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.

Optimal use of antithrombotic agents in recent small subcortical strokes accompanied by atrial fibrillation.

BACKGROUND: This study aimed to evaluate the efficacy and safety of anticoagulants (AC) and antiplatelets (APT) in patients with recent small subcortical infarctions (RSSI) and atrial fibrillation (AF). METHODS: We utilized a prospective multicenter stroke registry database to identify patients with RSSI with a concurrent diagnosis of AF. Propensity score matching analysis was used to balance baseline differences among the AC-only, APT-only, and their combination groups. The main outcomes of interest were time to occurrence of minor and major bleeding, stroke recurrence, and all-cause mortality. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for each outcome were calculated using the multivariable Cox proportional hazard regression analysis. RESULTS: Of the 404 eligible patients, 28.2% received APT only, 53.0% received AC only, and 18.9% received a combination of both. Notable differences were observed between these groups in terms of the 1-year stroke recurrence (APT, 32.5%; AC, 5.6%; APT + AC, 9.2%) and all-cause mortality (APT, 21.9%; AC, 6.1%; APT + AC, 14.5%), whereas the rates of bleeding events were comparable. The multivariable analysis indicated a significant association of AC alone with reduced risks of severe bleeding, stroke recurrence, and all-cause mortality compared with APT alone (aHR 0.64, 95% CI 0.41-0.98; aHR 0.11, 95% CI 0.06-0.22; aHR 0.22, 95% CI 0.11-0.44, respectively). The combination group showed a reduced risk of stroke recurrence compared to APT alone (aHR 0.19, 95% CI 0.08-0.46). These findings remained consistent with the propensity score-matched analysis. CONCLUSION: AC showed better clinical outcomes than APT in patients with RSSI and AF. Additionally, combination therapy with AC and APT was associated with a lower risk of stroke recurrence than APT alone.

Effects of Prior Metformin Use on Stroke Outcomes in Diabetes Patients with Acute Ischemic Stroke Receiving Endovascular Treatment.

Diabetes mellitus (DM) predisposes individuals to vascular injury, leading to poor outcomes after ischemic stroke and symptomatic hemorrhagic transformation (SHT) after thrombolytic and endovascular treatment (EVT). Metformin (MET), an oral antidiabetic drug, has shown potential neuroprotective effects, but its impact on stroke prognosis in DM patients undergoing EVT remains unclear. In a multicenter study, 231 patients with DM undergoing EVT for acute ischemic stroke were enrolled. Prior MET use was identified, and patients were stratified into MET+ and MET- groups. Demographics, clinical data, and outcomes were compared between groups. Multivariate analysis was used to assess the effect of MET on stroke prognosis. Of the enrolled patients, 59.3% were previously on MET. MET+ patients had lower initial infarct volumes and NIHSS scores compared to MET-taking patients. Multivariate analysis showed that MET+ was associated with a lower risk of stroke progression and SHT (with stroke progression as follows: odd ratio [OR] 0.24, 95% confidence interval [CI] [0.12-0.48], p < 0.001; SHT: OR 0.33, 95% CI [0.14-0.75], p = 0.01) and was also associated with better 3-month functional outcomes (mRS 0-2) after EVT. Prestroke MET use in DM patients undergoing EVT is associated with improved stroke prognosis, including reduced risk of stroke progression and SHT and better functional outcomes. These findings suggest the potential neuroprotective role of MET in this population and highlight its clinical utility as an adjunctive therapy in the management of ischemic stroke. Further research is warranted to elucidate the underlying mechanisms and to optimize MET therapy in this setting.

Impact of prior use of antiplatelet agents and non-vitamin K antagonist oral anticoagulants on stroke outcomes among endovascular-treated patients with high pre-stroke CHA2DS2-VASc score.

BACKGROUND: We assessed the influence of prior non-vitamin K antagonist (NOAC) use on stroke outcomes after endovascular treatment (EVT) in patients at a high risk of stroke based on their pre-stroke CHA2DS2-VASc score, and compared them with those who did not use any antithrombotic (NAU) or antiplatelet (APT) agents. METHODS: Data were collected from a multicenter database comprising consecutive acute ischemic stroke patients who underwent EVT during a span of 103 months. We evaluated pre-stroke CHA2DS2-VASc scores in enrolled patients and measured instances of successful reperfusion and symptomatic hemorrhagic transformation (SHT) following EVT as the main outcome measures. RESULTS: Among 12 807 patients with acute ischemic stroke, 3765 (29.4%) had a history of atrial fibrillation. Of these, 418 patients with CHA2DS2-VASc scores ≥2 received EVT alone. The prior NOAC group showed higher successful reperfusion rates compared with the prior NAU and APT groups (p=0.04). Multivariate analysis revealed that prior NOAC use increased the likelihood of successful reperfusion after EVT (OR [95% CI] 2.54 [1.34 to 4.83], p=0.004) and improved stroke outcomes, while the prior APT group did not. Furthermore, the prior NOAC use group was not associated with SHT after EVT. Propensity score matching confirmed these findings. CONCLUSION: Prior use of NOAC is associated with improved outcomes in high-risk stroke patients (pre-stroke CHA2DS2-VASc score ≥2) undergoing EVT.

U-shaped associations between glycated albumin and obesity and role of IL-10 in hyperacute ischemic stroke.

OBJECTIVE: There is growing interest in the use of new biomarkers such as glycated albumin (GA). In contrast to glycated hemoglobin (HbA1c), GA showed an inverse correlation with prestroke obesity status, but data are limited for ischemic stroke (IS). MATERIALS AND METHODS: We explored the association between GA and body mass index (BMI) and investigated inflammatory cytokines to support the academic background. In total, 155 patients with hyperacute IS (HIS) between 2011 and 2019 were included. To identify the association between GA and BMI, patients were divided into four groups according to BMI quartiles. Levels of inflammatory cytokines, including IL-1ß, IL-10, IL-6, TNF-α, and TNF-R1, were determined by ELISA using a ProcartaPlex multiplex immunoassay. RESULTS: The mean age of the 155 patients was 68 ± 12 years, and 67.1% were men. The lowest BMI group had higher GA levels (GA 2 T and 3 T = 80%) (p-value=0.017), and these U-shaped associations were maintained only for small vessel occlusion etiology (p-value= 0.004). Plasma IL-10 levels were positively correlated with BMI and showed a U-shaped pattern (p-value= 0.001). CONCLUSION: GA levels and BMI had U-shaped associations with HIS. IL-10, which acts as a protective cytokine for cardiovascular disease, may play a novel role in this association. Although GA is an emerging favorable clinical marker of cardiovascular outcomes, obesity status should be considered when interpreting these associations.

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.

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.

Cerebral Small Vessel Disease Burden and Futile Reperfusion after Endovascular Treatment for Patients with Acute Ischemic Stroke.

INTRODUCTION: Cerebral small vessel disease (SVD) burden includes increased risk of poor functional outcomes after acute ischemic stroke (AIS). We aimed to investigate the impact of cerebral SVD on 3-month functional outcomes in patients with AIS who received endovascular treatment (EVT) and to determine whether SVD is associated with futile reperfusion (FR). METHODS: Using a multicenter stroke registry, we analyzed consecutive patients with AIS with either intracranial and/or extracranial anterior circulation large artery occlusion, who were treated with EVT and achieved successful reperfusion (thrombolysis in cerebral infarction grade 2b-3). The cerebral SVD burden was evaluated using baseline brain magnetic resonance imaging using a modified Fazekas score (mFS). The main outcome variable was FR, defined as poor functional outcomes (modified Rankin scale 3-6) at 3 months after stroke, despite successful recanalization. Secondary outcomes included stroke progression/recurrence and any hemorrhagic transformation. RESULTS: Among 10,890 patients with AIS, 577 (5.3%) received EVT within 12 h of onset, including 354 who met study eligibility criteria. FR was observed in 191 patients (53.5%) and was positively associated with SVD burden. After adjustment for covariates including age, sex, stroke etiology, initial stroke severity, collateral status, Alberta stroke program early CT score, initial serum glucose, systemic blood pressure, and vascular risk factors, mFS grade 3 was significantly associated with FR (odds ratio: 3.93, 95% confidence interval: 1.602-9.619; p = 0.003). CONCLUSIONS: We demonstrated that cerebral SVD assessed with baseline brain MRI is associated with the futility of successful recanalization after EVT and any hemorrhagic transformation but not with early stroke progression or recurrence. Nevertheless, our findings do not justify withholding EVT in otherwise eligible patients with AIS based on the presence of severe SVD.

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.

Targeted Delivery of Iron Oxide Nanoparticle-Loaded Human Embryonic Stem Cell-Derived Spherical Neural Masses for Treating Intracerebral Hemorrhage.

This study evaluated the potential of iron oxide nanoparticle-loaded human embryonic stem cell (ESC)-derived spherical neural masses (SNMs) to improve the transportation of stem cells to the brain, ameliorate brain damage from intracerebral hemorrhage (ICH), and recover the functional status after ICH under an external magnetic field of a magnet attached to a helmet. At 24 h after induction of ICH, rats were randomly separated into three experimental groups: ICH with injection of phosphate-buffered saline (PBS group), ICH with intravenous injection of magnetosome-like ferrimagnetic iron oxide nanocubes (FION)-labeled SNMs (SNMs* group), and ICH with intravenous injection of FION-labeled SNMs followed by three days of external magnetic field exposure for targeted delivery by a magnet-embedded helmet (SNMs*+Helmet group). On day 3 after ICH induction, an increased Prussian blue-stained area and decreased swelling volume were observed in the SNMs*+Helmet group compared with that of the other groups. A significantly decreased recruitment of macrophages and neutrophils and a downregulation of pro-inflammatory cytokines followed by improved neurological function three days after ICH were observed in the SNMs*+Helmet group. Hemispheric atrophy at six weeks after ICH was significantly decreased in the SNMs*+Helmet group compared with that of the PBS group. In conclusion, we have developed a targeted delivery system using FION tagged to stem cells and a magnet-embedded helmet. The targeted delivery of SNMs might have the potential for developing novel therapeutic strategies for ICH.