Paper of the Month - European Stroke Organisation

February 2023

Endovascular therapy outcome in isolated posterior cerebral artery occlusion strokes: A multicenter analysis of the Swiss Stroke Registry

Data from this multicentre registry study suggest that in patients with isolated posterior cerebral artery occlusion intravenous thrombolysis and endovascular treatment achieve similarly good outcomes.

Source: Maulucci F, Disanto G, Bianco G, et al. Endovascular therapy outcome in isolated posterior cerebral artery occlusion strokes: A multicenter analysis of the Swiss Stroke Registry. European Stroke Journal. 2023;0(0).

January 2023

Risk Factors and Causes of Ischaemic Stroke in 1322 Young Adults

Among young adults aged 18 to 49 years with a cryptogenic ischaemic stroke according to the TOAST classification, risk factors for stroke are highly prevalent. Using a pediatric classification system provides new leads for the possible causes in cryptogenic stroke, and could potentially lead to more tailored treatment for young individuals with stroke.

Source: Ekker MS, Verhoeven JI, Schellekens MMI, Boot EM, van Alebeek ME, Brouwers PJAM, Arntz RM, van Dijk GW, Gons RAR, van Uden IWM, den Heijer T, de Kort PLM, de Laat KF, van Norden AGW, Vermeer SE, van Zagten MSG, van Oostenbrugge RJ, Wermer MJH, Nederkoorn PJ, Zonneveld TP, Kerkhoff H, Rooyer FA, van Rooij FG, van den Wijngaard IR, Klijn CJM, Tuladhar AM, de Leeuw FE. Risk Factors and Causes of Ischemic Stroke in 1322 Young Adults. Stroke. 2022 Dec 13. doi: 10.1161/STROKEAHA.122.040524. Epub ahead of print. PMID: 36511150.

December 2022

Sex Differences in Carotid Atherosclerosis: A Systematic Review and Meta-Analysis.

In this systematic review and meta-analysis the authors provide an overview on sex differences in atherosclerosis comprising different methods of plaque measurement. A key finding is a clear sex difference with higher prevalence in men for all measures of atherosclerosis including calcification, intraplaque hemorrhage and plaque ulceration. The authors also give an outline how these findings should be addressed in future trials.

Source: van Dam-Nolen DHK, van Egmond NCM, Koudstaal PJ, van der Lugt A, Bos D. Sex Differences in Carotid Atherosclerosis: A Systematic Review and Meta-Analysis. Stroke. 2022 Nov 29. doi: 10.1161/STROKEAHA.122.041046. Epub ahead of print. PMID: 36444718.

November 2022

Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.

Thus far we have depended on observational studies to determine what blood pressure targets to set after thrombecotmy. The Enchanted-2 MT RCT was conducted in 44 tertiary-level hospitals in China and tested whether a blood pressure target of 120 mm Hg systolic or less was better than 140-180 mm Hg. It was terminated early because of safety concerns in the intensive treament group after 821 our of a planned 2257 participants were enrolled, and showed significantly more early neurological deterioration and worse mRS at 90 days in the intensive blood pressure control group.

Source: Yang P, Song L, Zhang Y, Zhang X, Chen X, Li Y, Sun L, Wan Y, Billot L, Li Q, Ren X, Shen H, Zhang L, Li Z, Xing P, Zhang Y, Zhang P, Hua W, Shen F, Zhou Y, Tian B, Chen W, Han H, Zhang L, Xu C, Li T, Peng Y, Yue X, Chen S, Wen C, Wan S, Yin C, Wei M, Shu H, Nan G, Liu S, Liu W, Cai Y, Sui Y, Chen M, Zhou Y, Zuo Q, Dai D, Zhao R, Li Q, Huang Q, Xu Y, Deng B, Wu T, Lu J, Wang X, Parsons MW, Butcher K, Campbell B, Robinson TG, Goyal M, Dippel D, Roos Y, Majoie C, Wang L, Wang Y, Liu J, Anderson CS; ENCHANTED2/MT Investigators. Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial. Lancet. 2022 Nov 5;400(10363):1585-1596. doi: 10.1016/S0140-6736(22)01882-7. Epub 2022 Oct 28. PMID: 36341753.

October 2022

European Stroke Organisation (ESO) guideline on pharmacological interventions for long-term secondary prevention after ischaemic stroke or transient ischaemic attack.

A timely update. Please check the ESO guidelines section for a video and slides to accompany the guidance.

Source: Dawson J, Béjot Y, Christensen LM, De Marchis GM, Dichgans M, Hagberg G, Heldner MR, Milionis H, Li L, Pezzella FR, Taylor Rowan M, Tiu C, Webb A. European Stroke Organisation (ESO) guideline on pharmacological interventions for long-term secondary prevention after ischaemic stroke or transient ischaemic attack. Eur Stroke J. 2022 Sep;7(3):I-II.

September 2022

Cerebellar cognitive affective syndrome after acute cerebellar stroke

The cerebellum modulates both motor and cognitive behaviors, and a cerebellar cognitive affective syndrome (CCAS) was described after a cerebellar stroke in 1998. Yet, a CCAS is seldom sought for, due to a lack of practical screening scales. This paper provides an assessment of both the prevalence of CCAS after cerebellar acute vascular lesion and the yield of the CCAS-Scale (CCAS-S) in an acute stroke setting.

Source: Abderrakib A, Ligot N, Naeije G. Cerebellar cognitive affective syndrome after acute cerebellar stroke. Front Neurol. 2022 Aug 11;13:906293. doi: 10.3389/fneur.2022.906293. PMID: 36034280; PMCID: PMC9403248.

July 2022

Vitamin K antagonist versus novel oral anticoagulants for management of cervical artery dissection: Interactive systematic review and meta-analysis

Since the CADISS and TREAT-CAD RCTs established that in patients with cervical artery dissection antiplatelets and anticoagulation (with warfarin) were equally safe and effective DOACS have emerged as an alternative, but without RCT evidence. This systematic review compares DOACS with warfarin for patients with CAD. There was no significant difference in safety and efficacy, but a closer look at the paper shows trends which need to be tested in further clinical trials.

Source: Essibayi MA, Lanzino G, Keser Z. Vitamin K antagonist versus novel oral anticoagulants for management of cervical artery dissection: Interactive systematic review and meta-analysis. European Stroke Journal. July 2022. doi:10.1177/23969873221111051

June 2022

Role of Intravenous Thrombolytics Prior to Endovascular Thrombectomy

A timely review of the 6 trials addressing the question. For most of us the best approach will be to lyse first, but direct endovascular treament is not completely out. More information in the full paper.

Source: Campbell BCV, Kappelhof M, Fischer U. Role of Intravenous Thrombolytics Prior to Endovascular Thrombectomy. Stroke. 2022 Jun;53(6):2085-2092. doi: 10.1161/STROKEAHA.122.036929. Epub 2022 Mar 31. PMID: 35354294.

May 2022

Association of intraventricular fibrinolysis with clinical outcomes in ICH: an individual participant data meta-analysis

Time is brain for intracerebral haemorrhage in this individual patient metaanalyisis if two RCTs including 1501 patients who had an intraventricular drain placed for post-ICH hydrocephalus and were randomized to intraventricular alteplase or not. Patients included within less than 48 h from symptom onset had better functional outcomes at 6 months. Check out detail and implications in the full paper.

Source: Kuramatsu JB, Gerner ST, Ziai WC, Bardutzky J, Sembill JA, Sprügel MI, Mrochen A, Kölbl K, Ram M, Avadhani R, Falcone GJ, Selim MH, Lioutas VA, Endres M, Zweynert S, Vajkoczy P, Ringleb PA, Purrucker JC, Volkmann J, Neugebauer H, Erbguth FJ, Schellinger PD, Knappe UJ, Fink GR, Dohmen C, Minnerup J, Reichmann H, Schneider H, Röther J, Reimann G, Schwarz M, Bazner H, Classen J, Michalski D, Witte OW, Günther A, Hamann GF, Lücking H, Doerfler A, Ishfaq MF, Chang JJ, Testai FD, Woo D, Alexandrov AV, Staykov D, Goyal N, Tsivgoulis G, Sheth KN, Awad IA, Schwab S, Hanley DF, Huttner HB. Association of intraventricular fibrinolysis with clinical outcomes in ICH: an individual participant data meta-analysis. Stroke. 2022 May 6. doi: 10.1161/STROKEAHA.121.038455. Epub ahead of print. PMID: 35521958.

April 2022

Safety and efficacy of aspirin, unfractionated heparin, both, or neither during endovascular stroke treatment (MR CLEAN-MED): an open-label, multicentre, randomised controlled trial.

Van der Steen et al present the results of an open label 2×3 RCT of iv aspirin/no aspirin, and low dose/moderate dose/no iv heparin in 663 patients undergoing mechanical thrombectomy and found an increased risk of intracranial haemorrhage, and a trend towards worse functional recovery.

Source: van der Steen W, van de Graaf RA, Chalos V, Lingsma HF, van Doormaal PJ, Coutinho JM, Emmer BJ, de Ridder I, van Zwam W, van der Worp HB, van der Schaaf I, Gons RAR, Yo LSF, Boiten J, van den Wijngaard I, Hofmeijer J, Martens J, Schonewille W, Vos JA, Tuladhar AM, de Laat KF, van Hasselt B, Remmers M, Vos D, Rozeman A, Elgersma O, Uyttenboogaart M, Bokkers RPH, van Tuijl J, Boukrab I, van den Berg R, Beenen LFM, Roosendaal SD, Postma AA, Krietemeijer M, Lycklama G, Meijer FJA, Hammer S, van der Hoorn A, Yoo AJ, Gerrits D, Truijman MTB, Zinkstok S, Koudstaal PJ, Manschot S, Kerkhoff H, Nieboer D, Berkhemer O, Wolff L, van der Sluijs PM, van Voorst H, Tolhuisen M, Roos YBWEM, Majoie CBLM, Staals J, van Oostenbrugge RJ, Jenniskens SFM, van Dijk LC, den Hertog HM, van Es ACGM, van der Lugt A, Dippel DWJ, Roozenbeek B; MR CLEAN-MED investigators. Safety and efficacy of aspirin, unfractionated heparin, both, or neither during endovascular stroke treatment (MR CLEAN-MED): an open-label, multicentre, randomised controlled trial. Lancet. 2022 Mar 12;399(10329):1059-1069. doi: 10.1016/S0140-6736(22)00014-9. Epub 2022 Feb 28. PMID: 35240044.

March 2022

European Stroke Organisation (ESO)-European Society for Minimally Invasive Neurological Therapy (ESMINT) expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischemic stroke and anterior circulation large vessel occlusion.

In this paper the ESO guidelines group summarizes the evidence for bridging versus direct thrombolysis with endorsement for bridging unless thrombolysis is contraindicated. Check out this and the other recently published guidelines here.

Source: Turc G, Tsivgoulis G, Audebert HJ, Boogaarts H, Bhogal P, De Marchis GM, Fonseca AC, Khatri P, Mazighi M, Pérez de la Ossa N, Schellinger PD, Strbian D, Toni D, White P, Whiteley W, Zini A, van Zwam W, Fiehler J. European Stroke Organisation (ESO)-European Society for Minimally Invasive Neurological Therapy (ESMINT) expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischemic stroke and anterior circulation large vessel occlusion. J Neurointerv Surg. 2022 Mar;14(3):209. doi: 10.1136/neurintsurg-2021-018589. Epub 2022 Feb 3. PMID: 35115395.

February 2022

Long-Term Follow-up of Enhanced Holter-Electrocardiography Monitoring in Acute Ischemic Stroke

One sometimes wonders whether AF identified with long-term remote monitoring is clinically relevant. The findings of the RCT need confirmation in a larger study, but the trend suggests that monitoring does not only find AF earlier than standard monitoring, but also may prevent both strokes and deaths.

Source: Wachter R, Weber-Krüger M, Hamann GF, Kermer P, Liman J, Mende M, Seegers J, Wasser K, Gröschel S, Uphaus T, Poppert H, Köhrmann M, Zabel M, Laufs U, Heuschmann PU, Conen D, Gröschel K; Find-AFRANDOMISED Investigators and Coordinators. Long-Term Follow-up of Enhanced Holter-Electrocardiography Monitoring in Acute Ischemic Stroke. J Stroke. 2022 Jan;24(1):98-107. doi: 10.5853/jos.2021.01207. Epub 2021 Dec 17. PMID: 34911255.

January 2022

Noncontrast Computed Tomography vs Computed Tomography Perfusion or Magnetic Resonance Imaging Selection in Late Presentation of Stroke With Large-Vessel Occlusion

This study suggests that pain CT is as safe and reliable in predicting good outcomes for thrombectomy in patients presenting late as CT perfusion. These findings could affect the way thrombectomy decisions are made and simplify the pathway. It is sure to generate discussion.

Source: Nguyen TN, Abdalkader M, Nagel S, Qureshi MM, Ribo M, Caparros F, Haussen DC, Mohammaden MH, Sheth SA, Ortega-Gutierrez S, Siegler JE, Zaidi S, Olive-Gadea M, Henon H, Möhlenbruch MA, Castonguay AC, Nannoni S, Kaesmacher J, Puri AS, Seker F, Farooqui M, Salazar-Marioni S, Kuhn AL, Kaliaev A, Farzin B, Boisseau W, Masoud HE, Lopez CY, Rana A, Kareem SA, Sathya A, Klein P, Kassem MW, Ringleb PA, Cordonnier C et al. Noncontrast Computed Tomography vs Computed Tomography Perfusion or Magnetic Resonance Imaging Selection in Late Presentation of Stroke With Large-Vessel Occlusion. JAMA Neurol. 2022 Jan 1;79(1):22-31. doi: 10.1001/jamaneurol.2021.4082.

Additional Paper of Interest

International Post Stroke Epilepsy Research Consortium (IPSERC): A consortium to accelerate discoveries in preventing epileptogenesis after stroke

We added this paper to highlight the International Post Stroke Epilepsy Research Consortium (IPSERC). Please contact the lead author if you are interested in joining.

Source: Mishra NK, Engel J Jr, Liebeskind DS, Sharma VK, Hirsch LJ, Kasner SE, French JA, Devinsky O, Friedman A, Dawson J, Quinn TJ, Selim M, de Havenon A, Yasuda CL, Cendes F, Benninger F, Zaveri HP, Burneo JG, Srivastava P, Bhushan Singh M, Bhatia R, Vishnu VY, Bentes C, Ferro J, Weiss S, Sivaraju A, Kim JA, Galovic M, Gilmore EJ, Pitkänen A, Davis K, Sansing LH, Sheth KN, Paz JT, Singh A, Sheth S, Worrall BB, Grotta JC, Casillas-Espinos PM, Chen Z, Nicolo JP, Yan B, Kwan P; for International Post Stroke Epilepsy Research Consortium (IPSERC). International Post Stroke Epilepsy Research Consortium (IPSERC): A consortium to accelerate discoveries in preventing epileptogenesis after stroke. Epilepsy Behav. 2021 Dec 27;127:108502. doi: 10.1016/j.yebeh.2021.108502. Epub ahead of print. PMID: 34968775.

Archive

2019

Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation

This is an individual patient data pooled analysis of 5314 patients, which addresses the question whether patients who have an ischemic stroke while anticoagulated should be changed to a different anticoagulant or not. It is a clinically relevant topic and will help in decision making, but still many questions remain unanswered.

Seiffge DJ, De Marchis GM, Koga M, Paciaroni M, Wilson D, Cappellari M, et al. Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation. Ann Neurol 2020 Feb 12. https://onlinelibrary.wiley.com/doi/10.1002/ana.25700

Outcomes of patients with stroke treated with thrombolysis according to prestroke Rankin Scale scores

“Was the patient independent before this stroke?” The answer to this question is no longer needed to decide whether to give thrombolysis or not t a patient with ischaemic stroke presenting within 4.5 h from the event. Even patients with significant disability (mRS up to 4) may improve and return to their previous level if appropriately treated, according to this paper by Gumbinger et al, published recently in Neurology. The Authors found that intravenous thrombolysis in patients with pre-stroke mRS (pRS) scores of 0 to 4 was associated with a higher chance of returning to their baseline (or a modified Rankin Scale score of 0/1). Only patients with a pre-stroke Rankin of 5 did not benefit from thrombolysis. So another barrier to treatment is disappearing…

Anticoagulation after stroke in patients with atrial fibrillation: to bridge or not with low-molecular-weight heparin?

This month’s paper is of particular interest as it addresses an area of clinical uncertainty which affects daily practice. Should we bridge with full dose heparin/low molecular weight heparin when faced with a patient in AF who has had a minor stroke? Altavilla et al’s large observational study suggests ‘no’. Both ischemic and haemorrhagic strokes were more frequent in the bridged group. However, the study is not randomized, and neither multivariate analysis nor propensity matching can fully exclude biases. However, while we are waiting for results of on-going clinical trials such as ELAN, these results should make us stop and think when considering bridging.

2020

April – Burden of Stroke in Europe: Thirty-Year Projections of Incidence, Prevalence, Deaths, and Disability-Adjusted Life Years

This study gives the current burden of stroke within Europe and modelled predictions, based on Global Burden of Disease data. It will prove valuable for service and research planning.

May – Clinical prognosis of FLAIR hyperintense arteries in ischaemic stroke patients: a systematic review and meta-analysis

This review is of interest as it provides non-radiologists with a new way of looking at MRIs.

June – Safety and efficacy of dual antiplatelet pretreatment in ischemic stroke patients treated with IV thrombolysis: A systematic review and meta-analysis

In this paper, the authors report safety and efficacy of iv alteplase in ischemic stroke patients who were on dual antiplatelets. Antiplatelet pre-treatment is not an exclusion criterion for the use of iv alteplase; however, some concern persists particularly because of conflicting data and recent suggestions from ENCHANTED trial that prior antiplatelets use is associated with increased symptomatic intracerebral haemorrhage risk. This is therefore an important study which tackles an important clinically relevant question. Also, this is a robust meta analysis of almost 70 000 patients. In unadjusted analyses, they noted increased risk of symptomatic intracerebral haemorrhages amongst patients on dual anti platelets who received iv alteplase for acute ischemic stroke; this, however, was not associated with poor functional outcomes. In a adjusted analysis however, prior treatment with dual anti platelets was not associated with increased risk of symptomatic intracerebral haemorrhages. This meta analysis adds to our evidence in favour of the use of iv alteplase in ischemic stroke patients who are on dual anti platelets.

July – Age and Sex Differences in Ischemic Stroke Treatment in a Nationwide Analysis of 1.11 Million Hospitalized Cases

An interesting and methodologically balanced nationwide registry study examining changes of access to stroke units and recanalization therapies (both IVT and MT) over time, age and sex differences. Read this and contemplate why men are more likely to be admitted to a stroke unit, but women are more likely to be treated by mechanical thrombectomy.

August – International translation of Fever, Sugar, Swallow Protocols: The Quality in Acute Stroke Care Europe Project

Sometimes positive results are not enough. In 2011 Middleton et al demonstrated that a nurse-led protocol of managing fever, hyperglycaemia and swallowing dysfunction significantly reduced death and disability. However, there was little impact on practice. In this paper Middleton et al describe how ESO and the Angels initiative worked collaboratively to implement the FeSS protocol across 20 European countries. We hope that this paper is a stimulus for more stroke centres to put this evidence into practice.

September – DNA Content in Ischemic Stroke Thrombi Can Help Identify Cardioembolic Strokes Among Strokes of Undetermined Cause

Nishant Mishra comments: This study examines thrombus composition as a tool to identify stroke mechanism. Cardioembolic thrombi were found to have had significantly increased levels of DNA compared to non-cardioembolic thrombi. The investigators identified a threshold of 44.7 ng DNA/mg thrombus at which 47% of thrombi from undetermined cause could be classified as cardioembolic with a specificity of 90%. We need reliable biomarkers of the stroke mechanism, and this approach appears to identify one. The findings, however, need validation.

October – Early Recanalization in Patients With Cerebral Venous Thrombosis Treated With Anticoagulation

With increasing rates of sinus venous thrombosis in the wake of COVID-19 this observational study is of particular interest. It demonstrates that recanalization starts within the first 8 days of therapeutic anticoagulation and is predictive of good outcome.

November – Sex differences in the association between major risk factors and the risk of stroke in the UK Biobank cohort study

Results from just under half a million people entered in the UK Biobank confirm that men have a higher risk of stroke than women, but also show that Hypertension, smoking and low socioeconomic status are more strongly associated with stroke risk in men than in women.

December – Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Evidence supporting the use of thrombolysis for selected stroke patients with unknown time of onset has been strengthened with data from a new individual patient meta-analysis. This meta-analysis combined data from four clinical trials that included a total of 483 patients with stroke of unknown time of onset, using MRI or CT-perfusion imaging to identify patients with salvageable brain tissue.

2021

January – Carotid Artery Stenting Versus Endarterectomy for Treatment of Carotid Artery Stenosis

CAS can be safely offered as an alternative to CEA in patients with symptomatic carotid stenosis <70 years, provided both treatments are technically feasible. Older patients should be treated with CEA. In patients with asymptomatic carotid stenosis, the amount of evidence currently available is limited and further data from randomized trials are needed. Two large RCTs, ECST-2 and ACST-2, are in follow-up and expected to report in 2021.

February – Treatment and Outcome in Stroke Patients With Acute M2 Occlusion and Minor Neurological Deficits

This study by Dobrocky et al from Bern included 169 consecutive stroke patients with acute occlusion of the M2 segment and a minor stroke (NIHSS ≤5) between 2005 and 2020. The authors explored the efficacy and safety of recanalization therapies and demonstrated a similar effectiveness of intravenous thrombolysis (IVT) only versus endovascular therapy (EVT, including intra-arterial thrombolysis and mechanical thrombectomy), and of IVT only versus mechanical thrombectomy alone (without intra-arterial thrombolysis). Outcomes were best in patients treated after 2015 (Nicolas Martinez-Majander).

March – European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke

This guideline is a welcome summary and assessment of available evidence on thrombolysis after stroke. It gives graded recommendations, where evidence is available and considered expert opinion where it is not. It will be practice changing for many of us. Of particular interest is the recommendation to use tenecteplase for patients considered for thrombectomy, the recommendation to thrombolyse selected patients with pre-stroke disabilities and those with low NIHSS but nevertheless disabling deficits. It is a fitting memory to the late Eivind Berge who contributed greatly to its production.

April –Diagnosis of non-consensus transient ischaemic attacks with focal, negative, and non-progressive symptoms: population-based validation by investigation and prognosis

This paper has the potential to completely change the way we manage our TIA services, but also to improve outcomes.

Maria A. Tuna and the team form the Oxford Vascular Study found that patients with non-consensus TIA, i.e. those who do not fit our diagnostic criteria for TIA, and who are often sent back to their primary care team with no specific treatment, are at high early and long-term risk of stroke and have cardiovascular pathological findings on investigation similar to those of classic TIA. Designation of non-consensus TIAs as definite cerebrovascular events will increase overall TIA diagnoses by about 50%.

May –Stroke 20 20: Implementation goals for intravenous thrombolysis

Based on the IVT analysis in the Czech Republic, authors discuss that thrombolysis can be provided to ≥ 20% of all ischemic strokes nationwide and it is realistic to achieve median door-to-needle time 20 minutes. They propose Stroke 20–20 that could serve as national implementation target for intravenous thrombolysis and country specific implementation policies should be applied to achieve such target.

Guest Paper – Caplan-Fisher Rules

We see this paper as a classic which should be read by every aspiring and practising stroke neurologist.

June –Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): A randomised, blinded, pivotal, device trial

The authors tested a potential new approach for rehabilitation after stroke; the preliminary data showed safety and efficacy, i.e. the VNS group improved by 5.0 points on the FMA-UE scale, compared with a 2.4-point improvement in the sham-stimulation group, a significant difference. At 90 days, 47% of VNS patients had a clinically meaningful improvement, compared with 24% of the control group, also a significant difference. Larger trials are needed to show which subroups will have more benefit. Comment by Anita Arsovska

July –Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) – study protocol for a randomised controlled trial

This month the paper of the month is a trial protocol. CONVINCE is a multi-centre international (in 17 countries) Prospective, Randomised Open-label, Blinded-Endpoint assessment (PROBE) controlled Phase 3 clinical trial in 3154 participants. The intervention is colchicine 0.5 mg/day and usual care versus usual care alone (antiplatelet, lipid-lowering, antihypertensive treatment, lifestyle advice) in patients with non-severe ischaemic stroke or high-risk TIA.The primary outcome is time to first recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation with unstable angina (non-fatal or fatal).CONVINCE will provide high-quality randomised data on the efficacy and safety of anti-inflammatory therapy with colchicine for secondary prevention after stroke.

August- PRESERVE: Randomized Trial of Intensive Versus Standard Blood Pressure Control in Small Vessel Disease

Intensive blood pressure lowering reduces stroke risk, but it is unclear whether it this is safe in patients with severe small vessel disease and impaired cerebral autoregulation. The results of PRESERVE show that blood pressure lowering did not adversely affect white matter microstructure or cognitive function.

September –Sonothrombolysis in Patients With Acute Ischemic Stroke With Large Vessel Occlusion: An Individual Patient Data Meta-Analysis

Sonthrombolysis may enhance the effectiveness of thrombolysis, but could also increase the bleeding risk. Tsivgoulis et al included 7 randomized controlled studies and 1102 patients into this meta-analysis and report that sonothrobolysis significantly improved recanalization with no significant increase in intracranial haemorrhage and no difference in mRS at 90 days.

October – Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia

This study includes 78 patients with thrombotic thrombocytopenic syndrome and cerebral venous thrombosis after Covid-19 vaccination from multiple countries on 4 continents. Most (776/78) received the AstraZeneca vaccine. Mortality was very high initially at 62% but improved to 42% after the syndrome became better known, platelet transfusions were avoided, and non-heparin anticoagulants were given.

November –Female Gender Increases Risk of Stroke and Readmission after CEA and CAS

In this retrospective study of 106,568 patients, the authors found that female gender was associated with significantly increased rates of 30-day postoperative CVA/stroke in asymptomatic and symptomatic patients as well as readmission in asymptomatic patients following CEA or CAS. They conclude that we need adequate representation of female patients in studies to better understand gender-based disparities in carotid intervention.

December –Long-Term Impact of Urgent Secondary Prevention After Transient Ischemic Attack and Minor Stroke: Ten-Year Follow-Up of the EXPRESS Study

Luengo-Fernandez et al report the 10 year results of the Oxford-based EXPRESS study, which established that rapid (within 24 hours of onset) assessment and treatment of TIA saves strokes, reduces death and disability, and is cost-effective. This follow-up study demonstrates that the benefit persists over a 10 year period of follow-up. Time is brain, even for TIAs.

COVID-19 Publications Relevant for Stroke Diagnosis and Management

COVID-19 Vaccination and Cerebrovascular Events

Original Articles/Case Reports - All Vaccines

Original Articles/Case Reports - AstraZeneca Vaccine

Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis. Pavord S. et al. N Engl J Med. 2021 Aug 11.
Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicentre cohort study. Perry R.J. et al. Lancet. 2021 Aug 6:S0140-6736(21)01608-1.
Prothrombotic immune thrombocytopenia after COVID-19 vaccination. Tiede A. et al. Blood. 2021 Jul 29;138(4):350-353
Thrombotic Thrombocytopenia and Central Venous Sinus Thrombosis Post – COVID-19 Vaccination and its Treatment with Heparin Alternatives. Sheikh S. et al. J Coll Physicians Surg Pak. 2021 Jul;31(7):149.
Fatal cerebral venous sinus thrombosis after COVID-19 vaccination. Jamme M, Mosnino E. et al. Intensive Care Med. 2021 Jul;47(7):790-791.
Ischaemic stroke as a presenting feature of ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopaenia. Al-Mayhani T. et al. Journal of Neurology, Neurosurgery & Psychiatry Published Online First: 25 May 2021.
Cerebral venous sinus thrombosis associated with thrombocytopenia post-vaccination for COVID-19. Castelli G.P. et al. Crit Care. 2021 Apr 12;25(1):137. .
US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, See I. et al. March 2 to April 21, 2021. JAMA. Published online April 30, 2021.
Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study. Pottegård A. et al. BMJ. 2021 May 5;373:n1114.
Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination. Scully M. et al. N Engl J Med. 2021 Apr 16.
Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. Greinacher A et al. N Engl J Med. 2021 Apr 9.
Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. Schultz N.H. et al. N Engl J Med. 2021 Apr 9.
Towards Understanding ChAdOx1 nCov-19 Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT). Greinacher A. et al.

Original Articles / Case Reports - Johnson and Johnson/Janssen Vaccine

Original Articles / Case Reports - Moderna Vaccine

Original Articles / Case Reports - Pfizer/Biontech Vaccine

Polack F.P. et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-2615.
Taquet M. et al. Cerebral venous thrombosis: a retrospective cohort study of 513,284 confirmed COVID-19 cases and a comparison with 489,871 people receiving a COVID-19 mRNA vaccine. [preprint]

Guidance

Clinical Characteristics and Pharmacological Management of COVID-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia With Cerebral Venous Sinus Thrombosis: A Review. Rizk J.G. et al. JAMA Cardiol. 2021 Aug 10. doi: 10.1001/jamacardio.2021.3444. Epub ahead of print. PMID: 34374713.
European stroke organisation interim expert opinion on cerebral venous thrombosis occurring after SARS-CoV-2 vaccination. Ferro JM et al. European Stroke Journal. July 2021. doi:10.1177/23969873211030842
Brighton collaboration diagnostic guidelines https://brightoncollaboration.us/wp-content/uploads/2021/05/TTS-Interim-Case-Definition-v10.16.3-May-23-2021.pdf
American Heart Association/American Stroke Association Stroke Council Leadership. Diagnosis and Management of Cerebral Venous Sinus Thrombosis with Vaccine-Induced Thrombotic Thrombocytopenia. Stroke. 2021 Apr 29.
Oldenburg J. et al. Diagnosis and management of vaccine-related thrombosis following astrazeneca covid-19 vaccination: Guidance statement from the GTH. Hamostaseologie. 2021.
UK Guidance produced by the Expert Haematology Panel (EHP) focussed on Vaccine induced Thrombosis and Thrombocytopenia (VITT)
UK Management of cerebral venous sinus thrombosis following Covid-19 vaccination A neurosurgical guide

Comments and Editorials

Venous thromboembolism after vaccination or COVID-19

Additional Publications on COVID-19 and Stroke

July 2021 - Original Articles

July 2021 - Comment and Editorials

Original Articles

Guidance

Comments and Editorials