Digital therapeutics using virtual reality-based visual perceptual learning for visual field defects in stroke: A double-blind randomized trial.

INTRODUCTION: Visual field defects (VFDs) represent a debilitating poststroke complication, characterized by unseen parts of the visual field. Visual perceptual learning (VPL), involving repetitive visual training in blind visual fields, may effectively restore visual field sensitivity in cortical blindness. This current multicenter, double-blind, randomized, controlled clinical trial investigated the efficacy and safety of VPL-based digital therapeutics (Nunap Vision [NV]) for treating poststroke VFDs. METHODS: Stroke outpatients with VFDs (>6 months after stroke onset) were randomized into NV (defective field training) or Nunap Vision-Control (NV-C, central field training) groups. Both interventions provided visual perceptual training, consisting of orientation, rotation, and depth discrimination, through a virtual reality head-mounted display device 5 days a week for 12 weeks. The two groups received VFD assessments using Humphrey visual field (HVF) tests at baseline and 12-week follow-up. The final analysis included those completed the study (NV, n = 40; NV-C, n = 35). Efficacy measures included improved visual area (sensitivity ≥6 dB) and changes in the HVF scores during the 12-week period. RESULTS: With a high compliance rate, NV and NV-C training improved the visual areas in the defective hemifield (>72 degrees2) and the whole field (>108 degrees2), which are clinically meaningful improvements despite no significant between-group differences. According to within-group analyses, mean total deviation scores in the defective hemifield improved after NV training (p = .03) but not after NV-C training (p = .12). CONCLUSIONS: The current trial suggests that VPL-based digital therapeutics may induce clinically meaningful visual improvements in patients with poststroke VFDs. Yet, between-group differences in therapeutic efficacy were not found as NV-C training exhibited unexpected improvement comparable to NV training, possibly due to learning transfer effects.

Predictors of long-term medication adherence in stroke survivors: A multicentre, prospective, longitudinal study.

BACKGROUND: Although the optimal use of prescribed medications for stroke survivors is critical for preventing secondary stroke, longitudinal observations of the natural course of medication persistence and adherence in Korean stroke survivors are rare. Furthermore, studies are needed to identify strong predictors influencing medication adherence and to determine whether these predictors change over time. AIMS AND OBJECTIVES: To evaluate the longitudinal medication persistence and adherence at 3 months and 1 year after discharge in all stroke patients and to identify predictors of long-term medication adherence in patients who can self-medicate. DESIGN: A multicentre, prospective, longitudinal descriptive study. METHODS: A total of 600 consecutive ischaemic stroke patients were recruited from three stroke centres across Korea, from 1 September, 2017 to 28 February, 2019. Various factors related to medication adherence suggested by the World Health Organisation were investigated through face-to-face interviews at each centre during hospitalisation. Medication persistence and adherence were assessed at 3 months and 1 year after discharge using the eight-item Morisky Medication Adherence Scale through telephone interviews. RESULTS: Of 537 survivors at 3 months, 526 (98.0%) were persistent and 472 (89.7%) were adherent. Of 493 survivors at 1 year, 477 (96.8%) were persistent and 392 (82.2%) were adherent. Medication belief, income and health literacy were statistically significant predictors of three-month medication adherence, which predicted one-year medication adherence with older age and low income. CONCLUSIONS: Among Korean stroke survivors, three-month and one-year medication persistence and adherence were relatively good. Medication beliefs and three-month medication adherence were important and modifiable factors predicting three-month adherence and one-year adherence, respectively. RELEVANCE TO CLINICAL PRACTICE: To increase long-term adherence to medication, various strategies are needed to improve beliefs about medication, taking into account the patient's age and level of knowledge. These interventions need to be initiated during hospitalisation to form early medication habits after discharge.

Statin therapy in acute cardioembolic stroke with no guidance-based indication.

OBJECTIVE: It is uncertain whether patients with cardioembolic stroke and without a guidance-based indication for statin therapy should be administered a statin for prevention of subsequent vascular events. This study was performed to determine whether the statin therapy is beneficial in preventing major vascular events in this population. METHODS: Using a prospective multicenter stroke registry database, we identified patients with acute cardioembolic stroke who were hospitalized between 2008 and 2015. Patients who had other established indications for statin therapy according to current guidelines were excluded. Major vascular event was defined as a composite of stroke recurrence, myocardial infarction, and vascular death. We performed frailty model analysis with the robust sandwich variance estimator using the stabilized inverse probability of treatment weighting method to estimate hazard ratios of statin therapy on outcomes. RESULTS: Of 6,124 patients with cardioembolic stroke, 2,888 (male 44.6%, mean age 75.3 years, 95% confidence interval [CI] 74.8-75.8) were eligible, and 1,863 (64.5%) were on statin therapy during hospitalization. After a median follow-up of 359 days, cumulative incidences of major vascular events were 9.3% in the statin users and 20.5% in the nonusers (p < 0.001 by log-rank test). The adjusted hazard ratios of statin therapy were 0.39 (95% CI 0.31-0.48) for major vascular events, 0.81 (95% CI 0.57-1.16) for stroke recurrence, 0.28 (95% CI 0.21-0.36) for vascular death, and 0.53 (95% CI 0.45-0.61) for all-cause death. CONCLUSION: Starting statin during the acute stage of ischemic stroke may reduce the risk of major vascular events, vascular death, and all-cause death in patients with cardioembolic stroke with no guidance-based indication for statin.

Three-month modified Rankin Scale as a determinant of 5-year cumulative costs after ischemic stroke: An analysis of 11,136 patients in Korea.

OBJECTIVE: Stroke is a devastating and costly disease; however, there is a paucity of information on long-term costs and on how they differ according to 3-month modified Rankin scale (mRS) score, which is a primary outcome variable in acute stroke intervention trials. METHODS: We analyzed a prospective multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea) database through linkage with claims data from the National Health Insurance Service with follow-up to December 2016. Healthcare expenditures were converted into daily cost individually, and annual and cumulative costs up to 5 years were estimated and compared according to the 3-month mRS score. RESULTS: Between January 2011 and November 2013, 11,136 patients were enrolled in the study. The mean age was 68 years, and 58% were men. The median follow-up period was 3.9 years (range 0-5 years). Mean cumulative cost over 5 years was $117,576 (US dollars [USD]); the cost in the first year after stroke was the highest ($38,152 USD), which increased markedly from the cost a year before stroke ($8,718 USD). The mean 5-year cumulative costs differed significantly according to the 3-month mRS score (p < 0.001); the costs for a 3-month mRS score of 0 or 5 were $53,578 and $257,486 USD, respectively. Three-month mRS score was an independent determinant of long-term costs after stroke. CONCLUSIONS: We show that 3-month mRS score plays an important role in the prediction of long-term costs after stroke. Such estimates relating to 3-month mRS categories may be valuable when undertaking health economic evaluations related to stroke care.

Effect of Heart Rate on Stroke Recurrence and Mortality in Acute Ischemic Stroke With Atrial Fibrillation.

Background and Purpose- There is a paucity of information about the role of resting heart rate in the prediction of outcome events in patients with ischemic stroke with atrial fibrillation. We aimed to investigate the relationships between the level and variability of heart rate in the acute stroke period and stroke recurrence and mortality after acute ischemic stroke in patients with atrial fibrillation. Methods- Acute patients with ischemic stroke who had atrial fibrillation and were hospitalized within 48 hours of stroke onset were identified from a multicenter prospective stroke registry database. The acute stroke period was divided into early (within 24 hours of hospitalization) and late (72 hours to 7 days from onset) stages, and data on heart rate in both stages were collected. Moreover, the level and variability of heart rate were assessed using mean values and coefficients of variation. Outcome events were prospectively monitored up to 1 year after the index stroke. Results- Among 2046 patients eligible for the early acute stage analysis, 102 (5.0%) had a stroke recurrence, and 440 (21.5%) died during the first year after stroke. A statistically significant nonlinear J-shaped association was observed between mean heart rate and mortality (P<0.04 for quadratic and overall effect) but not between mean heart rate and stroke recurrence (P>0.1 for quadratic and overall effect). The nonlinear and overall effects of the coefficients of variation of heart rate were not significant for all outcome variables. The same results were observed in the late acute stage analysis (n=1576). Conclusions- In patients with atrial fibrillation hospitalized for acute ischemic stroke, the mean heart rate during the acute stroke period was not associated with stroke recurrence but was associated with mortality (nonlinear, J-shaped association). The relationships between heart rate and outcomes were not observed with respect to heart rate variability.

Digital Therapeutics: Emerging New Therapy for Neurologic Deficits after Stroke.

Digital therapeutics is an evidence-based intervention using high-quality software, with the sole purpose of treatment. As many healthcare systems are encountering high demands of quality outcomes, the need for digital therapeutics is gradually increasing in the clinical field. We conducted review of the implications of digital therapeutics in the treatment of neurological deficits for stroke patients. The implications of digital therapeutics have been discussed in four domains: cognition, speech and aphasia, motor, and vision. It was evident that different forms of digital therapeutics such as online platforms, virtual reality trainings, and iPad applications have been investigated in many trials to test its feasibility in clinical use. Although digital therapeutics may deliver high-quality solutions to healthcare services, the medicalization of digital therapeutics is accompanied with many limitations. Clinically validated digital therapeutics should be developed to prove its efficacy in stroke rehabilitation.

Efficacy of Combining Proximal Balloon Guiding Catheter and Distal Access Catheter in Thrombectomy with Stent Retriever for Anterior Circulation Ischemic Stroke.

OBJECTIVE: We evaluated efficacy of combining proximal balloon guiding catheter (antegrade flow arrest) and distal access catheter (aspiration at the site of occlusion) in thrombectomy for anterior circulation ischemic stroke. METHODS: We retrospectively analyzed 116 patients who underwent mechanical thrombectomy with stent retriever. The patients were divided by the techniques adopted, the combined technique (proximal balloon guiding catheter and large bore distal access catheter) group (n=57, 49.1%) and the conventional (guiding catheter with stent retriever) technique group (n=59, 50.9%). We evaluated baseline characteristics (epidemiologic data, clinical and imaging characteristics) and procedure details (the number of retrieval attempts, procedure time), as well as angiographic (thrombolysis in cerebral infarction (TICI) score, distal thrombus migration) and clinical outcome (National Institutes of Health Stroke Scale at discharge, modified Rankin Scale [mRS] at 3 months) of them. RESULTS: The number of retrieval attempts was lower (p=0.002) and the first-pass successful reperfusion rate was higher (56.1% vs. 28.8%; p=0.003) in the combined technique group. And the rate of final result of TICI score 3 was higher (68.4% vs. 28.8%; p<0.01) and distal thrombus migration rate was also lower (15.8% vs. 40.7%; p=0.021) in the combined technique group. Early strong neurologic improvement (improvement of National Institutes of Health Stroke Scale ≥11 or National Institutes of Health Stroke Scale ≤1 at discharge) rate (57.9% vs. 36.2%; p=0.02) and favorable clinical outcome (mRS at 3 months ≤2) rate (59.6% vs. 33.9%; p=0.005) were also better in the combined technique group. CONCLUSION: The combined technique needs lesser attempts, decreases distal migration, increases TICI 3 reperfusion and achieves better clinical outcomes.

White matter hyperintensity load on stroke recurrence and mortality at 1 year after ischemic stroke.

OBJECTIVE: To define the role and risks associated with white matter hyperintensity (WMH) load in a stroke population with respect to recurrent stroke and mortality after ischemic stroke. METHODS: A total of 7,101 patients at a network of university hospitals presenting with ischemic strokes were followed up for 1 year. Multivariable Cox proportional hazards model and competing risk analysis were used to examine the independent association between quartiles of WMH load and stroke recurrence and mortality at 1 year. RESULTS: Overall recurrent stroke risk at 1 year was 6.7%/y, divided between 5.6%/y for recurrent ischemic and 0.5%/y for recurrent hemorrhagic strokes. There was a stronger association between WMH volume and recurrent hemorrhagic stroke by quartile (hazard ratio [HR] 7.32, 14.12, and 33.52, respectively) than for ischemic recurrence (HR 1.03, 1.37, and 1.61, respectively), but the absolute incidence of ischemic recurrence by quartile was higher (3.8%/y, 4.5%/y, 6.3%/y, and 8.2%/y by quartiles) vs hemorrhagic recurrence (0.1%/y, 0.4%/y, 0.6%/y, and 1.3%/y). All-cause mortality (10.5%) showed a marked association with WMH volume (HR 1.06, 1.46, and 1.60), but this was attributable to nonvascular rather than vascular causes. CONCLUSIONS: There is an association between WMH volume load and stroke recurrence, and this association is stronger for hemorrhagic than for ischemic stroke, although the absolute risk of ischemic recurrence remains higher. These data should be helpful to practitioners seeking to find the optimal preventive/treatment regimen for poststroke patients and to individualize risk-benefit ratios.

Dual Versus Mono Antiplatelet Therapy in Large Atherosclerotic Stroke.

Background and Purpose- Two large-scale randomized controlled trials of recurrent stroke prevention suggest that dual antiplatelet therapy with clopidogrel plus aspirin is beneficial for prevention of subsequent ischemic events. There is a paucity of data, however, on the efficacy or effectiveness of such an approach in the treatment of stroke patients with symptomatic large artery atherosclerotic occlusive disease. Methods- We used a multicenter stroke registry database (Clinical Research Collaboration for Stroke in Korea) to analyze acute ischemic stroke patients due to large artery atherosclerotic occlusive disease who were treated with aspirin alone or combination of clopidogrel and aspirin from May 2008 to May 2015. The results were analyzed by intention-to-treat, per-protocol, and as-treated methodologies. The primary end point was the 1-year composite outcome of stroke recurrence, myocardial infarction, and all-cause death. To balance the differences between groups, a frailty model using propensity scores and inverse probability of treatment weighting was used. Results- A total of 5934 patients with symptomatic large artery atherosclerotic occlusive disease were treated either with clopidogrel plus aspirin (n=2903, 49%) or aspirin (n=3031, 51%). The frequency of the primary outcome was 12% (n=353) in the clopidogrel-aspirin group and 14% (n=410) in the aspirin group. The hazards of the primary outcome with combination over aspirin only were significantly reduced in the per-protocol and as-treated analyses (hazard ratio, 0.71; 95% CI, 0.57-0.88; P=0.002 and hazard ratio, 0.81; 95% CI, 0.69-0.96; P=0.02, respectively), but there was borderline significance in the intention-to-treat analysis (hazard ratio, 0.86; 95% CI, 0.74-1.01; P=0.06). Combination therapy was beneficial for all-cause death in all analyses but did not reduce recurrent stroke. Conclusions- Compared with patients receiving aspirin monotherapy, the primary outcome seemed to occur less frequently in patients receiving dual antiplatelet therapy, which is explained mainly by the decrease of all-cause death. Since this is a nonrandomized, retrospective, observational study, our study should be cautiously interpreted.

Estimation of Acute Infarct Volume with Reference Maps: A Simple Visual Tool for Decision Making in Thrombectomy Cases.

BACKGROUND AND PURPOSE: Thrombectomy within 24 hours can improve outcomes in selected patients with a clinical-infarct mismatch. We devised an easy-to-use visual estimation tool that allows infarct volume estimation in centers with limited resources. METHODS: We identified 1,031 patients with cardioembolic or large-artery atherosclerosis infarction on diffusion-weighted images (DWIs) obtained before recanalization therapy and within 24 hours of onset, and occlusion of the internal carotid or middle cerebral artery. Acute DWIs were mapped onto a standard template and used to create visual reference maps with known lesion volumes, which were then used in a validation study (with 130 cases) against software estimates of infarct volume. RESULTS: The DWI reference map chart comprises 144 maps corresponding to 12 different infarct volumes (0.5, 1, 2, 3, 5, 7, 9, 11, 13, 15, 17, and 19 mL) in each of 12 template slices (Montreal Neurological Institute z-axis -15 to 51 mm). Infarct volume in a patient is estimated by selecting a slice with a similar infarct size at the corresponding z-axis level on the reference maps and then adding up over all slices. The method yielded good correlations to software volumetrics and was easily learned by both experienced and junior physicians, with approximately 1 to 2 minutes spent per case. The sensitivity, specificity, and accuracy for detecting threshold infarct volumes (<21, <31, and <51 mL) were very high (all about >90%). CONCLUSION: s We developed easy-to-use reference maps that allow prompt and reliable visual estimation of infarct volumes for triaging patients to thrombectomy in acute 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.

Magnetic Resonance Imaging Versus Computed Tomography Angiography Based Selection for Endovascular Therapy in Patients With Acute Ischemic Stroke.

Background and Purpose- Randomized trials comparing the use of multimodal magnetic resonance imaging (MRI) to multimodal computed tomography (CT)/ CT angiography (CTA) for selecting candidates for endovascular therapy (EVT) have not been reported. This study aimed to elucidate whether MRI-based selection for EVT is safe and effective within and after a 6-hour time window compared with conventional CTA-based selection. Methods- Data from a prospective, nationwide, multicenter stroke registry were analyzed. Workflow timelines were compared between patients selected for EVT based on MRI (the MRI group) and CTA (the CTA group). Multivariable ordinal and binary logistic regression analyses were performed to explore the relationships between decision imaging for EVT and clinical outcomes, including good and excellent outcomes (modified Rankin Scale scores of 0-2 and 0-1, respectively) at 3-month, modified Rankin Scale score distributions and safety outcomes (symptomatic intracranial hemorrhage [SICH] and mortality). Results- Ultimately, 1265 patients (age, 69±12 yrs; men, 55%) were enrolled in this study. The median National Institutes of Health Stroke Scale score was 15 (11-19). All workflow time metrics were significantly delayed in the MRI group compared with the CTA group. There was no difference in good 3-month outcomes in patients arriving within 6 hours of onset between the MRI and CTA groups (38.1% versus 38.5%), but SICH and mortality rates were lower in the MRI group than the CTA group (3.8% versus 7.7%, P=0.01 for SICH; 15.4% versus 20.9%, P=0.04 for mortality). In the multivariable analysis, decision imaging was not significantly associated with 3-month functional outcomes (all P>0.1) or mortality ( P=0.051); however, the MRI group was less likely to develop SICH than the CTA group ( P=0.01; odds ratio, 0.34 [95% CI, 0.17-0.77]). Conclusions- Our study found MRI-based selection for EVT was not associated with improving functional outcome compared with CT-based selection, but may be better at reducing the risk of SICH, despite the delays in all workflow time metrics.

Comparative Effectiveness of Aspirin and Clopidogrel Versus Aspirin in Acute Minor Stroke or Transient Ischemic Attack.

Background and Purpose- This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel-aspirin to that of aspirin monotherapy in patients with acute minor cerebral ischemia using a prospective, nationwide, multicenter, stroke registry database in South Korea. Methods- CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events)-like patients who met eligibility criteria modeled on the CHANCE trial eligibility criteria, including (1) acute minor ischemic stroke defined as National Institutes of Health Stroke Scale score ≤3 or lesion positive transient ischemic attack within 24 hours of onset and (2) noncardioembolic stroke mechanism. Propensity scores using the inverse probability of treatment weighting was used to adjust for baseline imbalances. The primary outcome was the composite of all stroke (ischemic and hemorrhagic), myocardial infarction, and vascular death by 3 months. Results- Among 5590 patients meeting the eligibility criteria, age was 64±13 year and 62.6% were male. Aspirin and combination of clopidogrel-aspirin were administered in 66.1% and 33.9% of patients, respectively. In unadjusted analysis, rates of the 3-month primary vascular event outcome were lower with clopidogrel-aspirin versus aspirin, 9.9% versus 12.2% (hazard ratio, 0.79 [0.67-0.95]). In propensity-weighted Cox proportional hazards regression with robust estimation, clopidogrel-aspirin was associated with a lower risk of the primary vascular event outcome (hazard ratio, 0.76 [0.63-0.92]) and all stroke events (hazard ratio, 0.74 [0.61-0.90]). Among 6 predefined subgroup analyses, 3 showed potential modification of treatment effect, with lesser benefit associated with the absence of prior antiplatelet use (Pinteraction=0.01) and younger age (<75 years, Pinteraction=0.07), and absence of benefit associated with small vessel occlusion subtype (Pinteraction=0.08). Conclusions- Dual antiplatelet therapy with aspirin and clopidogrel was associated with reduced stroke, myocardial infarction, and vascular death in the 3 months following a presenting minor, noncardioembolic ischemic stroke. Benefits may be particularly magnified in patients with a history of prior antiplatelet therapy, older age, and nonsmall vessel disease stroke mechanism.

Executive Summary of Stroke Statistics in Korea 2018: A Report from the Epidemiology Research Council of the Korean Stroke Society.

Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the "Stroke Statistics in Korea" project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.

Hemispheric Asymmetry of White Matter Hyperintensity in Association With Lacunar Infarction.

Background White matter hyperintensities ( WMHs ) are commonly asymmetric between hemispheres but for unknown reasons. We investigated asymmetric WMHs associated with lacunar infarcts. Methods and Results A total of 267 consecutive patients with small first-ever supratentorial infarcts (≤20 mm) were included. None had a relevant vascular stenosis. WMH asymmetry was measured based on the hemispheric difference of a modified Scheltens scale score (≥3 defined as asymmetric). We analyzed the association of the hemispheric WMH asymmetry with old silent lacunar infarcts or acute lacunar infarcts. We compared lesion frequency maps between groups and generated t-statistics maps. The mean age of patients was 64 years, and 63% were men. Asymmetric WMH was more than 3-fold as frequent ( P<0.001) in the group with old silent lacunar infarcts (42%, 43/102) than in the group without old silent lacunar infarcts (15%, 24/165). In patients with left hemispheric dominance of WMHs , an acute lacunar infarct was more likely to be located in the left (versus right) hemisphere (74% versus 26%, P<0.001). In patients with right hemispheric dominance of WMHs , an acute lacunar infarct was more likely to be located on the right (versus left) hemisphere (81% versus 19%, P<0.001). Mapping studies showed that the side of hemispheric dominance of WMHs was associated with acute and silent lacunes on the same side. Conclusions These are the first data to show that asymmetric WMH s are associated with both old silent lacunar infarcts and acute lacunar infarcts ipsilateral to the greatest WMH burden. This suggests that the hemisphere with relatively large WMHs is more vulnerable to ischemia.

Trajectory Groups of 24-Hour Systolic Blood Pressure After Acute Ischemic Stroke and Recurrent Vascular Events.

Background and Purpose- Blood pressure dynamics in patients with acute ischemic stroke may serve as an important modifiable and prognostic factor. Methods- A total of 8376 patients with acute ischemic stroke were studied from a prospective multicenter registry. Patients were eligible if they had been admitted within 24 hours of symptom onset and had ≥5 systolic blood pressure (SBP) measurements during the first 24 hours of hospitalization. SBP trajectory groups in the first 24 hours were identified using the TRAJ procedure in SAS software with delta-Bayesian Information Criterion and prespecified modeling parameters. Vascular events, including recurrent stroke, myocardial infarction, and death, were prospectively collected. The risk of having vascular events was calculated using the frailty model to adjust for clustering by hospital. Results- The group-based trajectory model classified patients with acute ischemic stroke into 5 SBP trajectory groups: low (22.3%), moderate (40.8%), rapidly stabilized (11.9%), acutely elevated (18.5%), and persistently high (6.4%) SBP. The risk of having vascular events was increased in the acutely elevated (hazard ratio, 1.28 [95% confidence interval, 1.12-1.47]) and the persistently high SBP groups (hazard ratio, 1.67 [95% confidence interval, 1.37-2.04]) but not in the rapidly stabilized group (hazard ratio, 1.13 [95% confidence interval, 0.95-1.34]), when compared with the moderate SBP group. Conclusions- SBP during the first 24 hours after acute ischemic stroke may be categorized into distinct trajectory groups, which differ in relation to stroke characteristics and frequency of subsequent recurrent vascular event risks. The findings may help to recognize potential candidates for future blood pressure control trials.

Clinical and radiological factors associated with unfavorable outcome after intravenous thrombolysis in patients with mild ischemic stroke.

BACKGROUND: A significant proportion of patients with mild ischemic stroke become disabled despite receiving intravenous thrombolytic therapy. The purpose of this study was to assess the clinical and radiological factors associated with unfavorable outcomes in patients with minor ischemic stroke that received intravenous recombinant tissue plasminogen activator (rt-PA) therapy. METHODS: We identified anterior circulation stroke patients with initial National Institutes of Health Stroke Scale (NIHSS) scores ≤5 who received intravenous thrombolysis within 4.5 h of stroke onset and had pretreatment magnetic resonance (MR)/MR angiography using our prospective stroke database. We analyzed baseline characteristics, infarction patterns on diffusion-weighted imaging (DWI), and steno-occlusive lesions on MR angiography. Unfavorable outcome was defined as a modified Rankin Scale (mRS) score ≥ 2 at 90 days. Logistic regression was used to determine independent predictors of unfavorable outcomes. RESULTS: Among 121 patients (85 men; mean age, 63.4 ± 11.3 years) included in this study, 46 (38%) had unfavorable outcomes at 90 days and DWI lesion patterns showing infarction in the deep middle cerebral artery (MCA) territory involving the perforating artery area was observed in 47 (38.8%) patients. On multivariable analysis, unfavorable outcomes at 90 days were associated with diabetes [odds ratio (OR), 3.41; 95% confidence interval (CI), 1.06-10.9; P = 0.039), NIHSS score on admission (OR, 2.11; 95% CI, 1.35-3.30; P = 0.001), and infarction in the deep MCA territory on DWI (OR, 4.19; 95% CI, 1.63-10.8; P = 0.003). Lesions in the deep MCA territory was independently associated with early neurological deterioration (P = 0.032). The patients without deep MCA territory infarction had a higher prevalence of cardiac embolism (P = 0.009). CONCLUSIONS: Higher NIHSS scores, diabetes, and deep MCA territory infarction may be useful for predicting unfavorable outcomes in patients with minor stroke treated with intravenous rt-PA therapy.

Thrombolysis in Large Diffusion-Weighted Imaging Lesions: Lower Chance but Still a Chance.

BACKGROUND: We sought to investigate whether early thrombolytic treatment can result in favorable functional outcome even in patients with large diffusion-weighted imaging (DWI) lesions. MATERIALS AND METHODS: We analyzed 566 patients who received intravenous alteplase within 4.5 hours from onset, initially underwent DWI and magnetic resonance angiography, and had acute infarction confined to anterior circulation. DWI lesion volumes were measured semiautomatically. The association between DWI lesion volume and 3-month outcome in patients who achieved early recanalization was assessed. The DWI lesion volume cutoff, which predicts unfavorable outcome despite recanalization, was determined. In patients with large DWI lesions, the distributions of modified Rankin Scale (mRS) score were compared according to the recanalization status. RESULTS: Four hundred thirty-six patients achieved early recanalization. Among these patients, 283 (65%) patients had a favorable functional outcome (mRS score 0-2). DWI lesion volume (odds ratio [OR], 1.38 per 10 mL; 95% confidence interval [CI], 1.22-1.56) was an independent variable associated with poor outcome, along with hypertension (OR, 1.87; 95% CI, 1.12-3.10), National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.13; 95% CI, 1.08-1.19), and onset-to-needle time (OR, 1.08 per 10 minutes; 95% CI, 1.03-1.13). The DWI lesion of 60 mL or higher highly predicted an unfavorable outcome with a positive predictive value of 95.3%. In patients with a DWI lesion of 60 mL or higher, recanalization had no benefit for an mRS score of 0-2 but was significantly associated with an mRS score of 0-3 (OR, 4.64; 95% CI, 1.08-19.97). CONCLUSIONS: Despite early recanalization, the probability of favorable outcome is low in patients with a DWI lesion of 60 mL or higher. Nevertheless, the benefit of recanalization still persists in large DWI lesions.

Poststroke emotional disturbances and a tryptophan hydroxylase 2 gene polymorphism.

Objectives: Emotional dysfunction is a common finding in stroke patients. Despite reports on serotonergic involvement in the etiology of poststroke emotional dysfunction (PSED), the role of serotonin synthesizing tryptophan hydroxylase 2 (TPH2) genes in the development of PSED remains unclear. Methods: Genotyping of TPH2 rs4641528 and rs10879355 was performed from genomic DNA of 383 stroke patients collected previously and stored at -70°C. Potential associations between TPH2 genes and poststroke depression (PSD), poststroke emotional incontinence (PSEI), and poststroke anger proneness (PSAP) were investigated 3 months poststroke. Results: Among the 383 patients, 69 (18%) had PSD, 41 (11%) had PSEI, and 93 (24%) had PSAP. The TPH2 rs4641528 genotype frequencies differed significantly between patients with and without either PSD or PSEI, although no significant differences were found between the patients with and without PSAP. In multiple logistic regression analysis, PSD was related to the National Institutes of Health Stroke Scale (NIHSS) score at admission (95% confidence interval [CI]: 1.047-1.230, p < .01), modified Rankin scale score at 3 months (95% CI: 0.135-0.848, p < .05), and TPH2 rs4641528 C allele (95% CI: 1.039-5.631, p < .05), whereas PSEI was associated only with the NIHSS score at admission (95% CI: 1.053-1.259, p < .01) and the TPH2 rs4641528 C allele (95% CI: 1.029-11.678, p < .05). Conclusions: Our findings suggest that the TPH2 rs4641528 C allele may play a role in the pathogenesis of PSD and PSEI but not PSAP in Korean stroke patients.