Risk Factors and Clinical Characteristics of First-ever Ischemic Stroke Caused by ICAS with Leukoaraiosis.

Background: Previous studies have mostly investigated the risk factors affecting the occurrence of leukoaraiosis and the risk factors affecting the severity of leukoaraiosis in patients with ischemic stroke, but there are relatively few studies on the risk factors and clinical characteristics affecting the severity of leukoaraiosis in the population with the most common type of first-episode ischemic stroke caused by intracranial atherosclerotic stenosis in China. Methods: We retrospectively studied patients with first-ever ischemic stroke due to intracranial atherosclerotic stenosis. All patients underwent diffusion weight magnetic resonance imaging and adjunctive examinations such as magnetic resonance angiography and/or computed tomography angiography and/or digital subtraction angiography. The characteristics and clinical data were also statistically analyzed. Results: Of the 504 patients enrolled, 176 (34.92%), 202 (40.08%), and 126 (25.00%) patients were in the mild, moderate, and severe groups, respectively, and the patients were older in the severe group compared with the moderate and mild groups (p < 0.05). Hypertension was more severe in the severe group compared with the severe and mild groups (p < 0.05). The time to hospital admission was shorter in the severe group compared with the moderate and mild groups (p < 0.05). The admission National Institutes of Health stroke scale was higher in the severe group than in the moderate and mild groups (p < 0.05). homocysteine, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio, and ultrasensitive C-reactive protein to albumin ratio levels were significantly different between the three groups (p < 0.05). There was no significant correlation between the distribution of infarct foci in the anterior and posterior circulation in the three groups (p > 0.05). Conclusion: Age and homocysteine were independent risk factors for leukoaraiosis severity in patients with acute ischemic stroke, and all were positively associated with leukoaraiosis severity. Hypertension, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio and ultrasensitive C-reactive protein to albumin ratio levels were highly significant in evaluating the prognosis of patients.

Urinary microalbumin/creatinine ratio is a predictor of the occurrence and severity of leukoaraiosis.

OBJECTIVE: To investigate the correlation between the urinary microalbumin/creatinine ratio (UACR) and the occurrence and severity of leukoaraiosis. METHODS: A total of 323 patients were retrospectively recruited. Demographic, clinical, and laboratory data were collected at the time of admission, and the UACR was calculated based on the levels of urinary microalbumin and creatinine. All patients showed improvement in cranial magnetic resonance imaging (MRI) examination. The subjects were divided into leukoaraiosis and non-leukoaraiosis groups according to the results of the cranial MRI examination. According to the Fazekas standard score, the patients in the leukoaraiosis group were divided into the mild leukoaraiosis group: Fazekas (1-2 points), moderate leukoaraiosis group: Fazekas (3-4points); and severe leukoaraiosis group: Fazekas (5-6 points). RESULTS: A regression analysis was performed to adjust for confounding factors. (1) Compared with the non-leukoaraiosis group, UACR level was higher in the leukoaraiosis group at admission, and the difference between the groups was statistically significant (p < 0.05). (2) In the multivariate logistic regression analysis, UACR was correlated with the occurrence of leukoaraiosis, which may be an independent risk factor. (3) The UACR levels increased gradually in the mild, moderate and severe leukoaraiosis groups, and the difference was statistically significant (p< 0.05). (4) In the ordered multi-category logistic regression analysis, UACR was correlated with the severity of leukoaraiosis, which may be an independent risk factor. CONCLUSION: UACR is associated with the occurrence and severity of leukoaraiosis, and may be an independent risk factor.

Effect of leukoaraiosis on collateral circulation in acute ischemic stroke treated with endovascular therapy: a meta-analysis.

BACKGROUND AND OBJECTIVE: The recruitment of collateral circulation correlates with a balance of the microvasculature. Uncertainty remains to be made about the association of leukoaraiosis with leptomeningeal collaterals. To explore the effect of leukoaraiosis on leptomeningeal collaterals in patients treated with endovascular therapy. METHODS: Observational studies exploring the correlation between leukoaraiosis and leptomeningeal collaterals in large vessel occlusion treated with endovascular therapy were searched from PubMed, EMBASE, and Cochrane Libraries databases. Two independent reviewers retrieved eligible literature, extracted purpose-related data, and utilized the Newcastle-Ottawa Scale to evaluate the risk of bias. A Mantel-Haenszel method was used to calculate the odds ratio (OR). Meta-regression and subgroup analyses were conducted to clarify heterogeneity. RESULTS: Data from 10 studies with 1606 patients were extracted for pooled analysis. Compared to non-severe leukoaraiosis, patients with severe leukoaraiosis showed significant relevance to poor leptomeningeal collaterals (OR, 2.13; 95% confidence interval [1.27-3.57]; P = 0.004). Meta-regression indicated that sample size (coefficient = -0.007299, P = 0.035) and the number of female patients (coefficient = -0.0174709, P = 0.020) were sources of heterogeneity. Furthermore, all of the countries (USA versus France versus China, Q = 3.67, P = 0.159), various assessment scales of leukoaraiosis (the Fazekas scale versus Non-Fazekas scales, Q = 0.77, P = 0.379), and different imaging methods of leukoaraiosis (computed tomography versus magnetic resonance imaging, Q = 2.12, P = 0.146) and leptomeningeal collaterals (computed tomography angiography versus digital subtraction angiography, Q = 1.21, P = 0.271) showed no contribution to the effect size. CONCLUSION: Severe leukoaraiosis is associated with poor leptomeningeal collaterals in patients treated with endovascular therapy. Further studies may focus on whether the finding applies to different stroke subtypes.

Specificity and sensitivity of the SeLECT score in predicting late seizures in patients undergoing intravenous thrombolytic treatment and the effect of diabetes mellitus and leukoaraiosis.

BACKGROUND: Seizures after stroke can negatively affect the prognosis of ischemic stroke and cause a decrease in quality of life. The efficacy of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment in acute ischemic stroke has been demonstrated in many studies, and IV rt-PA treatment has been increasingly used around the world. The SeLECT score is a useful score for the prediction of late seizures after stroke and includes the severity of stroke (Se), large artery atherosclerosis (L), early seizure (E), cortical involvement (C), and the territory of the middle cerebral artery (T). However, the specificity and sensitivity of the SeLECT score have not been studied in acute ischemic stroke patients that received IV rt-PA treatment. OBJECTIVE: In the present study, we aimed to validate and develop the SeLECT score in acute ischemic stroke patients receiving IV rt-PA treatment. METHODS: The present study included 157 patients who received IV thrombolytic treatment in our third-stage hospital. The 1-year seizure rates of the patients were detected. SeLECT scores were calculated. RESULTS: In our study, we found that the SeLECT score had low sensitivity but high specificity for predicting the likelihood of late seizure after stroke in patients administered IV rt-PA therapy. In addition to the SeLECT score, we found that the specificity and sensitivity were higher when we evaluated diabetes mellitus (DM) and leukoaraiosis. CONCLUSION: We found that DM was an independent risk factor for late seizures after stroke in a patient group receiving thrombolytic therapy, and late seizures after stroke were less frequent in patients with leukoaraiosis.

ANTECEDENTES: As convulsões após o AVC podem afetar negativamente o prognóstico do AVC isquêmico e causar uma diminuição na qualidade de vida. A eficácia do tratamento com ativador do plasminogênio tecidual recombinante (rt-PA) intravenoso (IV) no AVC isquêmico agudo foi demonstrada em muitos estudos, e o tratamento com rt-PA IV tem sido cada vez mais usado em todo o mundo. A pontuação SeLECT é uma pontuação útil para a previsão de convulsões tardias após AVC e inclui a gravidade do AVC (Se), aterosclerose de grandes artérias (L), convulsão precoce (E), envolvimento cortical (C) e o território do meio artéria cerebral (T). No entanto, a especificidade e a sensibilidade do escore SeLECT não foram estudadas em pacientes com AVC isquêmico agudo que receberam tratamento IV com rt-PA. OBJETIVO: No presente estudo, objetivamos validar e desenvolver o escore SeLECT em pacientes com AVC isquêmico agudo recebendo tratamento IV com rt-PA. MéTODOS: O presente estudo incluiu 157 pacientes que receberam tratamento trombolítico IV em nosso hospital de terceiro estágio. As taxas de convulsão de 1 ano dos pacientes foram detectadas. Os escores SeLECT foram calculados. RESULTADOS: Em nosso estudo, descobrimos que o escore SeLECT apresentou baixa sensibilidade, mas alta especificidade para prever a probabilidade de convulsão tardia após AVC em pacientes que receberam terapia IV com rt-PA. Além do escore SeLECT, descobrimos que a especificidade e a sensibilidade foram maiores quando avaliamos diabetes mellitus (DM) e leucoaraiose. CONCLUSãO: Descobrimos que DM foi um fator de risco independente para convulsões tardias após AVC em um grupo de pacientes recebendo terapia trombolítica, e convulsões tardias após AVC foram menos frequentes em pacientes com leucoaraiose.

Leukoaraiosis severity is related to increased risk of early neurological deterioration in acute ischemic stroke: a retrospective observational study.

OBJECTIVES: The relationship between leukoaraiosis and early neurological deterioration in acute cerebral infarction patients remains controversial. We tried to determine whether an association existed between leukoaraiosis and early neurological deterioration in patients with acute ischemic stroke. MATERIALS AND METHODS: We retrospectively enrolled acute cerebral infarction patients admitted to our our department within 4.5-72.0 h of symptom onset between January 2016 and March 2022. On the basis of the van Swieten scale, leukoaraiosis was evaluated as supratentorial white matter hypoattenuation on admission head CT and graded as 0 (absent), 1 (mild), 2 (moderate) and 3-4 (severe). Early neurological deterioration was defined as an increase in the National Institute of Health Stroke Scale score by > = 2 points in the total score, or > = 1 point in motor power within the first seven days after admission. RESULTS: Among 736 patients, 522 (70.9%) patients had leukoaraiosis, and of these, 332 (63.6%) had mild leukoaraiosis, 41 (7.9%) had moderate leukoaraiosis, and 149 (28.5%) had severe leukoaraiosis. 118 (16.0%) patients experienced early neurological deterioration: 20 of the 214 (9.5%) patients without leukoaraiosis and 98 of the 522 (18.8%) patients with leukoaraiosis. In multiple regression analysis, we found van Swieten scale predicted early neurological deterioration independently (OR = 1.570; 95% CI: 1.226-2.012). CONCLUSIONS: Leukoaraiosis is common in acute cerebral infarction patients and leukoaraiosis severity is related to increased risk of early neurological deterioration in the patients.

Cortical atrophy and leukoaraiosis, imaging markers of cerebrovascular small vessel disease, are associated with driving behavior changes among cognitively normal older adults.

BACKGROUND: Cerebral small vessel disease (CSVD) as measured by cortical atrophy and white matter hyperintensities [leukoaraiosis], captured via magnetic resonance imaging (MRI) are increasing in prevalence due to the growth of the aging population and an increase in cardiovascular risk factors in the population. CSVD impacts cognitive function and mobility, but it is unclear if it affects complex, functional activities like driving. METHODS: In a cohort of 163 cognitively normal, community-dwelling older adults (age ≥ 65), we compared naturalistic driving behavior with mild/moderate leukoaraiosis, cortical atrophy, or their combined rating in a clinical composite termed, aging-related changes to those without any, over a two-and-a-half-year period. RESULTS: Older drivers with mild or moderate cortical atrophy and aging-related changes (composite) experienced a greater decrease in the number of monthly trips which was due to a decrease in the number of trips made within a one-to-five-mile diameter from their residence. Older drivers with CSVD experience a larger reduction in daily driving behaviors than drivers without CSVD, which may serve as an early neurobehavioral marker for functional decline. CONCLUSIONS: As CSVD markers, leukoaraiosis and cortical atrophy are standard MRI metrics that are widely available and can be used for screening individuals at higher risk for driving safety risk and decline in community mobility.

The Impact of Periventricular Leukoaraiosis in Post-stroke Oropharyngeal Dysphagia: A Swallowing Biomechanics and MRI-Based Study.

Oropharyngeal dysphagia is a highly prevalent post-stroke complication commonly associated with topographically specific gray-matter damage. In contrast, the role of damage to the extensive white matter brain network (leukoaraiosis) in post-stroke oropharyngeal dysphagia has not yet been clarified. We aim to assess the role of leukoaraiosis in post-stroke oropharyngeal dysphagia. We designed a cross-sectional study and retrospectively collected from our database patients with dysphagia affected by a recent stroke and on whom both a brain 1.5 T-MRI and a videofluoroscopy had been performed. Leukoaraiosis was assessed in brainstem and in cerebral regions (periventricular or deep) with Fazekas scale. Penetration-Aspiration-Scale and time to laryngeal vestibule closure and to upper esophageal sphincter opening were analyzed. Study population (n = 121; 57% men, 75.5 ± 9.4y) presented mostly supratentorial ischemic PACI-type strokes. Of the patients, 86% had unsafe swallows (PAS = 3.97 ± 2.04); 94.2% had cerebral leukoaraiosis (Fazekas = 3.36 ± 1.7) and 42.1% had brainstem-leukoaraiosis, hypertension being the main risk factor. We found both significant positive associations between degree of periventricular-leukoaraiosis and total-leukoaraiosis and presence of risk of aspirations (p = 0.016 and p = 0.023, respectively); and a correlation between periventricular-leukoaraiosis and PAS scale severity (r = 0.179, p = 0.049). No correlations/associations were found between stroke volume and dysphagia in this study. Our study supports a role for leukoaraiosis in the pathophysiology of dysphagia. Stroke is associated with chronic short-connection/circuit injury and damage to periventricular white matter long connections is a relevant neuro-pathophysiological mechanism contributing to impaired safety of swallow in post-stroke oropharyngeal dysphagia patients.

Impact of leukoaraiosis in patients with acute ischemic stroke treated with thrombectomy: a post hoc analysis of the DIRECT-MT trial.

BACKGROUND: The influence of leukoaraiosis in patients with acute ischemic stroke (AIS) given intra-arterial treatment (IAT) with or without preceding intravenous thrombolysis (IVT) remains unknown. OBJECTIVE: To assess the clinical and radiological outcomes of IAT in patients with or without leukoaraiosis. METHODS: Patients of the direct mechanical thrombectomy trial (DIRECT-MT) whose leukoaraiosis grade could be assessed were included. DIRECT-MT was a randomized clinical trial performed in China to assess the effect of direct IAT compared with intravenous thrombolysis plus IAT. We employed the Age-Related White Matter Changes Scale for grading leukoaraiosis (ARWMC, 0 indicates no leukoaraiosis, 1-2 indicates mild-to-moderate leukoaraiosis, and 3 indicates severe leukoaraiosis) based on brain CT. The primary outcome was the score on the modified Rankin Scale (mRS) assessed at 90 days. RESULTS: There were 656 patients in the trial, 649 patients who were included, with 432 patients without leukoaraiosis, and 217 (33.4%) patients with leukoaraiosis divided into mild-to-moderate (n=139) and severe groups (n=78). Leukoaraiosis was a predictor of a worse mRS score (adjusted OR (aOR)=0.7 (95% CI 0.5 to 0.8)) and higher mortality (aOR=1.4 (1.1 to 1.9)), but it was not associated with symptomatic intracranial hemorrhage (sICH) (aOR=0.9 (0.5 to 1.5)). IVT preceding IAT did not increase sICH risk for patients with no (aOR=1.4 (0.6 to 3.4)), mild-to-moderate (aOR=1.5 (0.3 to 7.8)), or severe (aOR=1.5 (0.1 to 21.3)) leukoaraiosis. CONCLUSION: Patients with leukoaraiosis with AIS due to large vessel occlusion are at increased risk of a poor functional outcome after IAT but demonstrate similar sICH rates, and IVT preceding IAT does not increase the risk of sICH in Chinese patients with leukoaraiosis.

Impact of leukoaraiosis or blood pressure on clinical outcome, mortality and symptomatic intracerebral hemorrhage after mechanical thrombectomy in acute ischemic stroke.

We aimed to study the impact of leukoaraiosis (LA) and blood pressure (BP) on clinical outcome, mortality and symptomatic intracerebral hemorrhage (sICH) in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). We analyzed data retrospectively from 521 patients with anterior large vessel occlusion treated with MT. LA was dichotomized in 0-2 (absent-to-moderate) versus 3-4 (moderate-to-severe) according to the van Swieten scale. Various systolic (SBP) and diastolic (DBP) BP parameters during the first 24 h were collected. Multivariable logistic regressions were performed to identify predictors of a poor 90-day outcome, mortality and sICH. LA was significantly associated with poor outcome (OR 3.2; p < 0.001) and mortality (OR 3.19; p = 0.008), but not sICH (p = 0.19). Higher maximum SBP was significantly associated with poor outcome (OR per 10 mmHg increase = 1.21; p = 0.009) and lower mean DBP was a predictor of mortality (OR per 10 mmHg increase = 0.53; p < 0.001). In the univariate analysis high SBP variability was associated with poor outcome, mortality and sICH, but not in the multivariate model. There was no association between BP and sICH. Severity of LA, SBP variability, high maximum SBP and low DBP are associated with either poor outcome or mortality in AIS patients undergoing MT. However, neither LA nor BP were associated with sICH in our cohort. Thus, mechanisms of the negative impact on outcome remain unclear. Further studies on impact of BP course and its mechanisms and interventions are needed to improve outcome in patients undergoing MT.

The contribution of white matter pathology, hypoperfusion, lesion load, and stroke recurrence to language deficits following acute subcortical left hemisphere stroke.

Aphasia, the loss of language ability following damage to the brain, is among the most disabling and common consequences of stroke. Subcortical stroke, occurring in the basal ganglia, thalamus, and/or deep white matter can result in aphasia, often characterized by word fluency, motor speech output, or sentence generation impairments. The link between greater lesion volume and acute aphasia is well documented, but the independent contributions of lesion location, cortical hypoperfusion, prior stroke, and white matter degeneration (leukoaraiosis) remain unclear, particularly in subcortical aphasia. Thus, we aimed to disentangle the contributions of each factor on language impairments in left hemisphere acute subcortical stroke survivors. Eighty patients with acute ischemic left hemisphere subcortical stroke (less than 10 days post-onset) participated. We manually traced acute lesions on diffusion-weighted scans and prior lesions on T2-weighted scans. Leukoaraiosis was rated on T2-weighted scans using the Fazekas et al. (1987) scale. Fluid-attenuated inversion recovery (FLAIR) scans were evaluated for hyperintense vessels in each vascular territory, providing an indirect measure of hypoperfusion in lieu of perfusion-weighted imaging. We found that language performance was negatively correlated with acute/total lesion volumes and greater damage to substructures of the deep white matter and basal ganglia. We conducted a LASSO regression that included all variables for which we found significant univariate relationships to language performance, plus nuisance regressors. Only total lesion volume was a significant predictor of global language impairment severity. Further examination of three participants with severe language impairments suggests that their deficits result from impairment in domain-general, rather than linguistic, processes. Given the variability in language deficits and imaging markers associated with such deficits, it seems likely that subcortical aphasia is a heterogeneous clinical syndrome with distinct causes across individuals.

Association between white matter hyperintensity volume and social functioning limitations among stroke survivors.

OBJECTIVE: Existing literature on white matter hyperintensity volume (WMHV) in stroke patients has rarely focused on post-stroke outcomes related to social functioning limitations, such as transportation, social interaction, food preparation, grocery shopping, and housekeeping. Using prospective data from the VITamin D and OmegA-3 TriaL (VITAL) study, we evaluated the association between WMHV and social functioning limitations among 151 ischemic stroke patients. MATERIALS AND METHODS: WMHV was ascertained from magnetic resonance imaging (MRI) collected at the time of the stroke event using a validated semiautomated method, and social functioning limitations were assessed using a stroke outcomes questionnaire administered a median of 1.25 years after the date of the MRI scan. Logistic regression was used to explore the association between WMHV and social functioning limitations. RESULTS: After adjusting for age and sex, a statistically significant association was found between WMHV and limitations in social interaction (OR=2.82; 95% CI: 1.21-7.55). Increased risks were seen for limitations related to food preparation (OR=2.06; 95% CI: 0.99-4.54), transportation (OR=1.39; 95% CI: 0.85-2.27), and housekeeping (OR=1.37; 95% CI: 0.91-2.11); however, the associations did not reach statistical significance. We observed no association between WMHV and limitations in grocery shopping (OR=1.08; 95% CI: 0.61-1.89). CONCLUSIONS: Future studies are needed to further explore the biological mechanisms underlying the relationship with limitations in social interaction and to replicate our findings using a larger and more diverse study sample.

Analysis of Factors Associated with Hemorrhagic Transformation in Acute Cerebellar Infarction.

OBJECTIVES: Hemorrhagic transformation (HT) is a frequent and severe complication of ischemic stroke. This study aimed to evaluate the factors associated with the occurrence of HT in patients with acute cerebellar infarction. MATERIALS AND METHODS: A total of 190 patients, 141 male (74.2%) and 49 female (25.8%) with mean age 61.84 ± 12.16 years, who were admitted within 72 h of acute cerebellar infarction onset from January 2017 to March 2021 were retrospectively recruited. The multivariate logistic regression analysis was used to evaluate the independent influent factors for HT and receiver-operating characteristic (ROC) curve was applied to calculate the predictive value of those factors for HT in patients with acute cerebellar infarction. RESULTS: 37 out of 190 recruited patients (19.47%) had HT within 14 days after acute cerebellar infarction onset. The incidence rates of HT occurring within 3 days, 3-7 days and 7-14 days were 13.5%, 40.5% and 45.9%, respectively. Results of the multivariable logistic regression analysis indicated that atrial fibrillation (AF) (OR 6.196, 95% CI 1.357-28.302, P = 0.019), infarct diameter (OR 5.813, 95% CI 2.932-11.526, P < 0.001), white matter hyperintensity (WMH) (OR 2.44, 95% CI 1.134-5.252, P = 0.023) were independent risk factors for HT in acute cerebellar infarction, while lymphocyte count (OR 0.319, 95% CI 0.142-0.716, P = 0.006) showed an independently protective effect. CONCLUSIONS: Infarct diameter, AF and WMH are independent risk factors for HT in patients with acute cerebellar infarction, while the lymphocyte count is a protective factor.

High-Density Lipoprotein Is Associated with Leukoaraiosis Severity in Patients with Acute Ischemic Stroke.

Many patients with acute ischemic stroke (AIS) are found to accompany with leukoaraiosis (LA) in brain imaging. The risk factors of LA in patients with AIS were examined in this study. Patients with AIS were recruited and underwent head magnetic resonance imaging. According to Fazekas scores, patients were divided into LA group and non-LA group. We compared demographic and laboratory characteristics in two groups. Multivariate logistic regression analysis demonstrated that high-density lipoprotein (HDL), age, stroke history, admission SBP, and homocysteine were independent risk factors for LA in patients with AIS (P < 0.05). Multinomial logistic regression analysis demonstrated that HDL was an independent risk factor for moderate LA (OR 4.151, 95% CI 1.898-9.078, P < 0.001) and severe LA (OR 3.151, 95% CI 1.350-7.358, P = 0.008). In order to further explore the correlation between HDL level and the severity of LA, HDL was categorized in quartiles and multinomial logistic regression analysis was presented. Regression analysis showed that HDL ≥ 1.34 mmol/L was correlated with moderate and severe LA after adjusting for corresponding confounding factors in different models. After 1-year follow-up, patients were divided into regular statin therapy group and irregular statin therapy group. There was no significant difference in HDL level between two groups; however, the proportion of patients with increased Fazekas scores in regular statin therapy group was significantly less than that in the irregular statin therapy group (P < 0.05). In conclusion, HDL was an independent risk factor for LA and associated with the severity of LA in patients with AIS; regular statin therapy may be negatively related with the progress of LA. These results provide more evidences for controlling risk factors and severity of LA in patient with AIS.

Cerebral small vessel disease and prognosis in intracerebral haemorrhage: A systematic review and meta-analysis of cohort studies.

BACKGROUND AND PURPOSE: The aim was to investigate whether cerebral small vessel disease (CSVD) markers and the total CSVD burden are associated with functional outcome, mortality, stroke recurrence and haematoma expansion in patients with spontaneous intracerebral haemorrhage (ICH). METHODS: Following a previously registered protocol (PROSPERO protocol: CRD42021287743), PubMed, Web of Science and Embase were systematically searched to identify relevant literature up to November 2021. Cohort studies that examined the association between CSVD markers (white matter hyperintensity [WMH], lacune, enlarged perivascular space [EPVS], cerebral microbleed [CMB] and brain atrophy) or CSVD burden and prognosis in patients with ICH were included. The pooled estimates were calculated using random effects models. RESULTS: Forty-one studies with 19,752 ICH patients were pooled in the meta-analysis. WMH (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.32-1.70), lacune (OR = 1.32, 95% CI 1.18-1.49), CMB (OR = 2.60, 95% CI 1.13-5.97) and brain atrophy (OR = 2.22, 95% CI 1.48-3.31) were associated with worse functional outcome. CSVD markers concerning increased risk of mortality were WMH (OR = 1.57, 95% CI 1.38-1.79) and brain atrophy (OR = 1.84, 95% CI 1.11-3.04), and markers concerning increased risk of stroke recurrence were WMH (OR = 1.62, 95% CI 1.28-2.04) and lacune (OR = 3.00, 95% CI 1.68-5.37). Enlarged perivascular space was not related to prognosis. There was a lack of association between CSVD markers and haematoma expansion. CSVD burden increased the risk of worse functional outcome, mortality and stroke recurrence by 57%, 150% and 44%, respectively. CONCLUSIONS: In patients with spontaneous ICH, WMH, lacune, CMB, brain atrophy and the total CSVD burden are associated with substantially increased risk of worse functional outcome, mortality or stroke recurrence.

Compromised cerebrovascular reactivity in migraineurs with right-to-left shunts: a potential mechanism of white matter hyperintensities.

OBJECTIVE: Our study aims to explore the changes of cerebrovascular reactivity (CVR) in migraineurs with right-to-left shunts (RLS), and further evaluate the association between CVR and the occurrence of the white matter hyperintensities (WMHs). METHODS: RLS was diagnosed based on a contrast enhancement transcranial Doppler (c-TCD) examination. The breath holding index (BHI), which represents CVR, was measured from the middle cerebral artery (MCA) using a TCD with the breath-holding method. WMHs was defined as clearly hyperintense areas in 3 T magnetic resonance imaging (MRI). All migraineurs underwent a standardized questionnaire for family and personal history and detailed migraine features. RESULTS: Three hundred and ninety-seven migraineurs and 100 controls were included in our study. The BHI was significantly lower in migraineurs than controls (0.527 ± 0.709 vs. 0.674 ± 0.489, P = 0.016). Moreover, migraineurs with RLS had lower BHI than those without RLS (0.504 ± 0.671 vs. 0.674 ± 0.721, p = 0.024). Migraineurs with WMHs had lower BHI than those without (0.47 ± 0.71 vs. 0.75 ± 0.49, p = 0.035). The reduced BHI was an independent influencing factor for WMHs in our study (OR = 0.338; 95% CI = 0.142-0.806, p = 0.014). CONCLUSION: Our results indicated that BHI was reduced in migraineurs, and the reduced BHI was associated with RLS. Moreover, the reduced CVR in migraineurs with RLS might be related to the occurrence of WMHs.

Social Determinants of Health Attenuate the Relationship Between Race and Ethnicity and White Matter Hyperintensity Severity but not Microbleed Presence in Patients with Intracerebral Hemorrhage.

BACKGROUND: The association between race and ethnicity and microvascular disease in patients with intracerebral hemorrhage (ICH) is unclear. We hypothesized that social determinants of health (SDOHs) mediate the relationship between race and ethnicity and severity of white matter hyperintensities (WMHs) and microbleeds in patients with ICH. METHODS: We performed a retrospective observational cohort study of patients with ICH at two tertiary care hospitals between 2013 and 2020 who underwent magnetic resonance imaging of the brain. Magnetic resonance imaging scans were evaluated for the presence of microbleeds and WMH severity (defined by the Fazekas scale; moderate to severe WMH defined as Fazekas scores 3-6). We assessed for associations between sex, race and ethnicity, employment status, median household income, education level, insurance status, and imaging biomarkers of microvascular disease. A mediation analysis was used to investigate the influence of SDOHs on the associations between race and imaging features. We assessed the relationship of all variables with discharge outcomes. RESULTS: We identified 233 patients (mean age 62 [SD 16]; 48% female) with ICH. Of these, 19% were Black non-Hispanic, 32% had a high school education or less, 21% required an interpreter, 11% were unemployed, and 6% were uninsured. Moderate to severe WMH, identified in 114 (50%) patients, was associated with age, Black non-Hispanic race and ethnicity, highest level of education, insurance status, and history of hypertension, hyperlipidemia, or diabetes (p < 0.05). In the mediation analysis, the proportion of the association between Black non-Hispanic race and ethnicity and the Fazekas score that was mediated by highest level of education was 65%. Microbleeds, present in 130 (57%) patients, was associated with age, highest level of education, and history of diabetes or hypertension (p < 0.05). Age, highest level of education, insurance status, and employment status were associated with discharge modified Rankin Scale scores of 3-6, but race and ethnicity was not. CONCLUSIONS: The association between Black non-Hispanic race and ethnicity and moderate to severe WMH lost significance after we adjusted for highest level of education, suggesting that SDOHs may mediate the association between race and ethnicity and microvascular disease.

Cerebral Microbleeds and Acute Hematoma Characteristics in the ATACH-2 and MISTIE III Trials.

BACKGROUND AND OBJECTIVES: To study the relationship between the presence of cerebral microbleeds (CMBs) and acute hematoma characteristics among patients with primary intracerebral hemorrhage (ICH). METHODS: We pooled individual patient data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 (MISTIE III) trial. We included individuals with a brain MRI scan. Exposure was the presence of a CMB. The coprimary outcomes were admission ICH volume and hematoma expansion. Mixed-effects linear and logistic regression models were used, with demographics and comorbid conditions considered fixed effects and the study cohort treated as a random effect. Additional analyses assessed the relationship between CMB topography and number and hematoma characteristics. RESULTS: Of the 1,499 patients with ICH enrolled in the parent trials, 466 (31.1%) were included in this analysis, and 231 (49.6%) patients had CMBs. In adjusted models, presence of CMBs was associated with smaller ICH volume (ß = -0.26, 95% confidence interval [CI] -0.44 to -0.08) and lower odds of hematoma expansion (odds ratio 0.65, 95% CI 0.40-0.95; p = 0.04). The strength of association between CMBs and hematoma characteristics increased with increasing number of CMBs. The location of the CMBs and the severity of leukoaraiosis did not modify these results. DISCUSSION: In a pooled cohort of patients with ICH, our results are consistent with the hypothesis that more severe underlying small vessel disease, as represented by CMBs, leads to smaller baseline hematoma volumes and reduced hematoma expansion. Underlying cerebral small vessel disease may be of prognostic significance after ICH. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT01176565 and NCT01827046. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the presence of microbleeds on MRI is associated with a smaller ICH volume at presentation and a lower rate of hematoma expansion on follow-up imaging.

Reduced Leukoaraiosis, Noncardiac Embolic Stroke Etiology, and Shorter Thrombus Length Indicate Good Leptomeningeal Collateral Flow in Embolic Large-Vessel Occlusion.

BACKGROUND AND PURPOSE: Acute leptomeningeal collateral flow is vital for maintaining perfusion to penumbral tissue in acute ischemic stroke caused by large-vessel occlusion. In this study, we aimed to investigate the clinically available indicators of leptomeningeal collateral variability in embolic large-vessel occlusion. MATERIALS AND METHODS: Among prospectively registered consecutive patients with acute embolic anterior circulation large-vessel occlusion treated with thrombectomy, we analyzed 108 patients admitted from January 2015 to December 2019 who underwent evaluation of leptomeningeal collateral status on pretreatment CTA. Clinical characteristics, extent of leukoaraiosis on MR imaging, embolic stroke subtype, time of imaging, occlusive thrombus characteristics, presenting stroke severity, and clinical outcome were collected. The clinical indicators of good collateral status (>50% collateral filling of the occluded territory) were analyzed using multivariate logistic regression analysis. RESULTS: Good collateral status was present in 67 patients (62%) and associated with independent functional outcomes at 3 months. Reduced leukoaraiosis (total Fazekas score, 0-2) was positively related to good collateral status (OR, 9.57; 95% CI, 2.49-47.75), while the cardioembolic stroke mechanism was inversely related to good collateral status (OR, 0.17; 95% CI, 0.02-0.87). In 82 patients with cardioembolic stroke, shorter thrombus length (OR, 0.91 per millimeter increase; 95% CI, 0.82-0.99) and reduced leukoaraiosis (OR, 5.79; 95% CI, 1.40-29.61) were independently related to good collateral status. CONCLUSIONS: Among patients with embolic large-vessel occlusion, reduced leukoaraiosis, noncardiac embolism mechanisms including embolisms of arterial or undetermined origin, and shorter thrombus length in cardioembolism are indicators of good collateral flow.

A pilot study of the association between leukoaraiosis and cerebral atherosclerosis using synthetic magnetic resonance imaging.

BACKGROUND: Leukoaraiosis is a type of lesion characterized by tissue rarefaction or myelin pallor resulting from axons loss and gliosis. Synthetic magnetic resonance imaging (MRI) could yield quantitative T1, T2, proton density (PD) values of leukoaraiosis in addition to information on the volume of the lesion. PURPOSE: To investigate the feasibility of quantifying leukoaraiosis using synthetic MRI and to explore the association between leukoaraiosis and cerebral small vascular diseases and cerebral atherosclerosis. MATERIAL AND METHODS: Patients with acute ischemic stroke were enrolled in this study. All participants underwent a conventional T2-weighted image, brain volume, CUBE fluid attenuated inversion recovery, and synthetic MRI acquisition using a 3.0-T MR system. A time-of-flight magnetic resonance angiography was also obtained. We evaluated the T1, T2, PD values and leukoaraiosis volume. RESULTS: Analysis of the leukoaraiosis volume ratios demonstrated a positive association with T2 values, a negative association with T1 values, and no association with PD values. Leukoaraiosis volume ratios were independently correlated with age (P < 0.001), lacunes (P = 0.022), and cerebral microbleeds (P = 0.010). A statistical association was found between both age (P < 0.001) and lacunes (P = 0.047) and leukoaraiosis T2 values. CONCLUSION: Synthetic MRI may enhance the evaluation of leukoaraiosis, in addition to providing information on its volume. Leukoaraiosis may represent a type of cerebral small vascular disease rather than cerebral atherosclerosis and may share the same pathological mechanism as lacunes and cerebral microbleeds.

Study on the Correlation Between Ischemic Leukoaraiosis and Cerebral Large Artery Stenosis Using the Stages of the Preinfarction Period Based on the Result of Computed Tomography Perfusion.

BACKGROUND AND OBJECTIVE: The influence of cerebral large artery stenosis (CLAS) on ischemic leukoaraiosis (LA) remains elusive. Based on the proposed stages of the preinfarction period, this study aimed to adopt the staging system to assess the correlation between ischemic LA and CLAS. MATERIALS AND METHODS: Patients with unilateral CLAS ≥50% and without cerebral stroke were screened. The severity and distribution of stenosis were evaluated on computed tomography angiography images. The degree of regional cerebral perfusion was rated according to the stages of preinfarction period: 0=normal, 1=stage Ia, 2=stage Ib, 3=stage IIa, 4=stage IIb. Stage I included stage Ia and stage Ib. Stage II included stage IIa and stage IIb. LA was scored with Fazakas scale on T2-weighted image and/or fluid-attenuated inversion recovery sequences. RESULTS: The cohort consisted of 212 patients (mean age, 66.89±11.39 y), including 145 (68.40%) males. CLAS severity and distribution did not differ between patients with and without LA (P>0.05). Normal, stage I, and stage II had significantly different incidences of LA and hemispheric LA scores in the left and right hemispheres (P<0.05). The degree of regional cerebral perfusion was independently associated with LA in the left (P=0.0094) and right hemispheres (P=0.0091). CONCLUSIONS: Ischemic LA is not directly related to CLAS but is independently associated with the degree of CLAS-induced cerebral hypoperfusion. The stages of the preinfarction period are helpful in identifying people at high risk of LA progression.