Efficacy of Endovascular Thrombectomy in Acute Basilar Artery Occlusion with Low PC-ASPECTS: A Nationwide Prospective Registry-Based Study.

OBJECTIVE: We evaluated the efficacy of endovascular thrombectomy (EVT) on the functional outcome of patients with acute basilar artery occlusion and low posterior circulation acute stroke prognosis early computed tomography score (PC-ASPECTS). METHODS: We identified patients with acute ischemic stroke due to basilar artery occlusion and PC-ASPECTS of 6 or less, presenting within 24 h between August 2008 and April 2022. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. The secondary outcomes included an mRS score of 0-2, a favorable shift in the ordinal mRS scale, the occurrence of symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. We compared the outcome of patients treated with EVT and those without EVT, using the inverse probability of treatment weighting methods. RESULTS: Out of 566 patients, 55.5% received EVT. In the EVT group, 106 (33.8%) achieved favorable outcomes, compared to 56 patients (22.2%) in the conservative group. EVT significantly increased the likelihood of achieving a favorable outcome compared to conservative treatment (relative risk [RR] 1.39, 95% confidence interval [CI], 1.11-1.74, p = 0.004). EVT was associated with a favorable shift in the mRS (RR 1.85, 95% CI, 1.49-2.29, p < 0.001) and reduced mortality without an increase in the risk of sICH. It did not have an impact on achieving an mRS score of 0-2. INTERPRETATION: Patients with acute basilar artery occlusion and a PC-ASPECTS of 6 or less might benefit from EVT without an increasing sICH. ANN NEUROL 2024;95:788-799.

Secular Trends in Outcomes and Impact of Novel Oral Anticoagulants in Atrial Fibrillation-Related Acute Ischemic Stroke.

BACKGROUND: Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend. METHODS: We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders. RESULTS: Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07-1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14-2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94-1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome. CONCLUSIONS: Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population.

Contemporary Statistics of Acute Ischemic Stroke and Transient Ischemic Attack in 2021: Insights From the CRCS-K-NIH Registry.

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively. Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques. There has been a decrease in intravenous thrombolysis rates, from 12% in 2017-2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for non-cardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.

Differences in Neuropathology between Nitroglycerin-Induced Mouse Models of Episodic and Chronic Migraine.

Multiple animal models of migraine have been used to develop new therapies. Understanding the transition from episodic (EM) to chronic migraine (CM) is crucial. We established models mimicking EM and CM pain and assessed neuropathological differences. EM and CM models were induced with single NTG or multiple injections over 9 days. Mechanical hypersensitivity was assessed. Immunofluorescence utilized c-Fos, NeuN, and Iba1. Proinflammatory and anti-inflammatory markers were analyzed. Neuropeptides (CGRP, VIP, PACAP, and substance P) were assessed. Mechanical thresholds were similar. Notable neuropathological distinctions were observed in Sp5C and ACC. ACC showed increased c-Fos and NeuN expression in CM (p < 0.001) and unchanged in EM. Sp5C had higher c-Fos and NeuN expression in EM (p < 0.001). Iba1 was upregulated in Sp5C of EM and ACC of CM (p < 0.001). Proinflammatory markers were strongly expressed in Sp5C of EM and ACC of CM. CGRP expression was elevated in both regions and was higher in CM. VIP exhibited higher levels in the Sp5C of EM and ACC of CM, whereas PACAP and substance P were expressed in the Sp5C in both models. Despite similar thresholds, distinctive neuropathological differences in Sp5C and ACC between EM and CM models suggest a role in the EM to CM transformation.

Clinical profile and treatment outcomes of idiopathic intracranial hypertension: a multicenter study from Korea.

BACKGROUND: Currently, there is a relative lack of detailed reports regarding clinical presentation and outcome of idiopathic intracranial hypertension in Asians. This study aims to describe the clinical features and treatment outcomes of Korean patients with idiopathic intracranial hypertension. METHODS: We prospectively recruited patients with idiopathic intracranial hypertension from one hospital and retrospectively analyzed the medical records of 11 hospitals in Korea. We collected data regarding preceding medical conditions or suspected medication exposure, headache phenotypes, other associated symptoms, detailed neuroimaging findings, treatments, and outcomes after 1-2 and 3-6 months of treatment. RESULTS: Fifty-nine (83.1% women) patients were included. The mean body mass index was 29.11 (standard deviation, 5.87) kg/m2; only 27 patients (45.8%) had a body mass index of ≥ 30 kg/m2. Fifty-one (86.4%) patients experienced headaches, patterns of which included chronic migraine (15/51 [29.4%]), episodic migraine (8/51 [15.7%]), probable migraine (4/51 [7.8%]), chronic tension-type headache (3/51 [5.9%]), episodic tension-type headache (2/51 [3.9%]), probable tension-type headache (2/51 [3.9%]), and unclassified (17/51 [33.3%]). Medication overuse headache was diagnosed in 4/51 (7.8%) patients. After 3-6 months of treatment, the intracranial pressure normalized in 8/32 (25.0%), improved in 17/32 (53.1%), no changed in 7/32 (21.9%), and worsened in none. Over the same period, headaches remitted or significantly improved by more than 50% in 24/39 patients (61.5%), improved less than 50% in 9/39 (23.1%), and persisted or worsened in 6/39 (15.4%) patients. CONCLUSION: Our findings suggest that the features of Asian patients with idiopathic intracranial hypertension may be atypical (i.e., less likely obese, less female predominance). A wide spectrum of headache phenotypes was observed. Medical treatment resulted in overall favorable short-term outcomes; however, the headaches did not improve in a small proportion of patients.

Improvement in Delivery of Ischemic Stroke Treatments but Stagnation of Clinical Outcomes in Young Adults in South Korea.

BACKGROUND: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population. METHODS: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed. RESULTS: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years (Ptrend=0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; Ptrend<0.01). Door-to-needle time improved (Ptrend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased (Ptrend<0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; Ptrend=0.04), although the difference was not significant after adjusting for sex and age. CONCLUSIONS: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress.

Predicting Role of Prestroke Glycemic Variability Estimated by Glycated Albumin for Reperfusion and Prognosis after Endovascular Treatment.

INTRODUCTION: Glycated hemoglobin is widely used for the diagnosis of diabetes, but it is not accurately correlated with blood glucose fluctuations. We evaluated the impact of prestroke glycemic variability, measured by glycated albumin (GA) on reperfusion rate and stroke outcomes after endovascular treatment (EVT). METHODS: We consecutively collected 310 EVT-treated patients for 60 months using a multicenter registry database. Primary outcome was unsuccessful reperfusion defined by modified Thrombolysis in Cerebral Infarction grade 0 to 2a. Secondary outcomes were occurrence of early neurologic deterioration (END), symptomatic hemorrhagic transformation (SHT) and a 3-month poor outcome (modified Rankin Scale >2). GA was measured in the morning after hospital admission with overnight fasting and determined to reflect high prestroke glycemic variability (GA ≥16.0%). RESULTS: Over the median follow-up of 60 months of 310 patients, there were 64 (20.6%) events of unsuccessful reperfusion, 66 (21.3%) of END, 21 (6.8%) of SHT, and 180 (58.1%) of 3-month poor outcome. In the higher GA group (130, 41.9%), proportion of unsuccessful reperfusion, END, SHT, and poor outcome were higher than lower GA group. The multivariate analysis showed that higher GA was associated with unsuccessful reperfusion after EVT (adjusted odds ratio 4.13; 95% confidence interval [CI], 1.93-8.85). The area under the receiver operating characteristic of GA (0.644; 95% CI: 0.634-0.740) for predicting poor outcome was better than that of glycated hemoglobin (0.586; 95% CI: 0.529-0.642, p for DeLong's pairwise comparison = 0.005). CONCLUSION: GA, reflecting prestroke glycemic variability, could be a reliable parameter for predicting reperfusion rate and acute ischemic stroke outcome in this study.

The association between malnutrition status and hemorrhagic transformation in patients with acute ischemic stroke receiving intravenous thrombolysis.

OBJECTIVES: We evaluated the impact of malnutrition as estimated by the controlling nutritional status (CONUT) score and prognostic nutritional index (PNI) on hemorrhagic transformation (HT) and stroke outcomes after intravenous thrombolysis (IVT). MATERIALS AND METHODS: Using a multicenter registry database, we enrolled 808 patients with acute ischemic stroke who received IVT between August 2013 and May 2021. We defined malnutrition as a CONUT score ≥ 2 and low PNI. The primary outcome measure was the occurrence of symptomatic HT contributing to early neurologic deterioration (END-SHT) after IVT. Multivariable analysis was performed to analyze the association between CONUT score, PNI, and END-SHT after IVT. RESULTS: The rate of END-SHT was higher with increasing CONUT scores and PNI values. In the multivariable analysis, CONUT score ≥ 5 and low PNI were significantly associated with END-SHT (odds ratio [95% confidence interval], CONUT score ≥ 5: 12.23 [2.41-62.07], p = 0.003; low PNI: 4.98 [1.76-14.09], p = 0.003). The receiver operating characteristic curve showed that both the CONUT score and PNI had good predictive ability. The cutoff values for CONUT and PNI were 5 and 42.3, respectively, for END-SHT. CONCLUSION: Malnutrition, as denoted by a higher CONUT score and lower PNI, was associated with END-SHT. The joint application of both nutritional markers could be useful in predicting END-SHT after IVT.

Auditory or Audiovisual Stimulation Ameliorates Cognitive Impairment and Neuropathology in ApoE4 Knock-In Mice.

We hypothesized that auditory stimulation could reduce the progression of Alzheimer's disease (AD), and that audiovisual stimulation could have additional effects through multisensory integration. We exposed 12 month old Apoetm1.1(APOE*4)Adiuj mice (a mouse model of sporadic AD) to auditory (A) or audiovisual stimulation (AV) at 40 Hz for 14 days in a soundproof chamber system (no stimulation, N). Behavioral tests were performed before and after each session, and their brain tissues were assessed for amyloid-beta expression and apoptotic cell death, after 14 days. Furthermore, brain levels of acetylcholine and apoptosis-related proteins were analyzed. In the Y-maze test, the percentage relative alternation was significantly higher in group A than in group N mice. Amyloid-beta and TUNEL positivity in the hippocampal CA3 region was significantly lower in group A and group AV mice than in group N mice (p < 0.05). Acetylcholine levels were significantly higher in group A and group AV mice than in group N mice (p < 0.05). Compared to group N mice, expression of the proapoptotic proteins Bax and caspase-3 was lower in group A, and expression of the antiapoptotic protein Bcl-2 was higher in group AV. In a mouse model of early-stage sporadic AD, auditory or audiovisual stimulation improved cognitive performance and neuropathology.

Frequency, management, and outcomes of early neurologic deterioration due to stroke progression or recurrence.

OBJECTIVE: The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated. MATERIALS AND METHODS: In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed. RESULTS: Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months. CONCLUSION: END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes.

Application of entire dental panorama image data in artificial intelligence model for age estimation.

BACKGROUND: Accurate age estimation is vital for clinical and forensic purposes. With the rapid advancement of artificial intelligence(AI) technologies, traditional methods relying on tooth development, while reliable, can be enhanced by leveraging deep learning, particularly neural networks. This study evaluated the efficiency of an AI model by applying the entire panoramic image for age estimation. The outcome performances were analyzed through supervised learning (SL) models. METHODS: Total of 27,877 dental panorama images from 5 to 90 years of age were classified by 2 types of grouping. In type 1 they were classified by each age and in type 2, applying heuristic grouping, the age over 20 years were classified by every 5 years. Wide ResNet (WRN) and DenseNet (DN) were used for supervised learning. In addition, the analysis with ± 3 years of deviation in both types were performed. RESULTS: For the DN model, while the type 1 grouping achieved an accuracy of 0.1016 and F1 score of 0.058, the type 2 achieved an accuracy of 0.3146 and F1 score of 0.2027. Incorporating ± 3years of deviation, the accuracy of type 1 and 2 were 0.281, 0.7323 respectively; and the F1 score were 0.1768, 0.6583 respectively. For the WRN model, while the type 1 grouping achieved an accuracy of 0.1041 and F1 score of 0.0599, the type 2 achieved an accuracy of 0.3182 and F1 score of 0.2071. Incorporating ± 3years of deviation, the accuracy of type 1 and 2 were 0.2716, 0.7323 respectively; and the F1 score were 0.1709, 0.6437 respectively. CONCLUSIONS: The application of entire panorama image data for supervised with classification by heuristics grouping with ± 3years of deviation for supervised learning models and demonstrated satisfactory outcome for the age estimation.

Stroke of Other Determined Etiology: Results From the Nationwide Multicenter Stroke Registry.

BACKGROUND: Stroke of other determined etiology (OE) includes patients with an uncommon cause of stroke. We described the general characteristics, management, and outcomes of stroke in OE and its subgroups. METHODS: This study is a retrospective analysis of a prospective, multicenter, nationwide registry, the Clinical Research Center for Stroke-Korea-National Institutes of Health registry. We classified OE strokes into 10 subgroups according to the literature and their properties. Each OE subgroup was compared according to clinical characteristics, sex, age strata, lesion locations, and management. Moreover, 1-year composites of stroke and all-cause mortality were investigated according to the OE subgroups. RESULTS: In total, 2119 patients with ischemic stroke with OE types (mean age, 55.6±16.2 years; male, 58%) were analyzed. In the Clinical Research Center for Stroke-Korea-National Institutes of Health registry, patients with OE accounted for 2.8% of all patients with stroke. The most common subtypes were arterial dissection (39.1%), cancer-related coagulopathy (17.3%), and intrinsic diseases of the arterial wall (16.7%). Overall, strokes of OE were more common in men than in women (58% versus 42%). Arterial dissection, intrinsic diseases of the arterial wall and stroke associated with migraine and drugs were more likely to occur at a young age, while disorders of platelets and the hemostatic system, cancer-related coagulopathy, infectious diseases, and hypoperfusion syndromes were more frequent at an old age. The composite of stroke and all-cause mortality within 1 year most frequently occurred in cancer-related coagulopathy, with an event rate of 71.8%, but least frequently occurred in stroke associated with migraine and drugs and arterial dissection, with event rates of 0% and 7.2%, respectively. CONCLUSIONS: This study presents the different characteristics, demographic findings, lesion locations, and outcomes of OE and its subtypes. It is characterized by a high proportion of arterial dissection, high mortality risk in cancer-related coagulopathy and an increasing annual frequency of cancer-related coagulopathy in patients with stroke of OE.

Associations between migraine and major cardiovascular events in type 2 diabetes mellitus.

BACKGROUND: Migraine is one of the most common primary headache disorders and a well-known risk factor for cardiovascular disorders. We aimed to investigate the association between migraine and major cardiovascular outcomes, including myocardial infarction (MI), ischemic stroke (IS), and cardiovascular death (CVD) in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 2,229,598 people from the nationwide Korean National Health Insurance Service database with type 2 diabetes but without a previous history of MI and IS were included in this study. We identified patients over 20 years of age with migraine using the claim data of International Statistical Classification of Diseases Related Health Problems, Tenth Revision (ICD-10) code G43. The patients with migraine were divided according to their migraine aura status. RESULTS: Migraine was present in 6.3% of the study population. Cases observed for MI, IS, CVD, and all-cause death were 2.6%, 3.6%, 5.9%, and 7.9%, respectively. The diagnosis of migraine was significantly associated with an increased risk of MI, IS, and CVD. The results remained significant after adjusting for covariates, including age, sex, body mass index, alcohol intake, smoking habits, physical activity, economic status, hypertension history, dyslipidemia, and duration of type 2 diabetes (MI, adjusted hazard ratio [aHR]: 1.182, 95% confidence interval [CI]: 1.146-1.219; IS, aHR: 1.111, 95% CI 1.082-1.14; CVD, aHR: 1.143, 95% CI 1.12-1.167). In particular, the presence of aura was associated with a higher risk of MI development compared to the non-aura group. The difference became more prominent with progressing age. CONCLUSIONS: In this nationwide population-based study, people with type 2 diabetes and migraines were found to be at a significantly higher risk for major cardiovascular events, including MI, IS, and CVD. The risk of MI and CVD significantly increased with the presence of aura symptoms among patients with migraine.

Risk of infective endocarditis associated with invasive dental procedures in patients with cardiac rhythm devices.

AIMS: The incidence of infective endocarditis related to cardiac implantable electronic devices (CIEDs) has gradually increased. The risk associated with dental procedures in patients with CIED implantation and the need for prevention of infective endocarditis remain unclear. The present study investigated the incidence and risk of infective endocarditis associated with invasive dental procedures in patients with CIEDs. METHODS AND RESULTS: We analysed a nationwide population-based cohort of patients with CIEDs who underwent dental procedures. We performed a self-controlled case series analysis and evaluated the incidence rate ratio of infective endocarditis 3 months after dental procedures. Of a total of 62 019 patients who underwent CIED implantation, 32 536 patients underwent at least one dental procedure during follow-up, and the mean number of dental procedures was 3.4 per patient. They were 152 infections with an incidence of 445 per 100 000 person-years in the dental procedure period and 500 events at an incidence of 255 per 100 000 person-years in the non-dental procedure period. The CIED-related infective endocarditis in the dental procedure period occurred significantly more frequently than during non-dental procedure periods (odds ratio, 1.75; 95% confidence interval, 1.48-2.05; P < 0.001). The mean time interval from dental procedure to infective endocarditis was 59.6 ± 47.3 days. CONCLUSION: Invasive dental procedures are associated with an increased risk of infective endocarditis in those who underwent CIED implantation. Appropriate preventive therapy might be needed in these patients.

Genotype and Phenotype Differences in CADASIL from an Asian Perspective.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small-vessel disease caused by mutations in the NOTCH3 gene. Classical pathogenic mechanisms are associated with cysteine gain or loss, but recent studies suggest that cysteine-sparing mutations might have a potential role as a pathogen. In comparison with CADASIL patients in Western countries, there are several differences in Asian patients: (1) prevalent locus of NOTCH3 mutations (exons 2-6 [particularly exon 4] vs. exon 11), (2) age at symptom onset, (3) prevalence of cerebral microbleeds and hemorrhagic stroke, (4) clinical symptoms, and (5) severity of white matter hyperintensities and typical involvement of the anterior temporal pole in magnetic resonance imaging. Both ethnicity and founder effects contribute to these differences in the clinical NOTCH3 spectrum in different cohorts. More functional investigations from diverse races are needed to clarify unknown but novel variants of NOTCH3 mutations. This review may broaden the spectrum of NOTCH3 variants from an Asian perspective and draw attention to the hidden pathogenic roles of NOTCH3 variants.

Underweight predicts poststroke cardiovascular events in patients without atrial fibrillation.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether underweight is associated with poststroke cardiovascular events and whether such association is different according to the presence of atrial fibrillation (AF). METHODS: Patients with acute stroke or transient ischemic attack who were prospectively registered in a multicenter stroke database from April 2008 to July 2020 were analyzed, excluding those aged 75 or older and those who were overweight. We prospectively captured major adverse cardiovascular events (MACE) within one year after stroke. Cox-proportional hazard regression analysis was conducted for each subgroup with or without AF after adjusting for predetermined vascular risk factors and potential confounders. RESULTS: Among 30,912 patients, 1494 (4.8%) cases were underweight and 29,418 (95.2%) cases were normal weight. The cumulative event rate of 1-year MACE was higher in the underweight group (9.0%) than in the normal weight group (5.6%). In Cox-proportional regression, underweight was associated with significantly higher MACE (adjusted hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.26-2.09) and recurrent stroke (adjusted HR: 1.42, 95% CI: 1.02-1.98) in all study patients. In patients with AF, the risk of MACE for the underweight group was not significantly increased. In contrast, in patients without AF, the underweight group had a consistently higher risk of MACE (adjusted HR: 1.66, 95% CI: 1.25-2.22) and recurrent stroke (adjusted HR: 1.50, 95% CI: 1.05-2.14). CONCLUSIONS: Underweight increased the risk of MACE and recurrent stroke within one year after acute stroke, especially in stroke without AF.

Pre-Stroke Glycemic Variability Estimated by Glycated Albumin Is Associated with Early Neurological Deterioration and Poor Functional Outcome in Prediabetic Patients with Acute Ischemic Stroke.

INTRODUCTION: Whether glycemic variability prior to stroke increases the risk of stroke outcomes in prediabetic patients presenting with acute ischemic stroke is still unclear. We evaluated whether pre-stroke glycemic variability, estimated by glycated albumin (GA), increased early neurological deterioration (END) and functional outcomes in prediabetic patients with acute ischemic stroke. METHODS: A total of 215 acute ischemic stroke patients with prediabetes were evaluated. The primary outcome was END, defined as an incremental increase in the National Institutes of Health Stroke Scale score by ≥1 point in motor power or ≥2 points in the total score within the 7 days after admission. The secondary outcome was poor functional status defined by a modified Rankin Scale at 3 months. Higher GA (≥16.0%) was determined to reflect glycemic fluctuation prior to ischemic stroke. RESULTS: Of the 215 prediabetic patients, 77 (35.8%) were in the higher GA group. In prediabetic patients, END occurrence and poor functional status were higher in the higher GA group than in the lower GA group. The multivariate analysis showed that a higher GA was associated with an increased risk of END occurrence and poor functional outcomes at 3 months (adjusted odds ratio [95% confidence interval], 4.58 [1.64-12.81], p = 0.004 and 2.50 [1.19-5.25], p = 0.02, respectively). CONCLUSION: Pre-stroke glycemic variability estimated by GA was associated with END occurrence and poor functional outcome after ischemic stroke in patients with prediabetes.

High Triglyceride Glucose Index Is Associated with Poor Outcomes in Ischemic Stroke Patients after Reperfusion Therapy.

INTRODUCTION: The triglyceride glucose index (TyG index) is a simple and reliable surrogate marker of insulin resistance (IR) that can predict functional outcomes and mortality after acute ischemic stroke (AIS). However, it is unclear whether the TyG index is associated with functional outcomes in patients with stroke who receive reperfusion therapy. Thus, we aimed to explore the prognostic value of the TyG index for the clinical outcomes of patients with AIS who underwent reperfusion therapy. METHODS: We retrospectively assessed patients with AIS, with occlusion of either the middle cerebral artery or internal carotid artery, who were evaluated using multiphase computed tomography angiography (mCTA) and received reperfusion therapy. The TyG index was calculated as "ln [fasting glucose level (mg/dL) × triglyceride level (mg/dL)]/2." Collateral status was evaluated using mCTA based on the University of Calgary Scale. Clinical outcomes included 3-month functional outcomes, early neurological deterioration, recanalization status, and hemorrhagic transformation. RESULTS: In all, 183 subjects (age 69.5 ± 12.4 years; men, 59.0%) were enrolled. The median initial National Institutes of Health Stroke Scale score was 15.0 (interquartile range [IQR] 11-18). The median TyG index was 4.8 (IQR, 4.6-5.1), and 158 patients had TyG levels >4.49, which represents the presence of IR. On univariate analysis, a higher TyG index was associated with both early neurological deterioration (18.4 vs. 0.0%, p = 0.041) and a 3-month poor functional outcome (mRS3-6) (61.4 vs. 32.0%, p = 0.011). After adjusting for multiple variables, including age, sex, type of reperfusion therapy, recanalization status, initial stroke severity, type of stroke, and history of hypertension and diabetes, high TyG index remained an independent predictor of a poor 3-month functional outcome (adjusted OR, 5.22; p = 0.014). However, TyG levels were not significantly associated with collateral status (p = 0.756). CONCLUSIONS: IR, represented by a high TyG index, may predict poor 3-month functional outcomes in patients with AIS who undergo reperfusion therapy.

Association between Osteoporosis and Cognitive Impairment during the Acute and Recovery Phases of Ischemic Stroke.

Background and objectives: Little is known about the effect of osteoporosis on cognitive function in the acute and recovery phases of stroke. Early bone mineral density assessments during acute stroke may be a useful marker of cognitive function. We evaluated the effect of osteoporosis on cognitive function at the early and recovery phase of ischemic stroke in patients aged >50 years. Materials and Methods: We retrospectively examined consecutive patients with acute stroke hospitalized between 2016 and 2018. Osteoporosis was defined as a T-score <-2.5 for the femoral neck or lumbar spine bone mineral density. The primary outcome was cognitive impairment measured by the Korean Mini-Mental State Examination in the acute phase and recovery phase of ischemic stroke. Results: Of the 260 included subjects (107 men and 153 women), 70 (26.9%) had osteoporosis. Cognitive impairment was more severe in the osteoporosis group than in the non-osteoporosis group (30.5% versus 47.1%, p = 0.001). After the recovery phase of stroke, the proportion of patients with cognitive impairment remained higher in the osteoporosis group. The multivariate analysis revealed a correlation between a low femoral neck bone mineral density and severe cognitive impairment in the acute and recovery phases of stroke (adjusted odds ratio (OR) 4.09, 95% confidence interval (CI) 1.11-15.14 in the acute phase, and adjusted OR 11.17, 95% CI 1.12-110.98 in the recovery phase). Conclusions: Low bone mineral density is associated with poor cognitive function in the acute and recovery phases of stroke.

Futile reperfusion and predicted therapeutic benefits after successful endovascular treatment according to initial stroke severity.

BACKGROUND: Futile reperfusion (poor functional status despite successful reperfusion) was observed in up to 67% of patients enrolled in recent endovascular treatment (EVT) clinical trials. We investigated the impact of baseline stroke severity on both futile reperfusion and therapeutic benefit of successful EVT. METHODS: Using a prospective multicenter stroke registry, we identified consecutive ischemic stroke patients with anterior circulation large artery occlusion, who were reperfused successfully by EVT (Thrombolysis in Cerebral Infarction grade 2b-3). The rate of futile reperfusion was assessed across the initial National Institutes of Health Stroke Scale (NIHSS) scores. The frequency of poor outcomes (modified Rankin scale [mRS] 3-6) according to NIHSS scores was compared between patients revascularized successfully by EVT and those who did not receive EVT, after standardizing for age. RESULTS: Among 21,591 patients with ischemic stroke, 972 (4.5%) received EVT within 12 h of onset, including 440 who met study eligibility criteria. Futile reperfusion was observed in 226 of the 440 study-eligible patients (51.4%) and was associated with stroke severity: 20.9% in NIHSS scores ≤5, 34.6% in 6-10, 58.9% in 11-20, and 63.8% in > 20 (p < 0.001). Nonetheless, the therapeutic benefit of EVT also increased with increasing stroke severity (p for interaction < 0.001): 0.1% in NIHSS ≤5, 18.6% in 6-10, 28.7% in 11-20, and 34.3% in > 20. CONCLUSIONS: EVT is more beneficial with increasing stroke severity, although futile reperfusion also increases with higher stroke severity.