Stroke最新文献

In many branches of medicine, treatment is guided by measuring its effects on underlying physiology. In this regard, the efficacy of rehabilitation/recovery therapies could be enhanced if their administration was guided by measurements that directly capture treatment effects on neural function. Measures of brain function via EEG may be useful toward this goal and have advantages such as ease of bedside acquisition, safety, and low cost. This review synthetizes EEG studies during the subacute phase poststroke, when spontaneous recovery is maximal, and focuses on movement. Event-related measures reflect cortical activation and inhibition, while connectivity measures capture the function of cortical networks. Several EEG-based measures are related to motor outcomes poststroke and warrant further evaluation. Ultimately, they may be useful for clinical decision-making and clinical trial design in stroke neurorehabilitation.

Artificial intelligence (AI) large language models (LLMs) now produce human-like general text and images. LLMs' ability to generate persuasive scientific essays that undergo evaluation under traditional peer review has not been systematically studied. To measure perceptions of quality and the nature of authorship, we conducted a competitive essay contest in 2024 with both human and AI participants. Human authors and 4 distinct LLMs generated essays on controversial topics in stroke care and outcomes research. A panel of Stroke Editorial Board members (mostly vascular neurologists), blinded to author identity and with varying levels of AI expertise, rated the essays for quality, persuasiveness, best in topic, and author type. Among 34 submissions (22 human and 12 LLM) scored by 38 reviewers, human and AI essays received mostly similar ratings, though AI essays were rated higher for composition quality. Author type was accurately identified only 50% of the time, with prior LLM experience associated with improved accuracy. In multivariable analyses adjusted for author attributes and essay quality, only persuasiveness was independently associated with odds of a reviewer assigning AI as author type (adjusted odds ratio, 1.53 [95% CI, 1.09-2.16]; P=0.01). In conclusion, a group of experienced editorial board members struggled to distinguish human versus AI authorship, with a bias against best in topic for essays judged to be AI generated. Scientific journals may benefit from educating reviewers on the types and uses of AI in scientific writing and developing thoughtful policies on the appropriate use of AI in authoring manuscripts.

Background: Branch atheromatous disease (BAD)-related stroke has emerged as a meaningful subtype of ischemic stroke yet remained understudied. We aimed to investigate the demographic, clinical, therapeutic, and prognostic characteristics of BAD-related stroke.

Methods: The BAD-study was a nationwide, multicenter, prospective, observational cohort study in 20 Chinese hospitals from June 2021 to June 2023, enrolling patients aged 18 to 80 years with BAD-related stroke within 72 hours of onset. Eligible single subcortical infarct in the territory of lenticulostriate artery and paramedian pontine artery was included. Clinical, laboratory, and treatment data were collected at baseline. The primary outcome was a proportion of good outcomes (modified Rankin Scale score, 0-2) at 90 days. Main secondary outcomes included early neurological deterioration (END), cerebrovascular event, major bleeding, and excellent outcome (modified Rankin Scale score, 0-1) during 90-day follow-up.

Results: We finally enrolled 476 patients, with a median age of 60 (interquartile range, 53-68) years, and 70.2% were male. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 2-6) at enrollment. Involvement of the lenticulostriate artery was more common than the paramedian pontine artery (60.7% versus 39.3%). END occurred in 14.7% of patients, with a median time from onset of 38 (interquartile range, 22-62) hours. The rates of good and excellent outcomes were 86.5% and 72%, respectively. Its 90-day stroke recurrence rate was 1.9%. Acute-phase therapy (from onset to 7 days of enrollment) showed heterogeneity and was not associated with prognosis. Multivariable logistic regression analysis identified the National Institutes of Health Stroke Scale score ≥4 at admission and END as negative predictors and extracranial artery stenosis as a positive predictor of good outcomes. Age ≥60 years, National Institutes of Health Stroke Scale score ≥4 at admission, and END were negative predictors of excellent outcomes.

Conclusions: With distinct demographic, clinical, and prognostic characteristics, along with a high incidence of END and a low risk of stroke recurrence, BAD-related stroke could be categorized as a separate disease entity. Moreover, its acute-phase treatment strategies were undetermined, awaiting further high-quality studies.

In the 2024 David G. Sherman Lecture, Steven J. Warach, illustrating with examples from his research, walks through the history of magnetic resonance imaging in acute stroke from the 1990s and early 2000s with the introduction, validation, and application of diffusion-weighted imaging, penumbral imaging (the diffusion-perfusion mismatch), and other imaging markers of the acute stroke pathology into routine clinical practice and stroke trials. The adaptation of diffusion-weighted imaging for clinical scanners in the acute hospital setting began a revolution in ischemic stroke diagnosis as the presence, location, and size of ischemic lesions could now be visualized at the earliest times after stroke onset when computed tomography and conventional magnetic resonance imaging still appeared normal. In combination with perfusion magnetic resonance imaging, diffusion-weighted imaging made imaging of the ischemic penumbra a practical reality for routine clinical use and feasible for integration as a selection tool into clinical trials. It was apparent from the initial use of diffusion-perfusion imaging in acute stroke that many patients had persistence of penumbra as late as 24 hours after stroke onset although the probability of penumbra decreased over time. The therapeutic time window for ischemic stroke selected by clinical and temporal criteria reflected the decreased proportion of patients with the therapeutic target over time rather than the absence of the penumbral target in all patients at later times. This work provided the empirical and conceptual framework for the shift toward selection and evaluation of patients for acute stroke therapies based on direct observation of the target pathology and away from the exclusive dependence on clinical and temporal surrogates to infer the presence of stroke therapeutic targets, a shift that has expanded the indications for acute reperfusion therapies over the last 10 years.

Background: For several decades, it has been recognized that overactivation of the glutamate-gated N-methyl-D-aspartate receptors (NMDARs) and subsequent Ca²⁺ toxicity play a critical role in ischemic brain injury. 24S-hydroxycholesterol (24S-HC) is a major cholesterol metabolite in the brain, which has been identified as a potent positive allosteric modulator of NMDAR in rat hippocampal neurons. We hypothesize that 24S-HC worsens ischemic brain injury via its potentiation of the NMDAR, and reducing the production of 24S-HC by targeting its synthetic enzyme CYP46A1 provides neuroprotection.

Methods: We tested this hypothesis using electrophysiological, pharmacological, and transgenic approaches and in vitro and in vivo cerebral ischemia models.

Results: Our data show that 24S-HC potentiates NMDAR activation in primary cultured mouse cortical neurons in a concentration-dependent manner. At 10 µmol/L, it dramatically increases the steady-state currents by 51% and slightly increases the peak currents by 20%. Furthermore, 24S-HC increases NMDA and oxygen-glucose deprivation-induced cortical neuronal injury. The increased neuronal injury is largely abolished by NMDAR channel blocker MK-801, suggesting an NMDAR-dependent mechanism. Pharmacological inhibition of CYP46A1 by voriconazole or gene knockout of Cyp46a1 dramatically reduces ischemic brain injury.

Conclusions: These results identify a new mechanism and signaling cascade that critically impacts stroke outcome: CYP46A1 → 24S-HC → NMDAR → ischemic brain injury. They offer proof of principle for further development of new strategies for stroke intervention by targeting CYP46A1 or its metabolite 24S-HC.

Background: The benefit of intravenous thrombolysis with alteplase before endovascular thrombectomy (EVT) for acute ischemic stroke due to large vessel occlusion remains debated. In this study, we analyzed the cost-effectiveness of EVT alone versus intravenous alteplase before EVT in patients directly admitted to EVT-capable stroke centers from the Dutch health care payer perspective.

Methods: A decision analysis was performed using a Markov model with 15-year simulated follow-up to estimate total costs, quality-adjusted life years, and an incremental cost-effectiveness ratio of intravenous alteplase before EVT compared with EVT alone. A hypothetical cohort of 10 000 patients with large vessel occlusion aged 70 years was run in Monte Carlo simulation. Functional outcome of each treatment was derived from pooled results of 6 randomized controlled trials (RCTs). Uncertainty was assessed by probabilistic analyses, scenario analyses, and 1-way sensitivity analyses.

Results: Using functional outcomes obtained from 6 RCTs (intention-to-treat population), intravenous alteplase before EVT resulted in 0.05 quality-adjusted life years gained at an additional $2817 compared with EVT alone, resulting in the incremental cost-effectiveness ratio of $62 287. Probabilistic analyses showed that intravenous alteplase before EVT had a probability of 45% and 54%, respectively, of being cost-effective at the $52 500 and $84 000 thresholds. Restricting functional outcomes from our post hoc modified as-treated analysis of 6 RCTs (scenario 1), European RCTs (scenario 2), or a Dutch RCT (scenario 3), intravenous alteplase before EVT was cost-effective in 64%, 81%, and 50% of simulations at the $52 500 threshold, and 79%, 91%, and 67% of simulations at the $84 000 threshold.

Conclusions: Intravenous alteplase before EVT was not cost-effective in patients with large vessel occlusion in the Netherlands at the $52 500 threshold but possibly cost-effective at the $84 000 threshold. Variable functional outcomes at 3 months based on different trial populations affected the cost-effectiveness of intravenous alteplase before EVT.