Hyperacute Phase Research Articles

Association between the cytokine storm, immune cell dynamics, and viral replicative capacity in hyperacute HIV infection

IntroductionImmunological damage in acute HIV infection (AHI) may predispose to detrimental clinical sequela. However, studies on the earliest HIV-induced immunological changes are limited, particularly in sub-Saharan Africa. We assessed the plasma cytokines kinetics, and their associations with virological and immunological parameters, in a well-characterized AHI cohort where participants were diagnosed before peak viremia.MethodsBlood cytokine levels were measured using Luminex and ELISA assays pre-infection, during the hyperacute infection phase (before or at peak viremia, 1–11 days after the first detection of viremia), after peak viremia (24–32 days), and during the early chronic phase (77–263 days). Gag-protease-driven replicative capacities of the transmitted/founder viruses were determined using a green fluorescent reporter T cell assay. Complete blood counts were determined before and immediately following AHI detection before ART initiation.ResultsUntreated AHI was associated with a cytokine storm of 12 out of the 33 cytokines analyzed. Initiation of ART during Fiebig stages I–II abrogated the cytokine storm. In untreated AHI, virus replicative capacity correlated positively with IP-10 (rho = 0.84, P < 0.001) and IFN-alpha (rho = 0.59, P = 0.045) and inversely with nadir CD4+ T cell counts (rho = − 0.58, P = 0.048). Hyperacute HIV infection before the initiation of ART was associated with a transient increase in monocytes (P < 0.001), decreased lymphocytes (P = 0.011) and eosinophils (P = 0.003) at Fiebig stages I–II, and decreased eosinophils (P < 0.001) and basophils (P = 0.007) at Fiebig stages III–V. Levels of CXCL13 during the untreated hyperacute phase correlated inversely with blood eosinophils (rho = − 0.89, P < 0.001), basophils (rho = − 0.87, P = 0.001) and lymphocytes (rho = − 0.81, P = 0.005), suggesting their trafficking into tissues. In early treated individuals, time to viral load suppression correlated positively with plasma CXCL13 at the early chronic phase (rho = 0.83, P = 0.042).ConclusionWhile commencement of ART during Fiebig stages I–II of AHI abrogated the HIV-induced cytokine storm, significant depletions of eosinophils, basophils, and lymphocytes, as well as transient expansions of monocytes, were still observed in these individuals in the hyperacute phase before the initiation of ART, suggesting that even ART initiated during the onset of viremia does not abrogate all HIV-induced immune changes.

Abstract WMP62: High Linfocytes B Cells In Intracranial Thrombi Represent A Biomarker Of Atherothrombotic Stroke

Approximately 30% of strokes are cryptogenic despite an exhaustive in-hospital work-up Analysis of clot composition following endovascular treatment could provide insight into stroke etiology. Objective: To evaluate different population of lymphocytes in the clot analyses obtained in the hyper acute phase of stroke, as an early marker of etiology of ischemic stroke. Material and Methods: Consecutively, intracranial clots were obtained in the hyper acute phase of stroke in endovascular treatment with solitaire device and analyzed by flow cytometry quantifying the relative proportion ( RP ) of main leukocyte, monocyte, granulocyte and total lymphocyte populations and lymphocyte sub populations of B line (CD19), T line (CD3, CD4, CD8), Cytotoxic and Natural Killer. The results were expressed as percentages (%). All patients included were studied with complete diagnostic work up that included at least complete arteriography , aortic Angio CT , complete cardiac holter monitoring until one month form hospital discharge and transthoracic echocardiography , The etiology of stroke was categorized: cardiomebolic ( major structural heart disease and Atrial Fibrillation) atherosclerotic ( AT) (severe symptomatic arterial stenosis or complicated aortic atheromatosis ulceration confirmed by trans esophageal echocardiography ) ,infrequent causes or unknown etiology . Results: 80 patients were included. 22, 5% AT (n = 18) strokes were associated with higher RP lymphocytes PR (16.55 % vs. 5. 37 % p &lt; 0,001), CD4 RP (5.74% vs. 2.03 % p = 0.001) and RP CD 19 (2.26 % vs. 0.37 % p&lt; 0,001) in clot cytometry Analysis than rest of of strokes etiologies (n= 72). Multivariate logistic regression analysis showed that RP CD 19 (OR 3.51; 95% CI, 1, 81-6.81) was an independent predictor of atherosclerotic stroke .The ROC curve showed AUC (0.83) (95% CI, 0.72-0.95) for RP CD 19 for diagnosis of atherosclerotic strokes with flow cytometry of the clot ,obtained in emergent endovascular treatment. Conclusion: High expression of lymphocytes B in intracranial thrombi is a marker of atherosclerotic etiology.

Abstract WP431: Comparing EMS and Emergency Department Last Known Well Times in Ohio

Introduction: During the hyperacute phase of acute stroke management, time the patient was last known well (LKW) is a critical data element. Hospital Emergency Department (ED) personnel rely on accurate information reported by Emergency Medical Services (EMS) prior to arrival, which triggers the intensity of resources organized to determine patient eligibility for revascularization therapy. Over-triage can cause “alarm fatigue”, provider burnout, and/or overutilization of valuable resources. Conversely, under triage may cause a delay in, or lack of, revascularization therapy, which can have significant negative impact on the patient’s outcome. A review of the literature revealed contradictory data about the accuracy of LKW as reported by EMS. Purpose: The purpose of this project is to determine frequency and magnitude of discrepancies between LKW as reported by EMS and ED. The data was analyzed for trends that may influence discrepancies, such as hospital size, location, and patient demographics. Methods: Data on 2,092 patients from 49 hospitals was analyzed from Get With The Guidelines®-Stroke. The difference in the LKW (ΔLKW) was calculated based on source of documentation from EMS or ED. Three datasets were created based on the magnitude of the ΔLKW. For each dataset, the mean, median and patient demographics such as mean age, race, and stroke type were calculated. Results: Of 2,092 patients, 951 (45%) showed an exact match between LKW as reported by EMS and ED (ΔLKW=0), whereas 1,141 patients (55%) showed a discrepancy in the LKW (ΔLKW&gt;0). Discrepancies were not influenced by hospital location or size. Of the overall population, 54% were male, 18% were black, and 73% were diagnosed with an ischemic stroke. The mean age was 72 years. Further collaboration is needed between EMS and ED personnel to improve the accuracy of LKW, and thereby improve patient care and provider efficiency.

A Study on Disaster Medical Response During the Great East Japan Earthquake Disaster Based on the Emergency Support Function – Nine Days at Iwate Prefecture from Hyperacute to Subacute Phase –

During the Great East Japan Earthquake Disaster, the medical team’s responses in the Iwate Prefecture Emergency Operation Center (EOC) experienced many difficulties, especially in the first nine days after disaster occurrence. In this paper we proposed to objectively reveal problems of response activities at the viewpoint of information processing by the After Action Review (AAR), focusing on the activity logs in the time series (chronologies). By using the Emergency Support Function (ESF) as a framework of our analysis, we clarified the gap between the task that should be performed and actual conditions in the operation of the Japan Disaster Medical Assistance Team (DMAT) from the hyperacute phase to the subacute phase of medical responses.

Wireless EEG in hyper-acute ischemic stroke: correlation between neurophysiological alterations and CTP total hypoperfused volume

Abstract Neuroimaging is crucial for stroke diagnosis and to establish the feasibility of reperfusion therapy, but is not practical for the assessment of continuous evolution of brain ischemia. Electroencephalography (EEG) in the early phase of brain ischemia could be a feasible instrument of functional monitoring. In this context, it would be of great research and clinical interest to assess the relation between EEG parameters and the hypoperfused volume measured by Computed Tomography Perfusion (CTP), as possible real-time surrogate parameters for extent of brain ischemia. This preliminary study aimed at investigating the relation between stroke-related EEG changes, measured on bedside with wireless EEG device, and the extent of hypoperfused volume assessed on CTP during the hyper-acute phase. We studied 12 consecutive ischemic stroke patients who underwent CTP assessment and EEG recording with wireless device within 4.5 hours from symptom onset. Total hypoperfused volume correlated significantly with the delta/alpha power ratio (ρ=0.72; p

Stroke mimics: Clinical characteristics and outcome.

Objectives:To study the prevalence and nature of stroke mimics (SM) among Saudi patients who came to the emergency department with a sudden neurological deficit and suspected stroke.Methods:The electronic health records from February 2016 to July 2018 of patients who were admitted to the Stroke Unit at King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia (KAMC-RD) with a suspected stroke were all reviewed. A comparison between SM and stroke was established. Our study identified the predictors of SM by using logistic regression analysis. This study was approved by the local institutional review board.Results:Out of 1, 063 patients, 131 (12.3%) had SM. The most common causes were a peripheral vestibular disorder (27.4%) followed by psychogenic causes (24.4%). Stroke mimics were more common among younger individuals and women. Arterial hypertension, diabetes, and smoking were less likely to be found in SMs. At discharge, individuals with SM were more likely to be independent, had milder deficits, and shorter hospital stays. Predictors of SM were young age, female gender, mild deficit at presentation, and good functional status before the stroke.Conclusion:The incidence of stroke mimics is common among suspected stroke patients. Practicing physicians should consider potential diagnostic errors, particularly in the hyperacute phase of the stroke.

Troponin T Predicts Cardioembolic Aetiology and Clinical Outcome in Undetermined Ischaemic Stroke in Hyperacute Phase

Background: Elevated high-sensitivity cardiac troponin T (hs-cTnT) levels have been related to clinical outcome in stroke patients. However, the role of hs-cTnT and its potential as a biomarker in ischaemic stroke (IS) has not been well established. This study aims to determine whether basal hs-cTnT determination in the hyperacute phase of undetermined IS and transient ischaemic attack (TIA) can predict the cardioembolic aetiology and clinical outcome. Methods: We prospectively studied 110 consecutive patients with undetermined acute IS and TIA. hs-cTnT levels were determined at hospital arrival. Large vessel stenosis/occlusion and previously known aetiologies at admission were exclusion criteria for this study. All patients were subjected to a complete aetiological evaluation. A 12-month follow-up was performed in all patients. The subtype of IS was evaluated following the SSS-TOAST criteria. We established two groups at admission: cardioembolic aetiology (group A) and noncardioembolic aetiologies (group B). Results: The number of patients in each group was similar (group A: 52, 47.27%; group B, 58, 52.73%). Patients in group A had elevated hs-cTnT more frequently (61.54% versus 17.24%; P < .001). Group A patients had significantly higher mortality at 3 months (14.29% versus 1.82%, P = .025). In the multivariate analysis, elevated hs-cTnT was the only independent predictor of cardioembolic aetiology (odds ratio: 14.821; 95% confidence interval: 3.717-59.102, P < .001). Conclusion: Baseline hs-cTnT assessment in undetermined strokes and TIA during the hyperacute phase is independently associated with cardioembolic aetiology.

PRONTO: Artemis in the Removal of Intraventricular Hemorrhage in the Hyper-Acute Phase

PRONTO: Artemis in the Removal of Intraventricular Hemorrhage in the Hyper-Acute Phase

Hyperoxemia during the hyperacute phase of aneurysmal subarachnoid hemorrhage is associated with delayed cerebral ischemia and poor outcome: a retrospective observational study.

The harmful effects of hyperoxemia have been reported in critically ill patients with various disorders, including those with brain injuries. However, the effect of hyperoxemia on aneurysmal subarachnoid hemorrhage (aSAH) patients is unclear. In this study the authors aimed to determine whether hyperoxemia during the hyperacute or acute phase in patients with aSAH is associated with delayed cerebral ischemia (DCI) and poor neurological outcome. In this single-center retrospective study, data from patients with aSAH treated between January 2011 and June 2017 were reviewed. The patients were classified into groups according to whether they experienced DCI (DCI group and non-DCI group) and whether they had a poor outcome at discharge (poor outcome group and favorable outcome group). The background characteristics and time-weighted average (TWA) PaO2 during the first 24 hours after arrival at the treatment facility (TWA24h-PaO2) and between the first 24 hours after arrival and day 6 (TWA6d-PaO2), the hyperacute and acute phases, respectively, were compared between the groups. Factors related to DCI and poor outcome were evaluated with logistic regression analyses. Of 197 patients with aSAH, 42 patients experienced DCI and 82 patients had a poor outcome at discharge. TWA24h-PaO2 was significantly higher in the DCI group than in the non-DCI group (186 [141-213] vs 161 [138-192] mm Hg, p = 0.029) and in the poor outcome group than in the favorable outcome group (176 [154-205] vs 156 [136-188] mm Hg, p = 0.004). TWA6d-PaO2 did not differ significantly between the groups. Logistic regression analyses revealed that higher TWA24h-PaO2 was an independent risk factor for DCI (OR 1.09, 95% CI 1.01-1.17, p = 0.037) and poor outcome (OR 1.17, 95% CI 1.06-1.29, p = 0.002). Hyperoxemia during the first 24 hours was associated with DCI and a poor outcome in patients with aSAH. Excessive oxygen therapy might have an adverse effect in the hyperacute phase of aSAH.

Aerobic Training and Mobilization Early Post-stroke: Cautions and Considerations.

Knowledge gaps exist in how we implement aerobic exercise programs during the early phases post-stroke. Therefore, the objective of this review was to provide evidence-based guidelines for pre-participation screening, mobilization, and aerobic exercise training in the hyper-acute and acute phases post-stroke. In reviewing the literature to determine safe timelines of when to initiate exercise and mobilization we considered the following factors: arterial blood pressure dysregulation, cardiac complications, blood-brain barrier disruption, hemorrhagic stroke transformation, and ischemic penumbra viability. These stroke-related impairments could intensify with inappropriate mobilization/aerobic exercise, hence we deemed the integrity of cerebral autoregulation to be an essential physiological consideration to protect the brain when progressing exercise intensity. Pre-participation screening criteria are proposed and countermeasures to protect the brain from potentially adverse circulatory effects before, during, and following mobilization/exercise sessions are introduced. For example, prolonged periods of standing and static postures before and after mobilization/aerobic exercise may elicit blood pooling and/or trigger coagulation cascades and/or cerebral hypoperfusion. Countermeasures such as avoiding prolonged standing or incorporating periodic lower limb movement to activate the venous muscle pump could counteract blood pooling after an exercise session, minimize activation of the coagulation cascade, and mitigate potential cerebral hypoperfusion. We discuss patient safety in light of the complex nature of stroke presentations (i.e., type, severity, and etiology), medical history, comorbidities such as diabetes, cardiac manifestations, medications, and complications such as anemia and dehydration. The guidelines are easily incorporated into the care model, are low-risk, and use minimal resources. These and other strategies represent opportunities for improving the safety of the activity regimen offered to those in the early phases post-stroke. The timeline for initiating and progressing exercise/mobilization parameters are contingent on recovery stages both from neurobiological and cardiovascular perspectives, which to this point have not been specifically considered in practice. This review includes tailored exercise and mobilization prescription strategies and precautions that are not resource intensive and prioritize safety in stroke recovery.

Silencing of microRNA-494 inhibits the neurotoxic Th1 shift via regulating HDAC2-STAT4 cascade in ischaemic stroke.

T helper cell 1 (Th1)-skewed neurotoxicity contributes to the poor outcome of stroke in rodents. Here, we have elucidated the mechanism of the Th1/Th2 shift in acute ischaemic stroke (AIS) patients at hyperacute phase and have looked for a miRNA-based therapeutic target. MiR-494 levels in blood from AIS patients and controls were measured by real-time PCR. C57BL/6J mice were subjected to transient middle cerebral artery occlusion, and cortical neurons were subjected to oxygen-glucose deprivation. Luciferase reporter system, chromatin immunoprecipitation sequencing (ChIP-Seq), and ChIP-PCR were used to uncover possible mechanisms. In lymphocytes from AIS patients, there was a Th1/Th2 shift and histone deacetylase 2 (HDAC2) was markedly down-regulated. ChIP-seq showed that HDAC2 binding sites were enriched in regulation of Th1 cytokine production, and ChIP-PCR confirmed that HDAC2 binding was changed at the intron of STAT4 and the promoter of T-box transcription factor 21 (T-bet) in lymphocytes from AIS patients. MiR-494 was the most significantly increased miRNA in lymphocytes from AIS patients, and miR-494-3p directly targeted HDAC2. A strong association existed between miR-494 and Th1 cytokines, and neurological deficit as measured by the National Institute of Health Stroke Scale (NIHSS) in AIS patients. In vitro and in vivo experiments showed that antagomir-494 reduced Th1 shift-mediated neuronal and sensorimotor functional damage in the mouse model of ischaemic stroke, via the HDAC2-STAT4 pathway. We demonstrated that miR-494 inhibition prevented Th1-skewed neurotoxicity through regulation of the HDAC2-STAT4 cascade.

Study on Disaster Medical Response During the Great East Japan Earthquake Disaster Based on Essential Elements of Information – Nine Days at Iwate Prefecture from Hyperacute Phase to Subacute Phase –

During the Great East Japan Earthquake Disaster, the medical team’s responses in Iwate Prefecture Disaster Emergency Operations Center experienced various difficulties, especially during the first 9 days. In this paper, we propose to objectively reveal problems of response activities from the viewpoint of operational information processing by the After Action Review, focusing on the activity logs in the time series (chronologies). By using Essential Elements of Information (EEI) as a framework of our analysis, we clarified the gap between the task that should be performed and the actual conditions in the operation of Japan Disaster Medical Assistance Team (DMAT), from the hyperacute phase to the subacute phase of medial responses.

P327Predictive value of platelet reactivity, neutrophil to lymphocyte ratio, and hs-CRP at presentation in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention

Abstract Background Patients with ST-elevation myocardial infarction (STEMI) exhibit enhanced platelet reactivity and a rise in inflammatory biomarkers such as neutrophil to lymphocyte ratio (NLR) and high-sensitivity C-reactive protein (hs-CRP). The extent of the prothrombotic and inflammatory state are predictive of adverse outcomes in patients with acute coronary syndromes. The relationship of these markers of inflammation and thrombosis in the hyperacute phase of STEMI and, whether together, they improve cardiovascular outcome prediction, is not known. Purpose The aim of this study was to assess the individual and combined predictive values of NLR, hs-CRP, and platelet reactivity for clinical outcomes in patients with STEMI. Method In a prospective study of 541 patients presenting with STEMI, acute admission bloods taken prior to emergency percutaneous coronary intervention, were analysed for NLR and hs-CRP. Platelet reactivity was measured using the point-of-care Global Thrombosis Test, which assesses platelet reactivity in native whole blood under high shear, and measures the occlusion time (OT, sec). Shorter occlusion time represents higher platelet reactivity. The study endpoint was occurrence of major adverse cardiovascular events (MACE, defined as composite of cardiovascular death [CVD], myocardial infarction [MI] or stroke [CVA]) at 30 days and 12 months. Results There was a weak, but significant, correlation between hs-CRP and NLR (r=0.25, p&lt;0.001), and hs-CRP and platelet reactivity (r=0.14, p=0.003) on admission. There was no correlation between platelet reactivity and NLR. Amongst 541 patients, 42 patients experienced a MACE within the first 30 days, and 50 within 12 months. Cut-values associated with the highest specificity and sensitivity for 12-month MACE were NLR 5.6, hs-CRP 8 mg/L and OT 302 sec. Platelet reactivity and hs-CRP were each only weakly predictive of MACE at 30 days (platelet reactivity: hazard ratio [HR] 1.004 [95% confidence interval (CI) 1.002–1.006,] p&lt;0.001; hs-CRP: HR 1.005 [95% CI 1.0009–1.009], p=0.016) and 12 months (platelet reactivity HR 1.004 (95% CI 1.002–1.006), p&lt;0.001; hs-CRP HR 1.005 (95% CI 1.001–1.01), p=0.014). NLR was not predictive of MACE at either 30 days or 12 months (p=NS). When patients were divided into quartiles based on hs-CRP and platelet reactivity, patients in the highest quartile for both hs-CRP and platelet reactivity had an HR 3.46 (95% CI 1.81–6.63), p&lt;0.001 compared to those in the lowest quartile for both (HR 0.04 (95% CI 0.005–0.27), p=0.001). The combination of enhanced platelet reactivity and raised hs-CRP was the strongest predictor of MACE at 30 days (HR 2.32 [95% CI 1.71–3.13], p&lt;0.001) and 12 months (HR 2.31 [95% CI 1.71–3.11], p&lt;0.001). Conclusion Both hs-CRP and platelet reactivity are very weakly predictive of MACE, but in combination provide a strong predictor of adverse outcome in STEMI.

White matter T2 hyperintensities and blood-brain barrier disruption in the hyperacute stage of subarachnoid hemorrhage in male mice: The role of lipocalin-2.

AimsThe current study examined whether white matter injury occurs in the hyperacute (4 hours) phase after subarachnoid hemorrhage (SAH) and the potential role of blood‐brain barrier (BBB) disruption and an acute phase protein, lipocalin 2 (LCN2), in that injury.MethodsSubarachnoid hemorrhage was induced by endovascular perforation in adult mice. First, wild‐type (WT) mice underwent MRI 4 hours after SAH to detect white matter T2 hyperintensities. Second, changes in LCN2 expression and BBB disruption associated with the MRI findings were examined. Third, SAH‐induced white matter injury at 4 hours was compared in WT and LCN2 knockout (LCN2 KO) mice.ResultsAt 4 hours, most animals had uni‐ or bilateral white matter T2 hyperintensities after SAH in WT mice that were associated with BBB disruption and LCN2 upregulation. However, some disruption and LCN2 upregulation was also found in mice with no T2‐hyperintensity lesion. In contrast, there were no white matter T2 hyperintensities in LCN2 KO mice after SAH. LCN2 deficiency also attenuated BBB disruption, myelin damage, and oligodendrocyte loss.ConclusionsSubarachnoid hemorrhage causes very early BBB disruption and LCN2 expression in white matter that is associated with and may precede T2 hyperintensities. LCN2 deletion attenuates MRI changes and pathological changes in white matter after SAH.

Brain oscillatory activity and CT perfusion in hyper-acute ischemic stroke

ObjectivesThe combined use of perfusion neuroimaging and brain oscillatory activity may provide a better clinical picture of neurovascular coupling of the injured area in ischemic stroke. The aim is to assess stroke-related topographic electroencephalography (EEG) changes during the earliest phase of ischemic stroke and to compare them with hypoperfusion identified by computer tomography perfusion (CTP). Patients and methodsThe study included 15 patients with ischemic stroke, who underwent both CTP and EEG recording within 4.5 h. Topographic representation of power for each band was calculated and compared with hypoperfusion areas estimated by CTP maps. ResultsPredominance of slow delta frequencies was found in all patients. The main finding is the agreement between slow rhythms hemispheric prevalence on EEG maps and cerebral hypoperfusion area identified using CTP. ConclusionThe results of this preliminary study show that the combined use of EEG and CTP, as highly available techniques, in acute ischemic stroke may be helpful in clinical practice and provide information about functional and metabolic aspects of brain involvement. The joint use of these methodologies may give a better clinical insight of the functionality of injured area in the hyperacute phase.

Innate-Like Lymphocytes Are Immediate Participants in the Hyper-Acute Immune Response to Trauma and Hemorrhagic Shock.

Adverse outcomes following severe traumatic injury are frequently attributed to a state of immunological dysfunction acquired during treatment and recovery. Recent genomic evidence however, suggests that the trajectory toward development of multiple organ dysfunction syndrome (MODS) is already in play at admission (<2 h following injury). Improved understanding of the molecular events during the hyper-acute immunological response to trauma, <2 h following injury, may reveal opportunities to ameliorate organ injury and expedite recovery. Lymphocytes have not previously been considered key participants in this early response; however, two observations in human trauma patients namely, raised populations of circulating NKT and NK cells during the hyper-acute phase and persistent lymphopenia beyond 48 h show association with the development of MODS during recovery. These highlight the need for greater understanding of lymphocyte function in the hyper-acute phase of inflammation. An exploratory study was therefore conducted in a well-established murine model of trauma and hemorrhagic shock (T&HS) to investigate (1) the development of lymphopenia in the murine model and (2) the phenotypic and functional changes of three innate-like lymphocyte subsets, NK1.1+ CD3–, NK1.1+ CD3+, γδTCR+ CD3+ cells, focusing on the first 6 h following injury. Rapid changes in phenotype and function were demonstrated in these cells within blood and spleen, but responses in lung tissue lagged behind. This study describes the immediacy of the innate-like lymphocyte response to trauma in different body compartments and considers new lines for further investigation to develop our understanding of MODS pathogenesis.

Treatment Strategy for Progressive Cervical Internal Carotid Artery Stenosis Under Restriction of the Use of Antiplatelet Drugs

Acute ischemic stroke caused by cervical internal carotid artery stenosis (ICS) with altered consciousness and progressive paralysis leads to a poor neurologic prognosis. When such a patient is brought to the hospital in the hyperacute phase, intravenous tissue plasminogen activator is first administered. However, when an indwelling carotid artery stent is required after administration, physicians often hesitate to use antithrombotic drugs. In this report, we propose performing staged angioplasty (SAP) for such cases. Four patients were retrospectively investigated. In all 4 patients, we immediately performed only percutaneous transluminal angioplasty (PTA) without antiplatelet drugs. If both cerebral perfusion on angiography and neurologic findings improved, no additional treatment was provided; otherwise, emergency carotid artery stenting (eCAS) was performed. In PTA-successful cases, eCAS or carotid endarterectomy (CEA) was performed with single or dual antiplatelet drugs at a later date. The success rate of PTA was 50% (2 of 4), and the overall treatment success rate was 100% (4 of 4). Three patients had favorable outcomes (modified Rankin Scale [mRS] score 0-2), but unfortunately, 1 patient had severe disability (mRS score >3) on discharge. The PTA-successful patients had no perioperative complications. On the other hand, 1 of the 2 patients who underwent eCAS experienced embolic complications, including distal embolization. In this investigation, both eCAS and SAP could be performed safety. However, performing SAP first without antiplatelet drugs to avoid hemorrhagic complications and cerebral hyperperfusion syndrome appears to have considerable validity.

Author response: The systolic blood pressure sweet spot after intracerebral hemorrhage: 130 mm Hg?

We appreciated Dr. Munakomi's response to our viewpoint1 on the data from Buletko et al.2 that suggested systolic blood pressure (BP) of 130 mm Hg as an ideal lower limit in BP reduction after spontaneous intracerebral hemorrhage (ICH). We agree with the comment on the remaining role for caution in aggressive BP reduction. However, a pressure autoregulatory shift to the right is disparate, complex, dynamic, not omnipresent,3 and should not prevail over compelling data that lower is better in BP reduction.4 Similarly, oxygen extraction fraction (OEF) as a predicate for therapeutic decision-making has not been successful.5 The focus of the index study was the lower limit of the targeted range.2 Clinicians may reconcile with a 130–160 mm Hg target, if worried about low goals. Others can use 120–140, but it may now be deemed unsafe to linger below 120, in view of the risk of ischemic deterioration.2 We agree that best management may lie ultimately in individualized goal-directed therapy, using autoregulation indices and neuroimaging biomarkers of ischemic risk (e.g., OEF). However, substantial observations have refuted a preponderant presence of perihematomal or regional ischemic penumbra in ICH.6 Serial OEF assessments in the hyperacute phase of ICH are seductive, but not readily applicable. Coupled with renal injury biomarkers, trending of multimodal neuromonitoring physiologic values may yield a U curve for stewardship of hyperacute BP reduction.

Early identification of ischemic stroke in noncontrast computed tomography

Early identification of stroke is critical for the treatment and subsequent recovery. Non-contrast computed tomography (ncCT) is a routinely employed imaging modality for stroke evaluation. However, the early identification of stroke in ncCT images is very difficult, since there are subtle differences between lesion and healthy tissue during the hyperacute phase. In this paper, an image patch classification-based method was developed to detect the early ischemic stroke that is invisible to the radiologist in ncCT. First, we proposed radiomics-based patch classification model to identify whether each patch in ncCT is stroke region or not. To improve the identification accuracy, a symmetry image patch classification was developed, in which an image patch in one brain hemisphere was combined with its contralateral image patch for classification. Second, based on the spatial dependencies between neighboring patches, we built a maximum a posteriori identification model which integrated the spatial constraint information to improve the identification performance. Finally, after performing morphological post-processing, we defined the detected results containing more than 300 voxels as the stroke region. 108 stroke cases that were all invisible to radiologists in ncCT were enrolled in the study and divided into one training cohort and two independent testing cohorts to validate the proposed method. The proposed method has achieved identification accuracies of 76.67% and 75.00% on the two independent testing cohorts, respectively. The results proved the potential of the proposed radiomics model in the task which possessed great clinical values.

Impact of MRI Selection on Triage of Endovascular Therapy in Acute Ischemic Stroke: The MRI in Acute Management of Ischemic Stroke (MIAMIS) Registry

Background: The recently published multicenter randomized DAWN trial confirmed greater outcome benefit of endovascular therapy (ET) for anterior circulation large vessel occlusion ischemic stroke from 6 to 24 h from symptom onset compared to medical management in patients selected by advanced imaging with MRI or perfusion CT to identify mismatch between clinical deficit and infarct volume, which represents salvageable penumbra. The debate of CT over MRI is usually the potentially increase time consumption and the difficulty in establishing an adequate standardized workflow utilizing MRI during the hyperacute phase. Purpose: While CT-based selection of patients is the current standard of care, we sought to determine the time impact of the alternative approach of MRI selection in the 0–12 h window. Methods: In the MRI in Acute Management of Ischemic Stroke (MIAMIS) registry, we retrospectively analyzed 89 consecutive patients from January 2008 to January 2010 who presented with acute stroke symptoms with a National Institutes of Health Stroke Scale score ≥5 or aphasia within 0–12 h from symptom onset. The presence of penumbra was determined by MR perfusion-diffusion mismatch or clinical diffusion mismatch. Patients were stratified based on the presence of mismatch and clinical outcomes in patients who received ET. Imaging times were recorded. Results: The MRI turnaround time was 95.5 ± 48.5 min. The total MRI time was 27.7 ± 12.8 min. Seventeen (19.1%) patients were found to have nonvascular etiology. Mismatch was found in 35 (48.6%) patients with acute ischemic stroke (AIS). Patients with nonvascular etiology were younger (55.7 vs. 65.6 years, p < 0.02), without any vessel occlusion or mismatch noticed in this group. We dichotomized the 39 AIS patients with vessel occlusion into two subgroups: these with mismatch and these without. Patients without mismatch were older (76.7 vs. 64.4 years, p < 0.05), more likely to have congestive heart failure (71.4 vs. 22%, p < 0.03), a higher total serum cholesterol level (196 vs. 156 mg/dL, p < 0.04), and medium to large lesions on diffusion-weighted imaging (DWI) (85.7 vs. 37.5%, p < 0.04). Conclusions: Multimodality MRI screening for AIS symptoms for ET is feasible. Optimizing each center’s protocol and the utilization of MRI with DWI only may be a time-saving alternative.