2024 Guideline for the Primary Prevention of Stroke: A Guideline From the American Heart Association/American Stroke Association.

AIM: The "2024 Guideline for the Primary Prevention of Stroke" replaces the 2014 "Guidelines for the Primary Prevention of Stroke." This updated guideline is intended to be a resource for clinicians to use to guide various prevention strategies for individuals with no history of stroke. METHODS: A comprehensive search for literature published since the 2014 guideline; derived from research involving human participants published in English; and indexed in MEDLINE, PubMed, Cochrane Library, and other selected and relevant databases was conducted between May and November 2023. Other documents on related subject matter previously published by the American Heart Association were also reviewed. STRUCTURE: Ischemic and hemorrhagic strokes lead to significant disability but, most important, are preventable. The 2024 primary prevention of stroke guideline provides recommendations based on current evidence for strategies to prevent stroke throughout the life span. These recommendations align with the American Heart Association's Life's Essential 8 for optimizing cardiovascular and brain health, in addition to preventing incident stroke. We also have added sex-specific recommendations for screening and prevention of stroke, which are new compared with the 2014 guideline. Many recommendations for similar risk factor prevention were updated, new topics were reviewed, and recommendations were created when supported by sufficient-quality published data.

Age differences in the change in cognition after stroke.

OBJECTIVE: To compare changes in cognitive trajectories after stroke between younger (18-64) and older (65+) adults, accounting for pre-stroke cognitive trajectories. MATERIALS AND METHODS: Pooled cohort study using individual participant data from 3 US cohorts (1971-2019), the Atherosclerosis Risk In Communities Study (ARIC), Framingham Offspring Study (FOS), and REasons for Geographic And Racial Differences in Stroke Study (REGARDS). Linear mixed effect models evaluated the association between age and the initial change (intercept) and rate of change (slope) in cognition after compared to before stroke. Outcomes were global cognition (primary), memory and executive function. RESULTS: We included 1,292 participants with stroke; 197 younger (47.2 % female, 32.5 % Black race) and 1,095 older (50.2 % female, 46.4 % Black race). Median (IQR) age at stroke was 59.7 (56.6-61.7) (younger group) and 75.2 (70.5-80.2) years (older group). Compared to the young, older participants had greater declines in global cognition (-1.69 point [95 % CI, -2.82 to -0.55] greater), memory (-1.05 point [95 % CI, -1.92 to -0.17] greater), and executive function (-3.72 point [95 % CI, -5.23 to -2.21] greater) initially after stroke. Older age was associated with faster declines in global cognition (-0.18 points per year [95 % CI, -0.36 to -0.01] faster) and executive function (-0.16 [95 % CI, -0.26 to -0.06] points per year for every 10 years of higher age), but not memory (-0.006 [95 % CI, -0.15 to 0.14]), after compared to before stroke. CONCLUSION: Older age was associated with greater post-stroke cognitive declines, accounting for differences in pre-stroke cognitive trajectories between the old and the young.

Trends over time in oral anticoagulation and stroke rates in atrial fibrillation: A community-based study.

OBJECTIVES: Over the last decade, direct oral anticoagulants (DOAC) have become preferred over warfarin for stroke prevention in atrial fibrillation (AF). The objectives of this study were to quantify the shift over time from warfarin to DOACs and parallel changes in ischemic and hemorrhagic stroke rates in AF. MATERIALS AND METHODS: This community-based retrospective study was undertaken within a single integrated health care network from 2011 to 2021. Changes over time in warfarin and DOAC use were quantified by year, both overall and stratified by CHA2DS2-VASc score. Ischemic and hemorrhagic stroke rate changes over time were evaluated by Poisson regression. Stroke rates were evaluated in different time eras: 2011-2015 and 2016-2021. RESULTS: Among 31,978 AF patients followed an average of 5.5 years, any OAC use increased from 50.2 % (2011) to 59.4 % (2020) (p < 0.001). Warfarin use decreased from 49.3 % to 30.8 %, while DOAC use increased from 2.0 % to 30.8 % (both p < 0.001). In 2020, patients with CHA2DS2-VASc 0-1 and 2-5 were more likely to use DOACs than warfarin (18.6 % vs. 6.7 %; 33.0 % vs. 28.2 %), whereas in CHA2DS2-VASc 6-9 DOACs were used less frequently (30.0 % vs. 40.8 %). Ischemic stroke rates significantly increased by 19 % (95 % CI: 7 %, 32 %) from 2011 to 2015, but significantly decreased by 18 % (10 %, 26 %) from 2016 to 2021. Hemorrhagic stroke rates stabilized in 2016-2021 (+3 %; -18 %, 30 %) after increasing in 2011-2015 (+36 %; 4 %, 78 %). CONCLUSION: Improvements in ischemic and hemorrhagic stroke rates coincided temporally with increased uptake of OACs and a shift toward increased uptake of DOACs relative to warfarin.

Stereotactic aspiration versus conservative management for primary brainstem hemorrhage: A systematic review and meta-analysis.

BACKGROUND: Primary brainstem hemorrhage (PBSH) is a fatal condition related to hypertension. PBSH definitive treatment remains controversial, mainly when surgical options are discussed. OBJECTIVE: To aid decision-making in PBSH scenarios, we aimed to perform a meta-analysis and evaluate the literature on stereotactic aspiration (SA) for PBSH in comparison to conservative management (CM). METHODS: The outcomes assessed were: 30-day mortality, mortality, 90-day good outcome (mRs ≤ 3), good outcome (mRs ≤ 3), good outcome (mRs ≤ 3 or GOS 4-5), 90-day poor outcome (mRs ≥ 4), poor outcome (mRs ≥ 4). RESULTS: We included 1189 patients from 9 studies. 433 (36,41 %) patients were treated with SA. The risk of 30-Day Mortality (RR 0.57; 95 % CI 0.41-0.81; p=0.002; I²=58 %), Mortality (RR 0.56; 95 % CI 0.41-0.75; p<0.001; I²=54 %), 90-Day Poor Outcome (mRS ≥ 4) (RR 0.83; 95 % CI 0.73-0.93; p=0.001; I²=25 %), Poor Outcome (mRS ≥ 4) (RR 0.83; 95 % CI 0.75-0.93; p=0.001; I²=0 %) and Poor Outcome (mRS ≥ 4 or GOS ≤ 3) (RR 0.82; 95 % CI 0.74-0.91; p<0.001; I²=12 %) were significantly lower in patients receiving SA treatment. Also, the risk of 90-Day Good Outcome (mRS ≤ 3) (RR 1.60; 95 % CI 1.06-2.39; p=0.024; I²=21 %), Good Outcome (mRS ≤ 3) (RR 1.48; 95 % CI 1.13-1.94; p=0.005; I²=0) and Good Outcome (mRS ≤ 3 or GOS 4-5) (RR 1.72; 95 % CI 1.17-2.53; p=0.006; I²=25 %) were significant higher in the SA group. CONCLUSION: SA demonstrated favorable outcomes, including reduced mortality rates and improved functional recovery. Further clinical trials are needed to validate these findings.

A case of hypertensive crisis following administration of nonionic low molecular weight contrast in hemorrhagic stroke patient: a case report.

Introduction: Radiocontrast agents can be iodinated or noniodinated. Iodinated agents are further divided into low and high molecular weights. In recent decades, LOCM has largely replaced the use of HOCM due to safety concerns, but an increasing number of severe side effects cases have been reported. Case presentation: A 62-year-old woman presented with acute right hemiparesis. A CT scan revealed ICH with IVH. A contrasted CTA was ordered, during which Iohexol was administered. Shortly after the injection, she developed a hypertensive crisis. She was transferred to the ICU, intubated, and given labetalol. Repeated CT scan showed increased IVH with posterior edema. Her family declined surgical intervention. Unfortunately, she died. Discussion: This represents a unique adverse effect of a low molecular weight contrast agent that has been rarely reported before, particularly in pheochromocytoma patients. Nevertheless, our patient had subtle hypertension that was revealed during hospital admission but without pheochromcytoma. Conclusion: This case represents an unusual instance of a severe adverse. It suggests that the malignant rise in blood pressure may not be catecholamine-induced.

A Comprehensive Study of Risk Factors, Etiology, and Infarction Patterns in Cerebrovascular Accidents at a Tertiary Care Hospital in India.

Background Stroke is a debilitating cerebrovascular condition characterized by sudden neurological deficits. The incidence of stroke is rising in India, posing significant public health concerns. This study aims to examine the risk factors and etiology of stroke using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and analyze infarct areas in cerebrovascular accidents (CVA) at a tertiary care hospital. Methodology This cross-sectional, hospital-based observational study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to Be University), Pune, India, from January 2023 to January 2024. The study included 100 adult patients diagnosed with CVA based on clinical and radiological criteria. Patients aged 18 years and older were eligible, while those with a history of head trauma or those below 18 years were excluded. The investigation protocol included routine biochemical assessments and radiological investigations, such as computed tomography (CT), magnetic resonance imaging (MRI) with angiography or venography, and Doppler ultrasound of bilateral carotid arteries. Results The study population consisted of 100 patients, with 84 males (84%) and 16 females (16%). Age distribution showed 44% were over 60 years old, 23% aged 51-60 years, 15% aged 31-40 years, 14% aged 41-50 years, and 4% aged 21-30 years. Hypertension was the most prevalent risk factor, affecting 75% of patients, with a higher occurrence in males (62%), compared to females (13%). Smoking was observed in 51% of patients, and alcohol consumption was seen in 50%. Other significant risk factors included dyslipidemia (39%), diabetes mellitus (33%), chronic kidney disease (11%), ischemic heart disease (10%), atrial fibrillation (4%), valvular heart disease (4%), and pregnancy or postpartum conditions (2%). Ischemic stroke was predominant, occurring in 80% of patients, while hemorrhagic stroke occurred in 20%. High occurrences of ischemic strokes were noted in the frontal lobe (41%), parietal lobe (37%), occipital lobe (27%), and temporal lobe (26%), with the internal capsule region also showing significant numbers (27%). According to the TOAST classification, the most prevalent cause of stroke in this study was undetermined etiology with two or more causes, accounting for 32% of cases, followed by large artery atherosclerosis, which accounted for 30%. Cardioembolic stroke was identified in 11% of the patients, with 4% due to atrial fibrillation, 3% due to acute myocardial infarction, 3% due to rheumatic valvular heart disease, and 1% due to infective endocarditis. Conclusion This study highlights the significant prevalence of hypertension, smoking, alcohol consumption, and hyperhomocysteinemia as major risk factors for stroke. Ischemic strokes were predominant, with high occurrences in the cerebral lobes and gangliocapsular region. These findings emphasize the need for targeted prevention strategies, including managing hypertension and lifestyle modifications such as smoking cessation and reducing alcohol consumption, to mitigate the risk of stroke. Effective management of blood pressure, lipid levels, and blood glucose is crucial for stroke prevention. Recognizing gender-specific differences and addressing comorbidities through an integrated approach can enhance patient outcomes and reduce the burden of stroke.

Author Response: Outcome Predictors of an Intracerebral Hemorrhage also Depend on the Causes of the Bleeding.

How to cite this article: Hazra D. Author Response: Outcome Predictors of an Intracerebral Hemorrhage also Depend on the Causes of the Bleeding. Indian J Crit Care Med 2024;28(9):892-893.

The role of glutathione peroxidase 4 in neuronal ferroptosis and its therapeutic potential in ischemic and hemorrhagic stroke.

Ferroptosis is a type of cell death that depends on iron and is driven by lipid peroxidation, playing a crucial role in neuronal death during stroke. A central element in this process is the inactivation of glutathione peroxidase 4 (GPx4), an antioxidant enzyme that helps maintain redox balance by reducing lipid hydroperoxides. This review examines the critical function of GPx4 in controlling neuronal ferroptosis following ischemic and hemorrhagic stroke. We explore the mechanisms through which GPx4 becomes inactivated in various stroke subtypes. In strokes, excess glutamate depletes glutathione (GSH) and products of hemoglobin breakdown overwhelm GPx4. Studies using genetic models with GPx4 deficiency underscore its vital role in maintaining neuronal survival and function. We also consider new therapeutic approaches to enhance GPx4 activity, including novel small molecule activators, adjustments in GSH metabolism, and selenium supplementation. Additionally, we outline the potential benefits of combining these GPx4-focused strategies with other anti-ferroptotic methods like iron chelation and lipoxygenase inhibition for enhanced neuroprotection. Furthermore, we highlight the significance of understanding the timing of GPx4 inactivation during stroke progression to design effective therapeutic interventions.

Association of the combined stereotactic radiosurgery and embolization strategy and long-term outcomes in brain arteriovenous malformations with a volume >10 ml: A nationwide multicenter observational prospective cohort study.

BACKGROUND: To assess the long-term outcome of large brain arteriovenous malformations (AVMs) (volume > 10 ml) underwent combined embolization and stereotactic radiosurgery (E+SRS) versus SRS alone. METHODS: Patients were recruited from a nationwide multicenter prospective collaboration registry (MATCH study, August 2011-August 2021) and categorized into E+SRS and SRS alone cohorts. Propensity score-matched survival analysis was employed to control for potential confounding variables. The primary outcome was a composite event of non-fatal hemorrhagic stroke or death. Secondary outcomes were favorable patient outcomes, AVM obliteration, favorable neurological outcomes, seizure, worsened mRS score, radiation-induced changes (RIC), and embolization complications. Furthermore, the efficacy of distinct embolization strategies was evaluated. Hazard ratios (HRs) were computed utilizing Cox proportional hazard models. RESULTS: Among 1063 AVMs who underwent SRS with or without prior embolization, 176 patients met the enrollment criteria. Following propensity score matching, the final analysis encompassed 98 patients (49 pairs). Median (interquartile range) follow-up duration for primary outcomes spanned 5.4 (2.7-8.4) years. Overall, the E+SRS strategy demonstrated a trend toward reduced incidence of primary outcomes compared to the SRS alone strategy (1.44 vs 2.37 per 100 patient-years; HR, 0.58 [95 % CI, 0.17-1.93]). Regardless of embolization degree or strategy, stratified analyses further consistently revealed a similar trend, albeit without achieving statistical significance. Secondary outcomes generally exhibited equivalence, but the combined approach showed potential superiority in most measures. CONCLUSIONS: This study suggests a trend toward lower long-term non-fatal hemorrhagic stroke or death risks with the E+SRS strategy when compared to SRS alone in large AVMs (volume > 10 ml).

Clinical features, hemorrhage risk and epilepsy outcomes of familial cerebral cavernous malformation: A 20-year observational pragmatic single-center study.

INTRODUCTION: Familial Cerebral Cavernous Malformations (fCCMs) are rare, hereditary conditions characterized by multiple central nervous system lesions. Despite their rarity, CCMs can cause significant clinical challenges when symptomatic, manifesting as seizure and symptomatic hemorrhage (CASH). Guidelines suggest neurosurgical intervention for symptomatic or previously symptomatic lesions, while conservative management is recommended for new-onset epilepsy. However, the natural history and optimal management remain unclear, necessitating further research. OBJECTIVE: This study aims to provide a comprehensive analysis of the clinical features, hemorrhage risk, and epilepsy outcomes in fCCM patients over an extended follow-up period, offering a more precise estimate of CASH and epilepsy rates in this population. METHODS: This retrospective longitudinal cohort study included fCCM patients enrolled from 2001 to May 2024. Data collected included demographic information, new neurological symptoms, symptomatic hemorrhages, seizures, and modified Rankin Scale (mRS) scores. Incidence rates of first symptomatic events and Kaplan-Meier survival curves were calculated, with logistic and Cox-proportional hazard regression models used to evaluate outcomes. RESULTS: A total of 47 patients were included in this study, with a mean age at diagnosis of 37.51 years. At diagnosis, 68 % were symptomatic, with 30 % having CASH and 36 % experiencing seizures without CASH. During a median follow-up of 126.0 months (interquartile range, 110.5 months), 17 % had a new CASH event, 20 % had seizures without CASH, and 60 % remained asymptomatic. The bleeding rate was 1.02 % per patient-year, with new focal neurological symptoms at 2.045 per 1000 patient-years and new CASH at 10.225 per 1000 patient-years. Most patients maintained minimal or no disability (mRS 0 or 1). Presenting with epilepsy at baseline significantly increased the odds of future seizures (OR 18.13, p = 0.001). CONCLUSION: This study highlights the complex presentation and progression of fCCMs, emphasizing the necessity for long-term monitoring. Baseline epilepsy is a significant predictor of future seizures, underscoring the need for individualized management strategies. Future research with larger cohorts and standardized criteria is essential to refine the understanding and management of fCCMs.

Multi-therapeutic-activity selenium nanodot toward preventing brain injury and restoring neurobehavioral functions following hemorrhagic stroke.

Intracerebral hemorrhage is a lethal cerebrovascular disease, and the inevitable secondary brain injury (SBI) is responsible for serious disability and death. Perfect therapeutic goal is to minimize SBI and restore neurobehavioral functions. Recently, neuroprotection is highlighted to reduce SBI, but it still faces "Neuronal survival but impaired functions" dilemma. Herein, this work further proposes a novel combinational therapeutic strategy of neuroprotection and neurogenesis toward this goal. However, appropriate therapeutic agents are rarely reported, and their discovery and development are urgently needed. Selenium participates in various physiological/pathological processes, which is hypothesized as a potential targeting molecule. To explore this effect, this work formulates an ultra-small selenium nanodot with a seleno-amino acid derived carbon dot domain and a hydrophilic PEG layer, surprisingly finding that it increases various selenoproteins levels at perihematomal region, to not only exert multiple neuroprotective roles at acute phase but promote neurogenesis and inhibit glial scar formation at recovery phase. At a safe dose, this combinational strategy effectively prevents SBI and recovers neurobehavioral functions to a normal level. Furthermore, its molecular mechanisms are revealed to broaden application scopes in other complex diseases.

Increased risk of depression and associated symptoms in poststroke aphasia.

Poststroke aphasia hinders patients' emotional processing and social adaptation. This study estimated the risks of depression and related symptoms in patients developing or not developing aphasia after various types of stroke. Using data from the US Collaborative Network within the TriNetX Diamond Network, we conducted a retrospective cohort study of adults experiencing their first stroke between 2013 and 2022. Diagnoses were confirmed using corresponding International Classification of Diseases, Tenth Revision, Clinical Modification codes. Patients were stratified by poststroke aphasia status and stroke type, with propensity score matching performed to control for confounders. The primary outcome was depression within one year post-stroke; secondary outcomes included anxiety, fatigue, agitation, emotional impact, and insomnia. Each matched group comprised 12,333 patients. The risk of depression was significantly higher in patients with poststroke aphasia (hazard ratio: 1.728; 95% CI 1.464-2.038; p < 0.001), especially those with post-hemorrhagic-stroke aphasia (hazard ratio: 2.321; 95% CI 1.814-2.970; p < 0.001). Patients with poststroke aphasia also had higher risks of fatigue, agitation, and emotional impact. Anxiety and insomnia risks were higher in those with post-hemorrhagic-stroke aphasia. Poststroke aphasia, particularly post-hemorrhagic-stroke aphasia, may increase the risks of depression and associated symptoms, indicating the need for comprehensive psychiatric assessments.

Advancing stroke diagnosis and management through nuclear medicine: a systematic review of clinical trials.

Introduction: Despite advancements in stroke care, challenges persist in timely triage and treatment initiation to prevent the burden of stroke-related disabilities. Although nuclear medicine has shown promise, no imaging technique has yet provided a sufficiently rapid, precise, and cost-effective approach to routine stroke management. This study aims to review the clinical application of nuclear medicine in stroke diagnosis and treatment. Methods: A systematic search of the Cochrane, EU Clinical Trials Register, ISRCTN, the International Stroke Trial, and the ClinicalTrials.gov database was conducted to find all registered trials reporting nuclear medicine's clinical applications in stroke up to June 07, 2024. Results: Among the 220 screened trials, 51 (36 interventional; 15 observational) met the eligibility criteria. Participants were older than 18 years old, with only six studies including pediatric under 17 years old, with a total of 11,262 stroke (9,232 ischemic; 2,030 haemorrhagic) participants. The bias risk varied across trials but remained mostly low to moderate. Discussion: The review highlighted nuclear medicine's significant contributions to stroke diagnosis and management, notably through mobile stroke units, pre-hospital acute stroke magnetic resonance image (MRI) based biomarkers, and MRI-based stroke mechanisms for 4D flow nuclear imaging. These advancements have generally reduced treatment delays and enhance clinical outcomes post-stroke. Specifically, radiopharmaceutical radiotracers can effectively discriminate between strokes and mimics, particularly in high-risk patients. Integrating novel positron emission tomography (PET) radiotracer 18F glycoprotein 1 and radionuclide angiography may improve sensitivity and specificity in thrombi detection for decisions regarding stenting or carotid endarterectomy, and the single-photon emission computed tomography and PET integration with ferumoxytol radiotracer-enhanced MRI enables functional imaging for evaluating cerebral perfusion, metabolic activity, and neuroinflammatory markers post-stroke. Overall, the integration of nuclear medicine into multimodal imaging equipment like computed-tomography PET and MRI-PET offers a more comprehensive picture of the brain. Nevertheless, further research is needed on novel stroke imaging techniques and standardization across stroke centers for optimal performance. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024541680, identifier PROSPERO CRD(42024541680).

The Role of High-Density Lipoprotein, C-reactive Protein, and Serum Ferritin in Ischemic and Hemorrhagic Stroke: An Observational Cross-Sectional Comparative Study.

Background Stroke is a significant global health issue, with a high prevalence of morbidity, mortality, and disability. We can classify strokes into two types: ischemic and hemorrhagic, with ischemic strokes being more common. This study aims to investigate the role of high-density lipoprotein (HDL), C-reactive protein (CRP), and serum ferritin levels in people who have had ischemic and hemorrhagic strokes in order to identify possible biomarkers for diagnosis and treatment. Materials and methods This observational cross-sectional comparative study included 100 stroke patients (50 ischemic and 50 hemorrhagic) from Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Pune. We collected data through clinical evaluations, laboratory tests, and imaging studies. We measured and analyzed HDL, CRP, and serum ferritin levels using appropriate statistical tests, such as the chi-square test and Student t-test, with a 95% confidence interval (CI) and a 5% p-value for significance. Results The mean age for ischemic stroke patients was 55.92 years, whereas for hemorrhagic stroke patients, it was 58.68 years. The study found significant differences in HDL, CRP, and ferritin levels between the two groups. The mean HDL level for ischemic stroke patients was significantly lower at 25.10 mg/dL, compared to 40.57 mg/dL in hemorrhagic stroke patients, with a p-value of <0.001. The mean CRP level was higher in ischemic stroke patients (28.90 mg/L) compared to hemorrhagic stroke patients (22.80 mg/L), with a p-value of <0.001. Ferritin levels were also higher in hemorrhagic stroke patients (587.98 ng/mL) compared to ischemic stroke patients (473.16 ng/mL), with a statistically significant p-value of <0.001. Conclusion This study highlights the significant role of HDL, CRP, and serum ferritin levels in distinguishing between ischemic and hemorrhagic stroke patients. Elevated HDL levels may protect against ischemic strokes due to their anti-inflammatory properties, while higher CRP levels in ischemic strokes indicate a strong inflammatory response. Elevated ferritin levels in hemorrhagic strokes suggest increased oxidative stress and inflammation.

Informing future randomized controlled trials of amantadine hydrochloride in neurocritical care and post-neurocritical care stroke patients through a retrospective study.

BACKGROUND: Amantadine hydrochloride has been increasingly prescribed as a neurostimulant for neurocritical care stroke patients to promote wakefulness during inpatient recovery. However, a lack of guidelines makes it difficult to decide who may benefit from this pharmacotherapy and when amantadine should be initiated during the hospital stay. This study aims to determine some factors that may be associated with favorable response to amantadine to inform future randomized controlled trials of amantadine in critical care or post-critical care stroke patients. METHODS: Retrospective chart review for this study included neurocritical care and post-neurocritical care patients with acute ischemic or hemorrhagic stroke who were started on amantadine (N = 34) in the years 2016-2019. Patients were labeled as either responders or nonresponders of amantadine within 9 days of initiation using novel amantadine scoring criteria utilized and published in Neurocritical Care in the year 2021, which included spontaneous wakefulness and Glasgow Coma Scale (GCS). Amantadine response status and predictive variables were analyzed using nonparametric tests and adjusted multivariable regression models. RESULTS: There were large but nonsignificant variations in the median total milligrams of amantadine received in the first 9 days (IQR = 700-1,450 mg, p = 0.727). GCS on the day before amantadine initiation was significantly higher for responders (median = 12, IQR = 9-14) than nonresponders (median = 9, IQR = 8-10, p = 0.009). Favorable responder status was significantly associated with initiation in the critical care unit versus the step-down unit or the general medical/surgical floor [𝛃=1.02, 95% CI (0.10, 1.93), p = 0.031], but there was no significant associations with hospital day number started [𝛃=-0.003, 95% CI (-0.02, 0.02), p = 0.772]. CONCLUSIONS: Future randomized controlled trials of amantadine in hospitalized stroke patients should possibly consider examining dose-dependent relationships to establish stroke-specific dosing guidelines, minimum GCS threshold for which amantadine is efficacious, and the impact of patients' determined level of acuity on clinical outcomes instead of solely examining the impact of earlier amantadine initiation by hospital day number. Future research with larger sample sizes is needed to further examine these relationships and inform future clinical trials.

Outcomes in ischemic and hemorrhagic stroke patients with cancer: The Japan Stroke Data Bank.

INTRODUCTION: Data on the impact of malignancy on outcomes in patients with stroke, especially hemorrhagic stroke, are limited. We aimed to clarify the association between cancer and outcomes for each stroke type (ischemic/hemorrhagic) using a hospital-based multicenter stroke registration database. PATIENTS AND METHODS: Study participants were adult patients within 7 days of the onset of ischemic stroke (IS) or hemorrhagic stroke (HS) between 2000 and 2020 in the Japan Stroke Data Bank (JSDB). The patients were categorized into two groups according to whether they had a history of cancer. Outcomes included good functional outcomes, representing a modified Rankin Scale score of 0-2 at discharge and in-hospital mortality. RESULTS: Of the 203,983 patients analyzed in this substudy, 152,591 (women, 39.9 %; median age, 75 years) had IS, and 51,392 (48.6 %; 69 years) had HS. Of these, 6409 IS (4.2 %) and 1560 HS (3.0 %) patients had any cancer. IS patients with cancer had a lower frequency of good functional outcomes (47.5 % vs. 56.3 %; adjusted odds ratio [aOR] 0.85, 95 % confidence interval [CI] 0.79-0.91) and a higher incidence of in-hospital mortality (6.7 % vs. 4.5 %; aOR 1.59, 95 % CI 1.41-1.80) than those without cancer. HS patients with cancer showed a lower frequency of good functional outcome (24.9 % vs. 35.7 %; aOR 0.88, 95 % CI 0.78-0.99) and higher incidence of in-hospital mortality (20.1 % vs. 16.0 %; aOR 1.26, 95 % CI 1.04-1.52) than those without cancer. CONCLUSIONS: Both IS and HS patients with cancer had significantly lower good functional outcomes and more in-hospital mortality.

The Cytidine N-Acetyltransferase NAT10 Promotes Thalamus Hemorrhage-Induced Central Poststroke Pain by Stabilizing Fn14 Expression in Thalamic Neurons.

The recognition of RNA N4-acetylcytidine (ac4C) modification as a significant type of gene regulation is growing; nevertheless, whether ac4C modification or the N-acetyltransferase 10 protein (NAT10, the only ac4C "writer" that is presently known) participates in thalamus hemorrhage (TH)-induced central poststroke pain (CPSP) is unknown. Here, we observed NAT10 was primarily located in the neuronal nuclei of the thalamus of mice, with Fn14 and p65. An increase of NAT10 mRNA and protein expression levels in the ipsilateral thalamus was observed from days 1 to 14 after TH. Inhibition of NAT10 by several different approaches attenuated Fn14 and p65 upregulation of TH mice, as well as tissue injury in the thalamus on the ipsilateral side, and the development and maintenance of contralateral nociceptive hypersensitivities. NAT10 overexpression increased Fn14 and p65 expression and elicited nociceptive hypersensitivities in naïve mice. Our findings suggest that ac4C modification and NAT10 participate in TH-induced CPSP by activating the NF-κB pathway through upregulating Fn14 in thalamic neurons. NAT10 could serve as a promising new target for CPSP treatment.

Epidemiology, Pathophysiology, and Current Treatment Strategies in Stroke.

Both ischemic and hemorrhagic strokes are critical health issues and the incidence is on the rise. The rapid neurological degeneration that can occur with either type of stroke warrants prompt medical attention. In the article, we critically reviewed the literature examining their incidence, pathophysiology, and present treatment strategies. Clinical trials show conflicting findings, with ischemic strokes accounting for 87% of all strokes. Brain injury following an ischemic stroke results in cell death and necrosis, immune cells being the primary actors in the process of neuroinflammation. In order to develop neuroprotective drugs against ischemic stroke, detailed investigation of glutamate production and metabolism as well as downstream pathways controlled by glutamate receptors provides significant information on the underlying mechanisms. The permeability of the blood-brain barrier and the degradation of glutamine synthase are two potential mechanisms by which peritoneal dialysis accelerates brain-to-blood glutamate clearance and thus reduces glutamate levels in the brain after a stroke. Oxidative stress in an ischemic stroke disturbs the oxidant-antioxidant balance, which is particularly problematic for brain cells that are high in polyunsaturated fatty acids. Because of demographic factors like age, sex, race/ethnicity, and socioeconomic status, the incidence and prevalence of stroke differ across people and regions. For rapid diagnosis and treatment decisions, diagnostic imaging tools such as vascular imaging, CT, and MRI are essential. To aid in the recovery and lessen neurological impairments following a stroke, novel avenues of research are under investigation on neuroprotective medications that target inflammation, oxidative stress, and neuronal death.

Stroke and COVID-19: An Umbrella Review.

Introduction: Acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) are among the acute cerebrovascular diseases (CVDs) that have been reported as a result of COVID-19. It will be a significant step forward if our research helps improve the compilation and analysis of existing data from other studies. Methods: The study is registered on PROSPERO with an ID of CRD42023464058. It encompasses articles published until December 2023 and involves searching databases such as PubMed, Scopus, Web of Knowledge, Embase, and Cochrane. Additionally, we conducted manual searches in respected publications within this discipline, utilized the Google Scholar search engine, and conducted reference checks, citation checks, and study of gray literature. The publications' reporting quality was assessed using the "Assessment of Multiple Systematic Reviews" (AMSTAR) checklist. The meta-analysis was conducted using Stata software (StataCorp, version 16). Results: We analyzed the findings of 23 meta-analyses, which included 795 articles and encompassed 5,937 patients who had previously experienced a stroke. The average age of these patients was 62.3 years, and 68.3% were male. The findings indicated that the collective incidence of stroke among individuals with COVID-19 is roughly 1.75% [95% confidence interval (CI): 0.4%-3.03], with 1.59% for ischemic strokes and 0.3% for hemorrhagic strokes. 32.3% (95% CI: 27.8%-36.9%) of COVID-19 patients with stroke passed away, approximately 27% were discharged from the hospital with very mild or no complications, and around 28.1% (95% CI: 14.1%-42.1%) were referred for rehabilitation. Conclusions: The overall rate of stroke in COVID-19 patients was approximately 1.75%, with a higher incidence in males and those with an average age of 62.3 years. Almost 80% of the strokes were ischemic, and the mortality rate was approximately 32%. Finally, 27% of the patients were discharged without complications, and 28% required rehabilitation.

Stroke as a rare complication of scorpion stings: A systematic review and analysis.

Approximately 1 million scorpion stings are recorded annually worldwide, resulting in 3000 deaths. Scorpion venom has various effects on the human body, with neurological complications occurring in about 2% of cases. Among these complications, stroke-whether ischemic or hemorrhagic-is particularly significant. A systematic literature review was conducted through a bibliographic search using key terms in the PubMed, Scopus, Scielo, Latin American and Caribbean Literature in Health Sciences (LILACS) and Google Schoolar databases without date restrictions. Articles related to stroke due to scorpion stings in Spanish, English, and Portuguese were included. Our protocol was registered in PROSPERO. A total of 24 articles met the inclusion criteria for this review. The primary neurological symptoms caused by scorpion stings include hemiplegia, hemiparesis, seizures, and limb weakness. Stroke should be suspected in the presence of these symptoms, as scorpion stings can lead to both hemorrhagic and ischemic strokes in both adults and pediatric populations. While stroke is a rare complication of scorpion stings, it is crucial to consider this diagnosis in patients presenting with neurological symptoms, necessitating the use of computed tomography or magnetic resonance imaging if stroke is suspected.