Small ischemic lesions accompanying intracerebral hemorrhage: The underlying influence of old lacunes and polyunsaturated fatty acids.

BACKGROUND AND AIMS: Small ischemic lesions (SILs) accompanying intracerebral hemorrhage (ICH) might be induced by small-vessel vulnerability and hypercoagulation. Some polyunsaturated fatty acids (PUFAs) have been associated with hypercoagulation in cardiovascular diseases. Our aim here is to determine how pre-existing small-vessel disease (SVD) and PUFAs may affect SILs. METHODS AND RESULTS: We screened consecutive ICH patients (October 2012-December 2021) meeting two inclusion criteria: (1) the patients were hospitalized for acute ICH and were undergoing magnetic resonance imaging and (2) the patients' PUFA measurements were available. After excluding patients with isolated intraventricular hemorrhage, we evaluated whether three SVD markers (white matter hyperintensities, old lacunes, cerebral microbleeds) and PUFAs might be associated with the development of SILs. We selected 319 participants from 377 screened consecutive ICH patients (median age = 64, males = 207 [65 %]). Of the 319 patients, 45 patients (14 %) developed SILs. In a multivariable logistic regression analysis, the factors associated with SILs were old lacunes (OR 3.255, 95 % CI 1.101-9.622, p = 0.033) and DHA/AA ratio (OR 0.180, 95 % CI 0.046-0.704, p = 0.013). Furthermore, in our multivariable analysis using DHA/AA ratio tertiles with and without SILs, we observed a linear trend between SILs and the Higher Tertile of the DHA/AA ratio (DHA/AA ratio Mid-Tertile: OR 1.330, 95%CI 0.557-3.177, p = 0.521, and DHA/AA ratio Lower Tertile: OR 2.632, 95%CI 1.124-6.162, p = 0.026). CONCLUSION: The presence of old lacunes and lower DHA/AA ratios might be associated with SILs accompanying ICH.

A Scoping Review on Biomarkers of Endothelial Dysfunction in Small Vessel Disease: Molecular Insights from Human Studies.

Small vessel disease (SVD) is a highly prevalent disorder of the brain's microvessels and a common cause of dementia as well as ischaemic and haemorrhagic strokes. Though much about the underlying pathophysiology of SVD remains poorly understood, a wealth of recently published evidence strongly suggests a key role of microvessel endothelial dysfunction and a compromised blood-brain barrier (BBB) in the development and progression of the disease. Understanding the causes and downstream consequences associated with endothelial dysfunction in this pathological context could aid in the development of effective diagnostic and prognostic tools and provide promising avenues for potential therapeutic interventions. In this scoping review, we aim to summarise the findings from clinical studies examining the role of the molecular mechanisms underlying endothelial dysfunction in SVD, focussing on biochemical markers of endothelial dysfunction detectable in biofluids, including cell adhesion molecules, BBB transporters, cytokines/chemokines, inflammatory markers, coagulation factors, growth factors, and markers involved in the nitric oxide cascade.

Lacune and Large Perivascular Space: Two Kinds of Cavities Are of Different Risk Factors and Stroke Risk.

BACKGROUND AND PURPOSE: To compare the risk factors and risk of stroke between lacune and large perivascular spaces (PVSs) in a community-based sample. METHODS: Large PVSs were assessed using 3.0T MRI in a population-based cohort consisting of 1,204 participants. The relationship between cardiovascular risk factors, neuroimaging changes, and incidental stroke risk and the presence of lacune or large PVSs was assessed with univariate and multivariable ordinal logistic regression analysis. RESULTS: Of the 1,204 study participants (55.7 ± 9.3 years, 37.0% men), a total of 347 large PVSs were detected in 235 (19.5%) subjects, while a total of 219 lacunes were detected in 183 subjects (15.2%). The presence of lacunes was found to be significantly associated with age, male gender, hypertension, and diabetes, whereas only age (p < 0.01) and ApoEε4 carrier status (p < 0.01) were related to the presence of large PVSs. Those who had lacunes detected on MRI at baseline had a significant increased risk of stroke (hazard ratio [HR] 4.68; 95% confidence interval [CI], 1.15-19.07) during the 3-year follow-up independent of age, gender, and other vascular risk factors. However, there was no significant relationship between the presence of large PVSs and incident stroke (HR 3.84; 95% CI, 0.82-18.04). CONCLUSIONS: The lack of association between large PVSs and cardiovascular risk factors or risk of stroke indicated a nonvascular pathogenic mechanism underlying large PVSs, suggesting the importance of distinguishing large PVSs from lacunes in clinical practice.

Magnetic resonance imaging and risk factors for progression of lacunar infarct lesions in Chinese patients.

PURPOSE: The proportion of acute symptomatic lacunar infarction lesions that undergo cavitation and the factors influencing cavity formation are yet unclear, particularly in the Chinese population. Hence, we investigated changes in the diameter of acute lacunar infarction lesions and identified the risk factors for the progression of these lesions. METHODS: A total of 160 patients (mean age 66 years) with acute symptomatic lacunar infarction lesions underwent two magnetic resonance imaging (MRI) examinations: diffusion-weighted imaging (DWI) at onset (lesion diameter < 20 mm) and T2-weighted imaging/fluid-attenuated inversion recovery sequences at follow-up (median follow-up time 389 days). Lacunar infarction lesion progression was categorized as complete cavitation (lacune), partial cavitation, white matter lesion (WML), or disappearance of the lesion. The risk factors for cavity formation were evaluated. RESULTS: Upon follow-up MRI, lesions had changed to lacunes in 20 (12.5%) patients, partial cavitation in 23 (14.4%), WMLs in 97 (60.6%), and had disappeared in 20 (12.5%). Lacune formation was related to hypertension (P = 0.026); cavity (lacune and partial cavitation) formation was related to diabetes (P = 0.009) and diameter change (P = 0.015). CONCLUSIONS: Approximately a quarter of the acute symptomatic lacunar infarction lesions observed with follow-up MRI were cavitated. Hypertension was negatively associated with lacune formation; diabetes and diameter change were negatively associated with cavity formation.

Magnetic Resonance Imaging-Visible Perivascular Spaces in Basal Ganglia Predict Cognitive Decline in Parkinson's Disease.

BACKGROUND: Growing evidence suggests an association between imaging biomarkers of small vessel disease and future cognitive decline in Parkinson's disease (PD). Recently, magnetic resonance imaging-visible perivascular space (PVS) has been considered as an imaging biomarker of small vessel disease, but its effect on cognitive decline in PD is yet to be investigated. OBJECTIVE: The objective of this study was to evaluate whether PVS can independently predict cognitive decline in PD. METHODS: A total of 271 PD patients were divided into 106 patients with intact cognition (PD-IC) and 165 patients with mild cognitive impairment (PD-MCI). After a mean follow-up of 5.0 ± 2.3 years, 18 PD-IC patients showed cognitive decline to PD-MCI and 34 PD-MCI patients showed cognitive decline to dementia. PVS was rated in the basal ganglia (BG) and centrum semiovale using a 4-point visual scale and then classified as high (score ≥ 2) or low (score < 2) according to severity. Lacunes and white matter hyperintensity severity were also assessed. Independent risk factors for cognitive decline were investigated using multivariable logistic regression analysis. RESULTS: In all patients, higher BG-PVS and white matter hyperintensity severity, higher levodopa-equivalent dose, hypertension, and lower Mini-Mental State Examination score were independent positive predictors of future cognitive decline. In the PD-IC subgroup, higher BG-PVS severity, hypertension, and more severe depressive symptoms were predictors of cognitive conversion. In the PD-MCI subgroup, higher BG-PVS and white matter hyperintensity severity, and lower Mini-Mental State Examination score were predictors of cognitive decline. CONCLUSIONS: BG-PVS may be a useful imaging marker for predicting cognitive decline in PD. © 2019 International Parkinson and Movement Disorder Society.

High triglyceride/HDL cholesterol ratio is associated with silent brain infarcts in a healthy population.

BACKGROUND: Triglycerides (TG)/high-density lipoprotein (HDL) cholesterol ratio is a marker of small/dense low-density lipoprotein particles, which are closely associated with various metabolic and vascular diseases. However, the role of TG/HDL cholesterol ratio in cerebrovascular diseases has not been well studied. In this study, we evaluated the relationship between TG/HDL cholesterol ratio and the presence of silent brain infarct (SBI) in a neurologically healthy population. METHODS: We retrospectively evaluated consecutive participants in health check-ups between January 2006 and December 2013. SBI was defined as an asymptomatic, well-defined lesion with a diameter of ≥3 mm on T1- or T2-weighted images. TG/HDL cholesterol ratio was calculated after dividing absolute TG levels by absolute HDL cholesterol levels. RESULTS: Of 3172 healthy participants, 263 (8.3%) had SBI lesions. In multivariate analysis, TG/HDL cholesterol ratio was independently associated with SBI (adjusted odds ratio [aOR] = 1.16, 95% confidence interval [CI] = 1.00 to 1.34, P = 0.047). This association was prominent in males (aOR = 1.23, 95% CI = 1.03 to 1.48, P = 0.021), but not in females. In the analyses of the relationships between lipid parameters and SBI lesion burden, TG/HDL cholesterol ratio was positively correlated, and total cholesterol/TG ratio was negatively correlated with SBI lesion burden, in dose-response manners (P for trend = 0.015 and 0.002, respectively). CONCLUSIONS: The TG/HDL cholesterol ratio was positively associated with the prevalence of SBI in a neurologically healthy population.

Pre-Existing Cerebral Small Vessel Disease Limits Early Recovery in Patients with Acute Lacunar Infarct.

BACKGROUND AND PURPOSE: To assess whether neuroimaging markers of chronic cerebral small vessel disease (cSVDm) influence early recovery after acute ischemic stroke (AIS). METHODS: Retrospective analysis of patients diagnosed with AIS and included in the Spanish Neurological Society Stroke Database. INCLUSION CRITERIA: (1) Brain MRI performed after acute stroke and (2) Premorbid modified Rankin scale (mRS) = 0. EXCLUSION CRITERIA: (1) Uncommon stroke etiologies, (2) AIS not confirmed on neuroimaging, or (3) Old territorial infarcts on neuroimaging. Patients scored from 0 to 2 according to the amount of cSVDm. Patients were divided into lacunar ischemic stroke (LIS) and nonlacunar ischemic stroke (NLIS) groups according to TOAST classification. PRIMARY OUTCOME: Distribution of mRS at discharge. SECONDARY OUTCOMES: NIHSS improvement more than or equal to 3 at 24 hours and at discharge, NIHSS worsening more than or equal to 3 points at 24 hours. RESULTS: We studied 4424 patients (3457 NLIS, 967 LIS). The presence of cSVDm increased the risk of worsening 1 category on the mRS at discharge in the LIS group ([1] cSVDm: OR 1.89 CI 95% 1.29-2.75, P = .001. [2] cSVDm: OR 1.87, CI 95% 1.37-2.56 P = .001) and was an independent factor for not achieving an improvement more than or equal to 3 points on the NIHSS at discharge for all the patients and the LIS group (all stroke patients: [1] cSVDm: OR 0.81 CI 95% .68-.97 P = .022. [2] cSVD: OR 0.58 CI95% .45-.77, P = .001./LIS: [1] cSVDm: OR 0.64, CI 95% .41-.98, P = .038. [2] cSVDm: OR 0.43, CI 95% .24-.75 P = .003). CONCLUSIONS: Pre-existing SVD limits early functional and neurological recovery after AIS, especially in LIS patients.

Why Are Only Some Subcortical Ischemic Lesions on Diffusion Magnetic Resonance Imaging Associated With Stroke Symptoms in Small Vessel Disease?

Background and Purpose- In cerebral small vessel diseases, small subcortical ischemic lesions (SSIL) on diffusion imaging are responsible for stroke manifestations but can also be occasionally observed in the absence of overt neurological symptoms. We aimed to determine, in a large cohort of young patients with CADASIL (Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), a severe monogenic condition leading to SSIL in young patients, the characteristics of SSIL and of surrounding cerebral tissue associated with the presence of stroke symptoms. Methods- Among a cohort of 323 genetically confirmed CADASIL patients who were systematically evaluated every 18 months clinically and with magnetic resonance imaging, we studied all visible SSIL and documented ischemic stroke events with available magnetic resonance imaging data. We used mixed-effect logistic regression models to determine whether the presence of stroke symptoms was associated with age, sex, the volume of SSIL, their location with respect to preexisting white matter hyperintensities and with the load of the different magnetic resonance imaging markers of small vessel disease. Results- We identified 73 SSIL (30 with stroke symptoms and 43 without) in 55 patients. In multivariable models, stroke symptoms were more frequent in male patients (estimate=1.94; SE=0.82; P=0.03) and less frequent when SSIL appeared in contact to preexisting white matter hyperintensities (estimate=-2.12; SE=0.83; P=0.01). Within pyramidal tracts, stroke symptoms were more frequent in patients with extensive white matter hyperintensities (estimate=3.8×10-5; SE=9.3×10-6; P<10-4). Conclusions- Altogether, our results suggest that when SSIL occur, the presence of stroke symptoms may depend on sex and alterations of the surrounding brain tissue rather than on the characteristics of the SSIL itself.

Mapping the contribution and strategic distribution patterns of neuroimaging features of small vessel disease in poststroke cognitive impairment.

OBJECTIVES: Individual neuroimaging features of small vessel disease (SVD) have been reported to influence poststroke cognition. This study aimed to investigate the joint contribution and strategic distribution patterns of multiple types of SVD imaging features in poststroke cognitive impairment. METHODS: We studied 145 first-ever ischaemic stroke patients with MRI and Montreal Cognitive Assessment (MoCA) examined at baseline. The local burdens of acute ischaemic lesion (AIL), white matter hyperintensity, lacune, enlarged perivascular space and cross-sectional atrophy were quantified and entered into support vector regression (SVR) models to associate with the global and domain scores of MoCA. The SVR models were optimised with feature selection through 10-fold cross-validations. The contribution of SVD features to MoCA scores was measured by the prediction accuracy in the corresponding SVR model after optimisation. RESULTS: The combination of the neuroimaging features of SVD contributed much more to the MoCA deficits on top of AILs compared with individual SVD features, and the cognitive impact of different individual SVD features was generally similar. As identified by the optimal SVR models, the important SVD-affected regions were mainly located in the basal ganglia and white matter around it, although the specific regions varied for MoCA and its domains. CONCLUSIONS: Multiple types of SVD neuroimaging features jointly had a significant impact on global and domain cognitive functionings after stroke on top of AILs. The map of strategic cognitive-relevant regions of SVD features may help clinicians to understand their complementary impact on poststroke cognition.

Low Yield of Extensive Workup for Embolic Sources in Lacunar Stroke Patients.

OBJECTIVE: We aimed to evaluate the yield of extensive etiologic workup in lacunar stroke patients. BACKGROUND: As lacunar strokes are infrequently caused by thromboembolism, the clinical relevance of extensive workup for thromboembolic sources is questioned. METHODS: Among consecutive stroke admissions to a single center over 3 years, the 100 cases initially classified as lacunar stroke and a sample of 100 cases classified as non-lacunar ischemic strokes were studied. Review of brain imaging resulted in reclassification of 24 cases, and exclusion of 3 cases, producing a final cohort of 86 confirmed lacunar strokes and 111 confirmed non-lacunar strokes. In each of these cases, results of echocardiographic and vascular imaging studies were evaluated. RESULTS: Echocardiography was performed in 93% of both the lacunar stroke cases and non-lacunar stroke cases. High-risk cardiac embolic sources were found less often in lacunar than in non-lacunar stroke cases (19% versus 34%). Findings potentially requiring anticoagulant therapy were found exclusively in the non-lacunar stroke patients. Vascular imaging studies (computed tomography angiography or magnetic resonance angiography) were also performed in similar proportions of lacunar and non-lacunar stroke cases (85% versus 84%). Cerebrovascular occlusions or high-grade stenoses were frequent (62%) in non-lacunar stroke patients but less frequent (25%) in lacunar stroke patients. In the non-lacunar stroke patients, identified vascular lesions were very frequently in a vessel anatomically related to the infarction, but in lacunar stroke patients, this occurred in only 6 cases. CONCLUSIONS: Echocardiography and vascular imaging studies rarely disclose findings of etiologic relevance, or of likelihood to change management, in patients with lacunar strokes.