BACKGROUND AND OBJECTIVE

The incidence of ischemic stroke typically increases with age; however, recent studies have shown a concerning trend of stroke cases among adults under the age of 45. This neurologic condition is called “Stroke in the Young” (SITY). SITY poses public health concerns due to its long-term consequences on individuals and their families. Despite significant impact, published literature on SITY among Filipinos is scarce. Given the potential differences in genetic background and lifestyle, the clinical characteristics and outcomes of SITY Filipinos may vary considerably from other populations. Therefore, the aim of this study is to describe the clinical features and outcomes of ischemic SITY Filipinos.

The study was a two-center, five-year retro- spective cohort design involving 19- to 45-year-old  patients admitted between January 1, 2017, and December 31, 2022, diagnosed clinically and radiologically with ischemic stroke for the first time. Medical records were reviewed, including demographic data, stroke symptoms, cardiovascular or non-cardiovascular risk factors, and laboratory results. Ischemic stroke subtypes were categorized into cardioembolic, small artery occlusion, stroke of other determined causes, and stroke of undetermined cause through the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. Functional outcomes on hospital discharge were assessed by the Modified Rankin Scale (mRS). All data were analyzed using descriptive statistics in the Statistical Package for the Social Sciences (SPSS software, version 29).

A total of 205 cases of ischemic SITY were chart reviewed. The mean age was 37.30, with a female predominance of 68.3%. The most reported cardiovascular risk factors were obesity (56.6%), hypertension (51.2%), heavy alcohol consumption (36.5%), and diabetes mellitus type 2 (19.5%). Concurrently, the non-cardiovascular risk factors identified were pregnancy, particularly in the postpartum period (4.8%), use of estrogen-containing pills (4.8%), and migraine without aura (4.4%). Based on TOAST classification, small vessel occlusion (42.1%) and large artery atherosclerosis (30.2%) were the most frequent ischemic stroke subtypes of SITY Filipino females. Mostly showed no symptoms of disability (35.1%) on hospital discharge.

This study highlights the difference in the clinical profile of young Filipino adults with ischemic stroke. Contrary to previous studies, ischemic stroke was more predominant among young females. Aside from hypertension, obesity has emerged as the leading cardio- vascular risk factor for ischemic SITY. Moreover, noncardiovascular risk factors, specific to females (pregnancy, use of estrogen-containing pills, and migraine), were also identified in the study. With regards to stroke subtypes, small vessel occlusion and large artery atherosclerosis were frequently seen in young female patients. These f indings suggest a need for gender-specific approaches in the evaluation, management, and prevention of ischemic SITY.

INTRODUCTION

Takayasu arteritis (TA) is a rare chronic large vessel vasculitis that affects the aorta and its major branches with a median age of onset of 25 years. The disease has a worldwide incidence of 1-2 per million, primarily affecting females with a 9:1 ratio. It is considered as an autoimmune disease that leads to progressive vessel thickening and stenosis, or aneurysmal dilatation. Coronary artery involvement is observed in 5.9%-58.2% of TA cases. We present a case of TA in a Filipino male presenting concurrently with myocardial infarction (MI) and ischemic stroke.

A 41-year-old Filipino male smoker with hypertension presented with chest pain, left-sided paresthesia and hemiparesis. Initial assessment revealed differential blood pressure between the arms, sensory and motor deficits, and abnormal ABI. Electrocardiogram confirmed anteroseptal ST-elevation MI and cranial computed tomography (CT) showed ischemic stroke. Arterial duplex scan had findings suggestive of hemodynamically significant lower extremity stenosis. A CT aortogram revealed multiple occlusions, including in the left subclavian artery, suggesting TA. Coronary angiography was attempted but was deferred due to peripheral arterial occlusion. A CT coronary angiogram revealed severe stenosis of the left anterior descending artery and moderate stenosis of the other coronaries. The patient was treated with dual antiplatelet therapy, statins, anticoagulation, corticosteroids and methotrexate. He experienced significant improvement in neurological symptoms and was chest pain-free upon discharge. At the 1-month follow-up, the patient remained asymptomatic.

Coronary involvement in TA can manifest as angina, MI, or other coronary lesions. The coexistence of MI and ischemic stroke in the same event is rare. Traditional risk factors for ischemic heart disease (IHD) in this patient such as hypertension and smoking may have contributed to the presentation, though TA itself is known to accelerate atherosclerosis. Limited vascular access hindered coronary intervention in this case and revascularization strategies remain challenging in active TA. The formation of extensive collateral arteries, along with early initiation of immunosuppressive therapy, likely contributed to the patient’s survival.

This case illustrates a rare and complex case of TA in a male patient with concurrent MI and ischemic stroke. Although coronary revascularization was not pursued due to occluded access, immunosuppressive therapy successfully managed the patient’s condition. Extensive collateral artery formation and early therapeutic intervention were key factors in the patient’s favorable outcome.

Ischemic stroke(IS) is a complex pathological process involving multiple cellular and molecular mechanisms and it is characterized by high mortality, high disability, and high recurrence. In recent years, the incidence of IS in China has been increasing year by year, and it has a trend of occurring in increasingly young individuals. Herb pairs are the smallest unit of traditional Chinese medicine(TCM) compatibility and an important part of TCM compounding, and the research on them is of great significance in guiding the clinical medication. Pharmacological studies have confirmed that certain herb pairs can exert anti-ischemic effects through various pathways such as reducing inflammation, alleviating oxidative stress, protecting the nervous system, and promoting neovascularization. By reviewing the relevant articles in the past decade, this paper probes into the combination rules, modern experimental studies, and combination ratios of the commonly used herb pairs from the etiology and pathogenesis of IS and summarizes 18 commonly used and deeply studied herb pairs, with a view to providing reference for the application, research, and development of clinical medicines.
Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Ischemic Stroke/metabolism* ; Medicine, Chinese Traditional

This study aimed to investigate the effect and mechanism of Buyang Huanwu Decoction in regulating endoplasmic reticulum stress via the inositol-requiring enzyme 1α(IRE1α)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway to improve neurological function in rats with cerebral ischemia/reperfusion injury(CIRI). SPF-grade male sprague-dawley(SD) rats were randomly divided into Sham group, model group, Buyang Huanwu Decoction group, and edaravone group. Except for the Sham group, the other groups were subjected to the modified suture method to establish a middle cerebral artery occlusion/reperfusion(MCAO/R) model. After treatment, neurological function was assessed using the Zea Longa scoring system. Gait analysis was used to detect the motor function. Detection of relative infarct area in brain tissue using 2,3,5-triphenyltetrazolium chloride(TTC) staining. Nissl staining was used to observe the structure of neuronal cells. Western blot and real-time fluorescence quantitative PCR(RT-qPCR) were used to detect IRE1α, ASK1, JNK, B cell lymphoma-2(Bcl-2), Bcl-2 related X protein(Bax), and Caspase-3 in the brain tissue. Immunohistochemistry was used to detect the positive expression of IRE1α, ASK1, and JNK. Immunofluorescence was used to detect the fluorescence expression levels of Bax, Bcl-2, and Caspase-3. The results showed that compared with the Sham group, the model group exhibited increased neurological scores(P<0.01), increased ratio of ground contact area and strength in both forelimbs(P<0.01), enlarged relative infarct area of brain tissue(P<0.05), and a reduced number of Nissl staining-positive cells(P<0.01). The protein and mRNA expression levels of IRE1α, ASK1, JNK, Bax, and Caspase-3 in brain tissue were significantly elevated, while those of Bcl-2 were decreased(P<0.05). Compared with the model group, both the Buyang Huanwu Decoction group and edaravone group showed reduced neurological scores(P<0.05), decreased ratio of ground contact area and strength in both forelimbs(P<0.05), smaller relative infarct area(P<0.05), alleviated neuronal damage, and increased number of Nissl staining-positive cells(P<0.05). The expression levels of IRE1α, ASK1, JNK, Bax, and Caspase-3 protein and mRNA in brain tissue were significantly reduced, while those of Bcl-2 were significantly increased(P<0.05). The results indicated that Buyang Huanwu Decoction can effectively improve brain injury in CIRI rats, and its mechanism of action may be related to regulating the endoplasmic reticulum stress IRE1α/ASK1/JNK signaling pathway.
Animals ; Male ; Rats, Sprague-Dawley ; Protein Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; MAP Kinase Kinase Kinase 5/genetics* ; Ischemic Stroke/physiopathology* ; Humans ; MAP Kinase Signaling System/drug effects* ; Apoptosis/drug effects* ; Endoribonucleases/genetics* ; JNK Mitogen-Activated Protein Kinases/genetics* ; Endoplasmic Reticulum Stress/drug effects* ; Multienzyme Complexes

BACKGROUND

Thrombolysis, or the administration of intravenous recombinant tissue plasminogen activator (IV rTPA) within the narrow therapeutic window following ischemic stroke onset, has emerged as a critical intervention in acute stroke care with the potential to restore blood flow and improve chances of functional recovery.

This study aimed to describe the demographic profile, risk factors, ischemic stroke subtypes, clinical course, and outcomes of stroke thrombolysis in a tertiary hospital in the Philippines over the past five years. It also aimed to evaluate key performance indicators in terms of benchmark times in the administration of IV rTPA.

This study used a retrospective observational design including all adult acute ischemic stroke patients who received IV rTPA at the University of the Philippines - Philippine General Hospital (UP-PGH). Data was collected through census and chart review.

One hundred eighty-eight patients received IV rTPA, majority were males (57.45%) with a median age of 60 years old. Hypertension (76.60%) was the most common risk factor for ischemic stroke. Partial anterior circulation infarcts (67.55%) and large artery atherosclerosis (49.47%) were the most common ischemic stroke subtype and etiology, respectively. The median door to needle time was 48 minutes, and the median length of hospital stay was five days. There was improvement in median NIHSS from 13 to 4, with a median modified Rankin scale of 3 indicating moderate disability upon discharge. Less than five percent (4.79%) had symptomatic intracerebral hemorrhage. The inhospital all-cause mortality rate among thrombolysed patients was 13.83%, mostly from non-neurologic causes. Nosocomial pneumonia and the need for neurosurgical interventions after thrombolysis were significantly associated with poor outcome (p < 0.05).

Our findings support the use of IV rTPA in the treatment of acute ischemic stroke. Existing stroke protocols in our institution are able to achieve the recommended thrombolysis benchmark times, leading to better functional outcomes for stroke patients.

Endovascular thrombectomy (EVT) has revolutionized the management of acute ischemic stroke (AIS) caused by large-vessel occlusion, significantly improving outcomes worldwide. This single-center case series evaluated the early outcomes of EVT in AIS patients treated at this institution, focusing on its implications within a low- or middleincome country setting. The study aimed to assess the feasibility, safety, and efficacy of EVT, analyzing premorbid comorbidities, time to treatment, revascularization rates, procedural complications, and clinical outcomes. Five consecutive cases of AIS due to large-vessel occlusion treated with EVT were analyzed. The patients in this series were aged 21 to 75 years, all with a baseline modified Rankin Scale (mRS) score of 0. The average NIH Stroke Scale (NIHSS) score on admission was 17. Four patients received Alteplase before EVT within four hours of symptom onset. Successful recanalization (TICI 2b-3) was achieved in all cases. Post-thrombectomy, two patients developed re-occlusion, with one resulting in mortality. Among the patients, 40% achieved a favorable outcome, defined as a modified Rankin Scale (mRS) score of 2 at three months. This initial experience demonstrates promising results in achieving successful recanalization and improving clinical outcomes in AIS patients with large-vessel occlusion. However, the study also highlights challenges such as procedural complications and post-thrombectomy re-occlusion, underscoring the need for ongoing evaluation and optimization of patient selection and procedural protocols in lowresource settings. Future studies with larger sample sizes are warranted to further validate these findings and refine EVT protocols tailored to local healthcare contexts.

Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

Acute ischemic stroke (AIS) is a cerebrovascular disease characterized by high morbidity, disability, and mortality, posing a significant threat to human health. Endovascular treatment has now been established as a key method for AIS management, in which stent retrievers that can mechanically remove blood clots play a key role in this technique. In recent years, stent retrievers have evolved in complexity and functionality to improve the ability of clot removing and surgical safety. However, the present instruments still have limitations on treatment efficiency, vascular adaptability, and operational precision, posing an urgent need for innovation in the design of stent retrievers. This paper systematically reviewed the structural features and working principles of AIS stent retrievers from the perspective of efficacy evaluation metrics, historical development, recent advancements in stent retrieval technology, and future prospects.
Humans ; Ischemic Stroke/surgery* ; Stents ; Endovascular Procedures/methods* ; Thrombectomy/methods* ; Device Removal/methods*

Stroke is the second leading cause of disability and mortality worldwide, imposing a substantial socioeconomic burden on individuals and healthcare systems. Annually, approximately 14 million people experience stroke, with ischemic stroke comprising nearly 85% of cases, of which 10% to 20% involve large vessel occlusions. Currently, recombinant tissue plasminogen activator (tPA) remains the only approved pharmacological intervention. However, its utility is limited due to a narrow therapeutic window and low recanalization rates, making it applicable to only a minority of patients. Therefore, there is an urgent need for novel therapeutic strategies, including pharmacological advancements and combinatory treatments. Small-molecule natural medicines, particularly those derived from traditional Chinese herbs, have demonstrated significant therapeutic potential in ischemic stroke management. These compounds exert multiple neuroprotective effects, such as antioxidation, anti-inflammatory action, and inhibition of apoptosis, all of which are critical in mitigating stroke-induced cerebral damage. This review comprehensively examines the pathophysiology of acute ischemic stroke (AIS) and highlights the recent progress in the development of small-molecule natural medicines as promising therapeutic agents for cerebral ischemic stroke.
Humans ; Ischemic Stroke/physiopathology* ; Animals ; Neuroprotective Agents/therapeutic use* ; Drugs, Chinese Herbal/chemistry* ; Biological Products/therapeutic use* ; Stroke/drug therapy*

Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal