Multiple Ischemic Strokes Research Articles

Quantification of human plasma metalloproteins in multiple sclerosis, ischemic stroke and healthy controls reveals an association of haptoglobin-hemoglobin complexes with age.

Advanced analytical methods play an important role in quantifying serum disease biomarkers. The problem of separating thousands of proteins can be reduced by analyzing for a ‘sub-proteome’, such as the ‘metalloproteome’, defined as all proteins that contain bound metals. We employed size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES) to analyze plasma from multiple sclerosis (MS) participants (n = 21), acute ischemic stroke (AIS) participants (n = 17) and healthy controls (n = 21) for Fe, Cu and Zn-metalloproteins. Using ANOVA analysis to compare the mean peak areas among the groups revealed no statistically significant differences for ceruloplasmin (p = 0.31), α2macroglobulin (p = 0.51) and transferrin (p = 0.31). However, a statistically significant difference was observed for the haptoglobin-hemoglobin (Hp-Hb) complex (p = 0.04), being driven by the difference between the control group and AIS (p = 0.012), but not with the MS group (p = 0.13), based on Dunnes test. A linear regression model for Hp-Hb complex with the groups now adjusted for age found no statistically significant differences between the groups (p = 0.95), but was suggestive for age (p = 0.057). To measure the strength of association between the Hp-Hb complex and age without possible modifications due to disease, we calculated the Spearman rank correlation in the healthy controls. The latter revealed a positive association (r = 0.39, 95% Confidence Interval = (-0.05, 0.83), which suggests that either the removal of Hp-Hb complexes from the blood circulation slows with age or that the release of Hb from red blood cells increases with age. We also observed that the Fe-peak corresponding to the Hp-Hb complex eluted ~100 s later in ~14% of all study samples, which was not correlated with age or disease diagnosis, but is consistent with the presence of the smaller Hp (1–1) isoform in 15% of the population.

S3676 Rare Case Report of Multiple Ischemic Strokes and Subarachnoid Hemorrhage After TACE Procedure

S3676 Rare Case Report of Multiple Ischemic Strokes and Subarachnoid Hemorrhage After TACE Procedure

Clinical features of Trousseau's syndrome with multiple acute ischemic strokes.

Trousseau's syndrome or migrating thrombophlebitis can cause venous or arterial thrombosis; however, multiple acute ischemic strokes (MAIS) caused by Trousseau's syndrome are rare. The aim of this study was to analyse the clinical features of Trousseau's syndrome with MAIS and to improve the awareness and the knowledge of this disease. Clinical data from fifteen patients who were diagnosed as Trousseau's syndrome with MAIS in Rizhao People's Hospital from January 2017 to April 2020 were collected and analysed. The clinical data included the following: patients' basic information (including gender, age, underlying diseases, and tumour stage), laboratory results, imaging features, treatment regimens, and short-term prognoses were collected. The mean age was 65.5years, with thirteen males and two females. Most patients (11/15) had a history of smoking and (or) drinking. The average score of NIHSS was 2.13. 6 of the 15 patients first presented with ischemic stroke and then found the primary tumour. Most common types of primary tumour was lung cancer (11/15), and other types of primary tumour were gastric adenocarcinoma, renal cell carcinoma, oesophageal adenosquamous carcinoma, and cholangiocarcinoma (one in each). All the 15 patients showed different levels of increase of D-dimer. The increase in CRP appears in 10 of the 15 patients. Various tumour markers were increased in the 15 patients, especially for CYFRA-211, all the patients of which were higher than normal. All of the 15 patients had multiple vascular territory lesions in DWI, and most lesions were near the cortex areas. Only 4 of the 15 patients (26.7%) occurred with peripheral venous thrombosis. Thirteen patients were given low molecular heparin for anticoagulant therapy, of which 9 patients were improved in short-term while 4 patients were not. Trousseau's syndrome with MAIS was associated with old-age male, smoking and (or) drinking history, low NIHSS score, increased D-dimer, CRP and tumour markers, and lesions near the cortex areas with multiple vascular territories in DWI. Patients with these features should be alert of malignant tumour. Most common types of primary tumour were lung cancer. Treatment with low molecular heparin may be effective in short term.

Papillary glioneural tumor presenting with multiple ischemic strokes: an aggressive presentation of a “benign” entity

Papillary glioneural tumors are infrequent neoplasms of the central nervous system, classically presenting with an indolent clinical course, rarely being related to an aggressive presentation, and not being associated with ischemic or another type of paraneoplastic phenomena. We describe the first case of this type of presentation with a literature review of the current knowledge of this entity. A 16-year-old female presented with a hemorrhagic intra-axial lesion, confirmed to be a papillary glioneural tumor in the histopathological analysis, being associated with multiple ischemic cerebral and posterior fossa strokes without another discernable cause than the presence of a paraneoplastic syndrome, not previously reported with this type of neoplasms. A literature review is presented detailing the current knowledge about this entity and emphasizing the need for greater knowledge about its natural history, immunobiology and treatment alternatives, opening a new window for the study of this pathology and establishing the need for a strict follow-up of patients who have this kind of tumors in order to learn more about their evolution. The papillary glioneural tumor, a rare entity having generally with a benign course, can have different presentations. Greater knowledge is needed to understand this behavior in order to optimize patient’s outcomes.

Papillary Glioneural Tumor Presenting with Multiple Ischemic Strokes: An Aggressive Presentation of a "Benign" Entity

Papillary glioneural tumors are infrequent neoplasms of the central nervous system, classically presenting with an indolent clinical course, rarely being related to an aggressive presentation, and not being associated with ischemic or another type of paraneoplastic phenomena. We describe the first case of this type of presentation with a literature review of the current knowledge of this entity.

Nutraceutical and therapeutic potential of Phycocyanobilin for treating Alzheimer’s disease

Alzheimer's disease (AD) is a devastating neurodegenerative condition provoking the loss of cognitive and memory performances. Despite huge efforts to develop effective AD therapies, there is still no cure for this neurological condition. Here, we review the main biological properties of Phycocyanobilin (PCB), accounting for its potential uses against AD. PCB, given individually or released in vivo from C-Phycocyanin (C-PC), acts as a bioactive-molecule-mediating antioxidant, is anti-inflammatory and has immunomodulatory activities. PCB/C-PC are able to scavenge reactive oxygen and nitrogen species, to counteract lipid peroxidation and to inhibit enzymes such as NADPH oxidase and COX-2. In animal models of multiple sclerosis and ischemic stroke, these compounds induce remyelination as demonstrated by electron microscopy and the expression of genes such as Mal up-regulation of and Lingo-1 down-regulation. These treatments also reduce pro-inflammatory cytokines levels and induce immune suppressive genes. PCB/C-PC protects isolated rat brain mitochondria and inactivate microglia, astrocytes and neuronal apoptosis mediators. Such processes are all involved in the pathogenic cascade of AD, and thus PCB may effectively mitigate the injury in this condition. Furthermore, PCB can be administered safely by oral or parenteral routes and therefore, could be commercially offered as a nutraceutical supplement or as a pharmaceutical drug.

MRI topography of lesions related to internuclear ophthalmoplegia in patients with multiple sclerosis or ischemic stroke.

Internuclear ophthalmoplegia is a dysfunction of conjugate eye movements, caused by lesions affecting the medial longitudinal fasciculus (MLF). Multiple sclerosis (MS) and ischemic stroke represent the most common pathophysiologies. While magnetic resonance imaging (MRI) allows for localizing lesions affecting the MLF, comprehensive comparative studies exploring potential different spatial characteristics of lesions affecting the MLF are missing until now. We retrospectively investigated MRI examinations of 82 patients (40 patients with MS and 42 patients with ischemic stroke). For lesion localization, the brainstem was segmented into (1) ponto-medullary junction, (2) mid pons, (3) upper pons, and (4) mesencephalon. Corresponding lesions affecting the MLF were observed in 29/40 (72.5%) MS and 38/42 (90.5%) stroke patients. Compared to stroke patients, MS patients had significantly more lesions in multiple locations (P < .001). Stroke patients showed more lesions at the level of the mesencephalon (P < .001), while lesions at the level of the ponto-medullary junction, mid, and upper pons did not statistically differ between the groups. Our results demonstrate that multiple lesions affecting the MLF make inflammatory-demyelination due to MS more likely, while lesion localization at the level of the mesencephalon favors ischemia.

The Case | Acute kidney injury associated with chronic myelomonocytic leukemia

A 70-year-old man with a history of high blood pressure and multiple ischemic strokes was diagnosed with stage 2 chronic myelomonocytic leukemia in 2014. At diagnosis, estimated glomerular filtration rate was normal (100 ml/min per 1.73 m2). Bone marrow aspiration showed 15% blasts, for which azacytidine was prescribed. The patient refused the recommended treatment, and hydroxyurea was introduced instead.

Protective Functions of Reactive Astrocytes Following Central Nervous System Insult.

Astrocytes play important roles in numerous central nervous system disorders including autoimmune inflammatory, hypoxic, and degenerative diseases such as Multiple Sclerosis, ischemic stroke, and Alzheimer’s disease. Depending on the spatial and temporal context, activated astrocytes may contribute to the pathogenesis, progression, and recovery of disease. Recent progress in the dissection of transcriptional responses to varying forms of central nervous system insult has shed light on the mechanisms that govern the complexity of reactive astrocyte functions. While a large body of research focuses on the pathogenic effects of reactive astrocytes, little is known about how they limit inflammation and contribute to tissue regeneration. However, these protective astrocyte pathways might be of relevance for the understanding of the underlying pathology in disease and may lead to novel targeted approaches to treat autoimmune inflammatory and degenerative disorders of the central nervous system. In this review article, we have revisited the emerging concept of protective astrocyte functions and discuss their role in the recovery from inflammatory and ischemic disease as well as their role in degenerative disorders. Focusing on soluble astrocyte derived mediators, we aggregate the existing knowledge on astrocyte functions in the maintenance of homeostasis as well as their reparative and tissue-protective function after acute lesions and in neurodegenerative disorders. Finally, we give an outlook of how these mediators may guide future therapeutic strategies to tackle yet untreatable disorders of the central nervous system.

Multiple Ischemic Strokes Associated with Childhood Progressive Radiation-Induced Occlusive Cerebral Vasculopathy

AbstractThere is little knowledge on the pathophysiology of pediatric stroke associated with radiation-induced occlusive cerebral vasculopathy (RIOCV). Herein, we present an extremely rare case of a child with multiple ischemic strokes in association with progressive RIOCV. The possibility of hemodynamic compromise and artery-to-artery embolism as a cause of the ischemic events is discussed.

Targeted re-sequencing in pediatric and perinatal stroke

Pediatric and perinatal stroke can present as an early symptom in undiagnosed syndromes characterized by simple Mendelian inheritance. In order to diagnose those patients affected with a monogenic disorder in which an arterial cerebrovascular event or arteriopathy may have preceded any other specific symptom, we aimed to establish and validate a targeted gene panel, and to determine its diagnostic yield and clinical utility. To this end, thirty-eight patients were selected with heterogeneous cryptogenic stroke phenotypes, mostly including multiple and recurrent ischemic or hemorrhagic arterial strokes and porencephalies, variably associated with calcifications, intracranial or systemic steno-occlusive arteriopathies, positive family history, and syndromic conditions. Clinical and neuroradiological data were collected for every patient enrolled in the study, and DNA samples were tested by means of a customized gene panel including 15 genes associated with known genetic diseases related to pediatric stroke. In four patients (10.5%) the analyses unraveled pathogenetic variants in ABCC6 and COL4A1 genes, leading to a definite genetic diagnosis with a great beneficial impact on patients management, while results were null in the remaining patients. These findings suggest a high complexity and variability of the included stroke phenotypes, that could not be fully accounted for by the genes tested in the present study. A wider gene panel or an unbiased genomic approach may be better suited and advisable to explain a greater proportion of pediatric and perinatal stroke events.

Multiple Acute Ischemic Strokes in a COVID-19 Patient: a Case Report.

We describe a case of a 47-year-old Italian, immunocompromised, and obese woman infected by COVID-19 presenting with fever (39.6 °C) and respiratory symptoms. Neurological examination was normal. Chest CT findings consist of bilateral interstitial pneumonia (visual score extension: 30%). The patient was treated with antiviral drugs and anti-inflammatory drugs with supportive care. Seven days after admission to Covid-19 Unit, the patient rapidly developed worsening respiratory failure and acute respiratory distress syndrome (ARDS). She suddenly developed partial left hemispheric syndrome. A new HRCT scan of her thorax revealed diffuse ground-glass opacities in both lungs (visual score extension: 90%). Brain CT performed 2 h after sudden-onset left-sided weakness showed subtle low attenuation within the right insular ribbon and frontal lobe (ASPECT Score 8). Multiphasic CT angiography (MCTA) demonstrated occlusion of both the dominant inferior division of the right middle cerebral artery and the A2 segment of the right anterior cerebral artery. After 24 h, her pupils became dilated and unreactive, and brain CT demonstrated large bilateral infarctions of both the cerebellar and cerebral hemispheres. She had a rapid progression of interstitial pneumonia from COVID-19, developed multiple strokes, and died 1 day later. SARS-CoV-2 infection seems to predispose pluripathological subjects to cerebrovascular complications.

Genetic Etiology Shared by Multiple Sclerosis and Ischemic Stroke.

Although dramatic progress has been achieved in the understanding and treatment of multiple sclerosis (MS) and ischemic stroke (IS), more precise and instructive support is required for further research. Recent large-scale genome-wide association studies (GWASs) have already revealed risk variants for IS and MS, but the common genetic etiology between MS and IS remains an unresolved issue. This research was designed to overlapping genes between MS and IS and unmask their transcriptional features. We designed a three-section analysis process. Firstly, we computed gene-based analyses of MS GWAS and IS GWAS data sets by VGEAS2. Secondly, overlapping genes of significance were identified in a meta-analysis using the Fisher’s procedure. Finally, we performed gene expression analyses to confirm transcriptional changes. We identified 24 shared genes with Bonferroni correction (Pcombined < 2.31E-04), and five (FOXP1, CAMK2G, CLEC2D, LBH, and SLC2A4RG) had significant expression differences in MS and IS gene expression omnibus data sets. These meaningful shared genes between IS and MS shed light on the underlying genetic etiologies shared by the diseases. Our results provide a basis for in-depth genomic studies of associations between MS and IS.

Arterial Ischemic Stroke in the Pediatric Population

Recognizing childhood arterial ischemic stroke risk factors and presentation are extremely important for a prompt diagnosis and administration of hyperacute treatment requiring a high level of clinical suspicion. Stroke presentation in the pediatric population is not very specific, yet it is imperative to distinguish it from other mimics that may require different medical management. Vascular imaging studies, including MRA, CTA, and advanced neuroimaging techniques (eg, arterial wall imaging and CT/MR perfusion images) are extremely useful in the diagnosis of arterial ischemic stroke. This article offers a review of arterial pediatric ischemic stroke risk factors, clinical presentation, and the imaging appearance of the most common arterial ischemic stroke etiologies.Learning Objective: To recognize multiple risk factors, etiologies, and imaging presentations of pediatric arterial ischemic strokes.

Lambl’s Excrescence Associated with Recurrent Ischemic Strokes

Lambl's excrescence (LE) is a rare thin, mobile, filiform frond on the endocardial surface of cardiac valves responsible for recurrent ischemic strokes due to embolic phenomena. Due to nonspecific symptoms, sometimes the diagnosis is challenging. It can be diagnosed by transesophageal echocardiogram (TEE) with increased sensitivity. Several case reports have been published with a strategy to manage LE but there is lack of consensus. We report a case of a 75-year-old patient with the LE arising from aortic valve resulting in recurrent ischemic strokes within a short period and its management. A 75-year-old male with multiple vascular risk factors presented with confusion, altered mental status of unknown onset and aphasia. He denied weakness, numbness, or other focal neurological deficits. National Institute of Health Stroke Scale was 5. IV tPA was not given due to the unknown onset of symptoms. The magnetic resonance imaging (MRI) revealed acute/subacute left thalamic lacunar infarct. TEE demonstrated a 7-mm linear fibrinous mass on the valve. The patient was on aspirin which was changed to clopidogrel. After 2 weeks, the patient readmitted with similar presentation. MRI showed subacute right parietal cortical infarct. The patient was advised to proceed with surgical resection of LE. Due to refusal for surgery, he was kept on 30 days cardiac monitor and had given anticoagulant therapy for secondary prevention of stroke. Although wide range from single or dual antiplatelet therapy to full dose anticoagulation have been tried, surgical intervention should be considered in case of multiple ischemic strokes to mitigate the risk of embolism.

Reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndrome is characterized by severe headaches with or without focal neurologic deficits and/or seizures, and segmental constriction of cerebral arteries that resolves within 3 months. This increasingly recognized syndrome is supposedly due to a transient disturbance in the control of cerebral vascular tone with sympathetic overactivity. It can cause stroke in the young. It affects mainly middle-aged women. More than half the cases occur after exposure to vasoactive substances or during postpartum. The manifestations have a monophasic course, without new clinical symptom after 4 weeks, and range from pure cephalalgic forms with recurrent thunderclap headaches over 1-2 weeks to rare catastrophic forms with multiple hemorrhagic and ischemic strokes, brain edema and death. Diagnosis may be hampered by the dynamic nature of clinicoradiological features. Convexity subarachnoid hemorrhage or stroke may occur a few days after initial normal imaging, and cerebral vasoconstriction is maximal on angiography 2-3 weeks after clinical onset. Symptomatic treatment includes rest and removal of vasoactive substances. Nimodipine has been proposed to reduce thunderclap headaches within 48 hours, but has no proven effect on the hemorrhagic and ischemic complications.

HYPEREOSINOPHILIC SYNDROME: A HARBINGER OF FULMINANT EOSINOPHILIC MYOCARDITIS

Eosinophilic myocarditis is uncommon but can be fulminant in patients with hypereosinophilic syndrome. A 46 year-old woman presented with acute encephalopathy in the setting of multiple bilateral ischemic strokes and profound eosinophilia (63%) of unknown etiology. Initial TTE and TEE showed normal

Shared Gene Expression Between Multiple Sclerosis and Ischemic Stroke.

Patients with multiple sclerosis (MS) appear to have an increased risk of ischemic stroke (IS). Although MS and IS have very different phenotypes, gene-based and pathway-based analyses of large-scale genome-wide association studies (GWAS) have increasingly enhanced our understanding of these two diseases. Whether there are common molecular mechanisms connecting MS and IS is still unclear. Here, we describe the outcome of gene-based test and pathway-based analysis of GWAS datasets that explored potential gene expression links between MS and IS. After identifying significant gene sets individually of MS and IS, we performed pathway-based analysis in four biological pathway databases (KEGG, PANTHER, REACTOME, and WikiPathways) and GO categories. We discovered that there were 9 shared pathways between MS and IS in KEGG, 2 in PANTHER, 14 in REACTOME, 1 in WikiPathways, and 194 in GO annotations (p < 0.05). These results provide an improved understanding about possible shared mechanisms and treatments strategies for MS and IS. They also provide some basis for further studies of how these two diseases are linked at the molecular level.

Multiple ischemic stroke in Osler-Rendu-Weber disease

Hereditary hemorrhagic teleangiectasia (HHT, Osler-Rendu-Weber disease) is an autosomal dominantly inherited disorder caused by the mutation of several possible genes and characterized by malformations of the arteriovenous system in multiple organs. The clinical diagnosis is based on the Curacao criteria ((1) spontaneous, recurrent epistaxis; (2) teleangiectasias in characteristic sites (lips, oral cavity, nose, fingers); (3) visceral lesions (gastrointestinal, pulmonary, cerebral, spinal); (4) affected first degree relative). The aim of this study is to present the first genetically confirmed Hungarian case of hereditary hemorrhagic teleangiectasia with multiple ischemic strokes. Our 70-year-old woman has been suffering from severe epistaxis since her childhood and presented gastrointestinal bleeding during her adulthood as well. The characteristic skin lesions developed in the 5th decade of life. She was admitted to our department with loss of consciousness and fluctuating speech and swallowing problems. MRI of the brain supplemented with angiography revealed multiple arteriovenous malformations and multiple subacute ischemic lesions. The EEG demonstrated slowing of electric activity in the left frontal lobe. The neuropsychological assessment showed deficits in anterograde memory and executive functions. The diagnostic work-up for other characteristic alterations identified an arteriovenous malformation in the left lung. The genetic analysis demonstrated a heterozygous mutation in the 7th exon of the ENG gene at position 834 resulting in a thymine duplication and an early stop codon by a frame shift. The present case is largely similar to those already described in literature and draws the attention to the importance of multidisciplinary collaboration in the care of HHT patients.

Potentially Common Therapeutic Targets for Multiple Sclerosis and Ischemic Stroke.

Ischemic stroke (IS) and multiple sclerosis (MS) are two pathologies of the central nervous system (CNS). At the first look, this appears to be the only similarity between the two diseases, as they seem quite different. Indeed IS has an acute onset compared to MS which develops chronically; IS is consecutive to blood clot migrating to cerebral blood vessels or decrease in cerebral blood flow following atherosclerosis or decreases in cardiac output, whereas MS is an immune disease associated with neurodegeneration. However, both pathologies share similar pathologic pathways and treatments used in MS have been the object of studies in IS. In this mini-review we will discuss similarities between IS and MS on astrocytes and neuroinflammation hallmarks emphasizing the potential for treatments.