Structural-electrical remodeling of myocardium in neurological deficits in patients with ischemic stroke: Is there a connection?

Abstract Funding Acknowledgements Type of funding sources: None. Theoretical and clinical questions of the correlation between structural-electrical remodeling of the heart and the severity of neurological deficits at stroke have not been developed or remain controversial so far. Available data in the literature suggests the key role of structural myocardial disorders mainly in hemorrhagic stroke, and cardiocerebral syndrome is considered only from the standpoint of cardioembolic stroke. The aim of the study. To study the peculiarities of structural-electrical remodeling of myocardium with severity of neurological deficit in patients with ischemic stroke. Materials and methods. 111 patients with ischemic stroke in the left hemisphere and 75 patients in the right brain hemisphere were examined. The average age was 56.7 ± 5.58 years. All subjects underwent an ultrasound examination of the heart using the ALOKA SSD 5000 apparatus (Japan) and the QT dispersion using the Polyspectro-8EX apparatus (Russia). Duration of QT dispersion interval more than 50 ms was considered pathological. Research results. Structural remodeling of the heart in patients with ischemic stroke was manifested by the prevalence of high values of the finite-systolic volume of the left ventricle in comparison with patients without stroke (45.8 ± 21.0 vs. 37.7 ± 16.9 ml; p < 0.05), and the finite-diastolic volume of the left ventricle (114.3 ± 38.5 vs. 100.9 ± 35.3 ml; p < 0.05), mainly in the right hemispheric localization of the stroke. Hypertrophy of the ventricular septum (11.3 ± 2.1 and 11.1 ± 2.2) and the posterior wall of the left ventricle (10.4 ± 1.8 and 10.3 ± 2.1 mm) was observed irrespective of the localization of the stroke, which was higher in comparison with patients without stroke (9.4 ± 1.5 mm). Violations of repolarization processes and their severity were characterized by higher values of duration of the corrected QT interval in patients with structural changes of myocardium in comparison with the patients without structural remodeling (0,46 ± 0,03 and 0,44 ± 0,02 sec; p = 0,025). The conjugation of the severity of the neurological deficit (7 and more points on the NIHSS scale) was associated with the terminal-systolic size of the LV (p = 0.025) and myocardial hypertrophy (11.3 ± 1.86 vs. 10.96 ± 1.8 mm; p = 0.04) in comparison with patients with a neurological deficit of less than 7 points (31.7 ± 3.6 vs. 30.68 ± 3.86 mm; p < 0.025). The severity of the neurological deficit according to the Goldstein criteria correlated with higher values of the corrected (56.0 ± 23.93 vs. 41.6 ± 23.3 ms.; p = 0.043) and normalized QT (17.5 ± 6.533 vs. 12.8 ± 6.7 ms.; p = 0.019) values in comparison with the lower neurological deficit. A similar relationship was revealed by the Brott criteria. Conclusions. Thus, the direct connection between structural-electrical remodeling of the heart and neurological deficit revealed in the course of the study reflects the cardiocerebral relationships in ischemic stroke.

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The anesthetic approach for endovascular recanalization therapy depends on the lesion site in acute ischemic stroke

Neuroradiology ◽

10.1007/s00234-021-02762-3 ◽

2021 ◽

Author(s):

Kilian Fröhlich ◽

Gabriela Siedler ◽

Svenja Stoll ◽

Kosmas Macha ◽

Thomas M. Kinfe ◽

...

Keyword(s):

Ischemic Stroke ◽

Middle Cerebral Artery ◽

Acute Ischemic Stroke ◽

Cerebral Artery ◽

Posterior Circulation ◽

Neurological Deficits ◽

Stroke Severity ◽

Lesion Volume ◽

Middle Cerebral Artery Territory ◽

Cerebral Lesion

Abstract Purpose Endovascular therapy (EVT) of large-vessel occlusion in acute ischemic stroke (AIS) may be performed in general anesthesia (GA) or conscious sedation (CS). We intended to determine the contribution of ischemic cerebral lesion sites on the physician’s decision between GA and CS using voxel-based lesion symptom mapping (VLSM). Methods In a prospective local database, we sought patients with documented AIS and EVT. Age, stroke severity, lesion volume, vigilance, and aphasia scores were compared between EVT patients with GA and CS. The ischemic lesions were analyzed on CT or MRI scans and transformed into stereotaxic space. We determined the lesion overlap and assessed whether GA or CS is associated with specific cerebral lesion sites using the voxel-wise Liebermeister test. Results One hundred seventy-nine patients with AIS and EVT were included in the analysis. The VLSM analysis yielded associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas. Stroke severity and lesion volume were significantly higher in the GA group. The prevalence of aphasia and aphasia severity was significantly higher and parameters of vigilance lower in the GA group. Conclusions The VLSM analysis showed associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas including the thalamus that are known to cause neurologic deficits, such as aphasia or compromised vigilance, in AIS-patients with EVT. Our data suggest that higher disability, clinical impairment due to neurological deficits like aphasia, or reduced alertness of affected patients may influence the physician’s decision on using GA in EVT.

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Abstract T P167: Emergent Identification of Type A Aortic Dissection as a Cause of Acute Ischemic Stroke

Stroke ◽

10.1161/str.45.suppl_1.tp167 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Tomoyuki Ohara ◽

Kazunori Toyoda ◽

Hiroyuki Yokoyama ◽

Kenji Minatoya ◽

Eijiro Tanaka ◽

...

Keyword(s):

Ischemic Stroke ◽

Back Pain ◽

Cerebral Ischemia ◽

Aortic Dissection ◽

Intravenous Thrombolysis ◽

Type A ◽

Neurological Deficits ◽

Diagnostic Tools ◽

Acute Cerebral Ischemia ◽

D Dimer

Background: Acute aortic dissection (AAD) sometimes presents with predominant neurological symptoms of acute cerebral ischemia. Fatal AAD patients after thrombolysis for stroke without noticing AAD were reported. The purpose of this study was to clarify the characteristics of AAD patients with acute cerebral ischemia and develop a score to emergently identify AAD for such patients. Methods: From the database of Stanford type A-AAD patients admitted in our hospital between 2007 and 2012, we selected those presenting with acute focal neurological deficits due to ischemic stroke/TIA. Patients presenting with shock state or cardiopulmonary arrest were excluded. Physiological, radiological, and blood examinations were assessed for AAD identification. Results: Of 187 AAD patients, 19 patients (10%) with focal neurological deficits as an initial presentation were studied. Involvement of one or more main branches of the aortic arch was observed in all of 19 patients. Stroke experts, not cardiovascular experts, were primarily called to ER in 18 patients, and 12 were potential candidates for intravenous thrombolysis. Left hemiparesis (14 patients, 74%) was the most common neurological symptom. Nine patients (47%) complained of chest or back pain. As components of the score, (1) systolic BP differential >20mmHg between upper extremities was present in 11 of 17 patients (65%), (2) mediastinal widening on chest radiography in 13/16 (81%), (3) occlusion or the intimal flap of the proximal common carotid artery on carotid ultrasonography in 14/16 (88%), (4) pericardial effusion on echocardiography in 10/19 (47%), and (5) abnormal elevation of D-dimer levels in all 19 (median 24.8 [range 4.2-406.2] μg/ml). Two components were positive in 4 patients, three in 6, four in 5, and all the five in 4. Conclusions: Only half of AAD patients with stroke/TIA complained of chest or back pain. All the AAD patients with stroke/TIA showed high D-dimer levels and one or more additional abnormal findings in physiological and radiological examinations. Combination of such handy diagnostic tools is helpful to identify AAD without long time delay and to avoid unnecessary thrombolysis for AAD patients.

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Mechanical thrombectomy beyond the circle of Willis: efficacy and safety of different techniques for M2 occlusions

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2021-017425 ◽

2021 ◽

pp. neurintsurg-2021-017425

Author(s):

Leonardo Renieri ◽

Iacopo Valente ◽

Adam A Dmytriw ◽

Ajit S Puri ◽

Jasmeet Singh ◽

...

Keyword(s):

Ischemic Stroke ◽

Clinical Outcome ◽

Mechanical Thrombectomy ◽

Circle Of Willis ◽

Stent Retriever ◽

National Institutes Of Health ◽

Neurological Deficits ◽

Stent Retrievers ◽

Subarachnoid Hemorrhages ◽

Combined Technique

BackgroundM2 segment occlusions represent approximately one-third of non-lacunar ischemic stroke and can lead to permanent neurological deficits. Various techniques are available for mechanical thrombectomy beyond the circle of Willis, but data evaluating their effectiveness and safety are lacking.MethodsA retrospective review of patients with ischemic stroke undergoing mechanical thrombectomy for M2 occlusions from 13 centers in North American and Europe was performed. Tandem or multiple-territory occlusions were excluded. The primary outcome was 90-day modified Rankin Scale and reperfusion rates across stent-retriever, direct aspiration and combined techniques.ResultsThere were 465 patients (mean age 71.48±14.03 years, 53.1% female) with M2 occlusions who underwent mechanical thrombectomy. Stent-retriever alone was used in 133 (28.6%), direct aspiration alone in 93 (20.0%) and the combined technique in 239 (51.4%) patients. Successful reperfusion was achieved with the combined technique in 198 (82.2%; OR 2.6 (1.1–6.9)), with stent-retriever alone in 112 (84.2%; OR 9.2 (1.9–44.6)) and with direct aspiration alone in 62 (66.7%; referencecategory). Intraprocedural subarachnoid hemorrhages (iSAH) were 36 (7.7%) and were more likely to occur in patients treated with the stent-retrievers (OR 5.0 (1.1–24.3)) and combined technique (OR 4.6 (1.1–20.9)). Good clinical outcome was achieved in 260 (61.8%) patients, while 59 (14.0%) patients died. Older age, higher baseline NIHSS (National Institutes of Health Stroke Scale), parenchymal hemorrhage and iSAH were associated with poor outcome while successful recanalization and higher baseline ASPECTS (Alberta Stroke Program Early CT Score) were associated with good outcome. No differences were found among the three techniques in terms of clinical outcome.ConclusionStent-retrievers and a combined approach for M2 occlusions seem more effective than direct aspiration, but with higher rates of iSAH. This leads to no detectable difference in clinical outcome at 3 months.

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Ischemic stroke with agraphestesia signal focus

10.5327/1516-3180.470 ◽

2021 ◽

Author(s):

Ana Luísa Lopes Espínola da Costa Reis ◽

Leonardo Henrique Gandolfi de Souza ◽

Vitor Roberto Pugliesi Marques

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Parietal Lobe ◽

Cerebral Arteries ◽

Sudden Onset ◽

Neurological Deficits ◽

Motor Deficits ◽

Ischemic Event ◽

The Right ◽

Sensory Ability

Introduction: The ischemic stroke is one of the main causes of death and disability in Brazil. Among the main risk factors are age, atrial fibrillation (AF), diabetes, dyslipidemia and physical inactivity. The main etiology of stroke is cardioembolic, resulting in obstruction of the cerebral arteries by a thrombus of cardiac origin. The artery most affected in ischemic strokes is the middle cerebral artery. The stroke has main characteristics, with emphasis on the sudden onset of symptoms, involvement of a focal area, ischemia caused by obstruction of a vessel and neurological deficits depending on the affected area. Graphesthesia is defined as a cutaneous sensory ability to recognize letters or numbers traced on the skin. The loss of this sensory ability is known as agraphesthesia. Case Report: M.A.F.O. female, 78a, arrived at the UPA complaining of mental confusion. Patient denies previous stroke. Personal history of systemic arterial hypertension. Upon physical examination, the patient was conscious, self and disoriented and inattentive. He was able to repeat and evoke words, without measurable motor déficits. Left upper limb with agraphestesia. Computed tomography was requested, which showed an extensive hypodense area in the right parietoccipital region, which leads to the erasure of the furrows between the adjacent gyres, which may correspond to a recent ischemic event. Magnetic resonance imaging, diffusion-restricted area with correspondence on the ADC map, located in the right temporoparietal region inferring an acute ischemic event. An electrocardiogram was also requested, which showed an irregular rhythm, characteristic of atrial fibrillation, resulting in a diagnostic hypothesis of cardioembolic ischemic stroke. Discussion: The involvement of post-central ischemic gyrus lesions may correspond to paresthesia, anesthesia, hypoesthesia; the involvement of secondary and terciary areas of sensitivity in the upper parietal lobe, especially in the active movements of the hand and in the modalities of integrated sensitivity, their lesions may be clinically affected by: apraxias, dysgraphias, hemineglect, agraphestesia, stereoagnosia and spacial disorientation.

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Neuroprotection via AT2 receptor agonists in ischemic stroke

Clinical Science ◽

10.1042/cs20171549 ◽

2018 ◽

Vol 132 (10) ◽

pp. 1055-1067 ◽

Cited By ~ 10

Author(s):

Douglas M. Bennion ◽

U. Muscha Steckelings ◽

Colin Sumners

Keyword(s):

Ischemic Stroke ◽

Neuronal Damage ◽

Recombinant Tissue Plasminogen Activator ◽

Neurological Deficits ◽

At2 Receptor ◽

Neuroprotective Effects ◽

Receptor Agonists ◽

Stroke Epidemiology ◽

The Brain

Stroke is a devastating disease that afflicts millions of people each year worldwide. Ischemic stroke, which accounts for ~88% of cases, occurs when blood supply to the brain is decreased, often because of thromboembolism or atherosclerotic occlusion. This deprives the brain of oxygen and nutrients, causing immediate, irreversible necrosis within the core of the ischemic area, but more delayed and potentially reversible neuronal damage in the surrounding brain tissue, the penumbra. The only currently approved therapies for ischemic stroke, the thrombolytic agent recombinant tissue plasminogen activator (rtPA) and the endovascular clot retrieval/destruction processes, are aimed at restoring blood flow to the infarcted area, but are only available for a minority of patients and are not able in most cases to completely restore neurological deficits. Consequently, there remains a need for agents that will protect neurones against death following ischemic stroke. Here, we evaluate angiotensin II (Ang II) type 2 (AT2) receptor agonists as a possible therapeutic target for this disease. We first provide an overview of stroke epidemiology, pathophysiology, and currently approved therapies. We next review the large amount of preclinical evidence, accumulated over the past decade and a half, which indicates that AT2 receptor agonists exert significant neuroprotective effects in various animal models, and discuss the potential mechanisms involved. Finally, after discussing the challenges of delivering blood–brain barrier (BBB) impermeable AT2 receptor agonists to the infarcted areas of the brain, we summarize the evidence for and against the development of these agents as a promising therapeutic strategy for ischemic stroke.

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Abstract WP120: MicroRNA Expression in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/str.48.suppl_1.wp120 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Janhavi M Modak ◽

Meaghan A Roy-O’Reilly ◽

Sarah E Conway ◽

Liang Zhu ◽

Louise D McCullough

Keyword(s):

Ischemic Stroke ◽

Differential Expression ◽

Expression Profiles ◽

Outpatient Setting ◽

Microrna Expression ◽

Neurological Deficits ◽

Stroke Patients ◽

Significant Differential Expression ◽

Blood Samples ◽

Mrna Targets

Background and Purpose: MicroRNAs (miRNAs) are a class of endogenous small non-coding ribonucleic acids that regulate gene expression and can impact cellular function by suppressing or activating downstream mRNA targets. Pre-clinical studies in animal models of stroke have demonstrated specific changes in miRNA expression profiles after ischemic stroke. Methods: Patients admitted to Hartford Hospital from January 2011 - March 2014 were considered for this study. Blood samples were collected within 24 hours of stroke presentation. miRNA profiles from peripheral blood samples of ischemic stroke patients were compared to controls. Patients with acute middle cerebral artery (MCA) cardioembolic strokes (based on TOAST criteria) were included (n=16). Blood collected from patients with no acute neurological deficits in an outpatient setting served as controls (n=8). Individuals with a history of active cancer, neoplastic brain lesions or traumatic brain injury were excluded. Based on literature review, 173 miRNAs were selected to assess for differential expression between cases and controls. miRNA profiling was conducted at Exiqon Services, Denmark, using miRCURY LNA™ microRNA Array. Statistical analysis was performed using SAS. Results: In patients with acute ischemic strokes, a statistically significant differential expression was observed in 14 miRNAs as compared to controls. MicroRNAs miR-1273e, miR-5187-3p were found to be downregulated in stroke patients (p=0.01). Other miRNAs showing a significant downregulation included let 7e-5p (p=0.03); miR-4709-3p, miR-4756-3p, miR-5584-3p, miR-647 (p=0.02); miR-4742-3p (p=0.03); miR-4764-5p, miR-4531 and miR-2116-5p (p=0.04). MicroRNAs miR-664a-3p (p=0.02), miR-943 (p=0.04) and miR-145-5p (p=0.03) were significantly upregulated. Differential expression in males and females was not observed. Conclusion: Ischemic stroke patients show a differential microRNA expression profile as compared to controls. Further studies can help identify microRNA signatures as well as the downstream targets involved in the ischemic stroke molecular cascade.

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Abstract WP291: Diabetes Impairs Long-term Functional Recovery in an Embolic Stroke Model in Sex Independent Manner

Stroke ◽

10.1161/str.48.suppl_1.wp291 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Weiguo Li ◽

Sherif Hafez ◽

John Paul Valenzuela ◽

Rebecca Ward ◽

Guangkuo Dong ◽

...

Keyword(s):

Ischemic Stroke ◽

Functional Recovery ◽

Hemorrhagic Transformation ◽

Cognitive Outcome ◽

Embolic Stroke ◽

Neurological Deficits ◽

Independent Manner ◽

Male And Female ◽

The Impact

Ischemic stroke is a leading cause of death and disability. Diabetes not only increases the risk of stroke, it also worsens the outcomes, increases the risk of hemorrhagic transformation (HT) and impairs recovery after stroke. It is well established that young females are more protected and show better outcomes than males after stroke. However, the impact of diabetes on long term recovery after stroke in both sexes was not clear. Accordingly, this study tested the hypothesis that diabetes impairs long term functional recovery after ischemic stroke in a sex independent manner. Methods: Diabetes was induced in male and female Wistar rats using high fat diet and low dose streptozotocin (30 mg/Kg). After 8 weeks of diabetes, animals were subjected to embolic stroke. Male and female Wistar normoglycemic age matched rats were used as controls. Motor (composite score: 14 best outcome and adhesive removal-ART) and cognitive (novel object recognition, NOR) deficits were assessed at day1, 3, 7 and 14. Results: Female control animals had better outcomes compared to the males. Mortality was higher in diabetic animals, especially in males. The neurological deficits were greater in diabetic animals with no difference between males and females. Conclusion: Diabetes impaired functional and cognitive outcome and recovery after ischemic stroke in a sex independent manner.

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Abstract TP269: Lncrna-u90926 Aggravates Ischemic Brain Injury via Promoting Neutrophils Infiltration After Experimental Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp269 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Jian Chen ◽

Yun Xu

Keyword(s):

Ischemic Stroke ◽

Brain Injury ◽

Expression Level ◽

Neurological Deficits ◽

Neurological Injury ◽

Experimental Stroke ◽

Ischemic Brain Injury ◽

Triphenyltetrazolium Chloride ◽

Ischemic Brain ◽

Severity Scores

Background: Long non-coding RNAs (LncRNAs) are expressed at high levels in the brain in a variety of neuropathologic conditions, including stroke. However, the potential role of LncRNAs in ischemic stroke-associated microglial biological function and neurological injury remains largely unknown. Methods: Oxygen-glucose deprivation and transient middle cerebral artery occlusion (MCAO) in C57BL/6 mice were used as in vitro and in vivo ischemic stroke models. Microarray analysis was performed to explore the overall expression level changes of LncRNAs. Real-time polymerase chain reaction (RT-qPCR) was used to detect expression level of LncU90926 in brain, plasma and microglia. ShRNA-LncU90926 in lentivirus and microglia specific Adeno-associated virus (AAV) were used to knockdown LncU90926 in vitro and in vivo separately. Infarct volumes and neurological impairments were assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining, Neurological Severity Scores (NSS), rotarod test and grip strength respectively. Immunofluorescence staining and flow cytometry were performed to detect the number of neutrophils recruited to brain. RT-qPCR was used to detect the level of chemokines (CXCL, CCL2) and inflammatory mediators associated with neutrophils (MPO, MMP3 and TIMP1). Results: (1). LncU90926 was markedly up-regulated in the infarcted brain and plasma after MCAO. Both MCAO and OGD treatment induced remarkable up-regulation of LncU90926 in microglia. (2). LncU90926 knockdown definitely attenuated brain infarct size and neurological deficits after ischemic stroke. (3). LncU90926 knockdown in microglia reduced the number of neutrophils recruited to brain, and CXCL1 and CCL2 were down-regulated in both MCAO and OGD models. LncU90926 knockdown also induced reduction of MPO, MMP3 and TIMP1 in the infarcted brain. Conclusions: LncU90926 was up-regulated in microglia after experimental stroke, and aggravates ischemic brain injury through facilitating neutrophils infiltration via up-regulating microglial chemokine.

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The Role of Alpha-Lipoic Acid in the Pathomechanism of Acute Ischemic Stroke

Cellular Physiology and Biochemistry ◽

10.1159/000491661 ◽

2018 ◽

Vol 48 (1) ◽

pp. 42-53 ◽

Cited By ~ 6

Author(s):

Qingqing Wang ◽

Chengmei Lv ◽

Yongxin Sun ◽

Xu Han ◽

Shan Wang ◽

...

Keyword(s):

Ischemic Stroke ◽

Lipoic Acid ◽

Nuclear Translocation ◽

Infarct Volume ◽

Neurological Deficits ◽

Experimental Stroke ◽

Enzyme Linked Immunosorbent Assay ◽

M2 Phenotype

Background/Aims: Ischemic stroke results in increased cerebral infarction, neurological deficits and neuroinflammation. The underlying mechanisms involving the anti-inflammatory and neuroprotective properties of α-Lipoic acid (α-LA) remain poorly understood. Herein, we investigated the potential role of α-LA in a middle cerebral artery occlusion (MCAO) rat model and an in vitro lipopolysaccharide (LPS)-induced microglia inflammation model. Methods: In the in vivo study, infarct volume was examined by TTC staining and Garcia score was used to evaluate neurologic recovery. The cytokines were evaluated by enzyme-linked immunosorbent assay, and protein expression of microglia phenotype and NF-κB were measured using western blot. In the in vitro study, the expressions of microglia M1/M2 phenotype were evaluated using qRT-PCR, and immunofluorescence staining was used to assess the nuclear translocation of NF-κB. Results: Both 20 mg/kg and 40 mg/kg of α-LA alleviated infarct size, brain edema, and neurological deficits. Furthermore, α-LA induced the polarization of microglia to the M2 phenotype, modulated the expression of IL-1β, IL-6, TNF-α and IL-10, and attenuated the activation of NF-κB after MCAO. α-LA inhibited the expression of M1 markers, increased activation of the M2 markers, and suppressed the nuclear translocation of NF-κB in LPS-stimulated BV2 microglia. Conclusions: α-LA improved neurological outcome in experimental stroke via modulating microglia M1/M2 polarization. The potential mechanism of α-LA might be mediated by inhibition of NF-κB activation via regulating phosphorylation and nuclear translocation of p65.

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