trials, cohorts, case series, and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal. RESULTS: Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were included further in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% confidence interval [CI] 36%-66%; I 2 = 61%). TTS was independently associated with a higher likelihood of CVST when compared to patients without TTS with thrombotic events after vaccination (odds ratio 13.8; 95% CI 2.0-97.3; I 2 = 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI 21%-36%) and 38% (95% CI 27%-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval 10 days; 95% CI 8-12) and affected predominantly women (69%; 95% CI 60%-77%) under age 45, even in the absence of prothrombotic risk factors. DISCUSSION: Approximately half of patients with TTS present with CVST; almost one-third of patients with TTS do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination. REGISTRATION INFORMATION: The prespecified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).

Eligibility for intravenous thrombolysis in acute ischemic stroke patients presenting in the 4.5-9 h window.

PURPOSE: Recent randomized-controlled clinical trials have provided preliminary evidence for expanding the time window of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients by applying certain neuroimaging criteria. We prospectively assessed the potential eligibility for IVT in the extended time window (4.5-9 h) among consecutive AIS patients treated in a comprehensive stroke center during a nine-month period. METHODS: Potential eligibility for IVT in the extended time window was evaluated by using inclusion criteria from the EXTEND trial. All patients were underwent baseline emergent neurovascular imaging using either computed tomography angiography/computed tomography perfusion (CTA/CTP) or magnetic resonance angiography/magnetic resonance perfusion (MRA/MRP). Images were post processed by the automated software RAPID. RESULTS: Our study population consisted of 317 AIS patients, and, among them, 31 (9.8 %) patients were presented in the time window of 4.5-9 h. Seven patients (2.2 %) fulfilled the EXTEND neuroimaging criteria. Four patients (1.3 %) were treated with IVT because they fulfilled both clinical and neuroimaging EXTEND criteria. Patients eligible for EXTEND neuroimaging criteria had no ischemic core lesion, whereas the mean volume of critical hypoperfusion was relatively small (17.0 ± 11.8 ml). There was no hemorrhagic complication in any of the patients treated with IVT. The median mRS score at three months was 0 (range: 0-3) among patients who were eligible for EXTEND neuroimaging criteria. CONCLUSION: Our everyday clinical practice experience suggests 9.8 % of consecutive AIS patients present in the 4.5-9 h window and 2.2 % adhere to EXTEND neuroimaging eligibility criteria for IVT. Only 1.3% of AIS is eligible for IVT according to EXTEND neuroimaging and clinical eligibility criteria.

Intravenous thrombolysis pretreatment and other predictors of infarct in a new previously unaffected territory (INT) in ELVO strokes treated with mechanical thrombectomy.

INTRODUCTION: One uncommon complication of mechanical thrombectomy (MT) is an infarct in a new previously unaffected territory (infarct in new territory (INT)). OBJECTIVE: To evaluate the predictors of INT with special focus on intravenous thrombolysis(IVT)pretreatmentbefore MT. METHODS: Consecutive patients with emergent large vessel occlusion (ELVO) treated with MT during a 5-year period were evaluated. INT was defined using standardized methodology proposed by ESCAPE investigators. The predictors of INT and its impact on outcomes were investigated. RESULTS: A total of 419 consecutive patients with ELVO received MT (mean age 64±15 years, 50% men, median baseline National Institutes of Health Stroke Scale score 16 points (IQR 11-20), 69% pretreated with IVT). The incidence of INT was lower in patients treated with combination therapy (IVTandMT) than in patients treated with MT alone, respectively (10% vs 20%; p=0.011). The INT group had more patients with posterior circulation occlusions than the group without INT (28% vs 10%, respectively; p<0.001). The rates of 3-month functional independence were lower in patients with INT (30% vs 50%; p=0.007). IVT pretreatment was not independently related to INT (OR=0.75; 95% CI 0.32 to 1.76), and INT did not emerge as an independent predictor of 3-month functional independence (OR=0.69; 95% CI 0.29 to 1.62) on multivariable logistic regression models. Location of posterior circulation occlusion was independently associated with a higher odds of INT (OR=3.33; 95% CI 1.43 to 7.69; p=0.005). CONCLUSIONS: IVT pretreatment is not independently associated with a lower likelihood of INT in patients with ELVO treated with MT. Patients with ELVO with posterior circulation occlusion are more likely to have INT after MT.

Performance of 18F-FDG, 11C-Methionine, and 18F-FET PET for Glioma Grading: A Meta-analysis.

PURPOSE: Gliomas constitute the most frequent primary brain tumors. Glioblastoma, the most common and malignant glioma in adults, has dismal prognosis with any current therapy. On the other hand, low-grade gliomas, the second most common type of gliomas, are potentially curative with appropriate treatment. METHODS: We conducted a meta-analysis to assess the performance of PET tracers with the best available evidence, namely, fluorodeoxyglucose (FDG), C-methionine (MET), and F-fluoroethyltyrosine (FET), in differentiating low- from high-grade gliomas. RESULTS: Twenty-three studies with a total of 994 participants were included in this meta-analysis. The pooled sensitivities of both MET PET and FET PET were found to be significantly higher than of FDG PET (94%, 88%, and 63% respectively, P < 0.001). The pooled specificity of FDG PET was found to be significantly greater compared with both MET PET and FET PET (89%, 55%, and 57%, respectively; P = 0.002). Fluorodeoxyglucose PET was superior in terms of higher positive likelihood ratio values compared with both FET PET and MET PET. CONCLUSIONS: This meta-analysis indicated that both MET and FET were superior to FDG in terms of sensitivity for identifying glioma grade.

Impact of pretreatment with intravenous thrombolysis on reperfusion status in acute strokes treated with mechanical thrombectomy.

INTRODUCTION: We sought to evaluate the impact of pretreatment with intravenous thrombolysis (IVT) on the rate and speed of successful reperfusion (SR) in patients with emergent large vessel occlusion (ELVO) treated with mechanical thrombectomy (MT) in a high-volume tertiary care stroke center. METHODS: Consecutive patients with ELVO treated with MT were evaluated. Outcomes were compared between patients who underwent combined IVT and MT (IVT+MT) and those treated with direct MT (dMT). The elapsed time between groin puncture to beginning of reperfusion (GPTBRT) and the numbers of device passes required to achieve SR were also documented. RESULTS: A total of 287 and 132 patients were treated with IVT+MT and dMT, respectively. The IVT+MT group had higher SR (73.8% vs 62.9%; p=0.023) and 3-month functional independence (modified Rankin Scale score 0-2;51.6% vs 38.2%; p=0.008) rates. The median GPTBRT was shorter in the IVT+MT group (48 (IQR 33-70) vs 70 (IQR 44-98) min; p<0.001). Among patients who achieved SR (n=292), the median number of required device passes was lower in the IVT+MT subgroup (1 (IQR 1-1) vs 2 (IQR 1-2); p<0.001), while the rate of patients requiring ≤2 device passes was higher (98% vs 77%; p<0.001). IVT+MT was independently related to higher odds of SR (OR 1.64; 95% CI 1.03 to 2.61; p=0.036) and shorter GPTBRT (unstandardized linear regression coefficient -20.39; 95% CI -27.56 to -13.22; p<0.001) on multivariable analyses adjusting for potential confounders. Among patients with SR, IVT+MT was independently associated with a higher likelihood of ≤2 device passes (OR 14.63; 95% CI 4.46 to 48.00; p<0.001). CONCLUSIONS: IVT pretreatment appears to increase the rates of SR and shortens the duration of the endovascular procedure by requiring fewer device passes in patients with ELVO treated with MT.

Minimally invasive endoscopic hematoma evacuation vs best medical management for spontaneous basal-ganglia intracerebral hemorrhage.

BACKGROUND: We conducted a case-control study to assess the relative safety and efficacy of minimally invasive endoscopic surgery (MIS) for clot evacuation in patients with basal-ganglia intracerebral hemorrhage (ICH). METHODS: We evaluated consecutive patients with acute basal-ganglia ICH at a single center over a 42-month period. Patients received either best medical management according to established guidelines (controls) or MIS (cases). The following outcomes were compared before and after propensity-score matching (PSM): in-hospital mortality; discharge National Institutes of Health Stroke Scale score; discharge disposition; and modified Rankin Scale scores at discharge and at 3 months. RESULTS: Among 224 ICH patients, 19 (8.5%) underwent MIS (mean age, 50.9±10.9; 26.3% female, median ICH volume, 40 (IQR, 25-51)). The interventional cohort was younger with higher ICH volume and stroke severity compared with the medically managed cohort. After PSM, 18 MIS patients were matched to 54 medically managed individuals. The two cohorts did not differ in any of the baseline characteristics. The median ICH volume at 24 hours was lower in the intervention group (40 cm3 (IQR, 25-50) vs 15 cm3 (IQR, 5-20); P<0.001). The two cohorts did not differ in any of the pre-specified outcomes measures except for in-hospital mortality, which was lower in the interventional cohort (28% vs 56%; P=0.041). CONCLUSIONS: Minimally invasive endoscopic hematoma evacuation was associated with lower rates of in-hospital mortality in patients with spontaneous basal-ganglia ICH. These findings support a randomized controlled trial of MIS versus medical management for ICH.

Skull Base Metastasis Revealed by Bone Scintigraphy in a Patient With Hypoglossal Nerve Palsy.

Even though different imaging modalities are available in sole or in combination for the optimal detection of bone metastases, whole-body bone scintigraphy (BS) in a single session seems to be advantageous. We present an 80-year-old male with unilateral left hypoglossal nerve palsy (HNP) and no other focal deficits on neurological examination. Initial brain computed tomography (CT) scan revealed no pathological findings, while the subsequent cranial CT and magnetic resonance imaging (MRI) scans uncovered only mild nonspecific sclerotic lesions in left occipital condyle. All laboratory examinations were within normal limits, except for an elevated alkaline phosphatase (170 U/L) and a markedly increased prostate-specific antigen (609 ng/mL). The patient underwent whole-body BS with technetium-99m that revealed increased radiotracer deposition compatible with metastases in multiple foci, including the left occipital condyle. Prostate biopsy confirmed the diagnosis of prostate adenocarcinoma. Our case suggests that a complete and thorough workup for hidden malignancies should be performed in all patients with HNP, even in the absence of a finding in brain neuroimaging. Bone scintigraphy is an essential investigation that should be considered in uncertain cases of HNP, and especially in those with negative CT and MRI scans.

Quantification of sweat gland innervation in patients with Fabry disease: A case-control study.

INTRODUCTION: Hypohidrosis and heat intolerance, frequently reported by men and women with Fabry disease (FD), is thought to be related not only to the deposition of globotriaosylceramide (Gb3) in eccrine sweat glands, but also to reduced sweat gland sympathetic innervation. METHODS: We performed a case-control study to compare the density of sweat gland innervation between patients with FD and healthy controls by examining lower leg skin punch biopsies. We used a standardized grid of circles superimposed upon the immunofluorescent specimen to create a simple pattern of circles over the sweat gland. Nerve fibers that crossed within the circles were manually counted ("crossed circles"). Nerve fibers that touched the edge of the circle but did not enter were spared ("uncrossed circles"). The percentage of crossed circles from all circles was determined. RESULTS: Biopsy specimens were available of 37 FD patients (median age 44 years, 19-67; n = 18 men) and 16 controls (median age 48 years, 24-83, n = 7 men). Totally there were 153 sweat glands from FD patients and 63 from controls, in which innervation was quantified. While mean sweat gland innervation per biopsy did not differ between the entire FD cohort and controls, data stratification for the reported sweating phenotype revealed a stepwise lower innervation in women with FD and hypohidrosis (n.s.) and anhidrosis (p < .05) compared to women reporting normal sweating. CONCLUSION: Sweat gland innervation is reduced in women with FD and anhidrosis compared to female patients without sweating impairment. Loss of sweat gland innervation may play a role in FD associated anhidrosis, at least in women.

Admission hyperglycemia and outcomes in large vessel occlusion strokes treated with mechanical thrombectomy.

BACKGROUND AND PURPOSE: Higher admission serum glucose levels have been associated with poor outcomes in patients with acute ischemic stroke (AIS) treated with IV thrombolysis. We sought to evaluate the association of admission serum glucose with early outcomes of patients with emergent large vessel occlusion (ELVO) treated with mechanical thrombectomy (MT). METHODS: Consecutive AIS patients due to ELVO treated with MT in three tertiary stroke centers were evaluated. The following outcomes were documented using standard definitions: symptomatic intracranial hemorrhage (sICH), complete reperfusion, mortality, functional independence (modified Rankin Scale (mRS) score of 0-2), and functional improvement (shift in mRS score) at 3 months. The association of admission serum glucose and admission hyperglycemia (>140 mg/dL) with outcomes was evaluated using univariable and multivariable binary and ordinal logistic regression models. RESULTS: 231 AIS patients with ELVO (mean age 62±14 years, 51% men, median admission National Institute of Health Stroke Scale score 16 points (IQR 12-21), median admission serum glucose 125 mg/dL (IQR 104-162)) were treated with MT. Admission hyperglycemia was associated with a lower likelihood of functional improvement (common OR 0.53; 95% CI 0.31 to 0.97; p=0.027) and higher odds of 3 month mortality (OR 2.76; 95% CI 1.40 to 5.44; p=0.004) in multivariable analyses adjusting for potential confounders. A 10 mg/dL increase in admission blood glucose was associated with a higher likelihood of sICH (OR 1.07; 95% CI 1.01 to 1.13; p=0.033) and 3 month mortality (OR 1.07; 95% CI 1.02 to 1.12; p=0.004) in multivariable models. There was no association between admission serum glucose or hyperglycemia and complete reperfusion. CONCLUSIONS: Higher admission serum glucose and admission hyperglycemia are independent predictors of adverse outcomes in ELVO patients treated with MT.

The value of transesophageal echocardiography in the investigation and management of cryptogenic cerebral ischemia: a single-center experience.

The diagnostic utility of transesophageal echocardiography (TEE) has often been challenged in patients with cryptogenic stroke (CS). We estimated the prevalence of different findings on TEE examination of CS patients, their impact on secondary stroke prevention and the presence of potential age or gender disparities. We reviewed all TEE examinations that were performed in a single echocardiography laboratory during a 7-year-old period to identify CS patients that underwent investigation with TEE. Of the 518 total TEE examinations, we identified 88 CS patients. TEE revealed abnormal findings in 69.3 % of them. Patent foramen ovale (PFO) and atrial septal aneurysm (ASA) were identified in 30.6 and 22.7 % of the patients. Ascending aorta and aortic arch atheromatosis was present in 26.1 % of the patients, with complex atheromatosis diagnosed in 14.7 % of them. Cardiac myxomas were uncovered in 2.3 %. Thrombi in the left atrium and in cardiac valves were reported in 3.4 and 2.3 % of the patients, respectively. Based on TEE findings, the therapeutic management would be very likely modified in 9.1 % of the patients. Subgroup analysis revealed no gender disparities on the prevalence of TEE findings and in secondary stroke prevention, while linear regression analyses revealed significant associations of age with the prevalence of PFO, ASA, aorta atheromatosis and complex aorta atheromatosis. TEE examination should be included in the diagnostic work-up of all CS patients, irrespective of age and gender status, since it can reveal potential sources of embolism and has a significant impact for secondary stroke prevention.

Inflammatory bowel disease and demyelination: more than just a coincidence?

Infliximab and other anti-TNF-α agents have been implicated for drug-induced demyelination in patients with inflammatory bowel diseases (IBDs). We evaluated existing data from MEDLINE and EMBASE and conducted a narrative review to investigate further the aforementioned association. Our literature search highlighted 34 case reports, 3 case-control studies, 1 prospective and 7 retrospective cohort studies published in English. Available data suggest that IBD patients can manifest demyelinating events in both central and peripheral nervous system, however, they are still insufficient to conclude whether anti-TNF-α therapies are an independent risk factor for demyelination. Prospective cohort studies with internal control groups are needed to estimate the true incidence of demyelinating disorders in patients with IBD and to elucidate if anti-TNF-α therapy increases further the risk of demyelination.

The role of remote ischemic preconditioning in the treatment of atherosclerotic diseases.

BACKGROUND: Remote ischemic preconditioning (RIPC) is the application of a transient and brief ischemic stimulus to a distant site from the organ or tissue that is afterward exposed to injury ischemia, and has been found to reduce ischemia-reperfusion injury (IRI) in various animal models. RIPC appears to offer two distinct phases of endothelial IRI protection, which are presumably mediated through neuronal and humoral pathways. METHODS: We conducted a comprehensive literature review on the available published data about the potential effect of RIPC in patients undergoing IRI in one or more vital organs. RESULTS: Our search highlighted 24 randomized clinical trials about the effect of RIPC on variable clinical settings (abdominal aortic aneurysm repair, open heart surgery, percutaneous coronary intervention, living donor renal transplantation, coronary angiography, elective decompression surgery, carotid endarterectomy, recent stroke, or transient ischemic attack combined with intracranial carotid artery stenosis). Most of the trials focused on postoperative cardiac or renal function after RIPC with conflicting results. Preconditioning protocols, age limits, comorbidities, and concomitant drug use varied significantly across trials, and therefore no firm conclusions can be drawn using the available data. However, no severe local adverse events were observed in any patient undergoing limb or arm preconditioning. CONCLUSIONS: RIPC is a safe and well-tolerated procedure that may constitute a potentially promising innovative treatment in atherosclerotic diseases. Large, multicenter, randomized clinical trials are required to determine an optimal protocol for the RIPC procedure, and to evaluate further the potential benefits of RIPC in human ischemic injury.

Electrocardiographic abnormalities and cardiac arrhythmias in structural brain lesions.

Cardiac arrhythmias and electrocardiographic abnormalities are frequently observed after acute cerebrovascular events. The precise mechanism that leads to the development of these arrhythmias is still uncertain, though increasing evidence suggests that it is mainly due to autonomic nervous system dysregulation. In massive brain lesions sympathetic predominance and parasympathetic withdrawal during the first 72 h are associated with the occurrence of severe secondary complications in the first week. Right insular cortex lesions are also related with sympathetic overactivation and with a higher incidence of electrocardiographic abnormalities, mostly QT prolongation, in patients with ischemic stroke. Additionally, female sex and hypokalemia are independent risk factors for severe prolongation of the QT interval which subsequently results in malignant arrhythmias and poor outcome. The prognostic value of repolarization changes commonly seen after aneurysmal subarachnoid hemorrhage, such as ST segment, T wave, and U wave abnormalities, still remains controversial. In patients with traumatic brain injury both intracranial hypertension and cerebral hypoperfusion correlate with low heart rate variability and increased mortality. Given that there are no firm guidelines for the prevention or treatment of the arrhythmias that appear after cerebral incidents this review aims to highlight important issues on this topic. Selected patients with the aforementioned risk factors could benefit from electrocardiographic monitoring, reassessment of the medications that prolong QTc interval, and administration of antiadrenergic agents. Further research is required in order to validate these assumptions and to establish specific therapeutic strategies.