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International Journal of Molecular... Oct 2020Stroke is the second leading cause of death and a major contributor to disability worldwide. The prevalence of stroke is highest in developing countries, with ischemic... (Review)
Review
Stroke is the second leading cause of death and a major contributor to disability worldwide. The prevalence of stroke is highest in developing countries, with ischemic stroke being the most common type. Considerable progress has been made in our understanding of the pathophysiology of stroke and the underlying mechanisms leading to ischemic insult. Stroke therapy primarily focuses on restoring blood flow to the brain and treating stroke-induced neurological damage. Lack of success in recent clinical trials has led to significant refinement of animal models, focus-driven study design and use of new technologies in stroke research. Simultaneously, despite progress in stroke management, post-stroke care exerts a substantial impact on families, the healthcare system and the economy. Improvements in pre-clinical and clinical care are likely to underpin successful stroke treatment, recovery, rehabilitation and prevention. In this review, we focus on the pathophysiology of stroke, major advances in the identification of therapeutic targets and recent trends in stroke research.
Topics: Animals; Fibrinolytic Agents; Humans; Neuroprotective Agents; Risk Factors; Stem Cell Transplantation; Stroke; Stroke Rehabilitation
PubMed: 33076218
DOI: 10.3390/ijms21207609 -
Journal of Clinical Neuroscience :... Nov 2021Ischemic stroke is the leading cause of disability and one of the leading causes of death. Ischemic stroke mimics (SMs) can account for a noteble number of diagnosed... (Review)
Review
BACKGROUND
Ischemic stroke is the leading cause of disability and one of the leading causes of death. Ischemic stroke mimics (SMs) can account for a noteble number of diagnosed acute strokes and even can be thrombolyzed.
METHODS
The aim of our comprehensive review was to summarize the findings of different studies focusing on the prevalence, type, risk factors, presenting symptoms, and outcome of SMs in stroke/thrombolysis situations.
RESULTS
Overall, 61 studies were selected with 62.664 participants. Ischemic stroke mimic rate was 24.8% (15044/60703). Most common types included peripheral vestibular dysfunction in 23.2%, toxic/metabolic in 13.2%, seizure in 13%, functional disorder in 9.7% and migraine in 7.76%. Ischemic stroke mimic have less vascular risk factors, younger age, female predominance, lower (nearly normal) blood pressure, no or less severe symptoms compared to ischemic stroke patients (p < 0.05 in all cases). 61.7% of ischemic stroke patients were thrombolysed vs. 26.3% among SMs (p < 0.001). (p < 0.001). Overall intracranial hemorrhage was reported in 9.4% of stroke vs. 0.7% in SM patients (p < 0.001). Death occurred in 11.3% of stroke vs 1.9% of SM patients (p < 0.001). Excellent outcome was (mRS 0-1) was reported in 41.8% ischemic stroke patients vs. 68.9% SMs (p < 0.001). Apart from HINTS manouvre or Hoover sign there is no specific method in the identification of mimics. MRI DWI or perfusion imaging have a role in the setup of differential diagnosis, but merit further investigation.
CONCLUSION
Our article is among the first complex reviews focusing on ischemic stroke mimics. Although it underscores the safety of thrombolysis in this situation, but also draws attention to the need of patient evaluation by physicians experienced in the diagnosis of both ischemic stroke and SMs, especially in vertigo, headache, seizure and conversional disorders.
Topics: Brain Ischemia; Female; Fibrinolytic Agents; Humans; Ischemic Stroke; Stroke; Thrombolytic Therapy; Treatment Outcome
PubMed: 34656244
DOI: 10.1016/j.jocn.2021.09.025 -
The Lancet. Neurology Feb 2015Constraint-induced movement therapy (CIMT) was developed to overcome upper limb impairments after stroke and is the most investigated intervention for the rehabilitation... (Review)
Review
Constraint-induced movement therapy (CIMT) was developed to overcome upper limb impairments after stroke and is the most investigated intervention for the rehabilitation of patients. Original CIMT includes constraining of the non-paretic arm and task-oriented training. Modified versions also apply constraining of the non-paretic arm, but not as intensive as original CIMT. Behavioural strategies are mostly absent for both modified and original CIMT. With forced use therapy, only constraining of the non-paretic arm is applied. The original and modified types of CIMT have beneficial effects on motor function, arm-hand activities, and self-reported arm-hand functioning in daily life, immediately after treatment and at long-term follow-up, whereas there is no evidence for the efficacy of constraint alone (as used in forced use therapy). The type of CIMT, timing, or intensity of practice do not seem to affect patient outcomes. Although the underlying mechanisms that drive modified and original CIMT are still poorly understood, findings from kinematic studies suggest that improvements are mainly based on adaptations through learning to optimise the use of intact end-effectors in patients with some voluntary motor control of wrist and finger extensors after stroke.
Topics: Exercise Therapy; Humans; Physical Therapy Modalities; Recovery of Function; Stroke
PubMed: 25772900
DOI: 10.1016/S1474-4422(14)70160-7 -
The Lancet. Diabetes & Endocrinology Apr 2020Adults with type 2 diabetes are at an increased risk of developing certain brain or mental disorders, including stroke, dementia, and depression. Although these... (Review)
Review
Adults with type 2 diabetes are at an increased risk of developing certain brain or mental disorders, including stroke, dementia, and depression. Although these disorders are not usually considered classic microvascular complications of diabetes, evidence is growing that microvascular dysfunction is one of the key underlying mechanisms. Microvascular dysfunction is a widespread phenomenon in people with diabetes, including effects on the brain. Cerebral microvascular dysfunction is also apparent in adults with prediabetes, suggesting that cerebral microvascular disease processes start before the onset of diabetes. The microvasculature is involved in the regulation of many cerebral processes that when impaired predispose to lacunar and haemorrhagic stroke, cognitive dysfunction, and depression. Main drivers of diabetes-related cerebral microvascular dysfunction are hyperglycaemia, obesity and insulin resistance, and hypertension. Increasing amounts of data from observational studies suggest that diabetes-related microvascular dysfunction is associated with a higher risk of stroke, cognitive dysfunction, and depression. Cerebral outcomes in diabetes might be improved following treatments targeting the pathways through which diabetes damages the microcirculation. These treatments might include drugs that reduce dicarbonyl compounds, augment cerebral insulin signalling, or improve blood-brain barrier permeability and cerebral vasoreactivity.
Topics: Cerebrovascular Circulation; Cognitive Dysfunction; Depression; Diabetes Mellitus, Type 2; Humans; Hypertension; Microcirculation; Stroke
PubMed: 32135131
DOI: 10.1016/S2213-8587(19)30405-X -
Stroke Feb 2019Background and Purpose- This study reports the detailed effects of canagliflozin on stroke, stroke subtypes, and vascular outcomes in participants with and without... (Randomized Controlled Trial)
Randomized Controlled Trial
Background and Purpose- This study reports the detailed effects of canagliflozin on stroke, stroke subtypes, and vascular outcomes in participants with and without cerebrovascular disease (stroke or transient ischemic attack) at baseline from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program. Methods- The CANVAS Program, comprising 2 similarly designed and conducted clinical trials, randomly assigned 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk to canagliflozin or placebo. Its primary outcome was a composite of major adverse cardiovascular events. The main outcome of interest for this report was fatal or nonfatal stroke. Additional exploratory outcomes were stroke subtypes and other vascular outcomes defined according to standard criteria. Results- There were 1 958 (19%) participants with prior stroke or transient ischemic attack at baseline. These individuals were older, more frequently women, and had higher rates of heart failure, atrial fibrillation, and microvascular disease (all P<0.001) compared with those without such a history. There were 309 participants with stroke events during follow-up (123 had prior stroke or transient ischemic attack at baseline and 186 did not), at a rate of 7.93/1000 patient-years among those assigned canagliflozin and 9.62/1000 patient-years among placebo (hazard ratio, 0.87; 95% CI, 0.69-1.09). Analysis of stroke subtypes found no effect on ischemic stroke (n=253, hazard ratio, 0.95; 95% CI, 0.74-1.22), a significant reduction for hemorrhagic stroke (n=30, hazard ratio, 0.43; 95% CI, 0.20-0.89) and no effect on undetermined stroke (n=29, hazard ratio, 1.04; 95% CI, 0.48-2.22). Effects on other cardiovascular outcomes were comparable among participants with and without stroke or transient ischemic attack at baseline. Conclusions- There were too few events in the CANVAS Program to separately define the effects of canagliflozin on stroke, but benefit is more likely than harm. The observed possible protective effect for hemorrhagic stroke was based on small numbers but warrants further investigation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629 and NCT01989754.
Topics: Aged; Canagliflozin; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Male; Middle Aged; Stroke
PubMed: 30591006
DOI: 10.1161/STROKEAHA.118.023009 -
Stroke Aug 2020With recent advances in secondary prevention management, stroke recurrence rates may have changed substantially. We aim to estimate risks and trends of stroke recurrence...
BACKGROUND AND PURPOSE
With recent advances in secondary prevention management, stroke recurrence rates may have changed substantially. We aim to estimate risks and trends of stroke recurrence over the past 2 decades in a population-based cohort of patients with stroke.
METHODS
Patients with a first-ever stroke between 1995 and 2018 in South London, United Kingdom (n=6052) were collected and analyzed. Rates of recurrent stroke with 95% CIs were stratified by 5-year period of index stroke and etiologic TOAST (Trial of ORG 10172 in Acute Stroke Treatment) subtype. Cumulative incidences were estimated and multivariate Cox models applied to examine associations of recurrence and recurrence-free survival.
RESULTS
The rate of stroke recurrence at 5 years reduced from 18% (95% CI, 15%-21%) in those who had their stroke in 1995 to 1999 to 12% (10%-15%) in 2000 to 2005, and no improvement since. Recurrence-free survival has improved (35%, 1995-1999; 67%, 2010-2015). Risk of recurrence or death is lowest for small-vessel occlusion strokes and other ischemic causes (36% and 27% at 5 years, respectively). For cardioembolic and hemorrhagic index strokes around half of first recurrences are of the same type (54% and 51%, respectively). Over the whole study period a 54% increased risk of recurrence was observed among those who had atrial fibrillation before the index stroke (hazard ratio, 1.54 [1.09-2.17]).
CONCLUSIONS
The rate of recurrence reduced until mid-2000s but has not changed over the last decade. The majority of cardioembolic or hemorrhagic strokes that have a recurrence are stroke of the same type indicating that the implementation of effective preventive strategies is still suboptimal in these stroke subtypes.
Topics: Aged; Aged, 80 and over; Cohort Studies; Female; Follow-Up Studies; Humans; London; Male; Middle Aged; Population Surveillance; Recurrence; Registries; Risk Factors; Secondary Prevention; Stroke
PubMed: 32646337
DOI: 10.1161/STROKEAHA.120.028992 -
BMC Geriatrics May 2022Post-stroke dysphagia (PSD) has been associated with high risk of aspiration pneumonia and mortality. However, limited evidence on pooled prevalence of post-stroke... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Post-stroke dysphagia (PSD) has been associated with high risk of aspiration pneumonia and mortality. However, limited evidence on pooled prevalence of post-stroke dysphagia and influence of individual, disease and methodological factors reveals knowledge gap. Therefore, to extend previous evidence from systematic reviews, we performed the first meta-analysis to examine the pooled prevalence, risk of pneumonia and mortality and influence of prognostic factors for PSD in acute stroke.
METHODS
Our search was conducted in CINAHL, Cochrane Library, EMBASE, Ovid-Medline, PubMed, and Web of Science an initial search in October 2020 and a follow-up search in May 2021. Data synthesis was conducted using the Freeman-Tukey double-arcsine transformation model for the pooled prevalence rate and the DerSimonian-Lard random-effects model for prognostic factors and outcomes of PSD.
RESULTS
The pooled prevalence of PSD was 42% in 42 studies with 26,366 participants. PSD was associated with higher pooled odds ratio (OR) for risk of pneumonia 4.08 (95% CI, 2.13-7.79) and mortality 4.07 (95% CI, 2.17-7.63). Haemorrhagic stroke 1.52 (95% CI, 1.13-2.07), previous stroke 1.40 (95% CI, 1.18-1.67), severe stroke 1.38 (95% CI, 1.17-1.61), females 1.25 (95% CI, 1.09-1.43), and diabetes mellitus 1.24 (95% CI, 1.02-1.51) were associated with higher risk of PSD. Males 0.82 (95% CI, 0.70-0.95) and ischaemic stroke 0.54 (95% CI, 0.46-0.65) were associated with lower risk of PSD. Haemorrhagic stroke, use of instrumental assessment method, and high quality studies demonstrated to have higher prevalence of PSD in the moderator analysis.
CONCLUSIONS
Assessment of PSD in acute stroke with standardized valid and reliable instruments should take into account stroke type, previous stroke, severe stroke, diabetes mellitus and gender to aid in prevention and management of pneumonia and thereby, reduce the mortality rate.
TRIAL REGISTRATION
https://osf.io/58bjk/?view_only=26c7c8df8b55418d9a414f6d6df68bdb .
Topics: Brain Ischemia; Deglutition Disorders; Female; Hemorrhagic Stroke; Humans; Male; Pneumonia; Prevalence; Stroke
PubMed: 35562660
DOI: 10.1186/s12877-022-02960-5 -
Swiss Medical Weekly 2017This review provides an update on interdisciplinary treatment for dizziness. Dizziness can have various causes and the treatment offered should depend on the cause.... (Review)
Review
This review provides an update on interdisciplinary treatment for dizziness. Dizziness can have various causes and the treatment offered should depend on the cause. After reading this article, the clinician will have an overview of current treatment recommendations. Recommendations are made for the most prevalent causes of dizziness including acute and chronic vestibular syndromes, vestibular neuritis, benign paroxysmal positional vertigo, endolymphatic hydrops and Menière’s disease, vestibular paroxysmia and vestibular migraine, cardiac causes, transient ischaemic attacks and strokes, episodic ataxia type 2, persistent postural-perceptual dizziness, bilateral vestibulopathy, degenerative, autoimmune and neoplastic diseases, upbeat- and downbeat nystagmus. Recommendations include clinical approaches (repositioning manoeuvres), medication (adding, removing or changing current medication depending on aetiology), vestibular physiotherapy, ergotherapy and rehabilitation, treatment of chest pain or stroke units and surgical interventions. If symptoms are acute and severe, medication with antivertigo agents is recommended as a first step, for a maximum period of 3 days. Following initial symptom control, treatment is tailored depending on aetiology. To assist the clinician in obtaining a useful overview, the level of evidence and number needed to treat are reported whenever possible based on study characteristics. In addition, warnings about possible arrhythmias due to medication are issued, and precautions to enable these to be avoided are discussed.
Topics: Dizziness; Humans; Interdisciplinary Studies; Ischemic Attack, Transient; Patient Positioning; Physical Therapy Modalities; Stroke; Vertigo; Vestibular Diseases
PubMed: 29282702
DOI: 10.4414/smw.2017.14566 -
International Journal of Stroke :... Feb 2019Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion...
RATIONALE
Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion of cryptogenic strokes.
AIMS
The aim of the ARCADIA trial is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy.
SAMPLE SIZE ESTIMATE
1100 participants.
METHODS AND DESIGN
Biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial conducted at 120 U.S. centers participating in NIH StrokeNet.
POPULATION STUDIED
Patients ≥ 45 years of age with embolic stroke of undetermined source and evidence of atrial cardiopathy, defined as ≥ 1 of the following markers: P-wave terminal force >5000 µV × ms in ECG lead V, serum NT-proBNP > 250 pg/mL, and left atrial diameter index ≥ 3 cm/m on echocardiogram. Exclusion criteria include any atrial fibrillation, a definite indication or contraindication to antiplatelet or anticoagulant therapy, or a clinically significant bleeding diathesis. Intervention: Apixaban 5 mg twice daily versus aspirin 81 mg once daily. Analysis: Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation.
STUDY OUTCOMES
The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage.
DISCUSSION
ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation.
Topics: Aged; Aged, 80 and over; Humans; Middle Aged; Aspirin; Biomarkers; Cardiomyopathies; Electrocardiography; Ischemia; Pyrazoles; Pyridones; Recurrence; Stroke; Survival Analysis; Treatment Outcome; United States
PubMed: 30196789
DOI: 10.1177/1747493018799981 -
Stroke Sep 2022GLP-1 RA (glucagon-like peptide-1 receptor agonists), including semaglutide, may reduce stroke risk in people with type 2 diabetes. This post hoc analysis examined the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
GLP-1 RA (glucagon-like peptide-1 receptor agonists), including semaglutide, may reduce stroke risk in people with type 2 diabetes. This post hoc analysis examined the subcutaneous and oral semaglutide effects, versus placebo, on stroke and its subtypes in people with type 2 diabetes at high cardiovascular risk.
METHODS
SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) and PIONEER 6 (Peptide Innovation for Early Diabetes Treatment) were randomized cardiovascular outcome trials of subcutaneous and oral semaglutide in people with type 2 diabetes at high cardiovascular risk, respectively. Time to first stroke and stroke subtypes were analyzed using a Cox proportional hazards model stratified by trial with pooled treatment as a factor. The impact of prior stroke, prior myocardial infarction or stroke, age, sex, systolic blood pressure, estimated glomerular filtration rate, and prior atrial fibrillation on treatment effects was assessed using interaction values. Risk of major adverse cardiovascular event was analyzed according to prior stroke.
RESULTS
A total of 106/6480 participants had a stroke (1.0 event/100 patient-years of observation [PYO]). Semaglutide reduced incidence of any stroke versus placebo (0.8 versus 1.1 events/100 PYO; hazard ratio, 0.68 [95% CI, 0.46-1.00]; =0.048), driven by significant reductions in risk of small-vessel occlusion (0.3 versus 0.7 events/100 PYO; hazard ratio, 0.51 [95% CI, 0.29-0.89]; =0.017). Hazard ratios for risk of any stroke with semaglutide versus placebo were 0.60 (95% CI, 0.37-0.99; 0.5 versus 0.9 events/100 PYO) and 0.89 (95% CI, 0.47-1.69; 2.7 versus 3.0 events/100 PYO) in those without and with prior stroke, respectively. Except for prior atrial fibrillation (=0.025), no significant interactions were observed between treatment effects on risk of any stroke and subgroups investigated, or between treatment effects on risk of major adverse cardiovascular event and prior stroke ( >0.05 for all).
CONCLUSIONS
Semaglutide reduced incidence of any first stroke during the trials versus placebo in people with type 2 diabetes at high cardiovascular risk, primarily driven by small-vessel occlusion prevention. Semaglutide treatment, versus placebo, lowered the risk of stroke irrespective of prior stroke at baseline.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT01720446 and NCT02692716.
Topics: Atrial Fibrillation; Diabetes Mellitus, Type 2; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Stroke
PubMed: 35582947
DOI: 10.1161/STROKEAHA.121.037775