Author: Professor Liz Lightbody

After a stroke, people may have a wide range of physical, psychological and social needs or concerns, which are often not addressed very well. The road to recovery has many highs and lows, and stroke survivors often have to adapt to lasting changes. The focus of this session convened by Professor Liz Lightbody and Professor Frank Becker was around how we can facilitate and support recovery and help stroke survivors to navigate life after a stroke. It highlighted some important messages with regard to recovery from cognitive impairments and dose and intensity in relation to recovery of aphasia, as well as the value of good discharge planning that addresses the individual’s needs.

Professor Dominique Cadilhac from Monash University and The Florey Institute, Australian, presented on Recovery-focused Community Support to Avoid readmissions and improve Participation after Stroke (ReCAPS).  The aim of the presentation on the ReCAPs study using aggregated data form 466 participants was to describe factors associated with unmet needs 7-14 days after discharge following acute stroke, and to describe prioritised goals to address unmet needs and if these are achieved by 90 days. The discharge satisfaction (PREPARED survey) and the Long-term Unmet Needs Survey (LUNS) were obtained by phone 7-14 days post discharge. At 90-days, the LUNS and goal attainment were re-assessed. Overall, the participants (median age 67 years, 33% female) reported a mean 2.6 unmet needs at baseline compared with 1.5 at 90-days; frequency at baseline differed by age, sex, length of stay, level of dependency, confidence to manage at home or feeling prepared to return home. Sixteen participants (3%) felt unprepared to return home and this group had more unmet needs: (7.1) than 77% who felt very prepared (2.2; p <0.01). Various unmet needs were reported although most improved significantly by 90-days. For example, 80% of health-related goals and 78% of everyday activities goals were partially or fully met. These results highlight the importance of preparing patients for discharge. If feasible, it might be beneficial to ‘check-in’ with patients early after discharge to discuss unmet needs.

Professor Katerina Hilari, from University of London presented the new ESO guidelines on aphasia rehabilitation, which is chaired/ co-chaired by Professors Marian Brady / Katerina Hilari. The guideline addresses 10 PICO questions on dose, intensity, frequency, as well as modes of delivery (digital vs in person; group vs one-to-one) of aphasia speech and language therapy (SLT). It also addresses tDCS brain stimulation + SLT vs sham brain stimulation + SLT, a PICO that involved six separate comparisons based on location and polarity of stimulation. In the interest of time, the presentation covered functional communication and quality of life outcomes and highlighted, among other things, the benefits of higher dose and higher intensity SLT. An ESO webinar will be organised to present the full guideline over the next few months.

The issue of post stroke cognitive impairment and dementia were outlined and new evidence of four trajectories covering improvement or decline was described by Associate Professor Nele Demeyere from the University of Oxford in her session on Recovery of Post-stroke cognitive impairments : domain-specific trajectories. Whilst most research on post-stroke cognition has tended to focus on prediction of decline or end-point cognitive impairment categories, this study aimed to better understand domain-specific cognitive changes over the long-term (attention, language, praxis, executive functioning).  The OX-CHRONIC study followed up 105 stroke survivors (average age 73, average acute NIHSS 7.4) who had completed acute and 6-month cognitive profiling with the Oxford Cognitive Screen at a time they were at least 2 years post stroke (range 2-9, average 4.5 years).

Overall there was a high prevalence of impairments both in terms of overall cognition (46% on OCS, 65% on a MoCA cut off of 26, 31% if using a MoCA cut off of 22) as well as in terms of different specific cognitive domains.  Importantly though, when modelling individual change over time, 47% demonstrated improvement over time (after 6 months), with 48% showing no change and mild impairments and only 5% of the sample showed a decline.

This study demonstrates that alongside risks of decline, there can be ongoing recovery past 6 months in domain-specific cognitive impairments, in parallel to known findings in motor recovery and aphasia.  The message that cognition does not necessarily always decline is likely to be an important one for stroke survivors to hear.

Mrs Diana Wong Ramos a former journalist and patient advocate from Portugal, had her stroke at the age of 34 and presented on Sex and intimacy following a stroke. She provided details of her recovery journey from the initial event when she was deemed by emergency services to be too young to have a stroke.  How in a split second everything in her life profoundly changed and she had to learn to do everything for herself again.  Her initial goal was to be able to hug her children again, then later thinking about how to rebuild an intimate relationship with her husband.  The stroke had impacted her body image, she described not feeling like a women or sexually attractive, she was unsure how to be intimate again and struggled to find the support she needed.  She challenged the audience to not ignore intimacy as an important aspect of reconnecting and feeling whole. She challenged clinicians to ask if people have questions about resuming sex after stroke.

Issues experienced by patients with stroke who require support up to 18 months after stroke because of ongoing or new symptoms were presented by Professor Torunn Askim, from Norwegian University of Science and Technology in her session on Life After STroke – Multimodal approaches to long-term follow up after stroke. “The LAST-long trial (Long term follow-up after stroke) is aiming to investigate the benefit of regular meetings with a community-based stroke coordinator, who is delivering a multimodal individualized intervention to prevent functional decline, for 18 months. Furthermore, the stroke coordinators use the LAST-long checklist as guide for a structured interview to assess risk-factors and shared decision making to agree on goals and action points for the next month. So far 301 participants have been included and the final follow-up assessment will be completed by September 2024.

Author: Zdravka Poljakovic

The last Session on day 2 held in Hall Montreal was all about neurointervention dealing with challenges and pitfalls in this exceptional stroke treatment field. Moderators were professors Wim Van Zwam (Maastricht, Netherlands) and Pooja Khatri (Cincinnati, United States), who managed to point out the most important conclusions from all lectures in an interesting and scientific discussion, keeping the whole session together and in perfect timing. 

First lecture, “The benefit of a complete over a successful reperfusion decreases with time”, given by Stefanos Finitsis from Thessaloniki, Greece, on behalf of ETIS Registry Investigators, posed a question about the benefit of thrombectomy over (extended) time. In order to answer the question, the authors analysed data from 4.444 patients from ETIS registry, a prospective, observational, multicentric study of acute ischemic stroke patients treated with endovascular treatment in 21 centers in France. Patients with anterior occlusions with known symptoms onset were analysed. The trial showed that the prognostic value of a complete over successful reperfusion progressively declined with time, with a clear-cut value of 5.7 hours.

The session continued with the talk given by Anne Berberich from Ludwigshafen, Germany, who discussed the Comparison of anesthetic strategies for endovascular therapy of isolated posterior cerebral occlusion: a PLATO study. In her talk, she showed the results from an analysis of 376 patients with isolated posterior cerebral occlusion, nearly half of them being under general anesthaesia (183). The groups were comparable except of GA group had a more severe stroke. The results did not show any difference in primary outcome, namely functional outcome in both groups, however showed higher rates of complete reperfusion in the first pass in the GA group. In conclusion, she emphasized that non-GA protocols were feasible and safe in patients with EVT for isolated PCA occlusion stroke, GA led to higher rates of successful reperfusion compared to non-GA, and that there were no differences in short and long-term functional outcomes between the anesthetic strategies. For sure, this finding supports further investigation.

Safety and efficacy of endovascular treatment for large-core ischaemic stroke: a systematic review and meta-analysis was presented by Georgios Tsivgoulis, from Athens, Greece where he, in his meta-analysis of six RCT’s comparing endovascular treatment with medical therapies with nearly 1900 patients, and very low risk of bias, clearly showed the benefit of EVT. Endovascular treatment is beneficial in all investigated points showing statistical significance in all but mortality where it showed benefit but did not reach statistical significance. The results also showed higher hemorrhagic transformation in spite of functional benefit in the endovascular group.

The next talk was a posthoc analysis of the ANGEL-ASPECT trial analysing clinical severity and endovascular therapy outcomes in patients with large infarcts, which was nicely presented in a talk by Qiyuan Lu, from Beijing, China. The aim of this trial was to investigate the efficacy and safety of EVT in patients with anterior-circulation large vessel occlusion and large infarcts, stratified by clinical severity of stroke by NIHSS score, based on ANGEL-ASPECT trial. In her conclusions, she emphasized that in this group of patients, EVT was again associated with better functional outcomes than medical therapy in the group of moderate stroke, but not in the group of severe stroke. Surprisingly, there was not even a trend towards better outcomes when treated with EVT  in severe stroke, which implies caution in selection for EVT but even more a pooled analysis of large infarct trials to verify this finding.

Coming into the other half of the Session, we heard the results of the analysis of the society of Vascular and interventional neurology registry about rescue therapy for failed mechanical thrombectomy, presented by Santiago Ortega-Gutierrez form Iowa City, USA. He began his talk by a short introduction where he reminded the audience about unsuccessful reperfusion in at least 20% of patients but also about lowel level of evidence about rescue therapy which raises questions about the optimal rescue therapy approach. So the aim of the presented study was actually to investigate whether rescue therapy yields superior functional outcomes compared to medical therapy in patients with acute ishemic stroke due to large vessel occlusion after failed mechanical thrombectomy. The study had its limitations, in the first place due to the fact that the SVIN registry contains non-randomized data. However, the results of the study showed that rescue therapy correlates with enhanced functional outcome and decreased haemorrhagic complications and mortality compared to medical therapy. The results of the study are published in Annals of Neurology. 

The next speaker, Thanh N.Nguyen from Boston, USA presented the results from “Noncontrast computed tomography selected thrombectomy versus medical management for late-window anterior large vessel occlusion” study inspired by the important fact that the availability of advanced imaging is not particularly high when comparing low to high-income countries. A crucial question in the study was whether the functional outcome in patients with large vessel occlusion presenting at a 6 to 24-hour window and selected with CT is better compared with medically treated patients, which actually confirmed the value of a noncontrast computed tomography, which was nicely pointed out in a sentence from prof Raul Nogueira who said: “CT in the late window is like a red wine – it gets better with time”…

Relation between first-line thrombectomy technique and outcomes in late-window stroke patients; an MRCLEAN late trial sub-study,  was presented by Robrecht Knapen, from Maastricht, Netherlands. The results of this sub-study showed that stent retriever thrombectomy, direct aspiration, or the combined technique as first-line techniques showed no significant difference in clinical outcome in late-window stroke patients. However, direct aspiration was accompanied by higher rates of symptomatic intracerebral haematomas and higher switch rates to other techniques compared to other groups.

The final lecture, “Effect of thrombolysis type on the efficacy of aspiration vs stent-retriever first-line thrombectomy: results from the ACT trial” was presented by Fouzi Baia from Tours in France. The aim of this group of investigators was to study the influence of i.v. tenecteplase versus alteplase on the efficacy of first-line thrombectomy strategy. The study is a secondary analysis of AcT trial and included 435 patients from which 51% received Tenecteplase, and reached an interesting result showing that IV Tenecteplase before EVT may enhance the efficacy of the first-line aspiration, but it may have no effect on stent-retrievers!

In conclusion, the audience has learned the results of several clinically important studies, which should for sure inspire further investigations but might as well influence some clinical decisions.

Author: Francesco Arba

The “Secondary Prevention” session was an interesting session chaired by Dr. Sheila Cristina Martins from Brazil and Paula Munoz Venturelli from Chile.

 The first speaker was Dr. Philip Nash, London, United Kingdom, who gave a talk about “Increased risk of recurrent stroke in patients with impaired kidney function: a pooled analysis of individual patient data”

Dr. Nash presented a pooled analysis of the Microbleeds International Collaborative Network (MICON), an international, multicentre collaboration. A total of 18 sites that provided renal data on more than 20000 patients. The aim of the present study was to investigate the relation between renal impairment and recurrent stroke risk. Between the two groups (renal impairment vs no renal impairment) the group with renal impairment had more vascular risk factors such as hypertension, diabetes, and so on. From an imaging point of view, the renal impairment group had a higher percentage of mixed (cortical and deep) cerebral microbleeds. The study demonstrated that renal impairment increased the rate of stroke recurrence with anaose-response effect, suggesting a direct biological relation. Conversely, renal impairment was not associated with higher intracerebral hemorrhage risk. The biological mechanisms supporting this association may be endothelial dysfunction and an increase of small vessel disease severity, so increasing the risk of stroke recurrency. The conclusion of Dr. Nash was that there was an overall increase of recurrent stroke of 33%, and that renal function should be routinely tested in clinical practice and evaluated in relation to stroke risk. 

 Dr. Jori Ruuskanen, from Turku, Finland, presented “Intensity of statin therapy after ischemic stroke and long term outcomes: a population-based study cohort study”

Although statins have been used in clinical practice for a long time, there are still controversies and inconsistencies about statin use in long-term secondary prevention: for example, AHA/ASA guidelines recommend statin use only in atherosclerotic disease, whereas in other guidelines there was no stratification across stroke subtype. This observational population-based study included data from around 45000 patients from 2005-2018, with a median follow-up of around six years. Data were extracted from a national registry; diagnosis of stroke was made with ICD-9 codes. Patients were divided into high-dose statins (e.g. Atorvastatin 80 mg, Rosuvastatin 40 mg, etc.) vs low-dose statins. The primary outcomes were all-cause death, secondary recurrent ischemic stroke, cardiovascular death, occurrence of intracerebral hemorrhage. The study found that a high-intensity statin regimen was associated with a lower risk of death and major cardiovascular outcomes, with a number needed-to-treat of 14.6 for death and 19.1 for recurrent stroke. Dr. Ruuskanen concluded that high-intensity statin use was feasible and has efficacy in the long term. 

However, many limitations should be acknowledged to this study, as pointed out by many questions from the participative audience.

 Dr. Nikolaos Avramiotis, from Basel, Switzerland, presented an updated systematic review and meta-analysis (the previous one was outdated -2010) of the management of secondary prevention therapy for extracranial carotid dissection (“Antithrombotic drugs for carotid artery dissection-update of a Cochrane Systematic Review”). Given that new therapeutic approaches have been established in clinical practice (e.g. Direct Anticoagulants Drugs) a new review appeared to be justified. The review followed the Cochrane methodology for reviews and included both randomized controlled trials and non-randomized studies and compared anticoagulant versus antiplatelet therapy. A total of 44 studies were included, of which 2 were randomized controlled trials, so little evidence came from RCT, whreas the majority of available evidence was from observational studies (i.e. higher risk of bias). Outcomes of interest were: death, death/disability as a composite outcome, recurrent stroke, symptomatic intracerebral hemorrhage. The results showed that death was lower in the anticoagulant group, similar to death/disability (perhaps driven by death), whereas the risk of recurrent stroke gave a neutral result. Conversely, symptomatic intracerebral hemorrhage was lower in the antiplatelets. Dr. Avramiotis acknowledged relevant limits to this study (e.g. many observational data, few RCT, heterogeneity in outcome reporting measurements, and length of follow-up), but suggested that treatment should be individualized. As the audience pointed out during the discussion, there are no data, however, regarding treatment timing, duration, and type of anticoagulants, so the conclusion was that more studies are needed. 

 Dr. Rustam Al-Shahi Salman, from Edinburgh, United Kingdom, presented “Medical Management +/- surgery for symptomatic cerebral cavernous malformation: a randomised pilot trial”

This pilot randomized controlled trial was focussed on a frequently overlooked pathology that may cause cerebral hemorrhage and epilepsy. Given the little available evidence about management in such cases, an RCT is warranted. However, before moving into a large clinical trial, feasibility on recruitment rate, feasibility of procedures. Another important objective tested in the study was to address barriers and identify strategies to improve recruitment in the trial. A multidisciplinary team (neurologist, neuroradiologist, neurosurgeons, etc) is needed for the management of cerebral cavernomas, and the speaker stressed the fact that usual care practices so far prevented equipoise in treatment allocation, and logistical issues led to different clinical practice. The study enrolled 60 participants, with baseline characteristics equally distributed in the two groups (medical vs surgery management). Outcomes were similar between the two groups, but the trial was underpowered to investigate meaningful statistical differences. The main conclusive remarks were that around a third of approached patients were randomized, and a larger phase III trial is feasible. However, to reach the planned sample size (between 590 and 1900 participants) a definitive trial will need to involve 36-259 enrolling sites, which could be a major issue for funding agencies. 

 Dr. Bonaventure Ym Ip, from Hong Kong, in his speech “Early stent-assisted angioplasty in symptomatic intracranial stenosis: a randomized trial”, presented the results of a single centre, randomized, open-label, outcome blinded trial on the management of intracranial stenosis in patients with recent non disabling stroke. The experimental arm was angioplasty/stent treatment and the control arm was double antiplatelet therapy (aspirin 80 mg and clopidogrel 75 mg). The trial enrolled 150 patients, almost a third of included patients were randomized within 14 days from the index stroke. The primary endpoint was the composite outcome stroke/death 30 days after randomization, and occurred in 24% in the medical arm vs 16% in the experimental arm, whereas ischemic stroke in the same vascular territory occurred in 20% in the control (medial) arm and in 12% of the experimental arm. Both results, although suggested a different treatment effect, were not statistically significant. The conclusion was that stent did not result in a lower risk of stroke/death, there were no major safety concerns. Some observations were that the trial was likely underpowered, and the medical arm has likely a different aspirin regimen than the one recommended by many guidelines. 

 The two following talks were about the subanalysis of the ELAN trial. 

In the first talk delivered by Dr. Roman Rohner, from Bern, Switzerland, the topic was “Early versus later anticoagulation after ischemic stroke in people with atrial fibrillation and hemorrhagic transformation”. In this study, authors looked more closely to differences in patients who experienced hemorrhagic transformation. Hemorrhagic transformation was classified accorting with the ECASS-II classification and divided into hemorrhagic infarction (HI) type 1, HI type 2, pranchymal hemorrhage (PH) type 1 and PH2. The groups analysed were early vs late introduction of anticoagulation as defined in the ELAN trial. The primary outcomes were: recurrent ischemic stroke, symptomatic intracerebral hemorrhage, major extracranial bleeding, systemic embolism, and vascular death at 30 days after randomization.  The 12% of whole ELAN trial population had HT of any grade. The authors found no major treatment effect heterogeneity or major safety concerns between the two groups, however, in patients with PH (i.e. the most severe grade of HT) there was a 25% of increased risk of poor functional outcome. The output of the study was to provide a possible recommendation for clinicians: in atrial fibrillation patients with HI early DOAC is reasonable, in those with PH1 an individualized benefit-risk assessment should be performed, in PH2 early DOAC is likely to be harmful. This information could be useful and guide clinicians in everyday practice. 

 In the second talk Dr. Masatoshi Koga, from Suita, Osaka, Japan, illustrated results from “Risk of Ischemic and Hemorrhage events with anticoagulation early after stroke -an analysis from ELAN trial”. In this subanalysis of the ELAN trial, the risk of both ischemic and hemorrhagic events in patients treated with DOAC were assessed. The primary outcome were composite recurrent ischemic stroke, symptomatic intracerebral hemorrhage, major extracranial bleeding. Dr. Koga showed us that there was no association of anticoagulation with bleeding events, although baseline NIHSS, history of heart failure, and body weight < 75 Kg had significant associations. The same speaker continued with the last talk, “Early direct oral anticoagulation initiation post intacranial hemorrhage among Japanese patients with atrial fibrillation”. The SAFE-ICH was a multicentre prospective, observational study to determine the incidence of thrombotic and bleeding events in Japanese atrial fibrillation patients after early (<=14 days) DOAC. The primary outcomes were symptomatic intracerebral hemorrhage, stroke, or death within 30 days from DOAC initiation. A total of 240 patients reinitiated DOAC use after-ICH. Spontaneous ICH represented 85% of all cerebral hemorrhages, 79% were spontaneous, 3%  were traumatic, 3% were cerebral amyloid angiopathy, then subdural hematoma. 

In 12 (5%) patients the primary endpoint occurred, no deaths were attributed to DOAC reinitiation in those with spontaneous intracerebral ICH, and all events occurred in patients with subdural heamatoma of traumatic hemorrhage. Dr. Koga concluded that early reinitiation of DOAC in patients with spontaneaous cerebral hemorrhage was overall safe, caution should be adopted when dealing with traumatic or subdural hemorrhage. 

Poster Walk by João Pedro Marto,

Department of Neurology, Hospital de Egas Moniz, Lisbon, Portugal

Member of the Young Stroke Physicians and Researchers Committee

What a great meeting and a wonderful way to celebrate the 10^th anniversary of ESO!

As in the past years, the ESOC was the perfect opportunity to meet colleagues from all around the world and listen to the top experts in the field of stroke.

We were all privileged to witness the presentation of numerous high-quality research studies in the main large clinical trials and scientific communication sessions.

However, many other studies presented as posters deserved our attention.

During the poster walk, I attempted to summarize some of the many interesting posters displayed on Thursday and Friday.

Among the posters on ACUTE MANAGEMENT, I would like to highlight the poster on DABITAGRAN ETEXILATE VERSUS WARFARIN IN CEREBRAL VENOUS THROMBOSIS IN CHINESE PATIENTS (CHOICE-CVT): AN OPEN-LABEL, RANDOMIZED CONTROLLED TRIAL by Duan J et al. which aimed to assess the safety and efficacy of dabigatran versus warfarin in patients with CVT. This trial was recently published in the International Journal of Stroke (DOI: 10.1177/17474930241234749), and its results align with previous studies such as RESPECT-CVT (RCT) and ACTION-CVT (retrospective observational study). Together, they support DOAC therapy as a safe and equally effective alternative to warfarin in patients with CVT.

On the CLINICAL TRIALS topic, the individual patient data meta-analysis presented by Kaufmaan JE et al. on ANTITHROMBOTIC TREATMENT FOR CERVICAL ARTERY DISSECTION also caught my attention. Just published in JAMA Neurology (DOI: 10.1001/jamaneurol.2024.1141.), this study included patients from the CADISS and TREAT CAD RCTs. The authors did not find a significant difference between anticoagulants and antiplatelets in preventing early recurrent events. Results from the recent large observational study STOP-CAD Study (doi: 10.1161/STROKEAHA.123.04573) introduce treatment duration and the presence of occlusive dissection as potentially important factors for individualized decisions.

On the topics of SMALL VESSEL DISEASE and COGNITION AND VASCULAR COGNITIVE IMPAIRMENT, I found two posters about cerebral amyloid angiopathy (CAA) particularly interesting. CEREBRAL AMYLOID ANGIOPATHY WITH AND WITHOUT CORTICAL SIDEROSIS: CAN WE TALK ABOUT MICROBLEEDERS AND MACROBLEEDERS by Losa M et al. characterized and compared patients with CAA depending on the presence of cortical superficial siderosis (cSS). As previously described, the authors showed that patients with cSS have a higher risk of intracerebral hemorrhage (ICH) during follow-up. Additionally, patients without cSS more frequently presented with cognitive symptoms and had a great degree of medial temporal lobe atrophy. Finally, in a subgroup of patients, those with cSS had lower CSF levels of Aβ40. In their conclusions, the authors advocate for a phenotypic spectrum of CAA with patients having a “cognitive-neurodegenerative CAA” while others have a “hemorrhagic CAA”. From another perspective, the work from Pinho J. et al. IMAGING MARKERS IN PATIENTS WITH CAA FROM A MEMORY CLINIC COHORT – EVIDENCE FOR A PATHOPHYSIOLOGICAL TIMELINE showed that patients with CAA and hemorrhagic markers were older, had longer symptom duration, lower global cognitive performance, and lower CSF Aβ42 levels in comparison with patients with CAA without hemorrhagic markers. The authors conclude that the presence of hemorrhagic markers in CAA patients with cognitive presentation is associated with a more advanced disease. Whether there are clear different CAA phenotypes and/or different stages of CAA progression is likely an interesting topic for future studies and discussion.

Finally, on the topic of SAH and ICH the work by Ouyang M et al. conveyed an important message for all stroke physicians. In their work entitled PREDICTIVE ACCURACY OF PHYSICIANS’ ESTIMATES OF DEATH AND RECOVERY AFTER ACUTE INTRACEREBRAL HEMORRHAGE, the authors assessed the capability of physicians to predict mortality, functional outcome, and quality of life at 6 months, during the first 7 days after ICH in patients included in the RCT INTERACT 3. While the capability of physicians to estimate the likelihood of survival for ICH patients was good, their ability to predict functional outcomes and quality of life was poor. These results reinforce the need to develop better prognostic tools for patients with ICH. Additionally, physicians should be aware of their limited capability in predicting prognosis while communicating with patients and their family members, and while taking treatment decisions.

And that’s it!

Looking forward to the ESOC 2025 in Helsinki! Hope to see you there!

The scientific session “Thrombolysis for Acute Ischemic Stroke – Exploring the Grey” provided a comprehensive exploration of the latest developments and research in thrombolytic therapy for acute ischemic stroke. Moderated by Sonia Alamowitch from Paris, France, and Simona Sacco from L’Aquila, Italy, the session featured insightful presentations from leading experts in the field, each addressing critical aspects of thrombolytic therapy.

Professor David Seiffge (Bern, Switzerland) opened the session with an enlightening presentation on the complexities of administering intravenous thrombolysis (IVT) to patients who are already on anticoagulant therapy, especially direct oral anticoagulants (DOACs). He presented recent data on more liberal decisions and observational studies that demonstrated the safety and potential efficacy of thrombolysis in this increasing subgroup. The stroke center in Bern did not experience safety issues with increasingly liberal IVT decisions in a preliminary, but reassuring analysis. Participation in the upcoming DO-IT projects is possible to overcome this main barrier to IVT. 

Professor Götz Thomalla (Hamburg, Germany) discussed the potential for extending the thrombolysis treatment window beyond the conventional limits, particularly in settings lacking advanced neuroimaging capabilities. His findings suggested that, with appropriate clinical judgment, extending the treatment window could significantly benefit patient outcomes without substantially increasing risks. Options include DWI/FLAIR mismatch in MRI centers, but more importantly also individually non-contrast CT might be enough to rule out a large baseline ischemic damage. Naturally, CT-perfusion is helpful to facilitate those borderline IVT decisions. 

Professor Christian Nolte (Berlin, Germany) focused on the interaction between IVT and cerebral small vessel disease, presenting advanced markers that could predict treatment responses. For example, although white matter disease is associated with poor prognosis and sICH, it does not modify the treatment effect of IVT and should not be a reason to withhold IVT. His research highlighted the importance of personalized IVT decision while not being afraid of imaging biomarkers of SVD.

Professor Georgios Tsivgoulis (Athens, Greece) explored the potential advantages of tenecteplase over the traditional alteplase in thrombolytic therapy. Through comparative studies, he illustrated tenecteplase’s favorable profile, including ease of administration resulting in faster time to treatment. The time has come to cross the Rubikon and transition to TNK and guidance has been laid out to do so for centers. 

Concluding the session, Professor Pooja Khatri presented innovative adjunct therapies aimed at enhancing reperfusion and preventing reocclusion following thrombolysis. She showcased emerging pharmacological strategies including Glenzocimab, Eptifibatide, Argatroban, amongst others. The recently presented ARAIS, MOST and ACTISAVE trials did not show benefit in terms of recanalization and funcitional outcome. Thus, the we have awakened from the dream of cocktail therapy for IVT. However, DNAse enhanced IVT is on the horizon and provides novel hope if efficient in upcoming trials. 

The session “Thrombolysis for Acute Ischemic Stroke – Exploring the Grey” was a resounding success, offering novel options for the greyzones of IVT stroke management. The diverse topics and expert presentations underscored the importance of ongoing innovation and tailored approaches in improving patient care. 

by Christian Boehme, ESO Social Media and PR Committee

Department of Neurology, Medical University of Innsbruck, Austria

Twitter: @chris7ianb

Gisele Sampaio from São Paulo, Brazil and Keith Muir from Glasgow, United Kingdom, chaired this afternoon session on the hottest topics in stroke thrombolysis.

Pierre Seners (Paris, France) sparked off the session with ARTERIAL RECANALIZATION DURING INTER-HOSPITAL TRANSFER FOR THROMBECTOMY. The study evaluated the incidence and predictors of arterial recanalization during inter-hospital transfer for thrombectomy, as well as the relationship between recanalization during transfer and clinical outcomes. Inter-hospital recanalization was determined by comparison of the baseline and post-transfer arterial imaging and was defined as revised Arterial Occlusive Lesion (rAOL) score 2b or 3. Of 520 patients from 2 prospective cohorts in primary stroke centers, 111 (21%) experienced inter-hospital recanalization of which ¾ were partial recanalizations. IVT-use had an OR of about 7 for recanalization. Pre-transfer variables independently associated with recanalization were intravenous thrombolysis, more distal occlusions, and smaller clot burden. Recanalization during transfer was associated with less inter-hospital infarct growth and greater inter-hospital NIHSS score improvement, with greater benefit from complete vs partial recanalization. Recanalization was independently associated with reduced 3-month disability with greater benefit from complete than partial recanalization.

Pierre concludes that substantial rates of recanalization are observed during inter-hospital transfer with a strong association with favorable clinical outcomes, even for partial recanalization. Broadening thrombolysis indications in primary stroke centers and developing

therapies that increase the rate of recanalization during transfer will likely improve clinical outcomes.

Ye Liu (Shanghai, China) was next with TENECTEPLASE THROMBOLYTIC THERAPY FOR ACUTE ISCHEMIC STROKE IN CHINA. A MULTI-CENTER REAL-WORLD STUDY.

This study retrospectively collected data using alteplase or tenecteplase in a 1:1 ratio for acute ischemic stroke <4.5 hours of onset in China. The primary outcome was the rate of sICH within 72 hours after thrombolysis and secondary outcomes included functional outcomes, among others. Patients treated with tenecteplase had better 90-day functional outcome and less any ICH compared to alteplase. No difference was found in the risk of sICH, systemic bleeding and death within 90 days. Ye concludes that thrombolysis with tenecteplase was associated with better 3-month functional outcomes compared to alteplase in acute ischemic stroke patients with no increased risk of sICH.

Lina Palaiodimou (Athens, Greece) followed with TENECTEPLASE VERSUS ALTEPLASE IN THE TREATMENT OF ACUTE ISCHEMIC STROKE WITHIN 4.5 HOURS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

This meta-analysis included all available RCTs that investigated efficacy and safety of tenecteplase 0.25mg/kg compared to alteplase for the treatment of acute ischemic stroke <4.5 hours of onset. 9 RCTs were included with 2,717 patients treated with tenecteplase versus 2,676 patients treated with alteplase. Tenecteplase was associated with a higher likelihood of excellent functional outcome (RR 1.07) and reduced disability compared to alteplase, while good functional outcome was similar between the groups. The meta-analysis showed similar rates of sICH and 3-month mortality. Lina concludes that there is similar safety of tenecteplase 0.25 mg/kg to alteplase, and tenecteplase might be superior to alteplase in achieving excellent functional outcome.

Johannes Kaesmacher (Bern, Switzerland) presented RUNNING ALTEPLASE INFUSION UPON RECANALIZATION WITH THROMBECTOMY: A SUBSTUDY OF THE IRIS META-ANALYSIS.

This study assessed whether the effect of IVT+EVT versus EVT alone is modified by whether

the infusion of IVT was still running at the timepoint of proximal flow restoration. The study used the IRIS individual participant data and assessed the treatment effect heterogeneity of IVT before EVT vs. EVT alone in groups with running or finished IVT-infusion upon recanalization. In 39% of patients, IVT was still running upon recanalization and outcomes between IVT+EVT were not different if IVT was running or not at time of recanalization. The effect of a running IVT infusion does not appear to be due to IVT. Johannes concludes that this analysis does not corroborate previous studies suggesting a positive clinical effect of IVT on outcomes if IVT is running after proximal recanalization. There is no apparent benefit of “delaying” IVT in these patients for the sake of overlap.

Philipp Bücke (Bern, Switzerland) presented INTRAVENOUS THROMBOLYSIS IN PATIENTS WITH RECENT DOAC INGESTION – A TARGET TRIAL ANALYSIS AFTER LIBERALISATION OF OUR GUIDELINES. Philipp points out the increase of patients using DOACs, mainly driven by aging of the population and expansion of indications.

This single-center observational study reports results on the safety and efficacy of off-label IVT after changing institutional guidelines allowing IVT for all patients with recent dOAC intake regardless of dOAC-activity, last-intake or reversal. Previous research by Meinel et al. reported exciting results on this topic and warrant extensive research. Safety and efficacy outcomes with recent DOAC intake (<48 h) otherwise qualifying for IVT were compared to patients not receiving IVT totaling 98 patients. IVT was given in 50% with median DOAC-activity level of 93 ng/ml. SICH occurred in no patient receiving IVT and in 2 of 49 patients not receiving IVT. Mortality rates at 3 months were comparable and IVT patients were more likely to have good outcome or return to baseline mRS. There was no significant difference in major bleeding or asymptomatic ICH.

Philipp concludes that after liberalizing the institutional approach to IVT regardless of recent dOAC intake, no safety concerns were observed. The association of IVT with better outcomes warrants prospective randomized studies like the upcoming DO-IT registry and trial which are underway to answer this question.

Marius Matusevicius (Stockholm, Sweden) followed with SAFETY AND OUTCOMES OF DABIGATRAN REVERSAL WITH IDARUCIZUMAB PRIOR TO IVT TREATMENT IN PATIENTS WITH ACUTE ISCHEMIC STROKE: A SITS REGISTRY STUDY.

This study investigated safety and outcomes of IVT after dabigatran reversal using idarucizumab in acute ischemic stroke patients. Data on IVT treated patients from the SITS International Stroke Thrombolysis Registry were analyzed for occurrence of any parenchymal hematoma (PH), sICH and death within 3 months. The secondary outcome was functional independence (mRS 0-2) at 3 months. Among >180,000 IVT treated patients, 142 received dabigatran reversal. After propensity score matching analysis with a good balance at baseline,

patients treated with dabigatran reversal before IVT had similar results in all outcomes as compared to patients without prior OAC. Marius concludes that, IVT treatment after dabigatran reversal was safe and had similar outcomes to IVT without previous OAC.

Fabiano Cavalcante (Amsterdam, Netherlands) was next with a talk on ACUTE STENTING WITH OR WITHOUT INTRAVENOUS THROMBOLYSIS IN STROKE PATIENTS WITH CAROTID TANDEM LESIONS.

This study assessed the effect of acute stenting during EVT, with and without IVT. Individual participant data from a meta-analysis of the IRIS collaboration were used. All patients with carotid tandem lesions and available information on intraprocedural stent placement were included. A total of 340 of 2334 patients directly transferred to EVT-capable centers with carotid tandem lesions were included, with 1/3 of patients receiving acute stenting. Stenting during EVT was associated with better functional outcomes. No effect heterogeneity was observed for patients receiving IVT plus EVT versus EVT alone.

Fabiano concludes that in stroke patients eligible for EVT presenting directly to EVT-capable centers, acute stenting of carotid tandem lesions is associated with better functional outcomes, also in patients treated with IVT.

Adnan Mujanovic (Bern, Switzerland) finished the session with EFFECT OF INTRAVENOUS THROMBOLYTICS ON DELAYED REPERFUSION FOLLOWING INCOMPLETE MECHANICAL THROMBECTOMY.

Adnan pointed out that 60% of endovascularly treated ischemic stroke patients with incomplete reperfusion show complete delayed reperfusion at 24h, which is associated with favortable outcomes compared to non-reperfusion. The study investigated the association between intravenous thrombolysis (IVT) and delayed reperfusion occurrence. Pooled individual-patient data from 3 RCTs (EXTEND-IA, EXTEND-IA TNK part 1 & 2) and 2 prospective stroke studies were analyzed. Out of 832 patients, 61% had delayed reperfusion.

Receiving IVT was associated with delayed reperfusion. Adnan concludes that pre-treatment with IVT was associated with the occurrence of delayed complete reperfusion among

by Christian Boehme, ESO Social Media and PR Committee

Department of Neurology, Medical University of Innsbruck, Austria

Twitter: @chris7ianb

On Day 2 of the 10th anniversary of ESOC 2024 in Basel, Urs Fischer invited for a morning run at 7 am where lots of early bird-healthy strokeologists took part to recharge energy for a further exciting day here in Basel.

Nikola Sprigg (Nottingham, United Kingdom) and Daniel Strbian (Helsinki, Finland) chaired this second large clinical trials session.

Xia Wang from Barangaroo, Australia sparked off the session with TIMING OF BP LOWERING TO MITIGATE HEMATOMA EXPANSION IN INTRACEREBRAL HEMORRHAGE: IPD POOLED ANALYSIS OF 4 INTERACT TRIALS.

The aim of the study was to determine effects of BP lowering in reducing hematoma growth in ICH in relation to the timing of treatment initiation. Outcomes were hematoma growth at 24 hours in absolute and relative growth. BP lowering had a significant effect on relative hematoma growth predominantly if treated to target within 2.5 hours of onset and in low ICH score events. The BP lowering effect on hematoma growth is related to timing of systolic BP reduction (“the earlier, the better”) and to severity of ICH (“the milder, the better”). BP lowering treatment is likely most effective in patients with milder acute ICH when initiated early (within 2 hours) and when done intensively (aiming for an SBP target <140 mmHg).

In clinical practice, Xia points out that BP control might be faster when not in the scope of a trial because of the time-consuming randomization process. The INTERACT 4 results will be presented later this morning so stay tuned.

Next, Yongjun Wang (Beijing, China) presented the results of the ORIGINAL trial: TENECTEPLASE VERSUS ALTEPLASE IN CHINESE PATIENTS WITH ACUTE ISCHAEMIC STROKE (ORIGINAL): A MULTICENTRE RANDOMISED PHASE III STUDY. The trial assessed if tenecteplase was non-inferior to alteplase regarding favorable functional outcome in acute ischemic stroke in Chinese patients when administered <4.5 hours after onset. As a distinct inclusion criterion, the study included NIHSS of 1-25 points at admission. The trial demonstrated that tenecteplase was non-inferior to alteplase in reaching an mRS 0-1 after 3 months, the findings were consistent across prespecified subgroups, including baseline NIHSS, age, time to administration, gender, comorbidities and thrombectomy use. Safety outcomes were also comparable. Therefore, these results are in line with previous trials evaluating tenecteplase use in acute ischemic stroke. 

Valerian Altersberger, a local here from Basel, Switzerland presented BRIDGING THROMBOLYSIS WITH TENECTEPLASE VERSUS ENDOVASCULAR TREATMENT ALONE FOR LARGE-VESSEL ANTERIOR CIRCULATION STROKE. The study used a target trial emulation of SWIFT DIRECT and EXTEND-IA TNK Part 1&2 using 0.25 mg/kg and 0.40 mg/kg of tenecteplase. The study which included 427 patients, showed no benefit of bridging thrombolysis with tenecteplase on increased rates of functional outcomes compared to direct mechanical thrombectomy but it resulted in improved functional outcome on the full ordinal mRS and in higher frequency of freedom of disability. The effect was predominantly driven by the lower mRS grades. The results remained unchanged when only including patients who underwent treatment with tenecteplase in a dosage of 0.25 mg/kg. The improvement of outcomes was more pronounced in patients where onset-to (expected) IVT time was <140 minutes. Valerian points out that external validation is needed and a RCT (DIRECT-TNK) is underway to answer this question.

Fabiano Cavalcante (Amsterdam, Netherlands) presented results from the MR CLEAN-NO IV trial: INTRAVENOUS THROMBOLYSIS BEFORE ENDOVASCULAR TREATMENT IN PATIENTS WITH CAROTID TANDEM LESIONS: MR CLEAN-NO IV RANDOMIZED CLINICAL TRIAL RESULTS. He highlights the fact that tandem lesions affect 15% of all patients undergoing EVT. Tandem lesion was defined as ipsilateral flow-limiting lesion (>50% stenosis, dissection, occlusion) and the primary outcome was mRS score at 90 days. The study included 88 patients with tandem lesions of the 539 patients in the MR CLEAN-NO IV trial. Tandem lesions significantly worsened functional outcomes on the mRS shift analysis as well as rates of favorable functional outcome and increased the risk for any ICH, but not statistically significant for sICH. Regarding treatment, IVT before EVT was less effective in patients with tandem lesions and more effective in patients without tandem lesions, whereby rates of ICH and sICH were similar. In recognition of these data, we are excited to hear the IRIS pooled results later today.

Santiago Ortega-Gutierrez (Iowa City, United States) followed with ENDOVASCULAR THROMBECTOMY FOR LARGE ISCHEMIC STROKES WITH TANDEM LESIONS: A SECONDARY ANALYSIS OF THE SELECT2 TRIAL. The study aimed to compare the effectiveness and safety outcomes of EVT with medical management in patients with extracranial ICA occlusions and large ischemic core. In this secondary analysis of the SELECT2-trial, 62 of 352 patients in the SELECT2 trial with complete occlusion of the extracranial ICA in addition to intracranial anterior LVO (including M2) were included.

The study found a shift in the 90-day mRS score towards better outcomes in the EVT group compared to medical management. Independence at 90 days occurred in 38% of patients in the EVT group compared to 8% in the medical management group. Risk of hemorrhagic transformation was higher in the EVT group mainly driven by an increase of petechial hemorrhage. Santiago concludes that, in patients with extracranial ICA occlusions and large ischemic core in addition to intracranial LVO, EVT appears to improve functional outcomes without major safety concerns compared to medical management. This study advocates for more extensive research to define the optimal treatment approach in these patients.

Mouhammad Jumaa (Toledo, United States) reported results of the CLEVER trial: CLEVIDIPINE INFUSION FOR BLOOD PRESSURE MANAGEMENT AFTER SUCCESSFUL REVASCULARIZATION IN ACUTE ISCHEMIC STROKE (CLEVER).

Several trials made a recommendation of SBP <140 mmHg after successful recanalization of anterior LVO-stroke. In this randomized trial using clevidipine, patients were randomized to an intensive blood pressure management group (90-120 mmHg) versus a standard BP management group (90-160 mmHg). The rates of excellent outcome (mRS 0-1), favorable functional outcome (mRS 0-2) and rates of sICH were not different between the treatment arms. In conclusion, clevidipine is safe and effective when used for blood pressure control after mechanical thrombectomy. Intensive SBP control with a cap of 120 mmHg did not reduce the rate of hemorrhagic transformation or sICH and resulted in a numerically lower rate of favorable functional outcome, albeit not showing a significant difference.

Götz Thomalla (Hamburg, Germany) presented FUNCTIONAL OUTCOME AND QUALITY OF LIFE AT 12 MONTHS AFTER THROMBECTOMY FOR STROKE WITH EXTENDED LESION IN THE TENSION TRIAL. These are extended results of the TENSION trial which demonstrated improved functional outcomes in patients treated with EVT and large infarcts (ASPECTS <6). Functional outcome at 12 months showed a significant treatment effect in median mRS scores, higher rates of favorable functional outcomes (mRS 0-2) and in preventing disability (mRS 0-3). Also, quality of life was better in the EVT group after 1 year. In conclusion, using EVT in patients with established large infarcts (ASPECTS <6), the intervention showed a reduction of mortality and dependency after 1 year and a reduced mortality during the first 12 months of follow-up. Götz concluded that in patients with acute ischemic stroke and LVO with established large infarct, thrombectomy results in better functional outcome, better quality of life and lower mortality at 12 months compared to medical treatment alone. After one year, thrombectomy was associated with a 17% absolute increase of patients able to walk unaided. Thrombectomy is associated with long-term improvement of survival of patients with large infarct with a relative mortality-reduction of 30%.

In my opinion, these results seem reassuring when physicians are in doubt to treat these severely affected patients and provide a quantitative basis for prognostic estimation, and Götz Thomalla pointed out that a reasonable number of patients (17%) further improved after 3 months until 12 months after the event.

Edo Richard from Nijmegen, Netherlands was the last speaker of this session and presented results of the PREVENTION OF DEMENTIA USING MOBILE PHONE APPLICATIONS (PRODEMOS) trial. The PRODEMOS trial assessed the efficacy of an app with an individual coach compared to a static app alone in changing the CAIDE dementia risk score including total cholesterol, systolic BP, BMI and physical activity. Patients with pre-stroke dementia and cognitive impairment were excluded from the trial. The coach-supported mHEALTH intervention for risk reduction was feasible to implement and the implementation in the low socioeconomic status population was possible, but challenging. The effects on improvement of risk factor control were small and significantly improved physical activity and smoking cessation. The clinical relevance of these findings is yet to be determined.

This second large clinical trial session brought very exciting results and made the thousands of spectators hungry for more in the next large clinical trial session later this morning.

by Dr. Inna Lutsenko, ESO Social Media and PR Committee, @inna_lutsenko

Prof. Julia Ferrari from Vienna, Austria and Prof. Rebecca Redwood London, United Kingdom moderated the session. 

The session started with the talk of Dr. Andrea Rossetti “Post-stroke seizures: early and late”. Dr. Rossetti brought attention to the correct semiology and the poststroke seizures. Acute symptomatic seizure starts within 7d of the insult (Begh,Epilepsia 2010) and epilepsy diagnosis will be considered if a patient experienced more than one seizure (nonprovoked = not acute symptomatic = late). Recurrence risk of poststroke seizures if they already manifested is more than 60% in the following stroke 10 years (Fisher Epilepsia 2014). And the status epilepticus would be considered if the seizures are lasting longer than 5 min (generalized convulsive), ≥ 10 min (focal) (Trinka,Elepsia 2015). Stroke is considered a leading cause of epilepsy and a status epilepticus. Pathophysiology of the early seizures is described in the imbalance between excitatory and inhibitory inputs and of the late seizures in the immunological changes in TNF1. 

Important notice was that the postroke seizures are often focal and non-convulsive. EEG helps to differentiate poststroke seizures from other conditions such as the TIA, stroke progression, hyperkinetic movements, drug withdrawal, syncopes and migraine. For the diagnosis first should be used thet clinical suspicion leading the neurologist to the acute EEG, which can register epileptiform discharges in 17% (Carrera, Neurology 2006). An epileptiform activity is not considered as an independent risk factor for epilepsy (Ferreira Atuesta, Ann Neurol 2021). CEEG vs rEEG does not improve prognosis (Rossetti, JAMA Neurol 2020). Perfusion imaging should also be considered in the suspicion of the seizures in the stroke onset or in the status epilepticus following the stroke (Hauf AINR 2009, Strambo J Neurol 2018, Merl UNNP 2024).

Antiepileptic medications should not be prescribed with the intention to make so called “antiseizure prophylaxis”. As an evident treatment are considered the following pharmacological considerations: enzyme inducers, but the high risk of interactions, osteoporosis and hypercholesterolemia (Minter Ellepsia 2020) and possible risk of functional impairment (PB), hypo-Na (CBZ, OXC, ESL) should not be overlooked. Enzyme inhibitor such as valproic acid is also used but the clinicians should look at the risk of interactions, osteoporosis, weight gain and the risk of encephalopathy (Loser CNS Drugs 2023). 

Post stroke spasticity management was presented by Maja Villseth (Norway). The concept of the muscle overactivity was explained starting from the lesions in the CNS exactly in the corticospinal tract and/or extrapyramidal system, leading to the imbalance between excitatory and inhibitory input from the brain and the spinal cord, which gives a supranuclear «drive» to the alpha-motor neurons in the spinal cord. This leads to the increased reflex activity in muscles and to the hyperexcitability of the stretch reflex. All pathologies affecting  the extrapyramidal system can cause muscle overactivity, and the indication for treatment is independent of etiology. Spasticity is a frequent stroke complication and present in 25% of the stroke patients already on day 3, appearing first at the elbow joint. Key risk factors associated with the development of spasticity are lower Barthel Index scores, severe degree of paresis, stroke-related pain, sensory deficits (Neurology. 2013 Jan Wissel J et al). 

Dr. Villseth offered to regularly use the Modified Ashworth Scale, which is the tool for the measurements of the spasticity for the monitoring of the effects. 

As an early (< 12 weeks!) intervention to prevent or to already treat the poststroke spasticity the early use of the Botulinum Neurotoxin (BoNT). Early BoNT may prevent severe spasticity, complications (contractures)1,3,5,6,8 and may improve rehabilitation outcome/function, no further cost for identification of predictors of spasticity development are needed. Drug costs (1-3 vials of BoNT-A1,3,56) for early BoNT treatment of PSS seems to be less expensive (lover dose of BoNT, only 50% of dose and longer duration of effect ,3,5) as BoNT treatment in the chronic poststroke spasticity phase. Sensory deficit is the key factor in the developing of the spasticity

So when treating the poststroke spasticity physicians should consider all the parts: pain relief, hygiene, involuntary movements, prevention of contractures and deformity, passive function, active function, recovery and to combine this with GAS (Goal attainment Scale) assessment. 

Post-stroke depression and the role of caregivers was presented by Orla Sheehan (Dublin, Ireland). Poststroke depression is underdiagnosed and undertreated. The risk factors include genetic factors: 5-HTTLPR, STin2 VNTR, polymorphisms of serotonin transporter gene, brain-derived neurotrophic factor, gender – in 30% of th  studies it was associated with the female gender, medical history: some associations for comorbidity, previous stroke, diabetes but inconsistent and psychiatric history: history of depression or family history depression associated with PSD in a number of studies. The screening tools are CES-D, Hamilton Depression Rating Scale & PHQ-9. PHQ-9 may be most practical. Optimal timing of screening remains unknown. CES-D has the highest utility out-patient setting. In in-patient settings Geriatric Depression Scale 15, Montgomery and Asberg Depression Rating Scale (MADRS) and others. Pharmacological treatment may include nortriptyline / fluoxetine which lead to improvements in depressive symptoms, ADL impairments, cognitive function & mortality. 

Cochrane Review included the 56 RCTs in 4059 patients highlighting the strong support for SSRIs to reduce dependence, disability, neurological impairment, anxiety and depression. Regretfully no effect on mortality, cognitive function or motor deficits was shown. Non-pharmacological treatments such as non-invasive brain stimulation, acupuncture, behavioral and psychosocial approaches have been incorporated in some clinical guidelines. Exercise, music, light, and art therapy remain investigational, there is some evidence for Folic acid, Vitamin B1, B6 and B12 supplements. 

The topic of caregiving in post stroke patients was also well presented by Dr. Sheehan.

80% of stroke survivors return to the community. Without support for daily living many stroke survivors would end up in institutional care. Most caregivers are spouses, often in their 6th decade or older, dealing with stroke patients’ difficulties in mobility, self-care, and communication, but also their cognitive impairment, depression, and personality changes. Caregivers report physical fatigue, psychological distress, loss of social relationships, financial worries, unmet needs and lack of social support. Caregiving stress / burden can result in negative emotional, social, environmental and health related difficulties for both the stroke survivor and the caregiver.

The session finished with the intensive discussion and a vivid interest from the audience, expressing the concerns regarding the recovering of the stroke patients from spasticity and dosage and combinations of the antiseizure medications. Watch an upcoming video interview with Dr.Rossetti on my Twitter account page. 

by Christian Boehme, ESO Social Media and PR Committee

Twitter: @chris7ianb

Arthur Liesz from Munich, Germany and Ethem Murat Arsava from Ankara, Türkiye chaired this last session of the day on inflammation in stroke.

Yaw Asare (Munich, Germany) presented Atherosclerotic Plaque Inflammation: Mechanistic insights from experimental studies. He pointed out that common variants in HDAC9 are associated with atherosclerotic phenotypes. An experimental study deleted the cis regulatory element (CRE) at HDAC9 which exacerbated atherosclerosis. Also, HDAC9 promotes inflammasome activation and is associated with increased atherosclerosis plaque instability in humans. HDAC9-targeted immunotherapy stabilizes atherosclerotic plaques thereby offering a poterntisl target for stroke prevention. NLRP3 inflammasome is a central inflammatory pathway driving atherosclerosis. HDAC9 is a major cardiovascular risk gene and an upstream modulator of NLRP3, therefore nanobiologics targeting HDAC9 at the site of myeloid-driven vascular inflammation confer vascular protection. These studies serve as basis for development of powerful anti-inflammatory drugs to reduce the risk of atherosclerotic stroke.

Alba Simats (Barcelona, Spain) followed with Systemic inflammation after ischemic stroke. She points out the role of the chronic immune response after stroke which lasts up to one year. Systemic inflammation is a risk factor for lots of diseases, among others, dementia, cerebrovascular disease and depression and i.e. bone and joint diseases or lung diseases. Systemic inflammation influences the brain-heart immune axis after stroke inducing development of AF, ECG abnormalities and LV-diastolic dysfunction. Stroke induces long-lasting transcriptomic changes in monocytes and drive chronic cardiac fibrosis, and in a study, blocking monocyte infiltration into the heart reduced LV-diastolic dysfunction. The exact mechanisms in the numerous comorbidities and their relevance in clinical outcomes are yet to be determined.

Next, Maria Moro (Madrid, Spain) did a presentation on The role of neutrophils as a therapeutic target in stroke. She emphasizes the role of neurophils in cerebral damage in case of ischemia. Previous studies showed that neutrophil depletion or inhibition of their infiltration improve stroke outcome after MCA occlusion in mice but this is not the case in all studies. There is evidence that neutrophil heterogeneity is an important feature in immune pathophysiology and that neutrophil ageing is regulated by the microbiome, which might be a source of neutrophil heterogeneity. Also, neutrophil heterogeneity is determined by circadian rhythms and Maria’s research on this topic will be published soon. These circadian effects might be an explanation for the translational failure in neuroprotection.

Furthermore, she implies that TLR4 might be a future therapeutic target in acute stroke and RCTs are needed to confirm this. She concludes that, regardless of the mechanism underlying phenotypic heterogeneity, strategies that interfere with the pathogenic function of deleterious neutrophil phenotypes are promising targets for stroke treatment.

Anna Bersano (Milan, Italy) followed with the Role of inflammation in cerebral amyloid angiopathy. She emphasized on the role of amyloid deposition into blood vessel walls which make them predispose for rupture, causing ICH. One proposed pathogenic mechanism of CAA is that inefficient Aß clearance leads to abnormal Aß accumulation in the brain and vessels, causing CAA in the aged brain. In rare cases, patients suffer from the inflammatory form of CAA – CAA-ri which has different histopathological features compared to CAA. CAA-ri patients do not frequently present with ICH, but more often with acute or subacute cognitive impairment, headaches, seizures and focal deficits. Recent research found laboratory differences including increased leukocytes, protein and tau levels. Regarding treatment, no standard treatment is recommended but clinical and neuroradiological improvement is achieved by using corticosteroids and immunosuppressants, albeit mortality is around 30%. In conclusion, CAA-ri expands the clinical spectrum of CAA, it is increasingly recognized and treatable, the clinical presentation is usually acute or subacute, bit may be similar to CAA. MRI shows characteristics of CAA features in addition to white matter lesions with extension to subcortical areas but also edema and/or contrast enhancement. The disease can be monophasic but also relapsing and usually responds fast to immune-modulating treatment. Limitations to the available evidence are the small size of the reported series and large multicenter studies are needed to improve diagnosis, treatment and outcomes in CAA-ri affected patients.

Aristeidis Katsanos (Hamilton, Canada) completed the session with a talk on Inflammation as a target in secondary prevention after ischemic vs. hemorrhagic stroke. He highlights the high risk of recurrence of stroke in ischemic and hemorrhagic stroke, especially in the first months after the event. The common unmet need of these entities is the need for novel treatments which lower the long-term risk of future cardiovascular events and that can be initiated early after stroke when patients are at most risk. A stufdy of 8,420 patients found that hsCRP and IL-6 were associated with recurrent vascular events after stroke. So the goal is clear, we have to try to reduce inflammation. CHANCE 3 assessed short-term use of colchicine and the results were neutral, CONVINCE assessed long-term use of colchicine and found lower risk for atherosclerotic events but was terminated prematurely. Ongoing trials include RIISC-THETIS from France assessing colchicine in combination with DAPT in ischemic stroke and ipsilateral atherosclerotic stenosis, CASPER from Australia assessing colchicine in ischemic stroke/TIA with increased CRP levels and CoVasc-ICH from Canada assessing colchicine in ICH patients. Patients after ischemic or hemorrhagic stroke are at risk for stroke recurrence and other atherosclerotic cardiovascular events. Targeting atherosclerosis-related inflammation in addition to standard care may attenuate this risk. Long-term colchicine treatment should be evaluated further in RCTs for stroke prevention and the prevention of atheroslcerotic cardiovascular events in stroke survivors.

Aristeidis finished the session with a quote from John Lennon: “You may say I’m a dreamer. But I’m not the only one. I hope someday you’ll join us”.