Lower admission stroke severity is associated with good collateral status in distal medium vessel occlusion stroke.

BACKGROUND AND PURPOSE: Distal medium vessel occlusions (DMVOs) are a significant contributor to acute ischemic stroke (AIS), with collateral status (CS) playing a pivotal role in modulating ischemic damage progression. We aimed to explore baseline characteristics associated with CS in AIS-DMVO. METHODS: This retrospective analysis of a prospectively collected database enrolled 130 AIS-DMVO patients from two comprehensive stroke centers. Baseline characteristics, including patient demographics, admission National Institutes of Health Stroke Scale (NIHSS) score, admission Los Angeles Motor Scale (LAMS) score, and co-morbidities, including hypertension, hyperlipidemia, diabetes, coronary artery disease, atrial fibrillation, and history of transient ischemic attack or stroke, were collected. The analysis was dichotomized to good CS, reflected by hypoperfusion index ratio (HIR) <.3, versus poor CS, reflected by HIR ≥.3. RESULTS: Good CS was observed in 34% of the patients. As to the occluded location, 43.8% occurred in proximal M2, 16.9% in mid M2, 35.4% in more distal middle cerebral artery, and 3.8% in distal anterior cerebral artery. In multivariate logistic analysis, a lower NIHSS score and a lower LAMS score were both independently associated with a good CS (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.82-0.95, p < .001 and OR: 0.77, 95% CI: 0.62-0.96, p = .018, respectively). Patients with poor CS were more likely to manifest as moderate to severe stroke (29.1% vs. 4.5%, p < .001), while patients with good CS had a significantly higher chance of having a minor stroke clinically (40.9% vs. 12.8%, p < .001). CONCLUSIONS: CS remains an important determinant in the severity of AIS-DMVO. Collateral enhancement strategies may be a worthwhile pursuit in AIS-DMVO patients with more severe initial stroke presentation, which can be swiftly identified by the concise LAMS and serves as a proxy for underlying poor CS.

Follow-up infarct volume on fluid attenuated inversion recovery (FLAIR) imaging in distal medium vessel occlusions: the role of cerebral blood volume index.

BACKGROUND: Distal medium vessel occlusions (DMVOs) contribute substantially to the incidence of acute ischemic strokes (AIS) and pose distinct challenges in clinical management and prognosis. Neuroimaging techniques, such as Fluid Attenuation Inversion Recovery (FLAIR) imaging and cerebral blood volume (CBV) index derived from perfusion imaging, have significantly improved our ability to assess the impact of strokes and predict their outcomes. The primary objective of this study was to investigate relationship between follow-up infarct volume (FIV) as assessed by FLAIR imaging in patients with DMVOs. METHODS: This prospectively collected, retrospective reviewed cohort study included patients from two comprehensive stroke centers within the Johns Hopkins Medical Enterprise, spanning August 2018-October 2022. The cohort consisted of adults with AIS attributable to DMVO. Detailed imaging analyses were conducted, encompassing non-contrast CT, CT angiography (CTA), CT perfusion (CTP), and FLAIR imaging. Univariable and multivariable linear regression models were employed to assess the association between different factors and FIV. RESULTS: The study included 79 patients with DMVO stroke with a median age of 69 years (IQR, 62-77 years), and 57% (n = 45) were female. There was a negative correlation between the CBV index and FIV in a univariable linear regression analysis (Beta = - 16; 95% CI, - 23 to - 8.3; p < 0.001) and a multivariable linear regression model (Beta = - 9.1 per 0.1 change; 95% CI, - 15 to - 2.7; p = 0.006). Diabetes was independently associated with larger FIV (Beta = 46; 95% CI, 16 to 75; p = 0.003). Additionally, a higher baseline ASPECTS was associated with lower FIV (Beta = - 30; 95% CI, - 41 to - 20; p < 0.001). CONCLUSION: Our findings underscore the CBV index as an independent association with FIV in DMVOs, which highlights the critical role of collateral circulation in determining stroke outcomes in this patient population. In addition, our study confirms a negative association of ASPECTS with FLAIR FIV and identifies diabetes as independent factor associated with larger FIV. These insights pave the way for further large-scale, prospective studies to corroborate these findings, thereby refining the strategies for stroke prognostication and management.

The Relative Cerebral Blood Volume (rCBV) < 42% Is Independently Associated with Collateral Status in Anterior Circulation Large Vessel Occlusion.

Background: The pretreatment CT perfusion (CTP) marker the relative cerebral blood volume (rCBV) < 42% lesion volume has recently been shown to predict 90-day functional outcomes; however, studies assessing correlations of the rCBV < 42% lesion volume with other outcomes remain sparse. Here, we aim to assess the relationship between the rCBV < 42% lesion volume and the reference standard digital subtraction angiography (DSA)-derived American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) collateral score, hereby referred as the DSA CS. Methods: In this retrospective evaluation of our prospectively collected database, we included acute stroke patients triaged by multimodal CT imaging, including CT angiography and perfusion imaging, with confirmed anterior circulation large vessel occlusion between 1 September 2017 and 1 October 2023. Group differences were assessed using the Student's t test, Mann-Whitney U test and Chi-Square test. Spearman's rank correlation and logistic regression analyses were used to assess associations between rCBV < 42% and DSA CS. Results: In total, 222 patients (median age: 69 years, 56.3% female) met our inclusion criteria. In the multivariable logistic regression analysis, taking into account age, sex, race, hypertension, hyperlipidemia, diabetes, atrial fibrillation, prior stroke or transient ischemic attack, the admission National Institute of Health stroke scale, the premorbid modified Rankin score, the Alberta stroke program early CT score (ASPECTS), and segment occlusion, the rCBV < 42% lesion volume (adjusted OR: 0.98, p < 0.05) was independently associated with the DSA CS. Conclusion: The rCBV < 42% lesion volume is independently associated with the DSA CS.

Ischemic Infarction in Young Adults.

Ischemic strokes in young adults are increasing in incidence and have emerged as a public health issue. The radiological features are not only diagnostic in identifying ischemic infarctions but also provide important clues in the investigation of the underlying causes or in the identification of risk factors. According to the different imaging patterns associated with ischemic stroke in young adults, the causes can be classified into 5 categories: cardioembolism, large vessel vasculopathy, small vessel vasculopathy, toxic-metabolic, and hypercoagulable disorders. The radiological features of each category and cause are described and summarized in this review.

Improving trauma care in exsanguinating patients with CHOP (critical haemorrhage to operating-room patient) resuscitation protocol-A cumulative summation (CUSUM) analysis.

INTRODUCTION: The standard protocol for exsanguinating trauma patients involves initial evaluation and resuscitation in the emergency department which then sets the stage for subsequent definitive care and disposition. This involves major coordination and mobilisation of resources which may cause a delay in intervention especially when most of these cases present after office hours. Our centre has employed a second-tier activation system (CHOP protocol) that immediately mobilises all respective trauma specialists including interventional radiologists and allows rapid access to the operating room. OBJECTIVE: We hypothesised that exsanguinating patients managed by CHOP protocol have better overall outcome and survival. METHODS: We identified trauma patients that fulfilled CHOP criteria from 2016 to 2019 and divided them into two groups: preCHOP (standard protocol) and CHOP. Data was extracted from a prospectively maintained trauma registry. Demographics, injury pattern and in-hospital data were analysed. The key outcome studied was the impact of CHOP protocol on the mortality rate. Success and failure of the two groups were analysed using CUSUM methodology. RESULTS: Thirty-seven patients were managed by CHOP protocol since its introduction in March 2018 compared to 36 patients who underwent standard protocol. Majority of the cases were blunt trauma (89% CHOP vs 92% preCHOP). The mean Injury Severity Score was 37 for CHOP group and 39 for preCHOP group. We observed a significant improvement in time to intervention in CHOP patients (78 min vs 113 min), both during and after office hours. CHOP patients had lower mortality compared to preCHOP group (11% vs 31%) and the effectiveness of the protocol was seen in achieving significantly lower mortality compared to the predicted model. CHOP protocol was able to produce a consistent trend of desired outcomes leading to the CUSUM curve exhibiting a sustained downward slope. CONCLUSION: The CHOP protocol, a relatively novel system in the local context, was able to achieve sustained improved outcomes compared to standard protocol. The CUSUM analysis concurred that implementation of CHOP protocol has helped to achieve consistent desired outcomes. It also suggested that the uptake and use of this protocol has integrated well into the existing workflow.

Carotid web prevalence in a large hospital-based cohort and its association with ischemic stroke.

Carotid artery webs are shelf-like protrusions of intimal fibrous tissue arising from the posterior wall of the carotid bulb, found to have a 2.3% prevalence in the United States. Previous studies have demonstrated its association with ipsilateral anterior circulation stroke. The aim of this study is to assess the prevalence of carotid webs in the largest US epidemiologic study to date, and to further characterize the clinical features of carotid web patients. We assembled a cohort of 1467 adult patients with CT angiogram neck from January 1, 2011 to January 1, 2017. CT angiograms were reviewed for diagnosis of carotid web. Demographic and clinical details of web patients were obtained. Differences in demographics and CT angiogram indication between patients with and without carotid web were assessed using appropriate statistical tests. Twenty-four (24/1467 = 1.6%) carotid web patients were identified (mean age: 63 years; 62.5% female; 50% African American). Twelve (12/24 = 50%) had ipsilateral anterior circulation stroke. Of them, 8 were deemed cryptogenic. Four (4/24 = 16.7%) web patients had at least one recurrent stroke in the ipsilateral anterior circulation. One case was reported on the radiology report at the time the study was initially performed. This study confirms a prevalence of 1.6% in our urban, North American cohort. Among carotid web patients, there was a high incidence of ipsilateral anterior circulation stroke, the majority of which were classified as cryptogenic. This study affirms the importance of the diagnosis of carotid web, especially in cryptogenic stroke patients, as a potential unrecognized stroke risk factor.

Targeting ferroptosis: A novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy.

BACKGROUND: Mitochondrial disease is a family of genetic disorders characterized by defects in the generation and regulation of energy. Epilepsy is a common symptom of mitochondrial disease, and in the vast majority of cases, refractory to commonly used antiepileptic drugs. Ferroptosis is a recently-described form of iron- and lipid-dependent regulated cell death associated with glutathione depletion and production of lipid peroxides by lipoxygenase enzymes. Activation of the ferroptosis pathway has been implicated in a growing number of disorders, including epilepsy. Given that ferroptosis is regulated by balancing the activities of glutathione peroxidase-4 (GPX4) and 15-lipoxygenase (15-LO), targeting these enzymes may provide a rational therapeutic strategy to modulate seizure. The clinical-stage therapeutic vatiquinone (EPI-743, α-tocotrienol quinone) was reported to reduce seizure frequency and associated morbidity in children with the mitochondrial disorder pontocerebellar hypoplasia type 6. We sought to elucidate the molecular mechanism of EPI-743 and explore the potential of targeting 15-LO to treat additional mitochondrial disease-associated epilepsies. METHODS: Primary fibroblasts and B-lymphocytes derived from patients with mitochondrial disease-associated epilepsy were cultured under standardized conditions. Ferroptosis was induced by treatment with the irreversible GPX4 inhibitor RSL3 or a combination of pharmacological glutathione depletion and excess iron. EPI-743 was co-administered and endpoints, including cell viability and 15-LO-dependent lipid oxidation, were measured. RESULTS: EPI-743 potently prevented ferroptosis in patient cells representing five distinct pediatric disease syndromes with associated epilepsy. Cytoprotection was preceded by a dose-dependent decrease in general lipid oxidation and the specific 15-LO product 15-hydroxyeicosatetraenoic acid (15-HETE). CONCLUSIONS: These findings support the continued clinical evaluation of EPI-743 as a therapeutic agent for PCH6 and other mitochondrial diseases with associated epilepsy.

Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase.

Ferroptosis is a form of programmed cell death associated with inflammation, neurodegeneration, and ischemia. Vitamin E (alpha-tocopherol) has been reported to prevent ferroptosis, but the mechanism by which this occurs is controversial. To elucidate the biochemical mechanism of vitamin E activity, we systematically investigated the effects of its major vitamers and metabolites on lipid oxidation and ferroptosis in a striatal cell model. We found that a specific endogenous metabolite of vitamin E, alpha-tocopherol hydroquinone, was a dramatically more potent inhibitor of ferroptosis than its parent compound, and inhibits 15-lipoxygenase via reduction of the enzyme's non-heme iron from its active Fe3+ state to an inactive Fe2+ state. Furthermore, a non-metabolizable isosteric analog of vitamin E which retains antioxidant activity neither inhibited 15-lipoxygenase nor prevented ferroptosis. These results call into question the prevailing model that vitamin E acts predominantly as a non-specific lipophilic antioxidant. We propose that, similar to the other lipophilic vitamins A, D and K, vitamin E is instead a pro-vitamin, with its quinone/hydroquinone metabolites responsible for its anti-ferroptotic cytoprotective activity.

Screening utilization among cancer survivors: a meta-analysis.

Background: Studies have been published showing both increased and decreased utilization of cancer screening services in cancer survivors compared with cancer-free counterparts. This study synthesizes existing evidence in a meta-analysis. Methods: A systematic literature review was conducted in August 2016. Studies were included if they compared the utilization of screening services for cervical, breast and colorectal cancer among adulthood cancer survivors to cancer-free controls. Random effects meta-analyses were conducted to pool estimates. Results: Of 3538 studies, 19 fulfilled the inclusion criteria. Cancer survivors were more likely to utilize screening services for breast cancer (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.13-1.42, P < 0.001), colorectal cancer (OR = 1.25, 95% CI: 1.15-1.37, P < 0.001) and cervical cancer (OR = 1.38, 95% CI: 1.08-1.75, P < 0.001) than cancer-free controls. Conclusions: Overall, cancer survivors were more likely to utilize cancer screening services when compared with cancer-free controls. Future studies should evaluate, whether the utilization of screening services translates into prolonged survival.