Risultati per: Stroke

Stroke, Ahead of Print. Background:Stroke remains a leading cause of death and disability, underscoring the urgent need for treatments that enhance recovery. Growth Differentiation Factor 11 (GDF11), a member of the TGF-β superfamily, is a circulating protein involved in cellular development and tissue repair. GDF11 has gained attention for its potential regenerative properties in aging and disease contexts, making it a candidate for stroke recovery therapies.Methods:The therapeutic benefits of recombinant GDF11 (rGDF11) were evaluated using a rat ischemic stroke model, in which focal cerebral infarcts were induced in 8 –10 week-old young adult male Sprague-Dawley rats by permanently occluding the proximal right middle cerebral artery. Rats received single or multiple doses of rGDF11 (0.1-4 mg/kg) or vehicle 24-72 hours post-injury. Sensorimotor functions were evaluated, and brain and serum samples were examined to determine mechanism of action and identify biomarkers, using immunofluorescence, target-specific ELISAs, and an aptamer-based proteomics platform.Results:We confirmed rGDF11 activity in vitro and in established in vivo mouse models of cardiac hypertrophy and glucose metabolism and assessed the efficacy of rGDF11 treatment in six preclinical stroke studies, using independent Contract Research Organizations with all study animals and treatment groups blinded. All six studies revealed consistent improvement of sensorimotor outcomes with rGDF11. rGDF11-treated rats showed increased cortical vascularization and radial glia in the ventricular zone. Serum analysis revealed rGDF11 dose-dependent decreases in C-reactive protein and identified novel pharmacodynamic biomarkers and pathways associated with potential mechanisms of action of rGDF11.Conclusion:These results demonstrate that systemically delivered rGDF11 enhances neovascularization, reduces inflammation, promotes neurogenesis, and improves sensorimotor function post-injury in a rat model of ischemic stroke. More importantly, these data define an optimized and clinically-feasible rGDF11 dosing regimen for therapeutic development in ischemic stroke and identify a panel of candidate pharmacodynamic and mechanistic biomarkers to support clinical translation.

Stroke, Ahead of Print. BACKGROUND:Communicative ability after stroke influences patient outcomes. Limited research has explored the impact of aphasia when it intersects with cultural or linguistic differences on receiving stroke care and patient outcomes. We investigated associations between requiring an interpreter and the provision of evidence-based stroke care and outcomes for people with aphasia in the inpatient rehabilitation setting.METHODS:Retrospective patient-level data from people with aphasia were aggregated from the Australian Stroke Foundation National Stroke Audit–Rehabilitation Services (2016–2020). Multivariable regression models compared adherence to processes of care (eg, home assessment complete, type of aphasia management) and in-hospital outcomes (eg, length of stay, discharge destination) by the requirement of an interpreter. Outcome models were adjusted for sex, stroke type, hospital size, year, and stroke severity factors.RESULTS:Among 3160 people with aphasia (median age, 76 years; 56% male), 208 (7%) required an interpreter (median age, 77 years; 52% male). The interpreter group had a more severe disability on admission, reflected by reduced cognitive (6% versus 12%,P=0.009) and motor Functional Independence Measure scores (6% versus 12%,P=0.010). The interpreter group were less likely to have phonological and semantic interventions for their aphasia (odds ratio, 0.57 [95% CI, 0.40–0.80]) compared with people not requiring an interpreter. They more often had a carer (68% versus 48%,P

Objective
Understanding future population needs is key for informing stroke service planning. This study aims to evaluate scenarios for future trends in stroke age-specific incidence and case fatality, and estimate their impact on projected stroke and poststroke dementia prevalence in Ireland.

Design
This is an epidemiological modelling study based on a probabilistic Markov model. We extrapolated trends in age-specific stroke incidence and case fatality from 1990 to 2019 and applied these to 2016 to 2046. We defined trend scenarios based on stability and low and high decline, broadly based on the lower and upper bounds of evidence for trends to date. We also examined nonlinear trends involving decelerating decline over time and varying trends by age.

Setting/participants
The study is conducted on the Irish population aged 40–89 years in the period 2022–2046. We used multiple data sources, including systematic review and observational evidence.

Interventions
Not applicable.

Primary and secondary outcome measures
We projected the incidence and prevalence of stroke (International Classification of Disease (ICD) codes I60–I61, I63–I64), poststroke dementia (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria) and poststroke disability (modified Rankin Scale 3–5).

Results
The stable scenario indicated a projected 85 834 stroke survivors in 2046 (95% uncertainty interval (UI)=82 366–89 655), an increase of 45.7% from 2022. Assuming a high incidence decline and low case-fatality decline indicated a 5.4% increase in prevalence. Intermediate scenarios based on lower rates of decline, or decline rates slowing over time, implied an increase between 25.8% and 40.3%. Results did not differ substantially when we varied trends by age.
In the stable scenario, we projected 16 978 poststroke dementia prevalent cases in 2046 (95% UI 14 958–19 157), an increase of 58.9% from 2022. In the high decline scenario, the increase would be 24.5%, with intermediate scenarios implying an increase between 41.3% and 56.3%.

Conclusions
Future stroke healthcare needs will vary substantially depending on epidemiological trends. There is an urgent need to both invest in prevention strategies and plan for likely increases in future stroke care needs.

Objectives
To determine patient-reported symptoms and clinical factors associated with mimics and differences in health-seeking behaviour versus stroke.

Design
This is a post-hoc analysis of a cross-sectional survey of interviews on patient-reported factors in patients admitted with suspected stroke. Patients were categorised as genuine stroke or mimic. The surveys were conducted from February 2018 to January 2019.

Setting
Two non-comprehensive stroke centres in Denmark.

Participants
Patients≥18 years (no upper age limit) admitted with symptoms of stroke to one of the non-comprehensive stroke centres or transferred from a comprehensive- or primary stroke centre were eligible for inclusion. 592 patients were included.

Outcome measures
Symptoms or clinical factors associated with stroke mimics. Logistic regression analysis was performed to identify factors associated with mimics. Secondarily, the number of strokes versus mimics presenting at a healthcare facility within 3 hours contacted the emergency medical service (EMS) and arrived by ambulance.

Results
Of 592 suspected patients with stroke, 113 (19.1%) were mimics; most frequently peripheral vertigo (24.7%) and migraine (11.5%). Factors associated with a higher likelihood of mimics were female sex (OR 1.79, 95% CI 1.14 to 2.79), high Scandinavian Stroke Scale scores (OR 1.05, 95% CI 1.02 to 1.09, per point increase), and vertigo (OR 1.86, 95% CI 1.18 to 2.95). Factors associated with a lower likelihood of mimics were increasing age (OR 0.96, 95% CI 0.95 to 0.98 per year increase), reported limb weakness (OR 0.52, 95% CI 0.30 to 0.89) and difficulty steering (OR 0.51, 95% CI 0.28 to 0.93).
There was no difference between groups in the proportion of patients for whom time from symptom onset to healthcare services contact exceeded 3 hours (52.2% vs 53.7%, p=0.78). Fewer mimics contacted the EMS first, were accepted at a primary stroke centre and arrived by ambulance (p

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Volume 178, Issue 2, Page JC15, February 2025.

Annals of Internal Medicine, Volume 178, Issue 2, Page JC16, February 2025.

Annals of Internal Medicine, Volume 178, Issue 2, Page JC18, February 2025.

Annals of Internal Medicine, Ahead of Print.

Circulation, Volume 151, Issue 5, Page 331-333, February 4, 2025.

Introduction
Stroke is a major cause of acquired disability globally, yet the neural mechanisms driving motor recovery post-stroke remain elusive. Recent research has underscored the growing significance of subcortical pathways in neural plasticity and motor control. Among these, the cortico-reticulospinal tract (CRST) has gained attention in rehabilitation due to its unique ascending and descending structural features as well as its cellular properties which position it as an excellent candidate to compensate for inadequate motor control post-stroke. However, the optimal strategies to harness the CRST for motor recovery remain unknown. Non-invasive modulation of the CRST presents a promising though challenging, therapeutic opportunity. Acoustic startle priming (ASP) training and intermittent theta burst stimulation (iTBS) are emerging as potential methods to regulate CRST function. This study aims to investigate the feasibility of segmentally modulating the cortico-reticular and reticulospinal tracts through ASP and iTBS while evaluating the resulting therapeutic effects.

Methods and analysis
This is a randomised, blinded interventional trial with three parallel groups. A total of 36 eligible participants will be randomly assigned to one of three groups: (1) iTBS+ASP group, (2) iTBS+non-ASP group, (3) sham iTBS+ASP group. The trial comprises four phases: baseline assessment, post-first intervention assessment, assessment after 3 weeks of intervention and a 4-week follow-up. The primary outcomes are the changes in the Fugl-Meyer Assessment-Upper Extremity and Modified Ashworth Scale after the 3-week intervention. Secondary outcomes include neurophysiological metrics and neuroimaging results from diffusion tensor imaging and resting-state functional MRI.

Ethics and dissemination
The trial is registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR2400085220) and Medical Ethics Committee of Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology (Registration No.TJ-IRB20231109). It will be conducted in the Departments of Rehabilitation Medicine and Radiology at Tongji Hospital in Wuhan, China. The findings will be disseminated through peer-reviewed journal publications and presentations at scientific conferences.

Trial registration number
ChiCTR2400085220.

Stroke, Volume 56, Issue Suppl_1, Page ATMP47-ATMP47, February 1, 2025. Background:Life’s Essential 8 (LE8) is a cardiovascular health (CVH) metric proposed by the American Heart Association (AHA) that includes blood glucose, blood pressure, lipid levels, diet, physical activity, nicotine exposure, body mass index, and sleep duration. LE8 is used as a tool to assess and improve CVH outcomes. Little is known about the association between LE8 and mortality after stroke.Methods:We included data from participants aged 20 and older with self-reported stroke who participated in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Data was linked with National Death Index mortality data through 2019. The association between poor and ideal LE8 scores and all-cause mortality and CV mortality rates after stroke were determined in 3 models: (1) unadjusted; (2) adjusted for sociodemographic factors (age, sex, race/ethnicity, poverty income ratio (PIR)) and (3) further adjusted for comorbidities (Charlson Comorbidity Index).Results:During the study period, 1,019 out of 26,670 individuals reported a prior stroke. When assessing mortality in those with poor CVH, although the direction of the hazard ratios (HR) suggested an increased risk of CV mortality with higher numbers of poor LS8 metrics, the associations were not significant in any of the models. However, for all-cause mortality, the risk increased with a higher number of poor CVH metrics. Possessing at least 4 poor CVH metrics was associated with a higher risk of all-cause mortality (Model 1 HR 1.69, 95%CI 1.13-2.52; Model 2 HR 2.25, 1.51-3.35; Model 3 HR 2.10, 1.39-3.20). Conversely, possessing at least 4 ideal metrics was associated with lower CV mortality in the unadjusted model, (HR 0.35, 0.15-0.85) but this association was no longer significant in Models 2 and 3. Possessing at least 4 ideal CVH characteristics was associated with lower all-cause mortality in all 3 models (Model 1 HR 0.50, 0.29-0.85; Model 2 HR 0.54, 0.31-0.92; Model 3 HR 0.56, 0.33-0.96). Higher LE8 scores were associated with lower CV mortality in Model 2 (HR per point LE8 score 0.98, 0.96-0.99) and Model 3 (0.98, 0.96-0.99) and all-cause mortality in Model 2 (0.98, 0.97-0.99) and Model 3 (0.98, 0.97-0.99).Conclusion:A higher LE8 score correlates with an increased risk of both CV and all-cause mortality in stroke survivors. Possession of at least 4 ideal CVH metrics is associated with a nearly two-thirds risk reduction in CV mortality and 50% risk reduction in all-cause mortality.

Stroke, Volume 56, Issue Suppl_1, Page ATMP37-ATMP37, February 1, 2025. Introduction:Limited studies have examined racial disparities in long-term survival after acute ischemic stroke (AIS) with inconsistent findings. We examined these disparities among Medicare fee-for-service (FFS) beneficiaries in U.S.Methods:We analyzed data on 1,997,487 Medicare FFS beneficiaries aged ≥65 years hospitalized with incident AIS (ICD-10 code I63) and survived >30 days from January 1, 2000 to December 31, 2017, and were followed-up until December 31, 2022. Cox proportional hazard models estimated the adjusted hazard ratio (aHR, 95% CI) and adjusted survival curves by race/ethnicity (non-Hispanic White (White), non-Hispanic Black (Black), Hispanic and Other). Models were adjusted for age, sex, and comorbidities.Results:The median age at AIS hospitalization was 78 years (IQR 72.0-84.0); 57.0% were women; 81.8%, 10.8%, 4.8% and 2.6% were White, Black, Hispanic and Other, respectively. Over a median follow-up of 4.9-years (IQR 1.7-8.8), there were 1,738,452 all-cause deaths. Adjusted 5-year survival after AIS improved from 2000-2004 to 2015-2017 for White (46.5% (95% CI 46.4-46.6) to 50.9% (50.7-51.1)), and Black (46.0% (45.8-46.3) to 48.9% (48.3-49.2)). For Hispanic and Other, survival remained largely unchanged: 54.4% (54.1-54.8) to 54.2% (53.6-54.8)) for Hispanic and 55.9% (55.4-56.4) to 54.7% (54.0-55.5) for Other. A clear pattern of long-term survival after AIS emerged by race/ethnicity showing similar survival between Hispanic and Other and between White and Black people (Figure). Stroke mortality risk was ~25% higher for White and Black compared to Hispanic and Other (aHR 1.25 (1.24-1.26)). This pattern was consistent across age groups and sex.Conclusions:Long-term survival after AIS has improved for White and Black Medicare FFS beneficiaries over time, while it remained largely unchanged for Hispanic and Other groups. This indicates persistent racial disparities in stroke outcomes.