Presence Of Small Vessel Disease Research Articles

Importance of small vessel disease as a possible cause of sudden sensorineural hearing loss.

Vascular disease like small-vessel disease (SVD) is the most likely cause among the potential causes of Sudden sensorineural hearing loss (SSNHL). Understanding the relationship between SVD and SSNHL is crucial for developing effective prevention and treatment strategies. To confirm the relationship between SVD and SSNHL, the effect of SVD is confirmed by focusing on the duration and recurrence of SSNHL. This article reports a retrospective observational study that investigated the relationship between SVD and SSNHL using the South Korea Health Insurance Review and Assessment Service (HIRA) database from 2010 to 2020. This retrospective observational study included 319,569 SSNHL patients between 2010 and 2020. Participant demographics were controlled using Propensity Score Matching. The hazard ratios (HR) for the effect of SVD on the duration of SSNHL were 1.045 for the group with SVD before the onset of SSNHL and 1.234 for the group with SVD after the onset of SSNHL. SVD was statistically significant for the recurrence of SSNHL, with an odds ratio of 1.312 in the group with SVD compared to the group without SVD. The HR for the period until a recurrence in the group with SVD was 1.062. The study identified SVD as a possible cause of SSNHL and found that the duration of SSNHL increased only in the presence of SVD. SVD also affected the recurrence of SSNHL, with the recurrence rate being 1.312 times higher in the group with SVD.

Longitudinal changes in blood flow, vessel pulsatility, and trans‐capillary pulse wave delay in small vessel disease and amyloid biomarker positive

AbstractBackgroundThis work characterized longitudinal changes in cerebrovascular health in humans with and without presence of small vessel disease (SVD) and amyloid‐β using different neuroimaging techniques.MethodParticipants (n = 41) were biomarker characterized into three groups: amyloid and SVD negative (A‐V‐; “control”), SVD positive (A‐V+), and amyloid positive (A+V‐). All were cognitively unimpaired except two participants clinically diagnosed with MCI (A‐V+) and dementia (A+V‐) (Table 1). MRI: Vascular imaging: Whole‐brain 4D‐Flow data were acquired to characterize cerebrovascular health. Two MRI time‐points were used to establish 4D‐Flow‐based longitudinal changes. Measurements were extracted from intracranial arteries and veins and included blood flow, vessel pulsatility index, and trans‐capillary pulse wave delay (TPWD). TPWD was defined as the time shift between arterial and venous cardiac waveforms. Structural imaging: TIV‐normalized WMH volumes were segmented from T2‐FLAIR images and used as surrogate for SVD. V+/‐ thresholds were determined from Gaussian Mixture Model on 930 participants. PET: Amyloid‐β burden was assessed using 11C‐PiB PET imaging. Amyloid positivity was established as mean cortical PiB DVR >1.16. Vascular changes were assessed using Kruskal‐Wallis followed by multiple comparisons (P<0.05 significance).ResultAfter ∼4.5 years, middle cerebral arteries (MCAs) blood flow decreased significantly more in amyloid than SVD groups, while vessel pulsatility increased significantly more in amyloid compared to SVD (Fig.1). TPWD shortened significantly in SVD compared to amyloid and control groups. All groups showed a decreased in blood flow, increased in vessel pulsatility and shortening of TPWD with time. At the time of the last MRI visit, MCAs blood flow was somewhat higher in SVD compared to amyloid and control groups, but not significantly (Fig.2). Vessel pulsatility was similar between groups, yet slightly higher in SVD and amyloid groups. TPWD was significantly shorter in SVD compared to the amyloid group.ConclusionThis work demonstrates the feasibility to measure longitudinal cerebrovascular changes using 4D‐Flow MRI in the context of SVD and AD biomarker positive groups. Preliminary results indicate 4D‐Flow‐based vascular markers can detect differences between SVD and amyloid groups both longitudinally and cross‐sectionally. Cerebrovascular changes in A+ suggest decreased metabolism and increased macro‐vessel stiffness, while findings in SVD positive supports stiffness of the micro‐circulation and capillaries.

White matter injury mediates the effects of PS1 mutation position on clinical measures in late disease stage

AbstractBackgroundClinical presentation of dominantly inherited Alzheimer disease (DIAD) varies across individuals with Presenilin‐1 (PS1) pathogenic mutations. Previous findings suggest that individuals with a PS1 mutation after codon 200 have more small vessel disease (SVD) pathology (Mann et al., 2001; Ryan et al., 2015). We investigated the effect of mutation position on clinical measures, including indirect effects via SVD as estimated by imaging markers of white matter injury.MethodWe evaluated 393 individuals with DIAD family history of PS1 mutations who underwent clinical and imaging assessments from the DIAN study. Among them, 245 carried a mutation before (Pre‐200MC, n = 83) or after codon‐200 (Post‐200MC, n = 162) and the remaining were non‐carriers (NC, n = 148). We assessed clinical disease stage with the Clinical Dementia Rating® Sum of Boxes (CDR®‐SB) scale and the estimated years to symptoms onset (EYO). White matter injury metrics included periventricular white matter hyperintensity (PVWMH) volumes from T2‐FLAIR and the peak width of skeletonized mean diffusivity (PSMD) from DTI (Shirzadi et al., 2022). Accounting for age of onset, sex, education, and APOE‐ɛ4 status, linear mixed‐effects models evaluated mutation position by EYO effect on SVD and on dementia in all participants. Further mediation analysis evaluated these effects within the carrier groups. Missing values were imputed using random forest algorithm.ResultPost‐200MC had more white matter injury with advanced EYO compared to Pre‐200MC (estimatesPVWMH = 65.3±31.8, P‐value<.05, estimatesPSMD = 0.01±0.003, P‐value<.0005) and to non‐carriers (estimatesPVWMH = 61.5±27.4, P‐value<.05, estimatesPSMD = 0.01±0.003, P‐value<.0005; Figure 1A). Post‐200MC presented higher CDR‐SB scores with advanced EYO compared to Pre‐200MC (estimatesCDR‐SB = 0.08±0.03, P‐value<.005) and to non‐carriers (estimatesCDR‐SB = 0.19±0.02, P‐value<.0001; Figure 1B). When EYO>0, the effects of mutation position on CDR‐SB were significantly mediated by PVWMH (e.g., average causal mediation effect at EYO = 0.5: estimatesCDR‐SB = 0.06[0.;0.14], P‐value<.05) or PSMD (e.g., average causal mediation effect at EYO = 0.5: estimatesCDR‐SB = 0.2[0.05;0.37], P‐value<.05; Table1).ConclusionThese findings give further insights on how mutation position within the PS1 gene influences clinical disease presentation in DIAD. This characterization may inform future clinical trials in this population as the presence of small vessel disease contributes to a more severe disease course, which may influence treatment outcome and decisions. Funding: AARFD‐20‐681815; U19AG032438.

Clinical implication of ticagrelor monotherapy in patients with small vessel coronary artery disease: results from the TICO randomized trial.

The aim of this study was to evaluate the efficacy and safety of ticagrelor monotherapy in patients with small vessel disease compared with ticagrelor-based DAPT within the Ticagrelor Monotherapy after 3 Months in the Patients Treated with New Generation Sirolimus Eluting Stent for Acute Coronary Syndrome (TICO) trial population. Reference vessel diameter ≤2.5 mm was considered as small vessel disease. We conducted a comparison of the incidence of target lesion failure (TLF) and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. TLF was defined as a composite of cardiac death, target lesion myocardial infarction, stent thrombosis, and target lesion revascularization. 652 patients among 3,056 TICO population (21.3%) had small vessel disease. Patients with small vessel disease showed a higher rate of TLF compared to those without small vessel disease (2.9% vs. 1.0%, log-rank p < 0.001). The presence of small vessel disease emerged as an independent predictor for 1-year TLF (HR 2.84, 95% CI 1.54-5.25), while it did not show a significant association with bleeding complications. The 12-month TLF rate was 1.6% for ticagrelor monotherapy after 3-month DAPT, and 4.2% for ticagrelor-based 12-month DAPT (p = 0.059) in patients with small vessel disease (HR 0.38, 95% CI 0.14-1.04, p for interaction = 0.261). The incidence of BARC type 3 or 5 bleeding rate 2.5% for ticagrelor monotherapy after 3-month DAPT, and 5.6% for ticagrelor-based 12-month DAPT (p = 0.052) in patients with small vessel disease (HR 0.44, 95% CI 0.19-1.01, p for interaction = 0.322). In the 3-month landmark analysis, ticagrelor monotherapy significantly reduced BARC type 3 or 5 bleeding in patients with small vessel disease (HR 0.09, 95% CI 0.01-0.69, log-rank p = 0.005) while demonstrating a similar incidence of TLF compared to ticagrelor based 12-month DAPT during the 3-12 months period. There are no significant interactions between the antiplatelet strategy regarding the 12-month incidence of ischemic and bleeding complications. Ticagrelor monotherapy demonstrated a reduction in bleeding complications after a 3-month period of DAPT without increasing the rate of TLF, when compared to ticagrelor-based 12-month DAPT, specifically in patients with small vessel disease. Clinical Trial Registration: www.ClinicalTrials.gov, identifier, NCT02494895.

Frequency, characteristics, and predictors of headache attributed to acute ischemic stroke

ObjectivesAlthough headache is a common symptom in acute ischemic stroke, the clinical and radiological factors associated with its occurrence are controversial. This work aimed to determine the frequency, characteristics, and predictors of headache occurrence among patients with acute ischemic stroke. MethodsThis cross-sectional study was conducted on 303 patients with acute ischemic stroke. The patients were submitted to detailed history taking, clinical and radiological assessment. A detailed analysis of headache was performed for the patients who experienced headache temporally related to stroke onset. ResultsDiagnosis of headache attributed to the ischemic stroke was established in 129 (42.6%) patients; sentinel headache in 17.2% of patients, and headache at stroke onset in 25.4% of patients. The headache group had a significantly younger age (P=0.017), lower NIHSS score (P=0.042), higher frequency of pre-existing headache disorders (P=0.001), substance use disorder (P=0.021), and fever (P=0.036), and lower frequency of chronic hypertension (P=0.013) and small vessel disease (P=0.004) than non-headache group. Infarction involving posterior circulation was more frequent in headache than in non-headache groups (P=0.003). The presence of migraine, tension-type headache, other types of headache, fever and posterior circulation stroke increased the odds of headache by 27.4 (95%CI=8.0–94.4), 7.6 (95%CI=3.93–14.6), 26.2 (95%CI=8.0–85.8), 3.75 (95%CI=1.22–11.6) and 3.15 (95%CI=1.65–6.0) times, respectively, whereas, the presence of small vessel disease decreased the odds of headache by 0.51 (95%CI=0.279–0.95) times. ConclusionPre-existing headache disorder, fever, and posterior circulation stroke were associated with headache occurrence in acute ischemic stroke patients.

1715-P: Osteopenic Obesity Is Associated with Small Vessel Disease in Old Adults—The Bunkyo Health Study

Obesity is one of the most important causes of metabolic disorders and cardiovascular events. Indeed, while the presence of cerebral small vessel disease (SVD) that includes silent brain infarcts, cerebral white matter lesions, and microhemorrhage increased the risk of stroke &amp;gt; 3-fold, and dementia &amp;gt; 2-fold, respectively, obesity has been identified as a risk factor for SVD. On the other hand, low bone mineral density (BMD), is also recognized as a risk factor for SVD. Whereas obesity is generally associated with high BMD, it has recently been reported that there is a special subtype of osteopenic obesity in which obesity and low BMD coexist. Thus, we hypothesized that this osteopenic obesity is at high risk for SVD. To test this hypothesis, we studied 1531 (641 male and 890 female) old adults aged 65 to 85 years without a history of stroke (Bunkyo Health Study). All subjects underwent dual-energy X-ray absorptiometry, brain MRI, and blood sampling, and they were classified into four groups according to the presence or absence of obesity and osteopenia (men) or osteoporosis (women) diagnosed by the BMD at the hip joint. The mean age of the subjects was 73.0 years. The prevalence of osteopenic obesity was 7.8% and 8.0% for men and women, respectively. While overall prevalence of SVD was 25% in men and 22% in women, the prevalence of SVD in osteopenic obesity was 46% and 42%, respectively. Logistic regression analysis revealed that odds ratio [95% CI] for SVD in control, obesity, osteopenia/osteoporosis and osteopenic obesity were 1.00, 1.203 [0.730-1.982], 0.970 [0.670-1.549] and 3.024 [1.560-5.861] in men and 1.00, 1.452 [0.818-2.575], 1.548 [1.012-2.368], 2.747 [1.489-5.069] in women, respectively. In conclusion, osteopenic obesity was independently associated with the presence of SVD in old adults without a history of stroke. Disclosure N.Ito: None. Y.Yoshizawa: None. H.Watada: Research Support; Boehringer Ingelheim Japan, Inc., Mitsubishi Tanabe Pharma Corporation, LifeScan Diabetes Institute, Eli Lilly Japan K.K., Sun Pharmaceutical Industries Ltd., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Kowa Company, Ltd., Merck Sharp &amp; Dohme Corp., Sanwa Kagaku Kenkyusho, Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., Novo Nordisk, Abbott Japan Co., Ltd., Astellas Pharma Inc., Merck Sharp &amp; Dohme Corp., Kissei Pharmaceutical Co., Ltd., AstraZeneca, Ono Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Inc., Sanofi, Sun Pharmaceutical Industries Ltd., Eli Lilly Japan K.K. Y.Tamura: None. H.Kaga: None. Y.Someya: None. H.Tabata: None. S.Kakehi: None. M.Kiya: None. T.Tajima: None. H.Naito: None. Funding Strategic Research Foundation at Private Universities (S1411006); Ministry of Education, Culture, Sports, Science and Technology of Japan (18H03184); Mizuno Sports Promotion Foundation; Mitsui Life Social Welfare Foundation

Methylenetetrahydrofolate reductase polymorphisms and elevated plasma homocysteine levels in small vessel disease.

Despite its public health importance, the causes of small vessel disease (SVD) are not fully understood. The presence of SVD in monogenic twins indicates the involvement of genetic factors in the pathogenesis of this disease. The purpose of this study was to investigate the association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with SVD risk. Patients with SVD and matched controls were recruited from Tianjin Union Medical Center and Tianjin Huanhu Hospital. Clinical and laboratory data were collected. Plasma total homocysteine (tHcy) and folate levels were measured, and MTHFR rs1801133 (C677T) and rs1801131 (A1298C) single-nucleotide polymorphisms were genotyped. We analyzed potential associations among SVD and MTHFR polymorphisms, tHcy, and folate levels. Patients with SVD displayed significantly decreased plasma folate levels (Z=-3.537, p<.001) and increased tHcy levels (Z=4.910, p<.001) compared with controls. Significantly different plasma tHcy levels were associated with rs1801133 (χ2 =6.664, p=.036), and post hoc analysis indicated higher plasma tHcy levels in individuals carrying the TT allele compared with levels in those carrying the TC allele (Z=2.478, p=.013). No significant differences in tHcy levels were observed for rs1801131 alleles. The genotype and allele frequencies of rs1801133 were different between SVD and control groups (χ2 =9.378, p=.009). There was no significant difference in distributions of rs1801131 genotypes between the two groups, and multivariable logistic regression analysis showed that rs1801131 and rs1801133 were not significantly associated with the risk of SVD. Our study indicates that an elevated plasma tHcy level is independently associated with the development of SVD. Although MTHFR rs1801133 is linked to increased plasma homocysteine (Hcy) levels, it is not a risk factor for SVD. rs1801131 is not related to Hcy levels or SVD risk.

Prognostic significance of small vessel coronary artery disease in patients with acute coronary syndromes treated with percutaneous coronary interventions.

Small vessel disease (SVD) usually refers to atherosclerosis within vessels of diameter of < 2.5 mm. Conflicting data exist regarding the outcomes of its revascularization. To evaluate the outcome of invasive treatment in patients with acute coronary syndromes (ACS) and SVD and the predictors of angina recurrence after percutaneous coronary intervention (PCI). This was an observational, retrospective, single-center study. It covered consecutive 127 patients (26.77% women; median age: 69.74 ±8.97 years) with ACS who underwent PCI in the Upper-Silesian Medical Center in Katowice between 2018 and 2020. The study population was stratified by means of presence of SVD defined by PCI of the culprit artery with a diameter of ≤ 2.5 mm. The major adverse cardiac and cerebrovascular events (MACCE) and angina recurrence were analyzed in a 12-month follow-up period. Overall 99 (77.95%) patients were diagnosed with small-vessel coronary artery disease. MACCE were documented in 14 (11.02%) patients. Univariate analysis revealed the following factors associated with MACCE: left ventricle ejection fraction (LVEF) (OR = 0.95, p = 0.0212), left main (LM) stenting (OR = 18.17, p = 0.0216), number of former PCIs (OR = 1.48, p = 0.0235). According to logistic regression analysis the factors were LM stenting (OR = 20.04, p = 0.0216) and number of former PCIs (OR = 1.53, p = 0.0203). Patients with SVD had more often refractory or recurrent angina in symptomatic class III/IV on follow-up (52.53% vs. 10.71%, p < 0.001). Outcome of invasive treatment in patients with ACS is related to LM stenting and former PCIs but not to SVD occurrence. Patients with SVD have a high rate of recurrent/refractory angina despite successful PCI in this clinical setting.

Impact of Cerebral Autoregulation Monitoring in Cerebrovascular Disease: A Systematic Review.

Cerebral autoregulation (CA) prevents brain injury by maintaining a relatively constant cerebral blood flow despite fluctuations in cerebral perfusion pressure. This process is disrupted consequent to various neurologic pathologic processes, which may result in worsening neurologic outcomes. Herein, we aim to highlight evidence describing CA changes and the impact of CA monitoring in patients with cerebrovascular disease, including ischemic stroke, intracerebral hemorrhage (ICH), and aneurysmal subarachnoid hemorrhage (aSAH). The study was preformed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. English language publications were identified through a systematic literature conducted in Ovid Medline, PubMed, and Embase databases. The search spanned the dates of each database's inception through January 2021. We selected case-control studies, cohort observational studies, and randomized clinical trials for adult patients (≥ 18years) who were monitored with continuous metrics using transcranial Doppler, near-infrared spectroscopy, and intracranial pressure monitors. Of 2799 records screened, 48 studies met the inclusion criteria. There were 23 studies on ischemic stroke, 18 studies on aSAH, 5 studies on ICH, and 2 studies on systemic hypertension. CA impairment was reported after ischemic stroke but generally improved after tissue plasminogen activator administration and successful mechanical thrombectomy. Persistent impairment in CA was associated with hemorrhagic transformation, malignant cerebral edema, and need for hemicraniectomy. Studies that investigated large ICHs described bilateral CA impairment up to 12days from the ictus, especially in the presence of small vessel disease. In aSAH, impairment of CA was associated with angiographic vasospasm, delayed cerebral ischemia, and poor functional outcomes at 6months. This systematic review highlights the available evidence for CA disruption during cerebrovascular diseases and its possible association with long-term neurological outcome. CA may be disrupted even before acute stroke in patients with untreated chronic hypertension. Monitoring CA may help in establishing individualized management targets in patients with cerebrovascular disease.

Endothelial dysfunction and cerebral small-vessel disease in brains of older people.

Cerebral small vessel disease (SVD) affects deep penetrating arteries in subcortical white matter and deep grey nuclei, and is a frequent finding at autopsy in brains of older people. SVD is seen as fibrotic thickening of deep penetrating arteries (outer diameter <200 µm), with loss of mural cells and sparing of endothelial cells (Hainsworth et al. 2015). SVD is the underlying cause of most lacunar stroke events, silent focal infarcts and subcortical microbleeds, and is associated with diffuse white matter hyperintensities seen on T2-weighted MRI scans. Brain lesions due to SVD are a major cause of vascular contributions to cognitive impairment and dementia (VCID). In semi-quantitative neuropathological studies of human brain tissue we have examined vascular expression of diverse proteins related to endothelial dysfunction and SVD. We found the antithrombotic protein thrombomodulin localised to small artery endothelia, with more extensive expression in older people with SVD, relative to those without (p=0.012). The inflammation markers ICAM1 and IL-6 were rarely evident in endothelia, and appeared unrelated to SVD. The angiogenic receptor VEGFR2 was robustly expressed in vascular myocytes of small arteries of older people and also those with monogenic SVD (CADASIL), suggesting a role for VEGF signalling in small artery remodelling. The extent of VEGFR2 labelling increased with age (p=0.0026) but not with presence of SVD. The extent of vascular basement membrane collagen-IV, types α1-IV and α2-IV (encoded by COL4A1/COL4A2, genetically associated with SVD) in small arteries was negatively correlated with radiological SVD severity (Spearman's rho: -0.427, p=0.005). Neuropathological studies in human brain tissue yield valuable molecular data on SVD pathology. These are hypothesis-generating for testing of interventions in preclinical models, and future clinical trials. Reference: Hainsworth et al. 2015. Endothelial Cells and Human Cerebral Small Vessel Disease. Brain Pathol. 25;44.

COVID-19-related neuropathology and microglial activation in elderly with and without dementia.

The actual role of SARS‐CoV‐2 in brain damage remains controversial due to lack of matched controls. We aim to highlight to what extent is neuropathology determined by SARS‐CoV‐2 or by pre‐existing conditions. Findings of 9 Coronavirus disease 2019 (COVID‐19) cases and 6 matched non‐COVID controls (mean age 79 y/o) were compared. Brains were analyzed through immunohistochemistry to detect SARS‐CoV‐2, lymphocytes, astrocytes, endothelium, and microglia. A semi‐quantitative scoring was applied to grade microglial activation. Thal‐Braak stages and the presence of small vessel disease were determined in all cases. COVID‐19 cases had a relatively short clinical course (0–32 days; mean: 10 days), and did not undergo mechanical ventilation. Five patients with neurocognitive disorder had delirium. All COVID‐19 cases showed non‐SARS‐CoV‐2‐specific changes including hypoxic‐agonal alterations, and a variable degree of neurodegeneration and/or pre‐existent SVD. The neuroinflammatory picture was dominated by ameboid CD68 positive microglia, while only scant lymphocytic presence and very few traces of SARS‐CoV‐2 were detected. Microglial activation in the brainstem was significantly greater in COVID‐19 cases (p = 0.046). Instead, microglial hyperactivation in the frontal cortex and hippocampus was clearly associated to AD pathology (p = 0.001), regardless of the SARS‐CoV‐2 infection. In COVID‐19 cases complicated by delirium (all with neurocognitive disorders), there was a significant enhancement of microglia in the hippocampus (p = 0.048). Although higher in cases with both Alzheimer's pathology and COVID‐19, cortical neuroinflammation is not related to COVID‐19 per se but mostly to pre‐existing neurodegeneration. COVID‐19 brains seem to manifest a boosting of innate immunity with microglial reinforcement, and adaptive immunity suppression with low number of brain lymphocytes probably related to systemic lymphopenia. Thus, no neuropathological evidence of SARS‐CoV‐2‐specific encephalitis is detectable. The microglial hyperactivation in the brainstem, and in the hippocampus of COVID‐19 patients with delirium, appears as a specific topographical phenomenon, and probably represents the neuropathological basis of the “COVID‐19 encephalopathic syndrome” in the elderly.

Abstract P626: Periodontal Disease is Independently Associated With Cerebral Small Vessel Disease

Background: Prior studies have shown the association between periodontal disease, lacunar strokes and cognitive impairment. Using the Atherosclerosis Risk in Communities (ARIC) cohort study we investigated the relationship between periodontal disease (PD) and the development of MRI verified small vessel disease. Methods: Using the ARIC database data we extracted data for 1143 (mean age 77 years, 76% white, 24% African-American and 45% male) participants assessed for PD (N=800) versus periodontal health (N=343). These participants were assessed for small vessel disease on 3T MRI as measured by the log of white matter hyperintensity volume (WMHV). WMHV were derived from a semiautomated segmentation of FLAIR images. Student t-test was then used to evaluate the relationship between small vessel disease as the log of WMHV in subjects with PD or periodontal health. Based on WMHV the patients were grouped into quartiles and the association of PD with WMHV were tested using the group in periodontal health and lowest quartile of WMHV as the reference groups. Multinomial logistic regression was used to compute crude and adjusted odds ratio (OR) for the higher quartiles of WMHV compared to the reference quartile. Results: There was a significant increase in the presence of small vessel disease measured as log WMHV in the PD cohort as compared to periodontal health cohort with p= 0.023 on Independent Sample t-est. Based on WMHV the subjects were grouped into quartiles 0-6.41, &gt;6.41-11.56, &gt;11.56-21.36 and &gt;21.36 cu mm3). PD was associated with only the highest quartile of WMHV on univariate (crude OR 1.77, 95% CI 1.23-2.56) and multivariable (adjusted OR 1.61, 95% CI 1.06-2.44) analyses. The later was adjusted for age, race, gender, hypertension, diabetes and smoking. Conclusion: Based on this prospective cohort there is data to suggest that PD may be associated with cerebral small vessel disease. Maintaining proper dental health may decrease future risk for the associated lacunar strokes and vascular cognitive impairment.

MarkVCID cerebral small vessel consortium: II. Neuroimaging protocols.

MarkVCID cerebral small vessel consortium: II. Neuroimaging protocols.

Small Vessel Disease and Ischemic Stroke Risk During Anticoagulation for Atrial Fibrillation After Cerebral Ischemia.

The causes of recurrent ischemic stroke despite anticoagulation for atrial fibrillation are uncertain but might include small vessel occlusion. We investigated whether magnetic resonance imaging markers of cerebral small vessel disease (SVD) are associated with ischemic stroke risk during follow-up in patients anticoagulated for atrial fibrillation after recent ischemic stroke or transient ischemic attack. We analyzed data from a prospective multicenter inception cohort study of ischemic stroke or transient ischemic attack anticoagulated for atrial fibrillation (CROMIS-2 [Clinical Relevance of Microbleeds in Stroke Study]). We rated markers of SVD on baseline brain magnetic resonance imaging: basal ganglia perivascular spaces (number ≥11); cerebral microbleeds (number ≥1); lacunes (number ≥1); and white matter hyperintensities (periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2). We investigated the associations of SVD presence (defined as presence of ≥1 SVD marker) and severity (composite SVD score) with the risk of ischemic stroke during follow-up using a Cox proportional hazards model adjusted for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65-74, female score. We included 1419 patients (mean age: 75.8 years [SD, 10.4]; 42.1% female). The ischemic stroke rate during follow-up in patients with any SVD was 2.20 per 100-patient years (95% CI, 1.60-3.02), compared with 0.98 per 100 patient-years (95% CI, 0.59-1.62) in those without SVD (P=0.008). After adjusting for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65-74, female score, SVD presence remained significantly associated with ischemic stroke during follow-up (hazard ratio, 1.89 [95% CI, 1.01-3.53]; P=0.046); the risk of recurrent ischemic stroke increased with SVD score (hazard ratio per point increase, 1.33 [95% CI, 1.04-1.70]; P=0.023). In patients anticoagulated for atrial fibrillation after ischemic stroke or transient ischemic attack, magnetic resonance imaging markers of SVD are associated with an increased risk of ischemic stroke during follow-up; improved stroke prevention treatments are required in this population. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02513316.

Cerebral Small Vessel Disease in Standard Pre-operative Imaging Reports Is Independently Associated with Increased Risk of Cardiovascular Death Following Carotid Endarterectomy

Cerebral white matter lesions (WMLs) and lacunar infarcts are surrogates of cerebral small vessel disease (SVD). WML severity as determined by trained radiologists predicts post-operative stroke or death in patients undergoing carotid endarterectomy (CEA). It is unknown whether routine pre-operative brain imaging reports as part of standard clinical practice also predict short and long term risk of stroke and death after CEA. Consecutive patients from the Athero-Express biobank study that underwent CEA for symptomatic high degree stenosis between March 2002 and November 2014 were included. Pre-operative brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) reports were reviewed for reporting of SVD, defined as WMLs or any lacunar infarcts. The primary outcome was defined as any stroke or any cardiovascular death over three year follow up. The secondary outcome was defined as the 30 day peri-operative risk of stroke or cardiovascular death. A total of 1038 patients were included (34% women), of whom 659 (63.5%) had CT images and 379 (36.5%) MRI images available. Of all patients, 697 (67%) had SVD reported by radiologists. Patients with SVD had a higher three year risk of cardiovascular death than those without (6.5% vs. 2.1%, adjusted HR 2.52 [95% CI 1.12-5.67]; p=.026) but no association was observed for the three year risk of stroke (9.0% vs. 6.7%, for patients with SVD vs. those without, adjusted HR 1.24 [95% CI 0.76-2.02]; p=.395). No differences in 30 day peri-operative risk were observed for stroke (4.4% vs. 2.9%, for patients with vs. those without SVD; adjusted HR 1.49 [95% CI 0.73-3.05]; p=.28), and for the combined stroke/cardiovascular death risk (4.4% vs. 3.5%, adjusted HR 1.20 [95% CI 0.61-2.35]; p=.59). Presence of SVD in pre-operative brain imaging reports can serve as a predictor for the three year risk of cardiovascular death in symptomatic patients undergoing CEA but does not predict peri-operative or long term risk of stroke.

Cerebral Small Vessel Diseases and Sleep Related Strokes

Background and Purpose: Sleep related Stroke (SRS) is common and has been associated with cerebral small vessel diseases (SVD) in ischemic strokes (ISs). We tested the hypothesis that SRS is associated with SVD in both ischemic and hemorrhagic stroke. Methods: Prospectively collected data from patients consecutively enrolled after intracerebral hemorrhage (ICH) related to SVD or after IS were analyzed. Symptom onset was recorded as SRS versus awake. Each ICH was grouped according to lobar and deep locations. The IS cohort was etiologically characterized based on the Causative Classification of Stroke system. Frequencies of SRS within and between ICH and IS cohorts as well as its associations (etiology, risk factors) were analyzed. Results: We analyzed 1812 IS (mean age 67.9 years ± 15.9 years, 46.4% female) and 1038 ICH patients (mean age 72.5 years ± 13.0 years, 45.4% female). SRS was significantly more common among SVD-related ICH patients (n = 276, 26.6%) when compared to all IS (n = 363, 20.0%, P < .001) and in both, small artery occlusion (SAO) related IS and lobar ICH within the respective IS and ICH cohorts (16.3% SRS versus 9.1% awake for SAO within all IS, P < .001; and 57.1% SRS versus 47.7% awake for lobar bleeds within all ICH, P = .008). These associations remained significant after controlling for age, sex and risk factors. Conclusions: SRS was associated with SVD. The SAO etiology and cerebral amyloid angiopathy related lobar ICH suggest that the presence of SVD can interact with sleep or arousal related hemodynamic changes to cause ischemic and hemorrhagic stroke.

Clinical Relevance of Cerebral Small Vessel Diseases.

Clinical Relevance of Cerebral Small Vessel Diseases.

Abstract WP88: Relationship Between Small Vessel Ischemic White Matter Disease and Collateral Recruitment in Patients With Acute Embolic Ischemic Stroke

Introduction: White matter hyperintensities (WMH) is the most prominent neuroimaging feature of small vessel disease (SVD). SVD is thought to be a result of arteriolosclerosis, chronic hypoperfusion of white matter, selective oligodendrocyte death and degeneration of myelinated fibers. The risk of ischemic stroke is significantly increased with the presence of WMH. The presence of intracranial collaterals is a strong predictor of salvageable neurological function in acute stroke; however, the factors affecting the ability to recruit collaterals are poorly understood. We wanted to study if the presence and severity of small vessel white matter disease had an adverse effect on cerebral collateral flow in acute embolic large vessel stroke. Methods: We identified a consecutive series of adult subjects with acute embolic large vessel strokes confirmed on CT angiography (CTA) from a 10-year institutional database. Patients without a brain MRI within six months of CTA were excluded. Collateral scores of the affected hemisphere were calculated on CTA using the modified Tan scale (0-4) by two independent trained reviewers and confirmed by a neuroradiologist. The WMH was quantified using the Fazekas scale (0-3) incorporating both deep and periventricular components. Areas of restricted diffusion on brain MRI in the peri-stroke period were eliminated from the assessment of Fazekas score. Spearman’s correlation tests were performed for the association between collateral scores and WMH. Results: A total of 234 patients (mean age 70±14 years, 47% [110/234] women) satisfied the inclusion criteria. The prevalence of periventricular and deep WMH was 83% and 87% respectively. Aging had a significant impact on periventricular WMH (r=0.48, p &lt;0.001) and deep WMH (r=0.47, p &lt;0.001). However, collateral scores exhibited no statistically significant relationship with the presence or severity of periventricular scores (r=0.08, p=0.17) or deep WMH scores (r=0.01, p=0.77). Conclusions: Our results indicate that the presence of SVD does not affect cerebral collateral flow. The vascular niche and risk factors of SVD appear to be distinct from that of intracranial vessels responsible for collateral reperfusion of ischemic territory in acute large vessel embolic stroke.

Brain atrophy and strategic lesion location increases risk of parkinsonism in cerebral small vessel disease

IntroductionIncident parkinsonism in patients with comparable cerebral small vessel disease (SVD) burden is not fully explained by presence of SVD alone. We therefore investigated if severity of SVD, SVD location, incidence of SVD and/or brain atrophy plays a role in this distinct development of parkinsonism. MethodsParticipants were from the RUN DMC study, a prospective cohort of 503 individuals with SVD. Parkinsonism was diagnosed according to the UKPDS brain bank criteria. Fine and Gray method was used to assess the association between SVD and incident parkinsonism. Differences in white matter hyperintensities (WMH) progression and brain atrophy were calculated with a linear mixed effect analysis. ResultsAfter a median follow-up of 8.6 years, 32 of 501 participants developed parkinsonism (6.4%). The highest WMH load was found in the frontal lobe for both groups. Presence of more than one lacune at baseline was higher in the group who developed parkinsonism, especially in the frontal lobe (22% versus 3%, p < 0.001) and basal ganglia (12.5% versus 1%, p-value <0.001). The annual rate of total brain atrophy was significantly higher for those who developed parkinsonism compared to those who did not (8.7 ml [95%CI 7.1–10.3] and 4.9 ml [95%CI 4.5–5.3], respectively). While WMH progression was not different, incidence of lacunes and microbleeds was higher in the group with parkinsonism. ConclusionThe risk of parkinsonism in patients with SVD is especially increased when WMH and lacunes are present in the frontal lobe. A higher brain atrophy rate might further increase this risk.

Poor Subpleural Perfusion Predicts Failure After Balloon Pulmonary Angioplasty for Nonoperable Chronic Thromboembolic Pulmonary Hypertension

Poor subpleural perfusion (PSP) in the capillary phase of pulmonary angiography predicts worse outcomes following pulmonary endarterectomy in operable chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) has emerged as a treatment for nonoperable CTEPH. The goal of the present article was to assess the association between PSP and BPA failure. Subpleural perfusion was classified as poor (defined as subpleural spaces either not perfused or minimally perfused in all segments) or normal. We retrospectively reviewed PSP and hemodynamic variables of 101 consecutive patients who underwent BPA from February 2014 to August 2016. The total cross-sectional area of bronchial arteries was also measured by using CT scanning. Patients were categorized according to hemodynamic results after the last BPA: a failure group (defined as mean pulmonary arterial pressure > 30mmHg and a decrease in pulmonary vascular resistance< 30%[n= 15]) or a success group (n= 86). Although baseline hemodynamic variables were similar between the two groups, PSP was observed in 46.7%of patients in the failure group vs13.9%in the success group (P=.003). Multivariate analysis revealed that PSP was the only predictor of BPA failure (OR, 4.02 [95%CI, 1.17-13.89]; P= .028). Patients with PSP exhibited poorly developed bronchial arteries compared with patients with normal perfusion (7.0 [5.8-9.6] mm2 vs8.7 [6.9-11.3] mm2; P= .032). PSP in the capillary phase, suggesting the presence of small vessel disease with diffuse distal thrombosis, is a predictor of BPA failure. PSP was also associated with less developed bronchial arteries, which suggests a key role of bronchial-pulmonary anastomoses in maintaining the pulmonary capillary bed open downstream of the pulmonary arterial obstruction. PSP affected approximately 15%of patients with nonoperable CTEPH who underwent BPA.