Hemorrhagic transformation of ischemic stroke

The article reviews the problem of hemorrhagic transformation (HT) of ischemic stroke. The frequency and relevance of this complication in clinical practice is high considering the widespread implementation of cerebral recanalization methods: intravenous thrombolytic therapy and intravascular thromboembolectomy. The etiology and pathogenesis, as well as alternative mechanisms underlying the development of HT are also discussed. The probability of HT increases in case of extensive cerebral ischemia commonly associated with cardiac embolism. The role of spontaneous and medication-induced arterial recanalization of cerebral arteries in the genesis HT is discussed. In particular, it is noted that arterial recanalization is not an essential factor for the occurrence of HT in cerebral infarction. The severity of HT is determined by the duration and degree of cerebral ischemia. There is a need for a targeted search for HT predictors. The classification of types and criteria of HT are presented. The risk factors and scales used to predict HT are studied. Risk factors for HT are combined into several groups: clinical, laboratory, genetic, neuroimaging. Their comparative analysis is carried out and practical significance is estimated.

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Migraine and Ischemic Stroke: A Debated Question

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2008.36 ◽

2008 ◽

Vol 28 (8) ◽

pp. 1399-1421 ◽

Cited By ~ 10

Author(s):

Elisabetta Del Zotto ◽

Alessandro Pezzini ◽

Alessia Giossi ◽

Irene Volonghi ◽

Alessandro Padovani

Keyword(s):

Ischemic Stroke ◽

Cerebral Ischemia ◽

Causal Relation ◽

Focal Cerebral Ischemia ◽

Cerebral Arteries ◽

Epidemiologic Studies ◽

High Prevalence ◽

Specific Disorders ◽

New Research

Numerous epidemiologic observations reporting high prevalence of migraine among young individuals with stroke as well as dysfunction of cerebral arteries during migraine attacks prompt speculation on the existence of a comorbidity between the two disorders. The recent finding of silent infarct-like brain lesions in migraineurs reinforced this hypothesis and raised questions on whether migraine may be a progressive disorder rather than simply an episodic disorder. Stroke can occur during the course of migraine attacks with aura, supporting the assumption of a causal relation between the two diseases. Migraine may accentuate other existing risk factors for stroke, and both jointly increase the risk of cerebral ischemia outside of migraine attacks. In this regard, the role of migraine might be that of predisposing condition for cerebral ischemia. Migraine and ischemic stroke may be the end phenotype of common pathogenic mechanisms. Evidence of a migraine-stroke relation in cases of specific disorders, such as CADASIL (cerebral autosomal—dominant arteriopathy with subcortical infarcts and leukoencephalopathy) and MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), strongly supports this concept. Finally, acute focal cerebral ischemia can trigger migraine attacks, and, thus, migraine may be the consequence of stroke. In this paper, we will review contemporary epidemiologic studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions.

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The Role of Microglia in Prevention of Hemorrhagic Transformation and Blood Flow Regulation after Ischemic Stroke

Journal of Neurological Surgery Part A Central European Neurosurgery ◽

10.1055/s-0034-1383758 ◽

2014 ◽

Vol 75 (S 02) ◽

Author(s):

M. Hugelshofer ◽

A. Keller ◽

M. Wurnig ◽

L. Regli ◽

A. Aguzzi

Keyword(s):

Blood Flow ◽

Ischemic Stroke ◽

Flow Regulation ◽

Hemorrhagic Transformation ◽

Blood Flow Regulation

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The role of genetic risk factors in arterial ischemic stroke in pediatric and adult patients: a critical review

Molecular Biology Reports ◽

10.1007/s11033-014-3295-2 ◽

2014 ◽

Vol 41 (7) ◽

pp. 4241-4251 ◽

Cited By ~ 14

Author(s):

Ilona Kopyta ◽

Beata Sarecka-Hujar ◽

Joanna Sordyl ◽

Ryszard Sordyl

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Critical Review ◽

Genetic Risk ◽

Genetic Risk Factors ◽

Adult Patients ◽

Arterial Ischemic Stroke

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Abstract P625: Rate of Hemorrhagic Transformation After Ischemic Stroke and Associated Risk Factors: The Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS)

Stroke ◽

10.1161/str.52.suppl_1.p625 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Robert J Stanton ◽

Eleni Antzoulatos ◽

Elisheva R Coleman ◽

Felipe De Los Rios La Rosa ◽

Stacie L Demel ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Case Fatality ◽

Population Based ◽

Hemorrhagic Transformation ◽

Incidence Rates ◽

Icd 10 ◽

Potential Risk Factors ◽

Adjusted Rate ◽

Associated Risk Factors

Background: Hemorrhagic transformation (HT) of ischemic stroke can have devastating consequences, leading to longer hospitalizations, increased morbidity and mortality. We sought to identify the rate of HT in stroke patients not treated with tPA within a large, biracial population. Methods: The GCNKSS is a population-based stroke epidemiology study from five counties in the Greater Cincinnati region. During 2015, we captured all hospitalized strokes by screening ICD-9 codes 430-436 and ICD-10 codes I60-I68, and G45-46. Study nurses abstracted all potential cases and physicians adjudicated cases, including classifying the degree of HT. Patients treated with thrombolytics were excluded. Incidence rates per 100,000 and associated 95% confidence intervals (CI) were estimated for HT cases, age and sex adjusted to the 2000 US population. Multiple logistic regression was used to examine risk factors associated with HT. Results: In 2015, there were 2301 ischemic strokes included in the analysis. Of these 104 (4.5%) had HT; 23 (22.1%) symptomatic, 55 (52.9%) asymptomatic and 26 (25%) unknown. Documented reasons for not receiving tPA in these patients were: time (71, 68.3%), anticoagulant use (1, 1.0%), other (18,17.3%) and unknown (14, 13.5%), which were not significantly different compared to those without HT. Only 29/104 (18.3%) had HT classified as PH-1 or PH-2. The age, sex and race-adjusted rate of HT was 9.8 (7.9, 11.6) per 100,000. The table shows rates of potential risk factors and the adjusted odds of developing HT. 90 day all-cause case fatality for patients with HT was significantly higher, 27.9% vs. 15.7%, p<0.0001. Conclusion: We found that 4.5% of non-tPA treated IS patients had HT. These patients had more severe strokes, were more likely to have abnormal coagulation tests or anticoagulant use, and were more likely to die within 90 days. We also report the first population-based incidence rate of HT in non-tPA treated of 9.8/100,000, a rate similar to the incidence of SAH.

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Role of risk factors in development of chronic posttraumatic instability of ankle joint

I P Pavlov Russian Medical Biological Herald ◽

10.23888/pavlovj20183430-439 ◽

2018 ◽

Vol 26 (3) ◽

pp. 430-439

Author(s):

Maksim A. Kurov ◽

Valery G. Gоlubev

Keyword(s):

Risk Factors ◽

Ankle Joint ◽

Clinical Presentation ◽

Practical Significance ◽

Common Mechanism ◽

Chronic Instability ◽

Sporting Activity ◽

Number Of Patients ◽

Posttraumatic Instability

Injuries of the ankle joint (AJ) are the most common traumas of musculo-skeletal apparatus and a common reason for seeking medical advice. Overstrains of the ligament apparatus of AJ are the most common mechanism of traumas in running, sporting activity, in unexpected fallings into rough surfaces or getting with a heel into ribbed coverings of metroescalators, in a sharp stoppage of public transport, in wearing footwear on high heels, etc. 20-40% Of patients develop a clinical presentation of a chronic instability of the ankle joint. In the article the analysis of the literature data on the role of risk factors in development of a chronic posttraumatic instability of the ankle joint is given. In result the authors make the conclusion that the influence of the internal risk factors on development of a chronic posttraumatic instability of the ankle jointis studied insufficiently, and further investigations in this direction are required. This scientific trend is important and is of high practical significance, since its results could be used for elaboration of the algorithm of organ-saving operations which will permit to optimize medico-surgical approach, to reduce the number of patients with disability and to return patients to their professional and sporting activity.

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Abstract W MP70: Characteristics of Patients With Microemboli Detected With Transcranial Doppler Monitoring

Stroke ◽

10.1161/str.45.suppl_1.wmp70 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Lauren Koffman ◽

Zubair Ahmed ◽

Rebecca Michael ◽

Leasa Baus ◽

Larry Raber ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Care Center ◽

Cerebral Arteries ◽

Tertiary Care ◽

Cryptogenic Stroke ◽

Final Analysis ◽

Stroke Patients ◽

Artery Disease ◽

Wbc Count

Introduction: TCD emboli monitoring (TCDe) is a non-invasive tool used to detect the presence of ongoing microembolic signals (MES) in the intracranial arterial vessels. The clinical utility of this test in the evaluation of acute stroke patients has been debated. Our goal was to evaluate clinical factors associated with MES in ischemic stroke patients who underwent TCDe to determine which patient population may benefit from TCDe. Methods: Retrospective cohort study of adult patients admitted to our tertiary care center for TIA or ischemic stroke from 2011 to 2012 who underwent TCDe. Monitoring was performed for 20 minutes using a standardized protocol. Inclusion criteria included insonatation of both middle cerebral arteries and completion of TCD bubble study (TCB). Repeat TCDe performed on the same patient were excluded from the analysis. Demographic, clinical and objective data were collected using our EMR system. Results: Of the 113 patients included in the final analysis, mean age was 57.9 years and 46.9% were female. MES occurred in 33.6% patients. Mean # of MES was 9.3 (SD 60.6). Patients with MES were significantly younger (51.8 years vs 61.0, p.006) and had fewer vascular risk factors: diabetes (10.5% vs 33.3%, p 0.006), hyperlipidemia (23.7% vs 49.3%, p 0.007), hypertension (47.4% vs 17.33%, p 0.067), atrial fibrillation (7.9% vs 17.33 %, p 0.16), congestive heart failure (5.3% vs 10.7%, p 0.32) and coronary artery disease (18.4 % vs 29.3%, p 0.2). Cryptogenic stroke and the presence of right to left shunt (RLS) was more frequent in patients with MES than those without. Mean WBC count and usCRP were both nonsignificantly higher in patients with MES. Conclusions: Clinical characteristics of patients with MES on TCDe differed from those without MES, which may have diagnostic and clinical implications. Patients with MES were younger and had fewer stroke risk factors. MES were seen more often in patients with RLS and in those with cryptogenic stroke, which raises the possibility of an association between these two factors. Interestingly, patients with MES also had higher usCRP and WBC values, suggesting a possible inflammatory component to the occurrence of MES. More research is needed with a larger sample size to better define the significance of the above findings.

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Abstract TP319: Risk Factors of Post-stroke Epilepsy

Stroke ◽

10.1161/str.51.suppl_1.tp319 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Tatyana Danilova ◽

Dina Khasanova

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Functional Neuroimaging ◽

Cerebral Arteries ◽

Transcranial Doppler Sonography ◽

Epileptic Seizures ◽

Brain Lesions ◽

Control Group ◽

Ischemic Brain ◽

Post Stroke

Purpose: The aim of the study was to identify the risk factors for seizures in patients with ischemic stroke using clinical, functional, neuroimaging research methods. Materials and methods: The results of the complex survey of 468 patients suffering from ischemic stroke (256 patients experienced epileptic seizures and 203 experienced no epileptic seizures) are presented. The diagnostic procedures included clinical evaluation, magnetic resonance imaging, electroencephalography, extracranial and transcranial Doppler sonography. In addition the assessment of the rate of sodium lithium countertransport (the marker of genetically determined on transport mechanisms of cell membranes) in patients with c ischemic stroke with the development of epileptic seizures and no seizures was carried out. Results: The focal seizures are the most common (92,5%). Cortical ischemic brain lesions prevailed in patients with seizures (81,1%), whereas in the control group cortex was affected in 38,9% patients (χ2=89.2, <0,001). Stenosis of cerebral arteries was more common in patients with epilepsy (82.3%) compared to patients without seizures (74.4%, <0.05). Reduced cerebrovascular reactivity (CVR) in vertebro-basilar basin was more frequently detected in patients with seizures (85.9%, p<0.001) compared to controls (71.6%). CVR < 10% was registered in 33.8% patients with seizures versus 13.4% controls (p<0.001). Patients with epileptic seizures showed cerebral perfusion reduction mostly in vertebro-basilar basin (85.9%) rather than in carotid basin (61.2%, p<0.001). Patients experienced epileptic seizures had high rates of sodium-lithium antitransport (> 346 μmol/liter cells x hour) more often than patients without epileptic seizures (52,6% and 35,5%, respectively, <0,05). Patients experienced epileptic seizures with high rates of sodium-lithium antitransport had a higher seizure frequency than patients with low rates of sodium-lithium antitransport. Conclusion: Thus, cortical ischemic brain lesions, significant stenosis of cerebral arteries, predominant perfusion reserve reduction in the posterior cerebral circulation, as well as a high rate of sodium lithium countertransport may be considered as risk factors for post-stroke epilepsy.

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Matrix metalloproteinase-9 : surrogate marker and therapeutic target against neurovascular impairment after cerebral ischemia

10.32469/10355/57732 ◽

2015 ◽

Author(s):

◽

Shanyan Chen

Keyword(s):

Endothelial Cells ◽

Ischemic Stroke ◽

Cerebral Ischemia ◽

Molecular Mechanisms ◽

Combined Treatment ◽

Cell Penetrating Peptides ◽

Therapeutic Window ◽

Gelatinase Activity

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Stroke ranks fourth among all causes of death, and acute ischemic stroke is the most common form. The neurovascular unit (NVU) describes a basic functional structure in the brain and is primarily composed of endothelial cells, pericytes, astrocytes, microglia and neurons. The dynamic structure of the NVU is highly regulated due to interactions between different cells and extracellular matrix (ECM) components. Proteolysis of the ECM by matrix metalloproteinases (MMPs), especially MMP-9, plays an important role in the pathophysiology of cerebral ischemia and administration of tissue plasminogen activator (tPA). The activation of gelatinases (MMP-2/9) is considered a key mechanism involved in the impairment of NVU. The overall goal of this research project is to examine the role of MMP-9 in the neurovascular impairment after ischemic stroke in mice. In this project, we implemented a new strategy using gelatinase-activatable cell-penetrating peptides (ACPPs) tagged with fluorescence and/or gadolinium-based contrast agents to investigate proteolysis of gelatinases as surrogate markers of neurovascular integrity. We presented evidence that the combination of a sensitive fluorescent chromatophore and MRI contrast enhancement agent can be used to monitor gelatinase activity and its distribution in cultured neurons as well as in mice after focal cerebral ischemia. Detection of the activity of gelatinases in vivo using ACPPs could provide insights into the underlying mechanism for gelatinase proteolysis that mediate ischemia-related neurovascular impairment. We also applied a two-dimensional (2D) gelatin zymography technique that combines isoelectric focusing (IEF) with zymographic electrophoresis. We demonstrated that the 2D zymography approach can improve separation of different isoforms of gelatinases in both in vitro and in vivo conditions. 2D zymography is an effective method to separate posttranslational modification isoforms of gelatinases and to identify modifications that regulate their enzymatic activity in acute brain injuries. In work that follows, we used a fibrin-rich blood clot to occlude the middle cerebral artery (MCA) in mice as a model to represent the critical thromboembolic features of ischemic stroke in humans. In this study, we evaluated effects of SB-3CT, a mechanism-based inhibitor selective for gelatinases. We demonstrated MMP-9 activation and neurovasculature impairment in this stroke model, and showed the ability of SB-3CT to inhibit MMP-9 activity in vivo, which in turn resulted in maintenance of laminin, antagonism of pericyte contraction and loss, preservation of laminin-positive pericytes and endothelial cells, and thus rescuing neurons from apoptosis and preventing intracerebral hemorrhage. We further demonstrated that SB-3CT/tPA combined treatment could attenuate MMP-9 -- mediated degradation of endothelial laminin, impairment of endothelial cells, and decrease of caveolae -- mediated transcytosis. Early inhibition of MMP-9 proteolysis by SB-3CT decreased brain damage, reduced BBB disruption, and prevented hemorrhagic transformation after delayed tPA treatment. Therefore usage of SB-3CT will be helpful in accessing combination therapy with tPA in ischemic stroke. Results from these studies indicate the important role of MMP-9 in cerebral ischemia and thus the need for further studies to explore the molecular mechanisms underlying its activation and regulation. Results further demonstrated that the combined use of MMP-9 inhibitor with tPA may extend tPA therapeutic window for mitigating stroke damage.

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