Enlarged Perivascular Spaces In Centrum Semiovale Research Articles

Comparison of Enlarged Perivascular Spaces in Early-Onset and Late-Onset Alzheimer Disease-related Cognitive Impairment: A Single Clinic-based Study in South Korea.

We examined whether there were differences in the presence of centrum semiovale-enlarged perivascular spaces (CSO-ePVS) and basal ganglia-ePVS (BG-ePVS) among patients with Alzheimer disease-related cognitive impairment (ADCI) based on their age of onset. Out of a total of 239 patients with cognitive impairment, 155 with positive amyloid-PET results were included. Among these, 43 had early-onset ADCI (EOADCI) and 112 had late-onset ADCI (LOADCI). Patients with LOADCI exhibited a higher prevalence of hypertension, lacunes, white matter hyperintensities, and BG-ePVS than those with EOADCI. BG-ePVS showed a significant correlation with age at the onset and the number of lacunes, whereas CSO-ePVS did not exhibit any association. The higher prevalence of BG-ePVS in patients with LOADCI might be attributable to vascular risk factors (hypertension) and cerebral small vessel disease (CSVD). These findings support the hypothesis that BG-ePVS is associated with CSVD and vascular risk factors, whereas CSO-ePVS is associated with cerebral amyloid angiopathy.

MRI-visible enlarged perivascular spaces in basal ganglia rather than centrum semiovale was associated with aneurysmal subarachnoid hemorrhage.

The subarachnoid space is continuous with the perivascular compartment in the central nervous system. However, whether the topography and severity of enlarged perivascular spaces (EPVS) correlates with spontaneous subarachnoid hemorrhage (SAH) remains unknown. Based on the underlying arteriopathy distributions, we hypothesized that EPVS in basal ganglia (BG-EPVS) are more closely associated with aneurysmal subarachnoid hemorrhage (aSAH) than other SAH without aneurysm. Magnetic resonance imaging (MRI) scans of 271 consecutive SAH survivors with and without aneurysm were analyzed for EPVS and other markers of imaging data. In the subgroup analysis, we compared the clinical characteristics and EPVS of SAH participants with and without pre-existing known risk factors (hypertension, diabetes, and smoking history) using multivariable logistic regression. Patients with aSAH (n = 195) had a higher severity of BG-EPVS and centrum semiovale EPVS (CSO-EPVS) than those without aneurysm (n = 76). Importantly, BG-EPVS predominance pattern (BG-EPVS>CSO-EPVS) only existed in aSAH survivors rather than other SAH without aneurysm. In the subgroup analysis, interestingly, we also found that a high degree of BG-EPVS showed an independent relationship with aSAH in patients without pre-existing risk factors (e.g., hypertension). In this cohort study, BG-EPVS predominance pattern was associated with aSAH patients compared with those without aneurysm. Moreover, BG-EPVS still showed a strong association with aSAH survivors without pre-existing vascular risk factors. Our present study suggested the BG-EPVS as a potential MRI-visible characteristic would shed light on the pathogenesis of glymphatic function at the skull base for aSAH.

Association between enlarged perivascular spaces and cerebrospinal fluid aquaporin-4 and tau levels: report from a memory clinic.

Perivascular spaces (PVS) are fluid-filled compartments that dilate in response to many different conditions. A high burden of enlarged PVS (EPVS) in the centrum semiovale (CSO) has been linked to neurodegeneration. Moreover, an increase in cerebrospinal fluid (CSF) levels of aquaporin-4 (AQP4), a water channel expressed on PVS-bounding astrocytes, has been described in patients with neurodegenerative dementia. Our aim was to investigate the relationship between neurodegenerative diseases and two putative glymphatic system biomarkers: AQP4 and EPVS. We included 70 individuals, 54 patients with neurodegenerative diseases and 16 subjects with non-degenerative conditions. EPVS were visually quantified on MRI-scans applying Paradise's scale. All subjects underwent lumbar puncture for the measurement of AQP4 levels in the cerebrospinal fluid (CSF). CSF levels of amyloid-β-1-42, phosphorylated and total tau (tTau) were also measured. Linear regression analyses were adjusted for age, sex, education and disease duration, after excluding outliers. Cerebrospinal fluid (CSF)-AQP4 levels were independent predictors of total (β = 0.28, standard error [SE] = 0.08, p = 0.001), basal ganglia (β = 0.20, SE = 0.08, p = 0.009) and centrum semiovale EPVS (β = 0.37, SE = 0.12, p = 0.003). tTau levels predicted CSO-EPVS (β = 0.30, SE = 0.15, p = 0.046). Moreover, increased levels of AQP4 were strongly associated with higher levels of tTau in the CSF (β = 0.35, SE = 0.13, p = 0.008). We provide evidence that CSO-EPVS and CSF-AQP4 might be clinically meaningful biomarkers of glymphatic dysfunction and associated neurodegeneration.

Mechanistic Implications of Cortical Superficial Siderosis in Patients With Mixed Location Intracerebral Hemorrhage and Cerebral Microbleeds.

Hypertensive cerebral small vessel disease (HTN-cSVD) is the predominant microangiopathy in patients with a combination of lobar and deep cerebral microbleeds (CMBs) and intracerebral hemorrhage (mixed ICH). We tested the hypothesis that cerebral amyloid angiopathy (CAA) is also a contributing microangiopathy in patients with mixed ICH with cortical superficial siderosis (cSS), a marker strongly associated with CAA. Brain MRIs from a prospective database of consecutive patients with nontraumatic ICH admitted to a referral center were reviewed for the presence of CMBs, cSS, and nonhemorrhagic CAA markers (lobar lacunes, centrum semiovale enlarged perivascular spaces [CSO-EPVS], and multispot white matter hyperintensity [WMH] pattern). The frequencies of CAA markers and left ventricular hypertrophy (LVH), a marker for hypertensive end-organ damage, were compared between patients with mixed ICH with cSS (mixed ICH/cSS[+]) and without cSS (mixed ICH/cSS[-]) in univariate and multivariable models. Of 1,791 patients with ICH, 40 had mixed ICH/cSS(+) and 256 had mixed ICH/cSS(-). LVH was less common in patients with mixed ICH/cSS(+) compared with those with mixed ICH/cSS(-) (34% vs 59%, p = 0.01). The frequencies of CAA imaging markers, namely multispot pattern (18% vs 4%, p < 0.01) and severe CSO-EPVS (33% vs 11%, p < 0.01), were higher in patients with mixed ICH/cSS(+) compared with those with mixed ICH/cSS(-). In a logistic regression model, older age (adjusted odds ratio [aOR] 1.04 per year, 95% CI 1.00-1.07, p = 0.04), lack of LVH (aOR 0.41, 95% CI 0.19-0.89, p = 0.02), multispot WMH pattern (aOR 5.25, 95% CI 1.63-16.94, p = 0.01), and severe CSO-EPVS (aOR 4.24, 95% CI 1.78-10.13, p < 0.01) were independently associated with mixed ICH/cSS(+) after further adjustment for hypertension and coronary artery disease. Among ICH survivors, the adjusted hazard ratio of ICH recurrence in patients with mixed ICH/cSS(+) was 4.65 (95% CI 1.38-11.38, p < 0.01) compared with that in patients with mixed ICH/cSS(-). The underlying microangiopathy of mixed ICH/cSS(+) likely includes both HTN-cSVD and CAA, whereas mixed ICH/cSS(-) is likely driven by HTN-cSVD. These imaging-based classifications can be important to stratify ICH risk but warrant confirmation in studies incorporating advanced imaging/pathology.

Enlarged perivascular spaces in patients with migraine: a case-control study based on 3T MRI.

To explore whether MRI-visible enlarged perivascular spaces (EPVS) are associated with migraine and may serve as a predictor of migraine. Then further explore its correlation with migraine chronification. A total of 231 participants (healthy control [HC] = 57, episodic migraine [EM] = 59, chronic migraine [CM] = 115) were included in this case-control study. A 3T MRI device and the validated visual rating scale were used to assess the grades of EPVS in centrum semiovale (CSO), midbrain (MB), and basal ganglia (BG). Comparisons between the two groups were made using the chi-square or Fisher's exact tests to initially determine whether high-grade EPVS were associated with migraine and migraine chronification. A multivariate logistic regression model was constructed to further investigate the role of high-grade EPVS in migraine. The prevalence of high-grade EPVS in CSO and MB were significantly higher in patients with migraine than in HCs (CSO: 64.94% vs. 42.11%, P = 0.002; MB: 55.75% vs. 29.82%, P = 0.001). Subgroup analysis showed no statistical difference between patients with EM and CM (CSO: 69.94% vs. 62.61%, P = 0.368; MB: 50.85% vs. 58.26%, P = 0.351). Individuals with high-grade EPVS in CSO (odds ratio [OR]: 2.324; 95% confidence interval [CI]: 1.136-4.754; P = 0.021) and MB (OR: 3.261; 95% CI: 1.534-6.935; P = 0.002) were more likely to suffer from migraine. This case-control study showed that high-grade EPVS in CSO and MB in clinical practice with the underlying mechanism of dysfunction of the glymphatic system could be a predictor of migraine, but no significant correlation had been found with migraine chronification.

Influence of Cortical Superficial Siderosis in Patients with Mixed Location Cerebral Microbleeds and Intracerebral Hemorrhage (S36.006)

Influence of Cortical Superficial Siderosis in Patients with Mixed Location Cerebral Microbleeds and Intracerebral Hemorrhage (S36.006)

Vascular risk factors, cerebral collateral efficiency and burden of small vessel disease in anterior circulation large vessel occlusion stroke (P11-5.025)

<h3>Objective:</h3> To determine the association between cerebral collateral circulation status and cerebral small vessel disease (CSVD) burden. <h3>Background:</h3> Subclinical ischemia is thought to play a central role in CSVD pathogenesis. In patients with large vessel occlusion, good collaterals on initial presentation are associated with improved outcomes. The relationship between an increased burden of CSVD and collateral network has not been explored in the setting of thrombectomy. <h3>Design/Methods:</h3> This was a retrospective single-center cohort of consecutive patients with anterior circulation large vessel occlusions with available brain MRI and CT-Angiogram. We identified the burden of individual CSVD markers[white matter hyperintensities (WMH), cerebral microbleeds(CMB), lacunes, and enlarged perivascular spaces (EPVS)] and computed the global CSVD burden on MRI obtained in the acute stroke. We used the Tan Collateral score (CS) in CT-Angiogram to grade collaterals (0–3; 0=absent supply, 3=100% collateral supply). We performed univariable and multivariable adjusted analyses to explore the association between collaterals and CSVD. <h3>Results:</h3> 237 patients (66.1±16.8 years), 123(52%) female were included. Mean CS was 2(IQR 1–3). WMH (89%), basal ganglia EPVS (77%) and centrum semiovale EPVS (77%) were the most prevalent markers. Older age(beta=0.15, p&lt;0.0001) had the most potent association with individual CSVD markers and higher global CSVD burden. Older age(beta=−0.01, p=0.002) was associated with lower CS. Although a trend was detected between lower CS score and higher WMH burden, it did not reach statistical significance after adjusting for confounders (beta=−0.21, p=0.15). <h3>Conclusions:</h3> In this cohort of large vessel occlusion patients, we found that older age is associated with higher individual CSVD marker and global CSVD burden and poor collateral status. We did not find an overt association between CS and WMH or global CSVD burden. <b>Disclosure:</b> Dr. McMillan has nothing to disclose. Ms. Carvalho has nothing to disclose. Sarah Marchina has nothing to disclose. Dr. Cole has nothing to disclose. Dr. Selim has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedRhythms Inc.. Dr. Lioutas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Qmetis. Dr. Lioutas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association.

Abstract WP118: Mechanistic Implications Of Cortical Superficial Siderosis In Patients With Mixed Location Intracerebral Hemorrhage And Cerebral Microbleeds

Introduction: Hypertensive cerebral small vessel disease (HTN-cSVD) is the predominant microangiopathy in patients with a combination of lobar and deep cerebral microbleeds (CMBs) and intracerebral hemorrhage (mixed ICH/CMB). We tested the hypothesis that cerebral amyloid angiopathy (CAA) is also a contributing microangiopathy in mixed ICH/CMB patients with cortical superficial siderosis (cSS), a marker that is strongly associated with CAA. Methods: Brain MRIs from a prospective database of consecutive non-traumatic ICH patients admitted to a single referral center (2003 to 2019) were reviewed for the presence of CMBs, cSS, and non-hemorrhagic CAA markers (lobar lacunes, centrum semiovale enlarged perivascular spaces (CSO-EPVS), and multispot pattern of leukoaraiosis). The frequency of CAA markers and left ventricular hypertrophy (LVH), a marker for hypertensive end-organ damage, were compared between mixed ICH/CMB patients with cSS (mixed +cSS ) and without cSS (mixed -cSS ) in univariate and multivariate models. Results: Of the 1824 ICH patients, 40 had mixed +cSS and 256 had mixed -cSS . LVH was less common in patients with mixed +cSS compared to those with mixed -cSS (34% vs. 59%, p = 0.01). The frequency of multispot pattern (18% vs. 4%, p &lt; 0.01) and severe CSO-EPVS (33% vs. 11%, p &lt; 0.01) were higher in patients with mixed +cSS compared to mixed -cSS , whereas lobar lacune frequency was similar (23% vs. 20%, p = 0.67). In a logistic regression model, older age (aOR 1.04 per year, 95% CI [1.01-1.08], p = 0.01), presence of multispot pattern (aOR 5.82, 95% CI [1.82-18.60], p &lt; 0.03), severe CSO-EPVS (aOR 4.08, 95% CI [1.73-9.61], p &lt; 0.01), and LVH (aOR 0.43, 95% CI [0.20-0.94], p = 0.03) were independently associated with mixed +cSS after further adjustment for sex and hypertension (Table). Conclusions: CAA and HTN-cSVD appear to confer injury in patients with mixed ICH/CMB and cSS, a finding that warrants confirmation in studies incorporating advanced imaging/pathology.

Cerebral Small Vessel Diseases and Outcomes for Acute Ischemic Stroke Patients after Endovascular Therapy

The correlation between cerebral small vessel disease (CSVD) and the outcomes of acute ischemic stroke (AIS) patients after endovascular therapy (EVT) remains elusive. We aimed to investigate the effect of combined white matter hyperintensities (WMH) and enlarged perivascular spaces (EPVS) as detected in magnetic resonance imaging (MRI) at baseline on clinical outcomes in patients with AIS who underwent EVT. AIS patients that experienced EVT were retrospectively analyzed in this single-center study. Using MRIs taken prior to EVT, we rated WMH and EPVS as the burden of CSVD and dichotomized the population into two groups: absent-to-moderate and severe. Neurological outcome was assessed at day 90 with a modified Rankin Scale (mRS). Symptomatic intracerebral hemorrhage (sICH), early neurological deterioration (END), malignant cerebral edema (MCE), and hospital death were secondary outcomes. Of the 100 patients (64.0% male; mean age 63.71 ± 11.79 years), periventricular WMHs (28%), deep WMHs (41%), EPVS in basal ganglia (53%), and EPVS in centrum semiovale (73%) were observed. In addition, 69% had an absent-to-moderate total CSVD burden and 31.0% had a severe burden. The severe CSVD was not substantially linked to either the primary or secondary outcomes. Patients with AIS who underwent EVT had an elevated risk (OR: 7.89, 95% CI: 1.0, 62.53) of END if they also had EPVS. When considering WMH and EPVS together as a CSVD burden, there seemed to be no correlation between severe CSVD burden and sICH, END, or MCE following EVT for AIS patients. Further studies are warranted to clarify the relationship between CSVD burden and the occurrence, progression, and prognosis of AIS.

Clinical Relevance of Cerebral Small Vessel Diseases.

Clinical Relevance of Cerebral Small Vessel Diseases.

Total small vessel disease burden and brain network efficiency in cerebral amyloid angiopathy

BackgroundCerebral amyloid angiopathy (CAA) is associated with hemorrhagic and nonhemorrhagic markers small vessel disease (SVD). A composite score to quantify the total burden of SVD on MRI specifically for CAA patients was recently developed. Brain network alterations related to individual MRI markers of SVD in CAA were demonstrated. ObjectivesConsidering diffusion based network measures sensitive to detect different relevant SVD-related brain injury, we investigated if increased overall SVD injury on MRI corresponds to worse global brain connectivity in CAA. MethodsSeventy-three patients (79.5% male, mean age 70.58±8.22years) with a diagnosis CAA were considered. SVD markers in total MRI SVD score included: lobar cerebral microbleeds, cortical superficial siderosis (cSS), white matter hyperintensities (WMH) and centrum semiovale-enlarged perivascular spaces. Diffusion imaging based network reconstruction was made. The associations between total MRI SVD score and global network efficiency (GNE) were analyzed. ResultsA modest significant inverse correlation between total MRI SVD score and GNE existed (p=0.013; R2=0.07). GNE was related with the presence of cSS and moderate-severe WMHs. ConclusionsAn increased burden of SVD neuroimaging markers corresponds to more reductions in global brain connectivity, implying a possible cumulative effect of overall SVD markers on disrupted physiology. GNE was related with some components of the score, specifically cSS and moderate-severe WMHs.

Higher ambulatory systolic blood pressure independently associated with enlarged perivascular spaces in basal ganglia

Backgrounds: Enlarged perivascular spaces (EPVS) have been identified as a marker of cerebral small vessel diseases (CSVD). Ambulatory blood pressure (ABP) is the strongest predictor of hypertension-related brain damage. However, the relationship between ABP levels and EPVS is unclear.Objectives: This study aimed to investigate the association between ABP levels and EPVS by 24-hour ambulatory blood pressure monitoring (ABPM).Methods: We prospectively recruited inpatients for physical examinations in our hospital from May 2013 to Jun 2016. 24-hour ABPM data and cranial magnetic resonance imaging information were collected. EPVS in basal ganglia (BG) and centrum semiovale (CSO) were identified and classified into three categories by the severity. White matter hyperintensities were scored by Fazekas scale. Spearman correlation analysis and multiple logistic regression analysis were used to determine the relationship between ABP levels and EPVS.Results: A total of 573 subjects were enrolled in this study. 24-hour, day and night systolic blood pressure (SBP) levels were positively related to higher numbers of EPVS in BG (24-hour SBP: r = 0.23, p < 0.01; day SBP: r = 0.25, p < 0.01; night SBP: r = 0.30, p < 0.01). The association was unchanged after controlling for confounders by multiple logistic regression analysis. 24-hour and day diastolic blood pressure (DBP) levels increased with an increasing degree of EPVS in CSO (p = 0.04 and 0.049, respectively). But the association disappeared after adjusting for confounders. Spearman correlation analysis indicated that ABP levels were not associated with higher numbers of EPVS in CSO (p > 0.05). DBP levels were not independently associated with the severity of EPVS in BG and CSO.Conclusion: Higher SBP levels were independently associated with EPVS in BG, but not in CSO, which supported EPVS in BG to be a marker of CSVD. Pathogenesis of EPVS in BG and CSO might be different.

Abstract TP324: Macrobleeds and Microbleeds: A Vascular Risk Factor Microangiopathy

Background: The predominant type of cerebral small vessel disease (SVD) and clinical outcomes of patients who present with a combination of lobar and deep intracerebral hemorrhage (ICH)/microbleed (MB) locations (Mixed-ICH, see figure) is unknown. Methods: Out of 391 consecutive ICH, 75 (19%) had Mixed-ICH, and their demographics, clinical/laboratory features, and SVD neuroimaging markers were compared to 191 probable Cerebral Amyloid Angiopathy (CAA-ICH) and 125 strictly deep-MB and ICH (Deep-ICH) patients. ICH-recurrence on follow up was also analyzed. Results: Mixed-ICH patients had a higher prevalence of hypertension, diabetes, left ventricular hypertrophy rates, higher creatinine values, as well as more prevalent lacunes and basal ganglia (BG) enlarged perivascular spaces (EPVS) than CAA-ICH (all p&lt;0.05). When compared to Deep-ICH, Mixed-ICH patients were older, had higher WMH volumes and MB count, and more prevalent lacunes and centrum semiovale EPVS (all p&lt;0.05). In multivariable models, Mixed-ICH diagnosis was associated with higher creatinine, more lacunes and BG EPVS, than CAA-ICH (all p&lt;0.05). When compared to Deep-ICH, Mixed-ICH patients were older and had more lacunes and MBs in multivariable models (all p&lt;0.05). Annual risk of ICH-recurrence was 5.1% for Mixed-ICH, higher compared to Strictly Deep-ICH but lower than CAA-ICH (1.6% and 10.4%, respectively). Conclusions: Mixed-ICH, commonly seen when MRI obtained during etiologic workup, appears to be mostly driven by vascular risk factors similar to Strictly Deep-ICH, but demonstrates more severe parenchymal damage and higher ICH-recurrence risk.

Brain Atrophy Correlates with Severe Enlarged Perivascular Spaces in Basal Ganglia among Lacunar Stroke Patients.

BackgroundEnlarged perivascular spaces (EPVS) correlate with cognitive impairment and incident dementia. However, etiologies for severe basal ganglia EPVS (BG-EPVS) are still unclear. Our aim was to investigate the independent risk factors for severe BG-EPVS in patients with acute lacunar stroke.MethodsWe prospectively identified patients with lacunar stroke (diameter on DWI ≤ 20mm) from Jan 2011 to May 2015. Patients with severe BG-EPVS were identified on T2 weighted MRI. Age (± 1 year) and sex matched controls were also recruited in the same population (two controls for one case). Vascular risk factors, clinical data, EPVS in centrum semiovale (rated 0 to 4), white matter hyperintensities (WMH) (by Fazekas scale), brain atrophy (rated 0 to 6) were compared between two groups. Logistic regression was performed to determine independent risk factors for severe BG-EPVS.ResultsDuring study period, 89 patients with severe BG-EPVS and 178 matched controls were included. Vascular risk factors did not differ between two groups. Patients with severe BG-EPVS had lower level of HbA1c and diastolic BP at admission, but presented with larger infarct size, more severe WMH (including total WMH, periventricular WMH and deep WMH) and brain atrophy. In logistic regression, brain atrophy (OR = 1.40; 95%CI 1.13, 1.73) and deep WMH (OR = 1.88; 95%CI 1.24, 2.83) were independent risk factors for severe BG-EPVS.ConclusionsBrain atrophy and deep WMH are independent risk factors for severe BG-EPVS, supporting the hypothesis that brain atrophy may be associated with the development of EPVS in basal ganglia.

Enlarged Perivascular Spaces and Cerebral Small Vessel Disease

Background and aimsEnlarged perivascular spaces (also known as Virchow–Robin spaces) on T2-weighted brain magnetic resonance imaging are common, but their etiology, and specificity to small vessel as opposed to general cerebrovascular disease or ageing, is unclear. We tested the association between enlarged perivascular spaces and ischemic stroke subtype, other markers of small vessel disease, and common vascular risk factors.MethodsWe prospectively recruited patients with acute stroke, diagnosed and subtyped by a stroke physician using clinical features and brain magnetic resonance imaging. A neuroradiologist rated basal ganglia and centrum semiovale enlarged perivascular spaces on a five-point scale, white matter lesions, recent and old infarcts, and cerebral atrophy. We assessed associations between basal ganglia-, centrum semiovale- and total (combined basal ganglia and centrum semiovale) enlarged perivascular spaces, stroke subtype, white matter lesions, atrophy, and vascular risk factors.ResultsAmong 298 patients (mean age 68 years), after adjusting for vascular risk factors and white matter lesions, basal ganglia–enlarged perivascular spaces were associated with increasing age (P = 0·001), centrum semiovale–enlarged perivascular spaces (P < 0·001), cerebral atrophy (P = 0·03), and lacunar stroke subtype (P = 0·04). Centrum semiovale–enlarged perivascular spaces were associated mainly with basal ganglia–enlarged perivascular spaces. Total enlarged perivascular spaces were associated with increasing age (P = 0·01), deep white matter lesions (P = 0·005), and previous stroke (P = 0·006).ConclusionsEnlarged perivascular spaces are associated with age, lacunar stroke subtype and white matter lesions and should be considered as another magnetic resonance imaging marker of cerebral small vessel disease. Further evaluation of enlarged perivascular spaces in studies of ageing, stroke, and dementia is needed to determine their pathophysiological importance.