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In patients with stroke caused by cardiac embolism, the responsible heart diseases include atrial fibrillation, acute myocardial infarction, sick sinus syndrome, valvular disease, and significant heart failure. When there is no clear source of the embolism, the condition is referred to as “embolic stroke with unknown source (ESUS).” Recent studies have shown that the most common cause of ESUS is a right-to-left cardiac shunt through a patent foramen ovale (PFO). However, considering that PFOs are found in up to 25% of the general population, their presence does not necessarily indicate causality. In patients with ESUS associated with a PFO, either anticoagulants or antiplatelets are used for the prevention of future strokes or transient ischemic attacks. However, it currently remains unclear which treatment is superior. Nevertheless, recent randomized clinical trials have shown that percutaneous closure of the PFO more effectively reduces the incidence of recurrent strokes compared to medical therapy alone in patients with PFO-related strokes. This benefit is especially significant when the PFO carries high-risk features, such as a large shunt or the presence of an atrial septal aneurysm. Furthermore, the effectiveness of PFO closure has been well documented in young patients (

Background and Purpose In young patients (aged 18–60 years) with patent foramen ovale (PFO)-associated stroke, percutaneous closure has been found to be useful for preventing recurrent ischemic stroke or transient ischemic attack (TIA). However, it remains unknown whether PFO closure is also beneficial in older patients. Methods Patients aged ≥60 years who had a cryptogenic stroke and PFO from ten hospitals in South Korea were included. The effect of PFO closure plus medical therapy over medical therapy alone was assessed by a propensity-score matching method in the overall cohort and in those with a high-risk PFO, characterized by the presence of an atrial septal aneurysm or a large shunt. Results Out of the 437 patients (mean age, 68.1), 303 (69%) had a high-risk PFO and 161 (37%) patients underwent PFO closure. Over a median follow-up of 3.9 years, recurrent ischemic stroke or TIA developed in 64 (14.6%) patients. In the propensity score-matched cohort of the overall patients (130 pairs), PFO closure was associated with a significantly lower risk of a composite of ischemic stroke or TIA (hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.24–0.84; P=0.012), but not for ischemic stroke. In a subgroup analysis of confined to the high-risk PFO patients (116 pairs), PFO closure was associated with significantly lower risks of both the composite of ischemic stroke or TIA (HR: 0.40; 95% CI: 0.21–0.77; P=0.006) and ischemic stroke (HR: 0.47; 95% CI: 0.23–0.95; P=0.035). Conclusion Elderly patients with cryptogenic stroke and PFO have a high recurrence rate of ischemic stroke or TIA, which may be significantly reduced by device closure.

Background and Purpose The accurate prediction of functional outcomes in patients with acute ischemic stroke (AIS) is crucial for informed clinical decision-making and optimal resource utilization. As such, this study aimed to construct an ensemble deep learning model that integrates multimodal imaging and clinical data to predict the 90-day functional outcomes after AIS. Methods We used data from the Korean Stroke Neuroimaging Initiative database, a prospective multicenter stroke registry to construct an ensemble model integrated individual 3D convolutional neural networks for diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), along with a deep neural network for clinical data, to predict 90-day functional independence after AIS using a modified Rankin Scale (mRS) of 3–6. To evaluate the performance of the ensemble model, we compared the area under the curve (AUC) of the proposed method with that of individual models trained on each modality to identify patients with AIS with an mRS score of 3–6. Results Of the 2,606 patients with AIS, 993 (38.1%) achieved an mRS score of 3–6 at 90 days post-stroke. Our model achieved AUC values of 0.830 (standard cross-validation [CV]) and 0.779 (time-based CV), which significantly outperformed the other models relying on single modalities: b-value of 1,000 s/mm2 (P

Background Atrial fibrillation detected after stroke (AFDAS) refers to the identification of newly diagnosed atrial fibrillation (AF) following an ischemic stroke in patients without known AF (KAF). The objective of this study was to compare the functional outcomes of patients diagnosed with AFDAS and those with KAF who underwent mechanical thrombectomy. Methods and Results We conducted a retrospective analysis of patients who underwent mechanical thrombectomy and with either new AF diagnosed during hospitalization or KAF. We compared the baseline characteristics, clinical, and procedure‐related variables between those with AFDAS and KAF. The primary outcome was the achievement of functional independence, defined as a modified Rankin Scale score of 0 to 2, at 3 months after stroke. Of the 252 patients, 101 (40.1%) were classified into the AFDAS group. The KAF group exhibited a higher rate of stroke history compared with the AFDAS group (32.5% versus 13.9%; P=0.001). Tandem occlusion was more common in the KAF group (13.2% versus 5.9%), while M2 occlusion was more common in the AFDAS group (11.3% versus 20.8%). The proportion of patients who achieved functional independence was higher in the AFDAS group (37.7% versus 52.5%; P=0.029). Multivariable analysis showed that AFDAS was associated with a favorable functional outcome (odds ratio, 2.67 [95% CI, 1.39–5.14]; P=0.003). Conclusions AFDAS demonstrated a positive association with functional independence in patients with stroke who underwent mechanical thrombectomy and were finally diagnosed to have AF during hospitalization. The observed disparities in occlusion site, intractable thrombus, and history of previous stroke may have contributed to these findings.

Background and Purpose The additive effects of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) remain unclear. We aimed to investigate the efficacy and safety of IVT prior to MT depending on the location of M1 occlusion. Methods We reviewed the cases of patients who underwent MT for emergent large-vessel occlusion of the M1 segment. Baseline characteristics as well as clinical and periprocedural variables were compared according to the location of M1 occlusion (i.e., proximal and distal M1 occlusion). The main outcome was the achievement of functional independence (modified Rankin Scale score, 0–2) at 3 months after stroke. The main outcomes were compared between the proximal and distal groups based on the use of IVT before MT. Results Among 271 patients (proximal occlusion, 44.6%; distal occlusion, 55.4%), 33.9% (41/121) with proximal occlusion and 24.7% (37/150) with distal occlusion underwent IVT prior to MT. Large-artery atherosclerosis was more common in patients with proximal M1 occlusion; cardioembolism was more common in those with distal M1 occlusion. In patients with proximal M1 occlusion, there was no association between IVT before MT and functional independence. In contrast, there was a significant association between the use of IVT prior to MT (odds ratio=5.30, 95% confidence interval=1.56–18.05, P=0.007) and functional independence in patients with distal M1 occlusion. Conclusion IVT before MT was associated with improved functional outcomes in patients with M1 occlusion, especially in those with distal M1 occlusion but not in those with proximal M1 occlusion.

Abstract Early neurological deterioration (END) in lenticulostriate artery (LSA) infarction is associated with perforating artery hypoperfusion. As middle cerebral artery (MCA) tortuosity may alter hemodynamics, we investigated the association between MCA tortuosity and END in LSA infarction. We reviewed patients with acute LSA infarction without significant MCA stenosis. END was defined as an increase of ≥ 2 or ≥ 1 in the National Institutes of Health Stroke Scale (NIHSS) total or motor score, respectively, within first 72 h. The MCA tortuosity index (actual /straight length) was measured. Stroke mechanisms were categorized as branch atheromatous disease (BAD; lesions > 10 mm and 4 axial slices) and lipohyalinotic degeneration (LD; lesion smaller than BAD). Factors associated with END in LD and BAD were investigated. END occurred in 104/390 (26.7%) patients. A high MCA tortuosity index (adjusted odds ratio, aOR 10.63, 95% confidence interval [2.57–44.08], p = 0.001) was independently associated with END. In patients with BAD, high initial NIHSS score (aOR 1.40 [1.03–1.89], p = 0.031) and presence of parental artery disease (stenosis

RationalePost-stroke fatigue (PSF) is a frequent problem in stroke survivors and often hinders their rehabilitation. PSF is difficult to treat, and pharmacological therapy is often ineffective. Transcranial direct current stimulation (tDCS) can modulate motor, sensory, cognitive and behavioral responses, as it alters neuronal activity by delivering a small amount of current via the scalp to the cortex, resulting in prolonged alterations to brain function. tDCS has been studied for the treatment of fatigue associated with other neurological diseases, namely, multiple sclerosis, Parkinson’s disease and post-polio syndrome.AimsThis proposed project will examine the effect of tDCS on PSF.Sample size estimatesWe will recruit 156 participants aged 18 to 80 with chronic stroke and allocate them equally to two groups (i.e., n = 78 per group).Methods and designThis proposed project will be a double-blind randomized control trial. The participants will be randomly divided into two groups. The control group will receive sham tDCS, and the treatment group will receive active tDCS. The latter treatment will involve application of a constant 2-mA current via one 5 × 5-cm anodal electrode positioned on the scalp over the C3 or C4 positions (motor cortex) of the lesioned hemisphere and one cathodal electrode positioned at the ipsilateral shoulder in two 20-min sessions per day for 5 days. The period of follow-up will be 4 weeks.Study outcome(s)The primary outcome measure will be a change in fatigue severity, as measured using the modified fatigue impact scale (MFIS). The participants’ scores on the MFIS (total score and physical, cognitive and psychosocial subscores) will be collected before treatment (T0), after 10 treatment sessions, i.e., 1 day after the fifth treatment day (T1), and 1 week (T2), 2 weeks (T3) and 4 weeks (T4) thereafter. Both per-protocol analysis and intention-to-treat analysis will be performed.DiscussionThis proposed project will provide proof-of-concept, i.e., demonstrate the benefits of tDCS for the treatment of PSF. The beneficiaries are the subjects participated in the study. This will stimulate further research to optimize tDCS parameters for the treatment of PSF.Clinical trial registrationwww.Chictr.org.cn, identifier: ChiCTR2100052515.

Background and purposeAtrial fibrillation-related stroke (AF-stroke) is associated with an adverse prognosis, characterized by a high incidence of progression, recurrence, and hemorrhagic transformation. Our study aims to investigate the potential benefits of stratified early administration of apixaban, taking into account infarct size during the acute phase, in order to enhance functional outcomes.MethodsWe conducted this study at a tertiary referral stroke center, enrolling acute AF-stroke patients who received apixaban during the acute phase. Infarct size was categorized as small, medium, or large based on diffusion-weighted imaging. Patients were divided into two groups: standard initiation (apixaban initiation based on guidelines, i.e., small: 4 days, medium: 7 days, large: 14 days after stroke) and early initiation (initiation before guideline recommendations) groups. We compared favorable outcomes (modified Rankin scale score ≤ 2) at 3 months post-stroke, stroke progression, early recurrence, and symptomatic hemorrhagic transformation (sHT) between the groups.ResultsOut of 299 AF-stroke patients, 170 (56.9%) were in the early initiation group. A favorable outcome was observed in 105 (61.8%) patients in the early initiation group and 62 (48.1%) patients in the standard initiation group (p = 0.019). Stroke progression or early recurrence occurred less frequently in the early initiation group (4.7% versus 13.2%, p = 0.007). Nevertheless, no difference in sHT was noted between the groups. Early initiation of apixaban was independently associated with favorable outcomes (odds ratio: 2.75, 95% confidence interval: 1.44–5.28, p = 0.002).ConclusionOur findings suggest that early initiation of apixaban, tailored to infarct size, could serve as a viable strategy to enhance functional outcomes. This approach may potentially decrease stroke progression and early recurrence without elevating the risk of sHT.

Background Vascular tortuosity affects the outcomes of mechanical thrombectomy (MT). We classified vertebral artery (VA) tortuosity into 3 types and investigated the effect of VA tortuosity on the outcomes in patients with basilar artery occlusion. Methods We retrospectively included patients who underwent MT for basilar artery occlusion between January 2012 and May 2022. Clinical and procedure‐related factors were obtained. VA tortuosity was classified into 3 types: type I: nontortuous VA; type II: S‐shaped vessel or a VA with a single acute angulation (1 location. The 3‐month modified Rankin scale, procedural outcomes, and post‐MT intracranial hemorrhage were assessed. Results A total of 106 patients with basilar artery occlusion were included. Age, baseline stroke severity, and 3‐month modified Rankin scale score were significantly different according to VA tortuosity (P = 0.003, P = 0.002, and P

Abstract Background Prognosis after vertebrobasilar stenting (VBS) may differ from that after carotid artery stenting (CAS). Here, we directly compared the incidence and predictors of in-stent restenosis and stented-territory infarction after VBS and compared them with those of CAS. Methods We enrolled patients who underwent VBS or CAS. Clinical variables and procedure-related factors were obtained. During the 3 years of follow-up, in-stent restenosis and infarction were investigated in each group. In-stent restenosis was defined as reduction in the lumen diameter > 50% compared with that after stenting. Factors associated with the occurrence of in-stent restenosis and stented-territory infarction in VBS and CAS were compared. Results Among 417 stent insertions (93 VBS and 324 CAS), there was no statistical difference in in-stent restenosis between VBS and CAS (12.9% vs. 6.8%, P = 0.092). However, stented-territory infarction was more frequently observed in VBS than in CAS (22.6% vs. 10.8%; P = 0.006), especially a month after stent insertion. HbA1c level, clopidogrel resistance, and multiple stents in VBS and young age in CAS increased the risk of in-stent restenosis. Diabetes (3.82 [1.24–11.7]) and multiple stents (22.4 [2.4–206.4]) were associated with stented-territory infarction in VBS. However, in-stent restenosis (odds ratio: 15.1, 95% confidence interval: 3.17–72.2) was associated with stented-territory infarction in CAS. Conclusions Stented-territory infarction occurred more frequently in VBS, especially after the periprocedural period. In-stent restenosis was associated with stented-territory infarction after CAS, but not in VBS. The mechanism of stented-territory infarction after VBS may be different from that after CAS.

Background and PurposeCardiac biomarkers including, elevated troponin (ET) and prolonged heart rate-corrected QT (PQTc) interval on electrocardiography are known to frequent and have a prognostic significance in patients with acute ischemic stroke (AIS). However, it is still challenging to practically apply the results for appropriate risk stratification. This study evaluate whether combining ET and PQTc interval can better assess the long-term prognosis in AIS patients.MethodsIn this prospectively registered observational study between May 2007 and December 2011, ET was defined as serum troponin-I ≥ 0.04 ng/ml and PQTc interval was defined as the highest tertile of sex-specific QTc interval (men ≥ 469 ms or women ≥ 487 ms).ResultsAmong the 1,668 patients [1018 (61.0%) men; mean age 66.0 ± 12.4 years], patients were stratified into four groups according to the combination of ET and PQTc intervals. During a median follow-up of 33 months, ET (hazard ratio [HR]: 4.38, 95% confidence interval [CI]: 2.94–6.53) or PQTc interval (HR: 1.53, 95% CI: 1.16–2.01) alone or both (HR: 1.77, 95% CI: 1.16–2.71) was associated with increased all-cause mortality. Furthermore, ET, PQTc interval alone or both was associated with vascular death, whereas only ET alone was associated with non-vascular death. Comorbidity burden, especially atrial fibrillation and congestive heart failure, and stroke severity gradually increased both with troponin value and QTc-interval.ConclusionsIn patients with AIS, combining ET and PQTc interval on ECG enhances risk stratification for long-term mortality while facilitating the discerning ability for the burden of comorbidities and stroke severity.

BackgroundVideo head impulse tests (vHITs), assessing the vestibulo-ocular reflex (VOR), may be helpful in the differential diagnosis of acute dizziness. We aimed to investigate vHITs in patients with acute posterior circulation stroke (PCS) to examine whether these findings could exhibit significant abnormalities based on lesion locations, and to evaluate diagnostic value of vHIT in differentiating dizziness between PCS and vestibular neuritis (VN).MethodsWe prospectively recruited consecutive 80 patients with acute PCS and analyzed vHIT findings according to the presence of dorsal brainstem stroke (DBS). We also compared vHIT findings between PCS patients with dizziness and a previously studied VN group (n = 29). Receiver operating characteristic (ROC) analysis was performed to assess the performance of VOR gain and its asymmetry in distinguishing dizziness between PCS and VN.ResultsPatients with PCS underwent vHIT within a median of 2 days from stroke onset. Mean horizontal VOR gain was 0.97, and there was no significant difference between PCS patients with DBS (n = 15) and without (n = 65). None exhibited pathologic overt corrective saccades. When comparing the PCS group with dizziness (n = 40) to the VN group (n = 29), patients with VN demonstrated significantly lower mean VOR gains in the ipsilesional horizontal canals (1.00 vs. 0.57, p

Background and Purpose We investigated the impact of comorbidity burden on troponin elevation, with separate consideration of neurological conditions, in patients with acute ischemic stroke (AIS). Methods This prospective, observational cohort study consecutively enrolled patients with AIS for 2 years. Serum cardiac troponin I was repeatedly measured, and disease-related biomarkers were collected for diagnosis of preassigned comorbidities, including atrial fibrillation (AF), ischemic heart disease (IHD), myocardial hypertrophy (MH), heart failure (HF), renal insufficiency (RI), and active cancer. The severity of neurological deficits and insular cortical ischemic lesions were assessed as neurological conditions. Adjusted associations between these factors and troponin elevation were determined using a multivariate ordinal logistic regression model and area under the receiver operating characteristic curve (AUC). Cox proportional hazards model was used to determine the prognostic significance of comorbidity beyond neurological conditions. Results Among 1,092 patients (66.5±12.4 years, 63.3% male), 145 (13.3%) and 335 (30.7%) had elevated (≥0.040 ng/mL) and minimally-elevated (0.040–0.010 ng/mL) troponin, respectively. In the adjusted analysis, AF, MH, HF, RI, active cancer, and neurological deficits were associated with troponin elevation. The multivariate model with six comorbidities and two neurological conditions exhibited an AUC of 0.729 (95% confidence interval [CI], 0.698–0.759). In Cox regression, AF, IHD, and HF were associated with adverse cardio-cerebrovascular events, whereas HF and active cancer were associated with mortality. Conclusion Troponin elevation in patients with AIS can be explained by the burden of comorbidities in combination with neurological status, which explains the prognostic significance of troponin assay.

Abstract Two different stroke mechanisms are involved in small vessel disease: branch atheromatous disease (BAD) and lipohyalinotic degeneration (LD). We compared mechanisms of stroke in lenticulostriate arteries (LSA) vs. anterior pontine arteries (APA) and verified factors associated with stroke mechanisms, including shape of middle cerebral artery (MCA) and basilar artery (BA). We retrospectively reviewed patients with acute ischemic stroke with penetrating artery territory confirmed by MRI. The mechanisms of stroke were categorized based on diffusion-weighted imaging; BAD was defined as lesion larger than 10 mm in LSA and lesions involving basal pontine in APA. Other lesions were classified as LD. The shapes of MCA and BA were classified as straight, with one angle, or with two angles (U, C or S shape, respectively) using anterior–posterior view. The study included 221 patients. LD was more common in LSA infarcts, but BAD was more common in APA infarcts (p

Post-stroke mood and emotional disturbances are frequent and diverse in their manifestations. Among them, post-stroke depression is the best known. Although post-stroke anger (PSA) has been studied relatively less, it can be as frequent as depression. Manifestations of PSA range from overt aggressive behaviors (including hitting or hurting others) to becoming irritable, impulsive, hostile, and less tolerable to family members. The possible pathophysiological mechanisms of PSA include neurochemical dysfunction due to brain injury, frustration associated with neurological deficits or unfavorable environments, and genetic predisposition. PSA causes distress in both patients and their caregivers, negatively influences the patient’s quality of life, and increases the burden on caregivers. It can be treated or prevented using various methods, including pharmacological therapies. In addition, anger or hostility may also be a risk or triggering factor for stroke. The hazardous effects of anger may be mediated by other risk factors, including hypertension or diabetes mellitus. The identification of anger as a result or cause of stroke is important because strategic management of anger may help improve the patient’s quality of life or prevent stroke occurrence. In this narrative review, we describe the phenomenology, prevalence, factors or predictors, relevant lesion locations, and pharmacological treatment of PSA. We further describe the current evidence on anger as a risk or triggering factor for stroke.

The online 2021 Asian-Pacific Heart and Brain Summit was organized to present and discuss experiences within leading Asian-Pacific centers with regard to institutional heart and brain teams managing the diagnosis, treatment, and follow-up of cryptogenic stroke (CS) patients with patent foramen ovale (PFO). This manuscript presents a narrative review of presentations and discussions during the summit meeting. Percutaneous PFO closure is an established therapy for CS patients in whom PFO is considered to be causal. Guidelines and consensus statements emphasize the importance of multidisciplinary clinical decision-making regarding PFO closure with the involvement of several clinical specialties, including neurology, cardiology, and hematology. It is also recommended that the patient be closely involved in this process. The heart and brain team is a collaborative platform that facilitates such a multidisciplinary decision-making process and patient involvement. It also creates opportunities for education and evaluation of the healthcare provided to patients with CS. This review provides insights into the implementation, composition, organization, and operation of a heart and brain team. Methods and metrics are suggested to evaluate the team’s role. We suggest that an efficient heart and brain team can implement guideline-recommended multidisciplinary clinical decision-making with regard to PFO closure in CS patients and play an important role in the management of these patients.

Background and Purpose We investigated the impact of stroke etiology on the endovascular treatment (EVT) procedure and clinical outcome of posterior circulation stroke (PCS) patients with EVT compared to anterior circulation stroke (ACS) patients. Methods We retrospectively analyzed ischemic stroke patients who underwent EVT between January 2012 and December 2020. Enrolled ACS and PCS patients were compared according to etiologies (intracranial arterial steno-occlusion [ICAS-O], artery-to-artery embolic occlusion [AT-O], and cardioembolic occlusion [CA-O]). EVT procedure and favorable clinical outcomes at 3 months (modified Rankin Scale 0–2) were compared between the ACS and PCS groups for each etiology. Results We included 419 patients (ACS, 346; PCS, 73) including 88 ICAS-O (ACS, 67; PCS, 21), 66 AT-O (ACS, 50; PCS, 16), and 265 CA-O (ACS, 229; PCS, 36) patients in the study. The onset-to-recanalization time was longer in the PCS group than in the ACS group (median 628.0 minutes vs. 421.0 minutes, P=0.01). In CA-O patients, the door-to-puncture time was longer, whereas the puncture-to-recanalization time was shorter in the PCS group than in the ACS group. The proportions of successful recanalization and favorable clinical outcomes were similar between the ACS and PCS groups for all three etiologies. Low baseline National Institutes of Health Stroke Scale (NIHSS) scores and absence of intracerebral hemorrhage at follow-up imaging were associated with favorable clinical outcomes in both groups, whereas successful recanalization (odds ratio, 11.74; 95% confidence interval, 2.60 to 52.94; P=0.001) was only associated in the ACS group. Conclusions The proportions of successful recanalization and favorable clinical outcomes were similar among all three etiologies between PCS and ACS patients who underwent EVT. Initial baseline NIHSS score and absence of hemorrhagic transformation were related to favorable outcomes in the PCS and ACS groups, whereas successful recanalization was related to favorable outcomes only in the ACS group.

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.

Background and purposeTop-of-basilar artery occlusion (TOB) is one of the most devastating strokes despite successful mechanical thrombectomy (MT). We aimed to investigate the impact of initial low cerebellum perfusion delay on the outcomes of TOB treated with MT.MethodsWe included patients who underwent MT for TOB. Clinical and peri-procedural variables were obtained. Perfusion delay in the low cerebellum was defined as (1) time-to-maximum (Tmax) >10 s lesions or (2) relative time-to-peak (rTTP) map >9.5 s with a diameter of ≥6 mm in the low cerebellum. The good functional outcome was defined as the achievement of a modified Rankin Scale score of 0–3 at 3 months after stroke.ResultsAmong the 42 included patients, 24 (57.1%) patients showed perfusion delay in the low cerebellum. The admission National Institutes of Health Stroke Scale (NIHSS) score was significantly higher in those with perfusion delay [17 (12–24) vs. 8 (6–15), P = 0.002]. Accordingly, the proportion of good functional outcomes was lower in those with perfusion delay than in those without [5 (20.8%) vs. 13 (72.2%), P = 0.003]. From the multivariable analysis, the admission NIHSS score [odds ratio (OR) = 0.86, 95% confidence intervals (CIs) = 0.75–0.98, P = 0.021] and low cerebellum perfusion delay (OR = 0.18, 95% Cis = 0.04–0.86, P = 0.031) were independently associated with the 3-month functional outcomes.ConclusionWe found that initial perfusion delay proximal to TOB in the low cerebellum might be a predictor for poor functional outcomes in TOB treated with MT.

BackgroundThe mechanism and characteristics of a post-transplantation stroke may differ between liver (LT) and kidney transplantation (KT), as the associated comorbidities and peri-surgical conditions are different. Herein, we investigated the characteristics and etiologies of stroke occurring after LT and KT.MethodsConsecutive patients who received LT or KT between January 2005 to December 2020 who were diagnosed with ischemic or hemorrhagic stroke after transplantation were enrolled. Ischemic strokes were further classified according to the etiologies. The characteristics of stroke, including in-hospital stroke, perioperative stroke, stroke etiology, and timing of stroke, were compared between the LT and KT groups.ResultsThere were 105 (1.8%) and 58 (1.3%) post-transplantation stroke patients in 5,950 LT and 4,475 KT recipients, respectively. Diabetes, hypertension, and coronary arterial disease were less frequent in the LT than the KT group. In-hospital and perioperative strokes were more common in LT than in the KT group (LT, 57.9%; KT, 39.7%; p = 0.03, and LT, 43.9%; KT, 27.6%; p = 0.04, respectively). Hemorrhagic strokes were also more common in the LT group (LT, 25.2%; KT, 8.6%; p = 0.01). Analysis of ischemic stroke etiology did not reveal significant difference between the two groups; undetermined etiology was the most common, followed by small vessel occlusion and cardioembolism. The 3-month mortality was similar between the two groups (both LT and KT, 10.3%) and was independently associated with in-hospital stroke and elevated C-reactive protein.ConclusionsIn-hospital, perioperative, and hemorrhagic strokes were more common in the LT group than in the KT group. Ischemic stroke subtypes did not differ significantly between the two groups and undetermined etiology was the most common cause of ischemic stroke in both groups. High mortality after stroke was noted in transplantation patients and was associated with in-hospital stroke.

Background and Purpose This study aimed to investigate the applicability of deep learning (DL) model using diffusion-weighted imaging (DWI) data to predict the severity of aphasia at an early stage in acute stroke patients. Methods We retrospectively analyzed consecutive patients with aphasia caused by acute ischemic stroke in the left middle cerebral artery territory, who visited Asan Medical Center between 2011 and 2013. To implement the DL model to predict the severity of post-stroke aphasia, we designed a deep feed-forward network and utilized the lesion occupying ratio from DWI data and established clinical variables to estimate the aphasia quotient (AQ) score (range, 0 to 100) of the Korean version of the Western Aphasia Battery. To evaluate the performance of the DL model, we analyzed Cohen’s weighted kappa with linear weights for the categorized AQ score (0–25, very severe; 26–50, severe; 51–75, moderate; ≥76, mild) and Pearson’s correlation coefficient for continuous values. Results We identified 225 post-stroke aphasia patients, of whom 176 were included and analyzed. For the categorized AQ score, Cohen’s weighted kappa coefficient was 0.59 (95% confidence interval [CI], 0.42 to 0.76; P

Background and Purpose Oral anticoagulants are needed in stroke patients with atrial fibrillation (AF) for the prevention of recurrent stroke. However, the risk of major events or bleeding may be greater in stroke patients than in those without, because the presence of cerebral atherosclerosis or small vessel disease may increase these risks. This study aimed to investigate the outcomes of apixaban-treated stroke patients with AF and assess whether these factors are associated with the outcome. Methods This was a sub-analysis of stroke patients with AF enrolled in a prospective, open-label, multicenter, post-marketing surveillance study in South Korea, who were treated with apixaban and underwent magnetic resonance imaging (MRI) (Clinical trial registration: NCT01885598). Results A total of 651 patients (mean age, 72.5±8.7 years) received apixaban for a mean duration of 82.7±37.4 weeks. Fifty-three bleeding events occurred in 39 patients (6.0%), and 10 (1.5%) experienced major bleeding. Seventeen patients (2.6%) had major events (stroke, n=15, 2.3%; all ischemic), systemic embolism (n=1, 0.2%), and death (n=3, 0.5%). MRI data showed no significant association between white matter ischemic changes and microbleeds, and major events or bleeding. Patients with cerebral atherosclerotic lesions had a higher rate of major events than those without (4.6% [n=10/219] vs. 1.7% [n=7/409], P=0.0357), which partly explains the increased prevalence of major outcomes in this group versus patients without stroke (0.7%, P=0.0002). Conclusions Apixaban is generally safe for patients with ischemic stroke. Increased primary outcomes in stroke patients may in part be attributed to the presence of cerebral atherosclerotic lesions, suggesting that further studies are needed to establish therapeutic strategies in this population.

Antithrombotic therapy is a cornerstone of acute ischemic stroke (AIS) management and secondary stroke prevention. Since the first version of the Korean Clinical Practice Guideline (CPG) for stroke was issued in 2009, significant progress has been made in antithrombotic therapy for patients with AIS, including dual antiplatelet therapy in acute minor ischemic stroke or high-risk transient ischemic stroke and early oral anticoagulation in AIS with atrial fibrillation. The evidence is widely accepted by stroke experts and has changed clinical practice. Accordingly, the CPG Committee of the Korean Stroke Society (KSS) decided to update the Korean Stroke CPG for antithrombotic therapy for AIS. The writing members of the CPG committee of the KSS reviewed recent evidence, including clinical trials and relevant literature, and revised recommendations. A total of 35 experts were invited from the KSS to reach a consensus on the revised recommendations. The current guideline update aims to assist healthcare providers in making well-informed decisions and improving the quality of acute stroke care. However, the ultimate treatment decision should be made using a holistic approach, considering the specific medical conditions of individual patients.

Hyperlipidemia is an important risk factor for ischemic stroke; the Stroke Prevention by Aggressive Reduction in Cholesterol Level and Treat Stroke to Target studies have shown that statins are beneficial for patients with stroke and that a low target for low-density lipoprotein cholesterol (LDL-C) concentration may maximize this benefit. Based on these results, recent guidelines have emphasized the application of “high-intensity statins” and “low LDL-C target” strategies in patients with stroke. However, it should be kept in mind that the role of blood lipids as a risk factor and benefit of lipid-lowering therapy are different among patients with different levels of cerebral arterial diseases. Studies have suggested that hypolipidemia, but not hyperlipidemia, is a risk factor for small vessel diseases (SVDs) such as intracerebral hemorrhages, microbleeds, white matter hyperintensities, and perhaps, lacunar infarction. Although lipid-lowering agents might benefit certain patients with SVD, high-intensity statin and low LDL-C target strategies cannot be applied. In contrast, these strategies are important in patients with extracranial atherosclerosis, such as internal carotid disease, considering ample evidence of the benefits of lipid-lowering agents. Imaging studies have shown that statins stabilize vulnerable plaques in these patients. Although lipid-lowering agents are likely to benefit patients with intracranial atherosclerosis, the degree of their benefit and appropriate target LDL-C level for these patients remain unclear. More studies are needed to elucidate the appropriate lipid-modifying strategies in patients with stroke with different levels of cerebral artery disease.

Background and Purpose Long-term changes in post-stroke depression (PSD), post-stroke emotional incontinence (PSEI), and post-stroke anger (PSA) have rarely been studied. Methods This is a sub-study of EMOTION, a randomized, placebo-controlled trial, that examined the efficacy of escitalopram on PSD, PSEI, and PSA in patients with stroke. We interviewed patients at the long-term period (LTP) using predefined questionnaires: Montgomery-Åsberg depression rating scale (MADRS) for PSD, modified Kim’s criteria for PSEI, and Spielberger trait anger scale for PSA. Additionally, the ENRICHD Social Support Instrument (ESSI) for the social support state and the modified Rankin Scale (mRS) were measured. We investigated the changes in and factors behind PSD, PSEI, and PSA at LTP. Results A total of 222 patients were included, and the median follow-up duration was 59.5 months (interquartile range, 50 to 70). Compared to the data at 6 months post-stroke, the prevalence of PSEI (11.7% at 6 months, 6.3% at LTP; P=0.05) and mean anger score (21.62, 16.24; P

Background and Purpose The outcome of endovascular treatment (EVT) may differ depending on the etiology of arterial occlusion. This study aimed to assess the differences in EVT outcomes in patients with intracranial arterial steno-occlusion (ICAS-O), artery-to-artery embolism (AT-O), and cardiac embolism (CA-O). Methods We retrospectively analyzed 330 patients with ischemic stroke who underwent EVT between January 2012 and August 2017. Patients were classified according to the etiology. The clinical data, EVT-related factors, and clinical outcomes were compared. The modified Rankin Scale (mRS) score at 3 months, determined using ordinal logistic regression (shift analysis), was the primary outcome. Results CA-O (n=149) was the most common etiology, followed by ICAS-O (n=63) and AT-O (n=49). Age, initial National Institutes of Health Stroke Scale (NIHSS) score, and rate of hemorrhagic transformation were significantly higher in patients with CA-O compared to AT-O and ICAS-O. The time from onset-to-recanalization was the shortest in the CA-O (356.0 minutes) groups, followed by the AT-O (847.0 minutes) and ICAS-O (944.0 minutes) groups. The rates of successful recanalization, mRS distribution, and favorable outcomes at 3 months (mRS 0–2; CA-O, 36.9%, AT-O, 53.1%; and ICAS-O, 41.3%) did not differ among the three groups. Baseline NIHSS score (odds ratio, 0.87; 95% confidence interval, 0.83 to 0.91) could independently predict a favorable shift in mRS distribution. Conclusions The functional outcomes of ICAS-O and AT-O were similar to those of CA-O, despite the delay in symptom onset-to-recanalization, suggesting that the therapeutic time window may be extended in these patients.

Background and Purpose Depression is common and debilitating illness accompanying many neurological disorders including non-traumatic subarachnoid hemorrhage (SAH). The aim of this systematic review was to identify and critically appraise all published studies that have reported the frequency, severity and time course of depression after SAH, the factors associated with its development and the impact of depression on patients’ quality of life after SAH. Methods The PubMed database was searched for studies published in English that recruited at least 40 patients (>18 years old) after SAH who were also diagnosed with depression. Results Altogether 55 studies covering 6,327 patients met study entry criteria. The frequency of depression ranged from 0% to 61.7%, with a weighted proportion of 28.1%. Depression remained common even several years after the index SAH. Depression after SAH was associated with female sex, premorbid depression, anxiety, substance use disorders or any psychiatric disorders, and coping styles. Comorbid cognitive impairment, fatigue, and physical disability also increased the risk of depression. Aneurysmal SAH and infarction may be related to depression as well. Depression reduces the quality of life and life satisfaction in patients after SAH. Conclusions Depression is common after SAH and seems to persist. Further research is needed to clarify its time course and identify the neuroendocrine and neurochemical factors and brain circuits associated with the development of post-SAH depression. Randomized controlled treatment trials targeting SAH-related depression are warranted.

Background and Purpose: The aim of this study was to determine the relationship between the heart rate-corrected QT (QTc) interval and the risk of incident long-term mortality in patients with acute ischemic stroke (AIS), considering the impact of sex differences on clinical characteristics, outcomes, and QTc intervals.Methods: We analyzed prospectively registered data included patients with AIS who visited the emergency room within 24 h of stroke onset and underwent routine cardiac testing, such as measurements of cardiac enzymes and 12-lead ECG. QTc interval was corrected for heart rate using Fridericia's formula and was stratified by sex-specific quartiles. Cox proportional hazards models were used to examine the association between baseline QTc interval and incident all-cause death.Results: A total of 1,668 patients with 1,018 (61.0%) men and mean age 66.0 ± 12.4 years were deemed eligible. Based on the categorized quartiles of the QTc interval, cardiovascular risk profile, and stroke severity increased with prolonged QTc interval, and the risk of long-term mortality increased over a median follow-up of 33 months. Cox proportional hazard model analysis showed that the highest quartile of QTc interval (≥479 msec in men and ≥498 msec in women; hazard ratio [HR]: 1.49, 95% confidence interval [CI]: 1.07–2.08) was associated with all-cause death. Furthermore, dichotomized QTc interval prolongation, defined by the highest septile of the QTc interval (≥501 ms in men and ≥517 m in women: HR: 1.33, 95% CI: 1.00–1.80) was significantly associated with all-cause mortality after adjusting for all clinically relevant variables, such as stroke severity.Conclusions: Prolonged QTc interval was associated with increased risk of long-term mortality, in parallel with the increasing trend of prevalence of cardiovascular risk profiles and stroke severity, across sex differences in AIS patients.

Background: Acute dizziness is a common symptom among patients visiting emergency medical centers. Extensive neurological examinations aimed at delineating the cause of dizziness often require experience and specialized training. We tried to diagnose central dizziness by machine learning using only basic clinical information.Methods: Patients were enrolled who had visited an emergency medical center with acute dizziness and underwent diffusion-weighted imaging. The enrolled patients were dichotomized as either having central (with a corresponding central lesion) or non-central dizziness. We obtained patient demographics, risk factors, vital signs, and presentation (non-whirling type dizziness or vertigo). Various machine learning algorithms were used to predict central dizziness. The area under the receiver operating characteristic curve (AUROC) was measured to evaluate diagnostic accuracy. The SHapley Additive exPlanations (SHAP) value was used to explain the importance of each factor.Results: Of the 4,481 visits, 414 (9.2%) were determined as central dizziness. Central dizziness patients were more often older and male and had more risk factors and higher systolic blood pressure. They also presented more frequently with non-whirling type dizziness (79 vs. 54.4%) than non-central dizziness. Catboost model showed the highest AUROC (0.738) with a 94.4% sensitivity and 31.9% specificity in the test set (n = 1,317). The SHAP value was highest for previous stroke presence (mean; 0.74), followed by male (0.33), presentation as non-whirling type dizziness (0.30), and age (0.25).Conclusions: Machine learning is feasible for classifying central dizziness using demographics, risk factors, vital signs, and clinical dizziness presentation, which are obtainable at the triage.

Endovascular recanalization therapy (ERT) has been a standard of care for patients with acute ischemic stroke due to large artery occlusion (LAO) within 6 hours after onset, since five landmark ERT trials conducted by 2015 demonstrated its clinical benefit. Recently, two randomized clinical trials demonstrated that ERT, even in the late time window of up to 16 hours or 24 hours after last known normal time, improved the outcome of patients who had a target mismatch, defined as either clinical-core mismatch or perfusion-core mismatch, which prompted the update of national guidelines in several countries. Accordingly, to provide evidence-based and up-to-date recommendations for ERT in patients with acute LAO in Korea, the Clinical Practice Guidelines Committee of the Korean Stroke Society decided to revise the previous Korean Clinical Practice Guidelines of Stroke for ERT. For this update, the members of the writing group were appointed by the Korean Stroke Society and the Korean Society of Interventional Neuroradiology. After thoroughly reviewing the updated evidence from two recent trials and relevant literature, the writing members revised recommendations, for which formal consensus was achieved by convening an expert panel composed of 45 experts from the participating academic societies. The current guidelines are intended to help healthcare providers, patients, and their caregivers make well-informed decisions and to improve the quality of care regarding ERT. The ultimate decision for ERT in a particular patient must be made in light of circumstances specific to that patient.

Tissue plasminogen activator (tPA) is the only therapeutic agent approved to treat patients with acute ischemic stroke. The clinical benefits of tPA manifest when the agent is administered within 4.5 hours of stroke onset. However, tPA administration, especially delayed administration, is associated with increased intracranial hemorrhage (ICH), hemorrhagic transformation (HT), and mortality. In the ischemic brain, vascular remodeling factors are upregulated and microvascular structures are destabilized. These factors disrupt the blood brain barrier (BBB). Delayed recanalization of the vessels in the presence of relatively matured infarction appears to damage the BBB, resulting in HT or ICH, also known as reperfusion injury. Moreover, tPA itself activates matrix metalloproteases, further aggravating BBB disruption. Therefore, attenuation of edema, HT, or ICH after tPA treatment is an important therapeutic strategy that may enable clinicians to extend therapeutic time and increase the probability of excellent outcomes. Recently, numerous agents with various mechanisms have been developed to interfere with various steps of ischemia/ reperfusion injuries or BBB destabilization. These agents successfully reduce infarct volume and decrease the incidence of ICH and HT after delayed tPA treatment in various animal stroke models. However, only some have entered into clinical trials; the results have been intriguing yet unsatisfactory. In this narrative review, I describe such drugs and discuss the problems and future directions. These “tPA helpers” may be clinically used in the future to increase the efficacy of tPA in patients with acute ischemic stroke.

Background and Purpose We aimed to assess whether early resting-state functional connectivity (RSFC) changes measured via functional magnetic resonance imaging (fMRI) could predict recovery from visual field defect (VFD) in acute stroke patients. Methods Patients with VFD due to acute ischemic stroke in the visual cortex and age-matched healthy controls were prospectively enrolled. Serial resting-state (RS)-fMRI and Humphrey visual field (VF) tests were performed within 1 week and at 1 and 3 months (additional VF test at 6 months) after stroke onset in the patient group. The control group also underwent RS-fMRI and a Humphrey VF test. The changes in RSFCs and VF scores (VFSs) over time and their correlations were investigated. Results In 32 patients (65±10 years, 25 men), the VFSs were lower and the interhemispheric RSFC in the visual cortices was decreased compared to the control group (n=15, 62±6 years, seven men). The VFSs and interhemispheric RSFC in the visual cortex increased mainly within the first month after stroke onset. The interhemispheric RSFC and VFSs were positively correlated at 1 month after stroke onset. Moreover, the interhemispheric RSFCs in the visual cortex within 1 week were positively correlated with the follow-up VFSs. Conclusions Interhemispheric RSFCs in the visual cortices within 1 week after stroke onset may be a useful biomarker to predict long-term VFD recovery.

Purpose Cigarette smoking (CS) is one of the major risk factors of cerebral atherosclerotic disease, however, its level of contribution to extracranial and intracranial atherosclerotic stenosis (ECAS and ICAS) was not fully revealed yet. The purpose of our study was to assess the association of CS to cerebral atherosclerosis along with other risk factors. Materials and Methods All consecutive patients who were angiographically confirmed with severe symptomatic cerebral atherosclerotic disease between January 2002 and December 2012 were included in this study. Multivariate logistic regression analyses were performed to identify risk factors for ECAS and ICAS. Thereafter, CS group were compared to non-CS group in the entire study population and in a propensity-score matched population with two different age-subgroups. Results Of 1709 enrolled patients, 794 (46.5%) had extracranial (EC) lesions and the other 915 (53.5%) had intracranial (IC) lesions. CS group had more EC lesions (55.8% vs. 35.3%, P

AimBehavioral dysexecutive syndrome (BDES) is one common neuropsychiatric comorbidity after stroke. Despite evidences suggesting the adverse effect of BDES on the survivors’ outcome, little is known about the association between BDES and the health-related quality of life (HRQoL) among stroke survivors and how BDES impacts the HRQoL. This study aimed to address these questions.MethodsThis study included 219 patients with acute ischemic stroke consecutively admitted to a regional hospital in Hong Kong. BDES was defined as a Chinese version of the Dysexecutive Questionnaire (DEX) score of ≥20 assessed at three months after stroke. The HRQoL was assessed with the Chinese version of the Stroke-Specific Quality of Life (SSQoL) questionnaire encompassing 12 domains. Multivariate linear regression models were employed to examine the association between BDES symptoms and the SSQoL total and domain scores. Structural equation model (SEM) was further constructed to delineate the linking pathways linking BDES and the HRQoL.ResultsThe study sample compromised mainly older patients with mild to moderate ischemic stroke. Compared with patients without BDES, those with BDES exhibited poorer performances regarding with the summarized SSQoL (226.2 ± 18.8 vs. 200.3 ± 29.8, p < 0.001) and almost all domains. The BDES symptoms were independently contributed to the whole HRQoL (SSQoL total score) (β = −0.20, p = 0.002), specifically to the domains in personality (β = −0.34, p < 0.001), language (β = −0.22, p = 0.01), and work/productivity (β = −0.32, p < 0.001), after adjusting demographic and clinical characteristics in linear models. The impacts of the BDES symptoms on the HRQoL were mainly explained by the indirect path mediated by depression and anxiety (path coefficient = −0.27, p < 0.05) rather than physical disability, while the resting was elucidated by the path directly linking BDES to the HRQoL (path coefficient = −0.17, p < 0.05).ConclusionThe present study preliminarily demonstrated a potential association between BDES and a lower level of the HRQoL, predominantly in domains of personality, language, and work/productivityafter acute ischemic stroke. This study also offered insights into the underlying mechanisms linking BDES and the HRQoL, implicating that integrative psychological therapies were urged to achieve better HRQoL after stroke.

Background Behavioral dysexecutive syndrome (BDES) is a common phenomenon following stroke. To date, research has focused mainly on individual behavioral symptoms rather than a more comprehensive characterization of goal‐directed behavior in stroke survivors. This cross‐sectional study evaluated the prevalence and clinical correlates of BDES in Hong Kong stroke survivors. Methods and Results A total of 369 stroke survivors were recruited from a regional hospital at 3 months after their index stroke. Patients’ demographic and clinical characteristics were extracted from a comprehensive stroke database. BDES was measured with the Chinese version of the Dysexecutive Questionnaire. Four neurocognitive batteries assessed domains of cognitive executive functions. The prevalence of BDES 3 months poststroke was 18.7%. At that time point, the Hospital Anxiety Depression Scale and Mini‐Mental State Examination scores and the presence of depression were significant predictors of BDES in a multivariate logistic regression analysis. These parameters remained significant predictors of the Dysexecutive Questionnaire score in a linear stepwise regression analysis and together accounted for 28.5% of the variance. Current depression was predictive of the Dysexecutive Questionnaire score in patients with BDES, with a variance of 9.7%. Furthermore, compared with the non‐BDES group, patients with BDES exhibited poor performance‐based executive function in the Chinese version of the Frontal Assessment Battery and color trails, arrow, and category fluency tests. Conclusions Symptoms of anxiety, current depression, and global cognitive function may be independent predictors of the presence and severity of BDES 3 months poststroke. Stroke survivors with BDES exhibit poor executive functioning, including goal maintenance and semantic memory.

Background and Purpose The pathophysiology of post-stroke depression (PSD) is complex and may differ according to an individual’s mood immediately after stroke. Here, we compared the therapeutic response and clinical characteristics of PSD at a later stage between patients with and without depression immediately after stroke. Methods This study involved a post hoc analysis of data from EMOTION (ClinicalTrials.gov NCT01278498), a placebo-controlled, double-blind trial that examined the efficacy of escitalopram (10 mg/day) on PSD and other emotional disturbances among 478 patients with acute stroke. Participants were classified into the Baseline-Blue (patients with baseline depression at the time of randomization, defined per the Montgomery-Asberg Depression Rating Scale [MADRS] ≥8) or the Baseline-Pink groups (patients without baseline depression). We compared the efficacy of escitalopram and predictors of 3-month PSD (MADRS ≥8) between these groups. Results There were 203 Baseline-Pink and 275 Baseline-Blue patients. The efficacy of escitalopram in reducing PSD risk was more pronounced in the Baseline-Pink than in the Baseline-Blue group (p for interaction=0.058). Several risk factors differentially affected PSD development based on the presence of baseline depression (p for interaction

Intracerebral hemorrhage (ICH) and lacunar infarction (LI) are the major acute clinical manifestations of cerebral small vessel diseases (cSVDs). Hypertensive small vessel disease, cerebral amyloid angiopathy, and hereditary causes, such as Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), constitute the three common cSVD categories. Diagnosing the underlying vascular pathology in these patients is important because the risk and types of recurrent strokes show significant differences. Recent advances in our understanding of the cSVD-related radiological markers have improved our ability to stratify ICH risk in individual patients, which helps guide antithrombotic decisions. There are general good-practice measures for stroke prevention in patients with cSVD, such as optimal blood pressure and glycemic control, while individualized measures tailored for particular patients are often needed. Antithrombotic combinations and anticoagulants should be avoided in cSVD treatment, as they increase the risk of potentially fatal ICH without necessarily lowering LI risk in these patients. Even when indicated for a concurrent pathology, such as nonvalvular atrial fibrillation, nonpharmacological approaches should be considered in the presence of cSVD. More data are emerging regarding the presentation, clinical course, and diagnostic markers of hereditary cSVD, allowing accurate diagnosis, and therefore, guiding management of symptomatic patients. When suspicion for asymptomatic hereditary cSVD exists, the pros and cons of prescribing genetic testing should be discussed in detail in the absence of any curative treatment. Recent data regarding diagnosis, risk stratification, and specific preventive approaches for both sporadic and hereditary cSVDs are discussed in this review article.

Intracranial large artery disease (ILAD) is the major cause of stroke worldwide. With the application of recently introduced diagnostic techniques, the prevalence of non-atherosclerotic ILAD is expected to increase. Herein, we reviewed recent reports and summarized progress in the diagnosis and clinical impact of differentiation between ILAD of atherosclerotic and non-atherosclerotic origin. Our review of the literature suggests that more careful consideration of non-atherosclerotic causes and the application of appropriate diagnostic techniques in patients with ILAD may not only provide better results in the treatment of patients, but it may also lead to more successful clinical trials for the treatment of intracranial atherosclerosis.

Background and Purpose Following the positive results from recent trials on endovascular therapy (EVT), bridging therapy (intravenous alteplase plus EVT) is increasingly being used for the treatment of acute ischemic stroke. However, the optimal dose of intravenous alteplase remains unknown in centers where bridging therapy is actively performed. The optimal dose for eventual recanalization and positive clinical outcomes in patients receiving bridging therapy also remains unknown. Methods In this prospective Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) sub-study, we explored the outcomes following treatment with two different doses (low- [0.6 mg/kg] or standard-dose [0.9 mg/kg]) of intravenous alteplase across 12 Korean centers where EVT is actively performed. The primary endpoint was a favorable outcome at 90 days (modified Rankin Scale scores 0 to 1). Secondary endpoints included symptomatic intracerebral hemorrhage (ICH) in all patients, and the recanalization rate and favorable outcome in patients who underwent cerebral angiography for EVT (ClinicalTrials.gov, number NCT01422616). Results Of 351 patients, the primary outcome occurred in 46% of patients in both the standard-(80/173) and low-dose (81/178) groups (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.72 to 1.81; P=0.582), although ICHs tended to occur more frequently in the standard-dose group (8% vs. 3%, P=0.056). Of the 67 patients who underwent cerebral angiography, there was no significant difference in favorable functional outcome between the standard- and low-dose groups (39% vs. 21%; OR, 2.39; 95% CI, 0.73 to 7.78; P=0.149). Conclusions There was no difference in functional outcome between the patients receiving different doses of alteplase in centers actively performing bridging therapy.