Cerebral venous sinus thrombosis - Current updates in the Asian context.

Background Cerebral venous sinus thrombosis (CVT) is a life-threatening cause of stroke in Asian countries. South Asia, comprising of India, Pakistan and Bangladesh and contributed to 40% of strokes in women. Major CVT registries are from the western nations, which differs from the Asian countries with respect to epidemiology, gender biases and risk factors. This review focusses on the various aspects of relevance in evaluation and management of patients with CVT in the Asian context. Summary The incidence of CVT is higher in Asia than in Western nations. Young age, female gender, especially in pregnancy and puerperal period, and dehydration appear to be the critical risk factors. Tropical infections like malaria, scrub typhus, and flaviviral encephalitis predispose to CVT. There is a higher prevalence of inherited thrombophilia in the Asian cohorts, contributing to prothrombotic states. Anticoagulation and supportive management offer excellent outcomes. Newer anticoagulants are safe and efficacious. In medically refractory cases, endovascular treatment offers modest benefits. Decompressive hemicraniectomy, when done early, offers mortality benefits in patients with large hemorrhagic venous infarctions. Key messages CVT is an important cause of stroke with high-burden in South Asian countries. Establishment of robust registries is the need of the hour; to study the natural history, course and outcomes and to develop management algorithms tailored to the available resources.

A Systematic Search and Review of Registered Pharmacological Therapies Investigated to Improve Outcomes after a Stroke.

INTRODUCTION: Stroke burden is largely due to long-term impairments requiring prolonged care and loss of productivity. We aim to identify and assess studies of different registered pharmacological therapies as treatments for improving post-stroke impairments and/or disabilities. METHODS: In a systematic search and review (PROSPERO registration: CRD42022376973), studies of treatments that have been investigated as recovery-enhancing or recovery-promoting treatments in adult patients who had suffered a stroke will be searched for, screened, and reviewed based on the following: participants (P): adult humans, aged 18 years or older, diagnosed with stroke; interventions (I): registered or marketed pharmacological therapies that have been investigated as recovery-enhancing or recovery-promoting treatments in stroke; comparators (C): active or placebo or no comparator; outcomes (O): stroke-related neurological impairments and functional/disability assessments. Data will be extracted from included papers, including patient demographics, study methods, keystroke inclusion criteria, details of intervention and control, and the reported outcomes. RESULT: "The best available studies" based on study design, study size, and/or date of publication for different therapies and stroke subtypes will be selected and graded for level of evidence by consensus. CONCLUSION: There are conflicting study results of pharmacological interventions after an acute stroke to enhance recovery. This systematic search and review will identify the best evidence and knowledge gaps in the pharmacological treatment of post-stroke patients as well as guide clinical decision-making and planning of future studies.

Predictive accuracy of clinicians estimates of death and recovery after acute intracerebral hemorrhage: pre-specified analysis in INTERACT3 study.

INTRODUCTION: Accurately predicting a patient's prognosis is an important component of decision-making in intracerebral hemorrhage (ICH). We aimed to determine clinicians' ability to predict survival, functional recovery, and return to premorbid activities in patients with ICH. METHODS: Pre-specified secondary analysis of the third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3), an international, multicenter, stepped-wedge cluster randomized controlled trial. Clinician perspectives on prognosis were collected at hospital admission and Day 7 (or before discharge). Prognosis questions were the likelihood of (i) survival at 48 hours and 6 months, (ii) favorable functional outcome (recovery walking and self-care) and (iii) return to usual activities at 6 months. Clinician predictions were compared with actual outcomes. RESULTS: Most clinician participants were from neurosurgery (75%) with a median of 8 working years (IQR 5-14) of experience. Of the 6305 randomized patients who survived 48 hours, 213 (3.4%) were predicted to die (positive predictive value [PPV] 0.99, 95% confidence interval [CI] 0.99-0.99). Of 5435 patients who survived 6 months, 209 (3.8%) were predicted to die (PPV 0.93, 95% CI 0.92-0.93). Predictions on favorable functional outcome (PPV 0.54, 95% CI 0.52-0.56) and satisfied ability to return to usual activities (PPV 0.50, 95% CI 0.49-0.52) were poor. Prediction accuracy varied by working years and region of practice. CONCLUSIONS: In patients with ICH, clinician estimates of death are very good but conversely they are poor in predicting higher levels of functional recovery and activities.

Adaptive Trials in Stroke: Current Use and Future Directions.

Inclusion of adaptive design features in a clinical trial provides preplanned flexibility to dynamically modify a trial during its conduct while preserving validity and integrity. Adaptive trials are needed to accelerate the conduct of more efficient, informative, and ethical clinical research in the field of neurology. Stroke is a natural candidate for adoption of these innovative approaches to trial design. This Research Methods in Neurology article is informed by a scoping review that identified 45 completed or ongoing adaptive clinical trials in stroke that were appraised: 15 trials had published results with or without a published protocol and 30 ongoing trials (14 trials had a published protocol, and 16 trials were registered only). Interventions spanned acute (n = 28), rehabilitation (n = 8), prevention (n = 8), and rehabilitation and prevention (n = 1). A subsample of these trials was selected to illustrate the utility of adaptive design features and discuss why each adaptive feature was incorporated in the design to best achieve the aim; whether each individual feature was used and whether it resulted in expected efficiencies; and any learnings during preparation, conduct, or reporting. We then discuss the operational, ethical, and regulatory considerations that warrant careful consideration during adaptive trial planning and reflect on the workforce readiness to deliver adaptive trials in practice. We conclude that adaptive trials can be designed, funded, conducted, and published for a wide range of research questions and offer future directions to support adoption of adaptive trial designs in stroke and neurologic research more broadly.

Anticoagulation Patterns in Ischemic Stroke Patients with Atrial Fibrillation in Developing Country: Insights from the Stroke Registry in Vietnam.

(1) Background: Atrial fibrillation (AF) poses a growing cardiovascular challenge globally, with significant implications in Vietnam. This study aimed to investigate the impact of AF on ischemic stroke/transient ischemic attack (TIA) and clinical outcomes, as well as the utilization of oral anticoagulation (OAC) therapy in Vietnam. (2) Methods: Data from the Registry of Stroke Care Quality (RES-Q) across 66 hospitals in Vietnam between 2017 and 2023 were utilized. Patients diagnosed with ischemic stroke or TIA were included, and clinical characteristics, pre- and post-hospitalization medication, and hospitalized outcomes were examined. (3) Results: Of 94,144 patients, 15.1% had AF. Patients with AF were older and had a higher prevalence of heart failure and more severe strokes. AF was associated with increased mortality during hospitalization and a poorer prognosis. In AF patients, anticoagulation therapy utilization increased from 15.8% pre-hospitalization to 82.4% at discharge, with a preference for direct oral anticoagulants. (4) Conclusions: AF significantly impacts ischemic stroke/TIA outcomes in Vietnam. Pre-hospitalization and anticoagulation therapy utilization were low but improved at discharge. These findings emphasize the need for improved AF management and stroke prevention strategies in developing countries.

Global Insights on Prehospital Stroke Care: A Comprehensive Review of Challenges and Solutions in Low- and Middle-Income Countries.

Stroke is a leading cause of disability and mortality worldwide, and it disproportionately affects low- and middle-income countries (LMICs), which account for 88% of stroke fatalities. Prehospital stroke care delays are a crucial obstacle to successful treatment in these settings, especially given the limited therapeutic window for thrombolytic treatments, which may greatly improve recovery chances when initiated early after stroke onset. These delays are caused by a lack of public understanding of stroke symptoms, sociodemographic and cultural variables, and insufficient healthcare infrastructure. This review discusses these issues in detail, emphasizing the disparities in stroke awareness and reaction times between locations and socioeconomic classes. Innovative options for reducing these delays include the deployment of mobile stroke units and community-based educational campaigns. This review also discusses how technology improvements and personalized educational initiatives might improve stroke awareness and response in LMICs. The primary goal is to give a thorough assessment of the challenges and potential remedies that might serve as the foundation for policy reforms and healthcare improvements in LMICs, eventually improving stroke care and lowering disease-related mortality and disability.

Challenges to Widespread Implementation of Stroke Thrombectomy.

Endovascular treatment (EVT) for acute ischemic stroke is one of the most efficacious and effective treatments in medicine, yet globally, its implementation remains limited. Patterns of EVT underutilization exist in virtually any health care system and range from a complete lack of access to selective undertreatment of certain patient subgroups. In this review, we outline different patterns of EVT underutilization and possible causes. We discuss common challenges and bottlenecks that are encountered by physicians, patients, and other stakeholders when trying to establish and expand EVT services in different scenarios and possible pathways to overcome these challenges. Lastly, we discuss the importance of implementation research studies, strategic partnerships, and advocacy efforts to mitigate EVT underutilization.

Remote Ischemic Conditioning to Reduce Perihematoma Edema in Patients with Intracerebral Hemorrhage (RICOCHET): A Randomized Control Trial.

Background: Early perihematomal edema (PHE) growth is associated with worse functional outcomes at 90 days. Remote Ischemic conditioning (RIC) may reduce perihematomal inflammation if applied early to patients with intracerebral hemorrhage (ICH). We hypothesize that early RIC, delivered for seven days in patients with spontaneous ICH, may reduce PHE growth. Methods: ICH patients presenting within 6 h of symptom onset and hematoma volume < 60 milliliters (mL) were randomized to an RIC + standard care or standard care (SC) group. The primary outcome measure was calculated edema extension distance (EED), with the cm assessed on day seven. Results: Sixty patients were randomized with a mean ± SD age of 57.5 ± 10.8 years, and twenty-two (36.7%) were female. The relative baseline median PHE were similar (RIC group 0.75 (0.5-0.9) mL vs. SC group 0.91 (0.5-1.2) mL, p = 0.30). The median EEDs at baseline were similar (RIC group 0.58 (0.3-0.8) cm vs. SC group 0.51 (0.3-0.8) cm, p = 0.76). There was no difference in the median day 7 EED (RIC group 1.1 (0.6-1.2) cm vs. SC group 1 (0.9-1.2) cm, p = 0.75). Conclusions: Early RIC therapy delivered daily for seven days was feasible. However, no decrease in EED was noted with the intervention.

Stroke in Asia.

BACKGROUND: There is a significant burden of stroke in Asia. Asia has the largest population in the world in 2023, estimated at 4.7 billion. Approximately 9.5-10.6 million strokes will be anticipated annually in the backdrop of a diverse group of well-developed and less developed countries with large disparities in stroke care resources. In addition, Asian countries are in varying phases of epidemiological transition. SUMMARY: In this review, we examined recent epidemiological features of ischaemic stroke and intracerebral haemorrhage in Asia with recent developments in hyperacute stroke reperfusion therapy and technical improvements in intracerebral haemorrhage. The article also discussed the spectrum of cerebrovascular diseases in Asia, which include intracranial atherosclerosis, intracerebral haemorrhage, infective aetiologies of stroke, moyamoya disease, vascular dissection, radiation vasculopathy, and cerebral venous thrombosis. KEY MESSAGES: The review of selected literature and recent updates calls for attention to the different requirements for resources within Asia and highlights the breadth of cerebrovascular diseases still requiring further research and more effective therapies.

STENOSIS: Long-term single versus dual antiplatelet therapy in patients with ischaemic stroke due to intracranial atherosclerotic disease - a randomised trial.

Rationale: Intracranial atherosclerotic disease (ICAD) is a pathological process that causes progressive stenosis and cerebral hypoperfusion, leading to stroke occurrence and recurrence around the world. The exact duration of dual antiplatelet therapy (DAPT) for ICAD is unclear in view of long-term risk of bleeding complications. Aim: The current study aims to study the efficacy and safety of long-term DAPT (up to 12 months) in patients with ICAD. Sample size: Using 80% power and an alpha error of 5 %, presuming a 10%-15% drop-out rate, a total of 2200 patients will be recruited for the study. Methodology: This is a prospective, randomised, double-blind, placebo controlled trial. Study outcomes: The primary outcomes include recurrent ischaemic stroke (IS) or transient ischaemic attack and any intracranial haemorrhage (ICH), major or minor systemic bleeding at the end of 12 months. Secondary outcomes include composite of any stroke, myocardial infarction or death at the end of 12 months. The safety outcomes include any ICH, major or minor bleeding as defined using GUSTO (Global Use of Streptokinase and tPA for occluded Coronary Arteries) classification at the end of 12 months and 1 month after completion of the drug treatment phase. Discussion: The study will provide level I evidence on the duration of DAPT among patients with IS due to ICAD of more than or equal to 50%.

RE-OPEN: Randomised trial of biosimilar TNK versus TPA during endovascular therapy for acute ischaemic stroke due to large vessel occlusions.

Rationale: Rapid and timely treatment with intravenous thrombolysis and endovascular treatment (EVT) in patients with acute ischaemic stroke (AIS) and large vessel occlusion (LVO) significantly improves patient outcomes. Bridging therapy is the current standard of care in these patients. However, an incompletely answered question is whether one thrombolytic agent is better than another during bridging therapy. Aim: The current study aims to understand if one thrombolytic agent is superior to the other during bridging therapy in the treatment of AIS and LVO. Sample size estimates: Using 80% power and an alpha error of 5 %, presuming a 10% drop out rate, a total of 372 patients will be recruited for the study. Methods and design: This study is a prospective, randomised, multicentre, open-label trial with blinded outcome analysis design. Study outcomes: The primary outcomes include proportion of patients who will be independent at 3 months (modified Rankin score (mRS) ≤2 as good outcome) and proportion of patients who achieve recanalisation modified thrombolysis in cerebral infarction grade 2b/3 at first angiography run at the end of EVT. Secondary outcomes include proportion of patients with early neurological improvement, rate of symptomatic intracerebral haemorrhage (ICH), rate of any ICH, rate of any systemic major or minor bleeding and duration of hospital stay. Safety outcomes include any intracranial bleeding or symptomatic ICH. Discussion: This trial is envisioned to confirm the theoretical advantages and increase the strength and quality of evidence for use of tenecteplase (TNK) in practice. Also, it will help to generate data on the efficacy and safety of biosimilar TNK. Trial registration number: CTRI/2022/01/039473.

A systematic-search-and-review of registered pharmacological therapies investigated to improve neuro-recovery after a stroke.

Background: Stroke burden is largely due to long-term impairments requiring prolonged care with loss of productivity. We aimed to identify and assess studies of different registered pharmacological therapies as treatments to improve post-stroke impairments and/or disabilities. Methods: We performed a systematic-search-and-review of treatments that have been investigated as recovery-enhancing or recovery-promoting therapies in adult patients with stroke. The treatment must have received registration or market authorization in any country regardless of primary indication. Outcomes included in the review were neurological impairments and functional/disability assessments. "The best available studies" based on study design, study size, and/or date of publication were selected and graded for level of evidence (LOE) by consensus. Results: Our systematic search yielded 7,801 citations, and we reviewed 665 full-text papers. Fifty-eight publications were selected as "the best studies" across 25 pharmacological classes: 31 on ischemic stroke, 21 on ischemic or hemorrhagic stroke, 4 on intracerebral hemorrhage, and 2 on subarachnoid hemorrhage (SAH). Twenty-six were systematic reviews/meta-analyses, 29 were randomized clinical trials (RCTs), and three were cohort studies. Only nimodipine for SAH had LOE A of benefit (systematic review and network meta-analysis). Many studies, some of which showed treatment effects, were assessed as LOE C-LD, mainly due to small sample sizes or poor quality. Seven interventions had LOE B-R (systematic review/meta-analysis or RCT) of treatment effects. Conclusion: Only one commercially available treatment has LOE A for routine use in stroke. Further studies of putative neuroprotective drugs as adjunctive treatment to revascularization procedures and more confirmatory trials on recovery-promoting therapies will enhance the certainty of their benefit. The decision on their use must be guided by the clinical profile, neurological impairments, and target outcomes based on the available evidence. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=376973, PROSPERO, CRD42022376973.

Global stroke statistics 2023: Availability of reperfusion services around the world.

BACKGROUND: Disparities in the availability of reperfusion services for acute ischemic stroke are considerable globally and require urgent attention. Contemporary data on the availability of reperfusion services in different countries are used to provide the necessary evidence to prioritize where access to acute stroke treatment is needed. AIMS: To provide a snapshot of published literature on the provision of reperfusion services globally, including when facilitated by telemedicine or mobile stroke unit services. METHODS: We searched PubMed to identify original articles, published up to January 2023 for the most recent, representative, and relevant patient-level data for each country. Keywords included thrombolysis, endovascular thrombectomy and telemedicine. We also screened reference lists of review articles, citation history of articles, and the gray literature. The information is provided as a narrative summary. RESULTS: Of 11,222 potentially eligible articles retrieved, 148 were included for review following de-duplications and full-text review. Data were also obtained from national stroke clinical registry reports, Registry of Stroke Care Quality (RES-Q) and PRE-hospital Stroke Treatment Organization (PRESTO) repositories, and other national sources. Overall, we found evidence of the provision of intravenous thrombolysis services in 70 countries (63% high-income countries (HICs)) and endovascular thrombectomy services in 33 countries (68% HICs), corresponding to far less than half of the countries in the world. Recent data (from 2019 or later) were lacking for 35 of 67 countries with known year of data (52%). We found published data on 74 different stroke telemedicine programs (93% in HICs) and 14 active mobile stroke unit pre-hospital ambulance services (80% in HICs) around the world. CONCLUSION: Despite remarkable advancements in reperfusion therapies for stroke, it is evident from available patient-level data that their availability remains unevenly distributed globally. Contemporary published data on availability of reperfusion services remain scarce, even in HICs, thereby making it difficult to reliably ascertain current gaps in the provision of this vital acute stroke treatment around the world.

Post-Stroke Resting-State EEG Connectivity: A Longitudinal Neuro-Rehabilitation Study.

Stroke is a leading cause of permanent disability worldwide. Even after adequate treatment, the majority of patients do not recover fully, making them dependent on others for carrying out Activities of Daily Living (ADL). An improved understanding of the underlying mechanism of plasticity will help us in customizing the translational approach for learning and rehabilitation following a stroke. For this study, a 2-minute resting state EEG data were recorded at 5 time-points for 3-months after stroke onset. Directed Transfer Function (DTF) was used to study neural reorganization for 3 months. DTF for different brain regions and sub-bands was correlated with FMA. The information flow was studied for different brain regions as well as Affected Region (AR). Occipital region showed good correlation (r = 0.45 to 0.47) with FMA. Contra-lesional and ipsi-lesional regions trajectories complement each other during acute and sub-acute phase. The information outflow vs inflow imbalance of AR was restored by the end of 3 months. DTF can be used as biomarker for studying neuroplasticity. Occipital, temporal and motor cortex regions play an important role during neuro-rehabilitation. The information about different regions during rehabilitation will help us in designing subject-specific interventions for better recovery.

Implementing stroke care in a lower-middle-income country: results and recommendations based on an implementation study within the Nepal Stroke Project.

Background: Globally, the majority of strokes affect people residing in lower- and lower-middle-income countries (LMICs), but translating evidence-based knowledge into clinical practice in regions with limited healthcare resources remains challenging. As an LMIC in South Asia, stroke care has remained a healthcare problem previously unaddressed at a national scale in Nepal. The Nepal Stroke Project (NSP) aims to improve acute stroke care in the tertiary healthcare sector of Nepal. We hereby describe the methods applied and analyze the barriers and facilitators of the NSP after 18 months. Methods: The NSP follows a four-tier strategy: (1) quality improvement by training healthcare professionals in tertiary care centers; (2) implementation of in-hospital stroke surveillance and quality monitoring system; (3) raising public awareness of strokes; and (4) collaborating with political stakeholders to facilitate public funding for stroke care. We performed a qualitative, iterative analysis of observational data to analyze the output indicators and identify best practices. Results: Both offline and online initiatives were undertaken to address quality improvement and public awareness. More than 1,000 healthcare professionals across nine tertiary care hospitals attended 26 stroke-related workshops conducted by Nepalese and international stroke experts. Monthly webinars were organized, and chat groups were made for better networking and cross-institutional case sharing. Social media-based public awareness campaigns reached more than 3 million individuals. Moreover, live events and other mass media campaigns were instituted. For quality monitoring, the Registry of Stroke Care Quality (RES-Q) was introduced. Collaboration with stakeholders (both national and international) has been initiated. Discussion: We identified six actions that may support the development of tertiary care centers into essential stroke centers in a resource-limited setting. We believe that our experiences will contribute to the body of knowledge on translating evidence into practice in LMICs, although the impact of our results must be verified with process indicators of stroke care.

Surveillance of stroke: a South-East Asia Region (SEAR) perspective.

Surveillance of stroke is critical to track its burden and assess progress in prevention and treatment. We reviewed the literature to evaluate stroke surveillance efforts in the South-East Asia Region (SEAR) countries, identify progress and assess gaps. Epidemiological data on all the major parameters such as the incidence, prevalence and mortality of stroke were available for India and Thailand but for none of the other SEAR countries. Most of the epidemiological data came from investigator-initiated studies. National stroke surveillance was present only in India in the form of a National Stroke Registry Programme and Thailand has a national database that was used to obtain epidemiological data for stroke. Research on novel methods for stroke registration, such as using information technology, was absent. This review identified serious gaps in the monitoring and surveillance of stroke in SEAR countries. Systematic efforts are needed to fill those gaps.

Stroke systems of care in South-East Asia Region (SEAR): commonalities and diversities.

The Southeast Asia Region (SEAR) accounts for nearly 50% of the developing world's stroke burden. With various commonalities across its countries concerning health services, user awareness, and healthcare-seeking behavior, SEAR still presents profound diversities in stroke-related services across the continuum of care. This review highlights the numerous systems and challenges in access to stroke care, acute stroke care services, and health care systems, including rehabilitation. The paper has also attempted to compile information on the availability of stroke specialized centers, Intravenous thrombolysis (IVT) ready centers, Endovascular therapy (EVT) ready centers, rehabilitation centers, and workforce against a backdrop of each country's population. Lastly, the efforts of WHO (SEARO)-CMCL (World Health Organization-South East Asia region, Christian Medical College & Hospital Ludhiana) collaboration towards improving stroke services and capacity among the SEAR have been described.