Prospective Study of Serum Uric Acid Levels and First Stroke Events in Chinese Adults With Hypertension

Objectives: We investigated the association between serum uric acid (SUA) levels and the risk of the first stroke in Chinese adults with hypertension.Methods: A total of 11, 841 hypertensive patients were selected from the Chinese Hypertension Registry for analysis. The relationship between SUA levels and first stroke was determined using multivariable Cox proportional hazards regression, smoothing curve fitting, and Kaplan–Meier survival curve analysis.Results: During a median follow-up of 614 days, 99 cases of the first stroke were occurred. Cox proportional hazards models indicated that SUA levels were not significantly associated with the first stroke event [adjusted-hazard ratio (HR) per SD increase: 0.98, 95% CI 0.76–1.26, P = 0.889]. In comparison to the group without hyperuricemia (HUA), there were no significantly higher risks of first stroke events (adjusted-HR: 1.22, 95% CI 0.79–1.90, P = 0.373) in the population with HUA. However, in the population less than 60 years old, subjects with HUA had a significantly higher risk of the first stroke than the population without HUA (adjusted-HR: 4.89, 95% CI 1.36–17.63, P = 0.015). In subjects older than 60 years, we did not find a significant relationship between HUA and first stroke (adjusted-HR: 0.97, 95% CI 0.60–1.56, P = 0.886). Survival analysis further confirmed this discrepancy (log-rank P = 0.013 or 0.899 for non-aging or aging group).Conclusion: No significant evidence in the present study indicated that increased SUA levels were associated with the risk of first stroke in the Chinese adults with hypertension. Age played an interactive role in the relationship between HUA and the first stroke event.

Nationwide screening for Fabry disease in unselected stroke patients

Background and aims Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by disease-associated variants in the alpha-galactosidase A gene (GLA). FD is a known cause of stroke in younger patients. There are limited data on prevalence of FD and stroke risk in unselected stroke patients. Methods A prospective nationwide study including 35 (78%) of all 45 stroke centers and all consecutive stroke patients admitted during three months. Clinical data were collected in the RES-Q database. FD was diagnosed using dried blood spots in a stepwise manner: in males—enzymatic activity, globotriaosylsphingosine (lyso-Gb3) quantification, if positive followed by GLA gene sequencing; and in females GLA sequencing followed by lyso-Gb3. Results 986 consecutive patients (54% men, mean age 70 years) were included. Observed stroke type was ischemic 79%, transient ischemic attack (TIA) 14%, intracerebral hemorrhage (ICH) 7%, subarachnoid hemorrhage 1% and cerebral venous thrombosis 0.1%. Two (0.2%, 95% CI 0.02–0.7) patients had a pathogenic variant associated with the classical FD phenotype (c.1235_1236delCT and p.G325S). Another fourteen (1.4%, 95% CI 0.08–2.4) patients had a variant of GLA gene considered benign (9 with p.D313Y, one p.A143T, one p.R118C, one p.V199A, one p.R30K and one p.R38G). The index stroke in two carriers of disease-associated variant was ischemic lacunar. In 14 carriers of GLA gene variants 11 strokes were ischemic, two TIA, and one ICH. Patients with positive as compared to negative GLA gene screening were younger (mean 60±SD, min, max, vs 70±SD, min, max, P = 0.02), otherwise there were no differences in other baseline variables. Conclusions The prevalence of FD in unselected adult patients with acute stroke is 0.2%. Both patients who had a pathogenic GLA gene variant were younger than 50 years. Our results support FD screening in patients that had a stroke event before 50 years of age.

Transient Ischemic Attacks Preceding Ischemic Stroke and the Possible Preconditioning of the Human Brain: A Systematic Review and Meta-Analysis

Stroke is a leading cause of mortality and disability worldwide. Transient ischemic attack (TIA) is defined as transient brain ischemia with temporary neurological deficits. In animal models, prior TIA seems to enhance brain ischemic tolerance to withstand further ischemic events, which might be explained by brain preconditioning. Thus, this review aims to formulate evidence of whether TIAs can induce positive preconditioning and enhance the functional outcomes in patients suffering from subsequent ischemic strokes. Five databases were searched (PubMed, Embase, SAGE, Web of Science, and Scopus), and twelve studies were included in the quantitative analysis. Studies were eligible when comparing patients with acute ischemic stroke (AIS) and previous TIA with those with AIS without TIA. Comparisons included the National Institute of Health Stroke Scale (NIHSS) score at admission and 7 days from the stroke event, modified Rankin score (mRS), and Trial of ORG 10,172 in Acute Stroke Treatment (TOAST) classification. Odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) were used to describe our results using the random effect model. Our results revealed that patients with stroke and prior TIAs had lower NIHSS scores at admission than those without prior TIAs. However, the NIHSS score was not significantly different between the two groups at 7 days. Furthermore, there was no statistically significant difference between both groups in terms of mortality. Despite the differences in the admission mRS score groups, patients with prior TIAs had lower mRS scores at discharge.

Association Between HDL Cholesterol and Incident Cognitive Impairment in Black and White Adults in The Reasons For Geographic and Racial Differences in Stroke Study

BACKGROUND: Low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with incident cognitive impairment (ICI) in some, but not all studies. METHODS: We examine the association between HDL-C and ICI among 18,378 Reasons for Geographic and Racial Differences in Stroke (REGARDS) study participants without cognitive impairment or stroke at baseline in 2003 to 2007, and who did not have a stroke event during follow-up. RESULTS: Over a median follow-up of 9.6 years, 1,359 participants developed ICI. In fully adjusted models, the RR for ICI was 1.51 (95% CI 1.06, 2.15) in White women and 1.25 (95% CI 0.95, 1.65) in Black women. The association was not statistically significant afrter adjustment for triglycerides. There was no evidence of an association between HDL-C and ICI among White or Black men. CONCLUSIONS: Low HDL-C was associated with a higher risk of ICI in White and Black women in models not including triglycerides.

A Retrospective Study on Statins and Post-stroke Patients: What About Functional Outcome and Follow-Up in a Stroke Rehabilitation Cohort?

Objective: Statins exert pleiotropic effects by influencing several mechanisms, including synaptogenesis, neurogenesis, cerebral flow regulation, and angiogenesis. Results from in vitro and animal models suggest that statins could have beneficial effect on functional recovery and outcome after stroke events. However, results in human studies are still controversial. The aim of our study was to evaluate the role of statin in influencing functional outcome and subsequent clinical follow-up in a large cohort of post-stroke rehabilitation patients.Methods: This retrospective study consecutively enrolled 413 adult patients with stroke event, admitted to the division of Neurorehabilitation of the IRCCS ICS Maugeri, Veruno (Italy), for an individual rehabilitation program between 2015 and 2017. Follow-up lasted 3–5 years after discharge. Demographic data, etiology, classification, and anatomical site of stroke lesion, functional assessment, use and duration of statin therapy, and death during hospitalization were collected at baseline and on discharge. Clinical data on subsequent follow-up were also evaluated, considering these as variables: stroke recurrence, bone fractures, cardiovascular complications, and death.Results: In our cohort, 177 patients (42.9%) were prescribed statin therapy, of whom 50 (28.2%) before the stroke event and 127 (71.8%) at the beginning of the rehabilitation process. The use and type of statin therapy as well as the duration of treatment were not associated with recovery and functional outcome, regardless of confounders including sex, age, etiology, and site of stroke lesion, and initial functional level. For what concern post-discharge clinical follow-up, the use of statin therapy was significantly associated with a lower risk of bone fractures (OR = 0.095, CI 95%: 0.012–0.743, p = 0.01) independently from age, sex, initial and final functional level, and comorbidities.Conclusions: The use of statins does not seem to influence the functional outcome in post-stroke patients. However, they could exert a protective role against bone fractures during post-discharge follow-up, suggesting further evaluation on this topic.

Self-Efficacy Is a Modifiable Factor Associated with Frailty in Those with Minor Stroke: Secondary Analysis of 200 Cohort Respondents

<b><i>Background:</i></b> Owing to the improvement in acute care, there has been an increase in the number of people surviving stroke and living with its impairments. Frailty is common in people with stroke and has a significant impact on the prognosis after stroke. To reduce frailty progression, potentially modifiable factors should be identified. Increasing levels of self-efficacy influence both behaviour and physical functioning, and therefore it could be a potential target to prevent frailty. <b><i>Methods:</i></b> This is a prospective cohort study that involved the secondary analysis of the RISE data to examine the relationship between self-efficacy and frailty. The RISE study is a longitudinal study that consists of 200 adults aged 18+ years after their first stroke event. Data were collected from the respondents at 3 weeks, 6 months, 12 months, and 24 months after their discharge from the hospital. Frailty was assessed using the multidimensional frailty index with scores ranging from 0 to 1, and self-efficacy was assessed using the SESx scale, which was dichotomized as low/moderate or high. Frailty trajectories were examined using the repeated linear model. The generalized estimating equation was used to examine the relationship between self-efficacy and frailty at baseline and in the future (6–24 months). The B coefficients were reported at 95% CI before and after adjusting for potential confounders (age, gender, stroke severity, education, and social support). <b><i>Results:</i></b> A total of 200 responses were analysed, and the mean age of the respondents was 67.78 ± 11.53. Females made up 64% of the sample, and the mean frailty score at baseline was 0.17 ± 0.09. After adjusting for confounders, respondents with low self-efficacy had an approximately 5% increase in their frailty scores at baseline and in the 24-month follow-up period compared to those with high self-efficacy. <b><i>Conclusion:</i></b> The result from this study showed that self-efficacy was significantly associated with frailty after stroke. Our findings suggest that self-efficacy may play a role in frailty progression among stroke survivors.

The Need for New Biomarkers to Assist with Stroke Prevention and Prediction of Post-Stroke Therapy Based on Plasma-Derived Extracellular Vesicles

The risk of having a stroke event doubles each decade after the age of 55. Therefore, it is of great interest to develop neurorestorative therapies of stroke which occurs mostly in elderly people. However, to date, patients at risk for these sequels of stroke are not duly diagnosed and treated due to the lack of reliable biomarkers. Extracellular vesicles (EVs) are lipid bilayer-delimited particles that are shed by the brain cells and are able to cross the blood–brain barrier and enter the blood stream; thus, they may be used to interrogate molecular and cellular events in the brain damaged area. In this review, we summarize the major molecular and cellular responses of astroglia and neurons to cerebral ischemia and assess their impact on post-stroke recovery and rehabilitation. In particular, we ask if EVs secreted by brain cells are responses to cerebral ischemia, and they may shed new light on the interplay between exosomes-mediated interactions between brain cells and the question of how to exploit it in order to predict the individual course of the disease and to introduce specific preventive or therapeutic strategies. Given these findings, we are left with two options: either to (i) transplant neuronal precursors into the damaged cortical area or (ii) to covert abundantly present proliferating astrocytes in the perilesional area into neurons by using recently developed genetic technologies. However, given the complexity of molecular and cellular responses to cerebral ischemia and our limited capabilities to restore brain structure and function, we are left with only one realistic aim: to invest more in prevention.

Long-term neurological and healthcare burden of adults with Japanese encephalitis: A nationwide study 2000-2015

Objective To assess the healthcare utilization, economic burden, and long-term neurological complications and mortality of an adult population with Japanese encephalitis (JE). Methods This study utilized two nationwide datasets in Taiwan: the Notifiable Disease Dataset of confirmed cases from the Centers for Disease Control to identify JE patients, and the National Health Insurance Research Database to obtain patients’ healthcare utilization. Survival analyses were performed to identify prognostic factors associated with the all-cause mortality of patients. Results This study included 352 adult cases with JE (aged≥20 years). The mean age of JE patients was 45 years. Stroke (event rate: 3.49/100 person-years) was the most common neurological complication, followed by epilepsy/convulsions (3.13/100 person-years), encephalopathy/delirium (2.20/100 person-years), and parkinsonism (1.97/100 person-years). Among the 336 hospitalized patients at JE diagnosis, 58.33% required intensive care. Among 79 patients who died following JE diagnosis, 48.84% of death events occurred within the year of diagnosis. The medical costs increased considerably at JE diagnosis and subsequent-year costs remained significantly higher than the costs before diagnosis (p<0.05). Having a four-dose JE vaccination (i.e., born after 1976) versus no JE vaccination history (i.e., born before 1963) was significantly associated with lower all-cause mortality (hazard ratio: 0.221 [95% confidence interval: 0.067, 0.725]). Comorbid diabetes and incident epilepsy/convulsion events significantly increased the mortality risk by 2.47- and 1.85-fold, respectively (p<0.05). Conclusion A considerable medical burden associated with JE was observed in affected adults, even in the years following JE diagnosis. Vaccination should be considered to prevent this sporadic, but lethal, viral infection.

Abstract P132: Clinical Outcomes In Ischemic Stroke Patients With Uncontrolled Hypertension

Background: Hypertension is considered major risk factor for incidence of ischemic stroke, controlling blood pressure reduces this risk, the relationship of uncontrolled blood pressure and stroke outcomes is complex, post stroke uncontrolled blood pressure remains one of the major contributing factors for stroke recurrence and mortality, in our study we studied the long term effects of uncontrolled hypertension in modern health care setting. Methodology: Patients in the study were admitted to the neurology department at KFSH-D between March 2015- August 2019, we included 102 acute ischemic stroke patients whom had hypertension, all patients had follow up appointments at stroke clinic a minimum of 2 visits over 4 years. We retrospectively compared blood pressure data from stroke patients with recurrent ischemic stroke events vs. patients with initial stroke event, and recurrent stroke, also we studied blood pressure readings for different stroke severity groups, patients who had severe stroke with mRS>4, compared to milder stroke group of mRS<4. Results: We found 48 patients identified with recurrent stroke event, those with uncontrolled hypertension had significantly higher stroke recurrence events (P=0.002), despite acute stroke treatment, patients who had history of uncontrolled hypertension were found to have more severe stroke deficits than those who had controlled blood pressure (P=0.029). We found significant difference in the long term stroke clinical outcomes between patients who had uncontrolled blood pressure and patients who had controlled blood pressure recordings within the same hospital setting (P=0.064). Conclusion: Based on our findings, uncontrolled hypertension was associated with higher risk of stroke recurrence, it also increased susceptibility to worse stroke clinical outcomes up to 1 year after initial stroke event, which deserved further close attention and better blood pressure control.

Extracellular Vesicles in Regeneration and Rehabilitation Recovery after Stroke

Patients that survive after a stroke event may present disabilities that can persist for a long time or permanently after it. If stroke prevention fails, the prompt and combinatorial intervention with pharmacological and rehabilitation therapy is pivotal for the optimal recovery of patients and the reduction of disabilities. In the present review, we summarize some key features of the complex events that occur in the brain during and after the stroke event, with a special focus on extracellular vesicles (EVs) and their role as both carriers of biomarkers and potential therapeutics. EVs have already demonstrated their ability to be used for diagnostic purposes for multiple brain disorders and could represent valuable tools to track the regenerative and inflammatory processes occurring in the injured brain after stroke. Last, but not least, the use of artificial or stem cell-derived EVs were proved to be effective in stimulating brain remodeling and ameliorating recovery after stroke. Still, effective biomarkers of recovery are needed to design robust trials for the validation of innovative therapeutic strategies, such as regenerative rehabilitation approaches.