Acute ischemic stroke treatment typically involves tissue-type plasminogen activator (tPA) or tenecteplase, but about 50% of patients do not achieve successful reperfusion. The causes of tPA resistance, influenced by thrombus composition and timing, are not fully clear. Neutrophil extracellular traps (NETs), associated with poor outcomes and reperfusion resistance, contribute to thrombosis. DNase-I, which degrades neutrophil extracellular traps, could improve thrombolytic efficacy. However, more studies are needed to understand the impact of DNase-I in tPA-sensitive stroke models, the safety of coadministering DNase-I and tPA regarding hemorrhagic transformation (HT), optimal timing for use, and effects on aspirin-treated animals.

Poor olfaction may be associated with adverse cerebrovascular events, but empirical evidence is limited. We aimed to investigate the association of olfaction with the risk of stroke in the Atherosclerosis Risk in Communities Study.

Sex-specific differences in stroke risk factors, clinical presentation, and outcomes are well documented. However, little is known about real-world differences in transient ischemic attack (TIA) hospitalizations and outcomes between men and women.

To study the risk of incident dementia after a non-traumatic intracranial hemorrhage in a diverse US population, and evaluate if this risk is different for the subtypes of intracranial hemorrhage. We performed a retrospective cohort study using both inpatient and outpatient claims data on Medicare beneficiaries between January 1, 2008 and December 31, 2018. The exposure was a new diagnosis of non-traumatic intracranial hemorrhage, defined as a composite of intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and subdural hemorrhage (SDH). The outcome was a first-ever diagnosis of dementia. The exposure and outcomes were identified using validated ICD-9 and ICD-10-CM diagnosis codes. We excluded patients who had prevalent intracranial hemorrhage or dementia, to ensure that only incident cases were counted in our analyses. In the primary analysis, we used Cox regression to study the risk of dementia after intracranial hemorrhage, after adjusting for demographics and comorbidities. In secondary analyses, the risks of dementia in different subtypes of intracranial hemorrhage were studied. Among 2.1 million patients, 14,775 had a diagnosis of intracranial hemorrhage. During a median follow up of 5.6 years (IQR, 3.0-9.1), incident dementia was diagnosed in 2527 (17.1%) patients with an intracranial hemorrhage and 260,691 (12.8%) in those without intracranial hemorrhage. The cumulative incidence rate of dementia was 8.6% (IQR, 8.1-8.9) among patients with an intracranial hemorrhage, and 2.2% (2.0-2.4) in patients without intracranial hemorrhage. In adjusted Cox regression analysis, intracranial hemorrhage was associated with an increased risk of incident dementia (HR, 2.0; CI, 1.9-2.2). In secondary analyses, a higher risk of incident dementia was observed with ICH (HR, 2.4; CI, 2.2-2.5), SAH (HR, 1.99; CI, 1.7-2.2), and SDH (HR, 1.6; CI, 1.4-1.7). In a large heterogeneous cohort of elderly US participants, intracranial hemorrhage was independently associated with a 2-fold increased risk of incident dementia. This elevated risk was consistently observed across subtypes of intracranial hemorrhage.

Many national initiatives focus on promoting early hospital arrival of patients with acute ischemic stroke (AIS) because treatment effectiveness is time-dependent. However, several studies reported time-delays in hospital arrival, especially during the COVID-19 pandemic. Our purpose was to evaluate the 10-year trends in last known well to arrival (LKWA) time and assess disparities in patients with AIS.

Since treatment with anticoagulants can prevent recurrent strokes, identification of patients at risk for incident AF after stroke is crucial. We aimed to investigate whether the addition of AF polygenic risk scores (PRS) to existing clinical risk predictors could improve prediction of AF after stroke. Patients diagnosed with ischemic stroke at Massachusetts General Hospital between 2003-2017 were included. Clinical AF risk was estimated using the Re-CHARGE-AF model and genetic risk was estimated using a contemporary AF PRS from 1,093,050 variants. Patients were divided into clinical and genetic risk tertiles. Cox proportional hazards models at different follow-up windows were fit, and C-indices and percentile-based Net Reclassification Index (NRI) were used to determine improvement of clinical risk models with the addition of AF PRS. Of 1004 stroke survivors, 900 (90%) were non-Hispanic White, 413 (41%) were female, and the mean age was 67 (SD 14). Of 1004 survivors, 239 (23.8%) had prevalent AF and 87/765 (11.4%) of the remaining patients developed incident AF during 5 years of follow-up. AF PRS was associated with greater risk of incident AF after stroke (HR 1.16 [95% Confidence Interval (CI) 0.94-1.44] per 1 SD increase), although the association was not statistically significant. PRS improved discrimination in the first month (AUC 0.78 [95% CI 0.70-0.82] vs AUC 0.71 [95% CI 0.60-0.82], p = 0.05), with more modest estimates across longer time windows. Addition of an AF PRS to clinical risk models may improve identification of individuals at risk of AF after stroke, particularly within the first month.

Cerebral autosomal-dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL) is the most prevalent monogenic inherited cause of cerebral small-vessel disease. Despite its prevalence, there is currently no proven therapy to prevent or reverse the progression of the disease. This study aimed to characterize the functional integrity of long white matter tracts in CADASIL transgenic mice, both with and without focal white matter lesions in the corpus callosum added on, utilizing optical resting-state functional connectivity imaging alongside behavioral examinations. Additionally, we examined the efficacy of tocotrienol, a neuroprotective derivative of vitamin E derived from palm oil, which has shown promise in preventing white matter disease progression in clinical trials involving patients with small vessel disease. At baseline, resting-state inter and intrahemispheric functional connectivity was significantly lower in Notch3R169C than in Notch3WT (p=0.004), and the grid walk test revealed a higher number of foot faults in the Notch3R169C group compared to Notch3WT. Sex did not interact with the genotype on the primary outcomes. Introducing a lesion in the corpus callosum compromised functional connectivity and behavior outcomes in both genotypes to a similar extent; lesion volumes did not differ between the genotypes. Tocotrienol treatment did not show any protective effect on any endpoint. These data show impaired resting-state functional connectivity and increased foot faults in the Notch3R169C mutant model of CADASIL. Future work will aim to test therapeutic or preventive interventions in CADASIL mutants using these measures.

Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the final infarct volume (FIV) on MRI only accounts for a minority of the treatment effect. An imaging biomarker that more strongly correlates with post-EVT functional outcome would be helpful for clinical prognosis and serve as a surrogate outcome measure in trials of EVT-adjuvant therapies. Here, we aimed to validate a novel MRI-based metric, infarct density, which leverages post-EVT apparent diffusion coefficient (ADC) as a marker of infarct severity. A retrospective cohort was derived from a single-center prospective EVT registry. Consecutive anterior circulation EVT patients were included from 2018-2019 who achieved successful reperfusion (mTICI ≥2b). MRI was performed 12-48 hours post-EVT and processed via RAPID to quantify FIV using the ADC <620 threshold. Lesion volume was also collected using ADC <470 threshold, and infarct density was calculated as: (volume <470/volume <620)x100%. Good outcome was defined as ≤2 on the 90-day modified Rankin Scale. Multivariable logistic regression models quantified the association between clinical/imaging variables and outcome. ROC analysis quantified model classification performance. Of 319 EVT patients, 272 met inclusion criteria. The mean age was 69 ±13 years, 41% were female, and 62% achieved a good outcome. After adjusting for clinical and radiographic factors, FIV (aOR 0.99 per 1mL; 95%CI: 0.98-1.00; p=0.03) and infarct density (aOR 0.95 per 1%; 95%CI: 0.94-0.97; p<0.001) were both independently inversely associated with good outcome. The final model incorporating both FIV and infarct density achieved excellent classification performance (AUC 0.87; 95%CI: 0.83-0.91). Removing infarct density from the model diminished its performance (AUC 0.83; 95%CI: 0.78-0.88; p=0.01). ADC-based infarct density after EVT is independently associated with long-term outcome and provides greater prognostic information than FIV alone. Post-EVT infarct density may be useful in clinical care and as a surrogate outcome measure in trials of EVT-adjuvant therapies.

Mobile stroke units, also sometimes called Mobile Stroke Treatment Units (MSTUs) are changing the paradigm of acute stroke care and are considered to be an extension of the time is brain concept. Of the <20 active Mobile Stroke Programs in the United States, most are rooted in urban settings. In July 2023, the first MSTU in Florida was launched in Alachua County, implementing a unique and innovative rendezvous process with rural emergency medical services (EMS). We compared stroke outcome metrics between the MSTU, including rendezvous patients, and the standard process of EMS to the emergency department (ED).

Remote ischemic conditioning (RIC) is a simple and low-cost intervention that is thought to increase collateral blood flow through the vasodilatory effects of nitric oxide (NO) produced by the endothelium and red blood cells (RBCs). This study aims to investigate whether RIC affects RBC deformability and levels of NO and nitrite in patients with ischemic stroke.

There is limited data on ultra-early hematoma growth dynamics and its clinical relevance in primary intracerebral hemorrhage (ICH). We aimed to estimate the incidence of hematoma expansion (HE) within the hyperacute period of ICH, describe hematoma dynamics over time, investigate the associations between ultra-early HE and clinical outcomes after ICH, and assess the effect of tranexamic acid on ultra-early HE. We performed a planned secondary analysis of the STOP-MSU international multicenter randomized controlled trial. Repeat CT imaging ~1 hour after treatment commencement was encouraged. Patients who underwent re-imaging up to 3 hours from baseline imaging were included in this descriptive study. Hematoma expansion was defined as either a ≥33% or ≥6 ml increase from baseline hematoma volume. We included 105 patients who had 1-hour imaging (median age 66years, 40% female, 53% tranexamic acid). Median time from onset to baseline imaging was 74min (IQR 56-87min), and between baseline and 1-hour imaging was 95min (IQR 74-132min). Forty-one patients (39%) had ultra-early HE. These patients had larger baseline hematoma volumes (15.9ml vs 9.1ml, p=0.03) compared to those with no early HE. Hematoma growth rate significantly reduced over time compared to the onset-to-baseline imaging period (clustered median regression p<0.01). In 92 patients with both 1-hour and 24-hour re-imaging, further HE between the 1-hour and 24-hour imaging was more common in those with ultra-early HE (29%) compared to those without (29% vs 6.6%, p<0.01). Ultra-early HE was associated with poor functional outcomes (mRS 3-6; aOR3.87 [1.21-12.40], p=0.02) and mortality (aOR6.16 [95% CI 2.15-17.68], p<0.01), adjusted for treatment group. There was no observed effect of tranexamic acid treatment on ultra-early hematoma expansion (41% vs. 37%, p=0.65). Most hematoma growth occurs in the ultra-early period. The presence of hyperacute hematoma expansion is associated with ongoing hematoma growth, and poor clinical outcomes, and represents a target for therapeutic intervention.

A minority of patients with stroke qualify for intravenous thrombolysis (IVT) within 4.5-hour window. The safety and efficacy of IVT beyond this period have not been well studied.

Contrary to the common belief, the most commonly used laboratory C57BL/6J mouse inbred strain presents a distinctive genetic and phenotypic variability, and for several traits, the genotype-phenotype link remains still unknown. Recently, we characterized the most important stroke survival factor such as brain collateral plasticity in 2 brain ischemia C57BL/6J mouse models (bilateral common carotid artery stenosis and middle cerebral artery occlusion) and observed a Mendelian-like fashion of inheritance of the posterior communicating artery (PcomA) patency. Interestingly, a copy number variant (CNV) spanning locus was reported to segregate in an analogous Mendelian-like pattern in the C57BL/6J colonies of the Jackson Laboratory. Given critical role in vascular plasticity, we hypothesized CNV may have explained PcomA variability in C57BL/6J inbred mice.

The optimal endovascular management of cervical carotid dissection causing tandem occlusion remains uncertain. We investigated the impact of emergent carotid stenting during endovascular treatment (EVT) for acute ischemic stroke (AIS) in patients with tandem occlusion secondary to cervical carotid artery dissection. This was a secondary analysis of patients treated with EVT for AIS due to occlusive carotid artery dissection and tandem occlusion included in the retrospective international Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection (STOP-CAD) study. We compared patients with and without emergent stenting. The primary efficacy and safety outcomes were 90-day functional independence (modified Rankin Scale 0-2) and symptomatic intracranial hemorrhage (sICH) within 24h after EVT. Procedural outcome was successful intracranial recanalization (mTICI 2b/3). We used mixed-effect logistic regression adjusting for site, age, and NIHSS. In additional analyses, we used inverse probability of treatment weighting and adjusted for ASPECTS. Of the 4023 patients enrolled in STOP-CAD, 328 presented with anterior circulation AIS due to tandem occlusion and underwent EVT. The median age was 51 years (interquartile range 44-58), and 96 patients (29.3%) were female. One hundred fifty patients (45.7%) underwent emergent stenting. There was no significant association between stenting and 90-day functional independence (62.0% vs 59.7%; aOR 1.23, 95% CI 0.82-1.86, p=0.315) or sICH (7.3% vs 7.9%; aOR OR 0.95, 95% CI 0.41-2.2, p=0.913). Emergent carotid stenting was associated with successful intracranial recanalization (81.8% vs 76.6% aOR 2.62, 95% CI 1.52-4.5, p<0.001). Results did not meaningfully change in additional analyses. In patients presenting with an acute anterior circulation tandem occlusion secondary to cervical carotid artery dissection, emergent stenting was associated with a higher likelihood of successful intracranial recanalization but not improved functional outcomes or increased sICH. It remains unclear whether emergent stenting led to successful intracranial recanalization or patients with successful intracranial recanalization were more likely to be stented. Randomized trials are warranted.