Spatial Relation Between White Matter Hyperintensities and Incident Lacunes of Presumed Vascular Origin: A 14-Year Follow-Up Study.

BACKGROUND: The underlying mechanisms of incident lacunes regarding their spatial distribution remain largely unknown. We investigated the spatial distribution pattern and MRI predictors of incident lacunes in relation to white matter hyperintensity (WMH) over 14 years follow-up in sporadic small vessel disease. METHODS: Five hundred three participants from the ongoing prospective single-center Radboud University Nijmegen Diffusion Tensor and Magnetic resonance Cohort (RUN DMC) were recruited with baseline assessment in 2006 and follow ups in 2011, 2015, and 2020. Three hundred eighty-two participants who underwent at least 2 available brain MRI scans were included. Incident lacunes were systematically identified, and the spatial relationship between incident lacunes located in subcortical white matter and WMH were determined using a visual rating scale. Adjusted multiple logistic regression and linear mixed-effect regression models were used to assess the association between baseline small vessel disease markers, WMH progression, and incident lacunes. Participants with atrial fibrillation were excluded in multivariable analysis. RESULTS: Eighty incident lacunes were identified in 43 patients (mean age 66.5±8.2 years, 37.2% women) during a mean follow-up time of 11.2±3.3 years (incidence rate 10.0/1000 person-year). Sixty percent of incident lacunes were in the white matter, of which 48.9% showed no contact with preexisting WMH. Baseline WMH volume (odds ratio=2.5 [95% CI, 1.6-4.2]) predicted incident lacunes after adjustment for age, sex, and vascular risk factors. WMH progression was associated with incident lacunes independent of age, sex, baseline WMH volume, and vascular risk factors (odds ratio, 3.2 [95% CI, 1.5-6.9]). Baseline WMH volume and progression rate were higher in participants with incident lacunes in contact with preexisting WMH. No difference in vascular risk factors was observed regarding location or relation with preexisting WMH. CONCLUSIONS: The 2 different distribution patterns of lacunes regarding their relation to WMH may suggest distinct underlying mechanisms, one of which may be more closely linked to a similar pathophysiology as that of WMH. The longitudinal relation between WMH and lacunes further supports plausible shared mechanisms between the 2 key markers.

PR interval duration is associated with the presence of white matter hyperintensities: Insights from the epidemiologic LIFE-Adult Study.

BACKGROUND: PR interval prolongation is a preliminary stage of atrial cardiomyopathy which is considered as an intermediate phenotype for atrial fibrillation (AF). AF is a known risk factor for cerebrovascular adverse outcomes including stroke. Cerebral ischemia is one cause of white matter hyperintensities (WMHs), and cognitive dysfunction. AIM: To analyze the relationship between PR interval and WMHs. MATERIALS AND METHODS: We performed a cross-sectional analysis with individuals from the LIFE-Adult-Study (a population-based cohort study of randomly selected individuals from Leipzig, Germany) with available brain MRI and ECG. The Fazekas stages were used to quantify WMHs (0 = none; 1 = punctate foci; 2 = beginning confluence; 3 = large confluent areas). Stages 2-3 were defined as advanced WMHs. The PR interval was measured from resting 12-lead ECG. PR duration >200ms was defined as PR interval prolongation. We used a binary logistic regression for statistical analysis. We examined the relationship between MRI and ECG measures and adjusted them for clinical risk factors. RESULTS: We included 2464 individuals (age 59±15 years, 47% women) into analyses. The median PR interval was 160ms (interquartile range 143-179), and 319 (13%) individuals with advanced WMHs, were significantly older, had more cardiovascular comorbidities and risk factors compared to individuals without WMHs (all p<0.005). On univariable analysis, PR interval duration (OR 1.01, 95%CI 1.01-1.02, p≤0.001) and PR interval ≥160 ms (OR 2.1, 95%CI 1.6-2.7, p≤0.001) were associated with advanced WMHs. In multivariable analysis, while PR interval duration was not associated with WMHs in the whole cohort, individuals with PR ≥160ms had higher risk for WMHs. CONCLUSION: PR interval duration is associated with advanced WMHs beside advanced age, hypertension, and history of stroke. Further research is needed to determine whether changes in PR interval indices are clinically relevant for changes in WMHs.

sTWEAK is a leukoaraiosis biomarker associated with neurovascular angiopathy.

OBJECTIVE: Leukoaraiosis (LA) refers to white matter lesions of undetermined etiology associated with the appearance and worsening of vascular pathologies. The aim is to confirm an increased frequency and intensity of LA in symptomatic patients with neurovascular pathology compared with asymptomatic subjects, and its association with circulating serum levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK). METHODS: An observational study was conducted in which two groups of patients were compared. Group I (N = 242) comprised of asymptomatic subjects with arterial hypertension and/or diabetes or with a history of transient ischemic attacks, and Group II (N = 382) comprised patients with lacunar stroke or deep hemispheric intracerebral hemorrhage (ICH) of hypertensive origin. Serum levels of sTWEAK were analyzed and correlated with prevalence and intensity of LA according to the Fazekas scale. RESULTS: The prevalence of LA was higher in symptomatic (85.1%) versus asymptomatic patients (62.0%). Logistic regression model showed a significant relation of LA with neurovascular pathologies (OR: 2.69, IC 95%: 1.10-6.59, p = 0.003). When stratified according to the Fazekas scale, LA of grade II (OR: 3.53, IC 95%: 1.10-6.59, p = 0.003) and specially grade III (OR: 4.66, 95% CI: 1.09-19.84, p = 0.037) showed correlation with neurovascular pathologies. Increased sTWEAK levels were found in the symptomatic group in all LA grades (p < 0.0001), and associated with 5.06 times more risk of presenting clinical symptoms (OR: 5.06, 95% CI: 2.66-9.75, p < 0.0001). INTERPRETATION: LA showed a higher prevalence in patients with symptomatic lacunar stroke or deep hemispheric ICH. There is an association between sTWEAK levels and LA degree.

Risk factors analysis according to regional distribution of white matter hyperintensities in a stroke cohort.

OBJECTIVES: The spectrum of distribution of white matter hyperintensities (WMH) may reflect different functional, histopathological, and etiological features. We examined the relationships between cerebrovascular risk factors (CVRF) and different patterns of WMH in MRI using a qualitative visual scale in ischemic stroke (IS) patients. METHODS: We assembled clinical data and imaging findings from patients of two independent cohorts with recent IS. MRI scans were evaluated using a modified visual scale from Fazekas, Wahlund, and Van Swieten. WMH distributions were analyzed separately in periventricular (PV-WMH) and deep (D-WMH) white matter, basal ganglia (BG-WMH), and brainstem (B-WMH). Presence of confluence of PV-WMH and D-WMH and anterior-versus-posterior WMH predominance were also evaluated. Statistical analysis was performed with SPSS software. RESULTS: We included 618 patients, with a mean age of 72 years (standard deviation [SD] 11 years). The most frequent WMH pattern was D-WMH (73%). In a multivariable analysis, hypertension was associated with PV-WMH (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.29-2.50, p = 0.001) and BG-WMH (OR 2.13, 95% CI 1.19-3.83, p = 0.012). Diabetes mellitus was significantly related to PV-WMH (OR 1.69, 95% CI 1.24-2.30, p = 0.001), D-WMH (OR 1.46, 95% CI 1.07-1.49, p = 0.017), and confluence patterns of D-WMH and PV-WMH (OR 1.62, 95% CI 1.07-2.47, p = 0.024). Hyperlipidemia was found to be independently related to brainstem distribution (OR 1.70, 95% CI 1.08-2.69, p = 0.022). CONCLUSIONS: Different CVRF profiles were significantly related to specific WMH spatial distribution patterns in a large IS cohort. KEY POINTS: • An observational study of WMH in a large IS cohort was assessed by a modified visual evaluation. • Different CVRF profiles were significantly related to specific WMH spatial distribution patterns. • Distinct WMH anatomical patterns could be related to different pathophysiological mechanisms.

The Clinical Characteristics of Patients with Pre-Existing Leukoaraiosis Compared to Those Without Leukoaraiosis in Acute Ischemic Stroke.

BACKGROUND: Leukoaraiosis (LA) is a finding in the elderly, that might be asymptomatic or can impact their motor and cognitive functions. We studied the presence of LA in the MRI of patients with AIS and its impact on functional outcome at 3 months. METHODS: 500 consecutive patients diagnosed as AIS were enrolled. Medical history included pre-medication by antiplatelets or statins, and vascular risk factors were reported by history and laboratory investigations. Severity of stroke was assessed by NIHSS and stroke outcome was evaluated on discharge and at 3 months by modified Rankin scale (mRS). LA was diagnosed by MRI-FLAIR sequence and delineated from acute infarction by diffusion-weighted image. And accordingly, patients were divided into group A (absent LA) and group B (present LA). RESULTS: 460 patients completed the study, with 53% of patients on antiplatelet therapy and 11.7% on statins prior to stroke. The percentage of patients with LA was significantly more than those without LA. Patients with LA showed a significantly higher age, more frequent and longer duration of diabetes and hypertension, ischemic heart disease, previous stroke/TIA and antiplatelet intake. Microbleeds were more and mRS was worse in LA group. CONCLUSION: The presence of LA in the background MRI of AIS patients is accompanied by the presence of more risk factors, and unfavorable outcome. Pre-medication with antiplatelets did not prevent the incidence of a new stroke especially in LA group. This might necessitate the identification of some medication for secondary prevention in patients with small vessel disease.

Association of White Matter Hyperintensities With HIV Status and Vascular Risk Factors.

OBJECTIVE: To test the hypothesis that brain white matter hyperintensities (WMH) are more common in people living with HIV (PLWH), even in the setting of well-controlled infection, and to identify clinical measures that correlate with these abnormalities. METHODS: Research brain MRI scans, acquired within longitudinal studies evaluating neurocognitive outcomes, were reviewed to determine WMH load using the Fazekas visual rating scale in PLWH with well-controlled infection (antiretroviral therapy for at least 1 year and plasma viral load <200 copies/mL) and in sociodemographically matched controls without HIV (CWOH). The primary outcome measure of this cross-sectional analysis was increased WMH load, determined by total Fazekas score ≥2. Multiple logistic regression analysis was performed to evaluate the effect of HIV serostatus on WMH load and to identify MRI, CSF, and clinical variables that associate with WMH in the PLWH group. RESULTS: The study included 203 PLWH and 58 CWOH who completed a brain MRI scan between April 2014 and March 2019. The multiple logistic regression analysis, with age and history of tobacco use as covariates, showed that the adjusted odds ratio of the PLWH group for increased WMH load is 3.7 (95% confidence interval 1.8-7.5; p = 0.0004). For the PLWH group, increased WMH load was associated with older age, male sex, tobacco use, hypertension, and hepatitis C virus coinfection, and also with the presence of measurable tumor necrosis factor α in CSF. CONCLUSION: Our results suggest that HIV serostatus affects the extent of brain WMH. This effect is mainly associated with aging and modifiable comorbidities.

Investigating the microstructural properties of normal-appearing white matter (NAWM) preceding conversion to white matter hyperintensities (WMHs) in stroke survivors.

Using advanced diffusion MRI, we aimed to assess the microstructural properties of normal-appearing white matter (NAWM) preceding conversion to white matter hyperintensities (WMHs) using 3-tissue diffusion signal compositions in ischemic stroke. Data were obtained from the Cognition and Neocortical Volume After Stroke (CANVAS) study. Diffusion-weighted MR and high-resolution structural brain images were acquired 3- (baseline) and 12-months (follow-up) post-stroke. WMHs were automatically segmented and longitudinal assessment at 12-months was used to retrospectively delineate NAWM voxels at baseline converting to WMHs. NAWM voxels converting to WMHs were further dichotomized into either: "growing" WMHs if NAWM adhered to existing WMH voxels, or "isolated de-novo" WMHs if NAWM was unconnected to WMH voxels identified at baseline. Microstructural properties were assessed using 3-tissue diffusion signal compositions consisting of white matter-like (WM-like: TW), gray matter-like (GM-like: TG), and cerebrospinal fluid-like (CSF-like: TC) signal fractions. Our findings showed that NAWM converting to WMHs already exhibited similar changes in tissue compositions at baseline to WMHs with lower TW and increased TC (fluid-like, i.e. free-water) and TG compared to persistent NAWM. We also found that microstructural properties of persistent NAWM were related to overall WMH burden with greater free-water content in patients with high WMH load. These findings suggest that NAWM preceding conversion to WMHs are accompanied by greater fluid-like properties indicating increased tissue water content. Increased GM-like properties may indicate a more isotropic microstructure of tissue reflecting a degree of hindered diffusion in NAWM regions vulnerable to WMH development. These results support the usefulness of microstructural compositions as a sensitive marker of NAWM vulnerability to WMH pathogenesis.

Impact of leukoaraiosis severity on the association of outcomes of mechanical thrombectomy for acute ischemic stroke: a systematic review and a meta-analysis.

BACKGROUND: Leukoaraiosis (LA) severity is associated with poor outcome after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) caused by large vessel occlusion. This meta-analysis aimed to assess the association of LA severity with AIS-related risk factors and outcomes of MT. METHODS: PubMed, Web of Science, EMBASE, and Cochrane Collaboration Database was searched for studies on MT for AIS with LA. We conducted a random-effects meta-analysis for the prevalence of stroke risk factors and the MT outcome in the absent to moderate LA and severe LA groups. RESULTS: We included seven cohort studies involving 1294 participants (1019 with absent to moderate LA and 275 with severe LA). The absent to moderate LA group had a significantly lower prevalence of coronary artery disease (odds ratio [OR] 0.43; 95% CI 0.29-0.66), atrial fibrillation (OR, 0.26; 95% CI 0.17-0.38), hypertension (OR, 0.39; 95% CI 0.24-0.61), and ischemic stroke (OR, 0.27; 95% CI 0.15-0.50) than the severe LA group. There were no significant between-group differences in symptom onset to recanalization time (364.4 versus 356.2 min, mean difference 19.4; 95% CI - 28.3 to 67.2), final recanalization rate (modified thrombolysis in cerebral infarction score of 2b/3; OR, 0.87; 95% CI 0.55-1.38), and symptomatic intracranial hemorrhage (OR, 0.62; 95% CI 0.34-1.11). The absent to moderate LA group had a higher good functional outcome (modified Rankin Scale score of 0-2 at 90 days; OR, 4.55; 95% CI 3.20-6.47) and a lower mortality rate (179/1019 vs 108/275; OR, 0.28; 95% CI 0.20-0.39). CONCLUSION: There are unique differences in the characteristics of risk factors and clinical outcomes of ischemic stroke across patients with LA of different severity. Patients with severe LA are more likely to be associated with risk factors for cerebrovascular disease and have a poor post-MT outcome.

Association between airflow limitation and leukoaraiosis of the brain.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have several comorbidities. Leukoaraiosis (LA) is an abnormal appearance of brain white matter on neuroimaging, and it has been linked to microangiopathy of the brain. In this study, we explored the association between airflow limitation (AL) and LA volume and localization. METHODS: This observational cross-sectional study included 3,945 subjects who underwent medical check-ups between January 2015 and December 2017. LA was automatically assessed and quantified on brain MRI images using a morphometric program. Spirometry without bronchodilator was performed, and AL was defined as the ratio of forced expiratory volume in 1 s/forced vital capacity <0.70. RESULTS: In the multivariate analysis, AL was an independent predictor of LA volume (t = 3.06, P < 0.01), in addition to age, hypertension, and dyslipidemia. Compared with the propensity-matched subjects without AL, the subjects with AL (n = 157) had significantly higher LA volumes (4.65 cm3 vs. 3.26 cm3, P < 0.05) and frequency of LA in the frontal lobe, but not in the parietal, temporal, and occipital lobes. CONCLUSIONS: Our findings suggest that AL is associated with increased LA volume and with more frequent localization of LA in the frontal lobe.

The presence of leukoaraiosis enhances the association between sTWEAK and hemorrhagic transformation.

OBJECTIVE: To investigate whether elevated serum levels of sTWEAK (soluble tumor necrosis factor-like inducer of apoptosis) might be involved in a higher frequency of symptomatic hemorrhagic transformation (HT) through the presence of leukoaraiosis (LA) in patients with acute ischemic stroke (IS) undergoing reperfusion therapies. METHODS: This is a retrospective observational study. The primary endpoint was to study the sTWEAK-LA-HT relationship by comparing results with biomarkers associated to HT and evaluating functional outcome at 3-months. Clinical factors, neuroimaging variables and biomarkers associated to inflammation, endothelial/atrial dysfunction or blood-brain barrier damage were also investigated. RESULTS: We enrolled 875 patients (mean age 72.3 ± 12.2 years; 46.0% women); 710 individuals underwent intravenous thrombolysis, 87 endovascular therapy and 78 both. HT incidence was 32%; LA presence was 75.4%. Patients with poor functional outcome at 3-months showed higher sTWEAK levels at admission (9844.2 [7460.4-12,542.0] vs. 2717.3 [1489.7-5852.3] pg/mL, P < 0.0001). By means of logistic regression models, PDGF-CC and sTWEAK were associated with mechanisms linked simultaneously to HT and LA. Serum sTWEAK levels at admission ≥6700 pg/mL were associated with an odds ratio of 13 for poor outcome at 3-months (OR: 13.6; CI 95%: 8.2-22.6, P < 0.0001). CONCLUSIONS: Higher sTWEAK levels are independently associated with HT and poor functional outcome in patients with IS undergoing reperfusion therapies through the presence of LA. sTWEAK could become a therapeutic target to reduce HT incidence in patients with IS.

Microvascular Brain Disease Progression and Risk of Stroke: The ARIC Study.

BACKGROUND AND PURPOSE: Data on the significance of combined white matter hyperintensities (WMH)/lacunar brain infarcts, and their progression over time for the prediction of stroke are scarce. We studied associations between the progression in combined measures of microvascular brain disease and risk of stroke in the ARIC study (Atherosclerosis Risk in Communities). METHODS: Prospective analysis of 907 stroke-free ARIC participants who underwent a brain magnetic resonance imaging (MRI) in 1993 to 1995, a second brain MRI in 2004 to 2006, and were subsequently followed for stroke incidence through December 31, 2017 (median [25%-75%] follow-up 12.6 [8.9-13.4] years). A combined measure of microvascular brain disease was defined at each visit and categorized by progression from first to second brain MRI as no progression; mild progression (increase of ≥1 unit in WMH grade or new lacune), and moderate progression (increase of ≥1 unit in WMH grade and new lacune). All definite/probable ischemic or hemorrhagic incident strokes occurring after this second MRI, and through 2017, were included. Associations between microvascular brain disease, progression in the combined measures, and stroke incidence were studied with Cox proportional hazard models, adjusting for age, sex, race, education level, time from first to second MRI, body mass index, smoking, hypertension, diabetes mellitus, and coronary heart disease. RESULTS: At the second brain MRI (mean age 72), the distribution of the combined measure was 37% WMH grade <2 and no lacune; 57% WMH grade ≥2 or lacune; and 6% WMH grade ≥2 and lacune. No progression in the combined measures was observed in 38% of participants, 57% showed mild progression and 5% showed moderate progression. Sixty-four incident strokes occurred during the follow-up period. Compared with no change in the combined measure, moderate progression of microvascular brain disease was significantly associated with higher risk of stroke (adjusted hazard ratio, 3.00 [95% CI, 1.30-6.94]). CONCLUSIONS: Progression of microvascular brain disease, manifesting as both new lacunes and increase in WMHs grade, is related to substantial increase in long-term risk of stroke.

Brain imaging abnormalities and outcome after acute ischaemic stroke: the ENCHANTED trial.

OBJECTIVE: To test the hypothesis that imaging signs of 'brain frailty' and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the alteplase dose arm of ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED). METHODS: Blinded assessors coded baseline images for acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions; and hyperattenuated arteries) and pre-existing changes (atrophy, leucoaraiosis and old ischaemic lesions). Logistic regression models assessed associations between imaging features and death at 7 and 90 days; good recovery (modified Rankin Scale scores 0-2 at 90 days) and sICH. Data are reported with adjusted ORs and 95% CIs. RESULTS: 2916 patients (67±13 years, National Institutes of Health Stroke Scale 8 (5-14)) were included. Visible ischaemic lesions, severe hypoattenuation, large ischaemic lesion, swelling and hyperattenuated arteries were associated with 7-day death (OR (95% CI): 1.52 (1.06 to 2.18); 1.51 (1.01 to 2.18); 2.67 (1.52 to 4.71); 1.49 (1.03 to 2.14) and 2.17 (1.48 to 3.18)) and inversely with good outcome. Severe atrophy was inversely associated with 7-day death (0.52 (0.29 to 0.96)). Atrophy (1.52 (1.08 to 2.15)) and severe leucoaraiosis (1.74 (1.20 to 2.54)) were associated with 90-day death. Hyperattenuated arteries were associated with sICH (1.71 (1.01 to 2.89)). No imaging features modified the effect of alteplase dose. CONCLUSIONS: Non-expert-defined brain imaging signs of brain frailty and acute ischaemia contribute to the prognosis of thrombolysis-treated AIS patients for sICH and mortality. However, these imaging features showed no interaction with alteplase dose.

Cognitive reserve and midlife vascular risk: Cognitive and clinical outcomes.

OBJECTIVE: Examine whether cognitive reserve moderates the association of 1) vascular risk factors and 2) white matter hyperintensity burden with risk of clinical progression and longitudinal cognitive decline. METHODS: BIOCARD Study participants were cognitively normal and primarily middle-aged (M = 57 years) at baseline and have been followed with annual cognitive and clinical assessments (M = 13 years). Baseline cognitive reserve was indexed with a composite score combining education with reading and vocabulary scores. Baseline vascular risk (N = 229) was assessed with a composite risk score reflecting five vascular risk factors. Baseline white matter hyperintensity load (N = 271) was measured with FLAIR magnetic resonance imaging. Cox regression models assessed risk of progression from normal cognition to onset of clinical symptoms of Mild Cognitive Impairment. Longitudinal mixed effects models measured the relationship of these variables to cognitive decline, using a global composite score, and executive function and episodic memory sub-scores. RESULTS: Both vascular risk and white matter hyperintensities were associated with cognitive decline, particularly in executive function. Higher vascular risk, but not white matter hyperintensity burden, was associated with an increased risk of progression to Mild Cognitive Impairment. Higher cognitive reserve was associated with a reduced risk of symptom onset and higher levels of baseline cognition but did not modify the associations between the vascular risk score and white matter hyperintensities with clinical progression or cognitive decline. INTERPRETATION: Although cognitive reserve has protective effects on clinical and cognitive outcomes, it does not mitigate the negative impact of vascular risk and small vessel cerebrovascular disease on these same outcomes.

White matter hyperintensities and risk of levodopa-induced dyskinesia in Parkinson's disease.

OBJECTIVE: To investigate whether the burden of white matter hyperintensities (WMHs) is associated with the risk of developing levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). METHODS: According to the Clinical Research Center for Dementia of South Korea WMH visual rating scale, 336 patients with drug-naïve early stage PD (follow-up >3 years) were divided into two groups of PD with minimal WMHs (PD-WMH-; n = 227) and moderate-to-severe WMHs (PD-WMH+; n = 109). The Cox regression model was used to estimate the hazard ratio for the development of LID in the PD-WMH + group compared with the PD-WMH- group, while adjusting for age at PD onset, sex, striatal dopamine depletion, and PD medication dose. Additionally, we assessed the effects of WMH burden rated by the Scheltens scale and regional WMH distribution on the development of LID. RESULTS: Patients in the PD-WMH + group were older and had more severe parkinsonian motor signs despite comparable striatal dopamine transporter availability than those in the PD-WMH- group. Patients in the PD-WMH + group had a higher risk of developing LID (hazard ratio, 2.66; P < 0.001) than those in the PD-WMH- group after adjustment for other confounding factors. A greater WMH burden was associated with earlier occurrence of LID (hazard ratio, 1.04; P = 0.001), although the effects of WMHs on LID development did not exhibit region-specific patterns. INTERPRETATION: The present study demonstrates that the burden of WMHs is associated with occurrence of LID in patients with PD, suggesting comorbid WMHs as a risk factor for LID.

Associations of Radiographic Cerebral Small Vessel Disease with Acute Intracerebral Hemorrhage Volume, Hematoma Expansion, and Intraventricular Hemorrhage.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the impact of radiographic cerebral small vessel disease (CSVD) on the severity of acute intracerebral hemorrhage (ICH) as measured by: ICH volume, hematoma expansion, and extension of intraventricular hemorrhage (IVH). METHODS: CSVD was determined on baseline computed tomography (CT) scans of patients from the Ethnic and Racial Variations of Intracerebral Hemorrhage study through the extent of leukoaraiosis and cerebral atrophy using visual rating scales. The associations of leukoaraiosis and atrophy with ICH volume, hematoma expansion, IVH presence, and severity of IVH were tested using multivariable regression models. Secondary analyses were stratified by hemorrhage location. Bonferroni correction was applied to correct for multiple testing. RESULTS: A total of 2579 patients (mean age 61.7 years, 59% male) met inclusion criteria. Median ICH volume was 10.5 (Interquartile range [IQR] 4.0-25.3) mL. IVH was detected in 971 patients (38%). Neither leukoaraiosis nor atrophy was associated with hematoma expansion. Increasing grades of leukoaraiosis were associated with increased risk of IVH in a dose-dependent manner, while cerebral atrophy was inversely associated with IVH (both P for trend < 0.001). Increasing grades of global atrophy were dose-dependently associated with lower ICH volumes (ß (95% Confidence Interval [CI]) - 0.30[- 0.46, - 0.14], - 0.33[- 0.49, - 0.17], - 0.40[- 0.60, - 0.20], and - 0.54[- 0.76, - 0.32], for grades 1, 2, 3 and 4 compared to 0; all P < 0.001). The associations of leukoaraiosis with ICH volume were consistent with those of atrophy, albeit not meeting statistical significance. CONCLUSIONS: Leukoaraiosis and cerebral atrophy appear to have opposing associations with ICH severity. Cerebral atrophy correlates with smaller ICH volume and decreased risk and severity of IVH, while leukoaraiosis is associated with increased risk of IVH. Whether these observations reflect overlapping or divergent underlying mechanisms requires further study.

Hyperhomocysteinemia can predict the severity of white matter hyperintensities in elderly lacunar infarction patients.

Background and Purpose: Hyperhomocysteinemia (Hhcy) is a risk factor for stroke. Several studies have demonstrated that Hhcy was more closely linked to small vessel occlusive disease and white matter hyperintensities (WMH) in general and elderly population. Studies on WMH and homocysteine in elderly subjects are rare, and the results were inconsistent. Our study aimed to investigate the relationship between the serum homocysteine (HCY) and the severity of WMH in elderly lacunar stroke patients.Methods: Consecutive elderly (≥60 years old) lacunar infarction patients were recruited in this cross-sectional study. All patients were divided into two groups according to periventricular WMH (PVWMH) and deep WMH (DWMH) Fazekas scores. Patients with a Fazekas score (PVWMH or DWMH) of 0, 1, 2 were in mild-moderate group and 3 were in severe group. Vascular risk factors and clinical features were compared between these two groups. Multiple logistic regression analysis was used to determine the relationship between severity of WMH and vascular risk factors.Results: A total of 587 participants aged 60-95 years were enrolled. Patients with severe PVWMH (n = 178) had higher age (p = 0.030) and higher incidence of stroke history (p<0.001) than those in mild-moderate group. The level of serum HCY was significantly higher in patients with severe PVWMH (p ＝ 0.002). Patients with severe DWMH (n = 142) had higher age (p<0.001) and often had a history of stroke (p<0.001). The level of HCY was higher in patients with severe degree of DWMH, but had no significance (p ＝ 0.153). Multivariable logistic regression analyses showed Hhcy were independently associated with severe PVWMH after adjusted for age and vascular risk factors (p ＝ 0.014).Conclusions: Hhcy was independently associated with severe PVWMH of elderly lacunar stroke patients, but not DWMH.

Impact of periventricular hyperintensities and cystatin C on different cognitive domains in the population of non-demented elderly Chinese.

OBJECTIVES: To investigate the impact of periventricular hyperintensities and serum cystatin C on mild cognitive impairment to provide a basis for the investigation of the pathogenesis. METHOD: 286 patients enrolled the study and underwent an examination in Shanghai Fifth People's Hospital from June 2017 to June 2018. The participants' cognitive function was evaluated by different cognitive domains using of mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), auditory verbal learning test, Huashan version (AVLT-H), digit span test (DST), symbol digit modalities test (SDMT), trail making test (TMT) and verbal fluency test (VFT). We measured the levels of serum cystatin C at the department of clinical laboratory in Shanghai Fifth People's Hospital and each subject took an MRI examination in the Department of Radiology of Shanghai Fifth People's Hospital. Multivariate linear regression analyses were used to assess the relationship of cognitive score and the level of cystatin C and periventricular hyperintensities severity. All statistical analyses were performed using the SPSS system. RESULTS: Among 286 eligible participants, 203 (71.0%) were enrolled to further analysis, including 69 male and 134 female (Mean age 67.93 ±â€¯6.19 years). Significant predictors of severe periventricular hyperintensities (PVH) were older age and hypertension. Significant predictors of severe deep white matter hyperintensities (DWMH) were older age only. PVH severity was independently associated with mild cognitive impairment and that the primary impairment was executive function and processing speed. DWMH had no significant effect on cognitive function. Cystatin C only affected the overall cognitive level, and the relationship with WMH severity was not significant. CONCLUSIONS: We demonstrated that in the chinese non-demented elderly, the severity of PVH was independent and significant associated with mild cognitive impairment and that the primary impairment was executive capacity and processing speed, while cystatin C may be an independent risk factor for overall cognitive impairment.

Subclinical Cerebrovascular Disease: Epidemiology and Treatment.

PURPOSE OF REVIEW: Subclinical cerebrovascular disease (sCVD) is highly prevalent in older adults. The main neuroimaging findings of sCVD include white matter hyperintensities and silent brain infarcts on T2-weighted MRI and cerebral microbleeds on gradient echo or susceptibility-weighted MRI. In this paper, we will review the epidemiology of sCVD, the current evidence for best medical management, and future directions for sCVD research. RECENT FINDINGS: Numerous epidemiologic studies show that sCVD, in particular WMH, is an important risk factor for the development of dementia, stroke, worse outcomes after stroke, gait instability, late-life depression, and death. Effective treatment of sCVD could have major consequences for the brain health of a substantial portion of older Americans. Despite the link between sCVD and many vascular risk factors, such as hypertension or hyperlipidemia, the optimal medical treatment of sCVD remains uncertain. Given the clinical equipoise about the risk versus benefit of aggressive medical management for sCVD, clinical trials to examine pragmatic, evidence-based approaches to management of sCVD are needed. Such a trial could provide much needed guidance on how to manage a common clinical scenario facing internists and neurologists in practice.

Prevalence of White Matter Hyperintensity in Young Clinical Patients.

OBJECTIVE. The purpose of this study was to investigate the prevalence of white matter hyperintensity (WMH) without specific causes in young clinical outpatients. MATERIALS AND METHODS. A total of 1249 young clinical outpatients who underwent an unenhanced head MRI examination between January 1, 2016, and December 31, 2016, were included in the study. The chi-square test was used to analyze differences in the prevalence and characteristics of WMH by sex, age, and history of cardiovascular disease (CVD). The prevalence of WMH among clinical patients with neurologic symptoms was also compared with that among participants without neurologic symptoms. Logistic regression was used to identify the patient characteristics that were the best predictors of WMH. RESULTS. The overall prevalence of WMH was 25.94% (324/1249). Most patients with WMH (85.49% [277/324]) had mild WMH, mainly in frontal and parietal subcortical white matter. There was no significant difference in the prevalence of WMH by sex (p > 0.05), but the prevalence of WMH was higher among older patients (p < 0.001) and patients with a history of CVD (p < 0.001). Compared with participants without neurologic symptoms, clinical patients with dizziness (p = 0.029) and light-headedness (p = 0.001) were more likely to have WMH, which was attributed to older age and CVD. Logistic regression analysis showed that age and CVD were the best predictors of WMH. CONCLUSION. WMH is frequently found in young clinical patients. Most WMH is the mild type and mainly located in frontal and parietal subcortical white matter. Older age and CVD are risk factors for WMH.

Association between excessive supraventricular ectopy and subclinical cerebrovascular disease: a population-based study.

BACKGROUND AND PURPOSE: The association between an increased supraventricular ectopic beat (SVEB) and subclinical cerebrovascular disease remains unclear. Given the emerging concept that an increased SVEB is a marker of atrial cardiomyopathy or atherosclerosis burden, we sought to determine whether excessive supraventricular ectopic activity (ESVEA) is associated with a higher burden of subclinical cerebrovascular disease in the middle-aged to older cohort with neither apparent stroke nor atrial fibrillation. METHODS: We conducted a cross-sectional population-based study of 462 men (mean age, 68.1 years) who underwent 24-h Holter electrocardiography and brain magnetic resonance imaging. ESVEA was defined as the presence of >10 SVEBs/h. Subclinical cerebrovascular diseases were defined as silent brain infarct (SBI), white matter hyperintensity (WMH) and intracranial atherosclerotic stenosis (ICAS). The association of ESVEA with the presence of subclinical cerebrovascular diseases was adjusted for potential confounding covariates. RESULTS: A total of 88 (19.0%) participants had ESVEA and 81 (17.5%), 91 (19.7%) and 109 (23.6%) had SBI, WMH and ICAS, respectively. In multivariable-adjusted Poisson regression with robust error variance, ESVEA was associated with the presence of WMH (relative risk, 1.58; 95% confidence interval, 1.06-2.36) and ICAS (relative risk, 1.49; 95% confidence interval, 1.02-2.18), but not with that of SBI (relative risk, 1.32; 95% confidence interval, 0.86-2.01). These associations were consistent when the graded distributions of subclinical cerebrovascular diseases were applied as outcomes in ordinal logistic regression. CONCLUSIONS: The ESVEA was independently associated with higher burdens of WMH and ICAS. This suggests that increased SVEBs might improve risk stratification of individuals at high risk of subclinical cerebrovascular disease and consequently apparent ischaemic stroke.