Tandem Carotid Lesions in Acute Ischemic Stroke: Mechanisms, Therapeutic Challenges, and Future Directions.
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ABSTRACT:
SUBMITTER: Poppe AY
PROVIDER: S-EPMC7357657 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite great improvement during the past several decades, the management of stroke is still far from satisfactory, which warrants alternative or adjunctive strategies. Remote ischemic conditioning (RIC), an easy-to-use and noninvasive therapy, can be performed in various clinical scenarios (e.g., prehospital transportation, intrahospital, and at home), and it has been widely investigated for stroke management. RIC has been demonstrated to be well tolerated in patients with acute ischemic stroke and aneurysm subarachnoid hemorrhage, and it may benefit these patients by improving clinical outcomes; in patients with intracranial atherosclerosis, long-term repeated RIC could be safely performed and benefit patients by reducing recurrent ischemic stroke and transient ischemic attack, as well as improving cerebral perfusion status; long-term repeated RIC may also benefit patients with cerebral small vessel disease by slowing cognitive decline and reducing volume of white matter hyperintensities on brain MRI; in patients with severe carotid atherosclerotic stenosis undergoing stenting, preprocedural RIC could reduce the odds of new brain lesions on postprocedural MRI. Previous clinical studies suggest broad future prospects of RIC in the field of cerebrovascular diseases. However, the optimal RIC protocol and the mechanisms that RIC protects the brain is not fully clear, and there is lack of sensitive and specific biomarkers of RIC, all these dilemmas prevent RIC from entering clinical practice. This review focuses on recent advances in clinical studies of RIC in stroke management, its challenges, and the potential directions of future studies.
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Project description:Ischemic stroke is a heterogeneous condition influenced by a combination of genetic and environmental factors. Recent advancements have explored genetics in relation to various aspects of ischemic stroke, including the alteration of individual stroke occurrence risk, modulation of treatment response, and effectiveness of post-stroke functional recovery. This article aims to review the recent findings from genetic studies related to various clinical and molecular aspects of ischemic stroke. The potential clinical applications of these genetic insights in stratifying stroke risk, guiding personalized therapy, and identifying new therapeutic targets are discussed herein.
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Project description:Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life. Many stroke victims are left with long-term neurological dysfunction, which adversely affects the well-being of the individual and the broader socioeconomic impact. Currently, post-stroke brain dysfunction is a major and difficult area of treatment. Vagus nerve stimulation is a Food and Drug Administration-approved exploratory treatment option for autism, refractory depression, epilepsy, and Alzheimer's disease. It is expected to be a novel therapeutic technique for the treatment of stroke owing to its association with multiple mechanisms such as altering neurotransmitters and the plasticity of central neurons. In animal models of acute ischemic stroke, vagus nerve stimulation has been shown to reduce infarct size, reduce post-stroke neurological damage, and improve learning and memory capacity in rats with stroke by reducing the inflammatory response, regulating blood-brain barrier permeability, and promoting angiogenesis and neurogenesis. At present, vagus nerve stimulation includes both invasive and non-invasive vagus nerve stimulation. Clinical studies have found that invasive vagus nerve stimulation combined with rehabilitation therapy is effective in improving upper limb motor and cognitive abilities in stroke patients. Further clinical studies have shown that non-invasive vagus nerve stimulation, including ear/cervical vagus nerve stimulation, can stimulate vagal projections to the central nervous system similarly to invasive vagus nerve stimulation and can have the same effect. In this paper, we first describe the multiple effects of vagus nerve stimulation in stroke, and then discuss in depth its neuroprotective mechanisms in ischemic stroke. We go on to outline the results of the current major clinical applications of invasive and non-invasive vagus nerve stimulation. Finally, we provide a more comprehensive evaluation of the advantages and disadvantages of different types of vagus nerve stimulation in the treatment of cerebral ischemia and provide an outlook on the developmental trends. We believe that vagus nerve stimulation, as an effective treatment for stroke, will be widely used in clinical practice to promote the recovery of stroke patients and reduce the incidence of disability.
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Project description:BackgroundBrain lesions on diffusion-weighted imaging (DWI) are frequently found after carotid artery stenting (CAS), but their clinical relevance remains unclear.ObjectivesThis study sought to investigate whether periprocedural ischemic DWI lesions after CAS or carotid endarterectomy (CEA) are associated with an increased risk of recurrent cerebrovascular events.MethodsIn the magnetic resonance imaging (MRI) substudy of ICSS (International Carotid Stenting Study), 231 patients with symptomatic carotid stenosis were randomized to undergo CAS (n=124) or CEA (n=107). MRIs were performed 1 to 7 days before and 1 to 3 days after treatment. The primary outcome event was stroke or transient ischemic attack in any territory occurring between the post-treatment MRI and the end of follow-up. Time to occurrence of the primary outcome event was compared between patients with (DWI+) and without (DWI-) new DWI lesions on the post-treatment scan in the CAS and CEA groups separately.ResultsMedian time of follow-up was 4.1 years (interquartile range: 3.0 to 5.2). In the CAS group, recurrent stroke or transient ischemic attack occurred more often among DWI+ patients (12 of 62) than among DWI- patients (6 of 62), with a cumulative 5-year incidence of 22.8% (standard error [SE]: 7.1%) and 8.8% (SE: 3.8%), respectively (unadjusted hazard ratio: 2.85; 95% confidence interval: 1.05 to 7.72; p=0.04). In DWI+ and DWI- patients, 8 and 2 events, respectively, occurred within 6 months after treatment. In the CEA group, there was no difference in recurrent cerebrovascular events between DWI+ and DWI- patients.ConclusionsIschemic brain lesions discovered on DWI after CAS seem to be a marker of increased risk for recurrent cerebrovascular events. Patients with periprocedural DWI lesions might benefit from more aggressive and prolonged antiplatelet therapy after CAS. (A Randomised Comparison of the Risks, Benefits and Cost Effectiveness of Primary Carotid Stenting With Carotid Endarterectomy: International Carotid Stenting Study; ISRCTN25337470).
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Project description:Stroke is one of the leading causes of death and disability worldwide, and the majority of the cases are ischemic stroke. However, it still lacks effective treatment except for thrombolytic therapy in an extremely narrow time window. Increased evidence suggests that histone deacetylase 4 (HDAC4) was dysregulated in ischemic stroke, which plays a key role in the pathogenesis of ischemic stroke and post-stroke recovery by affecting neuronal death, angiogenesis, and neurogenesis. Therefore, we aim to review the dysregulation of HDAC4 in ischemic stroke and the role of dysregulated HDAC4 in the pathogenesis of ischemic stroke. Furthermore, the therapeutic potential of modulating HDAC4 in ischemic stroke is discussed.
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Project description:Fifteen to 20% of patients with an acute ischaemic stroke have a tandem lesion defined by the combination of an intracranial large vessel thrombo-embolic occlusion and a high grade stenosis or occlusion of the ipsilateral internal carotid artery. These patients tend to have worse outcomes than patients with isolated intracranial occlusions, with higher rates of disability and death. The introduction of endovascular thrombectomy to treat the intracranial lesion clearly improved the outcome compared with treatment with intravenous thrombolysis alone. However, the best treatment strategy for managing the extracranial carotid artery lesion in patients with tandem lesions remains unknown. Current guidelines recommend carotid endarterectomy for patients with transient ischaemic attack or non-disabling stroke and moderate or severe stenosis of the internal carotid artery, within two weeks of the initial event, to prevent major stroke recurrence and death. Alternatively, the symptomatic carotid artery could be treated by endovascular placement of a stent during endovascular thrombectomy (EVT). This would negate the need for a second procedure, immediately reduce the risk of stroke recurrence, increase patient satisfaction, and could be cost effective. However, the administration of dual antiplatelet therapy could potentially increase the risk of symptomatic intracranial haemorrhage in patients with acute ischaemic stroke. Randomised controlled trials evaluating the efficacy and safety of immediate carotid artery stenting during EVT in acute stroke patients with tandem lesions are currently ongoing and will impact the current guidelines regarding the treatment of patients with acute ischaemic stroke due to these tandem lesions.
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Project description:AimsCarotid reocclusion (CRO) after mechanical thrombectomy (MT) in acute ischemic stroke (AIS) due to tandem lesion (TL) or isolated internal carotid occlusion (ICO) is associated with worse clinical outcomes. Our aim was to analyze the predictors and clinical impact of CRO.MethodsA retrospective single-center analysis of all patients with anterior circulation strokes who underwent MT prospectively included in a registry between 2017 and 2020 was performed. ICO and TL as stroke causes were included. Stent deployment was left to the discretion of the interventionist. All patients received at least intravenous aspirin during MT. CRO was assessed using ultrasound within the first 24 h after MT. Efficacy and safety of stenting were assessed.ResultsAmong 1304 AIS cases, 218 (16.7%) were related to TL or ICO. Of them, 5% (n=11) were associated with internal CRO 24 h after the endovascular procedure. After adjusting per confounders, multivariate analysis showed that the independent variables associated with CRO were the TICI recanalization grade [TICI 2b-3; OR 0.1, 95% confidence interval (CI) 0.01-0.89, p=0.040], pial collateral circulation presence (OR 0.09, 95% CI 0.02-0.45, p=0.03), stent deployment during MT (OR 0.17, 95% CI 0.03-0.84, p=0.030), and general anesthesia use (OR 2.92, 95% CI 1.13-7.90, p=0.034). CRO showed a trend toward worst outcomes (modified Rankin scale 3-6) at 3 months (OR 3.4, 95% CI 0.96-12, p=0.057). After multivariate analysis, variables independently associated with worse outcomes at 90 days were intrastent platelet aggregation phenomena during endovascular therapy, admission National Institute of Health Stroke Scale, and age. Conversely, intravenous thrombolysis and TICI 2b-3 recanalization grade were identified as independent predictors of good outcomes at 90 days.ConclusionsCRO has a relevant clinical impact in our study, associating lower rates of good functional outcomes at 3 months. Independent factors of CRO were the recanalization degree, presence of pial collateral circulation, use of a stent as a protective factor, and use of general anesthesia during thrombectomy.
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Project description:The brain vasculature has been increasingly recognized as a key player that directs brain development, regulates homeostasis, and contributes to pathological processes. Following ischemic stroke, the reduction of blood flow elicits a cascade of changes and leads to vascular remodeling. However, the temporal profile of vascular changes after stroke is not well understood. Growing evidence suggests that the early phase of cerebral blood volume (CBV) increase is likely due to the improvement in collateral flow, also known as arteriogenesis, whereas the late phase of CBV increase is attributed to the surge of angiogenesis. Arteriogenesis is triggered by shear fluid stress followed by activation of endothelium and inflammatory processes, while angiogenesis induces a number of pro-angiogenic factors and circulating endothelial progenitor cells (EPCs). The status of collaterals in acute stroke has been shown to have several prognostic implications, while the causal relationship between angiogenesis and improved functional recovery has yet to be established in patients. A number of interventions aimed at enhancing cerebral blood flow including increasing collateral recruitment are under clinical investigation. Transplantation of EPCs to improve angiogenesis is also underway. Knowledge in the underlying physiological mechanisms for improved arteriogenesis and angiogenesis shall lead to more effective therapies for ischemic stroke.
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Project description:Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability, which gravely burdens the global economy. Current relatively effective clinical treatments are limited to intravenous alteplase and thrombectomy. Even so, patients still benefit little due to the short therapeutic window and the risk of ischemia/reperfusion injury. It is therefore urgent to figure out the neuronal death mechanisms following ischemic stroke in order to develop new neuroprotective strategies. Regarding the pathogenesis, multiple pathological events trigger the activation of cell death pathways. Particular attention should be devoted to excitotoxicity, oxidative stress, and inflammatory responses. Thus, in this article, we first review the principal mechanisms underlying neuronal death mediated by these significant events, such as intrinsic and extrinsic apoptosis, ferroptosis, parthanatos, pyroptosis, necroptosis, and autophagic cell death. Then, we further discuss the possibility of interventions targeting these pathological events and summarize the present pharmacological achievements.
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