Papers will be suggested by members of the Paper of the Month (PoM) Working Group. All ESO members can nominate a paper by sending it directly to esoinfo@eso-stroke.org. Please note, you cannot nominate a paper in which you are a named author.
October 2025
“The authors aimed to determine whether the Edinburgh CT-only and CT-APOE diagnostic criteria for cerebral amyloid angiopathy-related lobar intracerebral haemorrhage are associated with recurrent intracerebral haemorrhage. They did a meta-analysis of individual patient data from cohort studies identified at the 2018 International cerebral amyloid angiopathy conference in Lille, France. In the primary two-stage meta-analysis of the CT-only criteria (562 patients from three European cohorts, median age 76 years , 282 [50%] female and 280 [50%] male), 69 patients had a recurrent intracerebral haemorrhage over 1381 person-years’ follow-up. The proportion with recurrent intracerebral haemorrhage during 5-year follow-up in the intermediate-risk and high-risk CT-only cerebral amyloid angiopathy criteria group was 48 (16%) of 307 patients compared with 21 (8%) of 255 patients in the low-risk group (adjusted sub-distribution hazard ratio 1·79, 95% CI 1·05–3·05, p=0·032). In the one-stage meta-analysis of the CT-only criteria (1620 patients with lobar intracerebral haemorrhage from eight cohorts, median age 73 years , 763 [47%] female and 857 [53%] male), 171 patients had a recurrent intracerebral haemorrhage over 3208 person-years’ follow-up. Cumulative 5-year incidence of recurrent intracerebral haemorrhage in the low-risk CT-only cerebral amyloid angiopathy criteria group was 45 (12%) of 727 patients compared with 54 (16%) of 513 patients in the intermediate-risk group (adjusted sub-distribution HR 1·68, 95% CI 1·21–2·32; p=0·0018), and 72 (26%) of 380 patients in the high-risk group (adjusted sub-distribution HR 2·97, 1·50–5·89, p=0·0018). They included six cohorts with 1021 eligible patients for the CT-APOE criteria. In the one-stage meta-analysis of the CT-APOE criteria (1006 patients, median age 71 years female and 529 [53%] male), 74 patients had a recurrent intracerebral haemorrhage over 1495 person-years’ follow-up. Cumulative 3-year incidence of recurrent intracerebral haemorrhage was 34 (15%) of 320 patients in the high-risk CT-APOE cerebral amyloid angiopathy criteria group versus 14 (8%) of 322 patients in the low-risk group (adjusted sub-distribution HR 2·22 [95% CI 1·36–3·61], p=0·0014). The authors concluded that the Edinburgh CT-only and CT-APOE diagnostic criteria for cerebral amyloid angiopathy-associated lobar intracerebral haemorrhage were associated with a greater incidence of recurrent intracerebral haemorrhage. These findings could aid personalised prediction and targeted secondary prevention in standard clinical practice where brain CT is available.”
Rodrigues MA, Seiffge D, Samarasekera N, Moullaali TJ, Wardlaw JM, Schreiber S, Behymer TP, Khandwala V, Stanton RJ, Vagal V and Woo D, Association between the Edinburgh CT and genetic diagnostic criteria for cerebral amyloid angiopathy-associated lobar intracerebral haemorrhage and recurrent intracerebral haemorrhage: an individual patient data meta-analysis. The Lancet Neurology. 2025; 24(10), pp. 828-839. https://doi.org/10.1016/S1474-4422(25)00285-6
September 2025
“This study evaluated the 10-year budget impact of DOACs in France, focusing on reductions in strokes/SE, MB, and monitoring costs (INRt). A retrospective budget impact model from 2014 to 2023 compared scenarios with and without DOACs, using clinical and cost data from the NAXOS study. Over a 10-year horizon, the introduction of DOACs is estimated to have prevented 73,009 strokes, 97,234 major bleeding, and 19,567 stroke-related deaths among patients with NVAF. DOAC introduction increased treatment costs by €5.15 billion over 10 years, and reduced costs for strokes/SE (-€4.24 billion), MB (-€3.22 billion), and INRt (-€1.14 billion), leading to €3.45 billion of savings for National Insurance over 10 years, with apixaban contributing 55% of savings. The authors concluded that over 10 years, the introduction of DOACs in France has generated substantial savings in AF-related costs, highlighting their clinical and economic benefits and the importance for authorities to valorise the external effects of therapeutic innovations.”
Guilmet C, Lesage H, Cotté FE, Moreau R, Marant Micallef C, Née M, Guitard-Dehoux D, Belhassen M, Danchin N. Nationwide extrapolation of economic benefit of therapeutic innovation: a 10-year retrospective budget impact of direct oral anticoagulants introduction in France. Journal of Medical Economics. 2025 Dec 31;28(1):859-70. https://doi.org/10.1080/13696998.2025.2514381
August 2025
Costs during the first year after stroke by degree of functional disability: A societal perspective.
“The authors performed a descriptive study of the cumulative costs incurred during 1-year follow-up of a cohort of patients with stroke in Catalonia (Spain) participating in a multicentre, population-based, cluster-randomised trial (RACECAT). Of the 567 patients included, 53% had ischaemic large vessel occlusion (LVO) stroke, 24% intracranial haemorrhage and 23% ischaemic non-LVO stroke. Mean cost per patient during the first year after stroke was €29,673 ± 28,632, and increased with degree of disability (mRS 0–2: €18,568 ± 12,244; mRS 3: €38,214 ± 28,172; mRS 4–5: €52,859 ± 36,383). Healthcare costs represented the highest proportion of total costs (63%; €18,724/patient) across all disability levels, with index hospitalisation being the highest (€12,319 ± 17,675); however, community care and patient/family costs represented over 40% of total cost in patients with higher disability levels.
These results are in line with other studies; the costs during the first year after stroke are high and increase with disability.”
Soler-Font M, Ribera A, Aznar-Lou I, Sánchez-Viñas A, Slof J, Vela E, Salvat-Plana M, Villa-García L, Serrano-Blanco A, Perez de la Osa N, Ribo M. Costs during the first year after stroke by degree of functional disability: A societal perspective. European Stroke Journal. 2025 Jun; 10(2): 513-23. doi: 10.1177/23969873241301904
July 2025
“The authors presented the results of the SECRETO multi-center case-control study that enrolled 503 patient-control pairs aged 18–49 years with imaging-positive acute cryptogenic ischemic stroke and 1:1 matched stroke-free controls. Lupus anticoagulant (LA), anticardiolipin (aCL), and anti-beta2-glycoprotein I (aβ2GPI) IgG antibodies were assessed from blood samples taken at two time points (baseline and 12-weeks) from patients and at a single time point from controls.
At either time-point, compared to healthy controls, patients had more frequently positive aβ2GPI (patients 11.9% vs controls 2.0%, p < 0.001). There was no significant difference in the presence of positive LA between patients and controls. In the logistic regression model, at either time-point positive aB2GI and aCL were associated with CIS (odds ratio [OR] 11.22, 95% confidence interval [CI] 4.35–28.95 and OR 20.85, 95% CI 204–213.16, respectively). The frequency of patients with positive aβ2GPI or aCL increased from baseline to 12 weeks (p < 0.001), whereas frequency of positive LA results decreased (p < 0.001).
The authors concluded that positive aβ2GPI and aCL, but not LA, detected either shortly after stroke or after 12 weeks were associated with early-onset CIS. After the acute phase, frequencies of positive aβ2GPI and aCL increased, whereas LA showed a reverse trend.”
Jaakonmäki N, Helin T, Szanto T, Zedde M, Sarkanen T, Martinez-Majander N, Sinisalo J, Junttola U, Redfors P, von Sarnowski B, Waje-Andreassen U. Anti-beta2-glycoprotein I IgG antibodies are associated with early-onset cryptogenic ischemic stroke. European Stroke Journal. 2025 Apr 1. https://doi.org/10.1177/23969873251351207
June 2025
“Randomised assessment of EVT in patients with large strokes in 6 clinical trials across 4 continents has yielded strong and consistent results, cementing the utility of reperfusion, even in those with substantial volumes of irreversible ischemia. Most importantly, the benefits of reperfusion outweighed the potential harms of reperfusion-infarcted brain tissue across clinical and imaging characteristics, indicating the safety of the intervention. These results have challenged our fundamental understanding of the utility of neuroimaging in estimating ischemic changes and our dichotomous view of infarcted versus noninfarcted tissue. Further pooled analyses from these trials are planned and should clarify the role of endovascular thrombectomy in subgroups such as the elderly, those with the largest ischemic core in the late time window, and those without significant mismatch assessed by perfusion imaging.”
Sarraj A, Yoshimura S, Thomalla G, Huo X, Arquizan C, Yoo AJ, Morimoto T, Bendszus M, Lapergue B, Nguyen TN, Campbell BC. Mechanical Thrombectomy for Large Ischemic Stroke: A Critical Appraisal of Evidence From 6 Randomised Controlled Trials. Stroke. 2025 Jul. doi.org/10.1161/STROKEAHA.125.050402
May 2025
“The 2-year interim analysis of ECST-2 found no evidence for a benefit of revascularisation in addition to OMT for patients with symptomatic and asymptomatic carotid stenosis of 50% or greater, with a 5-year predicted stroke risk of less than 20% (as assessed by the CAR score), in the first 2 years following the procedure. The risk of stroke in patients treated with OMT alone was substantially lower than recorded with best medical treatment in previous carotid stenosis trials. Further follow-up of ECST-2 up to 5 years from randomisation, and data from other trials, will be needed to confirm these findings. In the meantime, these results support treating patients with asymptomatic and low or intermediate risk symptomatic carotid stenosis with OMT alone. Applying individualised risk assessment could result in a reduction in revascularisation procedures and substantial cost savings in the future. Identifying patients with carotid stenosis who are at high risk of future stroke, who might benefit from revascularisation, should also be a goal of future research.”
Donners SJ, van Velzen TJ, Cheng SF, Gregson J, Hazewinkel AD, Pizzini FB, Emmer BJ, Simister R, Richards T, Lyrer PA and Maurer M. Optimised medical therapy alone versus optimised medical therapy plus revascularisation for asymptomatic or low-to-intermediate risk symptomatic carotid stenosis (ECST-2): 2-year interim results of a multicentre randomised trial. Lancet Neurol. 2025; 24(5): 389-399. doi.org/10.1016/S1474-4422(25)00107-3
April 2025
“The authors concluded that in patients presenting with an anterior circulation tandem occlusion secondary to cervical artery dissection, emergent stenting was associated with a higher likelihood of successful intracranial recanalisation, but not improved functional outcomes or increased symptomatic intracranial haemorrhage. It remains unclear whether emergent stenting led to successful intracranial recanalisation or patients with successful intracranial recanalisation were more likely to be stented.”
Sousa JA, Rodrigo-Gisbert M, Shu L, Luo A, Xiao H, Mahmoud NA, Shah A, Oliveira Santos AL, Moore M, Mandel DM, Heldner MR. Emergent Carotid Stenting During Thrombectomy in Tandem Occlusions Secondary to Dissection: A STOP-CAD Secondary Study. Stroke. 2025 Apr; 56(4): 808-817. doi.org/10.1161/STROKEAHA.124.048295
March 2025
“The rate of recurrent thrombosis and major bleeding did not differ between patients with CVT treated with DOACs versus VKAs. This study adds to the increasing evidence that DOACs are a reasonable treatment option for CVT alongside VKAs.“
van de Munckhof A, van Kammen MS, Tatlisumak T, Krzywicka K, Aaron S, Antochi F, Arauz A, Barboza MA, Conforto AB, Contreras DG, Heldner MR, Hernández-Pérez M, Hiltunen S, Ji X, Kam W, Kleinig TJ, Kristoffersen ES, Leker RR, Lemmens R, Poli S, Wasay M, Wu T, Yeşilot N, Chen J, Cotelli MS, Demeestere J, Duan J, Ergin N, Freitas TE, Gomes A, den Hertog HM, Lindgren E, Martinez-Majander N, Metanis I, Miraclin A, Rani LJ, Reddy YM, Saleem S, Scutelnic A, Shanmugasundaram S, van den Wijngaard IR, Gençdal IY, van Eekelen R, Vellema J, Arnold M, Neto L, Middeldorp S, de Sousa DA, Jood K, Putaala J, Ferro JM, Coutinho JM; DOAC-CVT investigators. Direct oral anticoagulants versus vitamin K antagonists for cerebral venous thrombosis (DOAC-CVT): an international, prospective, observational cohort study. Lancet Neurol. 2025 Mar; 24(3): 199-207. doi: 10.1016/S1474-4422(24)00519-2. PMID: 39986309.
February 2025
“The authors concluded that although treatment and outcome parameters seem to be in favor of men, most can be explained by older age, poorer prestroke independence, higher stroke severity, and more large vessel occlusion in women. Sex was not independently associated with worse 90-day functional outcome in women.”
Westphal LP, Rüttener L, Gasser T, Luft AR, Held U, Wegener S. Sex Differences in the Pre-and In-Hospital Setting of Patients With Stroke Are Driven by Higher Age and Stroke Severity. Stroke. 2025 Feb; https://doi.org/10.1161/STROKEAHA.124.048303
January 2025
Incidence and predictors of intracranial hemorrhage after intravenous thrombolysis with tenecteplase
“In this large real-life study, authors found that rates of parenchymal haemathoma (PH) and any intracerebral haemorrhage (ICH) after intravenous thrombolysis were 9.5% and 39.4%, respectively. In particular, older age, male gender, history of hypertension, higher baseline NIHSS and higher admission blood glucose levels were significantly associated with an increased risk of PH. These findings can help to identify patients presenting with an increased risk of ICH.”
Marnat G, Gerschenfeld G, Olindo S, Sibon I, Seners P, Clarençon F, Smadja D, Chausson N, Ben Hassen W, Piotin M, Caroff J. Incidence and predictors of intracranial hemorrhage after intravenous thrombolysis with tenecteplase. European Stroke Journal. 2024 May doi/10.1177/23969873241253660
Sharma et al demonstrate in this phase 2 RCT that the factor XIa inhibitior milvexian added to dual antiplatelets is safe, but did not significantly reduce the composite of ischaemic stroke or incident covert brain infarct on MRI at 90 days. No need to change practice yet, but a phase 3 study is planned.
In this study, patients with carotid artery plaque in which MNPs were detected had a higher risk of a composite of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than those in whom MNPs were not detected.
Decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep supratentorial intracerebral haemorrhage, but the evidence is weak. The point estimate of the treatment effect was higher than that seen with any other specific intervention previously tested in people with intracerebral haemorrhage. Based on the 95% CI a null effect is plausible, but harm is unlikely. The results of SWITCH apply to a subgroup of people with severe deep intracerebral haemorrhage and cannot be generalised to people with intracerebral haemorrhage in other locations. Irrespective of treatment, survival was associated with severe disability in both treatment groups.
This cross-sectional study found that a dynamic change in troponin was not associated with myocardial infarction in patients with ischemic stroke whereas baseline absolute troponin value was independently associated with type 1 myocardial infarction. The best cutoffs for predicting type 1 myocardial infarction were 5 to 10 times the upper limit of normal. In acute ischemic stroke, a dynamic change in troponin values is not helpful in detecting myocardial infarction, emphasizing that dynamic changes do not reveal the underlying pathophysiological mechanism of myocardial injury.
More than one-fifth of patients with acute cerebral ischemia (ACI) do not have an indication for statins, and statin overuse in these patients could annually lead to over 5600 adverse events each year in the United States, including diabetes, myopathy, and eye disease. These findings emphasize the importance of adhering to guideline indications for the start of statin therapy in ACI.
In a cohort study including 8119 patients with AF who started or restarted OAC after an IS, the risks of recurrent IS and mortality were high despite OAC treatment. In a nested case-control analysis, patients with OAC discontinuation had a significantly higher recurrent IS risk compared with patients who continued OAC use. The results suggest that OAC discontinuation is an important risk factor for recurrent IS, and there is a need to improve secondary prevention strategies for patients with AF.
Direct oral anticoagulants are the primary stroke prevention option in patients with atrial fibrillation. Anticoagulant use before stroke, however, might inhibit clinician comfort with thrombolysis if a stroke does occur. Resuming anticoagulants after ischemic stroke is also problematic for fear of hemorrhage. We describe extensive literature showing that thrombolysis is safe after stroke with direct anticoagulant use. Early reinstitution of direct anticoagulant treatment is associated with lower risk of embolic recurrence and lower hemorrhage risk. The use of direct anticoagulants before, during, and after thrombolysis appears to be safe and is likely to promote improved outcomes after ischemic stroke.
Tenecteplase 0·25 mg/kg was non-inferior to 0·9 mg/kg alteplase within 4·5 h of symptom onset in acute ischaemic stroke. Easier administration of tenecteplase, especially in the context of interhospital transfers, indicates that tenecteplase should be preferred to alteplase for thrombolysis in acute ischaemic stroke. The ATTEST-2 population was large and representative of thrombolysis-eligible patients in the UK and, together with findings from other trials, provides robust evidence supporting the introduction of tenecteplase in preference to alteplase.
The authors conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model. They included nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56–0.98; I2 = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43–0.95; I2 = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57–1.69; I2 = 21%), major bleeding (RR = 0.78; 95% CI:0.40–1.51; I2 = 0%), and mortality (RR = 0.94; 95% CI:0.61–1.45; I2 = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated.The authors concluded that early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation.
COVID-19 Vaccination and Cerebrovascular Events
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Venous thromboembolism after vaccination or COVID-19