Global Stroke Statistics 2023: Availability of reperfusion services around the world

Background: Disparities in the availability of reperfusion services for acute ischaemic stroke are considerable globally, and require urgent attention. Contemporary data on the availability of reperfusion services in different countries provide the necessary evidence to prioritise 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 papers, published up to January 2023, with the most recent, representative and relevant data for each country. Keywords included thrombolysis and telemedicine. We also screened reference lists of review papers, citation history of papers, and the grey literature. The information is provided as a narrative summary. // Results: Of 11,222 potentially eligible papers 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 (6463% 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 ambulances services (80% in HICs) around the world. // Conclusion: Despite remarkable advancements in reperfusion therapies for stroke, it is evident from available 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

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

NeuroBehcet’s-related intracranial hypertension without cerebral venous thrombosis: case report and review of literature

Abstract Background We present a rare case of NeuroBehcet’s-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of NeuroBehcet’s. In addition, we describe the novel use of subcutaneous tocilizumab for this indication. This is followed by a review of the literature on this topic. Case The patient was a 28-year-old lady of Southern Chinese origin with a known history of Behcet’s disease with oral ulcers and ocular findings for which she was on mycophenolate mofetil and adalimumab. She presented with a headache and bilateral disc swelling associated with an intracranial pressure (ICP) of > 40cmH20. There were no structural lesions or cerebral venous thrombosis (CVT) on imaging. Initial lumbar puncture had raised leucocytes and protein. We discuss diagnostic challenges given persistently elevated ICP despite subsequent non-inflammatory cerebrospinal fluid (CSF) profiles and non-response to acetazolamide. She eventually showed a response to immunosuppressant therapy in the form of pulsed methylprednisolone, cyclophosphamide and subsequently subcutaneous tocilizumab, supporting the diagnosis of NBrIHwCVT. Complete normalization of ICP remains challenging. Her disease course was severe, unusual for her ethnicity. Literature review We identified 34 patients (including ours) from 14 publications. We found that the majority of NBrIHwCVT patients were young (average age of 34 years), with a slight female preponderance. Of the 17 cases in the literature with available data on CSF profile, none had raised leucocytes whilst one patient had elevated protein. Patients were generally treated with steroids and occasionally azathioprine, in line with the suspected autoimmune pathophysiology. Of 22 patients with data on outcome, six (27%) were noted to have recurrence of symptoms generally occurring a few months later. Conclusion As demonstrated by this case, NBrIHwCVT can present with BD with raised ICP even if there is no prior history of NB, central Asian ethnicity, cerebral venous thrombosis or features of inflammation on the CSF. We demonstrated how novel use of Tocilizumab may have a role in the management of NBrIHwCVT. Based on our literature review, patients were more likely to be young, female, display a non-inflammatory CSF picture, be treated with steroids and harbour a possibility of recurrence

Cardioembolic stroke secondary to paroxysmal atrial fibrillation in a patient with systemic lupus erythematosus

A case is reported of a patient with systemic lupus erythematosus (SLE) presenting with ischemic stroke. This case highlights the need to search for various pathogenic mechanisms, including atrial fibrillation, which has a higher predilection with SLE, and its treatment with chloroquine

Non-Hypertensives and Those with Normal Cholesterol Are More Likely to Have Concomitant Cancer amongst Patients with Ischemic Stroke: A Retrospective Cross-Sectional Registry-Based Study

10.1159/000534267Cerebrovascular Diseases Extra13

The effectiveness of self-management interventions with action-taking components in improving health-related outcomes for adult stroke survivors: a systematic review and meta-analysis

Purpose This systematic review and meta-analysis aims to synthesise the evidence of the effectiveness of self-management interventions with action-taking components in improving self-efficacy, health-related quality of life, basic and instrumental activities of daily living, and depression for adult stroke survivors. Materials and methods Nine electronic databases were searched for relevant studies, including grey literature and ongoing studies. Randomised controlled trials targeting adult stroke survivors comparing health-related outcomes of patients receiving self-management interventions with action-taking components to usual care, placebo, or no-treatment were included. Screening, data extraction, and methodological quality assessment were conducted by two reviewers. Meta-analyses were performed. Overall quality of evidence was assessed using the GRADE tool. Results A total of seventeen studies were included. Meta-analyses showed that the intervention may result in a slight increase in self-efficacy (SMD = 0.29, 95% CI [0.07-0.52], p = 0.010, I-2 = 47%) and basic activities of daily living (SMD = 0.31, 95% CI [0.16-0.46], p < 0.001, I-2 = 0%), but not for the other outcomes. Conclusions Self-management interventions with action-taking components may result in a slight improvement in self-efficacy and rehabilitation of basic activities of daily living. Future research should investigate which core self-management skill, or combination of them, is most effective in improving short-term and long-term outcomes

Clinical applicability of methylome sequencing in a pilot study of ischemic stroke individuals

Despite recent progress in screening for genetic causes of cardiovascular disease using genome-wide association studies, identifying causative polymorphisms has not met initial expectations. This has led to interestin exploring the contribution of non-genetic factors in disease etiology. Elevated plasma homocysteine is an independent risk factor for cardiovascular disease but the mechanism for increased risk remains poorly understood. This study evaluates the clinical applicability of screeningfor genome-wide CpG methylation differences using methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq). Peripheral blood genomic DNA methylation in 8 Singaporean-Chinese ischemic stroke patients (4 male, 4 female) was profiled. Differential methylation of genes implicated in hyperhomocysteinemia was observed in males correlating withhomocysteine; namely CBS (cystathionine-beta-synthase) and MTHFR (methylenetetrahydrofolate reductase). In females, hypomethylation of the LDLR (low density lipoprotein receptor) and CELSR1 (cadherin, EGF LAGseven-pass G-type receptor 1) genes were observed in the hypertensive group (2 normal and 2 hypertensive individuals). While the number of clinical samples analysed is small, the findings of this evaluation suggest that MBD-seq is a suitable and sufficiently sensitive technology to determine methylation variability. The results presented warrant an expanded case-control study to determine the pathophysiological implications of DNA methylation for hyper-homocysteinemia

Plasma Vitamin D Levels are Lower among Ethnic Indians in Matched Pairs of Male Acute Ischaemic Stroke Patients of Indian and Chinese Ethnicity

Introduction: Ethnic Indians have a high burden of vascular disease. Vitamin D deficiency is associated with an increased risk of vascular disease including ischaemic stroke. Vitamin D levels are lower among ethnic Indians compared to ethnic Chinese in healthy individuals. We compared the plasma 25-hydroxyvitamin D [25(OH)D] levels between ethnic Indians and Chinese male ischaemic stroke patients. Methods: We prospectively recruited consecutive ethnic Indian acute ischaemic stroke male patients within seven days of symptom onset, who were admitted to the Singapore General Hospital. The subsequent ethnic Chinese acute ischaemic stroke male patient matched for age and diabetes status was recruited. Plasma 25(OH)D was measured using DiaSorin radioimmunoassay. Results: We studied 22 matched pairs of ethnic Indian and Chinese ischaemic stroke male patients. Mean plasma 25(OH)D level was lower among ethnic Indians (16.7 ± 6.1 μg/L) than ethnic Chinese patients (19.7 ± 4.4 μg/L) ( p =0.04). The mean difference was 2.9 ± 6.46 μg/L corresponding to 12.9 ± 33.1%. Conclusion: Ethnic Indian male ischaemic stroke patients had lower vitamin D levels compared to matched ethnic Chinese counterparts. Thus it is important to consider ethnicity in the understanding of stroke risk due to vitamin D deficiency

Using the full span of the SPAN-100 index to predict functional outcome in the CHIMES study

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