Stroke最新文献

Background: The health outcomes currently reported in aneurysmal subarachnoid hemorrhage (aSAH) research lack consistency and do not sufficiently reflect what is important to people most affected. The objective of this article was to establish consensus on the aspects of health (domains) clinicians and researchers should measure in aSAH research.

Methods: Informed by 2 international prioritizing surveys (involving 239 participants from over 25 countries and 6 continents), we used established consensus methodology in a hybrid in-person/online consensus meeting to establish which domains of health researchers should measure in aSAH research. Sixty-nine participants with lived experience with aSAH (35%), clinical and research leaders (62%), or from aSAH-related charity (3%) took part. International multidisciplinary working groups established consensus definitions for each domain.

Results: Consensus (>70% endorsement) was sought on a proposed group of 6 domains of health, and failing that, each domain individually. The 6 domains which reached consensus and were formally defined are (1) health-related quality of life, (2) survival, (3) cognition and executive function, (4) functional outcome, (5) delayed cerebral ischemia and cerebral infarction, and (6) rebleeding and aneurysm obliteration.

Conclusions: This International Position Statement reports the consensus process undertaken and the core domain set established to guide the choice of outcomes for evaluating new treatments for aSAH. It will ultimately help shape the future aSAH research agenda.

Background: Vascular cognitive impairment (VCI) is a cognitive decline attributed to vascular pathology. Human peripheral blood mononuclear cells (PBMCs) are the key drivers of immune and inflammatory responses in circulation and are thought to play an important role in VCI, but the mechanism is unclear. The nicotinamide adenine dinucleotide (NAD⁺) salvage pathway uses NAD⁺ breakdown products to synthesize new NAD⁺ and maintain its cellular levels. Dysregulation of this pathway may disrupt cellular metabolism and immune balance, contributing to disease. Here, we investigated whether peripheral inflammation triggered by PBMCs is linked to the aberrant NAD⁺ metabolism that occurs in VCI. Targeting the NAD⁺ salvage pathway was also explored as a potential therapeutic strategy for VCI.

Methods: PBMCs from patients with VCI or controls were subjected to RNA sequencing and cultured with autologous serum. The levels of proinflammatory cytokines in PBMCs and key components in the NAD⁺ salvage pathway were measured. These parameters were assessed in a VCI mouse model. The 5'-Phosphoribosyl-pyrophosphate (PRPP), a critical substrate for NAD⁺ salvage biosynthesis, was administered, and its therapeutic effects on cognitive function were evaluated.

Results: Peripheral PBMCs from VCI patients showed elevated proinflammatory cytokine levels, reduced iNAMPT (intracellular nicotinamide phosphoribosyltransferase) activity, and lower NAD⁺ levels, whereas eNAMPT (extracellular NAMPT) levels were significantly higher. Pharmacological inhibition of eNAMPT with FK866 reduced inflammation in VCI PBMCs. Additionally, blocking TLR4 or CCR5 alleviated the proinflammatory response triggered by eNAMPT. In the VCI mice model, the NAD⁺ salvage pathway was impaired in PBMCs, which exhibited proinflammatory activity. 5'-phosphoribosyl-pyrophosphate administration restored NAD⁺ levels, suppressed inflammation, and improved cognitive function.

Conclusions: Our findings suggest peripheral inflammation driven by impaired NAD⁺ salvage and elevated eNAMPT levels in PBMCs plays a key role in VCI pathogenesis. Restoring NAD⁺ homeostasis via 5'-phosphoribosyl-pyrophosphate treatment significantly improved cognition in VCI mice, highlighting NAD⁺ salvage as a potential therapeutic target.

The STAIR (Stroke Treatment Academic Industry Roundtable) sponsored a workshop during the STAIR XIII conference in Washington, DC on March 27 to 28, 2025, to develop consensus recommendations, particularly regarding research priorities and design elements for trials of reperfusion therapies. This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke, and industry representatives to discuss future developments in reperfusion therapies. The reperfusion trials session summarized and compared recent acute stroke trials. The workshop developed consensus recommendations for research priorities and trial design challenges. Given that the majority of patients eligible for reperfusion therapies present initially to primary stroke centers, developing research networks that allow trials to be conducted in the transfer setting and overcome the logistical challenges in such centers was identified as a key priority. A particular focus was the definition and investigation of microvascular reperfusion and the no-reflow phenomenon. Potential trial paradigms to advance the field were discussed. Recent acute stroke clinical trials have extended the scope of intravenous thrombolytics and endovascular thrombectomy. Recruitment for future trials at both primary and comprehensive stroke centers, in addition to standard of care, poses challenges, particularly for novel thrombolytics. Recommendations for enhancing stroke imaging research and the definition of macrovascular versus microvascular reperfusion are provided.

Background: Severe upper limb motor impairment is one of the most disabling consequences of stroke. Although brain-controlled rehabilitation technologies, such as brain/neural exoskeletons (B/NE), have been shown to be effective in promoting motor recovery, their clinical adoption remains limited because of insufficient integration of B/NE into existing clinical workflows. Here, we introduce and validate a fully portable B/NE system that overcomes this limitation by relying on brain (electroencephalography) and ocular (electrooculography) signals to restore bimanual activities of daily living within a novel therapeutic framework.

Methods: In this pilot study, we tested the feasibility of the novel approach in 5 stroke survivors (mean age, 51 years; SD=14.8) undergoing inpatient neurorehabilitation. Stroke survivors aged 18 to 80 years, who exhibited hemiparesis and sufficient cognitive ability to understand and follow instructions, were invited to participate in a 1-hour training session. This session included system setup and calibration, followed by performing B/NE-supported, self-paced bimanual activities of daily living. As primary outcome measures, we assessed control accuracy, the ability to reliably modulate electroencephalography and electrooculography signals, and time to initialize, defined as the time required to react to cues and initiate the task, serving as a measure of control intuitiveness. In addition, participants' B/NE control performance during assisted training of bimanual activities of daily living, as well as setup preparation time, were assessed via direct observation.

Results: Participants demonstrated reliable control accuracy in using both brain (mean, 83%; SD=15.36) and ocular (mean=100%) signals, as well as intuitive control (time to initialize <2 s). All participants reliably controlled the B/NE performing a battery of 10 bimanual activities of daily living. Moreover, setup and calibration times remained below 20 minutes.

Conclusions: These findings highlight the compatibility of the novel B/NE with existing clinical workflows and its feasibility to enable B/NE-supported stroke neurorehabilitation by facilitating seamless integration into clinical practice.

Background: Evidence on the association between the stress hyperglycemia ratio (SHR) and adverse outcomes in patients with mild ischemic stroke (IS) or high-risk transient ischemic attack remains limited.

Methods: This was a secondary analysis of the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis) randomized clinical trial. SHR was calculated as admission blood glucose (mmol/L) divided by (1.59* HbA1c [%]-2.59). Multivariable Cox regression models were used to assess the association between SHR and adverse clinical outcomes, adjusting for age, sex, and other potential factors. The primary efficacy outcome was any stroke (ischemic or hemorrhagic) within 90 days. Secondary efficacy outcomes comprised composite vascular events, recurrent IS, poor functional outcome, and early neurological deterioration. The primary safety outcome was moderate-to-severe bleeding within 90 days.

Results: The INSPIRES trial, ultimately enrolled 6100 patients with mild IS or high-risk transient ischemic attack caused by intracranial or extracranial atherosclerosis, of whom 4515 were included in this secondary analysis. The median age was 65 years (interquartile range, 57-71), and 2894 (64.10%) were male. During the 90-day follow-up, recurrent stroke occurred in 356 patients (7.88%), composite vascular events in 363 (8.04%), recurrent IS in 340 (7.53%), poor functional outcome in 474 (10.51%), and early neurological deterioration in 196 (4.34%). After adjustment for conventional confounders, compared with patients in the lower SHR group (Q1), those with higher SHR levels (Q4) had significantly increased risks of recurrent stroke (hazard ratio [HR], 1.84 [95% CI, 1.30-2.61]), composite vascular events (HR, 1.72 [95% CI, 1.22-2.41]), recurrent IS (HR, 1.79 [95% CI, 1.25-2.55]), poor functional outcome (HR, 1.56 [95% CI, 1.13-2.15]), and early neurological deterioration (HR, 1.62 [95% CI, 1.00-2.61]). In contrast, SHR was not significantly associated with any safety outcomes.

Conclusions: Among patients with acute mild IS or high-risk transient ischemic attack of presumed atherosclerotic cause, elevated SHR levels were independently associated with increased risks of recurrent stroke, composite vascular events, recurrent IS, poor functional outcome, and early neurological deterioration.

Background: Reperfusion therapies for ischemic stroke are a cornerstone of acute treatment, though only available for a subset of patients due to a narrow time window. Other supplementary treatment is warranted, as only half of the patients reach functional independence. GLP-1 RA (glucagon-like peptide-1 receptor agonists) are associated with decreased cardiovascular disease, mainly driven by reduced stroke risk, and have gained interest as therapeutic agents for stroke recovery in experimental stroke models. This review aims to evaluate the current data on the effect and safety of GLP-1 RA in nondiabetic patients with ischemic stroke and in animal models of cerebral ischemia. We will describe its potential neuroprotective mechanisms.

Methods: On June 20, 2024, keyword-based literature searches were conducted in PubMed and Embase and repeated on March 6, 2025. Records evaluating GLP-1-based therapies in animals and patients with ischemic stroke who did not have diabetes were included.

Results: In total, 35 studies, 31 preclinical and 4 clinical, applying 9 different GLP-1 therapies were reviewed. GLP-1 RA improved functional outcome and induced a marked infarct volume reduction compared with vehicle (placebo) in preclinical animal stroke models. The proposed mechanisms include reduced oxidative stress, hypoxia-triggered cell death, and inflammatory response following acute ischemic stroke. Despite these neuroprotective effects observed in stroke models, evidence for improved clinical outcomes in humans remains limited. Recent randomized trials have not shown a significant effect on stroke incidence or neurological recovery in patients without diabetes who are treated with GLP-1 RA. GLP-1 RA appears safe and well-tolerated in both acute and chronic settings.

Conclusions: GLP-1 RA improves functional outcome and reduces infarct volume in preclinical animal stroke models without diabetes. Translating these promising preclinical findings into clinical benefits remains a key challenge and a critical opportunity for future research.