Cerebrovascular Diseases最新文献

Introduction: Recruitment is complete in the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4), a multicenter, prospective, randomized, open-label, blinded endpoint assessed trial of prehospital blood pressure (BP) lowering initiated in the ambulance for patients with a suspected acute stroke and elevated BP in China. According to the registered and published trial protocol and developed by the blinded trial Steering Committee and Operations team, this manuscript outlines a detailed statistical analysis plan for the trial prior to database lock.

Methods: Patients were randomized (1:1) to intensive (target systolic BP 130-140 mm Hg within 30 min) or guideline-recommended BP management (BP lowering only considered if systolic BP >220 mm Hg) group. Primary outcome is an ordinal analysis of the full range of scores on the modified Rankin scale at 90 days. A modified sample size of 2,320 was estimated to provide 90% power to detect a 22% reduction in the odds (common odds ratio of 0.78) of a worse functional outcome using ordinal logistic regression, on the assumption of 5% patients with missing outcome and 6% patients with a stroke mimic.

Conclusion: The statistical analysis plan for the trial has been developed to ensure transparent, verifiable, and prespecified analysis and to avoid potential bias in the evaluation of the trial intervention.

Background: Professor Fisher's legacy, defined by meticulous observation, curiosity, and profound knowledge, has established a foundational cornerstone in medical practice. However, the advent of automated algorithms and artificial intelligence (AI) in medicine raises questions about the applicability of Fisher's principles in this era. Our objective was to propose adaptations to these enduring rules, addressing the challenges and leveraging the opportunities presented by digital health.

Summary: The adapted rules we propose advocate for the harmonious integration of traditional bedside manners with contemporary technological advancements. The judicious use of advanced devices for patient examination, recording, and sharing, while upholding patient confidentiality, is pivotal in modern practice and academic research. Additionally, the strategic employment of AI tools at the bedside, to aid in diagnosis and hypothesis generation, underscores their role as valued complements to clinical reasoning. These adapted rules emphasize the importance of continual learning from experience, literature, and colleagues, and stress the necessity for a critical approach toward AI-derived information, which further consolidates clinical skills. These aspects underscore the perpetual relevance of Professor Fisher's rules, advocating not for their replacement but for their evolution. Thus, a balanced methodology that adeptly utilizes the strengths of AI and digital tools, while steadfastly maintaining the core humanistic values, arises as essential in the modern practice of medicine.

Key messages: A commitment between traditional medical wisdom and modern technological capabilities may enhance medical practice and patient care. This represents the future of medicine - a resolute commitment to progress and technology, while preserving the essence of medical humanities.

Introduction: Patent foramen ovale (PFO)-stroke, a form of cryptogenic stroke, has certain identifying clinical and imaging features. However, data describing this stroke type remain inconsistent. This study examined the potential variations in PFO-stroke features, depending on age.

Methods: From a hospital registry, cryptogenic stroke patients were retrospectively selected, and PFO-strokes were identified by the presence of >10 microembolic signals on transcranial Doppler saline agitation test. Cryptogenic strokes were grouped according to age (<70 as young, ≥70 as elderly). Clinical and imaging variables of PFO-strokes and non-PFO-strokes were compared, with and without age considered.

Results: Of the 462 cryptogenic patients, 30.5% (141/462) were PFO-strokes, while majority (321/462) had no PFO. When cryptogenic strokes were analyzed by age, the significant difference was noted in the lesion number, pattern, and side. A single (72.8 vs. 57.9%, p = 0.020) and a small single lesion (51.1 vs. 35.5%, p = 0.039) were frequently seen in the younger PFO-strokes than the non-PFO counterpart, while mixed territory lesions identified the elderly PFO-strokes (30.6 vs. 8.9%, p = 0.001). A multivariate logistic regression analysis of PFO-strokes further showed that age was independently associated with lesion side (OR 1.12 [1.05-1.20], p < 0.001) and lesion number (OR 1.06 [1.02-1.10], p = 0.005).

Conclusions: Incorporating age-specific imaging criteria in the identification of PFO-strokes may be of additional value. Further, PFO may remain contributory to the stroke risk in the elderly, in association with vascular risk factors.

Introduction: Migraine symptoms are postulated to improve post-stroke. We aimed to determine post-stroke changes in patients with active migraine pre-stroke and explored the relation with stroke location and stroke-preventive medication use.

Methods: Patients with active migraine who had an ischemic stroke were retrieved from three research-cohorts between 2014 and 2021. By an interview, we retrospectively investigated first-year post-stroke changes for those ischemic stroke patients that suffered from migraine pre-stroke. Associations between change in migraine frequency/intensity/aura (decrease, no change, increase), stroke location (posterior location vs. other), and use of secondary stroke preventive medication were assessed by ordinal regression with adjustment for confounders.

Results: We included 78 patients (mean age 48 years, 86% women, 47% with aura). Change in migraine symptomatology was reported by 63 (81%) patients; 51 (81%) noticed a decrease in attack frequency (27 no attacks) and 12 (19%) an increase. Pain intensity change was reported by 18 (35%) patients (50% increase, 50% decrease). Aura symptomatology improved in 4 (11%). Reduced attack frequency was not related to posterior stroke (OR = 1.5, 95% CI: 0.6-3.9), or preventive medication (antiplatelets OR = 1.0, 95% CI: 0.2-3.7; coumarin OR = 2.7, 95% CI: 0.4-20.6).

Conclusions: Most patients with active pre-stroke migraine experience improvement of their symptoms in the first year after ischemic stroke. This change does not seem to be related to secondary stroke preventive medication or posterior stroke location.

Introduction: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with the functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).

Methods: END and DND (without END) were defined as scores of a ≥2-point increase on the National Institutes of Health Stroke Scale (NIHSS) or a ≥1-point decrease on the Glasgow coma scale or death, from baseline to 24 h and 24-72 h, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2-6 vs. 0-1 and 3-6 vs. 0-2 and death).

Results: Of 4,496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large-artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 h were all independent predictors for both END (all p ≤ 0.01) and DND (all p ≤ 0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12), higher diastolic BP variability within 24 h (OR 1.07, 95% CI 1.04-1.09), patients from Asia (OR 1.25, 95% CI 1.03-1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47-0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 h were the key predictors of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all p < 0.001).

Conclusion: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for AIS. Both END and DND predict unfavorable outcomes at 90 days.

Introduction: Cavernomas are vascular lesions with a genetic heritage that can be spotted on the central nervous system. Whenever these lesions are localized in eloquent regions, surgical resection is not recommended. In this type of situation, Gamma Knife stereotactic radiosurgery (GKSRS) could be a feasible option for treating patients. Thus, we aimed to explore the outcomes associated with this procedure.

Methods: We performed a systematic review and meta-analysis of reconstructed time-to-event data based on Kaplan-Meier curves. A thorough search was conducted on PubMed, Cochrane, Web of Science, and Embase databases targeting papers that provided information regarding hemorrhagic outcomes associated with GKSRS through Kaplan-Meier curves.

Results: After a systematic search in the specific databases, seven studies were included in this review. Notably, a total of 1,071 patients had 1,104 cavernomas treated by GKSRS. Assessment of short-term and long-term post-procedure outcomes was performed, with the estimated overall events-free rate at 2 years being 89.8% (95% CI: 87.7-91.5), while, at 10 years, the estimated overall events-free rate was 71.3% (95% CI: 67.2-75.1).

Conclusion: GKSRS seems to be a good alternative for the control of symptomatic events in early and long-term follow-up, despite the need for further investigation provided by future studies.

Introduction: This study aimed to elucidate the mechanisms underlying endothelial injury in the context of intracranial aneurysm formation and development, which are associated with vascular endothelial injury caused by hemodynamic abnormalities. Specifically, we focus on the involvement of PKCα, an intracellular signaling transmitter closely linked to vascular diseases, and its role in activating MAPK. Additionally, we investigate the protective effects of PPARγ, a vasculoprotective factor known to attenuate vascular injury by mitigating the inflammatory response in the vessel wall.

Methods: The study employs a modified T-chamber to replicate fluid flow conditions at the artery bifurcation, allowing us to assess wall shear stress effects on human umbilical vein endothelial cells in vitro. Through experimental manipulations involving PKCα knockdown and Ca2+ and MAPK inhibitors, we evaluated the phosphorylation status of PKCα, NF-κB, ERK5, ERK1/2, JNK1/2/3, and P38, as well as the expression levels of PPARγ, NF-κB, and MMP2 via Western blot analysis. The cellular localization of phosphorylated NF-κB was determined using immunofluorescence.

Results: Our results showed that impinging flow resulted in the activation of PKCα, followed by the phosphorylation of ERK5, ERK1/2, and JNK1/2/3, leading to a decrease in PPARγ expression, an increase in the expression of NF-κB and MMP2, and the induction of apoptotic injury. Inhibition of PKCα activation or knockdown of PKCα using shRNA leads to a suppression of ERK5, ERK1/2, JNK1/2/3, and P38 phosphorylation, an elevation in PPARγ expression, and a reduction in NF-κB and MMP2 expression, alleviated apoptotic injury. Furthermore, we observe that the regulation of PPARγ, NF-κB, and MMP2 expression is influenced by ERK5 and ERK1/2 phosphorylation, and activation of PPARγ effectively counteracts the elevated expression of NF-κB and MMP2.

Conclusion: Our findings suggest that the PKCα/ERK/PPARγ pathway plays a crucial role in mediating endothelial injury under conditions of impinging flow, with potential implications for vascular diseases and intracranial aneurysm development.

Introduction: Although statin therapy reduces cardiovascular events, statin use is associated with the risk of new-onset diabetes mellitus (NODM). Using a linked dataset, we evaluated the effect of statin treatment on vascular outcomes and NODM development in patients with ischemic stroke.

Methods: From the dataset, we identified 20,250 patients with acute ischemic stroke who had neither a prior history of DM nor a previous history of statin use before the index stroke. Patients were divided into statin users and non-users. The outcomes were NODM and vascular outcomes, including recurrent ischemic stroke and acute myocardial infarction (AMI).

Results: Of the 20,250 patients, 13,706 (67.7%) received statin treatment after the index stroke. For the risk of NODM, a time-response relationship was observed between the use of statins and NODM; a longer post-stroke follow-up duration substantially increased the risk of NODM. Among those with ischemic stroke exceeding 3 years, statin users had an approximately 1.7-fold greater risk of NODM than statin non-users. Statin therapy significantly reduced the risk of recurrent ischemic stroke by 54% (HR 0.46, 95% CI, 0.43-0.50, P < 0.001) across all stroke subtypes.

Conclusion: Statin therapy following ischemic stroke increased the occurrence of NODM in patients over a period of 3 years. Despite the increased risk of NODM, statin therapy shows a beneficial effect in reducing major cardiovascular events such as recurrent ischemic stroke and AMI in patients with ischemic stroke.

Background: Traditionally, non-contrast computed tomography (CT) alone was used in the initial assessment of acute ischaemic stroke patients mainly to exclude haemorrhage or alternative pathology.

Summary: Late-window (beyond 6 hours) and recent large-volume endovascular mechanical thrombectomy (MT) trials integrated CT Perfusion (CTP) imaging to guide MT and/or intravenous thrombolysis (IVT) decision-making in stroke patients.

Key messages: In current clinical practice, many patients are being excluded from reperfusion therapy due to a lack of data from urgent investigations to assess cerebral vasculature and perfusion. Here, we explore the potential benefits of CTP incorporated into the initial CT protocol assessment of stroke patients.