Circadian Biology and the Neurovascular Unit.

Mammalian physiology and cellular function are subject to significant oscillations over the course of every 24-hour day. It is likely that these daily rhythms will affect function as well as mechanisms of disease in the central nervous system. In this review, we attempt to survey and synthesize emerging studies that investigate how circadian biology may influence the neurovascular unit. We examine how circadian clocks may operate in neural, glial, and vascular compartments, review how circadian mechanisms regulate cell-cell signaling, assess interactions with aging and vascular comorbidities, and finally ask whether and how circadian effects and disruptions in rhythms may influence the risk and progression of pathophysiology in cerebrovascular disease. Overcoming identified challenges and leveraging opportunities for future research might support the development of novel circadian-based treatments for stroke.

Twenty Years of Cardiovascular Complications and Risk Factors in Patients With Type 2 Diabetes: A Nationwide Swedish Cohort Study.

BACKGROUND: The goal of this work was to investigate trends (2001-2019) for cardiovascular events and cardiometabolic risk factor levels in individuals with type 2 diabetes (T2D) and matched control subjects. METHODS: This study included 679 072 individuals with T2D from the Swedish National Diabetes Register and 2 643 800 matched control subjects. Incident outcomes comprised coronary artery disease, acute myocardial infarction, cerebrovascular disease, and heart failure (HF). Trends in time to first event for each outcome were analyzed with Cox regression and standardized incidence rates. In the group with T2D, Cox regression was also used to assess risk factor levels beyond target and outcomes, as well as the relative importance of each risk factor to each model. RESULTS: Among individuals with T2D, incidence rates per 10 000 person-years in 2001 and 2019 were as follows: acute myocardial infarction, 73.9 (95% CI, 65.4-86.8) and 41.0 (95% CI, 39.5-42.6); coronary artery disease, 205.1 (95% CI, 186.8-227.5) and 80.2 (95% CI, 78.2-82.3); cerebrovascular disease, 83.9 (95% CI, 73.6-98.5) and 46.2 (95% CI, 44.9-47.6); and HF, 98.3 (95% CI, 89.4-112.0) and 75.9 (95% CI, 74.4-77.5). The incidence for HF plateaued around 2013, a trend that then persisted. In individuals with T2D, glycated hemoglobin, systolic blood pressure, estimated glomerular filtration rate, and lipids were independently associated with outcomes. Body mass index alone potentially explained >30% of HF risk in T2D. For those with T2D with no risk factor beyond target, there was no excess cardiovascular risk compared with control subjects except for HF, with increased hazard with T2D even when no risk factor was above target (hazard ratio, 1.50 [95% CI, 1.35-1.67]). Risk for coronary artery disease and cerebrovascular disease increased in a stepwise fashion for each risk factor not within target. Glycated hemoglobin was most prognostically important for incident atherosclerotic events, as was body mass index for incident of HF. CONCLUSIONS: Risk and rates for atherosclerotic complications and HF are generally decreasing among individuals with T2D, although HF incidence has notably plateaued in recent years. Modifiable risk factors within target levels were associated with lower risks for outcomes. This was particularly notable for systolic blood pressure and glycated hemoglobin for atherosclerotic outcomes and body mass index for heart failure.

Mechanical Thrombectomy Workshops Improve Procedural Knowledge and Skills Among Neurointerventional Teams in Low- to Middle-Income Countries.

BACKGROUND: While mechanical thrombectomy (MT) is proven to be lifesaving and disability sparing, there remains a disparity in its access in low- to middle-income countries. We hypothesized that team-based MT workshops would improve MT knowledge and skills. METHODS: We designed a 22-hour MT workshop, conducted as 2 identical events: in English (Jamaica, January 2022) and in Spanish (Dominican Republic, May 2022). The workshops included participating neurointerventional teams (practicing neurointerventionalists, neurointerventional nurses, and technicians) focused on acute stroke due to large vessel occlusion. The course faculty led didactic and hands-on components, covering topics from case selection and postoperative management to device technology and MT surgical techniques. Attendees were evaluated on stroke knowledge and MT skills before and after the course using a multiple choice exam and simulated procedures utilizing flow models under fluoroscopy, respectively. Press conferences for public education with invited government officials were included to raise stroke awareness. RESULTS: Twenty-two physicians and their teams from 8 countries across the Caribbean completed the didactic and hands-on training. Overall test scores (n=18) improved from 67% to 85% (P<0.002). Precourse and postcourse hands-on assessments demonstrated reduced time to completion from 36.5 to 21.1 minutes (P<0.001). All teams showed an improvement in measures of good MT techniques, with 39% improvement in complete reperfusion. Eight teams achieved a Thrombolysis in Cerebral Infarction score of 3 on pre-course versus 15 of 18 teams on post-course. There was a significant reduction in total potentially dangerous maneuvers (70% pre versus 20% post; P<0.002). Universally, the workshop was rated as satisfactory and likely to change practice in 93% Dominican Republic and 75% Jamaica. CONCLUSIONS: A team-based hands-on simulation approach to MT training is novel, feasible, and effective in improving procedural skills. Participants viewed these workshops as practice-changing and instrumental in creating a pathway for increasing access to MT in low- to middle-income countries.

Impact of Sleep Disorders and Disturbed Sleep on Brain Health: A Scientific Statement From the American Heart Association.

Accumulating evidence supports a link between sleep disorders, disturbed sleep, and adverse brain health, ranging from stroke to subclinical cerebrovascular disease to cognitive outcomes, including the development of Alzheimer disease and Alzheimer disease-related dementias. Sleep disorders such as sleep-disordered breathing (eg, obstructive sleep apnea), and other sleep disturbances, as well, some of which are also considered sleep disorders (eg, insomnia, sleep fragmentation, circadian rhythm disorders, and extreme sleep duration), have been associated with adverse brain health. Understanding the causal role of sleep disorders and disturbances in the development of adverse brain health is complicated by the common development of sleep disorders among individuals with neurodegenerative disease. In addition to the role of sleep disorders in stroke and cerebrovascular injury, mechanistic hypotheses linking sleep with brain health and biomarker data (blood-based, cerebrospinal fluid-based, and imaging) suggest direct links to Alzheimer disease-specific pathology. These potential mechanisms and the increasing understanding of the "glymphatic system," and the recognition of the importance of sleep in poststroke recovery, as well, support a biological basis for the indirect (through the worsening of vascular disease) and direct (through specific effects on neuropathology) connections between sleep disorders and brain health. Given promising evidence for the benefits of treatment and prevention, sleep disorders and disturbances represent potential targets for early treatment that may improve brain health more broadly. In this scientific statement, we discuss the evidence supporting an association between sleep disorders and disturbances and poor brain health ranging from stroke to dementia and opportunities for prevention and early treatment.

Cortical Spreading Depolarization in Moyamoya Vasculopathy: A Case Series.

BACKGROUND: Spreading depolarization describes a near-complete electrical discharge with altered local cerebral blood flow. It is described in association with acute and chronic diseases like hemorrhagic stroke or migraine. Moyamoya vasculopathy is a chronic, progressive cerebrovascular disorder leading to cerebral hypoperfusion, hemodynamically insufficient basal collateralization, and increased cortical microvascularization. METHODS: In a prospective case series, we monitored for spontaneous spreading depolarization activity by using intraoperative laser speckle imaging for real-time visualization and measurement of cortical perfusion and cerebrovascular reserve capacity during cerebral revascularization in 4 consecutive patients with moyamoya. RESULTS: Spontaneous spreading depolarization occurrence was documented in a patient with moyamoya before bypass grafting. Interestingly, this patient also exhibited a marked preoperative increase in angiographic collateral vessel formation. CONCLUSIONS: The spontaneous occurrence of SDs in moyamoya vasculopathy could potentially provide an explanation for localized cortical infarction and increased cortical microvascular density in these patients.

Overweight in Adolescence and Young Adulthood in Association With Adult Cerebrovascular Disease: The NFBC1966 Study.

BACKGROUND: Risk factors for cerebrovascular disease in adulthood are well known. However, research on individuals' risk factors throughout their life span has been limited. This prospective cohort study aims to determine the effect of body mass index (BMI) and its changes in adolescence and young adulthood on early onset cerebrovascular disease. METHODS: This study includes 10 491 people (5185 women) from the Northern Finland Birth Cohort 1966. Height, weight, and BMI were measured at ages 14 and 31 years. Sex- and age-specific BMI ranges were used to define overweight and obesity. Data on ischemic and hemorrhagic cerebrovascular diseases between ages 14 and 54 years were extracted from national hospital and death registers. Cox proportion hazard models (95% CI) were used to estimate associations between BMI or its changes and cerebrovascular disease, while adjusting for sex, smoking, educational level, BMI at the other time point, and age at menarche for women. Additionally, sex-BMI interactions were calculated. RESULTS: A total of 452 individuals (4.7%) experienced cerebrovascular disease during the follow-up. The risk of ischemic cerebrovascular disease was increased for overweight women at ages 14 years (hazard ratio [HR], 2.49 [95% CI, 1.44-4.31]) and 31 years (HR, 2.13 [95% CI, 1.14-3.97]), as well as for obese women at ages 14 years (HR, 1.87 [95% CI, 0.76-4.58) and 31 years (HR, 2.67 [95% CI, 1.26-5.65]), with normal weight as the reference. These results were independent of earlier or later BMI. Similar associations were not found among men. The risk of hemorrhagic cerebrovascular disease was increased at age 31 years both among obese women (HR, 3.49 [95% CI, 1.13-10.7) and obese men (HR, 5.75 [95% CI, 1.43-23.1). The risk of any cerebrovascular disease related to overweight at age 14 years was 2.09× higher among girls than boys (95% CI, 1.06-4.15). The risk of ischemic cerebrovascular disease related to obesity at age 31 years was 6.96× higher among women than men (95% CI, 1.36-35.7). CONCLUSIONS: Among women, being overweight in adolescence or young adulthood increases the risk of cerebrovascular disease, especially ischemic, independent of their earlier or later BMI.

Cerebral dural arteriovenous fistulas in patients with PTEN-related hamartoma tumor syndrome.

Central nervous system (CNS) dural arteriovenous fistulas (DAVF) have been reported in PTEN-related hamartoma tumor syndrome (PHTS). However, PHTS-associated DAVF remain an underexplored field of the PHTS clinical landscape. Here, we studied cases with a PTEN pathogenic variant identified between 2007 and 2020 in our laboratory (n = 58), and for whom brain imaging was available. Two patients had DAVF (2/58, 3.4%), both presenting at advanced stages: a 34-year-old man with a left lateral sinus DAVF at immediate risk of hemorrhage, and a 21-year-old woman with acute intracranial hypertension due to a torcular DAVF. Interestingly, not all patients had 3D TOF/MRA, the optimal sequences to detect DAVF. Early diagnosis of DAVF can be lifesaving, and is easier to treat compared to developed, proliferative, or complex lesions. As a result, one should consider brain MRI with 3D TOF/MRA in PHTS patients at genetic diagnosis, with subsequent surveillance on a case-by-case basis.

The collateral map: prediction of lesion growth and penumbra after acute anterior circulation ischemic stroke.

OBJECTIVES: This study evaluated the collateral map's ability to predict lesion growth and penumbra after acute anterior circulation ischemic strokes. METHODS: This was a retrospective analysis of selected data from a prospectively collected database. The lesion growth ratio was the ratio of the follow-up lesion volume to the baseline lesion volume on diffusion-weighted imaging (DWI). The time-to-maximum (Tmax)/DWI ratio was the ratio of the baseline Tmax > 6 s volume to the baseline lesion volume. The collateral ratio was the ratio of the hypoperfused lesion volume of the phase_FU (phase with the hypoperfused lesions most approximate to the follow-up DWI lesion) to the hypoperfused lesion volume of the phase_baseline of the collateral map. Multiple logistic regression analyses were conducted to identify independent predictors of lesion growth. The concordance correlation coefficients of Tmax/DWI ratio and collateral ratio for lesion growth ratio were analyzed. RESULTS: Fifty-two patients, including twenty-six males (mean age, 74 years), were included. Intermediate (OR, 1234.5; p < 0.001) and poor collateral perfusion grades (OR, 664.7; p = 0.006) were independently associated with lesion growth. Phase_FUs were immediately preceded phases of the phase_baselines in intermediate or poor collateral perfusion grades. The concordance correlation coefficients of the Tmax/DWI ratio and collateral ratio for the lesion growth ratio were 0.28 (95% CI, 0.17-0.38) and 0.88 (95% CI, 0.82-0.92), respectively. CONCLUSION: Precise prediction of lesion growth and penumbra can be possible using collateral maps, allowing for personalized application of recanalization treatments. Further studies are needed to generalize the findings of this study. CLINICAL RELEVANCE STATEMENT: Precise prediction of lesion growth and penumbra can be possible using collateral maps, allowing for personalized application of recanalization treatments. KEY POINTS: • Cell viability in cerebral ischemia due to proximal arterial steno-occlusion mainly depends on the collateral circulation. • The collateral map shows salvageable brain extent, which can survive by recanalization treatments after acute anterior circulation ischemic stroke. • Precise estimation of salvageable brain makes it possible to make patient-specific treatment decision.

Ambient air pollution, covert cerebrovascular disease and cognition: results from the ISSYS study.

BACKGROUND AND PURPOSE: Although air pollution (AP) has been associated with stroke and dementia, data regarding its relationship with covert cerebrovascular disease (cCVD) and cognition over time are sparse. The aim of this study was to explore these relationships. METHODS: A prospective population-based study of 976 stroke-free and non-demented individuals living in Barcelona, Spain, was conducted during 2010-2016. A land use regression model was used to estimate the exposure of each participant to AP: NOx, NO2, PM2.5, PM10, PMcoarse and PM2.5 absorbance. Cognitive function and cCVD were assessed at baseline (n = 976) and 4 years after (n = 317). Multivariate-adjusted models were developed. RESULTS: At baseline, 99 participants (10.1%) had covert brain infarcts and 91 (9.3%) had extensive periventricular white matter hyperintensities (WMHs). Marked subcortical WMH progression was seen in 19.7%; the incidence of other covert cerebrovascular lessons ranged between 5% and 6% each. PM2.5 was related to higher odds of having a covert brain infarct (odds ratio [OR] 2.21; 95% confidence interval [CI] 1.06-4.60). PM2.5 absorbance was related to higher odds of having extensive subcortical WMHs (OR 1.72; 95% CI 1.13-2.60), whereas NO2 was related to higher odds of having extensive subcortical (OR 1.66; 95% CI 1.17-2.35) or periventricular (OR 1.96; 95% CI 1.10-3.50) WMHs and to higher odds of developing marked subcortical WMH progression (OR 1.40; 95% CI 1.05-1.90). NOx was related to incident cerebral microbleeds (OR 1.36; 95% CI 1.04-1.79). There was no association between AP and cognition. CONCLUSIONS: Air pollutant predicts the presence and accumulation of cCVD. Its impact on cognitive impairment remains to be determined.

Impact of Stent Size Selection and Vessel Evaluation on Skull Base Cerebrovascular Diseases Treated With Willis Covered Stents: A Multicenter Retrospective Analysis.

PURPOSE: This study aimed to evaluate the impact of the diverse stent size selection on the clinical and angiographic outcomes of Willis covered stent (WCS) for the treatment of skull base cerebrovascular diseases. MATERIALS AND METHODS: A total of 147 patients with 151 skull base cerebrovascular diseases treated with WCS in 3 centers between January 2015 and July 2022 were included in this study. Several parameters depicting stent size and parent artery condition were incorporated into the analysis of the outcomes. RESULTS: Complete occlusion was found in 106 cases (68.2%) immediately after deployment and 126 cases (83.4%) after technical adjustment. In the multivariate logistics analysis, the difference between stent diameter and parent artery diameter (DD) was significantly associated with immediate endoleak without adjustment (odds ratio [OR]=0.410; p=0.005) and late endoleak (OR=0.275; p=0.028). In addition, differences between stent diameter and parent artery diameter at wide landing point (DSW) and differences between stent diameter and parent artery diameter at narrow landing point (DSN) was also was significant associated with immediate endoleak without adjustment and balloon re-dilation respectively. CONCLUSIONS: This study demonstrated that the diameter selection of the WCS was associated with the occurrence of endoleak during the treatment of skull base cerebrovascular diseases. Precise selection and evaluation of stent size and vessel condition were significant factors for skull base cerebrovascular diseases treated by WCS. CLINICAL IMPACT: This study demonstrates a significant association between the diameter selection of the Willis covered stent (WCS) and the occurrence of endoleak in the management of skull base cerebrovascular diseases. The results offer valuable medical evidence that can inform stent selection for WCS. The study emphasizes the significance of precise evaluation of stent size and vessel condition as crucial factors in WCS procedures. These findings underscore the importance of meticulous consideration and individualized approaches to stent selection, ultimately improving treatment outcomes in clinical practice.

Prevalence and 3-month follow-up of cerebrovascular MRI markers in hospitalized COVID-19 patients: the CORONIS study.

PURPOSE: To investigate the prevalence of cerebrovascular MRI markers in unselected patients hospitalized for COVID-19 (Coronavirus disease 2019), we compared these with healthy controls without previous SARS-CoV-2 infection or hospitalization and subsequently, investigated longitudinal (incidental) lesions in patients after three months. METHODS: CORONIS (CORONavirus and Ischemic Stroke) was an observational cohort study in adult hospitalized patients for COVID-19 and controls without COVID-19, conducted between April 2021 and September 2022. Brain MRI was performed shortly after discharge and after 3 months. Outcomes included recent ischemic (DWI-positive) lesions, previous infarction, microbleeds, white matter hyperintensities (WMH) and intracerebral hemorrhage and were analysed with logistic regression to adjust for confounders. RESULTS: 125 patients with COVID-19 and 47 controls underwent brain MRI a median of 41.5 days after symptom onset. DWI-positive lesions were found in one patient (1%) and in one (2%) control, both clinically silent. WMH were more prevalent in patients (78%) than in controls (62%) (adjusted OR: 2.95 [95% CI: 1.07-8.57]), other cerebrovascular MRI markers did not differ. Prevalence of markers in ICU vs. non-ICU patients was similar. After three months, five patients (5%) had new cerebrovascular lesions, including DWI-positive lesions (1 patient, 1.0%), cerebral infarction (2 patients, 2.0%) and microbleeds (3 patients, 3.1%). CONCLUSION: Overall, we found no higher prevalence of cerebrovascular markers in unselected hospitalized COVID-19 patients compared to controls. The few incident DWI-lesions were most likely to be explained by risk-factors of small vessel disease. In the general hospitalized COVID-19 population, COVID-19 shows limited impact on cerebrovascular MRI markers shortly after hospitalization.

Long-term multisystemic efficacy of migalastat on Fabry-associated clinical events, including renal, cardiac and cerebrovascular outcomes.

BACKGROUND: Fabry disease is a rare, multisystemic disorder caused by GLA gene variants that lead to alpha galactosidase A deficiency, resulting in accumulation of glycosphingolipids and cellular dysfunction. Fabry-associated clinical events (FACEs) cause significant morbidity and mortality, yet the long-term effect of Fabry therapies on FACE incidence remains unclear. METHODS: This posthoc analysis evaluated incidence of FACEs (as a composite outcome and separately for renal, cardiac and cerebrovascular events) in 97 enzyme replacement therapy (ERT)-naïve and ERT-experienced adults with Fabry disease and amenable GLA variants who were treated with migalastat for up to 8.6 years (median: 5 years) in Phase III clinical trials of migalastat. Associations between baseline characteristics and incidence of FACEs were also evaluated. RESULTS: During long-term migalastat treatment, 17 patients (17.5%) experienced 22 FACEs and there were no deaths. The incidence rate of FACEs was 48.3 events per 1000 patient-years overall. Numerically higher incidence rates were observed in men versus women, patients aged >40 years versus younger patients, ERT-naïve versus ERT-experienced patients and men with the classic phenotype versus men and women with all other phenotypes. There was no statistically significant difference in time to first FACE when analysed by patient sex, phenotype, prior treatment status or age. Lower baseline estimated glomerular filtration rate (eGFR) was associated with an increased risk of FACEs across patient populations. CONCLUSIONS: The overall incidence of FACEs for patients during long-term treatment with migalastat compared favourably with historic reports involving ERT. Lower baseline eGFR was a significant predictor of FACEs.

The aneurysm occlusion and recurrence of posterior communicating artery aneurysms following the treatment with the pipeline embolization device.

Despite advancements in treatment modalities such as flow diverters, the optimal management of posterior communicating artery (PComA) aneurysms remains uncertain. While PComA aneurysms treated with the Pipeline Embolization Device (PED) has been reported, the characteristics and progression of incomplete occluded aneurysms remain unclear. Therefore, our study aims to investigate the occlusion status and recurrence rates of PComA aneurysms treated with PED. A retrospective review of consecutive PComA aneurysm patients treated with PED was conducted between January 2015 and December 2020. Only patients with radiological follow-up were included. PComA aneurysms were categorized into incomplete occlusion and complete occlusion group. The primary outcomes included the characteristics of incomplete occlusion at the follow-up angiography. Among 121 PComA aneurysms treated with PED at our institution, 80 aneurysms were eligible in our study. During the follow-up period, 19 (23.8%) aneurysms demonstrated incomplete occlusion. Notably, there were no instances of recurrence among the 80 followed-up cases. Baseline characteristics of patients and aneurysms were comparable between the groups with complete and incomplete occlusion. However, the incomplete occlusion group showed a lower rate of assisted coils embolization (21.2% vs. 55.7%, P = 0.017) and shorter median operative time (91.0 vs. 145.5 min, P = 0.039). Differences in functional outcomes, complications, and PComA occlusion status between the groups were not significant. Multivariate analysis revealed the use of coils was associated with lower odds of incomplete PComA aneurysm occlusion (OR 0.01, 95% CI 0.001-0.12; P = 0.001), while aneurysm size was associated with higher odds of incomplete occlusion (OR 1.25, 95% CI 1.10-1.46; P = 0.002). The treatment of PED for PComA aneurysm demonstrated favorable outcomes, with an acceptable rate of incomplete occlusion and no instances of recurrence observed. However, further research is needed to explore the optimal procedural strategy for large-sized PComA aneurysms.

Challenges and needs in cerebrovascular disease pathway: A qualitative descriptive study from the patients' and healthcare professionals' perspectives.

AIM(S): To understand patients' and healthcare professionals' experiences to improve care in and across different domains of the cerebrovascular disease pathway. DESIGN: A qualitative descriptive study. METHODS: Semi-structured in-person interviews were conducted among 22 patients diagnosed with acute cerebrovascular disease and 26 healthcare professionals taking care of them in a single tertiary-level hospital from August 2021 to March 2022. Data were analysed using deductive and inductive content analysis. The consolidated criteria for reporting qualitative research was used to ensure reliable reporting. RESULTS: Overall, 19 generic and 79 sub-categories describing perceived challenges with 17 generic and 62 sub-categories describing perceived needs were identified related to primary prevention, organization of stroke services, management of acute stroke, secondary prevention, rehabilitation, evaluation of stroke outcome and quality assessment, and life after stroke. CONCLUSION: Several challenges and needs were identified in and across the different domains of the cerebrovascular disease pathway. There is a requirement for adequate resources, early initiation of treatment, early diagnostics and recanalization, dedicated rehabilitation services, long-term counselling and support, and impact evaluation of services to improve cerebrovascular disease care. Future research on caregivers', and clinical leadership experiences in and across the cerebrovascular disease pathway is needed to explore the provision of services. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The results of this study can be applied by organizations, managers and research for developing and improving services in the cerebrovascular disease pathway. IMPACT: This study identified several patient-related, organizational and logistical needs and challenges, with suggestions for required actions, that can benefit the provision of effective, high-quality cerebrovascular disease care. REPORTING METHOD: We have adhered to relevant EQUATOR guidelines with the COREQ reporting method. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

Is early initiated cardiorespiratory fitness training within a model of stroke-integrated cardiac rehabilitation safe and feasible?

OBJECTIVE: To investigate the safety and feasibility of an early initiated stroke-integrated Cardiac Rehabilitation program. METHODS: People with acute first or recurrent ischaemic stroke, admitted to Epworth HealthCare were screened for eligibility and invited to participate. In addition to usual care neurorehabilitation, participants performed 1) cardiorespiratory fitness training 3-days/week during inpatient rehabilitation (Phase 1), and/or 2) 2-days/week centre-based cardiorespiratory fitness training plus education and 1-day/week home-based cardiorespiratory fitness training for 6-weeks during outpatient rehabilitation (Phase 2). Safety was determined by the number of adverse and serious adverse events. Feasibility was determined by participant recruitment, retention, and attendance rates, adherence to exercise recommendations, and participant satisfaction. RESULTS: There were no study-related adverse or serious adverse events. Of 117 eligible stroke admissions, 62 (53%) were recruited, while 10 (16.1%) participants withdrew. Participants attended 189 of 201 (94%) scheduled cardiorespiratory fitness training sessions in Phase 1 and 341/381 (89.5%) scheduled sessions in Phase 2. Only 220/381 (58%) scheduled education sessions were attended. The minimum recommended cardiorespiratory fitness training intensity (40% heart rate reserve) and duration (20 minutes) was achieved by 57% and 55% of participants respectively during Phase 1, and 60% and 92% respectively during Phase 2. All respondents strongly agreed (69%) or agreed (31%) they would recommend the stroke-integrated Cardiac Rehabilitation program to other people with stroke. CONCLUSION: Cardiorespiratory fitness training in line with multiple clinical practice guidelines included within a model of stroke-integrated Cardiac Rehabilitation appears to be safe and feasible in the early subacute phase post-stroke.

Management of Stroke in Patients With Chronic Liver Disease: A Practical Review.

Chronic liver disease (CLD) is a highly prevalent condition. There is burgeoning recognition that there are many people with subclinical liver disease that may nonetheless be clinically significant. CLD has a variety of systemic aberrations relevant to stroke, including thrombocytopenia, coagulopathy, elevated liver enzymes, and altered drug metabolism. There is a growing body of literature on the intersection of CLD and stroke. Despite this, there have been few efforts to synthesize these data, and stroke guidelines provide scant guidance on this topic. To fill this gap, this multidisciplinary review provides a contemporary overview of CLD for the vascular neurologist while appraising data regarding the impact of CLD on stroke risk, mechanisms, and outcomes. Finally, the review addresses acute and chronic treatment considerations for patients with stroke-ischemic and hemorrhagic-and CLD.

Risk of Midlife Stroke After Adverse Pregnancy Outcomes: The FinnGen Study.

BACKGROUND: Adverse pregnancy outcomes (APO) contribute to higher risk of maternal cerebrovascular disease, but longitudinal data that include APO and stroke timing are lacking. We hypothesized that APO are associated with younger age at first stroke, with a stronger relationship in those with >1 pregnancy with APO. METHODS: We analyzed longitudinal Finnish nationwide health registry data from the FinnGen Study. We included women who gave birth after 1969 when the hospital discharge registry was established. We defined APO as a pregnancy affected by gestational hypertension, preeclampsia, eclampsia, preterm birth, small for gestational age infant, or placental abruption. We defined stroke as first hospital admission for ischemic stroke or nontraumatic intracerebral or subarachnoid hemorrhage, excluding stroke during pregnancy or within 1 year postpartum. We used Kaplan-Meier survival curves and multivariable-adjusted Cox and generalized linear models to assess the relationship between APO and future stroke. RESULTS: We included 144 306 women with a total of 316 789 births in the analysis sample, of whom 17.9% had at least 1 pregnancy with an APO and 2.9% experienced an APO in ≥2 pregnancies. Women with APO had more comorbidities including obesity, hypertension, heart disease, and migraine. Median age at first stroke was 58.3 years in those with no APO, 54.8 years in those with 1 APO, and 51.6 years in those with recurrent APO. In models adjusted for sociodemographic characteristics and stroke risk factors, risk of stroke was greater in women with 1 APO (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.4]) and recurrent APO (adjusted hazard ratio, 1.4 [95% CI, 1.2-1.7]) compared with those with no APO. Women with recurrent APO had more than twice the stroke risk before age 45 (adjusted odds ratio, 2.1 [95% CI, 1.5-3.1]) compared with those without APO. CONCLUSIONS: Women who experience APO have earlier onset of cerebrovascular disease, with the earliest onset in those with more than 1 affected pregnancy.

Cost-Effectiveness of Smoking Cessation Interventions in Patients With Ischemic Stroke and Transient Ischemic Attack.

BACKGROUND: Smoking cessation rates after stroke and transient ischemic attack are suboptimal, and smoking cessation interventions are underutilized. We performed a cost-effectiveness analysis of smoking cessation interventions in this population. METHODS: We constructed a decision tree and used Markov models that aimed to assess the cost-effectiveness of varenicline, any pharmacotherapy with intensive counseling, and monetary incentives, compared with brief counseling alone in the secondary stroke prevention setting. Payer and societal costs of interventions and outcomes were modeled. The outcomes were recurrent stroke, myocardial infarction, and death using a lifetime horizon. Estimates and variance for the base case (35% cessation), costs and effectiveness of interventions, and outcome rates were imputed from the stroke literature. We calculated incremental cost-effectiveness ratios and incremental net monetary benefits. An intervention was considered cost-effective if the incremental cost-effectiveness ratio was less than the willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY) or when the incremental net monetary benefit was positive. Probabilistic Monte Carlo simulations modeled the impact of parameter uncertainty. RESULTS: From the payer perspective, varenicline and pharmacotherapy with intensive counseling were associated with more QALYs (0.67 and 1.00, respectively) at less total lifetime costs compared with brief counseling alone. Monetary incentives were associated with 0.71 more QALYs at an additional cost of $120 compared with brief counseling alone, yielding an incremental cost-effectiveness ratio of $168/QALY. From the societal perspective, all 3 interventions provided more QALYs at less total costs compared with brief counseling alone. In 10 000 Monte Carlo simulations, all 3 smoking cessation interventions were cost-effective in >89% of runs. CONCLUSIONS: For secondary stroke prevention, it is cost-effective and potentially cost-saving to deliver smoking cessation therapy beyond brief counseling alone.

Comparison of Prehospital Assessment by Paramedics and In-Hospital Assessment by Physicians in Suspected Stroke Patients: Results From 2 Prospective Cohort Studies.

BACKGROUND: It is unknown if ambulance paramedics adequately assess neurological deficits used for prehospital stroke scales to detect anterior large-vessel occlusions. We aimed to compare prehospital assessment of these stroke-related deficits by paramedics with in-hospital assessment by physicians. METHODS: We used data from 2 prospective cohort studies: the LPSS (Leiden Prehospital Stroke Study) and PRESTO study (Prehospital Triage of Patients With Suspected Stroke). In both studies, paramedics scored 9 neurological deficits in stroke code patients in the field. Trained physicians scored the National Institutes of Health Stroke Scale (NIHSS) at hospital presentation. Patients with transient ischemic attack were excluded because of the transient nature of symptoms. Spearman rank correlation coefficient (rs) was used to assess correlation between the total prehospital assessment score, defined as the sum of all prehospital items, and the total NIHSS score. Correlation, sensitivity and specificity were calculated for each prehospital item with the corresponding NIHSS item as reference. RESULTS: We included 2850 stroke code patients. Of these, 1528 had ischemic stroke, 243 intracranial hemorrhage, and 1079 stroke mimics. Correlation between the total prehospital assessment score and NIHSS score was strong (rs=0.70 [95% CI, 0.68-0.72]). Concerning individual items, prehospital assessment of arm (rs=0.68) and leg (rs=0.64) motor function correlated strongest with corresponding NIHSS items, and had highest sensitivity (arm 95%, leg 93%) and moderate specificity (arm 71%, leg 70%). Neglect (rs=0.31), abnormal speech (rs=0.50), and gaze deviation (rs=0.51) had weakest correlations. Neglect and gaze deviation had lowest sensitivity (52% and 66%) but high specificity (84% and 89%), while abnormal speech had high sensitivity (85%) but lowest specificity (65%). CONCLUSIONS: The overall prehospital assessment of stroke code patients correlates strongly with in-hospital assessment. Prehospital assessment of neglect, abnormal speech, and gaze deviation differed most from in-hospital assessment. Focused training on these deficits may improve prehospital triage.

Cerebrovascular Reactivity in Patients With Small Vessel Disease: A Cross-Sectional Study.

BACKGROUND: Cerebrovascular reactivity (CVR) is inversely related to white matter hyperintensity severity, a marker of cerebral small vessel disease (SVD). Less is known about the relationship between CVR and other SVD imaging features or cognition. We aimed to investigate these cross-sectional relationships. METHODS: Between 2018 and 2021 in Edinburgh, we recruited patients presenting with lacunar or cortical ischemic stroke, whom we characterized for SVD features. We measured CVR in subcortical gray matter, normal-appearing white matter, and white matter hyperintensity using 3T magnetic resonance imaging. We assessed cognition using Montreal Cognitive Assessment. Statistical analyses included linear regression models with CVR as outcome, adjusted for age, sex, and vascular risk factors. We reported regression coefficients with 95% CIs. RESULTS: Of 208 patients, 182 had processable CVR data sets (median age, 68.2 years; 68% men). Although the strength of association depended on tissue type, lower CVR in normal-appearing tissues and white matter hyperintensity was associated with larger white matter hyperintensity volume (BNAWM=-0.0073 [95% CI, -0.0133 to -0.0014] %/mm Hg per 10-fold increase in percentage intracranial volume), more lacunes (BNAWM=-0.00129 [95% CI, -0.00215 to -0.00043] %/mm Hg per lacune), more microbleeds (BNAWM=-0.00083 [95% CI, -0.00130 to -0.00036] %/mm Hg per microbleed), higher deep atrophy score (BNAWM=-0.00218 [95% CI, -0.00417 to -0.00020] %/mm Hg per score point increase), higher perivascular space score (BNAWM=-0.0034 [95% CI, -0.0066 to -0.0002] %/mm Hg per score point increase in basal ganglia), and higher SVD score (BNAWM=-0.0048 [95% CI, -0.0075 to -0.0021] %/mm Hg per score point increase). Lower CVR in normal-appearing tissues was related to lower Montreal Cognitive Assessment without reaching convention statistical significance (BNAWM=0.00065 [95% CI, -0.00007 to 0.00137] %/mm Hg per score point increase). CONCLUSIONS: Lower CVR in patients with SVD was related to more severe SVD burden and worse cognition in this cross-sectional analysis. Longitudinal analysis will help determine whether lower CVR predicts worsening SVD severity or vice versa. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: ISRCTN12113543.