Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation.

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet). METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76-4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04-1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. ANN NEUROL 2023;94:61-74.

Intracranial arterial stenosis in Caucasian versus Chinese patients with TIA and minor stroke: two contemporaneous cohorts and a systematic review.

BACKGROUND: Intracranial arterial stenosis (ICAS) is an important cause of stroke worldwide. Separate reports in Caucasians and Asians with stroke/transient ischaemic attack (TIA) have suggested lower ICAS prevalence in Caucasians, but there has been no direct comparisons of the two ethnic groups with the same criteria to define ICAS. METHODS: Acute minor stroke or TIA patients in two cohorts respectively recruiting patients in Oxford (2011-2018, predominantly Caucasians) and Hong Kong (2011-2015, predominantly Chinese) were compared. ICAS was defined as ≥50% stenosis/occlusion in any major intracranial artery in MR/CT angiography. Prevalence, distribution and risk factors of ICAS were compared between the two cohorts. We also systematically reviewed literature on ICAS prevalence in stroke/TIA patients in different populations. RESULTS: Among 1287 patients from Oxford and 691 from Hong Kong (mean age 69 vs 66), ICAS prevalence was higher in Chinese than in Caucasians (43.0% vs 20.0%; OR 3.02; 95% CI 2.47 to 3.70; p<0.001), independent of age (age-adjusted OR 3.73; 95% CI 3.00 to 4.63; p<0.001) and vascular risk factors (multivariable-adjusted OR 3.21; 95% CI 2.56 to 4.02; p<0.001). This ethnic difference was greater (p interaction=0.005) at age <70 years (OR 5.33; 95% CI 3.79 to 7.50; p<0.001) than at ≥70 years (OR 2.81; 95% CI 2.11 to 3.74; p<0.001). ICAS prevalence increased with age and with vascular risk factors in both cohorts, with equivalent prevalence in Chinese aged <60 years and Caucasians aged ≥80, and in Chinese with no vascular risk factor and Caucasians with two vascular risk factors. ICAS locations also differed between Chinese and Caucasian patients. CONCLUSIONS: Chinese are more susceptible to ICAS than Caucasians, with an earlier onset age and a higher prevalence, independent of vascular risk factors.

Kinect-based rapid movement training to improve balance recovery for stroke fall prevention: a randomized controlled trial.

BACKGROUND: Falls are more prevalent in stroke survivors than age-matched healthy older adults because of their functional impairment. Rapid balance recovery reaction with adequate range-of-motion and fast response and movement time are crucial to minimize fall risk and prevent serious injurious falls when postural disturbances occur. A Kinect-based Rapid Movement Training (RMT) program was developed to provide real-time feedback to promote faster and larger arm reaching and leg stepping distances toward targets in 22 different directions. OBJECTIVE: To evaluate the effectiveness of the interactive RMT and Conventional Balance Training (CBT) on chronic stroke survivors' overall balance and balance recovery reaction. METHODS: In this assessor-blinded randomized controlled trial, chronic stroke survivors were randomized to receive twenty training sessions (60-min each) of either RMT or CBT. Pre- and post-training assessments included clinical tests, as well as kinematic measurements and electromyography during simulated forward fall through a "lean-and-release" perturbation system. RESULTS: Thirty participants were recruited (RMT = 16, CBT = 14). RMT led to significant improvement in balance control (Berg Balance Scale: pre = 49.13, post = 52.75; P = .001), gait control (Timed-Up-and-Go Test: pre = 14.66 s, post = 12.62 s; P = .011), and motor functions (Fugl-Meyer Assessment of Motor Recovery: pre = 60.63, post = 65.19; P = .015), which matched the effectiveness of CBT. Both groups preferred to use their non-paretic leg to take the initial step to restore stability, and their stepping leg's rectus femoris reacted significantly faster post-training (P = .036). CONCLUSION: The RMT was as effective as conventional balance training to provide beneficial effects on chronic stroke survivors' overall balance, motor function and improving balance recovery with faster muscle response. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT03183635 , NCT03183635) on 12 June 2017.

Effects of wearable ankle robotics for stair and over-ground training on sub-acute stroke: a randomized controlled trial.

BACKGROUND: Wearable ankle robotics could potentially facilitate intensive repetitive task-specific gait training on stair environment for stroke rehabilitation. A lightweight (0.5 kg) and portable exoskeleton ankle robot was designed to facilitate over-ground and stair training either providing active assistance to move paretic ankle augmenting residual motor function (power-assisted ankle robot, PAAR), or passively support dropped foot by lock/release ankle joint for foot clearance in swing phase (swing-controlled ankle robot, SCAR). In this two-center randomized controlled trial, we hypothesized that conventional training integrated with robot-assisted gait training using either PAAR or SCAR in stair environment are more effective to enhance gait recovery and promote independency in early stroke, than conventional training alone. METHODS: Sub-acute stroke survivors (within 2 months after stroke onset) received conventional training integrated with 20-session robot-assisted training (at least twice weekly, 30-min per session) on over-ground and stair environments, wearing PAAR (n = 14) or SCAR (n = 16), as compared to control group receiving conventional training only (CT, n = 17). Clinical assessments were performed before and after the 20-session intervention, including functional ambulatory category as primary outcome measure, along with Berg balance scale and timed 10-m walk test. RESULTS: After the 20-session interventions, all three groups showed statistically significant and clinically meaningful within-group functional improvement in all outcome measures (p < 0.005). Between-group comparison showed SCAR had greater improvement in functional ambulatory category (mean difference + 0.6, medium effect size 0.610) with more than 56% independent walkers after training, as compared to only 29% for CT. Analysis of covariance results showed PAAR had greater improvement in walking speed than SCAR (mean difference + 0.15 m/s, large effect size 0.752), which was in line with the higher cadence and speed when wearing the robot during the 20-session robot-assisted training over-ground and on stairs. CONCLUSIONS: Robot-assisted stair training would lead to greater functional improvement in gait independency and walking speed than conventional training in usual care. The active powered ankle assistance might facilitate users to walk more and faster with their paretic leg during stair and over-ground walking. TRIAL REGISTRATION: ClinicalTrials.gov NCT03184259. Registered on 12 June 2017.

Translesional Pressure Gradient Alters Relationship Between Blood Pressure and Recurrent Stroke in Intracranial Stenosis.

Background and Purpose- There is debate over an optimal systolic blood pressure (SBP) in secondary stroke prevention of patients with symptomatic intracranial atherosclerotic stenosis (sICAS). We investigated whether translesional pressure gradient across sICAS would alter the relationship between SBP and risk of recurrent stroke in such patients. Methods- We recruited patients with sICAS (50%-99% stenosis) confirmed in computed tomography angiography. We simulated blood flow across sICAS with computed tomography angiography-based computational fluid dynamics models. Translesional pressure ratio (PR=Pressurepost-stenotic/Pressurepre-stenotic) was calculated in each case. Pressure ratio (PR) ≤ median was defined as low PR, indicating larger translesional pressure gradient across sICAS. All patients received optimal medical treatment. We investigated the interaction of translesional PR and mean SBP during follow-up (SBPFU) in determining the risk of the primary outcome, recurrent ischemic stroke in the same territory within 1 year. Results- Among 157 patients with sICAS, the median PR was 0.93. Multivariate Cox regression revealed significant PR-SBPFU interaction on the primary outcome (P=0.008): in patients with normal PR, risk of primary outcome significantly decreased with lower SBPFU (hazard ratio for 10 mm Hg decrement =0.46; P=0.018); however, in those with low PR, SBPFU≤130 mm Hg was associated with significantly increased risk of primary outcome, compared with 130

Regional High Wall Shear Stress Associated With Stenosis Regression in Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND AND PURPOSE: Understanding the mechanisms underlying progression/regression of symptomatic intracranial atherosclerotic stenosis (sICAS) will inform secondary prevention of the patients. Focal wall shear stress (WSS) may play an important role, which, however, had seldom been investigated. METHODS: Patients with acute ischemic stroke or transient ischemic attack (TIA) attributed to 50% to 99% intracranial atherosclerotic stenosis were recruited. All patients underwent cerebral computed tomography angiography at baseline, and a computational fluid dynamics model was built based on computed tomography angiography to simulate blood flow and quantify WSS in the vicinity of the sICAS lesion. All patients received optimal medical treatment and a second computed tomography angiography at 1 year. The change in the luminal stenosis from baseline to 1 year in sICAS was defined as progression (increased >10%), quiescence (±10%), or regression (decreased >10%). Associations between baseline WSS metrics and sICAS regression were analyzed. RESULTS: Among 39 patients (median age 62 years; 27 males), sICAS luminal stenosis progressed, remained quiescent and regressed in 6 (15.4%), 15 (38.5%), and 18 (46.2%) cases, respectively. A higher maximum WSS and larger high-WSS area, throughout the sICAS lesion or obtained separately in the proximal and distal parts of the lesion, were independently associated with regression of luminal stenosis in sICAS over 1 year. CONCLUSIONS: A majority of sICAS lesions regress or stay quiescent in the luminal stenosis over 1 year after stroke under optimal medical treatment, when higher focal WSS may facilitate stenosis regression. Further studies of the effects of hemodynamics including WSS in altering plaque vulnerability and stroke risks are needed.

Hemodynamics and stroke risk in intracranial atherosclerotic disease.

OBJECTIVE: To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid dynamics (CFD) model. METHODS: In a cohort study, we recruited patients with acute ischemic stroke attributed to 50 to 99% ICAS confirmed by computed tomographic angiography (CTA). With CTA-based CFD models, translesional pressure ratio (PR = pressurepoststenotic /pressureprestenotic ) and translesional wall shear stress ratio (WSSR = WSSstenotic - throat /WSSprestenotic ) were obtained in each sICAS lesion. Translesional PR ≤ median was defined as low PR and WSSR ≥4th quartile as high WSSR. All patients received standard medical treatment. The primary outcome was recurrent ischemic stroke in the same territory (SIT) within 1 year. RESULTS: Overall, 245 patients (median age = 61 years, 63.7% males) were analyzed. Median translesional PR was 0.94 (interquartile range [IQR] = 0.87-0.97); median translesional WSSR was 13.3 (IQR = 7.0-26.7). SIT occurred in 20 (8.2%) patients, mostly with multiple infarcts in the border zone and/or cortical regions. In multivariate Cox regression, low PR (adjusted hazard ratio [HR] = 3.16, p = 0.026) and high WSSR (adjusted HR = 3.05, p = 0.014) were independently associated with SIT. Patients with both low PR and high WSSR had significantly higher risk of SIT than those with normal PR and WSSR (risk = 17.5% vs 3.0%, adjusted HR = 7.52, p = 0.004). INTERPRETATION: This work represents a step forward in utilizing computational flow simulation techniques in studying intracranial atherosclerotic disease. It reveals a hemodynamic pattern of sICAS that is more prone to stroke relapse, and supports hypoperfusion and artery-to-artery embolism as common mechanisms of ischemic stroke in such patients. Ann Neurol 2019;85:752-764.

Plaque morphology in acute symptomatic intracranial atherosclerotic disease.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is globally a major ischaemic stroke subtype with high recurrence. Understanding the morphology of symptomatic ICAD plaques, largely unknown by far, may help identify vulnerable lesions prone to relapse. METHODS: We prospectively recruited patients with acute ischaemic stroke or transient ischaemic attack attributed to high-grade ICAD (60%-99% stenosis). Plaque morphological parameters were assessed in three-dimensional rotational angiography, including surface contour, luminal stenosis, plaque length/thickness, upstream shoulder angulation, axial/longitudinal plaque distribution and presence of adjoining branch atheromatous disease (BAD). We compared morphological features of smooth, irregular and ulcerative plaques and correlated them with cerebral ischaemic lesion load downstream in MRI. RESULTS: Among 180 recruited patients (median age=60 years; 63.3% male; median stenosis=75%), plaque contour was smooth (51 (28.3%)), irregular (101 (56.1%)) or ulcerative (28 (15.6%)). Surface ulcers were mostly at proximal (46.4%) and middle one-third (35.7%) of the lesions. Most (84.4%) plaques were eccentric, and half had their maximum thickness over the distal end. Ulcerative lesions were thicker (medians 1.6 vs 1.3 mm; p=0.003), had steeper upstream shoulder angulation (56.2° vs 31.0°; p<0.001) and more adjoining BAD (83.3% vs 57.0%; p=0.033) than non-ulcerative plaques. Ulcerative plaques were significantly associated with coexisting acute and chronic infarcts downstream (35.7% vs 12.5%; adjusted OR 4.29, 95% CI 1.65 to 11.14, p=0.003). Sensitivity analyses in patients with anterior-circulation ICAD lesions showed similar results in the associations between the plaque types and infarct load. CONCLUSIONS: Ulcerative intracranial atherosclerotic plaques were associated with vulnerable morphological features and had a higher cumulative infarct load downstream.

Stroke Mechanisms in Symptomatic Intracranial Atherosclerotic Disease: Classification and Clinical Implications.

Background and Purpose- In patients with symptomatic intracranial atherosclerotic stenosis, identifying the underlying stroke mechanisms may inform secondary prevention. We aimed to propose reproducible classification criteria for stroke mechanisms based on routine neuroimaging in symptomatic intracranial atherosclerotic stenosis and explore their clinical implications. Methods- We recruited patients with acute ischemic stroke attributed to 50% to 99% intracranial atherosclerotic stenosis in anterior circulation from 2 centers. Two investigators independently classified probable stroke mechanisms as parent artery atherosclerosis occluding penetrating artery, artery-to-artery embolism, hypoperfusion, and mixed mechanisms, with prespecified criteria based on infarct topography and magnetic resonance/computed tomography angiography. These stroke mechanisms were correlated with features of the patients at baseline and recurrent ischemic stroke in the same territory or relevant transient ischemic attack within 1 year. Results- Among 153 patients recruited, the most common stroke mechanisms were isolated hypoperfusion (35.3%) and mixed mechanism of artery-to-artery embolism and hypoperfusion (37.3%) that was associated with higher incidence of dyslipidemia (P=0.045) and hypertension (P=0.033) than patients with other stroke mechanisms. The proposed criteria showed substantial to excellent intrarater and interrater reproducibilities (κ, 0.791-0.908). Overall, 31 patients received interventional treatment of the diseased intracranial artery; 122 received medical treatment, among whom a mixed mechanism of artery-to-artery embolism and hypoperfusion at baseline was associated with higher risk of ischemic stroke in the same territory within 1 year (24.4% versus 7.8%; hazard ratio, 3.40; 95% CI, 1.25-9.20; log-rank P=0.010) than other mechanisms combined. Conclusions- Artery-to-artery embolism and hypoperfusion commonly coexist in ischemic stroke attributed to intracranial atherosclerotic stenosis, which may be associated with higher risk of stroke relapse.

Risk of intracerebral haemorrhage in Chinese patients with atrial fibrillation on warfarin with cerebral microbleeds: the IPAAC-Warfarin study.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs), which predict future intracerebral haemorrhage (ICH), may guide anticoagulant decisions for atrial fibrillation (AF). We aimed to evaluate the risk of warfarin-associated ICH in Chinese patients with AF with CMBs. METHODS: In this prospective, observational, multicentre study, we recruited Chinese patients with AF who were on or intended to start anticoagulation with warfarin from six hospitals in Hong Kong. CMBs were evaluated with 3T MRI brain at baseline. Primary outcome was clinical ICH at 2-year follow-up. Secondary outcomes were ischaemic stroke, systemic embolism, mortality of all causes and modified Rankin Scale ≥3. Outcome events were compared between patients with and without CMBs. RESULTS: A total of 290 patients were recruited; 53 patients were excluded by predefined criteria. Among the 237 patients included in the final analysis, CMBs were observed in 84 (35.4%) patients, and 11 had ≥5 CMBs. The mean follow-up period was 22.4±10.3 months. Compared with patients without CMBs, patients with CMBs had numerically higher rate of ICH (3.6% vs 0.7%, p=0.129). The rate of ICH was lower than ischaemic stroke for patients with 0 to 4 CMBs, but higher for those with ≥5 CMBs. CMB count (C-index 0.82) was more sensitive than HAS-BLED (C-index 0.55) and CHA2DS2-VASc (C-index 0.63) scores in predicting ICH. CONCLUSIONS: In Chinese patients with AF on warfarin, presence of multiple CMBs may be associated with higher rate of ICH than ischaemic stroke. Larger studies through international collaboration are needed to determine the risk:benefit ratio of oral anticoagulants in patients with AF of different ethnic origins.

Autonomic Dysfunction Predicts Clinical Outcomes After Acute Ischemic Stroke: A Prospective Observational Study.

BACKGROUND AND PURPOSE: Central autonomic dysfunction increases stroke morbidity and mortality. We aimed to investigate whether poststroke autonomic dysfunction graded by Ewing battery can predict clinical outcome. METHODS: In this prospective observational study, we assessed autonomic function of ischemic stroke patients within 7 days from symptom onset by Ewing battery. On the basis of the magnitude of autonomic dysfunction, we stratified patients into significant (definite, severe, or atypical) or minor (normal or early) autonomic function impairment groups and correlated the impairment with the 3-month modified Rankin Scale score (good outcome: modified Rankin Scale score 0≈2; poor outcome: modified Rankin Scale score 3≈6). RESULTS: Among the 150 patients enrolled (mean age, 66.4±9.9 years; 70.7% males), minor autonomic dysfunction was identified in 36 patients (24.0%), and significant autonomic dysfunction was identified in 114 patients (76.0%) based on Ewing battery. In 3 months, a poor functional outcome was found in 32.5% of significant group patients compared with 13.9% in the minor group (P=0.031). Crude odds ratios of the magnitude of autonomic dysfunction and 3-month unfavorable functional outcome after acute ischemic stroke were 2.979 (95% confidence interval, 1.071-8.284; P=0.036). After adjusting for confounding variables with statistical significance between the 2 functional outcome subgroups identified in univariate analysis (including sex and National Institutes of Health Stroke Scale score on admission), the magnitude of autonomic dysfunction still independently predicted an unfavorable outcome, with an odds ratio of 3.263 (95% confidence interval, 1.141-9.335; P=0.027). CONCLUSIONS: Autonomic dysfunction gauged by Ewing battery predicts poor functional outcome after acute ischemic stroke.

Correlation of non-vitamin K antagonist oral anticoagulant exposure and cerebral microbleeds in Chinese patients with atrial fibrillation.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are radiological markers which predict future intracerebral haemorrhage. Researchers are exploring how CMBs can guide anticoagulation decisions in atrial fibrillation (AF). The purpose of this study is to evaluate the correlation of non-vitamin K antagonist oral anticoagulants (NOAC) exposure and prevalence of CMBs in Chinese patients with AF. METHODS: We prospectively recruited Chinese patients with AF on NOAC therapy of ≥30 days for 3T MRI brain for evaluation of CMBs and white matter hyperintensities. Patients with AF without prior exposure to oral anticoagulation were recruited as control group. RESULTS: A total of 282 patients were recruited, including 124 patients in NOAC group and 158 patients in control group. Mean duration of NOAC exposure was 723.8±500.3 days. CMBs were observed in 103 (36.5%) patients. No significant correlation was observed between duration of NOAC exposure and quantity of CMBs. After adjusting for confounding factors (ie, age, hypertension, labile hypertension, stroke history and white matter scores), previous intracerebral haemorrhage was predictive of CMBs (OR 15.28, 95% CI 1.81 to 129.16), particularly lobar CMBs (OR 5.37, 95% CI 1.27 to 22.6). While white matter score was predictive of mixed lobar CMBs (OR 1.65, 95% CI 1.1 to 2.5), both exposure and duration of NOAC use were not predictive of presence of CMBs. CONCLUSIONS: In Chinese patients with AF, duration of NOAC exposure did not correlate with prevalence and burden of CMBs. Further studies with follow-up MRI are needed to determine if long-term NOAC therapy can lead to development of new CMBs.

Converting MMSE to MoCA and MoCA 5-minute protocol in an educationally heterogeneous sample with stroke or transient ischemic attack.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is psychometrically superior over the Mini-mental State Examination (MMSE) for cognitive screening in stroke or transient ischemic attack (TIA). It is free for clinical and research use. The objective of this study is to convert scores from the MMSE to MoCA and MoCA-5-minute protocol (MoCA-5 min) and to examine the ability of the converted scores in detecting cognitive impairment after stroke or TIA. METHODS: A total of 904 patients were randomly divided into training (n = 623) and validation (n = 281) samples matched for demography and cognition. MMSE scores were converted to MoCA and MoCA-5 min using (1) equipercentile method with log-linear smoothing and (2) Poisson regression adjusting for age and education. Receiver operating characteristics curve analysis was used to examine the ability of the converted scores in differentiating patients with cognitive impairment. RESULTS: The mean education was 5.8 (SD = 4.6; ranged 0-20) years. The entire spectrum of MMSE scores was converted to MoCA and MoCA-5 min using equipercentile method. Relationship between MMSE and MoCA scores was confounded by age and education, and a conversion equation with adjustment for age and education was derived. In the validation sample, the converted scores differentiated cognitively impaired patients with area under receiver operating characteristics curve 0.826 to 0.859. CONCLUSION: We provided 2 methods to convert scores from the MMSE to MoCA and MoCA-5 min based on a large sample of patients with stroke or TIA having a wide range of education and cognitive levels. The converted scores differentiated patients with cognitive impairment after stroke or TIA with high accuracy.

Impact of intracranial artery calcification on cerebral hemodynamic changes.

PURPOSE: Intracranial artery calcification (IAC) has been demonstrated to be correlated with ischemic stroke, cognitive decline, and other vascular events by accumulating evidences from both Western and Asian populations. The proposed study aimed to investigate its potential mechanisms by evaluating the blood flow velocity and pulsatility index (PI) of cerebral arteries. METHODS: Consecutive ischemic stroke patients admitted to the Prince of Wales Hospital were recruited after excluding those with atrial fibrillation or poor temporal window. Quantitative measurements of IAC severity were assessed on brain CT scans. Transcranial Doppler (TCD) ultrasonography was performed to evaluate the blood flow velocity of the middle cerebral artery (MCA) and vertebral-basilar artery (VBA). RESULTS: In total, 318 patients were analyzed. Spearman's correlation analysis demonstrated both high MCA systolic flow velocity and high MCA PI were correlated with IAC Agatston score, p < 0.001 individually. Similar correlation was also found between IAC Agatston score and high VBA velocity/high VBA PI, p ≤ 0.001 individually. Multiple logistic regression analysis showed IAC Agatston score was an independent risk factor for high MCA velocity (OR 1.533; 95% CI 1.235-1.903), high VBA velocity (OR 1.964; 95% CI 1.381-2.794), and high VBA PI (OR 1.200; 95% CI 1.016-1.418), respectively. CONCLUSION: Heavier IAC might cause generalized artery flow velocity changes and increased pulsatility index, which may indicate high resistance within cerebrovasculature.

Age-specific trends of atrial fibrillation-related ischaemic stroke and transient ischaemic attack, anticoagulant use and risk factor profile in Chinese population: a 15-year study.

BACKGROUND: Prevalence of atrial fibrillation (AF) is increasing globally, and the fivefold increase in stroke risk constitutes significant healthcare burden. AIMS: We aim to evaluate the trends of AF-related stroke and transient ischaemic attack (AF-stroke/TIA), prior anticoagulant use and their risk factors in different age groups in Chinese population. METHODS: Data were retrieved from the stroke registry at Prince of Wales Hospital. We compared the data at 5-year intervals over a 15-year period (years 1999, 2004, 2009 and 2014). RESULTS: A total of 3894 patients were included, 712 patients had AF-stroke/TIA. Over the 15 years, the total number of ischaemic stroke/TIA fluctuated slightly during the period from year 1999 to 2009, and increased by 21.5% in the year 2014. While AF-stroke/TIA increased continuously with time by 282.1%. Increasing trend of AF-stroke/TIA was observed in all age groups. Absolute growth was highest in patients aged ≥80 years; relative growth was most pronounced in those between 65 and 72 years (>3.5 fold increase). Throughout the 15 years, >70% of AF-stroke/TIA occurred in non-anticoagulated patients, and this proportion increased with age. Increasing trends in both hypertension and ischaemic heart disease were also observed in patients with AF aged ≥73 years. CONCLUSION: AF-stroke/TIA has increased continuously by >2.5 fold in Chinese population over a 15-year period, with the majority of AF-stroke/TIA occurring in non-anticoagulated patients. Strategic planning is needed to optimise anticoagulant use, particularly non-vitamin K antagonist oral anticoagulants in elderly patients, low-income group and those with ischaemic heart disease requiring concomitant antiplatelet therapy.

The prognosis of acute symptomatic seizures after ischaemic stroke.

OBJECTIVE: Acute symptomatic seizure (AS) after ischaemic stroke is defined as a seizure occurring ≤7 days of the stroke. There remains a lack of information on the prognosis of AS after ischaemic stroke and how it should be treated. METHODS: We prospectively recruited patients after their incidents of ischaemic stroke from a population-based stroke registry. Stroke aetiology was defined according to Trial-of-ORG-10172 in acute-stroke treatment (TOAST). Patients were examined for any transient complete-occlusion with recanalisation (TCOR) and haemorrhagic transformation. The seizure outcomes were (1) acute clustering of seizures ≤7 days, (2) seizure recurrence associated with stroke recurrence beyond the 7-day period and (3) unprovoked seizure (US) >7 days. RESULTS: 104 patients (mean age 65 years/55% female) with AS after ischaemic stroke were identified (mean follow-up 6.17 years). Comparison of the group of patients with AS and those without seizures showed that patients with AS had significantly less large-vessel and small-vessel disease but more cardioembolisms (p<0.05) and a higher proportion of TCOR (p<0.01), multiple territory infarcts (p=0.007) and haemorrhagic transformations (p<0.01). Using Kaplan-Meier statistics, the risk of acute clustering of seizures ≤7 days was 22%, with a statistical trend for TCOR as a predictive factor (p=0.06). The risk of seizure recurrence associated with worsening/recurrence of stroke beyond 7 days was 13.5% at 2 years, 16.4% at 4 years and 18% at 8 years. Presence of >2 cardiovascular risk factors (p<0.05) and status epilepticus (P<0.05) are predictive risk factors on Cox regression model. The risk of US was 19% at 2 years, 25% at 4 years and 28% at 8 years with epileptiform EEG as a predictive factor (p<0.05). CONCLUSIONS: Seizure recurrence following AS after ischaemic stroke may appear as acute clustering. Afterwards, seizures may occur as often with a recurrent stroke as without one within 4.2 years. We recommend the use of antiepileptic agents for up to 4 years if the underlying stroke aetiology cannot be fully treated.

Sex Differences Do Not Exist in Outcomes among Stroke Patients with Intracranial Atherosclerosis in China: Subgroup Analysis from the Chinese Intracranial Atherosclerosis Study.

BACKGROUND: To date, sex difference in outcomes among patients with intracranial atherosclerosis (ICAS) has rarely been discussed in China as well as in the world. This study aimed to estimate the sex difference in outcomes among patients with ICAS in Chinese cerebral ischemia patients. METHODS: We analyzed 1,335 men and women with ICAS who were enrolled in the Chinese Intracranial Atherosclerosis study. They were followed-up for ischemic stroke recurrence, any cause of death, cerebral vascular events (including transient ischemic attack, ischemic and hemorrhagic stroke), combined end points (including cerebral vascular events, angina or myocardial infarction, pulmonary embolism, peripheral vascular events), and unfavorable outcome (modified Rankin scale score of 3-6) at 1 year. RESULTS: During the follow-up period, 59 (13.44%) combined end points were documented in women and 107 (11.94%) in men. Of the combined end points, 47 were recurrent ischemic stroke events (14 in women and 33 in men), and 51 other causes of deaths (24 in women and 27 in men). There were 349 unfavorable end points (117 in women and 232 in men). The cumulative probability of death was higher in women, but after adjusting for age, diabetes mellitus, hypertension, family history of stroke, current smoker, heavy drinking, hyperhomocysteinemia, and heart disease, there was no significant difference. There was also a lack of difference in 1-year ischemic stroke recurrence, cerebral vascular events, combined end points, and unfavorable outcome between women and men at 1 year. CONCLUSIONS: These results suggest no sex difference in outcome among patients with ICAS in Chinese cerebral ischemia patients.

Benign Oligemia in Subacute Stage Is Associated with Borderzone Infarction in Stroke Patients Caused by Intracranial Large Artery Disease.

BACKGROUND: CT perfusion (CTP) imaging provides quantitative evaluation of cerebral perfusion flow and volume. Our previous findings showed that benign oligemia caused by intracranial large artery disease may be existent in subacute stroke. AIMS: We aimed at comparing the topographic patterns and clinical outcome of stroke patients with and without persistent benign oligemia as defined by CTP imaging. METHODS: Consecutive ischemic stroke patients who were referred for CTP in 2009 were screened. The topographic patterns (cortical, borderzone or perforating artery territory infarcts) were assessed by diffusion-weighted imaging (DWI). The clinical outcome was defined by modified Rankin score at 6 months after stroke onset. RESULTS: Totally, 26 stroke patients were recruited. Benign oligemia in subacute stage was detected in 15 patients. The occurrence of borderzone infarction was higher in stroke patients with benign oligemia than those without (p = 0.036). CONCLUSIONS: The topographic pattern of DWI may be different between the intracranial arterial disease patients with and without benign oligemia on CTP in subacute stroke.

External Counterpulsation Increases Beat-to-Beat Heart Rate Variability in Patients with Ischemic Stroke.

BACKGROUND AND PURPOSE: External counterpulsation (ECP) is a noninvasive method used to augment cerebral perfusion in ischemic stroke. However, the response of beat-to-beat heart rate variability (HRV) in patients with ischemic stroke during ECP remains unknown. METHODS: Forty-eight patients with unilateral ischemic stroke at the subacute stage and 14 healthy controls were recruited. Beat-to-beat heart rate before, during, and after ECP was monitored. The frequency components of HRV were calculated using power spectral analysis. Very low frequency (VLF; <.04 Hz), low frequency (LF; .04-.15 Hz), high frequency (HF; .15-.40 Hz), total power spectral density (TP; <.40 Hz), and LF/HF ratio were calculated. RESULTS: In stroke patients, although there were no statistical differences in all of the HRV components, the HRV at VLF showed a trend of increase during ECP compared with baseline in the left-sided stroke patients (P = .083). After ECP, the HRV at LF and TP remained higher than baseline in the right-sided stroke patients (LF, 209.4 versus 117.9, P = .050; TP, 1275.6 versus 390.2, P = .017, respectively). Besides, the HRV at TP also increased after ECP compared with baseline in the left-sided stroke patients (563.0 versus 298.3, P = .029). CONCLUSIONS: Irrespective of the side of the ischemia, patients showed an increased beat-to-beat HRV after ECP. Additionally, sympathetic and parasympathetic cardiac modulations were increased after ECP in patients after right-sided subacute stroke.

Cortical Microinfarcts in Patients with Middle Cerebral Artery Stenosis.

BACKGROUND: Cortical microinfarcts (CMIs) have been correlated to cognitive decline and dementia. It was previously considered only visible on microscope, but was recently reported to be visible on 3.0 Tesla magnetic resonance imaging (MRI) and linked to presence of intracranial stenosis. We aimed to investigate CMIs on 3.0 Tesla MRI in patients with M1 middle cerebral artery (MCA-M1) stenosis. METHODS: Patients with a recent non-cardioembolic ischemic stroke or transient ischemic attack and an atherosclerotic MCA-M1 stenosis were recruited. The severity of MCA stenosis was defined as moderate (50%-69%) or severe (70%-99% or focal flow void) on time-of-flight MR angiography (MRA). The distal to proximal signal intensity ratio (SIR) of MCA stenosis was measured on time-of-flight MRA to represent its hemodynamic significance. The presence of CMI(s) in the ipsilateral hemisphere was assessed on axial T1- or T2-weighted images and T2-weighted fluid-attenuated inversion-recovery images. RESULTS: Overall, 86 patients (mean age: 62.8 years; 77.9% males) were analyzed, 66 (76.7%) and 20 (23.3%), respectively, having moderate and severe MCA-M1 stenoses. The median SIR was .91. Forty-five (52.3%) patients had ipsilateral CMI(s). Multivariate logistic regression showed a history of dyslipidemia (odds ratio [OR] = 6.83, P = .008), and an SIR lower than the median (OR = 4.73, P = .014) were independently associated with presence of CMI(s) in ipsilateral hemisphere to an MCA-M1 stenosis. CONCLUSIONS: Patients with stroke and intracranial stenosis had a high burden of CMI. Except for a history of dyslipidemia, the hemodynamic significance of the arterial stenosis may contribute to the presence of ipsilateral CMI(s) in these patients, which warrants further investigation in prospective, longitudinal studies.