Neuroimaging Prediction of Hemorrhagic Transformation for Acute Ischemic Stroke

<b><i>Background:</i></b> Hemorrhagic transformation (HT) is a common complication of acute ischemic stroke, often resulting from reperfusion therapy. Early prediction of HT can enable stroke neurologists to undertake measures to avoid clinical deterioration and make optimal treatment strategies. Moreover, the trend of extending the time window for reperfusion therapy (both for intravenous thrombolysis and endovascular treatment) further requires more precise detection of HT tendency. <b><i>Summary:</i></b> In this review, we summarized and discussed the neuroimaging markers of HT prediction of acute ischemic stroke patients, mainly focusing on neuroimaging markers of ischemic degree and neuroimaging markers of blood-brain barrier permeability. This review is aimed to provide a concise introduction of HT prediction and to elicit possibilities of future research combining advanced technology to improve the accessibility and accuracy of HT prediction under emergent clinical settings. <b><i>Key Messages:</i></b> Substantial studies have utilized neuroimaging, blood biomarkers, and clinical variables to predict HT occurrence. Although huge progress has been made, more individualized and precise HT prediction using simple and robust imaging predictors combining stroke onset time should be the future goal of development.

Acute Basilar Artery Occlusion Presenting With Convulsive Movements: A Systematic Review

Background and Purpose: Convulsive seizures related to posterior circulation stroke are considered rare. However, some patients with acute basilar artery occlusion (BAO) can present with convulsive movements. Misdiagnosed as seizures may delay the reperfusion therapy for acute BAO. In this study, we have summarized the clinical features and possible mechanisms of BAO presenting with convulsive movements.Methods: We performed an Institutional Review Board-approved institutional database query from 2015 to 2020 and a literature search of the online database PubMed. Clinical data were collected and analyzed.Results: In total, 14 patients with acute BAO presented with convulsions. There were 10 men and 4 women, with a mean age of 53 (range, 23–77) years. All of these patients had different degrees of impaired consciousness (100.0%, 14/14). Convulsive movements were the initial symptoms in 78.6% (11/14) of patients. Further, 64.3% (9/14) of patients presented with paralysis or cranial nerve abnormalities, and 85.7% (12/14) of patients were treated with reperfusion therapy (thrombolysis, 35.7% [5/14]; endovascular thrombectomy, 64.3% [9/14]). The BAO etiology and mechanism were related to embolism, vessel dissections, and severe stenosis of the right vertebral artery in 57.1% (8/14), 21.4% (3/14), and 7.1% (1/14) of patients, respectively; they were undefined in 14.3% (2/14) of patients. Moreover, 42.9% (6/14) of patients had a 90-day modified Rankin Scale score of 0–2, and the mortality rate was 21.4% (3/14).Conclusions: Acute BAO, especially that related to embolism or vessel dissection, may present with convulsive movements. Acute BAO is a devastating, but treatable disease if diagnosed in time. Considering the possibility of BAO is important when dealing with patients presenting with acute-onset convulsive movements. Prompt diagnosis and reperfusion therapy may help achieve a better prognosis.

HARM revisited: Etiology of subarachnoid hyperintensities in brain FLAIR MRI

Background: The hyperintense acute reperfusion marker (HARM) describes a phenomenon with a hyperintense signal in the subarachnoid space in Fluid-Attenuated Inversion Recovery (FLAIR) magnetic resonance imaging (MRI) sequences, presumably based on blood–brain barrier breakdown in acute stroke with reperfusion. However, this imaging phenomenon was described in other medical conditions. Aim: Determination of the prevalence and associated clinical findings of this phenomenon in a large sample of patients with different neurological conditions. Methods: This is retrospective, single-center, observational study of 23,948 cerebral MRIs acquired in a Neurological University Clinic over 5 years. The prevalence of HARM, the underlying diagnosis, and damage pattern were examined by chart analysis; MRI was analyzed regarding the type of acute lesions, extent of microangiopathic lesions, and whether gadolinium-based contrast agent (GBCA) was given. Results: Among the MRI data, 84 images (0.35%) from 61 patients were HARM-positive without a subarachnoid signal abnormality in any other sequence. Etiologies were heterogeneous; 35 patients had a cerebrovascular disease (CVD; 19 patients received recanalization therapy), 12 patients had an inflammatory central nervous system (CNS) disease and 14 patients had epilepsy. GBCA was applied to 64% of the patients. Conclusion: HARM was a rare radiological finding in a range of different neurological pathologies, not limited to stroke, or to previous reperfusion therapy and was not dependent on previous GBCA administration. Our data suggest that the term is too narrow in terms of the concepts of the underlying pathology. We propose to use the term FLAIR Subarachnoid Hyperintensity (“FLASH”) phenomenon which might better reflect the observation that the radiological sign can be associated with a variety of central neurological conditions without a straightforward association with therapy.

Shenmai Injection Exerts Neuroprotective Functions by Down-regulating MicroRNA-19a in H 2 O 2 -induced PC12 Cells

Background: Acute ischemic stroke (AIS) and following reperfusion therapy-induced cerebral ischemia reperfusion (I/R) injury have been recognized as an important subject of cerebrovascular disease with high mortality. Oxidative stress is an important pathological process of cerebral I/R injury. microRNA-19a (miR-19a) is involved in I/R. As the organ protectant agent, Shenmai Injection (SMI) is widely used in the clinical treatment of cerebral infarction. Purpose: This study aims to explore whether SMI can reduce oxidative stress by regulating miR-19a, thereby treating I/R injury. Methods: The oxidative stress state of PC12 cells was induced by H2O2, and then the cells were cultured with SMI. The therapeutic effect of SMI was evaluated by detecting cellular superoxide dismutase (SOD), malondialdehyde (MDA) and other oxidative markers with the kit. Western blot, PCR, immunofluorescence and other techniques were used to elucidate the potential mechanism of SMI. Results: Cell viability assay results showed that SMI could improve the viability of PC12 cells stimulated by H2O2. Compared with the H2O2 group, after SMI treatment, the contents of MDA and reactive oxygen species (ROS) were significantly reduced, while the activity of SOD was significantly increased, and SMI could reduce apoptosis by increasing the content of adenosine 5'-triphosphate (ATP) in cells and enhancing the mitochondrial membrane potential (∆Ψm). Western blot and qRT-PCR results showed that these effects were partially achieved through the AMPK/Sirt1/PGC-1α pathway. The level of miR-19a was significantly increased in H2O2 group, and SMI could protect the cells by reducing miR-19a. Further investigated the target of miR-19a, and transfected cells with miR-19a mimic and inhibitor respectively. We found that AdipoR2 was a direct target of miR-19a, and miR-19a could inhibit AdipoR2/PI3K/Akt/mTOR pathway. Conclusion:SMI can activate AMPK/Sirt1/PGC-1α and AdipoR2/PI3K/Akt/mTOR pathways by reducing miR-19a levels, and protect PC12 cells stimulated by H2O2.

A Narrative Review of Contemporary Global Perspectives into Epidemiology, Treatment, and Prognosis of Vertebrobasilar Strokes

Blood flow interruptions to the posterior cerebral circulation hallmark vertebrobasilar strokes (VBS), leading to mortality and significant disabilities, yet optimal therapy prevails unpublished. Recent epidemiological evidence indicates that VBS account for nearly 1/5 of all ischemic strokes globally, with acute basilar artery occlusion (BAO) contributing significant disabilities in nearly 1/3 of the victims. The prevalence of VBS in Africa is close to 5%, majorly in large intracranial vessels. Etiologically, Stenosis accounts for 20% of all VBS, while aneurysms face up to a 3% rupture rate. Furthermore, intravenous alteplase is the gold standard medical therapy for the cases presenting within 3 to 4.5 hours post-baseline regarding management options. Nevertheless, there is no consensus for BAO beyond 4.5 hours post-onset. Stent retrievers are the first-line endovascular reperfusion therapy device proposed. However, an 18% risk of in-stent restenosis is a significant drawback. Comprehensive prognostic factors are addressed in this review. However, prospective, multicenter, controlled studies are needed to clarify the time window dilemmas facing posterior circulation strokes. This narrative review explores recent VBS epidemiology, management advances, and prognosis.Rwanda J Med Health Sci 2021;4(3):418-429

Identification of Immune Activation-Related Biomarkers in Acute Myocardial Infarction (AMI) by Bioinformatic Analysis and Clinical Validation

Background: Although reperfusion therapy is widely performed in patients with acute myocardial infarction (AMI), the residual risk of poor outcomes remains substantial. The immune system plays an important role in AMI, and therapies targeting immune cells have proved effective in improving prognosis after AMI. However, the activation and regulation of immune signaling pathways during AMI have not been systematically studied.Objective: This study aimed to reveal the activation status of immune-related signals and the immune status after AMI.Methods and results: Three publicly available datasets (GSE48060, GSE66360, and GSE97320) from the Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed genes (DEGs) using peripheral blood tissue samples from 22 AMI patients and 22 individuals without AMI. Subsequent weighted gene correlation network analysis (WGCNA) was performed for CD4+ T cells, macrophages, and regulatory T cells, and the 387 genes with the most significant correlations with the three immune cells were identified. Then, we intersected the 192 DEGs with 387 genes from WGCNA to reveal , a total of 151 overlapping genes. Protein-protein interaction (PPI) network analysis was performed to identify the hub genes. Furthermore, we recruited 44 patients and collected blood samples to validate the stability and reliability of the predicted hub tragets TLR2, TLR4, TLR8, MMP-9 and TYROBP using qRT-PCR assay.Conclusions： The immune-related genes TLR2, TLR4, TLR8, MMP9 and TYROBP may be potential biomarkers to identify immune signal activation after AMI, therefore providing information for the evaluation of both immune status and early intervention.

A Novel Insight Into the Fate of Cardiomyocytes in Ischemia-Reperfusion Injury: From Iron Metabolism to Ferroptosis

Ischemia-reperfusion injury (IRI), critically involved in the pathology of reperfusion therapy for myocardial infarction, is closely related to oxidative stress the inflammatory response, and disturbances in energy metabolism. Emerging evidence shows that metabolic imbalances of iron participate in the pathophysiological process of cardiomyocyte IRI [also termed as myocardial ischemia-reperfusion injury (MIRI)]. Iron is an essential mineral required for vital physiological functions, including cellular respiration, lipid and oxygen metabolism, and protein synthesis. Nevertheless, cardiomyocyte homeostasis and viability are inclined to be jeopardized by iron-induced toxicity under pathological conditions, which is defined as ferroptosis. Upon the occurrence of IRI, excessive iron is transported into cells that drive cardiomyocytes more vulnerable to ferroptosis by the accumulation of reactive oxygen species (ROS) through Fenton reaction and Haber–Weiss reaction. The increased ROS production in ferroptosis correspondingly leads cardiomyocytes to become more sensitive to oxidative stress under the exposure of excess iron. Therefore, ferroptosis might play an important role in the pathogenic progression of MIRI, and precisely targeting ferroptosis mechanisms may be a promising therapeutic option to revert myocardial remodeling. Notably, targeting inhibitors are expected to prevent MIRI deterioration by suppressing cardiomyocyte ferroptosis. Here, we review the pathophysiological alterations from iron homeostasis to ferroptosis together with potential pathways regarding ferroptosis secondary to cardiovascular IRI. We also provide a comprehensive analysis of ferroptosis inhibitors and initiators, as well as regulatory genes involved in the setting of MIRI.

The role of process mining tools in STEMI networks: where should we build a new primary PCI centre?

Background In ST-segment elevation myocardial infarction (STEMI), time delay between symptom onset and treatment is critical to improve outcome. The expected transport delay between patient location and percutaneous coronary intervention (PCI) centre is paramount for choosing the adequate reperfusion therapy. The “Centre” region of Portugal has heterogeneity in PCI assess due to geographical reasons. Purpose We aimed to explore time delays between regions using process mining (PM) tools. Methods We retrospectively assessed the Portuguese Registry of Acute Coronary Syndromes for patients with STEMI from October 2010 to September 2019, collecting information on geographical area of symptom onset, reperfusion option, and in-hospital mortality. We used a PM toolkit (PM4H – PMApp Version) to build two models (one national and one regional) that represent the flow of patients in a healthcare system, enhancing time differences between groups. One-way analysis of variance was employed for the global comparison of study variables between groups and post hoc analysis with Bonferroni correction was used for multiple comparisons. Results Overall, 8956 patients (75% male, 48% from 51 to 70 years) were included in the national model (Fig. 1A), in which primary PCI was the treatment of choice (73%), with the median time between admission and primary PCI &lt;120 minutes in every region; “Lisboa” and “Centro” had the longest delays, (orange arrows). Fibrinolysis was performed in 4.5%, with a median time delay &lt;1 hour in every region. In-hospital mortality was 5%, significantly higher for those without reperfusion therapy compared to PCI and fibrinolysis (10% vs. 4% vs. 4%, P&lt;0.001). In the regional model (Fig. 1B) corresponding to the “Centre” region of Portugal divided by districts (n=773, 74% male, 47% from 51 to 70 years), only 61% had primary PCI, with “Guarda” (05:04) and “Castelo Branco” (06:50) showing significant longer delays between diagnosis and reperfusion treatment (orange and red arrows, respectively) than “Coimbra” (01:19) (green arrow); only 15% of patients from “Castelo Branco” had primary PCI. Fibrinolysis was chosen in 10% of patients, mostly in “Castelo Branco” (53%), followed by “Guarda” (30%), with a median time delay of 39 and 48 minutes, respectively. Regarding mortality, PCI and fibrinolysis groups had similar death rates while those patients without reperfusion had higher mortality (5% vs. 3% vs. 13%, P=0.001). Conclusion Process mining tools help to understand referencing networks visually, easily highlighting inefficiencies and potential needs for improvement. The “Centre” region of Portugal has lower rates and longer delay to primary PCI partially due to the geographical reasons, with worse outcomes in remote regions. The implementation of a new PCI centre in one of these districts, is critical to offer timely first-line treatment to their population. Funding Acknowledgement Type of funding sources: None. Figure 1