Behavior of Extracranial-to-Intracranial Extended Arterial Dissections of the Vertebral Artery.

BACKGROUND: Vertebral artery dissections (VADs) may extend from the extracranial to the intracranial vasculature (e+iVAD). We evaluated how the characteristics of e+iVAD differed from those of intracranial VAD (iVAD). METHODS AND RESULTS: From 2002 to 2019, among consecutive patients with cervicocephalic dissection, those with iVAD and e+iVAD were included, and their clinical characteristics were compared. In patients with unruptured dissections, a composite clinical outcome of subsequent ischemic events, subsequent hemorrhagic stroke, or mortality was evaluated. High-resolution magnetic resonance images were analyzed to evaluate intracranial remodeling index. Among 347 patients, 51 (14.7%) had e+iVAD and 296 (85.3%) had iVAD. The hemorrhagic presentation occurred solely in iVAD (0.0% versus 19.3%), whereas e+iVAD exhibited higher ischemic presentation (84.3% versus 27.4%; P<0.001). e+iVAD predominantly presented steno-occlusive morphology (88.2% versus 27.7%) compared with dilatation patterns (11.8% versus 72.3%; P<0.001) of iVAD. The ischemic presentation was significantly associated with e+iVAD (iVAD as a reference; adjusted odds ratio, 3.97 [95% CI, 1.67-9.45]; P=0.002]). Patients with unruptured VAD showed no differences in the rate of composite clinical outcome between the groups (log-rank, P=0.996). e+iVAD had a lower intracranial remodeling index (1.4±0.3 versus 1.6±0.4; P<0.032) and a shorter distance from dural entry to the maximal dissecting segment (6.9±8.4 versus 15.7±7.4; P<0.001). CONCLUSIONS: e+iVAD is associated with lower rates of hemorrhages and higher rates of ischemia than iVAD at the time of admission. This may be explained by a lower intracranial remodeling index and less deep intrusion of the dissecting segment into the intracranial space.

RNF213 variant and autophagic impairment: A pivotal link to endothelial dysfunction in moyamoya disease.

Moyamoya disease (MMD) is closely associated with the Ring Finger Protein 213 (RNF213), a susceptibility gene for MMD. However, its biological function remains unclear. We aimed to elucidate the role of RNF213 in the damage incurred by human endothelial cells under oxygen-glucose deprivation (OGD). We analyzed autophagy in peripheral blood mononuclear cells (PBMCs) derived from patients carrying either RNF213 wildtype (WT) or variant (p.R4810K). Subsequently, human umbilical vein endothelial cells (HUVECs) were transfected with RNF213 WT (HUVECWT) or p.R4810K (HUVECR4810K) and exposed to OGD for 2 h. Immunoblotting was used to analyze autophagy marker proteins, and endothelial function was analyzed by tube formation assay. Autophagic vesicles were observed using transmission electron microscopy. Post-OGD exposure, we administered rapamycin and cilostazol as potential autophagy inducers. The RNF213 variant group during post-OGD exposure (vs. pre-OGD) showed autophagy inhibition, increased protein expression of SQSTM1/p62 (p < 0.0001) and LC3-II (p = 0.0039), and impaired endothelial function (p = 0.0252). HUVECR4810K during post-OGD exposure (versus pre-OGD) showed a remarkable increase in autophagic vesicles. Administration of rapamycin and cilostazol notably restored the function of HUVECR4810K and autophagy. Our findings support the pivotal role of autophagy impaired by the RNF213 variant in MMD-induced endothelial cell dysfunction.

Prediction of Intracranial Atherosclerotic Disease-Related Large-Vessel Occlusion Stroke on the Basis of Novel Cerebral Blood Volume Parameters.

BACKGROUND: Mechanical thrombectomy is an effective treatment method for large-vessel occlusion stroke (LVOS); however, it has limited efficacy for intracranial atherosclerotic disease (ICAD)-related LVOS. We investigated the use of cerebral blood volume (CBV) maps for identifying ICAD as the underlying cause of LVOS before the initiation of endovascular treatment (EVT). METHODS AND RESULTS: We reviewed clinical and imaging data from patients who presented with LVOS and underwent endovascular treatment between January 2011 and May 2021. The CBV patterns were analyzed to identify an increase in CBV within the hypoperfused area and estimate infarct patterns within the area of decreased CBV. Comparisons were made between the patients with an increase in CBV and those without, and among the estimated infarct patterns: territorial, cortical wedge, basal ganglia-only, subcortical, and normal CBV. Overall, 243 patients were included. CBV increase in the hypoperfused area was observed in 23.5% of patients. A significantly higher proportion of ICAD was observed in those with increased CBV than in those without (56.4% versus 19.8%; P<0.001). Regarding the estimated infarct patterns on the CBV, ICAD was most frequently observed in the normal CBV group (territorial, 14.9%; cortical wedge, 10.0%; basal ganglia-only, 43.8%; subcortical, 35.7%; normal, 61.7%). CBV parameters, including "an increase in CBV," "normal CBV infarct pattern," and "an increase in CBV or normal CBV infarct pattern composite," were independently associated with ICAD. CONCLUSIONS: An increased CBV or normal CBV pattern may be associated with ICAD LVOS on the pretreatment perfusion imaging.

Significance of headache in intracranial vertebrobasilar artery dissections: an observational study.

Headache may represent acute phase of intracranial vertebrobasilar artery dissection (iVBAD). We aimed to evaluate its clinical significance in iVBAD. Consecutive acute iVBAD patients were grouped into ruptured iVBAD, unruptured iVBAD with no headache, isolated headache, or concurrent headache with neurological symptoms. Composite hemorrhagic/ischemic endpoints, and dynamic arterial changes were graded. Clinical characteristics of the four groups, and association between headache and composite outcomes was evaluated. Headaches were precedent in 79% of the ruptured iVBAD patients (maximal delay, 10D). In unruptured iVBAD, when patients with no headache (N = 69), concurrent headache (N = 111), and isolated headache (N = 126) were compared, concurrent headache was associated with ischemic endpoints (isolated headache as reference, adjusted odds ratio: 6.40, 95% confidence interval [2.03-20.19]). While there were no differences in hemorrhagic endpoints, dynamic arterial changes were higher in the isolated headache group (aOR: 3.98, 95% CI [1.72-9.18]) but not for the concurrent headache group (aOR: 1.59 [0.75-3.38]) compared to no headache group. Headache was more commonly severe (48.4% vs. 17.3%, p < 0.001) and ipsilateral (59.7% vs. 45.5%, p = 0.03) for isolated headache compared to concurrent headache, indicating a higher causal relationship. In iVBAD, isolated headache may be considered an acute-phase biomarker, associated with dynamic arterial changes.

Cerebral artery signal intensity gradient from Time-of-Flight Magnetic Resonance Angiography and clinical outcome in lenticulostriate infarction: a retrospective cohort study.

Purpose: Lenticulostriate infarction requires further research of arterial hemodynamic factors, as the disease is diagnosed in the absence of major arterial stenosis or cardioembolism. Methods: In this multicenter retrospective cohort study, we included patients who were hospitalized for lenticulostriate infarction from January 2015 to March 2021 at three stroke centers in South Korea. We obtained hemodynamic information on cerebral arteries using signal intensity gradient (SIG), an in-vivo approximated wall shear stress (WSS) derived from Time-of-Flight Magnetic Resonance Angiography (TOF-MRA). A favorable outcome was defined as a modified Rankin Scale of 0 to 2 at hospital discharge. Results: A total of 294 patients were included, of whom 146 (49.7%) had an unfavorable outcome. The unfavorable outcome group showed significantly lower SIG in both middle cerebral arteries (MCAs) than the favorable group (5.2 ± 1.2 SI/mm vs. 5.9 ± 1.2, p < 0.001), and similar findings were observed in other cerebral arteries. The SIGs in both MCAs were independently associated with favorable outcome, with an odds ratio of 1.42 (95% confidence interval, 1.11-1.80; p = 0.005) for the right MCA and 1.49 (95% CI, 1.15-1.93; p = 0.003) for the left MCA, after adjusting for potential confounders. Similar findings were observed in other cerebral artery SIGs. Conclusion: Cerebral artery SIG from TOF-MRA was significantly associated with short-term functional outcomes in patients with lenticulostriate infarction. Further studies are needed to investigate the temporal relationships of SIG in patients with cerebral infarction.

Clinical evaluation of a deep-learning model for automatic scoring of the Alberta stroke program early CT score on non-contrast CT.

BACKGROUND: Automated measurement of the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) can support clinical decision making. Based on a deep learning algorithm, we developed an automated ASPECTS scoring system (Heuron ASPECTS) and validated its performance in a prespecified clinical trial. METHODS: For model training, we used non-contrast computed tomography images of 487 patients with acute ischemic stroke (AIS). For the clinical trial, 326 patients (87 with AIS, 56 with other acute brain diseases, and 183 with no brain disease) were enrolled. The results of Heuron ASPECTS were compared with the consensus generated by two stroke experts using the Bland-Altman agreement. A mean difference of less than 0.35 and a maximum allowed difference of less than 3.8 were considered the primary outcome target. The sensitivity and specificity of the model for the 10 regions of interest and dichotomized ASPECTS were calculated. RESULTS: The Bland-Altman agreement had a mean difference of 0.03 [95% confidence interval (CI): -0.08 to 0.14], and the upper and lower limits of agreement were 2.80 [95% CI: 2.62 to 2.99] and -2.74 [95% CI: -2.92 to -2.55], respectively. For ASPECTS calculation, sensitivity and specificity to detect the early ischemic change for 10 ASPECTS regions were 62.78% [95% CI: 58.50 to 67.07] and 96.63% [95% CI: 96.18 to 97.09], respectively. Furthermore, in a dichotomized analysis (ASPECTS >4 vs. ≤4), the sensitivity and specificity were 94.01% [95% CI: 91.26 to 96.77] and 61.90% [95% CI: 47.22 to 76.59], respectively. CONCLUSIONS: The current trial results show that Heuron ASPECTS reliably measures the ASPECTS for use in clinical practice.

Transcriptome profiling of skeletal muscles from Korean patients with Bethlem myopathy.

Bethlem myopathy is one of the collagens VI-related muscular dystrophies caused by mutations in the collagen VI genes. The study was designed to analyze the gene expression profiles in the skeletal muscle of patients with Bethlem myopathy. Six skeletal muscle samples from 3 patients with Bethlem myopathy and 3 control subjects were analyzed by RNA-sequencing. 187 transcripts were significantly differentially expressed, with 157 upregulated and 30 downregulated transcripts in the Bethlem group. Particularly, 1 (microRNA-133b) was considerably upregulated, and 4 long intergenic non-protein coding RNAs, LINC01854, MBNL1-AS1, LINC02609, and LOC728975, were significantly downregulated. We categorized differentially expressed gene using Gene Ontology and showed that Bethlem myopathy is strongly associated with the organization of extracellular matrix (ECM). Kyoto Encyclopedia of Genes and Genomes pathway enrichment reflected themes with significant enrichment of the ECM-receptor interaction (hsa04512), complement and coagulation cascades (hsa04610), and focal adhesion (hsa04510). We confirmed that Bethlem myopathy is strongly associated with the organization of ECM and the wound healing process. Our results demonstrate transcriptome profiling of Bethlem myopathy, and provide new insights into the path mechanism of Bethlem myopathy associated with non-protein coding RNAs.

A Deep Learning-Based Automatic Collateral Assessment in Patients with Acute Ischemic Stroke.

This study aimed to develop a supervised deep learning (DL) model for grading collateral status from dynamic susceptibility contrast magnetic resonance perfusion (DSC-MRP) images from patients with large vessel occlusion (LVO) acute ischemic stroke (AIS) and compare its performance against experts' manual grading. Among consecutive LVO-AIS at three medical center sites, DSC-MRP data were processed to generate collateral flow maps consisting of arterial, capillary, and venous phases. With the use of expert readings as a reference, a DL model was developed to analyze collateral status with output classified into good and poor grades. The resulting model was externally validated in a later-collected population from one medical center site. The model was trained on 255 patients and externally validated on 72 patients. In the all-site internal validation population, DL grading of good collateral probability yielded a c statistic of 0.91; in the external validation population, the c statistic was 0.85. In the external validation population, there was moderate agreement between the experts' grades and DL grades (kappa = 0.53, 95% CI = 0.32-0.73, p < 0.0001). Day 7 infarct growth volume was higher in DL-graded poor collateral group than good collateral group patients (median volume [26 mL vs. 6 mL], p = 0.01) in patients with successful reperfusion (modified treatment in cerebral infarction (mTICI) = 2b-3). In all patients with a 90-day modified Rankin Scale (mRS) score, there was a shift to more favorable outcomes in the good collateral group, with a common odds ratio of 2.99 (95% CI = 1.89-4.76, p < 0.0001). The DL-based collateral grading was in good agreement with expert manual grading in both development and validation populations. After exclusion of patients with large infarct volume, early reperfusion is more likely to benefit patients with the poor collateral flow, and the DL method has the potential to aid the assessment of collateral status.

Association Between White Matter Networks and the Pattern of Striatal Dopamine Depletion in Patients With Parkinson Disease.

OBJECTIVES: Individual variability in nigrostriatal dopaminergic denervation is an important factor underlying clinical heterogeneity in Parkinson's disease (PD). This study aimed to explore whether the pattern of striatal dopamine depletion was associated with white matter (WM) networks in PD. METHODS: A total of 240 newly diagnosed PD patients who underwent 18F-FP-CIT PET scans and brain diffusion tensor imaging at initial assessment were enrolled in this study. We measured 18F-FP-CIT tracer uptake as an indirect marker for striatal dopamine depletion. Factor analysis-derived striatal dopamine loss patterns were estimated in each patient to calculate the composite scores of four striatal subregion factors (caudate, more- and less-affected sensorimotor striata, and anterior putamen) based on the availability of striatal dopamine transporter. The WM structural networks that were correlated with the composite scores of each striatal subregion factor were identified using a network-based statistic analysis. RESULTS: A higher composite score of caudate (i.e., relatively preserved dopaminergic innervation in the caudate) was associated with a strong structural connectivity in a single subnetwork comprising the left caudate and left frontal gyri. Selective dopamine loss in the caudate was associated with strong connectivity in the structural subnetwork whose hub nodes were bilateral thalami and left insula, which were connected to the anterior cingulum. However, no subnetworks were correlated with the composite scores of other striatal subregion factors. The connectivity strength of the network with a positive correlation with the composite score of caudate affected the frontal/executive function either directly or indirectly through the mediation of dopamine depletion in the caudate.

Nelonemdaz for Patients With Acute Ischemic Stroke Undergoing Endovascular Reperfusion Therapy: A Randomized Phase II Trial.

BACKGROUND: Nelonemdaz is a multitarget neuroprotectant that selectively blocks N-methyl-D-aspartate receptors and scavenges free radicals, as proven in preclinical ischemia-reperfusion studies. We aimed to evaluate the safety and efficacy of nelonemdaz in patients with acute ischemic stroke receiving endovascular reperfusion therapy. METHODS: This phase II randomized trial involved participants with large-artery occlusion in the anterior circulation at baseline who received endovascular reperfusion therapy <8 hours from symptom onset at 7 referral stroke centers in South Korea between October 29, 2016, and June 1, 2020. Two hundred thirteen patients were screened and 209 patients were randomly assigned at a 1:1:1 ratio using a computer-generated randomization system. Patients were divided into 3 groups based on the medication received-placebo, low-dose (2750 mg) nelonemdaz, and high-dose (5250 mg) nelonemdaz. The primary outcome was the proportion of patients with modified Rankin Scale scores of 0-2 at 12 weeks. RESULTS: Two hundred eight patients were assigned to the placebo (n=70), low-dose (n=71), and high-dose (n=67) groups. The groups had similar baseline characteristics. The primary outcome was achieved in 183 patients, and it did not differ among the groups (33/61 [54.1%], 40/65 [61.5%], and 36/57 [63.2%] patients; P=0.5578). The common odds ratio (90% CI) indicating a favorable shift in the modified Rankin Scale scores at 12 weeks was 1.55 (0.92-2.60) between the placebo and low-dose groups and 1.61 (0.94-2.76) between the placebo and high-dose groups. No serious adverse events were reported. CONCLUSIONS: The study arms showed no significant difference in the proportion of patients achieving modified Rankin Scale scores of 0-2 at 12 weeks. Nevertheless, nelonemdaz-treated patients showed a favorable tendency toward achieving these scores at 12 weeks, without serious adverse effects. Thus, a large-scale phase III trial is warranted. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02831088.

Influence of endothelial function and arterial stiffness on the behavior of cervicocephalic arterial dissections: An observational study.

Background: The mechanical and physiological properties of the arterial wall might affect the behavior of spontaneous cervicocephalic arterial dissections (CCAD). We aimed to determine the effects of endothelial function and arterial stiffness on the clinical characteristics and outcomes of CCAD using brachial flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (PWV). Methods: From a single-center database, we identified patients admitted from April 2011 to December 2021 with a diagnosis of CCAD who underwent both FMD and PWV. FMD was classified as normal and decreased according to institutional thresholds. PWV was categorized into tertiles. Comparative and multivariable analyses were performed to determine the effects of FMD and PWV values on major clinical outcomes. Results: A total of 146 patients (age: 47 ± 11 years; men: 77.4%) were included. The main presentation was ischemic stroke in 76.7% of the patients, while 23.3% presented with headache or other symptoms. Healing of the dissection was observed in 55.8%. In multivariable analysis, Normal FMD levels (vs. decreased; adjusted OR: 4.52, 95% CI [1.95 -10.52]) were associated with spontaneous healing of the dissection. Highest PWV tertile (vs. lowest; adjusted OR: 17.05, 95% CI [3.07-94.82]) was associated with ischemic presentation. There was a higher ischemic stroke recurrence in the 3rd PWV tertile, and more frequent aneurysmal enlargement in the lowest PWV tertile, but their frequency was low, precluding multivariable analysis. Conclusion: In spontaneous CCAD, preserved endothelial function was associated with spontaneous arterial healing. Arterial stiffness is associated with ischemic presentation.

Selective Brain Cooling: A New Horizon of Neuroprotection.

Therapeutic hypothermia (TH), which prevents irreversible neuronal necrosis and ischemic brain damage, has been proven effective for preventing ischemia-reperfusion injury in post-cardiac arrest syndrome and neonatal encephalopathy in both animal studies and clinical trials. However, lowering the whole-body temperature below 34°C can lead to severe systemic complications such as cardiac, hematologic, immunologic, and metabolic side effects. Although the brain accounts for only 2% of the total body weight, it consumes 20% of the body's total energy at rest and requires a continuous supply of glucose and oxygen to maintain function and structural integrity. As such, theoretically, temperature-controlled selective brain cooling (SBC) may be more beneficial for brain ischemia than systemic pan-ischemia. Various SBC methods have been introduced to selectively cool the brain while minimizing systemic TH-related complications. However, technical setbacks of conventional SBCs, such as insufficient cooling power and relatively expensive coolant and/or irritating effects on skin or mucosal interfaces, limit its application to various clinical settings. This review aimed to integrate current literature on SBC modalities with promising therapeutic potential. Further, future directions were discussed by exploring studies on interesting coping skills in response to environmental or stress-induced hyperthermia among wild animals, including mammals and birds.

Significance of Vertigo, Imbalance, and Other Minor Symptoms in Hyperacute Treatment of Posterior Circulation Stroke.

Background: This study aimed to determine the clinical significance of acute vestibular syndrome (AVS)/acute imbalance syndrome (AIS) in posterior circulation stroke (PCS) and how it should be addressed in the thrombolysis code. Methods: Our institution has recently changed its thrombolysis code from one that is generous to AVS/AIS to one that is exclusive. The subjects in this study were patients with PCS who presented before this transition (May 2016 to April 2018, period 1) and those who presented after (January 2019 to December 2020, period 2) with an onset-to-door time of 4.5 h. Hyperacute stroke treatment was compared between the two periods. The clinical significance of AVS/AIS was evaluated by dichotomizing the patients' clinical severity to minor or major deficits, then evaluating the significance of AVS/AIS in each group. Presenting symptoms of decreased mental alertness, hemiparesis, aphasia (anarthria), or hemianopsia were considered major PCS symptoms, and patients who did not present with these symptoms were considered minor PCS. Results: In total, 114 patients presented in period 1 and 114 in period 2. Although the code activation rate was significantly lower in period 2 (72.8% vs. 59.7%), p = 0.04, there were no between-group differences in functional outcomes (mRS score at 3 months; 1 [0-3] vs. 0 [0-3], p = 0.18). In 77 patients with PCS and AVS/AIS, the difference in code activation rate was not significant according to changes in thrombolysis code. In minor PCS, AVS/AIS was associated with lower NIHSS scores, lower early neurological deterioration rates, and favorable outcomes. In major PCS, while AVS/AIS was not associated with outcomes, the majority of cases were prodromal AVS/AIS which simple vertigo and imbalance symptoms were followed by a major PCS symptom. Conclusions: This study failed to show differences in outcome in patients with PCS according to how AVS/AIS is addressed in the stroke thrombolysis code. In patients with minor PCS, AVS/AIS was associated with a benign clinical course. Prompt identification of prodromal AVS/AIS is essential.

Endovascular Treatment for Posterior Circulation Stroke: Ways to Maximize Therapeutic Efficacy.

The efficacy of endovascular treatment (EVT) in patients with posterior circulation stroke has not been proven. Two recent randomized controlled trials failed to show improved functional outcomes after EVT for posterior circulation stroke (PC-EVT). However, promising results for two additional randomized controlled trials have also been presented at a recent conference. Studies have shown that patients undergoing PC-EVT had a higher rate of futile recanalization than those undergoing EVT for anterior circulation stroke. These findings call for further identification of prognostic factors beyond recanalization. The significance of baseline clinical severity, infarct volume, collaterals, time metrics, core-penumbra mismatch, and methods to accurately measure these parameters are discussed. Furthermore, their interplay on EVT outcomes and the potential to individualize patient selection for PC-EVT are reviewed. We also discuss technical considerations for improving the treatment efficacy of PC-EVT.

Transdural Revascularization by Multiple Burrhole After Erythropoietin in Stroke Patients With Cerebral Hypoperfusion: A Randomized Controlled Trial.

BACKGROUND: In patients with acute symptomatic stroke, reinforcement of transdural angiogenesis using multiple burr hole (MBH) procedures after EPO (erythropoietin) treatment has rarely been addressed. We aimed to investigate the efficacy and safety of cranial MBH procedures under local anesthesia for augmenting transdural revascularization after EPO treatment in patients with stroke with perfusion impairments. METHODS: This prospective, randomized, blinded-end point trial recruited patients with acute ischemic stroke with a perfusion impairment of grade ≥2 within 14 days of symptom onset, steno-occlusive mechanisms on imaging examinations, and absence of transdural collaterals on transfemoral cerebral angiography. Patients were randomly assigned to receive MBH + EPO or MBH alone. The primary and secondary outcomes were revascularization success (trans-hemispheric and trans-burr hole) at 6 months and adverse events, respectively. RESULTS: We evaluated 42 of the 44 targeted patients, with 2 patients lost to follow-up. The combined and MBH-only (n=21 each) groups showed no differences in demographic characteristics and baseline perfusion parameters. Significantly, more cases of trans-hemispheric (19/21 [90.5%] versus 12/21 [57.1%]) and trans-burr hole (42/58 [72.4%] versus 30/58 [51.7%]) revascularization and significant improvements in perfusion parameters were observed in the combined group relative to the MBH-only group. No differences in treatment-related complications were observed between groups. Even after adjustment for potential covariates, EPO usage was an independent factor of successful hemispheric revascularization in this study (odds ratio, 6.41 [95% CI, 1.08-38.02]). CONCLUSIONS: The combination of MBH and EPO is safe and feasible for reinforcing transdural revascularization in acute steno-occlusive patients with perfusion impairments. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02603406.

Simultaneous monitoring of the middle cerebral and basilar arteries to detect right-to-left shunts using transcranial Doppler by agitated saline administration.

Transcranial Doppler (TCD) is an easy, non-invasive, and real-time monitoring device for detecting right-to-left shunts (RLS). Nonetheless, it has limited benefits in patients with poor temporal windows. Therefore, we aimed to investigate whether the basilar artery (BA) window was as effective as the middle cerebral artery (MCA) in detecting RLS during TCD monitoring. Overall, we enrolled 344 patients with stroke, transient ischemic attack, headache, or dizziness. MCA and BA were monitored using a modified headset. To investigate the feasibility of the suboccipital window in detecting RLS, we instituted an evaluation tool with three tiers to evaluate microembolic signals (MESs) during TCD monitoring. Tier 1: TCD monitoring of the MCA (bilaterally) in the resting state, tier 2: TCD monitoring of the MCA (bilaterally) while performing the Valsalva maneuver, and tier 3: TCD monitoring of the index MCA and BA while performing the Valsalva maneuver. In tiers 2 and 3, a high agreement rate of 0.808 and 0.809 (p < 0.001), respectively, on the weighted kappa index, and a high intra-class correlation coefficient of 0.982 and 0.986 (p < 0.001), respectively, were observed on detecting MESs. Our data suggests that the BA window is as effective as the MCA window for detecting RLS on TCD.

Evaluating the Risk of Paroxysmal Atrial Fibrillation in Noncardioembolic Ischemic Stroke Using Artificial Intelligence-Enabled ECG Algorithm.

Background: The identification of latent atrial fibrillation (AF) in patients with ischemic stroke (IS) attributed to noncardioembolic etiology may have therapeutic implications. An artificial intelligence (AI) model identifying the electrocardiographic signature of AF present during normal sinus rhythm (NSR; AI-ECG-AF) can identify individuals with a high likelihood of paroxysmal AF (PAF) with NSR electrocardiogram (ECG). Objectives: Using AI-ECG-AF, we aimed to compare the PAF risk between noncardioembolic IS subgroups and general patients of a university hospital after controlling for confounders. Further, we sought to compare the risk of PAF among noncardioembolic IS subgroups. Methods: After training AI-ECG-AF with ECG data of university hospital patients, model inference outputs were obtained for the control group (i.e., general patient population) and NSRs of noncardioembolic IS patients. We conducted multiple linear regression (MLiR) and multiple logistic regression (MLoR) analyses with inference outputs (for MLiR) or their binary form (set at threshold = 0.5 for MLoR) used as dependent variables and patient subgroups and potential confounders (age and sex) set as independent variables. Results: The number of NSRs inferenced for the control group, cryptogenic, large artery atherosclerosis (LAA), and small artery occlusion (SAO) strokes were 133,340, 133, 276, and 290, respectively. The regression analyses indicated that patients with noncardioembolic IS had a higher PAF risk based on AI-ECG-AF relative to the control group, after controlling for confounders with the "cryptogenic" subgroup having the highest risk (odds ratio [OR] = 1.974, 95% confidence interval [CI]: 1.371-2.863) followed by the "LAA" (OR = 1.592, 95% CI: 1.238-2.056) and "SAO" subgroups (OR = 1.400, 95% CI: 1.101-1.782). Subsequent regression analyses failed to illustrate the differences in PAF risk based on AI-ECG-AF among noncardioembolic IS subgroups. Conclusion: Using AI-ECG-AF, we found that noncardioembolic IS patients had a higher PAF risk relative to the general patient population. The results from our study imply the need for more vigorous cardiac monitoring in noncardioembolic IS patients. AI-ECG-AF can be a cost-effective screening tool to identify high-risk noncardioembolic IS patients of PAF on-the-spot to be candidates for receiving additional prolonged cardiac monitoring. Our study highlights the potential of AI in clinical practice.

Influence of cerebral microbleeds on mechanical thrombectomy outcomes.

In ischemic stroke patients undergoing endovascular treatment (EVT), we aimed to test the hypothesis that cerebral microbleeds (CMBs) are associated with clinical outcomes, while estimating the mediating effects of hemorrhagic transformation (HT), small-vessel disease burden (white matter hyperintensities, WMH), and procedural success. From a multicenter EVT registry, patients who underwent pretreatment MR imaging were analyzed. They were trichotomized according to presence of CMBs (none vs. 1-4 vs. ≥ 5). The association between CMB burden and 3-month mRS was evaluated using multivariable ordinal logistic regression, and mediation analyses were conducted to estimate percent mediation. Of 577 patients, CMBs were present in 91 (15.8%); 67 (11.6%) had 1-4 CMBs, and 24 (4.2%) had ≥ 5. Increases in CMBs were associated with hemorrhagic complications (ß = 0.27 [0.06-0.047], p = 0.010) in multivariable analysis. The CMB effect on outcome was partially mediated by post-procedural HT degree (percent mediation, 14% [0-42]), WMH (23% [7-57]) and lower rates of successful reperfusion (6% [0-25]). In conclusion, the influence of CMBs on clinical outcomes is mediated by small-vessel disease burden, post-procedural HT, and lower reperfusion rates, listed in order of percent mediation size.

A novel global ischemia-reperfusion rat model with asymmetric brain damage simulating post-cardiac arrest brain injury.

BACKGROUND: Post-cardiac arrest brain injury (PCABI) is a major cause of disability and death in patients with post-cardiac arrest syndrome (PCAS). However, there have been no suitable animal models with characteristic behaviors and cerebral damage adequately mimicking clinical PCABI. NEW METHOD: We established a chimeric model by increasing transient middle cerebral artery occlusion-mediated ipsilateral hemisphere damage in the 4-vessel occlusion (4VO) model, thereby inducing global forebrain asymmetric hemisphere ischemia. Severity of brain damage was then evaluated by behavioral and histological approaches. Neuroprotection was assessed by performing targeted temperature management (TTM) for two hours. RESULTS: Comatose behaviors were observed in both groups. Compared to the 4VO group, the chimeric group exhibited a higher neurological deficit score (NDS) (70.5 ± 17.6 vs. 139.5 ± 16.8, p = 0.0002), decreased brain cell viability (88.6 ± 18.0% vs. 5.7 ± 2.7%, p < 0.0001), and increased inflammation in the cortex (10.3 ± 1.6% vs. 16.9 ± 1.1%, p = 0.0061). After TTM neuroprotection, the chimeric-TTM group showed improvement in NDS (139.5 ± 16.8 vs. 0.0 ± 0.0, p < 0.0001), cortex and hippocampus cell viability (5.7 ± 2.7% vs. 72.8 ± 10.0%, p < 0.0001; and 2.5 ± 1.5% vs. 75.5 ± 10.3%, p < 0.0001, respectively) and inflammation (16.9 ± 1.1% vs. 11.0 ± 2.3%, p = 0.190; and 30.9 ± 1.7% vs. 16.6 ± 1.2%, p < 0.0001, respectively) compared to the chimeric group. COMPARISON WITH EXISTING METHOD: Unlike the extensive brain damage found in clinical PCAS settings, the existing 4VO models showed only global forebrain damage involving CA1 lesions on both hippocampi. Our model induced global forebrain and additional asymmetric hemisphere ischemic damages, which resulted in simulating PCABI-specific clinical manifestations than conventional models. CONCLUSIONS: Our model adequately simulates clinical PCABI and reflects appropriate neuroprotective effects of TTM.