David John Werring

Background and ObjectivesIatrogenic cerebral amyloid angiopathy (iCAA), likely caused by transmission of amyloid-beta by medical procedures, is a rare but distinct cerebral amyloid angiopathy (CAA)...

Background and ObjectivesDiffusion-weighted imaging (DWI)-positive lesions are increasingly recognized as markers of cerebral small vessel disease (cSVD) in acute intracerebral hemorrhage (ICH), bu...

Background and ObjectivesEnlarged perivascular spaces (EPVSs) in the basal ganglia (BG-EPVS) are an important marker of cerebral small vessel disease (cSVD), and EPVS in the centrum semiovale (CSO-...

Stroke incidence is rising rapidly in low- and middle-income countries (LMICs), particularly in sub-Saharan Africa, yet access to organised stroke care remains extremely limited. Although stroke units are among the most effective and cost-efficient interventions for improving outcomes after stroke, implementation in resource-constrained settings remains challenging. We describe the development of the first dedicated stroke unit in Malawi, established in 2022 at Queen Elizabeth Central Hospital (QECH), Blantyre. The QECH Comprehensive Stroke Service (QSS) was developed through a partnership involving the Malawi Ministry of Health, QECH, Malawi-Liverpool-Wellcome Research Programme (MLW), Kamuzu University of Health Sciences (KUHeS), University College London Hospitals (UCLH), and academic collaborators in Malawi and the UK. This paper focuses on health-system development rather than clinical outcomes. We describe the processes underpinning implementation, including partnership building, workforce development, infrastructure creation, pathway design, governance, and integration of data systems. Existing research infrastructure provided a foundation for service evaluation, registry development, and future interventional studies. Key lessons from the first three years included the importance of strong nursing leadership, task-shifting, phased implementation, multidisciplinary mentorship, and early alignment with Ministry of Health priorities in addressing workforce shortages and limited specialist capacity. Dedicated clinical space and integration with surveillance and research infrastructure supported sustainability, while weak digital systems and service overload remained ongoing challenges. Our experience demonstrates that organised stroke services can be developed in LMIC settings through adaptive clinical–academic partnerships integrated within existing health systems.

Background: Lacunar stroke can cause cognitive decline and dependency. The LACI‐2 (Lacunar Intervention Trial‐2) trial showed that 12 months of treatment with isosorbide‐mononitrate (ISMN) or cilostazol improved these outcomes. We tested whether this effect was present at 6 months. Methods: LACI‐2 was a prospective randomized open‐label blinded‐end point 2×2‐factorial phase‐2b trial assessing feasibility, safety, and proof‐of‐concept of 1 year of ISMN (40–60 mg) or cilostazol (200 mg). Participants aged >30 years had clinical lacunar stroke, compatible neuroimaging, and capacity to consent. The primary clinical outcome was the composite of stroke, myocardial infarction, dependency (modified Rankin Scale score >2), cognitive impairment ( Diagnostic and Statistical Manual version 5, 7‐level >0) and death; key secondary outcomes included the composite components, mood and stroke impact scale. Global analysis of the stroke impact scale was analyzed using the Wei–Lachin test with result given as Mann–Whitney difference. Results: Baseline characteristics were balanced across 363 participants: median age 64 (56–72) years, 31% female, and median onset to randomization 79 (27–244) days. At 6 months, participants allocated to ISMN versus control had fewer composite events (adjusted odds ratio [OR], 0.74 [95% CI, 0.55–0.99]) and improved stroke impact (Mann–Whitney difference, −0.15 [95% CI −0.25 to −0.05]). Cilostazol versus control improved cognition ( Diagnostic and Statistical Manual version 5, 7‐level scale, adjusted common OR, 0.64 [95% CI, 0.41–0.99]). ISMN/cilostazol versus control improved cognition ( Diagnostic and Statistical Manual version 5, 7‐level adjusted common OR, 0.40 [95% CI, 0.21–0.78]), mood (Zung adjusted mean difference, −6.94 [95% CI, −12.25 to −1.64]) and global stroke impact (Mann–Whitney difference, −0.23 [95% CI, −0.37 to −0.09]). Conclusions: A reduction in the composite outcome, cognitive impairment, dependency, and stroke impact was seen within 6 months of starting ISMN or cilostazol. Registration: URL: www.isrctn.com ; Unique Identifier: ISRCTN14911850.

Background: Adverse non-motor outcomes are common after stroke, yet their true prevalence and prognosis remain uncertain, partly due to substantial methodological heterogeneity across studies. We aim to undertake a comprehensive synthesis of the available evidence on adverse non-motor outcomes after stroke. First, we aim to examine prevalence across study settings (hospital-based vs. population-based cohorts) and to evaluate the influence of outcome definitions, measurement instruments (validated vs. non-validated), stroke type (ischemic stroke, intracerebral hemorrhage (ICH), or mixed), and duration of follow-up. Second, we aim to identify study-level characteristics associated with adverse outcomes. Methods: We searched PubMed, MEDLINE, EMBASE, Scopus, Web of Science, and PsycINFO via Ovid (1 January 1999—30 November 2025) for prospective cohorts reporting 11 non-motor outcomes: anxiety, depression, apathy, fatigue, sleep disturbance, social participation, pain, bladder, bowel, and sexual dysfunction. Pooled prevalence according to study setting (hospital vs. population) was estimated using random-effects models; outcome definitions and measures were synthesized using descriptive statistics, and meta-regression analysis was used to identify associated factors. The quality of all included studies was assessed with the Newcastle–Ottawa Scale. Results: A total of 352 prospective cohort studies (247,541 participants; mean age 64 years; 247 male-predominant studies) were included, with a follow-up between 30 days and 10 years after stroke, with median follow-up duration of 6 months (IQR 3–12). Half of the studies were hospital based (181/352 [51%]). Of the included studies, 195 (55%) enrolled participants with ischemic stroke, 148 (42%) included participants with ischemic stroke or intracerebral hemorrhage, while only 10 (3%) included participants with intracerebral hemorrhage. Across all analyses, heterogeneity I ² ranged from 41% to 99%. We found no significant differences in the prevalence of adverse non-motor outcomes between hospital versus population settings, except, bowel dysfunction was more frequently reported in population-based studies (61%, 95% CI 54%–67% vs. 47%, 95% CI 37%–58%, p = 0.005). Non-validated outcome measures were used in 155/352 studies (44.3%). Studies using non-validated outcome measures showed higher pooled prevalence of anxiety (34%, 95% Cl 29%–40%, vs. 25%, 95% CI 20%–33%, p < 0.001), apathy (32%, 95% CI 27%–36%, vs. 22%, 95% CI 13%–41%, p = 0.005), sleep disturbance (62%, 95% CI 54%–73%, vs. 51%, 95% CI 44%–58%, p < 0.001), and bowel dysfunction (56%, 95% CI 43%–69%, vs. 49%, 95% CI 38%–60%, p = 0.027). Majority of studies (207/352 [59%]) were conducted within 30 days to 6 months after stroke, whereas only 41 (12%) examined non-motor outcomes beyond 2 years post stroke. Older age (>60 years), stroke due to ICH, and use of non-validated outcome measures were significantly associated with a higher prevalence of adverse non-motor outcomes across multiple domains. Conclusions: Non-motor outcomes are highly prevalent after stroke in hospital and population settings. However, we found methodological limitations across included studies, including limited evidence on non-motor outcomes after ICH, poor characterization of stroke type, frequent use of non-validated outcome measures, and few studies assessing outcomes beyond 2 years after stroke. Our findings indicate an urgent need for long-term, methodologically rigorous studies of non-motor outcomes after stroke to enable consistent assessment, inform life-after-stroke pathways, and improve clinical care.

Introduction: Platform trials are an efficient trial design which enables testing of multiple interventions simultaneously. They could advance knowledge of treatments for intracerebral haemorrhage (ICH). We aimed to investigate the views of clinicians involved in stroke research on recruitment to a future platform trial for ICH. Methods: Between April and July 2025, we conducted a UK-wide online survey of clinicians actively involved in stroke research using convenience sampling through professional organisations. Participants considered factors related to the consent process and research environment and could provide optional free text responses about additional barriers or facilitators to recruitment. We used descriptive statistics for quantitative data and content analysis for qualitative data. Results: Among 73 respondents, 46 (63%) were female, 36 (49%) were stroke physicians, 24 (33%) nurses, 6 (8%) allied health professionals, and 7 (10%) were in other roles. A total of 35 (48%) had >20 years’ clinical experience, 44 (60%) reported spending <10% of their role in research. 66 (90%) thought that a platform trial would be a good option for testing interventions for patients with stroke due to ICH. Across 11 modifiable factors, clinicians most frequently rated the perceived importance of the research question and a research-positive culture in the clinical team as facilitators of recruitment (both 92%), while clinician preference for specific treatments was most frequently rated as a barrier (48%). Two themes emerged from free text responses: study design and infrastructure. Regarding study design, respondents perceived consent procedures (n = 9), study materials (n = 8), study procedures (n = 8), eligibility assessment (n = 6), the research question (n = 3), and randomisation (n = 3) as important for a future platform trial. Regarding infrastructure, emergent factors were staffing (n = 17), local research culture and capacity (n = 9), research governance and delivery (n = 6), and training (n = 6). Conclusion: The overwhelming majority of respondents from the UK clinical stroke community supported a platform trial for ICH, although the influence of survey responder bias is unknown.

Introduction: Stroke is often followed by vascular cognitive impairment and vascular dementia, the most feared complications of stroke. However, understanding of post-stroke cognitive impairment remains limited. Methods: Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD) is an observational cohort study of post-stroke cognition. Patients with haemorrhagic or ischaemic stroke, or transient ischaemic attack, were recruited within six weeks of stroke from hospitals across the UK. Consent was obtained from patients with capacity or from relatives/friends in those without capacity. The primary outcome is dementia rate and its severity at two years assessed using a 7-level ordinal cognition outcome. Final dementia rate will be compared in those with mild stroke/TIA (worst NIHSS <=7) versus severe stroke (NIHSS >7). Secondary outcomes will include cognitive impairment, function, mood and quality of life, and predictors of cognitive impairment at one and two years. Data are shown as number (%), median [interquartile range, IQR] or mean (standard deviation, SD). Results: We recruited 2441 patients from 50 hospitals. Of these, 2432 (99.6%) had a qualifying event of stroke or TIA. The mean age was 68.2 years (SD 13.5), females 979 (40.3%), ethnic minority 170 (7.0%), NIHSS <=7 1962 (80.7%), onset to recruitment 5 days [IQR 3-13] and diagnosis ICH 192 (7.9%), ischaemic stroke 2097 (86.2%), TIA 143 (5.9%). The distribution of cognition at baseline (within 6 weeks of onset) was: normal 1300 (53.5%), minor neurocognitive disorder-single domain 351 (14.4%), minor neurocognitive disorder-multi domain 263 (10.8%), major neurocognitive disorder-mild 387 (15.9%), major neurocognitive disorder-moderate 108 (4.4%) and major neurocognitive disorder-severe 23 (0.1%). Participants with more severe stroke were recruited later (8 [IQR 3-17] vs 5 [2-11] days, p<0.001), less likely to have capacity (86.3% vs 96.8%, p<0.001) and more likely to have had an intracerebral haemorrhage (12.0% vs 6.8%, p<0.001). Conclusion: We provide baseline data with the statistical analysis plan in the appendix. The data highlight the substantial under-appreciated cognitive burden of stroke, even in the first few days and weeks after onset.