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IntroductionConflicting results from multiple randomised trials indicate that the methods and effects of blood pressure (BP) reduction after acute intracerebral haemorrhage (ICH) are complex. The Blood pressure in Acute Stroke Collaboration is an international collaboration, which aims to determine the optimal management of BP after acute stroke including ICH.Methods and analysisA systematic review will be undertaken according to the Preferred Reporting Items for Systematic review and Meta-Analysis of Individual Participant Data (IPD) guideline. A search of Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE from inception will be conducted to identify randomised controlled trials of BP management in adults with acute spontaneous (non-traumatic) ICH enrolled within the first 7 days of symptom onset. Authors of studies that meet the inclusion criteria will be invited to share their IPD. The primary outcome will be functional outcome according to the modified Rankin Scale. Safety outcomes will be early neurological deterioration, symptomatic hypotension and serious adverse events. Secondary outcomes will include death and neuroradiological and haemodynamic variables. Meta-analyses of pooled IPD using the intention-to-treat dataset of included trials, including subgroup analyses to assess modification of the effects of BP lowering by time to treatment, treatment strategy and patient’s demographic, clinical and prestroke neuroradiological characteristics.Ethics and disseminationNo new patient data will be collected nor is there any deviation from the original purposes of each study where ethical approvals were granted; therefore, further ethical approval is not required. Results will be reported in international peer-reviewed journals.PROSPERO registration numberCRD42019141136.

The Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial-2 (RIGHT-2) reported no overall treatment difference between glyceryl trinitrate (GTN) and sham at day 90. Here we assess participants' outcomes 1 year after randomisation. RIGHT-2 was an ambulance-based prospective randomised controlled trial where patients with presumed stroke and systolic blood pressure (BP) of >120 mm Hg received either GTN (5 mg/day) or sham patch. Centralised blinded telephone follow-up was performed at days 90 (primary endpoint) and 365 (secondary endpoint). The lead outcome was dependency assessed with the modified Rankin Scale (mRS). 1149 patients were recruited to RIGHT-2 between October 2015 and May 2018, and 1097 (95.5%) had outcome data recorded at day 365. At baseline, the patients were; female (48%), had a mean age of 73 (15) years, BP of 162 (25)/92 (18) mm Hg, onset to randomisation of 70 (45-115) min, diagnosis of ischaemic stroke (52%), intracerebral haemorrhage (ICH) (13%), transient ischaemic attack (TIA) (9%) and mimics (26%). There was no effect of GTN on mRS score at day 365 in participants with confirmed stroke/TIA (adjusted common odds ratio (acOR) 1.10, 95% CI 0.86 to 1.42) or in all patients. In patients randomised to GTN, mRS at day 365 tended to be worse in those with ICH (acOR 1.65, 95% CI 0.84 to 3.25) and better in those with a mimic diagnosis (acOR 0.53, 95% CI 0.33 to 0.84). At 1 year post randomisation, dependency did not differ between GTN and sham treatment in either the target population or overall. In prespecified subgroup analyses, GTN was associated with reduced dependency in participants with a final diagnosis of mimic and a non-significant worse outcome in participants with ICH. ISRCTN26986053.

The management of blood pressure variability (BPV) in acute stroke presents a complex challenge with profound implications for patient outcomes. This narrative review examines the role of BPV across various stages of acute stroke care, highlighting its impact on treatment strategies and prognostic considerations. In the prehospital setting, while guidelines lack specific recommendations for BP management, emerging evidence suggests a potential link between BPV and outcomes. Among ischaemic stroke patients who are ineligible for reperfusion therapies, BPV independently influences functional outcomes, emphasising the need for individualised approaches to BP control. During intravenous thrombolysis and endovascular therapy, the intricate interplay between BP levels, recanalisation status, and BPV is evident. Striking a balance between aggressive BP lowering and avoiding hypoperfusion-related complications is essential. Intracerebral haemorrhage management is further complicated by BPV, which emerges as a predictor of mortality and disability, necessitating nuanced BP management strategies. Finally, among patients with acute subarachnoid haemorrhage, increased BPV may be correlated with a rebleeding risk and worse outcomes, emphasizing the need for BPV monitoring in this population. Integration of BPV assessment into clinical practice and research protocols is crucial for refining treatment strategies that are tailored to individual patient needs. Future studies should explore novel interventions targeting BPV modulation to optimise stroke care outcomes.

Despite the growing interest in gender medicine, the influence of sex and gender on human diseases, including stroke, continues to be underestimated and understudied. The COVID-19 pandemic has overall impacted not only the occurrence and management of stroke but has also exacerbated sex and gender disparities among both patients and healthcare providers. This paper aims to provide an updated overview on the influence of sex and gender in stroke pathophysiology and care during COVID-19 pandemic, through biological, clinical, psychosocial and research perspectives. Gender equity and awareness of the importance of sexual differences are sorely needed, especially in times of health crisis but have not yet been achieved to date. To this purpose, the sudden yet worldwide diffusion of COVID-19 represents a unique learning experience that highlights critical unmet needs also in gender medicine. The failures of this recent past should be kept as food for thought to inspire proper strategies reducing inequalities and to address women’s health and wellbeing issues, particularly in case of future pandemics.

Purpose: To review the current evidence on anticoagulation for intracranial haemorrhage (ICrH) survivors with atrial fibrillation (AF). Method: Narrative review of the literature. Findings: AF and ICrH are age-related conditions whose prevalence and comorbidity is expected to increase with the ageing population. Patients with ICrH were excluded from pivotal randomized trials of anticoagulation in AF and guidelines do not provide strong recommendations on if and when to (re)initiate anticoagulation in patients with AF and ICrH. Pooled analyses of phase II randomized trials have reported reduced risk of ischaemic major adverse cardiovascular events with anticoagulation in this population, but there remains uncertainty regarding the effects of anticoagulation on recurrent ICrH and death, as well as potential heterogeneity of treatment effect in higher risk subgroups, such as patients with cerebral amyloid angiopathy. There are no reported randomized trials investigating the optimal timing of anticoagulation (re)initiation in ICrH survivors with AF and the findings from observational studies have been inconsistent. Conclusion: Whether or not OAC should be resumed in ICrH survivors with AF and the optimal timing of OAC (re)initiation are challenging clinical dilemmas that are becoming more frequent with our ageing population. The existing prevalence of AF in patients with ICrH and changing global demographics highlight the importance of ongoing and future randomized trials addressing unresolved questions surrounding optimal stroke prevention strategies in this vulnerable patient population.

Purpose: Intracerebral haemorrhage (ICH) is an important complication of direct oral anticoagulation (DOAC) therapy, where risks and prognosis are potentially modified by effective blood pressure (BP) control, both in the acute phase and for secondary prevention. Herein, we review BP management in the context of general anticoagulation associated ICH and specifically in DOAC-ICH, considering current evidence and highlighting outstanding questions. Method: Narrative review. Findings: Pooled analyses of major trials of BP lowering in acute ICH patients without anticoagulants demonstrate a reduction in the risk of haematoma expansion. As anticoagulant-associated ICH patients tend to be older, have more co-morbidities, and larger haematomas at baseline with a greater risk of expansion, the risks and benefits of intensive BP lowering treatment might both be higher. Small observational studies of DOAC-ICH patients suggest that lower achieved BP is associated with less expansion, lower mortality, and better functional outcomes. Care bundles including both anticoagulant reversal and intensive BP lowering might reduce the risk of death and disability in DOAC-ICH. Optimal control of BP in survivors of ICH reduces the risk of both ischaemic and haemorrhagic stroke but whether this modulates the risks and benefits of restarting a DOAC is unknown. Discussion: Limited evidence suggests that BP should be well managed in DOAC-ICH patients, in the same way as ICH patients not on anticoagulants, both in the hyperacute phase and for secondary prevention. Hypothetical differences in the effects of BP lowering treatment in DOAC-ICH need to be tested in clinical trials.

Professor Eivind Berge, MD, PhD died from cancer on 6 February 2020. He was a highly respected stroke expert, clinical trialist and clinician scientist who made substantial contributions to evidence-based stroke medicine and the work of the European Stroke Organisation.

BackgroundThe effect of transdermal glyceryl trinitrate (GTN, a nitrovasodilator) on clinical outcome when administered before hospital admission in suspected stroke patients is unclear. Here, we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2).MethodsRIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4 hours of onset. The primary outcome was a shift in scores on the modified Rankin scale (mRS) at day 90. Secondary outcomes included death; a global analysis (Wei-Lachin test) containing Barthel Index, EuroQol-5D, mRS, telephone interview for cognitive status-modified and Zung depression scale; and neuroimaging-determined ‘brain frailty’ markers. Data were reported as n (%), mean (SD), median [IQR], adjusted common OR (acOR), mean difference or Mann-Whitney difference (MWD) with 95% CI.Results597 of 1149 (52%) patients had a final diagnosis of ischaemic stroke; age 75 (12) years, premorbid mRS>2 107 (18%), Glasgow Coma Scale 14 (2) and time from onset to randomisation 67 [45, 108] min. Neuroimaging ‘brain frailty’ was common: median score 2 [2, 3] (range 0–3). At day 90, GTN did not influence the primary outcome (acOR for increased disability 1.15, 95% CI 0.85 to 1.54), death or global analysis (MWD 0.00, 95% CI −0.10 to 0.09). In subgroup analyses, there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1 hour of symptom onset and in those with more severe stroke.ConclusionsIn patients who had an ischaemic stroke, ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.

Background The proper imaging modality for use in the selection of patients for endovascular thrombectomy (EVT) presenting in the late window remains controversial, despite current guidelines advocating the use of advanced imaging in this population. We sought to understand if clinicians with different specialty training differ in their approach to patient selection for EVT in the late time window. Methods We conducted an international survey of stroke and neurointerventional clinicians between January and May 2022 with questions focusing on imaging and treatment decisions of large vessel occlusion (LVO) patients presenting in the late window. Interventional neurologists, interventional neuroradiologists, and endovascular neurosurgeons were defined as interventionists whereas all other specialties were defined as non-interventionists. The non-interventionist group was defined by all other specialties of the respondents: stroke neurologist, neuroradiologist, emergency medicine physician, trainee (fellows and residents) and others. Results Of 3000 invited to participate, 1506 (1027 non-interventionists, 478 interventionists, 1 declined to specify) physicians completed the study. Interventionist respondents were more likely to proceed directly to EVT (39.5% vs. 19.5%; p  < 0.0001) compared to non-interventionist respondents in patients with favorable ASPECTS (Alberta Stroke Program Early CT Score). Despite no difference in access to advanced imaging, interventionists were more likely to prefer CT/CTA alone (34.8% vs. 21.0%) and less likely to prefer CT/CTA/CTP (39.1% vs. 52.4%) for patient selection ( p  < 0.0001). When faced with uncertainty, non-interventionists were more likely to follow clinical guidelines (45.1% vs. 30.2%) while interventionists were more likely to follow their assessment of evidence (38.7% vs. 27.0%) ( p  < 0.0001). Conclusion Interventionists were less likely to use advanced imaging techniques in selecting LVO patients presenting in the late window and more likely to base their decisions on their assessment of evidence rather than published guidelines. These results reflect gaps between interventionists and non-interventionists reliance on clinical guidelines, the limits of available evidence, and clinician belief in the utility of advanced imaging.

Background Cerebellar and cerebral infarctions caused by the syndrome of cervical rib with thrombosis of subclavian artery are very unusual. Case presentation We report the case of a 49-year-old male patient with a right cervical rib compression leading to subclavian arterial thrombosis and both cerebellar and cerebral infarctions secondary to retrograde thromboembolisation. Follow-up imaging revealed partial resolution of the thrombosis after combined anti-coagulant and anti-platelet therapy. The cervical rib and first costa were surgically removed to prevent additional events. Conclusion Cervical rib vascular compression should be promptly diagnosed and treated in order to avoid further complications, including cerebrovascular ischemic events.