Antiplatelet and Anticoagulant Therapies for Prevention of Ischemic Stroke.

Ischemic stroke represents one of the leading causes of death and disability in both the United States and abroad, particularly for patients with prior ischemic stroke or transient ischemic attack (TIA). A quintessential aspect of secondary stroke prevention is the use of different pharmacological agents, mainly antiplatelets and anticoagulants. Antiplatelets and anticoagulants exhibit their effect by blocking the activation pathways of platelets and the coagulation cascade, respectively. Clinical trials have demonstrated the safety and efficacy of antiplatelets for noncardioembolic stroke prevention, while anticoagulants are more often used for cardioembolic stroke prevention. Commonly used antiplatelets include aspirin, clopidogrel, and aggrenox (aspirin plus extended-release dipyridamole). Furthermore, commonly used anticoagulants include warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban. Each of these drugs has a unique mechanism of action, and they share some common adverse events such as gastrointestinal bleeding and intracranial hemorrhage in more serious cases. Consequently, physicians should carefully assess the benefits and risks of using different antiplatelet or anticoagulant therapies when managing patients with previous ischemic stroke or TIA. This review discuses the published literature on major clinical trials assessing the efficacy of different antiplatelet and anticoagulant drugs under varying circumstances and the subsequent guidelines that have been developed by the American Heart Association/American Stroke Association. Additionally, the role of imaging in stroke prevention is discussed.

Chronic Traumatic Encephalopathy in Athletes Involved with High-impact Sports.

BACKGROUND AND PURPOSE: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease occurring most commonly in athletes and is caused by repeated concussive or subconcussive blows to the head. The main purpose of this review is to evaluate the published literature on chronic traumatic encephalopathy (CTE) in athletes participating in high-impact sports. In particular, we highlight the significance of concussive and subconcussive impacts in multiple sports, elucidate the differences between clinical/pathological features of CTE and related neurodegenerative diseases, and provide an explanation for the variation in clinical presentation between athletes of different sports. METHODS: A review targeting relevant publications to CTE was performed. The PubMed/MEDLINE index was searched for keywords such as "chronic traumatic encephalopathy," "repetitive traumatic brain injury," "mild traumatic brain injury," and "concussion" from year 1924 through March 1, 2016. RESULTS: A consensus panel's recent identification of a pathognomonic pathology in CTE, characterized by an irregular distribution of phosphorylated tau deposits, is an important step in developing consensus diagnostic criteria and clinicopathological studies. After review of major clinical studies, evidence suggests that there are clear differences in neuropathological features, clinical progression, and manifestation of symptoms between CTE and other neurodegenerative diseases. The literature suggests boxers tend to have more severe symptoms than other athletes due to more frequent rotational and shearing impacts. Data regarding genetic predispositions of CTE have been inconsistent in part due to low subject populations. Positron emission tomography imaging involving tau-binding ligands has recently proven effective in differentiating CTE from control groups and other neurodegenerative diseases. CONCLUSIONS: Further longitudinal studies should be conducted to correlate the number of suffered concussive/subconcussive forces to the likelihood of developing chronic traumatic brain injury symptoms. Research striving for a reliable antemortem CTE diagnosis would be immensely beneficial, leading to more accurate estimates of prevalence, allowing clinicians to assess future risk of athletes' continued participation in sports, and enabling clinicians to make appropriate preventive recommendations.

Cognitive Decline in Patients with Leukoaraiosis Within 5 Years after Initial Stroke.

BACKGROUND: Leukoaraiosis (LA) is closely associated with cognitive deficits. The association between LA and cognitive disorders, such as mild cognitive impairment (MCI) and dementia, after initial stroke has not been systematically studied. In this study, we sought to identify whether LA contributes to the occurrence of certain type of cognitive disorders after initial stroke. METHODS: Data from our Stroke Registry were examined, and 5-year follow-up data for LA and cognitive disorders were analyzed. We performed Kaplan-Meier analysis and log-rank test to assess the predictive value of LA for risk of cognitive decline and the Cox proportional hazards model to test the risk factors studied as independent determinants of cognitive impairment. RESULTS: The frequency of patients with normal cognitive function decreased significantly at 5 years compared with initial stroke (78% vs 70%; odds ratio, 1.51; 95% confidence interval, 1.41-1.62). Of 8784 patients, 1659 (19%) had dementia and 964 (11%) had MCI at the final analysis. After 5 years of follow-up, survival analysis showed that all patients with LA had an increased probability of MCI compared with those without LA (P < .0001). Patients with LA had an increased chance of dementia compared with those without LA (P < .0001) at the end of follow-up. Cognitive decline probability was significantly higher in patients with severe LA compared with those with mild/moderate LA (P < .0001). Cox regression analyses showed that recurrence of stroke (hazard ratio [HR], 3.92 [95% CI, 3.26-4.72]), hypertension (HR, 1.11 [95% CI, 1.0-1.22]), LA (HR, 1.15 [95% CI, 1.05-1.25]), age (HR, 1.05 [95% CI, 1.04-1.06]), hypercholesterolemia (HR, .86 [95% CI, .77-.95]), higher LDL cholesterol (HR, 1.21 [95% CI, 1.11-1.32]), lower HDL cholesterol (HR, .90 [95% CI, .83-.98]), coronary heart disease (HR, .85 [95% CI, .77-.94]), and National Institutes of Health Stroke Scale score at admission (HR, .77 [95% CI, .72-.82]) were also significantly associated with cognitive impairments. CONCLUSIONS: Our findings suggest that patients with LA may be at risk of developing new cognitive impairments at long-term period after initial stroke. The evaluation of the concomitant risk factors, besides providing insights about the possible mechanisms behind the cognitive dysfunction present in LA, may be of help for the prevention of cognitive impairments.

Association of leukoaraiosis with stroke recurrence within 5 years after initial stroke.

BACKGROUND: Leukoaraiosis (LA) is closely associated with stroke. Despite the fact that LA has consistently been shown to predict development of recurrent stroke, prior studies on the association of LA and stroke subtypes have been unsatisfactory. In this study, we sought to identify whether LA contributes to the recurrence of certain subtypes of stroke at long term. METHODS: Data from the Ege Stroke Registry were examined, and 5 years follow-up data for LA and stroke recurrence were analyzed. We performed survival curves using the Kaplan-Meier method (unadjusted) and log-rank tests in patients with stroke to determine the relationship between LA and recurrent stroke by stroke subtypes within a time period of 5 years. Multivariate survival analyses were undertaken using Cox proportional hazards models to determine the prognostic value of LA, stroke subtypes, and other vascular risk factors before recurrent stroke. RESULTS: Of 9522 patients with stroke, 1280 (26%) with LA and 901 (19%) without LA experienced a stroke recurrence within 5 years of follow-up (odds ratio, 1.53; 95% confidence interval, 1.39-1.69). After stratification by stroke subtypes, multivariable analysis revealed a significant association between LA and large artery disease (LAD; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.18-1.64), small artery disease (SAD; OR, 1.57; 95% CI, 1.27-1.94), and intracerebral hemorrhage (ICH; OR, 1.88; 95% CI, 1.32-2.66), except cardioembolic stroke and "other" stroke subtypes at 5 years after stroke onset. The survival analysis showed that stroke recurrence was significantly higher in patients with severe LA compared with those with mild/moderate LA (log-rank test [Mantel-Cox], P < .001). CONCLUSIONS: Our results showed that LA is related to the recurrent strokes in patients with stroke within 5 years after stroke, specifically to the LAD, SAD and ICH.