Biomedicines

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Open AccessEditorial

EDITORIAL: Stroke—Pathophysiology and New Therapeutic Strategies

by Roger E. Kelley

Biomedicines 2022, 10(7), 1529; https://doi.org/10.3390/biomedicines10071529 - 28 Jun 2022

Viewed by 1266

Abstract

This Special Issue of Biomedicines highlights recent advances in stroke evaluation and management and provides some pertinent information about potential new directions of stroke intervention in the research realm [...] Full article

(This article belongs to the Special Issue Stroke—Pathophysiology and New Therapeutic Strategies)

Research

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12 pages, 1093 KiB

Open AccessArticle

The Spectrum of Acute Cerebrovascular Disease in Patients with COVID-19

by Rachel Triay, Prabandh Buchhanolla, Alexas Gaudet, Victoria Winter, Alexandra Gaudet, Mehdi Faraji, Eduardo Gonzalez-Toledo, Harish Siddaiah, Hugo H. Cuellar-Saenz, Steven Bailey, Vijayakumar Javalkar, Rosario Maria S. Riel-Romero, Roger E. Kelley, Felicity N. E. Gavins and Junaid Ansari

Biomedicines 2022, 10(2), 435; https://doi.org/10.3390/biomedicines10020435 - 13 Feb 2022

Cited by 2 | Viewed by 2693

Abstract

(1) Background: COVID-19 infection is responsible for the ongoing pandemic and acute cerebrovascular disease (CVD) has been observed in COVID-19 patients. (2) Methods: We conducted a retrospective, observational study of hospitalized adult patients admitted to our hospital with SARS-CoV-2 and acute cerebrovascular disease. [...] Read more.

(1) Background: COVID-19 infection is responsible for the ongoing pandemic and acute cerebrovascular disease (CVD) has been observed in COVID-19 patients. (2) Methods: We conducted a retrospective, observational study of hospitalized adult patients admitted to our hospital with SARS-CoV-2 and acute cerebrovascular disease. All clinical data were reviewed including epidemiology, clinical features, laboratory data, neuroradiological findings, hospital management and course from 32 patients hospitalized for COVID-19 management with acute cerebrovascular disease. (3) Results: Acute CVD with COVID-19 was associated with higher NIH stroke scale on discharge compared to non-COVID-19 CVDs. Seizures complicated the hospital course in 16% of COVID-19 patients with CVD. The majority of the acute CVDs were ischemic (81%) in nature followed by hemorrhagic (22%). Acute CVD with COVID-19 resulted in average hospital stays greater than twice that of the control group (13 days in COVID-19, 5 days in control). Acute CVD with COVID-19 patients had worse clinical outcomes with 31% patient deaths and 6% discharged to hospice. In the control group, 6% of patients died. (4) Conclusions: Acute CVD associated with COVID-19 tends to be more complicated with unique and adverse clinical phenotype, longer hospital admissions, and worse clinical outcomes. Full article

(This article belongs to the Special Issue Stroke—Pathophysiology and New Therapeutic Strategies)

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16 pages, 6739 KiB

Open AccessArticle

Treatment Efficacy Analysis in Acute Ischemic Stroke Patients Using In Silico Modeling Based on Machine Learning: A Proof-of-Principle

by Anthony Winder, Matthias Wilms, Jens Fiehler and Nils D. Forkert

Biomedicines 2021, 9(10), 1357; https://doi.org/10.3390/biomedicines9101357 - 29 Sep 2021

Cited by 6 | Viewed by 2924

Abstract

Interventional neuroradiology is characterized by engineering- and experience-driven device development with design improvements every few months. However, clinical validation of these new devices requires lengthy and expensive randomized controlled trials. This contribution proposes a machine learning-based in silico study design to evaluate new [...] Read more.

Interventional neuroradiology is characterized by engineering- and experience-driven device development with design improvements every few months. However, clinical validation of these new devices requires lengthy and expensive randomized controlled trials. This contribution proposes a machine learning-based in silico study design to evaluate new devices more quickly with a small sample size. Acute diffusion- and perfusion-weighted MRI, segmented one-week follow-up imaging, and clinical variables were available for 90 acute ischemic stroke patients. Three treatment option-specific random forest models were trained to predict the one-week follow-up lesion segmentation for (1) patients successfully recanalized using intra-arterial mechanical thrombectomy, (2) patients successfully recanalized using intravenous thrombolysis, and (3) non-recanalizing patients as an analogue for conservative treatment for each patient in the sample, independent of the true group membership. A repeated-measures analysis of the three predicted follow-up lesions for each patient revealed significantly larger lesions for the non-recanalizing group compared to the successful intravenous thrombolysis treatment group, which in turn showed significantly larger lesions compared to the successful mechanical thrombectomy treatment group (p < 0.001). A groupwise comparison of the true follow-up lesions for the three treatment options showed the same trend but did not reach statistical significance (p = 0.19). We conclude that the proposed machine learning-based in silico trial design leads to clinically feasible results and can support new efficacy studies by providing additional power and potential early intermediate results. Full article

(This article belongs to the Special Issue Stroke—Pathophysiology and New Therapeutic Strategies)

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Review

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11 pages, 2187 KiB

Open AccessReview

Endovascular Intervention in Acute Ischemic Stroke: History and Evolution

by Junaid Ansari, Rachel Triay, Sandeep Kandregula, Nimer Adeeb, Hugo Cuellar and Pankaj Sharma

Biomedicines 2022, 10(2), 418; https://doi.org/10.3390/biomedicines10020418 - 10 Feb 2022

Cited by 11 | Viewed by 3842

Abstract

Stroke is a leading cause of serious long-term disability in the US. Endovascular therapy (EVT), in the form of mechanical thrombectomy, is now a standard of care for patients with acute ischemic stroke with a large vessel occlusion. This article reviews the evolution [...] Read more.

Stroke is a leading cause of serious long-term disability in the US. Endovascular therapy (EVT), in the form of mechanical thrombectomy, is now a standard of care for patients with acute ischemic stroke with a large vessel occlusion. This article reviews the evolution of EVT in the management of acute ischemic stroke and how it has led to the concept of tissue window over the widely publicized time window. Full article

(This article belongs to the Special Issue Stroke—Pathophysiology and New Therapeutic Strategies)

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15 pages, 296 KiB

Open AccessReview

Endovascular Management of Hemorrhagic Stroke

by Basel Musmar, Nimer Adeeb, Junaid Ansari, Pankaj Sharma and Hugo H. Cuellar

Biomedicines 2022, 10(1), 100; https://doi.org/10.3390/biomedicines10010100 - 4 Jan 2022

Cited by 8 | Viewed by 3398

Abstract

Significant advances in endovascular neurosurgery tools, devices, and techniques are changing the approach to the management of acute hemorrhagic stroke. The endovascular treatment of intracranial aneurysms emerged in the early 1990s with Guglielmi detachable coils, and since then, it gained rapid popularity that [...] Read more.

Significant advances in endovascular neurosurgery tools, devices, and techniques are changing the approach to the management of acute hemorrhagic stroke. The endovascular treatment of intracranial aneurysms emerged in the early 1990s with Guglielmi detachable coils, and since then, it gained rapid popularity that surpassed open surgery. Stent-assisted coiling and balloon remodeling techniques have made the treatment of wide-necked aneurysms more durable. With the introduction of flow diverters and flow disrupters, many aneurysms with complex geometrics can now be reliably managed. Arteriovenous malformations and fistulae can also benefit from endovascular therapy by embolization using n-butyl cyanoacrylate (NBCA), Onyx, polyvinyl alcohol (PVA), and coils. In this article, we describe the role of endovascular treatment for the most common causes of intracerebral and subarachnoid hemorrhages, particularly ruptured aneurysms and vascular malformations. Full article

(This article belongs to the Special Issue Stroke—Pathophysiology and New Therapeutic Strategies)

13 pages, 2293 KiB

Open AccessReview

Neutrophils and Platelets: Immune Soldiers Fighting Together in Stroke Pathophysiology

by Junaid Ansari and Felicity N. E. Gavins

Biomedicines 2021, 9(12), 1945; https://doi.org/10.3390/biomedicines9121945 - 19 Dec 2021

Cited by 8 | Viewed by 4277

Abstract

Neutrophils and platelets exhibit a diverse repertoire of functions in thromboinflammatory conditions such as stroke. Most cerebral ischemic events result from longstanding chronic inflammation secondary to underlying pathogenic conditions, e.g., hypertension, diabetes mellitus, obstructive sleep apnea, coronary artery disease, atrial fibrillation, morbid obesity, [...] Read more.

Neutrophils and platelets exhibit a diverse repertoire of functions in thromboinflammatory conditions such as stroke. Most cerebral ischemic events result from longstanding chronic inflammation secondary to underlying pathogenic conditions, e.g., hypertension, diabetes mellitus, obstructive sleep apnea, coronary artery disease, atrial fibrillation, morbid obesity, dyslipidemia, and sickle cell disease. Neutrophils can enable, as well as resolve, cerebrovascular inflammation via many effector functions including neutrophil extracellular traps, serine proteases and reactive oxygen species, and pro-resolving endogenous molecules such as Annexin A1. Like neutrophils, platelets also engage in pro- as well as anti-inflammatory roles in regulating cerebrovascular inflammation. These anucleated cells are at the core of stroke pathogenesis and can trigger an ischemic event via adherence to the hypoxic cerebral endothelial cells culminating in aggregation and clot formation. In this article, we review and highlight the evolving role of neutrophils and platelets in ischemic stroke and discuss ongoing preclinical and clinical strategies that may produce viable therapeutics for prevention and management of stroke. Full article

(This article belongs to the Special Issue Stroke—Pathophysiology and New Therapeutic Strategies)

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14 pages, 293 KiB

Open AccessReview

Antithrombotic Therapy in the Prevention of Stroke

by Shyamal Bir and Roger E. Kelley

Biomedicines 2021, 9(12), 1906; https://doi.org/10.3390/biomedicines9121906 - 14 Dec 2021

Cited by 6 | Viewed by 3923

Abstract

Overview: Ischemic stroke is a leading cause of death and disability throughout the world. Antithrombotic therapy, which includes both antiplatelet and anticoagulant agents, is a primary medication of choice for the secondary prevention of stroke. However, the choices vary with the need to [...] Read more.

Overview: Ischemic stroke is a leading cause of death and disability throughout the world. Antithrombotic therapy, which includes both antiplatelet and anticoagulant agents, is a primary medication of choice for the secondary prevention of stroke. However, the choices vary with the need to incorporate evolving, newer information into the clinical scenario. There is also the need to factor in co-morbid medical conditions as well as the cost ramifications for a particular patient as well as compliance with the regimen. Pertinent Updates: In the acute setting, dual antiplatelet therapy from three weeks to up to three months has become recognized as a reasonable approach for patients with either minor stroke or transient ischemic attack or those with symptoms associated with higher-grade intracranial stenosis. This approach is favored for non-cardioembolic stroke as a cardiogenic mechanism tends to be best managed with attention to the cardiac condition as well as anticoagulant therapy. Risk stratification for recurrent stroke is important in weighing potential risk versus benefits. For example, prolonged dual antiplatelet therapy, with a combination such as aspirin and clopidogrel or aspirin and ticagrelor, tends to have negation of the potential clinical benefit of stroke prevention, over time, by the enhanced bleeding risk. Anticoagulant choices are now impacted by newer agents, initially identified as novel oral anticoagulants (NOACs), which also became associated with “non-vitamin K” agents as they are no longer considered novel. Alternatively, they are now often identified as direct oral anticoagulants (DOACs). They tend to be viewed as superior or non-inferior to warfarin with the caveat that warfarin is still viewed as the agent of choice for stroke prevention in patients with mechanical heart valves. Conclusion: Based upon cumulative information from multiple clinical trials of secondary prevention of stroke, there is an increasing array of approaches in an effort to provide optimal management. Antithrombotic therapy, including in combination with anticoagulant therapy, continues to evolve with the general caveat that “one size does not fit all”. In view of this, we desire to provide an evidence-based approach for the prevention of stroke with antithrombotic agents. Full article

(This article belongs to the Special Issue Stroke—Pathophysiology and New Therapeutic Strategies)

14 pages, 844 KiB

Open AccessReview

Heart–Brain Relationship in Stroke

by Roger E. Kelley and Brian P. Kelley

Biomedicines 2021, 9(12), 1835; https://doi.org/10.3390/biomedicines9121835 - 4 Dec 2021

Cited by 18 | Viewed by 6075

Abstract

The patient presenting with stroke often has cardiac-related risk factors which may be involved in the mechanism of the stroke. The diagnostic assessment is predicated on recognition of this potential relationship. Naturally, an accurate history is of utmost importance in discerning a possible [...] Read more.

The patient presenting with stroke often has cardiac-related risk factors which may be involved in the mechanism of the stroke. The diagnostic assessment is predicated on recognition of this potential relationship. Naturally, an accurate history is of utmost importance in discerning a possible cause and effect relationship. The EKG is obviously an important clue as well as it allows immediate assessment for possible cardiac arrhythmia, such as atrial fibrillation, for possible acute ischemic changes reflective of myocardial ischemia, or there may be indirect factors such as the presence of left ventricular hypertrophy, typically seen with longstanding hypertension, which could be indicative of a hypertensive mechanism for a patient presenting with intracerebral hemorrhage. For all presentations in the emergency room, the vital signs are important. An elevated body temperature in a patient presenting with acute stroke raises concern about possible infective endocarditis. An irregular–irregular pulse is an indicator of atrial fibrillation. A markedly elevated blood pressure is not uncommon in both the acute ischemic and acute hemorrhagic stroke setting. One tends to focus on possible cardioembolic stroke if there is the sudden onset of maximum neurological deficit versus the stepwise progression more characteristic of thrombotic stroke. Because of the more sudden loss of vascular supply with embolic occlusion, seizure or syncope at onset tends to be supportive of this mechanism. Different vascular territory involvement on neuroimaging is also a potential indicator of cardioembolic stroke. Identification of a cardiogenic source of embolus in such a setting certainly elevates this mechanism in the differential. There have been major advances in management of acute cerebrovascular disease in recent decades, such as thrombolytic therapy and endovascular thrombectomy, which have somewhat paralleled the advances made in cardiovascular disease. Unfortunately, the successful limitation of myocardial damage in acute coronary syndrome, with intervention, does not necessarily mirror a similar salutary effect on functional outcome with cerebral infarction. The heart can also affect the brain from a cerebral perfusion standpoint. Transient arrhythmias can result in syncope, while cardiac arrest can result in hypoxic–ischemic encephalopathy. Cardiogenic dementia has been identified as a mechanism of cognitive impairment associated with severe cardiac failure. Structural cardiac abnormalities can also play a role in brain insult, and this can include tumors, such as atrial myxoma, patent foramen ovale, with the potential for paradoxical cerebral embolism, and cardiomyopathies, such as Takotsubo, can be associated with precipitous cardioembolic events. Full article

(This article belongs to the Special Issue Stroke—Pathophysiology and New Therapeutic Strategies)

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18 pages, 2202 KiB

Open AccessReview

The Role of the ACE2/MasR Axis in Ischemic Stroke: New Insights for Therapy

by Mansoureh Barzegar, Karen Y. Stokes, Oleg Chernyshev, Roger E. Kelley and Jonathan S. Alexander

Biomedicines 2021, 9(11), 1667; https://doi.org/10.3390/biomedicines9111667 - 11 Nov 2021

Cited by 12 | Viewed by 8291

Abstract

Ischemic stroke remains the leading cause of neurologically based morbidity and mortality. Current stroke treatment is limited to two classes of FDA-approved drugs: thrombolytic agents (tissue plasminogen activator (tPA)) and antithrombotic agents (aspirin and heparin), which have a narrow time-window (<4.5 h) for [...] Read more.

Ischemic stroke remains the leading cause of neurologically based morbidity and mortality. Current stroke treatment is limited to two classes of FDA-approved drugs: thrombolytic agents (tissue plasminogen activator (tPA)) and antithrombotic agents (aspirin and heparin), which have a narrow time-window (<4.5 h) for administration after onset of stroke symptoms. While thrombolytic agents restore perfusion, they carry serious risks for hemorrhage, and do not influence damage responses during reperfusion. Consequently, stroke therapies that can suppress deleterious effects of ischemic injury are desperately needed. Angiotensin converting enzyme-2 (ACE2) has been recently suggested to beneficially influence experimental stroke outcomes by converting the vasoconstrictor Ang II into the vasodilator Ang 1–7. In this review, we extensively discuss the protective functions of ACE2-Ang (1–7)-MasR axis of renin angiotensin system (RAS) in ischemic stroke. Full article

(This article belongs to the Special Issue Stroke—Pathophysiology and New Therapeutic Strategies)

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29 pages, 443 KiB

Open AccessReview

Overview of Acute Ischemic Stroke Evaluation and Management

by Tasneem F. Hasan, Hunaid Hasan and Roger E. Kelley

Biomedicines 2021, 9(10), 1486; https://doi.org/10.3390/biomedicines9101486 - 16 Oct 2021

Cited by 39 | Viewed by 8656

Abstract

Stroke is a major contributor to death and disability worldwide. Prior to modern therapy, post-stroke mortality was approximately 10% in the acute period, with nearly one-half of the patients developing moderate-to-severe disability. The most fundamental aspect of acute stroke management is “time is [...] Read more.

Stroke is a major contributor to death and disability worldwide. Prior to modern therapy, post-stroke mortality was approximately 10% in the acute period, with nearly one-half of the patients developing moderate-to-severe disability. The most fundamental aspect of acute stroke management is “time is brain”. In acute ischemic stroke, the primary therapeutic goal of reperfusion therapy, including intravenous recombinant tissue plasminogen activator (IV TPA) and/or endovascular thrombectomy, is the rapid restoration of cerebral blood flow to the salvageable ischemic brain tissue at risk for cerebral infarction. Several landmark endovascular thrombectomy trials were found to be of benefit in select patients with acute stroke caused by occlusion of the proximal anterior circulation, which has led to a paradigm shift in the management of acute ischemic strokes. In this modern era of acute stroke care, more patients will survive with varying degrees of disability post-stroke. A comprehensive stroke rehabilitation program is critical to optimize post-stroke outcomes. Understanding the natural history of stroke recovery, and adapting a multidisciplinary approach, will lead to improved chances for successful rehabilitation. In this article, we provide an overview on the evaluation and the current advances in the management of acute ischemic stroke, starting in the prehospital setting and in the emergency department, followed by post-acute stroke hospital management and rehabilitation. Full article

(This article belongs to the Special Issue Stroke—Pathophysiology and New Therapeutic Strategies)

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