Stroke最新文献

Background: Infarct growth rate is remarkably heterogeneous in acute ischemic stroke, reflecting diverse clinical-physiological phenotypes. We compared different methods of estimating infarct growth rate in patients with acute ischemic stroke undergoing thrombectomy using multimodal computed tomography (CT) stroke imaging.

Methods: Secondary analysis of the international ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) which evaluated the effect of nerinetide in patients with large vessel occlusion undergoing thrombectomy. Infarct growth rate was estimated leveraging each component of multimodal stroke CT imaging: (1) 10 minus baseline Alberta Stroke Program Early CT Score (ASPECTS) divided by hours elapsed from symptom onset on noncontrast CT (ASPECTS decay per hour); (2) collateral status on multiphase CT angiography (mCTA), and (3) hypoperfusion intensity ratio on CT perfusion. Patients were dichotomized into intermediate and slow progressors (since fast progressors were likely to be excluded from ESCAPE-NA1 based on trial enrollment criteria) according to median ASPECTS decay, presence of good versus moderate/poor mCTA collaterals, and median hypoperfusion intensity ratio, respectively. Associations between progressor phenotypes and 90-day modified Rankin Scale score were assessed across neuroimaging modalities using adjusted logistic regression analyses.

Results: Among 1105 patients enrolled in ESCAPE-NA1 between 2017 and 2019, 619 (56.0%) were assessed for progressor phenotypes using noncontrast CT, 1084 (98.1%) with mCTA, and 415 (37.6%) with CT perfusion. Median ASPECTS decay per hour was 1.05 (interquartile range, 0.05-1.85), 188/1084 (17%) patients had good collateral status on mCTA, and the median hypoperfusion intensity ratio was 0.44 (interquartile range, 0.28-0.59). Intermediate progressors showed worse functional outcomes compared with slow progressors only in CT perfusion strata: adjusted common odds ratio for modified Rankin Scale ordinal shift analysis of 1.69 (95% CI, 1.14-2.49). No significant association between progressor phenotypes and 90-day modified Rankin Scale was seen when the noncontrast CT and the mCTA approaches were used.

Conclusions: Stroke progressor phenotypes based on CT perfusion criteria (using the hypoperfusion intensity ratio approach) were associated with clinical outcomes, while stroke progressor phenotypes based on noncontrast CT (ASPECTS decay) and mCTA (collateral status) criteria were not.

Background: Although the relationship between cervical carotid tortuosity and cardiovascular risk in patients with Loeys-Dietz syndrome has been studied, it is unclear whether cervical carotid tortuosity influences the risk of neurovascular events.

Methods: This is a single-institution retrospective cohort study. Cervical carotid tortuosity and morphology were assessed in patients with Loeys-Dietz syndrome who underwent baseline computed tomography/magnetic resonance imaging of the cervical and cerebral arteries from 2010 to 2022. The primary end point was a composite of adverse neurovascular events (multiple vessel cervical artery dissection, ischemic stroke, intracerebral hemorrhage, and any neurovascular intervention) at 5- and 10-year follow-ups. Independent risk factors were identified using univariate and multivariate logistic regression analyses. Single-variable predictors of 5- and 10-year outcomes were analyzed via receiver operating curve analyses. Cutoff values were determined per the Youden J index. Stratification analyses were performed for ages <60 and ≥60 years.

Results: Of 105 eligible participants, 63 were included (mean age, 40±17 years; 52% female). During a mean follow-up of 8.7±4.1 years, 23 (37%) developed an adverse neurovascular event. Five-year follow-up was achieved in 86% and 10-year follow-up in 48%. Carotid total absolute curvature (TAC; P=0.008), coiling morphology (P=0.012), and TGFBR1/2 genetic variant (P=0.037) were independently associated with 5-year events. Stratification analyses revealed that the age group <60 years was more vulnerable to high TAC (unadjusted odds ratio, 7.2 [95% CI, 2.0-25.4]; P=0.002). Baseline TAC was the only independent predictor of adverse events at 5 years (area under the curve, 0.84; P<0.001) and 10 years (area under the curve, 0.75; P=0.007) in this age group. An optimal threshold for predicting neurovascular events was TAC ≥16.5. None were predictive in the age group ≥60 years.

Conclusions: Cervical carotid tortuosity is associated with a long-term increased risk of neurovascular events in Loeys-Dietz syndrome. Angiographic findings of high-risk features such as increased TAC and coiling morphology may help to identify neurovascular vulnerability noninvasively at an early stage.

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.

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<0.001) and were more likely to be discharged home with supports (odds ratio, 1.48 [95% CI, 1.08-2.04]). The interpreter group had longer lengths of stay (median 31 versus 26 days, P=0.005).

Conclusions: Some processes of care and outcomes differed in inpatient rehabilitation for people with poststroke aphasia who required an interpreter compared with those who did not. Equitable access to therapy is imperative and greater support for cultural/linguistic minorities during rehabilitation is indicated.

Background: The frequency and prognostic significance of subacute neurological improvement (SNI) on 90-day outcomes after acute intracerebral hemorrhage are unknown.

Methods: Secondary analyses of participant data from the INTERACT2 trial (second Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trial). SNI included any, moderate, significant, and substantial neurological improvement defined as ≥1, ≥2, ≥3, and ≥4 points decrease, respectively, on the National Institutes of Health Stroke Scale from 24 hours to 7 days after intracerebral hemorrhage. Logistic regression models were used to assess associations of SNI and death or major disability (modified Rankin Scale score of 3-6), major disability (modified Rankin Scale scores, 3-5), and death alone at 90 days. Data are reported as odds ratios and 95% CIs.

Results: Of 2571 patients included in analyses, 1492 (58.0%), 1057 (41.1%), 731 (28.4%), and 490 (19.1%) patients experienced any, moderate, significant, and substantial SNI (24 hours to 7 days) after intracerebral hemorrhage, respectively. After adjustment for key confounders, any SNI was associated with 49%, 25%, and 65% reduced odds of death or major disability (odds ratio, 0.51 [95% CI, 0.42-0.63]), major disability alone (odds ratio, 0.75 [95% CI, 0.63-0.90]), and death (odds ratio, 0.35 [95% CI, 0.24-0.50]), respectively. Moderate, significant, and substantial SNI were also significantly associated with decreased odds of death or major disability at 90 days. The relationship between any SNI and study outcomes was consistent in most subgroups, including age and baseline hematoma volume. Early intensive blood pressure-lowering treatment did not increase the odds of SNI.

Conclusions: SNI from 24 hours to 7 days is common after intracerebral hemorrhage and predicts a lower likelihood of death or major disability.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00716079.

Background: Cardiac computed tomography (CT) is increasingly used to search for cardioembolic sources of acute ischemic stroke (AIS). We assessed the association between high-risk cardioembolic sources on cardiac CT and AIS.

Methods: We performed a case-control study using data from a prospective cohort including consecutive adult patients with suspected stroke who underwent cardiac CT acquired during the initial stroke imaging protocol between 2018 and 2020. Cases were patients with a final diagnosis of AIS. Controls were patients with a stroke mimic (SMi). We excluded patients with a transient ischemic attack. Diagnoses were established by an adjudication committee. Cardiac radiologists assessed the presence of structural high-risk sources of cardioembolism according to predefined criteria. We used the Firth penalized likelihood method to perform a logistic regression, adjusted for age, sex, and history of myocardial infarction to determine the association between high-risk embolic sources and AIS. For the primary analysis, we excluded patients with a history of atrial fibrillation. In a secondary analysis, patients with known atrial fibrillation were included.

Results: Of 774 patients, we excluded 167 patients due to no written informed consent or the diagnosis of transient ischemic attack. Of 607 patients, 107 patients had known atrial fibrillation and were excluded from the primary analysis. Of 500 included patients, 375 had AIS (75%, median age 70, 61% male) and 125 SMi (25%, median age 69, 42% male). A high-risk cardioembolic source was found on CT in 32/375 (8.5%) patients with AIS and 0/125 (0%) patients with SMi (adjusted odds ratio, 23.8 [95% CI, 3.3-3032.5]). Cardiac thrombi were the most commonly observed abnormality, present in 23 (6.1%) patients with AIS and 0 (0%) patients with SMi.

Conclusions: A high-risk source of cardioembolism was detected on cardiac CT more frequently in patients with AIS than in patients with SMi. These data substantiate the clinical relevance of cardioembolic sources detected on acute cardiac CT in patients with ischemic stroke.

Background: Ischemic stroke is a leading cause of death and disability. Society guidelines recommend pharmacotherapies for secondary stroke prevention. However, the role of sex differences in prescription and adherence to guideline-directed medical therapies (GDMT) after ischemic stroke remains understudied. The aim of this study was to examine sex differences in prescription patterns and adherence to GDMT at 1 year after ischemic stroke in a cohort of commercially insured patients.

Methods: Using the Truven Health MarketScan database from 2016 to 2020, we identified patients admitted with ischemic stroke. GDMT was defined as any statin, antihypertensive agents, or oral anticoagulant prescription within 30 days after discharge. Medication adherence was estimated using the proportion of days covered at 1 year. The proportion of days covered <0.80 was used to define nonadherence. A multivariable model adjusting for covariates was performed to identify the factors associated with nonadherence at 1 year. This analysis was restricted to new users of GDMT.

Results: Among 155 220 patients admitted with acute ischemic stroke during the study period, 15 919 met the inclusion criteria. The mean age was 55.7 years, and 8218 (51.7%) were women. Women were less likely to be prescribed statins (58.0% versus 71.8%) and antihypertensive agents (27.7% versus 41.8%). In this subset of patients with atrial flutter/fibrillation, women were also less likely to be prescribed oral anticoagulants (41.2% versus 45.0%). Women were more likely to be nonadherent (ie, proportion of days covered <0.80) to statins (47.3% versus 41.6%; P<0.0001), antihypertensives (33.3% versus 32.2%; P=0.005), and the combination of both (49.6% versus 45.0%; P=0.003). On multivariable analysis, women were likely to be nonadherent to statins and antihypertensive agents at 1 year (odds ratio, 1.23 [95% CI, 1.08-1.41]).

Conclusions: In this real-world analysis of commercially insured patients with ischemic stroke, women were less likely initiated on GDMT within 30 days after discharge. Women were more likely to be nonadherent to statins and antihypertensive agents at 1 year. Future efforts and novel interventions are needed to understand the reasons and minimize these disparities.