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.

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.

Evolution of intracranial atherosclerotic disease under modern medical therapy.

OBJECTIVE: Understanding how symptomatic intracranial atherosclerotic disease (ICAD) evolves with current medical therapy may inform secondary stroke prevention. METHODS: In a prospective academic-initiated study, we recruited 50 patients (mean age = 63.4 ± 9.0 years) with acute strokes attributed to high-grade (≥70%) intracranial atherosclerotic stenosis for 3-dimensional rotational angiograms before and after intensive medical therapy for 12 months. Treatment targets included low-density lipoprotein ≤ 70mg/dl, glycosylated hemoglobin (HbA1c) ≤ 6.5%, and systolic blood pressure ≤ 140 mmHg. We analyzed infarct topography and monitored microembolic signal in recurrent strokes. The reference group was a published cohort of 143 ICAD patients. RESULTS: Overall, the stenoses regressed from 79% at baseline (interquartile range [IQR] = 71-87%) to 63% (IQR = 54-74%) in 1 year (p < 0.001). Specifically, the qualifying lesions (n = 49) regressed (stenosis reduced >10%) in 24 patients (49%), remained quiescent (stenosis same or ±10%) in 21 patients (43%), and progressed (stenosis increased >10%) in 4 patients (8%). There was no difference in intensity of risk factor control between groups of diverging clinical or angiographic outcomes. Higher HbA1c at baseline predicted plaque regression at 1 year (odds ratio = 4.4, 95% confidence interval = 1.4-14.5, p = 0.006). Among the 6 patients with recurrent strokes pertaining to the qualifying stenosis, 5 patients had solitary or rosarylike acute infarcts along the internal or anterior border zones, and 2 patients showed microembolic signals in transcranial Doppler ultrasound. INTERPRETATION: A majority of symptomatic high-grade intracranial plaques had regressed or remained quiescent by 12 months under intensive medical therapy. Artery-to-artery thromboembolism with impaired washout at border zones was a common mechanism in stroke recurrence.

Delayed-onset dementia after stroke or transient ischemic attack.

INTRODUCTION: Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. METHODS: Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. RESULTS: Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. DISCUSSION: Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group.

Risk factors for incident dementia after stroke and transient ischemic attack.

BACKGROUND: We hypothesized that chronic brain changes are important substrates for incident dementia after stroke and transient ischemic attack (TIA). METHODS: We compared clinical and imaging features between patients with consecutive stroke/TIA with (n = 88) and without (n = 925) incident dementia at 3 to 6 months after a stroke/TIA. Pittsburg compound B (PiB) positron emission tomography was performed in 50 patients, including those with (n = 37) and without (n = 13) incident dementia. RESULTS: Age, history of diabetes mellitus, severity of white matter changes (WMCs), and medial temporal lobe atrophy (MTLA) were associated with incident dementia. Alzheimer's disease (AD)--like PiB retention was found in 29.7% and 7.7% (P = .032) of patients with and without incident dementia, respectively. CONCLUSIONS: Chronic brain changes including WMCs, MTLA, and AD pathology are associated with incident dementia after stroke/TIA. Interventions targeting these chronic brain changes may reduce burden of vascular cognitive impairment.

Evaluation of carotid angioplasty and stenting for radiation-induced carotid stenosis.

BACKGROUND AND PURPOSE: We aimed to evaluate the procedural safety, clinical, and angiographic outcome of carotid angioplasty and stenting for high-grade (≥70%) radiation-induced carotid stenosis (RIS) using atherosclerotic stenosis (AS) as a control. METHODS: In this 6-year prospective nonrandomized study, we compared the carotid angioplasty and stenting outcome of 65 consecutive patients (84 vessels) with RIS with that of a control group of 129 consecutive patients (150 vessels) with AS. Study end points were 30-day periprocedural stroke or death, ipsilateral ischemic stroke, technical success, procedural characteristics, instent restenosis (ISR; ≥50%) and symptomatic ISR. RESULTS: The median follow-up was 47.3 months (95% confidence interval, 26.9-61.6). Imaging assessment was available in 74 vessels (RIS) and 120 vessels (AS) in 2 years. Comparing RIS group with AS group, the rates of periprocedural stroke or death were 1.5% (1/65) versus 1.6% (2/129; P=1); ipsilateral ischemic stroke rates were 4.6% (3/65) versus 4.7% (6/129; P=1); the annual risks of ipsilateral ischemic stroke were 1.2% (3 patient/254.7 patient year) versus 1.2% (6 patient/494.2 patient year; P=0.89); technical success rates were both 100%. Stenting of common carotid artery and the use of multiple stents was more common in the RIS group (P=0 in both cases); ISR rates were 25.7% (19/74) versus 4.2% (5/120; P<0.001); symptomatic ISR rates were 6.8% (5/74) versus 0.8% (1/120; P=0.031). CONCLUSIONS: The safety, effectiveness, and technical difficulty of carotid angioplasty and stenting for RIS are comparable with that for AS although it is associated with a higher rate of ISR. CLINICAL TRIAL REGISTRATION: This trial was not registered as enrollment started in 2006.

Cerebral hemodynamics and stroke risks in symptomatic intracranial atherosclerotic stenosis with internal versus cortical borderzone infarcts: A computational fluid dynamics study.

There may be different mechanisms underlying internal (IBZ) and cortical (CBZ) borderzone infarcts in intracranial atherosclerotic stenosis. In 84 patients with symptomatic, 50-99% atherosclerotic stenosis of M1 middle cerebral artery (MCA-M1) with acute borderzone infarcts in diffusion-weighted imaging, we classified the infarct patterns as isolated IBZ (n = 37), isolated CBZ (n = 31), and IBZ+CBZ (n = 16) infarcts. CT angiography-based computational fluid dynamics models were constructed to quantify translesional, post-stenotic to pre-stenotic pressure ratio (PR) in the MCA-M1 lesion. Those with IBZ infarcts were more likely to have a low PR (indicating impaired antegrade flow across the lesion) than those without (p = 0.012), and those with CBZ infarcts were more likely to have coexisting small cortical infarcts (indicating possible embolism) than those without (p = 0.004). In those with isolated IBZ or CBZ infarcts, low PR was independently associated with isolated IBZ infarcts (adjusted odds ratio = 4.223; p = 0.026). These two groups may also have different trajectories in the stroke risks under current medical treatment regimen, with a higher risk of same-territory ischemic stroke recurrence within 3 months in patients with isolated IBZ infarcts than isolated CBZ infarcts (17.9% versus 0.0%; log-rank p = 0.023), but similar risks later in 1 year.

Hemodynamic significance of intracranial atherosclerotic disease and ipsilateral imaging markers of cerebral small vessel disease.

INTRODUCTION: Cerebral small vessel disease (CSVD) commonly exists in patients with symptomatic intracranial atherosclerotic disease (sICAD). We aimed to investigate the associations of hemodynamic features of sICAD lesions with imaging markers and overall burden of CSVD. PATIENTS AND METHODS: Patients with anterior-circulation sICAD (50%-99% stenosis) were analyzed in this cross-sectional study. Hemodynamic features of a sICAD lesion were quantified by translesional pressure ratio (PR = Pressurepost-stenotic/Pressurepre-stenotic) and wall shear stress ratio (WSSR = WSSstenotic-throat/WSSpre-stenotic) via CT angiography-based computational fluid dynamics modeling. PR ⩽median was defined as low ("abnormal") PR, and WSSR ⩾ fourth quartile as high ("abnormal") WSSR. For primary analyses, white matter hyperintensities (WMHs), lacunes, and cortical microinfarcts (CMIs) were assessed in MRI and summed up as overall CSVD burden, respectively in ipsilateral and contralateral hemispheres to sICAD. Enlarged perivascular spaces (EPVSs) and cerebral microbleeds (CMBs) were assessed for secondary analyses. RESULTS: Among 112 sICAD patients, there were more severe WMHs, more lacunes and CMIs, and more severe overall CSVD burden ipsilaterally than contralaterally (all p < 0.05). Abnormal PR and WSSR (vs normal PR and WSSR) was significantly associated with moderate-to-severe WMHs (adjusted odds ratio = 10.12, p = 0.018), CMI presence (5.25, p = 0.003), and moderate-to-severe CSVD burden (12.55; p = 0.033), ipsilaterally, respectively independent of contralateral WMHs, CMI(s), and CSVD burden. EPVSs and CMBs were comparable between the two hemispheres, with no association found with the hemodynamic metrics. DISCUSSION AND CONCLUSION: There are more severe WMHs and CMI(s) in the hemisphere ipsilateral than contralateral to sICAD. The hemodynamic significance of sICAD lesions was independently associated with severities of WMHs and CMI(s) ipsilaterally.

Risk stratification in symptomatic intracranial atherosclerotic disease with conventional vascular risk factors and cerebral haemodynamics.

BACKGROUND AND PURPOSE: Symptomatic intracranial atherosclerotic stenosis (sICAS) is associated with a considerable risk of recurrent stroke despite contemporarily optimal medical treatment. Severity of luminal stenosis in sICAS and its haemodynamic significance quantified with computational fluid dynamics (CFD) models were associated with the risk of stroke recurrence. We aimed to develop and compare stroke risk prediction nomograms in sICAS, based on vascular risk factors and these metrics. METHODS: Patients with 50%-99% sICAS confirmed in CT angiography (CTA) were enrolled. Conventional vascular risk factors were collected. Severity of luminal stenosis in sICAS was dichotomised as moderate (50%-69%) and severe (70%-99%). Translesional pressure ratio (PR) and wall shear stress ratio (WSSR) were quantified via CTA-based CFD modelling; the haemodynamic status of sICAS was classified as normal (normal PR&WSSR), intermediate (otherwise) and abnormal (abnormal PR&WSSR). All patients received guideline-recommended medical treatment. We developed and compared performance of nomograms composed of these variables and independent predictors identified in multivariate logistic regression, in predicting the primary outcome, recurrent ischaemic stroke in the same territory (SIT) within 1 year. RESULTS: Among 245 sICAS patients, 20 (8.2%) had SIT. The D2H2A nomogram, incorporating diabetes, dyslipidaemia, haemodynamic status of sICAS, hypertension and age ≥50 years, showed good calibration (P for Hosmer-Lemeshow test=0.560) and discrimination (C-statistic 0.73, 95% CI 0.60 to 0.85). It also had better performance in risk reclassification and provided larger net benefits in decision curve analysis, compared with nomograms composed of conventional vascular risk factors only, and plus the severity of luminal stenosis in sICAS. Sensitivity analysis in patients with anterior-circulation sICAS showed similar results. CONCLUSIONS: The D2H2A nomogram, incorporating conventional vascular risk factors and the haemodynamic significance of sICAS as assessed in CFD models, could be a useful tool to stratify sICAS patients for the risk of recurrent stroke under contemporarily optimal medical treatment.

Cerebral Hemodynamics Underlying Artery-to-Artery Embolism in Symptomatic Intracranial Atherosclerotic Disease.

Artery-to-artery embolism (AAE) is a common stroke mechanism in intracranial atherosclerotic disease (ICAD), associated with a considerable risk of recurrent stroke. We aimed to investigate cerebral hemodynamic features associated with AAE in symptomatic ICAD. Patients with anterior-circulation, symptomatic ICAD confirmed in CT angiography (CTA) were recruited. We classified probable stroke mechanisms as isolated parent artery atherosclerosis occluding penetrating artery, AAE, hypoperfusion, and mixed mechanisms, largely based on infarct topography. CTA-based computational fluid dynamics (CFD) models were built to simulate blood flow across culprit ICAD lesions. Translesional pressure ratio (PR = Pressurepost-stenotic/Pressurepre-stenotic) and wall shear stress ratio (WSSR = WSSstenotic-throat/WSSpre-stenotic) were calculated, to reflect the relative, translesional changes of the two hemodynamic metrics. Low PR (PR ≤ median) and high WSSR (WSSR ≥ 4th quartile) respectively indicated large translesional pressure and elevated WSS upon the lesion. Among 99 symptomatic ICAD patients, 44 had AAE as a probable stroke mechanism, 13 with AAE alone and 31 with coexisting hypoperfusion. High WSSR was independently associated with AAE (adjusted OR = 3.90; P = 0.022) in multivariate logistic regression. There was significant WSSR-PR interaction on the presence of AAE (P for interaction = 0.013): high WSSR was more likely to associate with AAE in those with low PR (P = 0.075), but not in those with normal PR (P = 0.959). Excessively elevated WSS in ICAD might increase the risk of AAE. Such association was more prominent in those with large translesional pressure gradient. Hypoperfusion, commonly coexisting with AAE, might be a therapeutic indicator for secondary stroke prevention in symptomatic ICAD with AAE.

A cross-sectional study of COVID-19 vaccination patterns among patients with epilepsy in Hong Kong.

OBJECTIVE: As Hong Kong faced the 5th wave of the COVID-19 pandemic, the facilitators and hurdles toward effective vaccination is important for healthcare professionals to understand the vaccination gap among patients with epilepsy. METHODS: A cross-sectional, pragmatic study of COVID-19 vaccination was performed at a tertiary epilepsy center with regards to patterns of vaccination and any unusually high rate of adverse events. Patients having recent visits at the epilepsy center (4 months) had their anonymized electronic linkage records examined 12 months after the inception of vaccination program for types of vaccines, seizure demographics, and adverse events following immunization (AEFI). RESULTS: A total of 200 patients with epilepsy and their anonymized data were analyzed. The vaccine uptake was approximately 60% of that of the general population. Twice as many patients with epilepsy chose to receive mRNA vaccine as compared with inactivated vaccine. The proportion of patients who kept up-to-date with all available dosing was 7%. Patients with epilepsy with genetic etiology were least likely to receive vaccination (13/38, 34%, P = .02). There was no unreasonably high rate of unacceptable side effects after vaccination among patients with epilepsy. Only 3 patients reported worsening of seizures without meeting the criteria for AEFI. Refractory epilepsy, allergy to antiseizure medications and elder age (≥65) did not confer any significant difference in vaccination patterns or adverse effects. SIGNIFICANCE: A vaccination gap exists among epilepsy patients which calls for actionable strategies for improving vaccine uptake, including education and outreach programs.

Evolving ischemic stroke subtypes in 15 years: A hospital-based observational study.

BACKGROUND: Depicting the time trends of ischemic stroke subtypes may inform healthcare resource allocation on etiology-based stroke prevention and treatment. AIM: To reveal the evolving ischemic stroke subtypes from 2004 to 2018. METHODS: We determined the stroke etiologies of consecutive first-ever transient ischemic attack or ischemic stroke patients admitted to a regional hospital in Hong Kong from 2004 to 2018. We analyzed the age-standardized incidences and the two-year recurrence rate of major ischemic stroke subtypes. RESULTS: Among 6940 patients admitted from 2004 to 2018, age-standardized incidence of ischemic stroke declined from 187.0 to 127.4 per 100,000 population (p < 0.001), driven by the decrease in large artery disease (43.0-9.67 per 100,000 population (p < 0.001)), and small vessel disease (71.9-45.7 per 100,000 population (p < 0.001)). Age-standardized incidence of cardioembolic stroke did not change significantly (p = 0.2). Proportion of cardioembolic stroke increased from 20.4% in 2004-2006 to 29.3% in 2016-2018 (p < 0.001). Two-year recurrence rate of intracranial atherothrombotic stroke reduced from 19.3% to 5.1% (p < 0.001) with increased prescriptions of statin (p < 0.001) and dual antiplatelet therapy (p < 0.001). In parallel with increased anticoagulation use across the study period (p < 0.001), the two-year recurrence of AF-related stroke reduced from 18.9% to 6% (p < 0.001). CONCLUSION: Etiology-based risk factor control might have led to the diminishing stroke incidences related to atherosclerosis. To tackle the surge of AF-related strokes, arrhythmia screening, anticoagulation usage, and mechanical thrombectomy service should be reinforced. Comparable preventive strategies might alleviate the enormous stroke burden in mainland China.

Risk factors for delayed-onset dementia after stroke or transient ischemic attack-A five-year longitudinal cohort study.

BACKGROUND: Stroke not only substantially increases the risk of incident dementia early after stroke but also the risk remains elevated years after. AIM: We aimed to determine the risk factors of dementia onset more than three to six months after stroke or transient ischemic attack. METHODS: This is a single-center prospective cohort study. We recruited consecutive subjects with stroke/transient ischemic attack without early-onset dementia. We conducted an annual neuropsychological assessment for five years. We investigated the association between baseline demographic, clinical, genetic (APOEɛ4 allele), and radiological factors as well as incident recurrent stroke with delayed-onset dementia using Cox proportional hazards models. RESULTS: In total, 1007 patients were recruited, of which 88 with early-onset dementia and 162 who lost to follow-ups were excluded. Forty-nine (6.5%) out of 757 patients have incident delayed-onset dementia. The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline Hong Kong version of the Montreal Cognitive Assessment (MoCA) score were significantly associated with delayed-onset dementia. APOEɛ4 allele, medial temporal lobe atrophy, and recurrent stroke were not predictive. CONCLUSION: The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline MoCA score are associated with delayed-onset dementia after stroke/transient ischemic attack.

Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease.

OBJECTIVES: The predisposition of intracranial atherosclerotic disease (ICAD) to East Asians over Caucasians infers a genetic basis which, however, remains largely unknown. Higher prevalence of vascular risk factors (VRFs) in Chinese over Caucasian patients who had a stroke, and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD. METHODS: Unrelated symptomatic patients with ICAD were recruited for genome sequencing (GS, 60-fold). Rare and potentially deleterious single-nucleotide variants (SNVs) and small insertions/deletions (InDels) were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes. Rare aneuploidies, copy number variants (CNVs) and chromosomal structural rearrangements were also investigated. Lastly, candidate genes were used for pathway and gene ontology enrichment analysis. RESULTS: Among 92 patients (mean age at stroke onset 61.0±9.3 years), GS identified likely ICAD-associated rare genomic variants in 54.3% (50/92) of patients. Forty-eight patients (52.2%, 48/92) had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes. None of the 59 rare variants were identified in local subjects without ICAD (n=126). 31 SNVs/InDels were related to conventional VRFs, and 28 were discovered in genes related to other stroke subtypes. Our study also showed that rare CNVs (n=7) and structural rearrangement (a balanced translocation) were potentially related to ICAD in 8.7% (8/92) of patients. Lastly, candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process. CONCLUSIONS: Our GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients.

Elevated Neutrophil to Lymphocyte Ratio Associated With Increased Risk of Recurrent Vascular Events in Older Minor Stroke or TIA Patients.

BACKGROUND: The risk of recurrent stroke following a minor stroke or transient ischemic attack (TIA) is high, when inflammation might play an important role. We aimed to evaluate the value of neutrophil to lymphocyte ratio (NLR) in predicting composite cardiovascular events in patients with minor stroke and TIA. METHODS: Consecutive patients with acute minor stroke or TIA admitted within 24 h of symptoms onset during a 5-year period in a prospective stroke registry were analyzed. We calculated the NLR dividing absolute neutrophil count by absolute lymphocyte count tested within 24 h of admission. NLR ≥4th quartile was defined as high NLR. A composite outcome was defined as stroke, acute coronary syndrome or vascular death within 1 year. We investigated associations between NLR and the composite outcome in univariate and multivariate analyses, among all patients and in those aged over 60 years (i.e., older patients). RESULTS: Overall, 841 patients (median age 68 years; 60.4% males) were recruited. No significant independent association was found between NLR and the composite outcome in multivariate analysis in the overall cohort. Among the 612 older patients (median age 73 years; 59.2% males), the median NLR was 2.76 (interquartile range 1.96-4.00) and 148 (24.2%) patients had high NLR. The composite outcome occurred in 77 (12.6%) older patients, who were more likely to have a high NLR (39.0% versus 22.1%; p = 0.001) than those without a composite outcome. In multivariate logistic regression, high NLR (adjusted odds ratio 2.00; 95% confidence interval 1.07-3.75; p = 0.031) was independently associated with the composite outcome in older patients. CONCLUSION: In older (aged ≥60 years) patients with acute minor stroke or TIA, a higher NLR, a marker of systemic inflammation that can be easily obtained in routine blood tests, is an independent predictor of subsequent cardiovascular events.

Sustaining cerebral perfusion in intracranial atherosclerotic stenosis: The roles of antegrade residual flow and leptomeningeal collateral flow.

We aimed to investigate the roles of antegrade residual flow and leptomeningeal collateral flow in sustaining cerebral perfusion distal to an intracranial atherosclerotic stenosis (ICAS). Patients with apparently normal cerebral perfusion distal to a symptomatic middle cerebral artery (MCA)-M1 stenosis were enrolled. Computational fluid dynamics models were built based on CT angiography to obtain a translesional pressure ratio (PR) to gauge the residual antegrade flow. Leptomeningeal collaterals (LMCs) were scaled on CT angiography. Cerebral perfusion metrics were obtained in CT perfusion maps. Among 83 patients, linear regression analyses revealed that both translesional PR and LMC scale were independently associated with relative ipsilesional mean transit time (rMTT). Subgroup analyses showed that ipsilesional rMTT was significantly associated with translesional PR (p < 0.001) rather than LMC scale in those with a moderate (50-69%) MCA stenosis, which, however, was only significantly associated with LMC scale (p = 0.051) in those with a severe (70-99%) stenosis. Antegrade residual flow and leptomeningeal collateral flow have complementary effects in sustaining cerebral perfusion distal to an ICAS, while cerebral perfusion may rely more on the collateral circulation in those with a severe stenosis.