Pathology of lacunar ischemic stroke in humans--a systematic review.
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ABSTRACT:
SUBMITTER: Bailey EL
PROVIDER: S-EPMC8057646 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo quantitatively characterize domain-specific cognition in individuals with symptomatic lacunar stroke in a systematic review.MethodsSystematic searches of MEDLINE and EMBASE were conducted. Inclusion criteria were all articles published prior to December 2011 evaluating domain-specific cognitive status in individuals with a symptomatic lacunar infarct. Data extraction identified cognitive domains with reported impairment and effect size calculations and heterogeneity analyses were completed to assess the magnitude of this impairment for all studies with control group data.ResultsResults of the search yielded 12 cross-sectional and 5 longitudinal studies that met inclusion criteria. Effect size calculations revealed small to medium effect sizes (ES) estimations for impairment after stroke in the domains of executive function (ES -0.44, 95% confidence interval [CI] -0.83, -0.50), memory (ES -0.55, 95% CI -0.96, -0.13), language (ES -0.63, 95% CI -0.92, -0.33), attention (ES -0.37, 95% CI -0.67, -0.07), and visuospatial abilities (ES -0.61, 95% CI -1.03, 0.19), and large effect sizes for global cognition (ES -0.90, 95% CI -1.48, -0.31) and information processing speed (ES -0.93, 95% CI -1.63, -0.23). Heterogeneity analyses revealed that a subset of these domains were heterogeneous and identified moderating factors accounting for this heterogeneity.ConclusionsResults of this systematic review are consistent with previous characterizations of cognitive impairment associated with lacunar strokes. However, impaired cognition in this stroke subtype appears less selective than previously thought, involving all major cognitive domains.
| S-EPMC3589178 | biostudies-literature
Project description:Currently 1 in 10 patients with ischemic stroke have comorbid cancer, and this frequency is expected to increase with continued advances in cancer therapeutics prolonging median survival. Well known for its association with venous thrombosis, cancer has recently emerged as a significant risk factor for arterial thromboembolism, including stroke; however, the underlying mechanisms are uncertain. In addition, the optimal strategies to prevent and acutely treat stroke in cancer patients are yet to be established. This review summarizes the current evidence on ischemic stroke risk, biomarkers, pathophysiology, treatments, and prognosis in cancer patients, emphasizing knowledge gaps and the potential strategies to address them. Ann Neurol 2018;83:873-883.
| S-EPMC6021225 | biostudies-literature
Project description:Background and purposeStatins have pleiotropic effects of potential neuroprotection. However, because of lack of large randomized clinical trials, current guidelines do not provide specific recommendations on statin initiation in acute ischemic stroke (AIS). The current study aims to systematically review the statin effect in AIS.MethodsFrom literature review, we identified articles exploring prestroke and immediate post-stroke statin effect on imaging surrogate markers, initial stroke severity, functional outcome, and short-term mortality in human AIS. We summarized descriptive overview. In addition, for subjects with available data from publications, we conducted meta-analysis to provide pooled estimates.ResultsIn total, we identified 70 relevant articles including 6 meta-analyses. Surrogate imaging marker studies suggested that statin might enhance collaterals and reperfusion. Our updated meta-analysis indicated that prestroke statin use was associated with milder initial stroke severity (odds ratio [OR] [95% confidence interval], 1.24 [1.05-1.48]; P=0.013), good functional outcome (1.50 [1.29-1.75]; P<0.001), and lower mortality (0.42 [0.21-0.82]; P=0.0108). In-hospital statin use was associated with good functional outcome (1.31 [1.12-1.53]; P=0.001), and lower mortality (0.41 [0.29-0.58]; P<0.001). In contrast, statin withdrawal was associated with poor functional outcome (1.83 [1.01-3.30]; P=0.045). In patients treated with thrombolysis, statin was associated with good functional outcome (1.44 [1.10-1.89]; P=0.001), despite an increased risk of symptomatic hemorrhagic transformation (1.63 [1.04-2.56]; P=0.035).ConclusionsThe current study findings support the use of statin in AIS. However, the findings were mostly driven by observational studies at risk of bias, and thereby large randomized clinical trials would provide confirmatory evidence.
| S-EPMC4635713 | biostudies-literature
Project description:BackgroundCognitive impairment and dementia are common after stroke. It is unclear if risk differs between ischaemic stroke subtypes. Lacunar strokes might be less likely to affect cognition than more severe, larger cortical strokes, except that lacunar strokes are associated with cerebral small vessel disease (SVD), which is the commonest vascular cause of dementia.MethodsWe searched MEDLINE and PsychINFO for studies of mild cognitive impairment (MCI) or dementia after lacunar or cortical ischaemic stroke. We calculated the OR for cognitive impairment/dementia in lacunar versus non-lacunar stroke, and their incidence and prevalence in lacunar stroke as a pooled proportion.FindingsWe identified 24 relevant studies of 7575 patients, including 2860 with lacunar stroke; 24% had MCI or dementia post stroke. Similar proportions of patients with lacunar and non-lacunar stroke (16 studies, n=6478) had MCI or dementia up to 4 years after stroke (OR 0.72 (95% CI 0.43 to 1.20)). The prevalence of dementia after lacunar stroke (six studies, n=1421) was 20% (95% CI 9 to 33) and the incidence of MCI or dementia (four studies, n=275) was 37% (95% CI 23 to 53). Data were limited by short follow-up, subtype classification methods and confounding.InterpretationCognitive impairment appears to be common after lacunar strokes despite their small size, suggesting that associated SVD may increase their impact. New prospective studies are required with accurate stroke subtyping to assess long term outcomes while accounting for confounders.
| S-EPMC3717603 | biostudies-literature
Project description:Remote ischemic conditioning (RIC) has well-established cardioprotective effects in preclinical studies and promising results in preclinical stroke research. Effective translation from preclinical studies to clinical trials has yet to be accomplished, perhaps because of the use of multiple applications of RIC (e.g., pre-, per-, or post-conditioning) in preclinical studies by both invasive and non-invasive protocols, some of which not clinically applicable. Our systematic review conformed to PRISMA guidelines and addressed differences in clinically relevant RIC applications and outcomes between preclinical and clinical studies. We retrieved a total of 30 studies (8 human; 22 animal) that met the inclusion criteria of testing clinically relevant procedures; namely, non-invasive and per- or post-conditioning protocols. Per-conditioning was applied in 6 animal and 3 human studies, post-conditioning was applied in 16 animal and 5 human studies, and both conditioning methods were applied in 2 animal studies. Application of RIC varied between human and animal studies regarding initiation, duration, repetition, and number of limbs included. Study designs did not systematically apply blinding, randomization, or placebo controls. On only a few occasions did preclinical studies include animals with clinically relevant comorbidities. Clinical trials were challenged by not completing the intended number of RIC cycles or addressing this deficit in the data analysis. Consistency and transferability of methods used for positive animal studies and subsequent human studies are essential for the optimal translation of results. Consensus on preclinical and clinical RIC procedures should be reached for a full understanding of the possible beneficial effects of RIC treatment in stroke.
| S-EPMC8351389 | biostudies-literature
Project description:Small, noncoding, microRNAs (miRNAs) have emerged as key mediators of posttranscriptional gene silencing in both pathogenic and pathological aspects of ischemic stroke biology. In stroke etiology, miRNA have distinct expression patterns that modulate pathogenic processes including atherosclerosis (miR-21, miR-126), hyperlipidemia (miR-33, miR-125a-5p), hypertension (miR-155), and plaque rupture (miR-222, miR-210). Following focal cerebral ischemia, significant changes in the miRNA transcriptome, independent of an effect on expression of miRNA machinery, implicate miRNA in the pathological cascade of events that include blood brain barrier disruption (miR-15a) and caspase mediated cell death signaling (miR-497). Early activation of miR-200 family members improves neural cell survival via prolyl hydroxylase mRNA silencing and subsequent HIF-1α stabilization. Pro- (miR-125b) and anti-inflammatory (miR-26a, -34a, -145, and let-7b) miRNA may also be manipulated to positively influence stroke outcomes. Recent examples of successfully implemented miRNA-therapeutics direct the future of gene therapy and offer new therapeutic strategies by regulating large sets of genes in related pathways of the ischemic stroke cascade.
| S-EPMC3110894 | biostudies-literature
Project description:Although intravenous thrombolysis increases the probability of a good functional outcome in carefully selected patients with acute ischemic stroke, a substantial proportion of patients who receive thrombolysis do not have a good outcome. Several recent trials of mechanical thrombectomy appear to indicate that this treatment may be superior to thrombolysis. We therefore conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of new-generation mechanical thrombectomy devices with intravenous thrombolysis (if eligible) compared with intravenous thrombolysis (if eligible) in patients with acute ischemic stroke caused by a proximal intracranial occlusion. We systematically searched seven databases for randomized controlled trials published between January 2005 and March 2015 comparing stent retrievers or thromboaspiration devices with best medical therapy (with or without intravenous thrombolysis) in adults with acute ischemic stroke. We assessed risk of bias and overall quality of the included trials. We combined the data using a fixed or random effects meta-analysis, where appropriate. We identified 1579 studies; of these, we evaluated 122 full-text papers and included five randomized control trials (n=1287). Compared with patients treated medically, patients who received mechanical thrombectomy were more likely to be functionally independent as measured by a modified Rankin score of 0-2 (odds ratio, 2.39; 95% confidence interval, 1.88-3.04; I2=0%). This finding was robust to subgroup analysis. Mortality and symptomatic intracerebral hemorrhage were not significantly different between the two groups. Mechanical thrombectomy significantly improves functional independence in appropriately selected patients with acute ischemic stroke.
| S-EPMC4926268 | biostudies-literature
Project description:Remote ischemic conditioning (RIC) is the application of brief periods of ischemia to an organ or tissue with the aim of inducing protection from ischemia in a distant organ. It was first developed as a cardioprotective strategy but has been increasingly investigated as a neuroprotective intervention. The mechanisms by which RIC achieves neuroprotection are incompletely understood. Preclinical studies focus on the hypothesis that RIC can protect the brain from ischemia reperfusion (IR) injury following the restoration of blood flow after occlusion of a large cerebral artery. However, increasingly, a role of chronic RIC (CRIC) is being investigated as a means of promoting recovery following an ischemic insult to the brain. The recent publication of two large, randomized control trials has provided promise that RIC could improve functional outcomes after acute ischemic stroke, and that there may be a role for CRIC in the prevention of recurrent stroke. Although less developed, there is also proof-of-concept to suggest that RIC may be used to reduce vasospasm after subarachnoid hemorrhage or improve cognitive outcomes in vascular dementia. As a cheap, well-tolerated and almost universally applicable intervention, the motivation for investigating possible benefit of RIC in patients with cerebrovascular disease is great. In this review, we shall review the current evidence for RIC as applied to cerebrovascular disease.
| S-EPMC10903142 | biostudies-literature
Project description:ImportanceStroke is the second leading cause of death in the world, and nearly one-third of ischemic strokes are lacunar strokes (LSs) or small subcortical infarcts. Although smaller in size, they create large problems, leaving many patients with intellectual and physical disabilities. Because there are limitations in understanding the underlying pathophysiology of LS, the development of novel therapies has been slow.ObservationsWhen the term lacune was described in the 1800s, its underlying pathophysiological basis was obscure. In the 1960s, C. Miller Fisher, MD, performed autopsy studies that showed that vessels supplying lacunes displayed segmental arteriolar disorganization, characterized by vessel enlargement, hemorrhage, and fibrinoid deposition. For these pathologic changes, he coined the term lipohyalinosis. Since that time, few attempts have been made to reconcile this pathologic description with modern mechanisms of cerebral small vessel disease (CSVD). During the past 6 years, progress has been made in understanding the clinical mechanisms, imaging characteristics, and genetic basis of LS.Conclusions and relevanceQuestions persist regarding the order of events related to the initiation and progression of CSVD, how LS is related to other sequelae of CSVD, and whether LS is part of a systemic disease process. The relative roles of aging, oxidative stress, mechanical stress, genetic predisposition, and other vascular risk factors should be further studied, especially in the era of widespread antihypertensive use. Although understanding of endothelial dysfunction has increased, future work on the role of media and adventitial dysfunction should be explored. Recent advances in mapping the brain vasculome may generate new hypotheses. The investigation of new therapeutic targets, aimed at reversing CSVD processes and promoting neural repair after LS, depends upon further understanding these basic mechanisms.
| S-EPMC7426021 | biostudies-literature
Project description:ObjectiveTo determine any differential efficacy and safety of low- vs standard-dose IV alteplase for lacunar vs nonlacunar acute ischemic stroke (AIS), we performed post hoc analyzes from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) alteplase dose arm.MethodsIn a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence (definite/according to prespecified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin Scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration or death) and treatment effects of low- vs standard-dose alteplase across lacunar and nonlacunar AIS with adjustment for baseline covariables.ResultsOf 2,588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n = 490) or nonlacunar AIS (n = 2,098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% confidence interval] 0.60 [0.47-0.77]) and other clinical or safety outcomes compared to participants with nonlacunar AIS. Low-dose alteplase (versus standard) had no differential effect on functional outcomes (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of symptomatic ICH in all included participants. There were no differential treatment effects of low- vs standard-dose alteplase on all outcomes across lacunar and nonlacunar AIS (all p interaction ≥0.07).ConclusionsWe found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/probable lacunar AIS.Classification of evidenceThis study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safety over standard-dose alteplase.Clinical trial registrationClinicaltrials.gov identifier NCT01422616.
| S-EPMC8032382 | biostudies-literature