Safety and Outcome of Admission to Step-Down Level of Care in Patients with Low-Risk Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis.

Spontaneous intracerebral hemorrhage (ICH) is the most devastating type of stroke, and it is associated with high morbidity and mortality. Patients with a spontaneous ICH are routinely admitted to an intensive care unit (ICU). However, an ICU is a valuable and limited resource, and not all patients may require this level of care. The authors conducted a systematic review and meta-analysis evaluating the safety and outcome of admission to a step-down level of care or stroke unit (SU) compared to intensive care in adult patients with low-risk spontaneous ICH. PubMed, Embase, and the Cochrane Library were searched for randomized clinical trials and observational cohort studies. The Mantel-Haenszel method or inverse variance, as applicable, was applied to calculate an overall effect estimate for each outcome by combining the specific risk ratio (RR) or standardized mean difference. Risk of bias was analyzed using the Newcastle-Ottawa Scale. The protocol was registered in PROSPERO (CRD42023481915). The primary outcome examined was in-hospital mortality. Secondary outcomes were unfavorable short-term outcome, length of hospital stay, and (re)admission to the ICU. Five retrospective cohort studies involving 1347 patients were included in the qualitative analysis. Two of the studies had severity-matched groups. The definition of low-risk ICH was heterogeneous among the studies. Admission to an SU was associated with a similar rate of mortality compared to admission to an ICU (1.4% vs. 0.6%; RR 1.66; 95% confidence interval [CI] 0.24-11.41; P = 0.61), a similar rate of unfavorable short-term outcome (14.6% vs. 19.2%; RR 0.77; 95% CI 0.43-1.36; P = 0.36), and a significantly shorter mean length of stay (standardized mean difference - 0.87 days; 95% CI - 1.15 to - 0.60; P < 0.01). Risk of bias was low to moderate for each outcome. The available literature suggests that a select subgroup of patients with ICH may be safely admitted to the SU without affecting short-term outcome, potentially saving in-hospital resources and reducing length of stay. Further studies are needed to identify specific and reliable characteristics of this subgroup of patients.

Early poststroke clinically significant fatigue predicts functional independence: a prospective longitudinal study.

Background: Poststroke fatigue is a prevalent issue among stroke survivors, significantly impeding functional recovery and diminishing their quality of life. Aim: This prospective cohort study aims to investigate the association between poststroke fatigue and the extent of functional recovery in survivors of ischemic and hemorrhagic strokes. Additionally, it seeks to delineate the temporal progression of poststroke fatigue in these two stroke subtypes. Methods: We assessed a cohort of 79 patients recovering from acute ischemic or hemorrhagic strokes. Poststroke fatigue was quantified using the Fatigue Severity Scale (FSS) and the Numeric Rating Scale (NRSfatigue). Patients' condition was evaluated using the National Institute of Health Stroke Scale (NIHSS), and functional independence levels were determined using the Barthel Index for Activities of Daily Living (BIADL) and the Modified Rankin Scale (MRS). Depressive mood and pain were measured using the Beck Depression Inventory (BDI) and the Numeric Rating Scale for pain (NRSpain), respectively. Results: Our primary findings indicate that the early manifestation of clinically significant fatigue (CSF) is predictive of a poorer trajectory in functional independence levels during recovery. Furthermore, we observed differing patterns of fatigue progression between ischemic and hemorrhagic strokes. Fatigue tends to ameliorate over time in hemorrhagic stroke cases, paralleling functional recovery, while it remains stable over time in ischemic stroke cases. Conclusion: Our results underscore the detrimental impact of early poststroke fatigue on long-term outcomes. Furthermore, they highlight the imperative of managing poststroke fatigue, particularly during the subacute phase of stroke recovery.

Sex-Based Differences in Patients With Left Ventricular-Assisted Devices and Strokes.

Background: Sex-based differences in clinical outcomes among patients with stroke related to left ventricular assist devices (LVADs) are not well described. Objectives: In this study, the authors examined differences in clinical characteristics and outcomes in men and women who had a stroke during LVAD hospitalization. Methods: The National Inpatient Sample from 2010 and 2019 was used to identify patients with stroke during LVAD hospitalization. Outcomes of interest include inpatient mortality and clinical complications among men vs women. Weighted logistic regression was used to determine the association of sex and outcomes. Adjustments were made for age and the Elixhauser comorbidity index. Results: In total, 35,820 patients underwent LVAD implantation (77% men), and 6.12% (n = 2,192) of patients experienced stroke. Women who had stroke were younger than men who had stroke (mean age in women was 51 years vs men 59 years, P < 0.001). Men with strokes had a higher burden of comorbidities than women. While there were no differences in the odds of ischemic stroke, women had higher odds of hemorrhagic stroke compared to men (OR: 1.49 [95% CI: 1.02-2.18]). Mortality in patients with LVAD who had stroke was significantly higher than in those without stroke. Between 2010 and 2019, stroke rates significantly increased among men, while the trend remained variable among women. Conclusions: In this national cohort, men had a higher comorbidity burden and had worsening stroke trends over the last decade compared to women. Women had fewer LVAD implants and a higher incidence of hemorrhagic stroke. Understanding the factors that contribute to sex-related outcome disparities among LVAD stroke patients is crucial in addressing these diverging trends.

The Spectrum of Cerebral Small Vessel Disease: Emerging Pathophysiologic Constructs and Management Strategies.

Cerebral small vessel disease (CSVD) is a spectrum of disorders that affect small arterioles, venules, cortical and leptomeningeal vessels, perivascular spaces, and the integrity of neurovascular unit, blood brain barrier, and surrounding glia and neurons. CSVD is an important cause of lacunar ischemic stroke and sporadic hemorrhagic stroke, as well as dementia-which will constitute some of the most substantive population and public health challenges over the next century. This article provides an overview of updated pathophysiologic frameworks of CSVD; discusses common and underappreciated clinical and neuroimaging manifestations of CSVD; and reviews emerging genetic risk factors linked to sporadic CSVD.

Advances and Future Trends in the Diagnosis and Management of Intracerebral Hemorrhage.

Spontaneous intracerebral hemorrhage accounts for approximately 10% to 15% of all strokes in the United States and remains one of the deadliest. Of concern is the increasing prevalence, especially in younger populations. This article reviews the following: epidemiology, risk factors, outcomes, imaging findings, medical management, and updates to surgical management.

The impact of mechanical thrombectomy on the blood-brain barrier in patients with acute ischemic stroke: A non-contrast MR imaging study using DP-pCASL and NODDI.

BACKGROUND AND PURPOSE: While mechanical thrombectomy (MT) achieves restoration of cerebral blood flow to the area at risk in patients with acute ischemic stroke (AIS), the influx of blood flow may exacerbate the blood-brain barrier (BBB) disruption and extravasation across the BBB, and it therefore remains unclear how reperfusion impacts the blood-brain barrier integrity. In this study, we use diffusion-prepared pseudocontinuous ASL (DP-pCASL) and Neurite Orientation Dispersion and Density Imaging (NODDI) sequence to measure the water exchange rate (kw) in patients who underwent either MT or medical management and determine its impact on the brain tissue microstructure in order to elucidate the impact of MT on BBB complex integrity. MATERIALS AND METHODS: We prospectively enrolled 21 patients with AIS treated at our institution from 10/2021 to 6/2023 who underwent MR imaging at a 3.0-Tesla scanner. Patients underwent DP-pCASl and NODDI imaging in addition to the standard stroke protocol which generated cerebral blood flow (CBF), arterial transit time (ATT), water exchange rate (kw), orientation dispersion index (ODI), intracellular volume fraction (ICVF), and free water fraction (FWF) parametric maps. RESULTS: Of the 21 patients, 11 underwent MT and 10 were treated non-operatively. The average age and NIHSS for the MT cohort and non-MT cohorts were 69.3 ± 16.6 years old and 15.0 (12.0-20.0), and 70.2 ± 10.7 (p = 0.882) and 6.0 (3.8-9.0, p = 0.003) respectively. The average CBF, ATT, and kw in the infarcted territory of the MT cohort were 38.2 (18.4-59.6), 1347.6 (1182.5-1842.3), and 107.8 (79.2-140.1) respectively. The average CBF, ATT, and kw in the stroke ROI were 16.0 (8.8-36.6, p = 0.036), 1090.8 (937.1-1258.9, p = 0.013), 89.7 (68.0-122.7, p = 0.314) respectively. Linear regression analysis showed increasing CBF (p = 0.008) and undergoing mechanical thrombectomy (p = 0.048) were significant predictors of increased kw. CONCLUSION: Using our multimodal non-contrast MRI protocol, we demonstrate that increased CBF and mechanical thrombectomy increased kw, suggesting a better functioning BBB complex. Higher kw suggests less disruption of the BBB complex in the MT cohort.

Cerebral amyloid angiopathy and the immune system.

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid protein in the walls of cerebral blood vessels. This deposition of amyloid causes damage to the cerebral vasculature, resulting in blood-brain barrier disruption, cerebral hemorrhage, cognitive decline, and dementia. The role of the immune system in CAA is complex and not fully understood. While the immune system has a clear role in the rare inflammatory variants of CAA (CAA related inflammation and Abeta related angiitis), the more common variants of CAA also have immune system involvement. In a protective role, immune cells may facilitate the clearance of beta-amyloid from the cerebral vasculature. The immune system can also contribute to CAA pathology, promoting vascular injury, blood-brain barrier breakdown, inflammation, and progression of CAA. In this review, we summarize the role of the immune system in CAA, including the potential of immune based treatment strategies to slow vascular disease in CAA and associated cognitive impairment, white matter disease progression, and reduce the risk of cerebral hemorrhage. HIGHLIGHTS: The immune system has a role in cerebral amyloid angiopathy (CAA) which is summarized in this review. There is an inflammatory response to beta-amyloid that may contribute to brain injury and cognitive impairment. Immune cells may facilitate the clearance of beta-amyloid from the cerebral vasculature. Improved understanding of the immune system in CAA may afford novel treatment to improve outcomes in patients with CAA.

Long-term exposure to particulate matter pollution and incidence of ischemic and hemorrhagic stroke: A prospective cohort study in Eastern China.

Although epidemiological studies have demonstrated significant associations of long-term exposure to particulate matter (PM) air pollution with stroke, evidence on the long-term effects of PM exposure on cause-specific stroke incidence is scarce and inconsistent. We incorporated 33,282 and 33,868 individuals aged 35 to 75 years without a history of ischemic or hemorrhagic stroke at the baseline in 2014, who were followed up till 2021. Residential exposures to particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and particulate matter with an aerodynamic diameter less than 10 µm (PM10) for each participant were predicted using a satellite-based model with a spatial resolution of 1×1 km. We employed time-varying Cox proportional hazards models to assess the long-term effect of PM pollution on incident stroke. We identified 926 cases of ischemic stroke and 211 of hemorrhagic stroke. Long-term PM exposure was significantly associated with increased incidence of both ischemic and hemorrhagic stroke, with almost 2 times higher risk on hemorrhagic stroke. Specifically, a 10 µg/m³ increase in 3-year average concentrations of PM2.5 was linked to a hazard ratio (HR) of 1.35 (95% confidence interval (CI): 1.18-1.54) for incident ischemic stroke and 1.79 (95% CI: 1.36-2.34) for incident hemorrhagic stroke. The HR related to PM10, though smaller, remained statistically significant, with a HR of 1.25 for ischemic stroke and a HR of 1.51 for hemorrhagic stroke. The excess risks are larger among rural residents and individuals with lower educational attainment. The present cohort study contributed to the mounting evidence on the increased risk of incident stroke associated with long-term PM exposures. Our results further provide valuable evidence on the heightened sensitivity of hemorrhagic stroke to air pollution exposures compared with ischemic stroke.

Association between elevated fibrosis-4 index of liver fibrosis and risk of hemorrhagic stroke.

BACKGROUND: Cirrhosis is associated with an increased risk of hemorrhagic stroke. Liver fibrosis, typically a silent condition, is antecedent to cirrhosis. The objective of this study was to test the hypothesis that elevated Fibrosis-4 (FIB-4) index, indicating a high probability of liver fibrosis, is associated with an increased risk of hemorrhagic stroke. METHODS: We performed a cohort analysis of the prospective United Kingdom Biobank cohort study. Participants 40-69 years old were enrolled between 2007 and 2010 and had available follow-up data until March 1, 2018. We excluded participants with prevalent hemorrhagic stroke or thrombocytopenia. High probability of liver fibrosis was defined as having a value >2.67 of the validated FIB-4 index. The primary outcome was hemorrhagic stroke (intracerebral or subarachnoid hemorrhage), defined based on hospitalization and death registry data. Secondary outcomes were intracerebral and subarachnoid hemorrhage, separately. We used Cox proportional hazards models to evaluate the association of FIB-4 index >2.67 with hemorrhagic stroke while adjusting for potential confounders including hypertension, alcohol use, and antithrombotic use. RESULTS: Among 452,994 participants (mean age, 57 years; 54% women), approximately 2% had FIB-4 index >2.67, and 1241 developed hemorrhagic stroke. In adjusted models, FIB-4 index >2.67 was associated with an increased risk of hemorrhagic stroke (HR, 2.0; 95% CI, 1.6-2.6). Results were similar for intracerebral hemorrhage (HR, 2.0; 95% CI, 1.5-2.7) and subarachnoid hemorrhage (HR, 2.2; 95% CI, 1.5-3.5) individually. CONCLUSIONS: Elevated FIB-4 index was associated with an increased risk of hemorrhagic stroke.

Stroke in Qatar: a decade of insights from a national registry.

BACKGROUND: Stroke is a major cause of death and disability worldwide and presents a significant burden on healthcare systems. This retrospective study aims to analyze the characteristics and outcomes of stroke patients admitted to Hamad General Hospital (HGH) stroke service in Qatar from January 2014 to July 2022. METHODS: The medical records of 15,859 patients admitted during the study period were analyzed. The data collected included patient demographics, stroke types, admission location, procedures performed, mortality rates, and other clinical characteristics. RESULTS: Of the total cohort, 70.9% were diagnosed with a stroke, and 29.1% were diagnosed with stroke mimics. Of the stroke patients, 85.3% had an ischemic stroke, and 14.7% had a hemorrhagic stroke. Male patients below 65 years old (80.2%) and of South Asian ethnicity (44.6%) were the most affected. The mortality rate was 4.6%, significantly higher for hemorrhagic stroke than ischemic stroke (12.6% vs. 3.2%). Female patients had a higher stroke-related mortality rate than male patients (6.8% vs. 4%). The thrombolysis rate was 9.5%, and the thrombectomy rate was 3.4% of the ischemic stroke cohort. The mean door-to-needle time for thrombolysis was 61.2 minutes, and the mean door-to-groin time for thrombectomy was 170 minutes. Stroke outcomes were good, with 59.3% of patients having favorable outcomes upon discharge (mRS ≤2), which improved to 68.2% 90 days after discharge. CONCLUSION: This study provides valuable insights into stroke characteristics and outcomes in Qatar. The findings suggest that stroke mortality rates are low, and favorable long-term disability outcomes are achievable. However, the study identified a higher stroke-related mortality rate among female patients and areas for improvement in thrombolysis and thrombectomy time.

Extreme Temperatures and Stroke Mortality: Evidence From a Multi-Country Analysis.

BACKGROUND: Extreme temperatures contribute significantly to global mortality. While previous studies on temperature and stroke-specific outcomes presented conflicting results, these studies were predominantly limited to single-city or single-country analyses. Their findings are difficult to synthesize due to variations in methodologies and exposure definitions. METHODS: Within the Multi-Country Multi-City Network, we built a new mortality database for ischemic and hemorrhagic stroke. Applying a unified analysis protocol, we conducted a multinational case-crossover study on the relationship between extreme temperatures and stroke. In the first stage, we fitted a conditional quasi-Poisson regression for daily mortality counts with distributed lag nonlinear models for temperature exposure separately for each city. In the second stage, the cumulative risk from each city was pooled using mixed-effect meta-analyses, accounting for clustering of cities with similar features. We compared temperature-stroke associations across country-level gross domestic product per capita. We computed excess deaths in each city that are attributable to the 2.5% hottest and coldest of days based on each city's temperature distribution. RESULTS: We collected data for a total of 3 443 969 ischemic strokes and 2 454 267 hemorrhagic stroke deaths from 522 cities in 25 countries. For every 1000 ischemic stroke deaths, we found that extreme cold and hot days contributed 9.1 (95% empirical CI, 8.6-9.4) and 2.2 (95% empirical CI, 1.9-2.4) excess deaths, respectively. For every 1000 hemorrhagic stroke deaths, extreme cold and hot days contributed 11.2 (95% empirical CI, 10.9-11.4) and 0.7 (95% empirical CI, 0.5-0.8) excess deaths, respectively. We found that countries with low gross domestic product per capita were at higher risk of heat-related hemorrhagic stroke mortality than countries with high gross domestic product per capita (P=0.02). CONCLUSIONS: Both extreme cold and hot temperatures are associated with an increased risk of dying from ischemic and hemorrhagic strokes. As climate change continues to exacerbate these extreme temperatures, interventional strategies are needed to mitigate impacts on stroke mortality, particularly in low-income countries.

Thiazolidinediones Decrease the Recurrence of Intracerebral Hemorrhage in Type 2 Diabetes Mellitus Patients: A Nested Case-Control Study.

INTRODUCTION: Preclinical evidence demonstrated the therapeutic potential of thiazolidinediones (TZDs) for the treatment of intracerebral hemorrhage (ICH). The present study conducted an investigation of cerebrovascular and cardiovascular outcomes following ICH in patients with type 2 diabetes mellitus (T2DM) treated with or without TZDs. METHODS: This retrospective nested case-control study used data from the Taiwan National Health Insurance Research Database. A total of 62,515 T2DM patients who were hospitalized with a diagnosis of ICH were enrolled, including 7,603 TZD users. Data for TZD non-users were extracted using propensity score matching. Primary outcomes included death and major adverse cardiovascular events (MACEs), which were defined as a composite of ischemic stroke, hemorrhagic stroke (HS), acute myocardial infarction, and congestive heart failure. Patients aged <20 years with a history of traumatic brain injury or any prior history of MACEs were excluded. RESULTS: TZD users had significantly lower MACE risks compared with TZD non-users following ICH (adjusted hazard ratio [aHR]: 0.90, 95% confidence interval [CI]: 0.85-0.94, p < 0.001). The most significant MACE difference reported for TZD users was HS, which possessed lower incidence than in TZD non-users, especially for the events that happened within 3 months following ICH (aHR: 0.74, 95% CI: 0.62-0.89 within 1 month, p < 0.01; aHR: 0.68, 95% CI: 0.54-0.85 between 1 and 3 month). CONCLUSION: The use of TZD in patients with T2DM was associated with a lower risk of subsequent HS and mortality following ICH.

Tetrahydrofolate Attenuates Cognitive Impairment after Hemorrhagic Stroke by Promoting Hippocampal Neurogenesis via PTEN Signaling.

Intracerebral hemorrhage (ICH), the most common subtype of hemorrhagic stroke, leads to cognitive impairment and imposes significant psychological burdens on patients. Hippocampal neurogenesis has been shown to play an essential role in cognitive function. Our previous study has shown that tetrahydrofolate (THF) promotes the proliferation of neural stem cells (NSCs). However, the effect of THF on cognition after ICH and the underlying mechanisms remain unclear. Here, we demonstrated that administration of THF could restore cognition after ICH. Using Nestin-GFP mice, we further revealed that THF enhanced the proliferation of hippocampal NSCs and neurogenesis after ICH. Mechanistically, we found that THF could prevent ICH-induced elevated level of PTEN and decreased expressions of phosphorylated AKT and mTOR. Furthermore, conditional deletion of PTEN in NSCs of the hippocampus attenuated the inhibitory effect of ICH on the proliferation of NSCs and abnormal neurogenesis. Taken together, these results provide molecular insights into ICH-induced cognitive impairment and suggest translational clinical therapeutic strategy for hemorrhagic stroke.

Associations Between Neuroinflammation-Related Conditions and Alzheimer's Disease: A Study of US Insurance Claims Data.

Background: Early detection of Alzheimer's disease (AD) is a key component for the success of the recently approved lecanemab and aducanumab. Patients with neuroinflammation-related conditions are associated with a higher risk for developing AD. Objective: Investigate the incidence of AD among patients with neuroinflammation-related conditions including epilepsy, hemorrhage stroke, multiple sclerosis (MS), and traumatic brain injury (TBI). Methods: We used Optum's de-identified Clinformatics Data Mart Database (CDM). We derived covariate-matched cohorts including patients with neuroinflammation-related conditions and controls without the corresponding condition. The matched cohorts were: 1) patients with epilepsy and controls (N = 67,825 matched pairs); 2) patients with hemorrhage stroke and controls (N = 81,510 matched pairs); 3) patients with MS and controls (N = 9,853 matched pairs); and 4) patients TBI and controls (N = 104,637 matched pairs). We used the Cox model to investigate the associations between neuroinflammation-related conditions and AD. Results: We identified that epilepsy, hemorrhage stroke, and TBI were associated with increased risks of AD in both males and females (hazard ratios [HRs]≥1.74, p < 0.001), as well as in gender- and race-conscious subpopulations (HRs≥1.64, p < 0.001). We identified that MS was associated with increased risks of AD in both males and females (HRs≥1.47, p≤0.004), while gender- and race-conscious subgroup analysis shown mixed associations. Conclusions: Patients with epilepsy, hemorrhage stroke, MS, and/or TBI are associated with a higher risk of developing AD. More attention on cognitive status should be given to older patients with these conditions.

How the elastase-induced rabbit aneurysm heals following flow diverter treatment: a histopathological study.

OBJECTIVE: Fibrin deposition is integral to thrombus formation and wound healing. The role of fibrin deposition and subsequent metabolism following flow diversion for aneurysm treatment remains poorly characterized. This study aimed to evaluate the role of fibrin in early thrombus organization after flow diverter treatment. METHODS: Thirty-five elastase-induced aneurysms were induced in New Zealand white rabbits and subjected to endoluminal flow diversion treatment. The device-bearing arteries were harvested at 1, 3, and 6 months postimplantation and processed for histopathological examination, including a modified picro-Mallory stain (Carstairs method) to visualize fibrin and platelets, immunohistochemical targeting of smooth muscle actin (SMA), and H&E staining for conventional morphological evaluation. Quantitative analysis of tissue components was carried out using the Orbit Image Analysis software. The samples were also assessed qualitatively to investigate the morphology and location of fibrin and other thrombus components within the intra-aneurysmal thrombi. Statistical analyses were conducted using R software version 4.3.1. RESULTS: Fibrin constituted 27.9% of the thrombus tissue within the aneurysm sac for aneurysms harvested at 1 month, and this rate was significantly lower in the 3-month group (10.2%, p = 0.018). The proportion of blood cells within the sac was also notably higher in the 1-month group compared with other time points. The primary tissue filling the dome at 1 month (14/15, 93%) was an unorganized thrombus primarily composed of fibrin, platelets, and red blood cells. Conversely, aneurysms harvested at 1 month had the lowest collagen level (25.6%). However, collagen became the dominant tissue component within the aneurysm sac, accounting for 71.8% of tissue in the 3-month group (p = 0.007). There were no differences observed among the examined components between the 3-month and 6-month groups. On qualitative analysis, collagen-producing SMA-positive myofibroblasts were located near or in between fibrin molecules. Healed aneurysms exhibited myofibroblasts, collagen, and a well-organized fibrin network on the aneurysm neck. In contrast, unhealed aneurysms displayed a poorly organized fibrin network with scattered myofibroblasts at the neck area. CONCLUSIONS: These findings indicate that fibrin plays a foundational role in the gradual occlusion of aneurysms after flow diverter treatment. Endovascular approaches that enhance fibrin accumulation could potentially improve aneurysm occlusion rates. Further research is needed to establish the precise role of fibrin in aneurysm occlusion.

Intracerebral Hemorrhage in a Patient With Newly Diagnosed Immune Thrombocytopenic Purpura Precipitated by a Viral Illness.

Intracerebral hemorrhage (ICH) is a rare and severe complication of immune thrombocytopenic purpura (ITP) that can be spontaneous. Viral illnesses, other infections, autoimmune disorders, and medications can cause ITP. ITP causes a significant decrease in platelet levels, increasing bleeding risk. ITP can be treated by steroids, intravenous immunoglobulin, plasmapheresis, platelet transfusion, biological agents, and splenectomy. ICH treatment involves the treatment of underlying ITP, as well as any neuro-interventional procedures needed. In this case report, we look at the presenting symptoms and treatment course of an interesting case of ICH in a patient who developed ITP after a viral upper respiratory infection.

Nurr1 overexpression in the primary motor cortex alleviates motor dysfunction induced by intracerebral hemorrhage in the striatum in mice.

Hemorrhage-induced injury of the corticospinal tract (CST) in the internal capsule (IC) causes severe neurological dysfunction in both human patients and rodent models of intracerebral hemorrhage (ICH). A nuclear receptor Nurr1 (NR4A2) is known to exert anti-inflammatory and neuroprotective effects in several neurological disorders. Previously we showed that Nurr1 ligands prevented CST injury and alleviated neurological deficits after ICH in mice. To prove direct effect of Nurr1 on CST integrity, we examined the effect of Nurr1 overexpression in neurons of the primary motor cortex on pathological consequences of ICH in mice. ICH was induced by intrastriatal injection of collagenase type VII, where hematoma invaded into IC. Neuron-specific overexpression of Nurr1 was induced by microinjection of synapsin I promoter-driven adeno-associated virus (AAV) vector into the primary motor cortex. Nurr1 overexpression significantly alleviated motor dysfunction but showed only modest effect on sensorimotor dysfunction after ICH. Nurr1 overexpression also preserved axonal structures in IC, while having no effect on hematoma-associated inflammatory events, oxidative stress, and neuronal death in the striatum after ICH. Immunostaining revealed that Nurr1 overexpression increased the expression of Ret tyrosine kinase and phosphorylation of Akt and ERK1/2 in neurons in the motor cortex. Moreover, administration of Nurr1 ligands 1,1-bis(3'-indolyl)-1-(p-chlorophenyl)methane or amodiaquine increased phosphorylation levels of Akt and ERK1/2 as well as expression of glial cell line-derived neurotrophic factor and Ret genes in the cerebral cortex. These results suggest that the therapeutic effect of Nurr1 on striatal ICH is attributable to the preservation of CST by acting on cortical neurons.

Characterization of Demographic, Clinical, and Laboratory Risk Factors for Stroke in a Tertiary Hospital in Riyadh, Saudi Arabia.

Background Stroke is a major cause of death and long-term disability worldwide, with varying incidence and risk factors across different populations. This study aims to analyze demographic, clinical, and laboratory risk factors for stroke among the Saudi Arabian population to enhance the understanding of its behavior and associated mortality. Methods In this retrospective cohort study, we analyzed data from 3586 patients diagnosed with hemorrhagic or non-hemorrhagic stroke at King Fahad Medical City from January 1, 2020, to November 11, 2022. We collected data on demographic variables, past medical history, social history, nationality, and laboratory components. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 27.0. (Armonk, NY: IBM Corp.), with significance set at p<0.05. Results The study population was predominantly male (57.86%) and within the age group of 51 to 80 years (58.8%). A significant portion of patients were Saudi nationals (99.6%), with hypertension (50.2%) and diabetes (40.4%) being the most common comorbidities. Laboratory abnormalities related to sodium and potassium levels were strongly linked to mortality rates. Notably, ischemic stroke was the most common type across all age groups, except for patients under age 16, where hemorrhagic stroke was more prevalent. Conclusions Our findings reveal significant associations between stroke risk factors and mortality within the Saudi Arabian population, highlighting the impact of hypertension, diabetes, and electrolyte imbalances. The study underscores the need for targeted stroke prevention and management strategies in Saudi Arabia, aligning with global trends to mitigate the burden of this disease.