Effect of Statin Therapy on Cardiovascular Outcome in Stroke Patients with Low Baseline Low-Density Lipoprotein Cholesterol.

OBJECTIVES: To investigate whether post-stroke statin therapy reduces subsequent major vascular events in statin-naïve patients with pretreatment low-density lipoprotein cholesterol (LDL-C) below the recommended target (≤70 mg/dL for atherosclerotic stroke and ≤100 mg/dL for non-atherosclerotic stroke) at stroke onset. METHODS: Patients from an ongoing stroke registry who had an ischemic stroke between 2011 and 2020 were screened. Statin naïve patients with baseline LDL-C below the target were assessed. The effect of post-stroke statin therapy on major vascular events (composite of recurrent stroke, myocardial infarction, and death) was investigated using weighted Cox regression analyses using stabilized inverse probability treatment weighting. RESULTS: The baseline LDL-C level of the 1,858 patients (mean age 67.9 ± 15.3 years, 61.4% men, 13.2% atherosclerotic stroke) included in the study was 75.7 ± 17.0 mg/dL. Statins were prescribed to 1,256 (67.7%) patients (low-to-moderate intensity, 23.5%; high intensity, 44.1%). Post-stroke statin therapy was associated with a lower risk of major vascular events during 1-year follow-up (weighted hazard ratio 0.55, 95% confidence interval 0.42-0.71). In a subgroup of patients who were at very high risk of atherosclerotic cardiovascular disease with LDL-C <55 mg/dL or patients who were not at very high risk of atherosclerotic cardiovascular disease with LDL-C <70 mg/dL, post-stroke statin therapy was also associated with a reduction in major vascular events (weighted hazard ratio 0.45, 95% confidence interval 0.29-0.70). The intensity of the most beneficial statin varied by subtype of stroke. INTERPRETATION: Statin therapy may improve vascular outcomes after ischemic stroke, even in cases of LDL-C below the target without pre-stroke lipid-lowering therapy. ANN NEUROL 2024;95:876-885.

Covert Brain Infarction as a Risk Factor for Stroke Recurrence in Patients With Atrial Fibrillation.

BACKGROUND: We aimed to evaluate covert brain infarction (CBI), frequently encountered during the diagnostic work-up of acute ischemic stroke, as a risk factor for stroke recurrence in patients with atrial fibrillation (AF). METHODS: For this prospective cohort study, from patients with acute ischemic stroke hospitalized at 14 centers between 2017 and 2019, we enrolled AF patients without history of stroke or transient ischemic attack and divided them into the CBI (+) and CBI (-) groups. The 2 groups were compared regarding the 1-year cumulative incidence of recurrent ischemic stroke and all-cause mortality using the Fine and Gray subdistribution hazard model with nonstroke death as a competing risk and the Cox frailty model, respectively. Each CBI lesion was also categorized into either embolic-appearing (EA) or non-EA pattern CBI. Adjusted hazard ratios and 95% CIs of any CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were estimated. RESULTS: Among 1383 first-ever stroke patients with AF, 578 patients (41.8%) had CBI. Of these 578 with CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were 61.8% (n=357), 21.8% (n=126), and 16.4% (n=95), respectively. The estimated 1-year cumulative incidence of recurrent ischemic stroke was 5.2% and 1.9% in the CBI (+) and CBI (-) groups, respectively (P=0.001 by Gray test). CBI increased the risk of recurrent ischemic stroke (adjusted hazard ratio [95% CI], 2.91 [1.44-5.88]) but did not the risk of all-cause mortality (1.32 [0.97-1.80]). The EA pattern CBI only and both CBIs elevated the risk of recurrent ischemic stroke (2.76 [1.32-5.77] and 5.39 [2.25-12.91], respectively), while the non-EA pattern only did not (1.44 [0.40-5.16]). CONCLUSIONS: Our study suggests that AF patients with CBI might have increased risk of recurrent stroke. CBI could be considered when estimating the stroke risk in patients with AF.

Pharmacological inhibition of STriatal-Enriched protein tyrosine Phosphatase by TC-2153 reduces hippocampal excitability and seizure propensity.

OBJECTIVE: STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific tyrosine phosphatase. Membrane-bound STEP61 is the only isoform expressed in hippocampus and cortex. Genetic deletion of STEP enhances excitatory synaptic currents and long-term potentiation in the hippocampus. However, whether STEP61 affects seizure susceptibility is unclear. Here we investigated the effects of STEP inhibitor TC-2153 on seizure propensity in a murine model displaying kainic acid (KA)-induced status epilepticus and its effect on hippocampal excitability. METHODS: Adult male and female C57BL/6J mice received intraperitoneal injection of either vehicle (2.8% dimethylsulfoxide [DMSO] in saline) or TC-2153 (10 mg/kg) and then either saline or KA (30 mg/kg) 3 h later before being monitored for behavioral seizures. A subset of female mice was ovariectomized (OVX). Acute hippocampal slices from Thy1-GCaMP6s mice were treated with either DMSO or TC-2153 (10 µM) for 1 h, and then incubated in artificial cerebrospinal fluid (ACSF) and potassium chloride (15 mM) for 2 min prior to live calcium imaging. Pyramidal neurons in dissociated rat hippocampal culture (DIV 8-10) were pre-treated with DMSO or TC-2153 (10 µM) for 1 h before whole-cell patch-clamp recording. RESULTS: TC-2153 treatment significantly reduced KA-induced seizure severity, with greater trend seen in female mice. OVX abolished this TC-2153-induced decrease in seizure severity in female mice. TC-2153 application significantly decreased overall excitability of acute hippocampal slices from both sexes. Surprisingly, TC-2153 treatment hyperpolarized resting membrane potential and decreased firing rate, sag voltage, and hyperpolarization-induced current (Ih ) of cultured hippocampal pyramidal neurons. SIGNIFICANCE: This study is the first to demonstrate that pharmacological inhibition of STEP with TC-2153 decreases seizure severity and hippocampal activity in both sexes, and dampens hippocampal neuronal excitability and Ih . We propose that the antiseizure effects of TC-2153 are mediated by its unexpected action on suppressing neuronal intrinsic excitability.

Risk Factors for Intravenous Propacetamol-Induced Blood Pressure Drop in the Neurointensive Care Unit: A Retrospective Observational Study.

BACKGROUND: Intravenous propacetamol is commonly used to control fever and pain in neurocritically ill patients in whom oral administration is often difficult. However, several studies reported that intravenous propacetamol may cause blood pressure drop. Thus, we aimed to investigate the occurrence and risk factors for intravenous propacetamol-induced blood pressure drop in neurocritically ill patients. METHODS: This retrospective study included consecutive patients who were administered intravenous propacetamol in a neurointensive care unit at a single tertiary academic hospital between April 2013 and June 2020. The exact timing of intravenous propacetamol administration was collected from a database of the electronic barcode medication administration system. Blood pressure drop was defined as a systolic blood pressure below 90 mm Hg or a decrease by 30 mm Hg or more. Blood pressure, pulse rate, and body temperature were collected at baseline and within 2 h after intravenous propacetamol administration. The incidence of blood pressure drop was evaluated, and multivariable logistic regression analysis was performed to identify risk factors for blood pressure drop events. RESULTS: A total of 16,586 instances of intravenous propacetamol administration in 4916 patients were eligible for this study. Intravenous propacetamol resulted in a significant decrease in systolic blood pressure (baseline 131.1 ± 17.8 mm Hg; within 1 h 124.6 ± 17.3 mm Hg; between 1 and 2 h 123.4 ± 17.4 mm Hg; P < 0.01). The incidence of blood pressure drop events was 13.5% within 2 h after intravenous propacetamol. Older age, lower or higher baseline systolic blood pressure, fever, higher Acute Physiology and Chronic Health Evaluation II score, and concomitant administration of vasopressors/inotropes or analgesics/sedatives were significant factors associated with the occurrence of blood pressure drop events after intravenous propacetamol administration. CONCLUSIONS: Intravenous propacetamol can induce hemodynamic changes and blood pressure drop events in neurocritically ill patients. This study identified the risk factors for blood pressure drop events. On the basis of our results, judicious use of intravenous propacetamol is warranted for neurocritically ill patients with risk factors that make them more susceptible to hemodynamic changes.

Size-Related Differences in Computed Tomography Markers of Hematoma Expansion in Acute Intracerebral Hemorrhage.

BACKGROUND: Noncontrast computed tomography (NCCT) markers for hematoma expansion (HE) in intracerebral hemorrhage (ICH) are difficult to be found in small ICHs, of which can also expand. We aimed to investigate whether there were size-related differences in the prevalence of NCCT markers and their association with HE. METHODS: This retrospective analysis of prospectively collected stroke registry included 267 consecutive patients with ICH who underwent baseline NCCT within 12 h of onset. Qualitative NCCT markers, including heterogeneous density and irregular shape, were assessed. Hematoma density, defined as mean Hounsfield unit of hematoma, and hematoma volume were measured by semiautomated planimetry. Hematoma volume was categorized as small (≤ 10 ml) and large (> 10 ml). Associations of NCCT markers with HE were analyzed using multivariable logistic regression analyses. The model performances of NCCT markers and hematoma density were compared using receiver operating characteristic curves. RESULTS: Hematoma expansion occurred in 29.9% of small ICHs and 35.5% of large ICHs. Qualitative NCCT markers were less frequently observed in small ICHs. Heterogeneous density, irregular shape, and hematoma density were associated with HE in small ICH (adjusted odds ratios [95% confidence interval] 3.94 [1.50-10.81], 4.23 [1.73-10.81], and 0.72 [0.60-0.84], respectively), and hematoma density was also related to HE in large ICH (0.84 [0.73-0.97). The model performance was significantly improved in small ICHs when hematoma density was added to the baseline model (DeLong's test, p = 0.02). CONCLUSIONS: The prevalence of NCCT markers and their association with HE differed according to hematoma volume. Quantitative hematoma density was associated with HE, regardless of hematoma size.

Therapeutic Temperature Modulation for a Critically Ill Patient with COVID-19.

We report a rapidly deteriorating coronavirus disease 2019 (COVID-19) patient, a-58-year-old woman, with severe acute respiratory distress syndrome and shock with hyperpyrexia up to 41.8°C, probably due to the cytokine storm syndrome. Considering extracorporeal membrane oxygenation (ECMO) as the last resort, we applied therapeutic temperature modulation for management of hyperpyrexia. The patient demonstrated rapid improvement in oxygenation and shock after achieving normothermia, and fully recovered from COVID-19 three weeks later. Therapeutic temperature modulation may have successfully offloaded the failing cardiorespiratory system from metabolic cost and hyperinflammation induced by hyperpyrexia. The therapeutic temperature modulation can safely be applied in a specific group of patients with cytokine storm syndrome and hyperpyrexia, which may reduce the number of patients requiring ECMO in the global medical resource shortage.

Blood Pressure Drop and Penumbral Tissue Loss in Nonrecanalized Emergent Large Vessel Occlusion.

Background and Purpose- For patients with emergent large vessel occlusion who may not benefit from timely recanalization treatment, maintaining adequate cerebral perfusion to prevent penumbral tissue loss is a key therapeutic strategy. Cerebral perfusion should be proportional to systemic blood pressure (BP) due to the loss of autoregulation properties in ischemic brain tissue. We hypothesized that acute fluctuations in BP would lead to aggravated penumbral tissue loss in persistent large vessel occlusion. Methods- A total of 80 patients with persistent large vessel occlusion of internal carotid artery or middle cerebral artery admitted within 24 hours after onset, and with a baseline, National Institutes of Health Stroke Scale score ≥4-point were included. Baseline and follow-up (median 88 hours) magnetic resonance images were analyzed, and penumbra was defined as the Tmax>6 s region excluding baseline infarction. The hypoperfusion intensity ratio (Tmax>10 s/Tmax>6 s) was calculated within the penumbra. Penumbral tissue loss (%) was defined as the proportion of follow-up infarct in the penumbra. With serial BP measurements in the first 24 hours (median 29, interquartile range 26-35), BP and BP variability parameters, including BPdropmax (change from local maxima to minima), were calculated and compared. Generalized linear models were applied to examine the association between BP parameters and the penumbral tissue loss. Results- The median penumbral volume was 79.3 mL (interquartile range, 38.2-129.6) and median penumbral tissue loss was 36.7% (interquartile range, 12.0-56.1). In a multivariable analysis, systolic BP (SBP) SBPdropmax (ß±SE of fourth quartile, 17.82±6.58; P value, 0.01) and diastolic BP (DBP) DBPdropmax (ß±SE of fourth quartile, 14.04±6.38; P value, 0.01) were associated with increasing penumbral tissue loss, independently of age, baseline infarction and hypoperfusion intensity ratio. DBPincmax, SBPmax, DBPmax, SBPmax-min, DBPmax-min, and most of the DBP variability indices were associated with penumbral tissue loss. Conclusions- BP fluctuations, even a brief and drastic BP drop in the first 24 hours, significantly contributed to penumbral tissue loss irrespective of baseline hypoperfusion.

Evaluation of Diffusion Lesion Volume Measurements in Acute Ischemic Stroke Using Encoder-Decoder Convolutional Network.

Background and Purpose- Automatic segmentation of cerebral infarction on diffusion-weighted imaging (DWI) is typically performed based on a fixed apparent diffusion coefficient (ADC) threshold. Fixed ADC threshold methods may not be accurate because ADC values vary over time after stroke onset. Deep learning has the potential to improve the accuracy, provided that a large set of correctly annotated lesion data is used for training. The purpose of this study was to evaluate deep learning-based methods and compare them with commercial software in terms of lesion volume measurements. Methods- U-net, an encoder-decoder convolutional neural network, was adopted to train segmentation models. Two U-net models were developed: a U-net (DWI+ADC) model, trained on DWI and ADC data, and a U-net (DWI) model, trained on DWI data only. A total of 296 subjects were used for training and 134 for external validation. An expert neurologist manually delineated the stroke lesions on DWI images, which were used as the ground-truth reference. Lesion volume measurements from the U-net methods were compared against the expert's manual segmentation and Rapid Processing of Perfusion and Diffusion (RAPID; iSchemaView Inc) analysis. Results- In external validation, U-net (DWI+ADC) showed the highest intraclass correlation coefficient with manual segmentation (intraclass correlation coefficient, 1.0; 95% CI, 0.99-1.00) and sufficiently high correlation with the RAPID results (intraclass correlation coefficient, 0.99; 95% CI, 0.98-0.99). U-net (DWI+ADC) and manual segmentation resulted in the smallest 95% Bland-Altman limits of agreement (-5.31 to 4.93 mL) with a mean difference of -0.19 mL. Conclusions- The presented deep learning-based method is fully automatic and shows a high correlation of diffusion lesion volume measurements with manual segmentation and commercial software. The method has the potential to be used in patient selection for endovascular reperfusion therapy in the late time window of acute stroke.

Gamma-glutamyl transferase predicts future stroke: A Korean nationwide study.

OBJECTIVE: Although gamma-glutamyl transferase (GGT) is generally regarded as an alternative biomarker for alcohol consumption, its independent role in vascular diseases emerged recently. However, its role in stroke remains unknown. The aim of this study is to clarify the impact of GGT on stroke in a large-sized, national, standardized population cohort in Korea. METHODS: In Korea, the National Health Insurance Service (NHIS) provides full-coverage health insurance service for all citizens. Using data from the NHIS, the NHIS-National Sample Cohort was designed by randomly selecting 2% of Koreans, carefully considering demographic characteristics. We analyzed eligible individuals from this standardized cohort. The Cox proportional hazards model was used for the study investigating the relationship between GGT and stroke. RESULTS: Among the 456,100 eligible participants, 7,459 patients (1.64%) developed stroke as follows: 5,789 ischemic strokes, 1,046 intracerebral hemorrhages (ICHs), and 624 subarachnoid hemorrhages. GGT was independently correlated with increased risk of stroke after adjustment for alcohol consumption and stroke risk factors (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.29-1.51). The risks of both ischemic stroke (HR = 1.45, 95% CI = 1.32-1.58) and ICH (HR = 1.46, 95% CI = 1.18-1.80) were significantly elevated with increasing GGT. Despite some effect modifications by sex, age, and alcohol, the risk of total stroke and ischemic stroke in association with GGT remained significant in all subgroups. INTERPRETATION: In a standard Korean population, GGT was a novel biomarker predicting stroke risk, independently from alcohol consumption and other risk factors. Ann Neurol 2018;83:375-386.

Posttreatment National Institutes of Health Stroke Scale Is Superior to the Initial Score or Thrombolysis in Cerebral Ischemia for 3-Month Outcome.

BACKGROUND AND PURPOSE: The majority of ischemic stroke patients receiving endovascular recanalization therapy (EVT) experience variable changes of neurological severities during the hyperacute period. We hypothesized that the National Institutes of Health Stroke Scale (NIHSS) score after EVT is a better prognostic factor compared with the initial NIHSS score or revascularization status. METHODS: We identified 566 stroke patients who received EVT at Seoul National University Bundang Hospital between April 2008 and December 2015. We prospectively collected post-EVT NIHSS score, which was measured in the angiography suite by on-duty physicians after completion of EVT. Model 1 included baseline predictors including an initial NIHSS score. In model 2, 3, and 4, revascularization status, post-EVT NIHSS score, or both were additionally included. The discrimination powers for modified Rankin Scale score of 0 to 2 at 3 months were assessed using C statistic, integrated discrimination index, and category-free net reclassification index. RESULTS: The median of initial and post-EVT NIHSS score were 14 (9-19) and 11 (5-17) points, respectively (an improvement, 58.8%; no change, 20.7%; deterioration, 20.5%). A modified Rankin Scale score 0 to 2 at 3 months was achieved in 47%. Based on the results of differences among the C statistics, both model 3 and model 4 (C statistics: 0.896 and 0.906) showed significantly increased discrimination power for modified Rankin Scale score 0 to 2 at 3 months than the model 1 or 2 (C statistics: 0.802 and 0.834, P values<0.001 for all comparisons). Model 4 showed significant improvement of both integrated discrimination index and net reclassification index as compared with all other models, but the magnitude of improvement from model 3 to model 4 (integrated discrimination index, 0.021; net reclassification index, 0.322) was modest. CONCLUSIONS: Incorporation of post-EVT NIHSS score conferred better discrimination power to the statistical models for functional recovery. Post-EVT NIHSS score may be an appropriate baseline factor when evaluating an intervention after hyperacute period.

Ceria Nanoparticles Synthesized With Aminocaproic Acid for the Treatment of Subarachnoid Hemorrhage.

Background and Purpose- Despite early aneurysm repair and aggressive management for complications, subarachnoid hemorrhage (SAH) results in at least 25% mortality rate and 50% persistent neurological deficit. We investigated whether ceria nanoparticles which have potent antioxidative activities can protect against subarachnoid hemorrhage via attenuating fatal brain injuries. Methods- Uniform, 3 nm, water-dispersed ceria nanoparticles were prepared from short sol-gel reaction of cerium (III) ions with aminocaproic acid in aqueous phase. SAH was induced by endovascular perforation of middle cerebral artery of rats. A single dose of ceria nanoparticles (0.5 mg Ce/kg) or saline control was randomly administered intravenously at an hour post-SAH. Neuronal death, macrophage infiltration, SAH grade, and brain edema were evaluated at 72 hours. Mortality and neurological function were assessed for 14 days. Results- The obtained ceria nanoparticles with high Ce3+ to Ce4+ ratio demonstrated potent antioxidative, cytoprotective, and anti-inflammatory activities in vitro. In rodent SAH models, the severity of hemorrhage was comparable between the ceria nanoparticles- and saline-treated groups. However, ceria nanoparticles significantly reduced neuronal death, macrophage infiltration, and brain edema after SAH. Ceria nanoparticles successfully improved survival rates (88.2% in the ceria nanoparticles group versus 21.1% in the control group; P<0.001) and neurological outcomes (modified Garcia score: 12.1±0.5 in the ceria nanoparticles group versus 4.4±0.5 in the control group; P<0.001) of the animals with SAH. Conclusions- Ceria nanoparticles, totally synthesized in aqueous phase using aminocaproic acid, demonstrated promising results against SAH via potent antioxidative, neuroprotective and anti-inflammatory activities. Given the obvious limitations of current therapies for SAH, ceria nanoparticles can be a potential therapeutic agent which might result in a paradigm shift in SAH treatment.

Tenacity of Collateral Perfusion in Proximal Cerebral Arterial Occlusions 6-12 h after Onset.

BACKGROUND: Clinical trials have shown that benefits of endovascular recanalization (EVT) for acute ischemic stroke patients with sizable penumbral tissues seems plausible even beyond 6 h after their last seen normal (LSN). Persistency of ischemic penumbra remains unclear in delayed periods. METHODS: From a prospective stroke registry database, we identified 111 acute ischemic stroke patients who had internal carotid artery or middle cerebral artery occlusion with baseline National Institutes of Health Stroke Scale scores ≥6 points and arrived 6-12 h after LSN. Baseline information and functional outcomes were prospectively collected as a clinical registry. Attending physicians made treatment decisions for EVT based on the current guidelines and institutional protocols. MR image parameters, including the volume of diffusion-restricted lesions and mapping of the -hypoperfused area, were quantified using automated commercial software. Binary logistic regression analysis models, with modified Rankin Scale (mRS) scores of 0-1 at 3 months after stroke included as a dependent variable, were constructed. RESULTS: Between 6 and 12 h after onset, 58% had a mismatch ratio of ≥1.8 at baseline and 42% had favorable imaging profiles as determined by DEFUSE 2 study. After 9 h, there was a mismatch ratio of ≥1.8 in 47 and 38% favorable profiles. EVT was performed in 54% of cases. A 3-month mRS score of 0-1 was found in 19% (25% in EVT and 12% in medical treatment groups) of cases. EVT was associated with an increased OR of having a mRS score of 0-1 at 3 months after stroke (adjusted OR 7.59 [95% CI 1.28-61.60]). CONCLUSIONS: Penumbral tissues were persistent in a substantial proportion of anterior circulation occlusion cases 6-12 h after LSN. EVT at 6-12 h in a predominantly Asian cohort resulted in better outcomes.

Prediction of Stroke Subtype and Recanalization Using Susceptibility Vessel Sign on Susceptibility-Weighted Magnetic Resonance Imaging.

BACKGROUND AND PURPOSE: The susceptibility vessel sign (SVS) is a hypointense signal visualized because of the susceptibility effect of thrombi, sensitively detected on susceptibility-weighted magnetic resonance imaging. The relationship of SVS parameters with the stroke subtype and recanalization status after endovascular treatment remains uncertain. METHODS: The data from 89 patients with acute stroke caused by anterior circulation infarcts who underwent susceptibility-weighted magnetic resonance imaging before endovascular treatment were examined. Independent reviewers, blinded to the stroke subtype and recanalization status, measured the SVS diameter, length, and estimated volume. The intra- and interrater agreements of the SVS parameters were assessed. RESULTS: The SVS was identified in 78% of the patients. SVS was more commonly associated with cardioembolism than with noncardioembolism (P=0.01). The SVS diameter (P<0.01) and length (P=0.01) were larger in the cardioembolism group. The SVS diameter was larger in the recanalization group (thrombolysis in cerebral infarction ≥2b) than in the nonrecanalization group (P=0.04). Multivariable analysis revealed that the SVS diameter was an independent predictor of cardioembolism (adjusted odds ratio, 1.97; 95% confidence interval, 1.34-2.90; P<0.01). There was no significant association between the SVS volume and the recanalization status (adjusted odds ratio, 1.003; 95% confidence interval, 0.999-1.006; P=0.12). The optimal cutoff value of the SVS diameter for the cardioembolism was 5.5 mm (sensitivity, 45.6%; specificity, 93.8%). CONCLUSIONS: Increased SVS diameter on susceptibility-weighted magnetic resonance imaging may predict cardioembolism. No clear association was found between SVS volume and endovascular recanalization.

Ceria-Zirconia Nanoparticles as an Enhanced Multi-Antioxidant for Sepsis Treatment.

The two oxidation states of ceria nanoparticles, Ce3+ and Ce4+ , play a pivotal role in scavenging reactive oxygen species (ROS). In particular, Ce3+ is largely responsible for removing O2- and . OH that are associated with inflammatory response and cell death. The synthesis is reported of 2 nm ceria-zirconia nanoparticles (CZ NPs) that possess a higher Ce3+ /Ce4+ ratio and faster conversion from Ce4+ to Ce3+ than those exhibited by ceria nanoparticles. The obtained Ce0.7 Zr0.3 O2 (7CZ) NPs greatly improve ROS scavenging performance, thus regulating inflammatory cells in a very low dose. Moreover, 7CZ NPs are demonstrated to be effective in reducing mortality and systemic inflammation in two representative sepsis models. These findings suggest that 7CZ NPs have the potential as a therapeutic nanomedicine for treating ROS-related inflammatory diseases.

Nocturnal Desaturation in the Stroke Unit Is Associated With Wake-Up Ischemic Stroke.

BACKGROUND AND PURPOSE: Wake-up stroke (WUS) represents a quarter of all ischemic strokes and may be a specific subgroup. Nocturnal desaturation secondary to sleep-disordered breathing is an independent risk factor for stroke, but the association between nocturnal desaturation and WUS remains unclear. We investigated the relationship between nocturnal desaturation using oxygen desaturation index and WUS in patients with acute stroke in the stroke unit. METHODS: A total of 298 patients admitted for acute ischemic stroke to the stroke unit between July 2013 and May 2015 were enrolled. The oxygen desaturation index was calculated using pulse oximetry data sampled every 1 minute during 9 hours on the first night (10:00 pm-7:00 am) of the stroke unit admission, and nocturnal desaturation was defined as an oxygen desaturation index of 5 at least per hour. We compared the clinical characteristics and nocturnal desaturations between patients with and without WUS. RESULTS: Among all patients (age, 67.7±12.6 years; male, 54.4%), 26.5% patients had WUS. The proportion of nocturnal desaturation was significantly greater in patients admitted with WUS (29.1% versus 12.3%, P=0.001). The age, sex, risk factors except for hyperlipidemia, stroke severity, and stroke mechanisms were similar between the 2 groups. After adjustment for covariates, it was found that nocturnal desaturation was significantly more common in the WUS group (odds ratio, 3.25; 95% confidence interval, 1.63-6.46). CONCLUSIONS: Nocturnal desaturation was more frequently observed in patients admitted with WUS during the first night in the stroke unit. This suggests that nocturnal desaturation is a possible modifiable risk factor for the occurrence of WUS.

Visceral Fat Is an Independent Predictor of Cerebral Microbleeds in Neurologically Healthy People.

BACKGROUND: Obesity has a significant contribution to the risk of intracerebral hemorrhage (ICH). However, little is known about the association between central obesity and the presence of cerebral microbleeds (CMBs), a precursor of ICH. We sought to assess whether visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are associated with the presence of CMB. METHODS: We conducted a cross-sectional study of 1,737 neurologically healthy people (mean age 55.9 ± 9.1; 790 men), who underwent brain MRI and abdominal CT. Risk factors, anthropometric parameters and clinical information were obtained. CMBs were evaluated through T2*-weighted gradient-recalled echo MRI. The cross-sectional surface areas of the abdominal fat compartments were calculated. Study subjects were stratified into quartiles according to the distribution of VAT/SAT ratio. RESULTS: A total of 75 (4.3%) subjects were found to have CMBs. Subjects with a greater quartile of VAT/SAT ratio were more likely to have higher numbers of CMBs (0 to ≥2; p = 0.001). In multivariable analysis, age and history of hypertension were associated with the presence of CMB (OR 1.09, 95% CI 1.06-1.13, p < 0.001; OR 1.70, 95% CI 1.01-2.84, p = 0.046, respectively). A dose-response relationship was observed between the extent of VAT/SAT quartile and CMB: compared to the lowest VAT/SAT quartile, OR 2.14 (95% CI 0.86-5.35) for second VAT/SAT quartile; OR 2.26 (95% CI 0.86-5.92) for third VAT/SAT quartile; and OR 2.91 (95% CI 1.04-8.12) for the highest VAT/SAT quartile (p for trend 0.03). CONCLUSION: In our study, higher VAT/SAT ratios were found to be independent predictors of CMBs in neurologically healthy people. This finding strengthens previous data, suggesting that visceral fat distribution is an important contributor to cerebral small vessel disease.

Neuroimaging markers for early neurologic deterioration in single small subcortical infarction.

BACKGROUND AND PURPOSE: Early neurological deterioration (END) occurs in ≥20% of single small subcortical infarctions (SSSIs; axial diameter ≤20 mm in the perforator territories) and deters functional recovery. Both microvasculopathies and atherosclerosis have been proposed to independently contribute to the occurrence of END in SSSI cases. We hypothesized that the occurrence of END in SSSIs differs according to the pathological process. METHODS: We collected data from 587 patients with SSSI within 48 hours of onset from a prospective stroke registry containing 4961 case records. Independent reviewers, blinded to END information, rated neuroimaging characteristics, including relevant artery stenosis (0% to 50% stenosis of the adjacent arteries on magnetic resonance angiography), branch atheromatous lesions (≥4 consecutive axial cuts or extensions from the basal surface of the pons), white matter hyperintensities, old lacunar infarctions, and cerebral microbleeds. RESULTS: END occurred in 79 (13.5%) cases, including 6 recurrences, 68 progressions, 1 symptomatic hemorrhagic transformation, 1 others, and 3 unknowns. END increased the National Institutes of Health Stroke Scale score by 2.3±1.4 points. Patients with END showed higher frequencies of modified Rankin Scale scores of 3 to 6 after 3 months compared with patients without END (49% versus 23%). Patients with relevant artery stenosis (adjusted odds ratio, 1.91; 95% confidence interval, 1.13-3.21) and branch atheromatous lesions (adjusted odds ratio, 2.98; 95% confidence interval, 1.80-4.93) had significantly higher odds of exhibiting END. However, such an association was not detected with small vessel disease markers. CONCLUSIONS: Our analysis indicated a potential contribution of the localized atherosclerotic process to END in SSSIs. Precautionary measures might be used for SSSIs suggestive of atherosclerotic pathologies.

Tricuspid regurgitation: a hidden risk factor for atrial fibrillation related stroke?

Background and purpose: Tricuspid regurgitation (TR) is a common but overlooked valvular disease, and its association with the etiologic subtypes of ischemic stroke is unclear. We explored the relationship between TR and atrial fibrillation (AF) in patients with acute ischemic stroke. Methods: This retrospective analysis of ongoing stroke registry assessed 6,886 consecutive acute ischemic stroke patients who underwent transthoracic echocardiography during their in-hospital care. Multivariable logistic regression models adjusted for age, sex, stroke characteristics, and echocardiographic indices were used to investigate the association between TR and total AF, and newly diagnosed AF during hospitalization and a 1-year follow-up period, respectively. Results: TR was present in 877 (12.7%) patients (mild, 9.9%; moderate, 2.4%; severe, 0.5%). AF was identified in 24.1% (medical history, 11.1%; first detected in the emergency room, 6.6%; newly diagnosed after admission, 6.4%). TR was associated with AF [adjusted odds ratio (aOR) 4.87 (95% confidence interval (CI), 2.63-9.03)], compared with no/trivial TR. The association between TR and AF was consistent regardless of severity (aOR [95% CI], 4.57 [2.63-7.94] for mild and 7.05 [2.57-19.31] for moderate-to-severe TR) or subtype of TR (5.44 [2.91-10.14] for isolated and 3.81 [2.00-7.28] for non-isolated TR). Among the AF-naïve patients at admission, TR was associated with newly diagnosed AF during hospitalization and a 1-year follow-up period (aOR [95% CI], 2.68 [1.81-3.97]). Conclusions: TR is associated with AF in acute ischemic stroke patients regardless of severity and subtypes of TR. TR is also associated with newly diagnosed AF after stroke.

Long-term outcomes and quantitative radiologic analysis of extracranial-intracranial bypass for hemodynamically compromised chronic large artery occlusive disease.

This study aimed to demonstrate the effectiveness of nonemergent extracranial-to-intracranial bypass (EIB) in symptomatic chronic large artery atherosclerotic stenosis or occlusive disease (LAA) through quantitative analysis of computed tomography perfusion (CTP) parameters using RAPID software. We retrospectively analyzed 86 patients who underwent nonemergent EIB due to symptomatic chronic LAA. CTP data obtained preoperatively, immediately postoperatively (PostOp0), and 6 months postoperatively (PostOp6M) after EIB were quantitatively analyzed through RAPID software, and their association with intraoperative bypass flow (BF) was assessed. The clinical outcomes, including neurologic state, incidence of recurrent infarction and complications, were also analyzed. The time-to-maximum (Tmax) > 8 s, > 6 s and > 4 s volumes decreased significantly at PostOp0 and up through PostOp6M (preoperative, 5, 51, and 223 ml (median), respectively; PostOp0, 0, 20.25, and 143 ml, respectively; PostOp6M, 0, 7.5, and 148.5 ml, respectively; p < 0.001, p < 0.001, and p < 0.001, respectively). The postoperative improvement in the Tmax > 6 s and > 4 s volumes was significantly correlated with the BF at PostOp0 and PostOp6M (PostOp0, r = 0.367 (p = 0.001) and r = 0.275 (p = 0.015), respectively; PostOp6M r = 0.511 (p < 0.001) and r = 0.391 (p = 0.001), respectively). The incidence of recurrent cerebral infarction was 4.7%, and there were no major complications that produced permanent neurological impairment. Nonemergent EIB under strict operation indications can be a feasible treatment for symptomatic, hemodynamically compromised LAA patients.

Automated deep neural network analysis of lateral cephalogram data can aid in detecting obstructive sleep apnea.

STUDY OBJECTIVES: Information on obstructive sleep apnea (OSA) is often latently detected in diagnostic tests conducted for other purposes, providing opportunities for maximizing value. This study aimed to develop a convolutional neural network (CNN) to identify the risk of OSA using lateral cephalograms. METHODS: The lateral cephalograms of 5,648 individuals (mean age, 49.0 ± 15.8 years; men, 62.3%) with or without OSA were collected and divided into training, validation, and internal test datasets in a 5:2:3 ratio. A separate external test dataset (n = 378) was used. A densely connected CNN was trained to diagnose OSA using a cephalogram. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC). Gradient-weighted class activation mapping (Grad-CAM) was used to evaluate the region of focus, and the relationships between the model outputs, anthropometric characteristics, and OSA severity were evaluated. RESULTS: The AUROC of the model for the presence of OSA was 0.82 (95% confidence interval, 0.80-0.84) and 0.73 (95% confidence interval, 0.65-0.81) in the internal and external test datasets, respectively. Grad-CAM demonstrated that the model focused on the area of the tongue base and oropharynx in the cephalogram. Sigmoid output values were positively correlated with OSA severity, body mass index, and neck and waist circumference. CONCLUSIONS: Deep learning may help develop a model that classifies OSA using a cephalogram, which may be clinically useful in the appropriate context. The definition of ground truth was the main limitation of this study. CITATION: Jeong H-G, Kim T, Hong JE, et al. Automated deep neural network analysis of lateral cephalogram data can aid in detecting obstructive sleep apnea. J Clin Sleep Med. 2023;19(2):327-337.