Embolic Stroke

One of the most important causes of neurological morbidity and mortality in the world is ischemic stroke. It can be a result of multiple events such as embolism with a cardiac origin, occlusion of small vessels in the brain, and atherosclerosis affecting the cerebral circulation. Increasing evidence shows the intricate function played by the immune system in the pathophysiological variations that take place after cerebral ischemic injury. Following the ischemic cerebral harm, we can observe consequent neuroinflammation that causes additional damage provoking the death of the cells; on the other hand, it also plays a beneficial role in stimulating remedial action. Immune mediators are the origin of signals with a proinflammatory position that can boost the cells in the brain and promote the penetration of numerous inflammatory cytotypes (various subtypes of T cells, monocytes/macrophages, neutrophils, and different inflammatory cells) within the area affected by ischemia; this process is responsible for further ischemic damage of the brain. This inflammatory process seems to involve both the cerebral tissue and the whole organism in cardioembolic stroke, the stroke subtype that is associated with more severe brain damage and a consequent worse outcome (more disability, higher mortality). In this review, the authors want to present an overview of the present learning of the mechanisms of inflammation that takes place in the cerebral tissue and the role of the immune system involved in ischemic stroke, focusing on cardioembolic stroke and its potential treatment strategies.

One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies.

Background and purposePeriodontitis has been implicated in the incidence of ischemic stroke. However, the generalizability of results to individuals with different subtypes of periodontitis is unknown. We aimed to investigate the causal relationship of chronic periodontitis (CP) and aggressive periodontitis (AgP) with ischemic stroke and its subtypes in the Mendelian randomization framework.MethodsThe genetic proxies of CP were derived from large-scale summary statistics from the UK Biobank datasets (950 cases and 455,398 controls). The genetic associations of AgP were selected from another large genome-wide association study of European ancestry (851 cases and 6836 controls). The instruments of ischemic stroke (34,217 cases and 406,111 controls) and its subtypes were selected from the MEGASTROKE consortium of European ancestry. The inverse variant weighted method was performed to determine the causal inference and a comprehensive set of sensitivity analyses to test the robustness of the results.ResultsIn population-wide genetic analysis, there was no association of genetically predicted AgP (odds ratio [OR], 0.982; 95% confidence interval [CI], 0.956-1.009; p = .197) with ischemic stroke or its subtypes. For patients with CP, there was also no significant causal inference on ischemic stroke (OR, 1.017; 95% CI, 0.992-1.043; p = .184). However, regarding the stroke subtypes, the genetic analysis provided evidence of a causal relationship of CP with cardioembolic stroke (OR, 1.052; 95% CI, 1.002-1.104; p = .042), but not with large artery atherosclerosis (OR, 1.005; 95% CI, 0.944-1.069; p = .875) or small vessel occlusion (OR, 1.039; 95% CI, 0.981-1.101; p = .193).ConclusionThis study suggested that there was a potential causal effect of CP on cardioembolic stroke.

IntroductionCardiac disease is a leading cause of arterial ischaemic stroke (AIS) in children, yet data on paediatric cardioembolic stroke remain limited. This study investigated the incidence rate, underlying cardiac diseases and outcome of paediatric cardioembolic stroke in Denmark.Patients and methodsIn a nationwide registry, we identified all children with a stroke or stroke-related diagnosis (2013-2020). Arterial ischaemic stroke events were confirmed by medical record review and classified using the Childhood AIS Standardized Classification and Diagnostic Evaluation (CASCADE) criteria as definite cardioembolic, probable cardioembolic or non-cardioembolic. Neuroimaging and neurological outcomes were extracted from medical records. Follow-up time was 2 years.ResultsCardioembolic stroke was identified in 31 (24.6%) of 126 children with AIS, corresponding to an incidence rate of 0.28 (95% CI, 0.20-0.40) per 100,000 person-years. Congenital heart diseases were the most common underlying conditions (n = 26, 83.9%). Among children undergoing angiography, LVOs were present in 41.2% of the cardioembolic group and in 18.5% of the non-cardioembolic group (P-value .060). The frequency of neurological impairments was similar between cardioembolic and non-cardioembolic AIS (48.4% vs 43.6%, P = .681). When limiting analysis to definite cardioembolic stroke, neurological impairment was more common in the cardioembolic than the non-cardioembolic group (73.3% vs 43.6%, P = .050), though this association was non-significant after adjusting for stroke severity.DiscussionCardioembolic stroke accounted for nearly one-quarter of paediatric AIS events. While clinical outcomes were similar between cardioembolic and non-cardioembolic AIS, definite cardioembolic stroke was associated with a higher risk of incomplete neurological recovery, highlighting the need for improved preventive strategies.