Radiological examination of the brain is a critical determinant of stroke care pathways. Accessible neuroimaging is essential to detect the presence of intracerebral hemorrhage (ICH). Conventional ...magnetic resonance imaging (MRI) operates at high magnetic field strength (1.5-3 T), which requires an access-controlled environment, rendering MRI often inaccessible. We demonstrate the use of a low-field MRI (0.064 T) for ICH evaluation. Patients were imaged using conventional neuroimaging (non-contrast computerized tomography (CT) or 1.5/3 T MRI) and portable MRI (pMRI) at Yale New Haven Hospital from July 2018 to November 2020. Two board-certified neuroradiologists evaluated a total of 144 pMRI examinations (56 ICH, 48 acute ischemic stroke, 40 healthy controls) and one ICH imaging core lab researcher reviewed the cases of disagreement. Raters correctly detected ICH in 45 of 56 cases (80.4% sensitivity, 95%CI: 0.68-0.90). Blood-negative cases were correctly identified in 85 of 88 cases (96.6% specificity, 95%CI: 0.90-0.99). Manually segmented hematoma volumes and ABC/2 estimated volumes on pMRI correlate with conventional imaging volumes (ICC = 0.955, p = 1.69e-30 and ICC = 0.875, p = 1.66e-8, respectively). Hematoma volumes measured on pMRI correlate with NIH stroke scale (NIHSS) and clinical outcome (mRS) at discharge for manual and ABC/2 volumes. Low-field pMRI may be useful in bringing advanced MRI technology to resource-limited settings.
Approximately 10% of dementia patients have idiopathic normal pressure hydrocephalus (iNPH), an expansion of the cerebrospinal fluid (CSF)-filled brain ventricles. iNPH and Alzheimer’s disease (AD) ...both exhibit sleep disturbances, build-up of brain metabolic wastes and amyloid-β (Aβ) plaques, perivascular reactive astrogliosis, and mislocalization of astrocyte aquaporin-4 (AQP4). The glia–lymphatic (glymphatic) system facilitates brain fluid clearance and waste removal during sleep via glia-supported perivascular channels. Human studies have implicated impaired glymphatic function in both AD and iNPH. Continued investigation into the role of glymphatic system biology in AD and iNPH models could lead to new strategies to improve brain health by restoring homeostatic brain metabolism and CSF dynamics.
iNPH constitutes ∼10% of the 50 million people currently diagnosed with a dementia-related disorder. This is expected to exceed 150 million by 2050.iNPH and AD share multiple clinical and pathologic features such as Aβ deposition, cerebrovascular inflammation, impaired localization of perivascular AQP4, and sleep disturbances.Although glymphatic system dysfunction has been extensively studied in AD, it has not yet been thoroughly examined in model systems of iNPH and other types of hydrocephalus.Several studies analyzing brain magnetic resonance imaging of human iNPH patients have shown reduced perivascular influx and efflux of intrathecally injected contrast agent compared to controls, suggesting impairment of glymphatic function iNPH.The relationship between glymphatic system function and iNPH requires further investigation because it may point toward identifiable risk factors or therapeutic targets.
Epigenetics refers to chromatin-based pathways important in the regulation of gene expression and includes 3 distinct, but highly interrelated, mechanismsDNA methylation, histone density and ...posttranslational modifications, and RNA-based mechanisms. Together, they offer a newer perspective on transcriptional control paradigms in vascular endothelial cells and provide a molecular basis for how the environment impacts the genome to modify disease susceptibility. This review provides an introduction to epigenetic concepts for vascular biologists. Using endothelial nitric oxide synthase (NOS3) as an example, we examine the growing body of evidence implicating epigenetic pathways in the control of vascular endothelial gene expression in health and disease.
IMPORTANCE: Unruptured intracranial aneurysms (UIAs) are relatively common in the general population and are being increasingly diagnosed; a significant proportion are tiny (≤3 mm) aneurysms. There ...is significant heterogeneity in practice and lack of clear guidelines on the management of incidental, tiny UIAs. It is important to quantify the implications of different management strategies in terms of health benefits to patients. OBJECTIVE: To evaluate the effectiveness of routine treatment (aneurysm coiling) vs 3 strategies for imaging surveillance compared with no preventive treatment or routine follow-up of tiny UIAs. DESIGN, SETTING, AND PARTICIPANTS: A decision-analytic model-based comparative effectiveness analysis was conducted from May 1 to June 30, 2017, using inputs from the medical literature. PubMed searches were performed to identify relevant literature for all key model inputs, each of which was derived from the clinical study with the most robust data and greatest applicability. Analysis included 10 000 iterations simulating adult patients with incidental detections of UIAs 3 mm or smaller and no history of subarachnoid hemorrhage. INTERVENTIONS: The following 5 management strategies for tiny UIAs were evaluated: annual magnetic resonance angiography (MRA) screening, biennial MRA screening, MRA screening every 5 years, aneurysm coiling and follow-up, and no treatment or preventive follow-up. MAIN OUTCOMES AND MEASURES: A Markov decision model for lifetime rupture was constructed from a societal perspective per 10 000 patients with incidental, tiny UIAs. Outcomes were assessed in terms of quality-adjusted life-years. Probabilistic, 1-way, and 2-way sensitivity analyses were performed. RESULTS: In this analysis of 10 000 iterations simulating adult patients with a mean age of 50 years, the base-case calculation shows that the management strategy of no treatment or preventive follow-up has the highest health benefit (mean SD quality-adjusted life-years, 19.40 0.31). Among the management strategies that incorporate follow-up imaging, MRA every 5 years is the best strategy with the next highest effectiveness (mean SD quality-adjusted life-years, 18.05 0.62). The conclusion remains robust in probabilistic and 1-way sensitivity analyses. No routine follow-up remains the optimal strategy when the annual growth rate and risk of rupture of growing aneurysms are varied. When the annual risk of rupture of nongrowing UIAs is less than 1.7% (0.23% in base case scenario), no follow-up is the optimal strategy. If annual risk of rupture is more than 1.7%, coiling should be performed directly. CONCLUSIONS AND RELEVANCE: Given the current literature, no preventive treatment or imaging follow-up is the most effective strategy in patients with aneurysms that are 3 mm or smaller, resulting in better health outcomes. More aggressive imaging surveillance for aneurysm growth or preventive treatment should be reserved for patients with a high risk of rupture. Given these findings, it is important to critically evaluate the appropriateness of current clinical practices, and potentially determine specific guidelines to reflect the most effective management strategy for patients with incidental, tiny UIAs.
Flow diversion for posterior circulation aneurysms performed using the Pipeline embolization device (PED) constitutes an increasingly common off-label use for otherwise untreatable aneurysms. The ...safety and efficacy of this treatment modality has not been assessed in a multicenter study.
A retrospective review of prospectively maintained databases at 8 academic institutions was performed for the years 2009 to 2016 to identify patients with posterior circulation aneurysms treated with PED placement.
A total of 129 consecutive patients underwent 129 procedures to treat 131 aneurysms; 29 dissecting, 53 fusiform, and 49 saccular lesions were included. At a median follow-up of 11 months, complete and near-complete occlusion was recorded in 78.1%. Dissecting aneurysms had the highest occlusion rate and fusiform the lowest. Major complications were most frequent in fusiform aneurysms, whereas minor complications occurred most commonly in saccular aneurysms. In patients with saccular aneurysms, clopidogrel responders had a lower complication rate than did clopidogrel nonresponders. The majority of dissecting aneurysms were treated in the immediate or acute phase following subarachnoid hemorrhage, a circumstance that contributed to the highest mortality rate in those aneurysms.
In the largest series to date, fusiform aneurysms were found to have the lowest occlusion rate and the highest frequency of major complications. Dissecting aneurysms, frequently treated in the setting of subarachnoid hemorrhage, occluded most often and had a low complication rate. Saccular aneurysms were associated with predominantly minor complications, particularly in clopidogrel nonresponders.
BACKGROUND:Anecdotal reports suggest fewer patients with stroke symptoms are presenting to hospitals during the coronavirus disease 2019 (COVID-19) pandemic. We quantify trends in stroke code calls ...and treatments at 3 Connecticut hospitals during the local emergence of COVID-19 and examine patient characteristics and stroke process measures at a Comprehensive Stroke Center (CSC) before and during the pandemic.
METHODS:Stroke code activity was analyzed from January 1 to April 28, 2020, and corresponding dates in 2019. Piecewise linear regression and spline models identified when stroke codes in 2020 began to decline and when they fell below 2019 levels. Patient-level data were analyzed in February versus March and April 2020 at the CSC to identify differences in patient characteristics during the pandemic.
RESULTS:A total of 822 stroke codes were activated at 3 hospitals from January 1 to April 28, 2020. The number of stroke codes/wk decreased by 12.8/wk from February 18 to March 16 (P=0.0360) with nadir of 39.6% of expected stroke codes called from March 10 to 16 (30% decrease in total stroke codes during the pandemic weeks in 2020 versus 2019). There was no commensurate increase in within-network telestroke utilization. Compared with before the pandemic (n=167), pandemic-epoch stroke code patients at the CSC (n=211) were more likely to have histories of hypertension, dyslipidemia, coronary artery disease, and substance abuse; no or public health insurance; lower median household income; and to live in the CSC city (P<0.05). There was no difference in age, sex, race/ethnicity, stroke severity, time to presentation, door-to-needle/door-to-reperfusion times, or discharge modified Rankin Scale.
CONCLUSIONS:Hospital presentation for stroke-like symptoms decreased during the COVID-19 pandemic, without differences in stroke severity or early outcomes. Individuals living outside of the CSC city were less likely to present for stroke codes at the CSC during the pandemic. Public health initiatives to increase awareness of presenting for non-COVID-19 medical emergencies such as stroke during the pandemic are critical.
Both endovascular coiling and the Pipeline embolization device (PED) have been shown to be safe and clinically effective for treatment of small (< 10 mm) aneurysms. The authors conducted a ...comparative effectiveness analysis to compare the utility of these treatment methods in terms of health benefits.
A decision-analytical study was performed with Markov modeling methods to simulate patients with small unruptured aneurysms undergoing endovascular coiling, stent-assisted coiling (SAC), or PED placement for treatment. Input probabilities were derived from prior literature, and 1-way, 2-way, and probabilistic sensitivity analyses were performed to assess model and input parameter uncertainty.
The base case calculation for a 50-year-old man reveals PED to have a higher health benefit (17.48 quality-adjusted life years QALYs) than coiling (17.44 QALYs) or SAC (17.36 QALYs). PED is the better option in 6020 of the 10,000 iterations in probabilistic sensitivity analysis. When the retreatment rate of PED is lower than 9.53%, and the coiling retreatment is higher than 15.6%, PED is the better strategy. In the 2-way sensitivity analysis varying the retreatment rates from both treatment modalities, when the retreatment rate of PED is approximately 14% lower than the retreatment rate of coiling, PED is the more favorable treatment strategy. Otherwise, coiling is more effective. SAC may be better than PED when the unfavorable outcome risk of SAC is lower than 70% of its reported current value.
With the increasing use of PEDs for treatment of small unruptured aneurysms, the current study indicates that these devices may have higher health benefits due to lower rates of retreatment compared to both simple coiling and stent-assisted techniques. Longer follow-up studies are needed to document the rates of recurrence and retreatment after coiling and PED to assess the cost-effectiveness of these strategies.
BACKGROUND AND PURPOSE—Multiple studies have shown that negative computed tomographic angiograms (CTAs) are reliable in excluding aneurysms in patients with isolated perimesencephalic subarachnoid ...hemorrhage (pSAH). We evaluate the use of digital subtraction angiography versus CTA for initial diagnosis and of angiographic follow-ups in patients with pSAH by performing an institutional analysis and a meta-analysis of literature.
METHODS—Retrospective institutional analysis of patients with pSAH was performed from 2008 to 2014. The number and types of follow-up imaging studies were tabulated. Initial and follow-up studies were evaluated by an experienced neuroradiologist for intracranial aneurysm. Meta-analysis of literature was performed to assess the use of initial digital subtraction angiography and of follow-up imaging.
RESULTS—Our institutional review revealed no additional use of initial digital subtraction angiography or of any angiographic follow-up after initial negative CTA in patients with pSAH on noncontrast CT. Meta-analysis of 40 studies yielded a total of 1031 patients. Only 8 aneurysms were first diagnosed on follow-ups (0.78%). Careful review showed that some of these aneurysms reported on follow-up are of questionable validity. Initial digital subtraction angiography and follow-up imaging after a negative initial CTA showed no statistically significant benefits.
CONCLUSIONS—In patients meeting the strict imaging criteria of pSAH, initial negative CTA is reliable in excluding aneurysms. A critical review of the literature through meta-analysis shows no foundation for multiple follow-up studies in patients with pSAH.
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