Intracranial Large Artery Stenosis Research Articles

Abstract WP255: Association Between Asymptomatic Intracranial Large Artery Stenosis and Neurofilament Light Chain: The Northern Manhattan Study

Introduction: The Neurofilament light chain (NfL) is a neuronal cytoplasmic protein and a reliable biomarker for assessing axonal damage in neurological diseases and traumatic brain injury. Asymptomatic intracranial large artery stenosis (ILAS) has been associated with higher risk of stroke and dementia. Although widely studied in the last few years, the role of NfL concentrations in ILAS is not well understood. Methods: We leveraged data from stroke-free participants in the population-based cohort Northern Manhattan Study (NOMAS) for a pilot study. Arterial stenosis was measured on magnetic resonance angiography in 11 intracranial large arteries and graded as 0 = no stenosis, 1 ≤ 50%, 2 = 50-69%, 3 ≥ 70% stenosis and 4 = flow gap. An asymptomatic Intracranial Large Artery Stenosis (ILAS) score was then developed to reflect the global stenotic burden, with a range of 0 to 44. We also dichotomized the ILAS score into any stenosis > 50% versus none to reflect a more clinically relevant definition of ILAS. NfL concentrations were measured in plasma using Quanterix Simoa™ platform. We conducted generalized linear models adjusting for demographic and vascular risk factors and Wald Chi-Square test to analyze the association between NfL and ILAS score. Results: We included 79 stroke-free NOMAS participants (66% women, 77% Hispanic/Latino, and 75% with hypertension). The mean concentration of NFL was 0.19±0.10 pg/mL with a mean intra-assay coefficient of variation equal to 8.2%. In a model adjusted for age, sex, race/ethnicity, hypertension, diabetes, dyslipidemia and smoking, a higher ILAS score was associated with increased levels of NfL (B=0.01 ± 0.004, p=0.007). In an adjusted model, any stenosis >50% was also associated with increased levels of NfL (B=0.11 ± 0.03, p<0.001). Conclusions: The increased levels of plasma NfL associated with asymptomatic ILAS suggest neuronal injury that may implicate development of neurodegeneration. Confirming these results in a larger sample and longitudinal evaluation of NfL may advance the understanding of the mechanisms by which ILAS may increase the risk of dementia.

Abstract WP239: Apolipoprotein E4 Allele Effect on the Prevalence of Intracranial Large Artery Stenosis

Introduction: Apolipoprotein E4 (ApoE4) allele is linked to increased LDL-Cholesterol, one of the main risk factors for intracranial large artery stenosis (ICAS). Evidence shows that in diabetic men, intima-media thickness is significantly higher in those with ApoE4 than those with ApoE3. While the link between ApoE4 and extracranial atherosclerosis and vascular risk factors is established, the association of these vascular factors with ICAS is unknown. This study investigates the relationship between ApoE4 carrier status and ICAS and whether vascular risk factors influence this relationship. Methods: We rated intracranial large arteries on MR-angiography for their degree of stenosis as 0=no stenosis, 1=<50% stenosis, 2=50-69%, 3=70% or flow gap. We added the score of each of the 11 intracranial arteries to reflect a composite measure of the severity of ICAS. We then related ApoE4 carrier status to the ICAS score using generalized linear models with a Poisson link, adjusting for demographics, vascular risk factors, and cohort. We ran pre-specified interaction models with demographics and vascular risk factors. Results: 4099 individuals from six cohorts were included; 58% were women, the prevalence of hypertension was 76%, diabetes 31%, dyslipidemia 64%, and current smoking 13% (Table). There was no association between ApoE4 carrier and ICAS score (B= 0.08+0.06, p=0.19), but we found statistical interactions between ApoE4 carrier and male sex (p=<0.001), current smoking (p=0.05), and hypertension (p=0.003). ApoE4 carrier status was associated with higher ICAS score among hypertensive men (B=0.52±0.11, P=<0.001) and hypertensive people who smoke (B=0.58±0.20, p=0.01. Conclusion: ApoE4 carrier status was not associated with ICAS overall, but there were associations in subgroups defined by sex, hypertension, and smoking. Whether these interactions influence the risk of stroke and dementia should be further investigated.

Thromboelastographic and Gene Polymorphism Bimodality Detection for Dual Antiplatelet Aggregation Therapy in Individuals with Clopidogrel-resistant Symptomatic Intracranial Artery Stenosis.

Recent research indicates that clopidogrel resistance is connected with a patient's future ischemia risk, hence increasing the likelihood of recurrent ischemic cerebrovascular disease. Thromboelastographic and clopidogrel gene polymorphism testing can be used to see how a person responds to antiplatelet therapy and change the treatment plan accordingly. This may be a good way to make antiplatelet aggregation therapy more effective and safer. The objective of this study was to investigate the efficacy of dual antiplatelet aggregation therapy in patients with symptomatic intracranial large artery stenosis being resistant to clopidogrel tablets. The thromboelastographic and gene polymorphism bimodality detection techniques were used to analyze the clopidogrel resistance influencing factors. 89 patients with symptomatic intracranial large arterial stenosis who were admitted to our hospital from February 2021 to February 2022 were selected, classified as large artery atherosclerotic type by TOAST, and confirmed as having severe intracranial large arterial stenosis (70 % to 99 %) by magnetic resonance angiography (MRA), computed tomographic angiography (CTA), and digital subtraction angiography (DSA). All patients were treated with dual antiplatelet therapy with aspirin and clopidogrel, and thromboelastography and clopidogrel gene polymorphism were monitored 1 week later. 44 of 89 patients were clopidogrel-resistant. Among 44 patients, 20 were ticagrelorresistant and 24 were cilostazol-resistant. Clopidogrel had a resistance rate of 49.4%. The recurrence of ischemic cerebrovascular disease in the three groups was statistically significant (P<0.05) after 3 months of follow-up treatment, but bleeding (intracranial, gastrointestinal, respiratory, urinary, and mucocutaneous) and dyspnea were not. The clopidogrel-resistant group had a higher number of females, as well as higher levels of hypertension, diabetes, and platelet count than the sensitive group (P<0.05), but there was no significant difference in age, smoking, alcohol consumption, previous stroke, glycosylated haemoglobin, creatinine, or low-density cholesterol. Using thromboelastographic and gene polymorphism bimodality detection, we found switching to ticagrelor antiplatelet aggregation therapy as better than switching to cilostazol in patients with symptomatic intracranial large artery stenosis being resistant to clopidogrel tablets. The results may be biased due to the study being a single-centre study and having a limited sample size.

JAK2 V617F Mutation and Large Cerebral Artery Disease in Patients with Myeloproliferative Neoplasms.

The aim of the present study was to clarify the association between the Janus kinase 2 (JAK2) V617F mutation and large cerebral artery disease (LCAD) in patients with myeloproliferative neoplasms (MPNs). We retrospectively analysed patients diagnosed with MPNs between June 1992 and June 2022 who underwent brain magnetic resonance imaging. LCAD was defined as extracranial or intracranial large artery stenosis (≥ 50%) or occlusion on magnetic resonance angiography. A total of 86 patients (47 males; median age, 69 years old) were enrolled in this study. JAK2 V617F mutation was detected in 63 (73.3%) patients and LCAD in 35 (40.7%) patients. Univariate analysis showed that history of ischaemic stroke (LCAD, 62.9% vs. non-LCAD, 11.8%; P＜0.001), JAK2 V617F mutation (91.4% vs. 60.8%, P=0.002), and age ≥ 60 years (85.7% vs. 60.8%, P=0.016) were significantly associated with LCAD. Multiple logistic regression analysis showed that, in addition to ischaemic stroke, age ≥ 60 years and diabetes mellitus, JAK2 V617F mutation (odds ratio 29.2, 95% confidence interval 1.2-709.8, P=0.038) was independently associated with LCAD. LCAD was frequently observed in the intracranial carotid (14/35, 40.0%) and middle cerebral (13/35, 37.1%) arteries. This study revealed a significant association between the JAK2 V617F mutation and LCAD in patients with MPNs. This suggests that the JAK2 V617F mutation may promote cerebrovascular atherosclerosis and could be very important in determining therapeutic strategies for patients with not only JAK2 V617F-mutated MPNs but also LCAD-related stroke.

Immune Markers Are Associated With Asymptomatic Intracranial Large Artery Stenosis and Future Vascular Events in NOMAS.

Inflammation contributes to atherosclerosis but is incompletely characterized in intracranial large artery stenosis (ICAS). We hypothesized that immune markers would be associated with ICAS and modify the risk ICAS confers on future vascular events. This study included a subsample of stroke-free participants in the prospective NOMAS (Northern Manhattan Study), who had blood samples analyzed with a 60-plex immunoassay (collected from 1993 to 2001) and ICAS assessment with time-of-flight magnetic resonance angiography (obtained from 2003 to 2008). We dichotomized ICAS as either ≥50% stenosis or not (including no ICAS). We ascertained post-magnetic resonance imaging vascular events. We used least absolute shrinkage and selection operator procedures to select immune markers independently associated with ICAS. Then, we grouped selected immune markers into a derived composite Z score. Using proportional odds regression, we quantified the association of the composite immune marker Z score, ICAS, and risk of vascular events. Among 1211 participants (mean age, 71±9 years; 59% women; 65% Hispanic participants), 8% had ≥50% ICAS. Using least absolute shrinkage and selection operator regression, we identified CXCL9 (C-X-C motif chemokine ligand 9), HGF (hepatocyte growth factor), resistin, SCF (stem cell factor), and VEGF-A(vascular endothelial growth factor A) to have the strongest positive relationships with ≥50% ICAS in fully adjusted models. Selected markers were used to derive a composite immune marker Z score. Over an average follow-up of 12 years, we found that each unit increase in immune marker Z scores was associated with an 8% (95% CI, 1.05-1.11), 11% (95% CI, 1.06-1.16), and 5% (95% CI, 1.01-1.09) increased hazard of death, vascular death, and any vascular event, respectively, in adjusted models. We did not find a significant interaction between immune marker Z scores and ICAS in their relationship with any longitudinal outcome. Among a diverse stroke-free population, selected serum immune markers were associated with ICAS and future vascular events. Further study is needed to better understand their role in the pathogenesis of ICAS and as a potential therapeutic target in stroke prevention.

Early detection of stroke at the sudden sensorineural hearing loss stage.

Sudden sensorineural hearing loss (SSNHL) can be a prodromal symptom of ischemic stroke, especially posterior circulation strokes in the anterior inferior cerebellar artery (AICA) area. Early diagnosis and optimal treatment for vascular SSNHL provide an opportunity to prevent more extensive area infarction. The objective of our research was to find clues that suggest stroke at the stage of isolated sudden hearing loss. We retrospectively investigated the medical records of patients who received an initial diagnosis of sudden sensorineural hearing loss upon admission from January 2017 to December 2022 at Capital Medical University Affiliated Beijing Tiantan Hospital. Among these patients, 30 individuals who developed acute ischemic stroke during their hospital stay were enrolled as the case group. To create a control group, we matched individuals from the nonstroke idiopathic SSNHL patients to the case group in terms of age (±3 years old) at a ratio of 1:4. We collected the clinical characteristics, pure tone hearing threshold test results, and imaging information for all patients included in the study. Three models were constructed to simulate different clinical situations and to identify vascular sudden sensorineural hearing loss (SSNHL). The results revealed that patients with SSNHL who had three or more stroke risk factors, bilateral hearing loss, moderately severe to total hearing loss, and any intracranial large artery stenosis and occlusion (≥50%) were at a higher risk of developing ischemic stroke during hospitalization. Consistent with previous studies, the presence of vertigo at onset also played a significant role in the early detection of upcoming stroke. Clinicians should be alert to SSNHL patients with bilateral hearing loss, moderately severe to total hearing loss and other aforementioned features. Early pure tone audiometric hearing assessment and vascular assessment are necessary for high-risk patients with SSNHL.

Mediterranean-style diet and intracranial large artery stenosis in the Northern Manhattan Study

ObjectivesGiven Mediterranean-style diet (MeDi) reduces risk of cardiovascular events, we hypothesized MeDi may also be protective against intracranial large artery stenosis (ICAS), a common cause of stroke worldwide. MethodsThis cross-sectional study included stroke-free participants of the Northern Manhattan Study, a diverse population-based study of stroke risk factors. We represented MeDi continuously (range 0-8) based on enrollment food frequency questionnaires, excluding alcohol consumption. We evaluated ICAS both dichotomously at clinically relevant stenosis severities and continuously as a score (possible range 0-44), summated from stenosis severity scores of major intracranial arteries from time-of-flight magnetic resonance angiography. We used logistic or zero-inflated Poisson regression, adjusting for key confounders. ResultsAmong 912 included participants (mean age 64±8 years, 59% female, 65% Hispanic, mean MeDi score 4±1.5), 5% and 8% of participants had ≥50% or ≥70% ICAS, respectively (score median [interquartile range]: 0 [0-2]). Increased MeDi score was inversely associated with ICAS, but did not reach statistical significance (≥50% stenosis odds ratio (OR) [95% confidence interval (CI)]: 0.89 [0.79-1.06]; ≥70% stenosis OR [95% CI]: 0.91 [0.74-1.13]; stenosis score β-estimate [95% CI]: -0.02 [-0.06-0.01]). ConclusionIn this stroke-free subsample, we did not find a significant association between MeDi and ICAS. We may have been limited by statistical power.

Intraluminal arterial transit artifact as a predictor of intracranial large artery stenosis on 3D time of flight MR angiography: Expanding the application of arterial spin labeling MRI in ischemic stroke.

The objective of this study was to evaluate the diagnostic value of "intraluminal arterial transit artifact" in the prediction of intracranial large artery stenosis and to determine if this finding is predictive of ischemic stroke in the territory of the involved artery. The presence of arterial transit artifact (ATA) within the lumen of an intracranial large vessel was noted on three-dimensional time of flight (3D-TOF) magnetic resonance angiography (MRA) (ATA group). The patients with stenosis but with no ATA (no-ATA group), patients with total occlusion (total occlusion group), and patients with no stenosis/occlusion (normal group) were included in the analysis. There were four groups of patients included in the final analysis, the ATA group (n = 22), the no-ATA group (n = 23), the normal group (n = 25), and the total occlusion group (n = 9). Among patients with any demonstrable stenosis (n = 45), the presence of ATA within the stenotic segment was predictive of stenosis of ≥56% (Sensitivity of 100% [85.2-100, 95% CI], specificity of 100% [86.4-100, 95% CI]), with area under curve of 1.0 (0.92-.0, 95% CI). The presence of intra-arterial ATA signal was significantly associated with ischemic stroke as compared with the no-ATA group (86.36% vs. 26.08%, P = 0.0003). Intraluminal ATA was found to be an independent predictor of infarction in the territory of the involved artery. Intraluminal ATA is predictive of stenosis of at least 56% in the involved artery on 3D-TOF MRA. Intraluminal ATA sign may be an independent predictor of infarction in the territory of the involved artery.

The role of intracranial artery calcification (IAC) in stroke subtype and risk of vascular events

ObjectiveTo test the hypothesis that intracranial arterial calcification (IAC) is associated with intracranial large artery stenosis (ILAS) and a higher risk of vascular events and mortality. MethodWe leveraged data from two cohorts, the New York-Presbyterian Hospital/Columbia University Irving Medical Center Stroke Registry Study (NYP/CUIMC-SRS) and the Northern Manhattan Study (NOMAS) to test our hypotheses. We measured IAC using CT scans of participants in both cohorts and expressed IAC as present (vs not) and in tertiles. For the CUIMC-SRS, demographic, clinical and ILAS status was collected retrospectively. In NOMAS, we used research brain MRI and MRA to define asymptomatic ILAS and covert brain infarcts(CBI). We built models adjusted for demographics and vascular risk factors for cross-sectional and longitudinal analyses. ResultsCross-sectionally, IAC was associated with ILAS in both cohorts (OR 1.78, 95% CI: 1.16-2.73 for ILAS-related stroke in the NYP/CUIMC-SRS and OR 3.07, 95%CI 1.13-8.35 for ILAS-related covert brain infarcts in NOMAS). In a meta-analysis of both cohorts, IAC in the upper (HR 1.25, 95%CI 1.01-1.55) and middle tertile (HR 1.27, 95%CI 1.01-1.59) was associated with higher mortality compared with participants with no IAC. There were no longitudinal associations between IAC and risk of stroke or other vascular events. ConclusionIn these multiethnic populations, IAC is associated with symptomatic and asymptomatic ILAS as well as higher mortality. IAC may be a useful marker of higher mortality, the role of IAC as an imaging marker of risk of stroke is less certain.

Improving the diagnostic performance of computed tomography angiography for intracranial large arterial stenosis by a novel super-resolution algorithm based on multi-scale residual denoising generative adversarial network

BackgroundComputed tomography angiography (CTA) is very popular because it is characterized by rapidity and accessibility. However, CTA is inferior to digital subtraction angiography (DSA) in the diagnosis of intracranial artery stenosis or occlusion. DSA is an invasive examination, so we optimized the quality of cephalic CTA images. MethodsWe used 5000 CTA images to train multi-scale residual denoising generative adversarial network (MRDGAN). And then 71 CTA images with intracranial large arterial stenosis were treated by Super-Resolution based on Generative Adversarial Network (SRGAN), Enhanced Super-Resolution based on Generative Adversarial Network (ESRGAN) and post-trained MRDGAN, respectively. Peak signal-to-noise ratio (PSNR) and structural similarity index measurement (SSIM) of the SRGAN, ESRGAN, MRDGAN and original CTA images were measured respectively. The qualities of MRDGAN and original images were visually assessed using a 4-point scale. The diagnostic coherence of digital subtraction angiography (DSA) with MRDGAN and original images was analyzed. ResultsThe PSNR was significantly higher in the MRDGAN CTA images (35.96 ± 1.51) than in the original (31.51 ± 1.43), SRGAN (25.75 ± 1.18) and ESRGAN (30.36 ± 1.05) CTA images (all P < 0.001). The SSIM was significantly higher in the MRDGAN CTA images (0.95 ± 0.02) than in the SRGAN (0.88 ± 0.03) and ESRGAN (0.90 ± 0.02) CTA images (all P < 0.01). The visual assessment was significantly higher in the MRDGAN CTA images (3.52 ± 0.58) than in the original CTA images (2.39 ± 0.69) (P < 0.05). The diagnostic coherence between MRDGAN and DSA (κ = 0.89) was superior to that between original images and DSA (κ = 0.62). ConclusionOur MRDGAN can effectively optimize original CTA images and improve its clinical diagnostic value for intracranial large artery stenosis.

Genetic determinants of intracranial large artery stenosis in the northern Manhattan study

BackgroundIntracranial stenosis is one of the most common causes of stroke worldwide. Several single nucleotide polymorphisms have been associated with intracranial atherosclerosis, which is inferred to be the most common underlying cause of intracranial large artery stenosis (ILAS). We previously reviewed known genetic variants related to ILAS in predominantly Asian cohorts, but their prevalence and role in ILAS among western multiethnic populations are uncertain. MethodsWe leveraged existing imaging and genetic data from the Northern Manhattan Study, a multiethnic prospective cohort study. Based on literature review, we selected adiponectin Q (ADIPOQ) rs2241767 and rs182052, ring finger protein 213 (RNF213) rs112735431, apolipoprotein E (APOE) rs429358, phosphodiesterase 4D (PDE4D) rs2910829, lipoprotein lipase (LPL) rs320, and aldosterone synthase (CYP11B2) rs1799998 variants as candidates to explore. We defined ILAS as luminal stenosis >50% in any intracranial large artery using time-of-flight magnetic resonance angiography (MRA). ResultsWe included 1109 participants (mean age 70 ± 9 years, 70% Hispanic, 60% women) in this study. ILAS was identified in 81 (7%) NOMAS participants. Logistic regression analyses adjusted for age, sex, principal components, and vascular risk factors showed ILAS prevalence associated with CYP11B2 rs1799998 under the dominant model (OR = 0.56, 95%CI: 0.35–0.89) and LPL rs320 heterozygote genotype (OR = 1.68, 95%CI: 1.05–2.71). The genotype distributions of ADIPOQ rs2241767 and rs182052, APOE rs429358 and CYP11B2 rs1799998 variants were significantly different among non-Hispanic white and Black, and Hispanic groups. When participants were further stratified by race/ethnicity, the estimates were consistent for CYP11B2 rs1799998 across race/ethnic groups but not for LPL rs320. ConclusionThe CYP11B2 rs1799998 variant may be a protective genetic factor for ILAS across race/ethnic groups, but the risk of ILAS associated with LPL rs320 varies by race/ethnic group. Further functional studies may help elucidate the role that these variants play in the pathophysiology of ILAS.

Intracranial Large Artery Stenosis and Past Infectious Exposures: Results From the NOMAS Cohort.

Intracranial large artery stenosis (ILAS) is an important contributor to ischemic stroke in the United States and worldwide. There is evidence to suggest that chronic exposure to certain infectious agents may also be associated with ILAS. We aimed to study this association further in an ethnically diverse, prospective, population-based sample of Northern Manhattan. We enrolled a random sample of stroke-free participants from an urban, racially, and ethnically diverse community in 1993. Participants have been followed prospectively and a subset underwent brain magnetic resonance angiograms from 2003 to 2008. Intracranial stenoses of the circle of Willis and vertebrobasilar arteries were scored as 0=no stenosis, 1≤50% (or luminal irregularities), 2=50% to 69%, 3≥70% stenosis, and 4=flow gap. We summed the individual score of each artery to produce a global ILAS score (possible range, 0-44). Past infectious exposure to Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus 1 and 2 was determined using serum antibody titers. Among 572 NOMAS (Northern Manhattan Study) participants (mean age 71.0±8.0 years, 60% women, 68% Hispanic) with available magnetic resonance angiogram and serological data, herpes simplex virus 2 (beta=0.051, P<0.001) and cytomegalovirus (beta=0.071, P<0.05) were associated with ILAS score after adjusting for demographics and vascular risk factors. Stratifying by anterior and posterior circulations, herpes simplex virus 2 remained associated with the anterior circulation (beta=0.055 P<0.01) but not with posterior circulation ILAS score. Chronic infectious exposures, specifically herpes simplex virus 2 and cytomegalovirus were associated with asymptomatic ILAS as seen on magnetic resonance angiogram imaging. This may represent an additional target of intervention in the ongoing effort to stem the substantial global burden of strokes related to ILAS.

Chronic hypoperfusion due to intracranial large artery stenosis is not associated with cerebral β-amyloid deposition and brain atrophy.

Background:Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans.Methods:We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient.Results:The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47–76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion.Conclusion:Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.

Cerebrovascular Contributions to Neurocognitive Disorders in People Living With HIV.

To investigate a comprehensive array of magnetic resonance imaging (MRI)-based biomarkers of cerebrovascular disease (CVD) in a cohort of people living with HIV (PLWH) and relate these imaging biomarkers to cognition. Cross-sectional, community-based study. Participants were PLWH in New York City, aged 50 years or older. They underwent a brain magnetic resonance angiography or MRI to ascertain 7 MRI markers of CVD: silent brain infarcts, dilated perivascular spaces, microhemorrhages, white matter hyperintensity volume, white matter fractional anisotropy and mean diffusivity (measures of white matter integrity), and intracranial large artery stenosis. Participants underwent a battery of neurocognitive tests to obtain individual and global cognitive scores representative of various aspects of cognition. We included 85 participants (mean age 60 ± 6 years, 48% men, 78% non-Hispanic Black), most of them with well-controlled HIV (75% with CD4 cell count > 200 cells/mm3 and viral load < 400 copies/mL at or near the time of the MRI scan). Silent brain infarcts, intracranial large artery stenosis, and poor white matter integrity were associated with poorer performance in at least one cognitive domain, but the sum of these 3 MRI markers of CVD was associated with lower working memory (B = -0.213, P = 0.028), list learning (B = -0.275, P = 0.019), and global cognition (B = -0.129, P = 0.007). We identified silent brain infarcts, intracranial large artery stenosis, and poor white matter integrity as exposures that may be modifiable and may, therefore, influence cognitive decline. In addition, these MRI markers of CVD may help in identifying PLWH at higher risk of cognitive decline, which may be more amenable to targeted therapies.

Multiple hypointense vessels on susceptibility-weighted imaging predict early neurological deterioration in acute ischaemic stroke patients with severe intracranial large artery stenosis or occlusion receiving intravenous thrombolysis

Background and purposeEarly neurological deterioration (END) is a common feature in patients with acute ischaemic stroke (AIS) receiving thrombolysis. This study aimed to investigate whether the presence of multiple hypointense...

Asymmetrical cortical vessel sign predicts prognosis after acute ischemic stroke.

IntroductionTo assess whether the asymmetrical cortical vessel sign (ACVS) on susceptibility‐weighted imaging (SWI) could predict 90‐day poor outcomes in anterior circulation acute ischemic stroke (AIS) patients treated with recombinant tissue plasminogen activator (r‐tPA).MethodsClinical data of consecutive patients with anterior circulation AIS treated with r‐tPA were retrospectively analyzed. Clinical variables included age, sex, vascular risk factors, NIHSS score, onset to treatment time, and initial hematologic and neuroimaging findings. Follow‐up was performed 90 days after onset. Poor outcome was defined as a modified Rankin scale (mRS) ≥3 at 90 days.ResultsA total of 145 patients were included, 35 (24.1%) patients presented with ACVS (≥Grade 1) on SWI. Fifty‐three (36.6%) patients had a poor outcome at 90 days. ACVS (≥Grade 1) occurred in 21 (39.6%) patients with poor outcome compared with 14 (15.2%) patients with favorable outcome (p = .001). Univariate analysis indicated that age, NIHSS score on admission, previous stroke, hemorrhagic transformation, severe intracranial large artery stenosis or occlusion (SILASO), and ACVS were associated with 90‐day poor outcome (p < .05). Since SILASO and ACVS were highly correlated and ACVS had different grades, we used three logistic regression models. Results from the three models showed that ACVS was associated with 90‐day poor outcome.ConclusionsIn r‐tPA‐treated patients with anterior circulation AIS, ACVS might be a helpful neuroimaging predictor for poor outcome at 90 days.

Design of stroke imaging package study of intracranial atherosclerosis: a multicenter, prospective, cohort study.

Intracranial atherosclerosis (ICAS) is a major cause of stroke worldwide. However, much remains unknown regarding its underlying pathophysiology. High-resolution magnetic resonance imaging (HR-MRI) can clearly display intracranial vessel wall lesions in vivo. The aim of stroke imaging package study of ICAS (SIPS-ICAS) study is to explore the stroke mechanisms of symptomatic ICAS, the dynamic changes under aggressive medical treatment and their associations with clinical events using conventional MRI sequences plus HR-MRI. This is a multicenter, prospective, cohort study recruiting first-ever acute ischemic stroke patients attributed to intracranial large artery stenosis (>50% or occlusion). Subjects undergo a pre-designed stroke imaging packages at baseline and are recommended to receive aggressive medical treatments. Participants will be followed up for functional outcome, stroke recurrence, and death events at 3, 6 and 12 months and retake HR-MRI imaging at 6 months. Enrollment began in November 2018 and 96 patients have been enrolled as of September 2019. The SIPS-ICAS study will provide insights into the pathophysiology of ICAS and identify specific imaging markers for risk stratification and prognosis prediction. At the same time, the feasibility and validity of the new stroke imaging package including HR-MRI will be assessed, which is promising for clinical routine use.

Risk factors outperform intracranial large artery stenosis predicting unfavorable outcomes in patients with stroke

BackgroundThis study examined how intracranial large artery stenosis (ILAS), symptomatic and asymptomatic ILAS, and risk factors affect unfavorable outcome events after medical treatment in routine clinical practice.MethodsThis was a 24-month prospective observational study of consecutively recruited stroke patients. All participants underwent magnetic resonance angiography, and their clinical characteristics were assessed. Outcome events were vascular outcome, recurrent stroke, and death. Cox regression analyses were performed to identify potential factors associated with an unfavorable outcome, which included demographic and clinical characteristics, the risk factors, and stenosis status.ResultsThe analysis included 686 patients; among them, 371 were assessed as ILAS negative, 231 as symptomatic ILAS, and 84 as asymptomatic ILAS. Body mass index (p < .05), hypertension (p = .01), and old infarction (p = .047) were factors relating to vascular outcomes. Hypertension was the only factor for recurrent stroke (p = .035). Poor glomerular filtration rate (< 30 mL/min/1.73 m2) (p = .011) and baseline National Institutes of Health Stroke Scale scores (p < .001) were significant predictors of death.ConclusionsThis study extended previous results from clinical trials to a community-based cohort study by concurrently looking at the presence/absence of stenosis and a symptomatic/asymptomatic stenotic artery. Substantiated risk factors rather than the stenosis status were predominant determinants of adverse outcome. Although the degree of stenosis is often an indicator for treatment, we suggest risk factors, such as hypertension and renal dysfunction, should be monitored and intensively treated.

A13006 Association of ATP2B1 Common Variants with Asymptomatic Intracranial and Extracranial Large Artery Stenosis in Hypertension patients

A13006 Association of ATP2B1 Common Variants with Asymptomatic Intracranial and Extracranial Large Artery Stenosis in Hypertension patients

Association of ATP2B1 common variants with asymptomatic intracranial and extracranial large artery stenosis in hypertension patients

ABSTRACTBackground and aims: Genetic factors play an important role in the cervico-cerebral large-artery atherosclerotic stenosis (LAS), and ATP2B1 gene has been associated with the process of atherosclerosis disorders, such as coronary artery disease and arterial stiffness. But there is little information about the relationship between ATP2B1 gene and atherosclerosis in the intracranial arteries. We hereby investigated the association of common variants in ATP2B1 gene with LAS in asymptomatic Chinese hypertension patients. Methods: The stenosis of intracranial and extracranial arteries were evaluated in 899 subjects through computerized tomography angiography from the aortic arch to the skull base. A total of 11 ATP2B1 common variants were genotyped. Multivariate logistic regression was carried out in a dominant model with confounding factors adjusted. Results: rs17249754-A (OR = 0.43, p = 0.0002) and rs1401982-G (OR = 0.47, p = 0.0007) were associated with decreased susceptibility of concurrent extra and intracranial stenosis even after Bonferroni correction. These two minor alleles were also significantly associated with less stenotic arteries and moderate-to-severe stenosis. Conclusion: rs17249754 and rs1401982 were associated with asymptomatic LAS in stroke-free Chinese hypertension patients and might benefit early recognition of LAS patients in clinical practice.