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1. Sex differences in functional outcomes of intravenous thrombolysis among patients with lacunar stroke

Author

Patrizia Wueger, Roberta Noseda, Alberto Pagnamenta, Giovanni Bianco, David Seiffge, Patrik Michel, Krassen Nedeltchev, Leo Bonati, Georg Kägi, Julien Niederhauser, Thomas Nyffeler, Andreas Luft, Susanne Wegener, Ludwig Schelosky, Friedrich Medlin, Biljana Rodic, Nils Peters, Susanne Renaud, Marie Luise Mono, Emmanuel Carrera, Urs Fischer, Gian Marco De Marchis, and Carlo W. Cereda

Subjects
lacunar stroke, intravenous thrombolysis, sex differences, functional outcome, cohort study, Neurology. Diseases of the nervous system, RC346-429
Abstract

BackgroundThis study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS).MethodsConsecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke.ResultsA total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th–75th percentiles 67–84 years versus 70 years, 25th–75th percentiles 60–80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01–2.19, value of p 0.044).ConclusionThis study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.

Published
2024
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2. Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage

Author

Martina B. Goeldlin, Achim Mueller, Bernhard M. Siepen, Madlaine Mueller, Davide Strambo, Patrik Michel, Michael Schaerer, Carlo W. Cereda, Giovanni Bianco, Florian Lindheimer, Christian Berger, Friedrich Medlin, Roland Backhaus, Nils Peters, Susanne Renaud, Loraine Fisch, Julien Niederhaeuser, Emmanuel Carrera, Elisabeth Dirren, Christophe Bonvin, Rolf Sturzenegger, Timo Kahles, Krassen Nedeltchev, Georg Kaegi, Jochen Vehoff, Biljana Rodic, Manuel Bolognese, Ludwig Schelosky, Stephan Salmen, Marie-Luise Mono, Alexandros A. Polymeris, Stefan T. Engelter, Philippe Lyrer, Susanne Wegener, Andreas R. Luft, Werner Z’Graggen, David Bervini, Bastian Volbers, Tomas Dobrocky, Johannes Kaesmacher, Pasquale Mordasini, Thomas R. Meinel, Marcel Arnold, Javier Fandino, Leo H. Bonati, Urs Fischer, and David J. Seiffge

Subjects
cerebral hemorrhage, etiology, ischemic stroke, outcome, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background and Purpose Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce. Methods We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019). Results We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI], 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031). Conclusions Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage.

Published
2022
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3. Correlation of disability with quality of life in patients with multiple sclerosis treated with natalizumab: primary results and post hoc analysis of the TYSabri ImPROvement study (PROTYS)

Author

Krassen Nedeltchev, Chiara Zecca, Jens Kuhle, Andreas Lutterotti, Claudio Gobbi, Stefanie Mueller, Oliver Findling, Lutz Achtnichts, Christian P Kamm, Camille Viviani, and Emanuela Villiger-Borter

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Background In patients with multiple sclerosis (MS), relapses and disability progression have been associated with decreased health-related quality of life (HRQoL).Methods PROTYS, a prospective, multicentre, single-arm, observational study in seven Swiss MS centres, evaluated correlations between change in disability status (measured through the Expanded Disability Status Scale (EDSS)) and HRQoL changes (measured through the global Multiple Sclerosis International Quality of Life (MusiQoL) index questionnaire) in 35 patients with relapsing remitting MS on natalizumab for 1 year. In addition, several other scales were also used, such as: Multiple Sclerosis Intimacy and Sexuality Questionnaire-19, EuroQoL-5 Dimension, and Fatigue Scale of Motor and Cognitive Function. A post hoc analysis further assessed the association between HRQoL changes after 1 year and the MusiQoL subscores and other patient-reported outcome (PRO) measures.Results At 1 year, patients were categorised into ‘EDSS improved’ (6/35), ‘EDSS stable’ (28/35) and ‘EDSS worsened’ (1/35). Mean disability scores decreased for ‘EDSS improved’ and ‘EDSS stable’ but increased for ‘EDSS worsened’. Mean MusiQoL index score for ‘EDSS improved’ increased from 61.2 at baseline to 66.3 at 1 year, while the ‘EDSS stable’ group increased from 67.9 to 70.8. No meaningful statistical relationship was observed between EDSS group and changes in MusiQoL score. For the post hoc analysis, patients were categorised in ‘MusiQoL improved’ (n=21) and ‘MusiQoL worsened’ (n=14) groups. MusiQoL subscores for ‘symptoms,’ ‘psychological well-being’ and ‘activities of daily living’, as well as scores for several related PRO measures, correlated with improvement of the MusiQoL global index. There was no correlation between the changes in MusiQoL global index and EDSS score.Conclusions Natalizumab treatment for 1 year resulted in either improved or stable EDSS status in most patients, and although no significant relationship was observed between global HRQoL change and EDSS change, several domains of HRQoL seemed to improve with natalizumab treatment.Trial registration number NCT02386566.

Published
2023
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4. Central Retinal Artery Occlusion: Current Practice, Awareness and Prehospital Delays in Switzerland

Author

Elena Ardila Jurado, Veit Sturm, Florian Brugger, Krassen Nedeltchev, Marcel Arnold, Leo H. Bonati, Emmanuel Carrera, Patrik Michel, Carlo W. Cereda, Manuel Bolognese, Sylvan Albert, Friedrich Medlin, Christian Berger, Ludwig Schelosky, Susanne Renaud, Julien Niederhauser, Christophe Bonvin, Marie-Luise Mono, Biljana Rodic, Alexander A. Tarnutzer, Guido Schwegler, Stephan Salmen, Andreas R. Luft, Nils Peters, Jochen Vehoff, Georg Kägi, and The Swiss Stroke Registry Investigators

Subjects
central retinal artery occlusion (CRAO), incidence, ischemic stroke, awareness, prehospital, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background and PurposeCentral retinal artery occlusion (CRAO) often leads to permanent monocular blindness. Hence, early recognition and rapid re-perfusion is of paramount importance. This study aims to describe prehospital pathways in CRAO compared to stroke and study the knowledge about CRAO.Methods(1) Description of baseline characteristics, prehospital pathways/delays, and acute treatment (thrombolysis/thrombectomy vs. standard of care) of patients with CRAO and ischemic stroke registered in the Swiss Stroke Registry. (2) Online survey about CRAO knowledge amongst population, general practitioners (GPs) and ophthalmologists in Eastern Switzerland.ResultsThree hundred and ninety seven CRAO and 32,816 ischemic stroke cases were registered from 2014 until 2019 in 20 Stroke Centers/Units in Switzerland. In CRAO, 25.6% arrived at the hospital within 4 h of symptom onset and had a lower rate of emergency referrals. Hence, the symptom-to-door time was significantly longer in CRAO compared to stroke (852 min. vs. 300 min). The thrombolysis/thrombectomy rate was 13.2% in CRAO and 30.9% in stroke. 28.6% of the surveyed population recognized CRAO-symptoms, 55.4% of which would present directly to the emergency department in contrast to 90.0% with stroke symptoms. Almost 100% of the ophthalmologist and general practitioners recognized CRAO as a medical emergency and 1/3 of them considered IV thrombolysis a potentially beneficial therapy.ConclusionsCRAO awareness of the general population and physician awareness about the treatment options as well as the non-standardized prehospital organization, seems to be the main reason for the prehospital delays and impedes treating CRAO patients. Educational efforts should be undertaken to improve awareness about CRAO.

Published
2022
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5. Recognizing myorhythmia 4 months after stroke – A teaching video

Author

Sebastian Finkener, Tobias Piroth, Magdalena Högg, Stephan Rüegg, Krassen Nedeltchev, Julien F. Bally, and Markus Gschwind

Subjects
Myorhythmia, Stroke, Guillain-Mollaret triangle, Red nucleus, Thalamus, Superior cerebellar peduncle, Neurology. Diseases of the nervous system, RC346-429
Abstract

In this case study with video and neurophysiology, we describe a rare case of hemimyorhythmia occurring 4 months after a stroke with bilateral affection of the thalamus and right superior cerebellar peduncle (Guillain-Mollaret-triangle). This case and especially the video with the clinical and EMG presentation of a synchronous rhythmic pattern at 3,1 Hz makes an important educational contribution to the recognition of myorhythmia and discussed differential diagnoses.

Published
2022
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6. Acute revascularization in ischemic stroke: Updated Swiss guidelines

Author

Patrik Michel, Michael Diepers, Pasquale Mordasini, Tilman Schubert, David Bervini, Jean-Daniel Rouvé, Yvan Gasche, Guido Schwegler, Christophe Bonvin, Krassen Nedeltchev, Emmanuel Carrera, Georg Kägi, Carlo Cereda, Thomas Nyffeler, Stephan Wetzel, Susanne Wegener, Henrik Gensicke, Stefan Engelter, and Marcel Arnold

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

In acute ischemic stroke, intravenous thrombolysis (IVT) and acute endovascular therapy (EVT) have been shown to reduce long-term disability in randomized trials. International guidelines are partially not up to date and may not address situations for which there is limited scientific evidence. The goals of the present guidelines are to summarize the current scientific data for acute revascularization treatments to make sure that all Swiss Centers apply a similar, evidence, or consensus-based treatment standard. A multidisciplinary working group of the Swiss Stroke Society (SSS) searched and reviewed the literature on new randomized controlled trials (RCTs), large case series, meta-analyses, and other guidelines since the previous recommendations in 2009 to elaborate the consensus guidelines. The new RCTs have confirmed the effectiveness of IVT in various populations up to 4.5 h and proven the benefit of acute EVT up to approximately 8 h. For patients with unknown onset (including wake-up stroke), IVT and EVT can be effective up to 24 h after last proof of good health if patients are selected with advanced neuroimaging. Multiple case series and meta-analyses allow narrowing down the indications and relative and absolute contraindications to optimize the benefit–risk ratio of acute revascularization.

Published
2021
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7. Swiss guidelines for the prehospital phase in suspected acute stroke

Author

Georg Kägi, David Schurter, Julien Niederhäuser, Gian Marco De Marchis, Stefan Engelter, Patrick Arni, Olivier Nyenhuis, Paul Imboden, Christophe Bonvin, Andreas Luft, Susanne Renaud, Krassen Nedeltchev, Emmanuel Carrera, Carlo Cereda, Urs Fischer, Marcel Arnold, and Patrik Michel

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Acute stroke treatment has advanced substantially over the last years. Important milestones constitute intravenous thrombolysis, endovascular therapy (EVT), and treatment of stroke patients in dedicated units (stroke units). At present in Switzerland there are 13 certified stroke units and 10 certified EVT-capable stroke centers. Emerging challenges for the prehospital pathways are that (i) acute stroke treatment remains very time sensitive, (ii) the time window for acute stroke treatment has opened up to 24 h in selected cases, and (iii) EVT is only available in stroke centers. The goal of the current guideline is to standardize the prehospital phase of patients with acute stroke for them to receive the optimal treatment without unnecessary delays. Different prehospital models exist. For patients with large vessel occlusion (LVO), the Drip and Ship model is the most commonly used in Switzerland. This model is challenged by the Mothership model where stroke patients with suspected LVO are directly transferred to the stroke center. This latter model is only effective if there is an accurate triage by paramedics, hence the patient may benefit from the right treatment in the right place, without loss of time. Although the Cincinnati Prehospital Stroke Scale is a well-established scale to detect acute stroke in the prehospital setting, it neglects nonmotor symptoms like visual impairment or severe vertigo. Therefore we suggest “acute occurrence of a focal neurological deficit” as the trigger to enter the acute stroke pathway. For the triage whether a patient has a LVO (yes/no), there are a number of scores published. Accuracy of these scores is borderline. Nevertheless, applying the Rapid Arterial Occlusion Evaluation score or a comparable score to recognize patients with LVO may help to speed up and triage prehospital pathways. Ultimately, the decision of which model to use in which stroke network will depend on local (e.g. geographical) characteristics.

Published
2021
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8. Comparison of different carotid stent designs in endovascular therapy of severe carotid artery stenosis

Author

Philipp Gruber, Jatta Berberat, Timo Kahles, Javier Anon, Michael Diepers, Krassen Nedeltchev, and Luca Remonda

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Background: One of the major periprocedural risks of carotid artery stenting is embolism caused either by plaque debris or by local thrombus forming. Double-layer micromesh stent design has shown to lower the chance of debris embolism but might have a slightly higher risk of local thrombus forming. Thus, we compared two different stent designs regarding safety and outcome profile in elective patients with high-grade carotid artery stenosis using a self-expanding, double-layer micromesh carotid stent system (DLCS) or a self-expanding hybrid carotid stent system (HCS). Methods: A single-center, open-label, retrospective cohort study of 67 consecutive, elective patients with high-grade symptomatic and asymptomatic carotid stenosis was executed at a comprehensive stroke center. Outcome measures were reocclusion rate, periprocedural symptomatic ischemic events, as well as other periprocedural complications, and recurrent stroke and mortality at 30 days’ follow-up. Results: Thirty-two patients (24% women, median age 75 years (interquartile range (IQR) 71–80) were treated with DLCS, and 35 patients (29% women, median age 71 years (IQR 63–76) years) with HCS. In both groups, pretreatment carotid stenosis degree was similar (median NASCET of 80%). Successful deployment was achieved in all cases without technical failure, and both groups did not differ in reocclusion rates, recurrent stroke, and mortality within 30 days. Conclusions: DCLS and HCS revealed to have similar safety and outcome profile in elective patients with high-grade symptomatic as well as asymptomatic carotid artery stenosis.

Published
2020
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9. Prior Stroke in PFO Patients Is Associated With Both PFO-Related and -Unrelated Factors

Author

Timo Kahles, Patrik Michel, Alexander Hapfelmeier, Franz R. Eberli, Marialuisa Zedde, Vincent Thijs, Markus Kraemer, Stefan T. Engelter, Joaquin Serena, Christian Weimar, Achim Mallmann, Andreas Luft, Dimitri Hemelsoet, David E. Thaler, Andreas Müller-Eichelberg, Adinda De Pauw, Roman Sztajzel, Carmel Armon, David M. Kent, Bernhard Meier, Heinrich P. Mattle, Urs Fischer, Marcel Arnold, Marie-Luise Mono, Krassen Nedeltchev, and for the International PFO Consortium NCT

Subjects
patent foramen ovale, PFO, right-to-left shunt, cryptogenic stroke, prior stroke, risk factor, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background and Purpose: To identify factors associated with prior stroke at presentation in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO).Methods: We studied cross-sectional data from the International PFO Consortium Study (NCT00859885). Patients with first-ever stroke and those with prior stroke at baseline were analyzed for an association with PFO-related (right-to-left shunt at rest, atrial septal aneurysm, deep venous thrombosis, pulmonary embolism, and Valsalva maneuver) and PFO-unrelated factors (age, gender, BMI, hypertension, diabetes mellitus, hypercholesterolemia, smoking, migraine, coronary artery disease, aortic plaque). A multivariable analysis was used to adjust effect estimation for confounding, e.g., owing to the age-dependent definition of study groups in this cross-sectional study design.Results: We identified 635 patients with first-ever and 53 patients with prior stroke. Age, BMI, hypertension, diabetes mellitus, hypercholesterolemia, coronary artery disease, and right-to-left shunt (RLS) at rest were significantly associated with prior stroke. Using a pre-specified multivariable logistic regression model, age (Odds Ratio 1.06), BMI (OR 1.06), hypercholesterolemia (OR 1.90) and RLS at rest (OR 1.88) were strongly associated with prior stroke.Based on these factors, we developed a nomogram to illustrate the strength of the relation of individual factors to prior stroke.Conclusion: In patients with CS and PFO, the likelihood of prior stroke is associated with both, PFO-related and PFO-unrelated factors.

Published
2020
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10. SARS-CoV-2 mRNA Vaccination in People with Multiple Sclerosis Treated with Fingolimod: Protective Humoral Immune Responses May Develop after the Preferred Third Shot

Author

Lutz Achtnichts, Arkady Ovchinnikov, Barbara Jakopp, Michael Oberle, Krassen Nedeltchev, Christoph Andreas Fux, Johann Sellner, and Oliver Findling

Subjects
SARS-CoV-2, S1PR-modulator, fingolimod, humoral immune response, vaccination, COVID-19, Medicine
Abstract

Evidence suggests limited development of protective IgG responses to mRNA-based vaccines in sphingosine-1-phosphate receptor (S1PR)-modulator treated individuals with multiple sclerosis (MS). We studied the extent of the humoral immune response after the preferred third mRNA SARS-CoV-2 vaccine in S1PR-modulator treated people with MS (pwMS) and insufficient IgG responses after the standard immunization scheme. Eight pwMS that were treated with fingolimod received a third homologous SARS-CoV-2 mRNA vaccine dose, either the Moderna’s mRNA-1273 or Pfizer-BioNTech’s BNT162b2 vaccine. We quantified the serum levels of IgG antibodies against the receptor-binding domain of SARS-CoV-2 four weeks later. An antibody titer of 100 AU/mL or more was considered protective. After the third vaccination, we found clinically relevant IgG titers in four out of eight individuals (50%). We conclude that the humoral immune response may reach protective levels after the third preferred dose of the homologous SARS-CoV-2 mRNA vaccine. Vaccine shots in S1PR-modulator treated pwMS ahead of schedule may be a strategy to overcome insufficient humoral immune responses following the standard vaccination scheme.

Published
2022
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11. Prediction of post-acute care demand in medical and neurological inpatients: diagnostic assessment of the post-acute discharge score – a prospective cohort study

Author

Antoinette Conca, Angela Gabele, Barbara Reutlinger, Philipp Schuetz, Alexander Kutz, Sebastian Haubitz, Lukas Faessler, Marcus Batschwaroff, Ursula Schild, Zeljka Caldara, Katharina Regez, Susanne Schirlo, Gabi Vossler, Timo Kahles, Krassen Nedeltchev, Anja Keller, Andreas Huber, Sabina De Geest, Ulrich Buergi, Petra Tobias, Martine Louis Simonet, Beat Mueller, and Petra Schäfer-Keller

Subjects
Discharge planning, Post-acute care discharge score, Diagnostic accuracy, Post-acute care facilities, Screening tool, Social worker referral, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Early identification of patients requiring transfer to post-acute care (PAC) facilities shortens hospital stays. With a focus on interprofessional assessment of biopsychosocial risk, this study’s aim was to assess medical and neurological patients’ post-acute care discharge (PACD) scores on days 1 and 3 after hospital admission regarding diagnostic accuracy and effectiveness as an early screening tool. The transfer to PAC facilities served as the outcome (“gold standard”). Methods In this prospective cohort study, registered at ClinicalTrial.gov (NCT01768494) on January 2013, 1432 medical and 464 neurological patients (total n = 1896) were included consecutively between February and October 2013. PACD scores and other relevant data were extracted from electronic records of patient admissions, hospital stays, and interviews at day 30 post-hospital admission. To gauge the scores’ accuracy, we plotted receiver operating characteristic (ROC) curves, calculated area under the curve (AUC), and determined sensitivity and specificity at various cut-off levels. Results Medical patients’ day 1 and day 3 PACD scores accurately predicted discharge to PAC facilities, with respective discriminating powers (AUC) of 0.77 and 0.82. With a PACD cut-off of ≥8 points, day 1 and 3 sensitivities were respectively 72.6% and 83.6%, with respective specificities of 66.5% and 70.0%. Neurological patients’ scores showed lower accuracy both days: using the same cut-off, respective day 1 and day 3 AUCs were 0.68 and 0.78, sensitivities 41.4% and 68.7% and specificities 81.4% and 83.4%. Conclusion PACD scores at days 1 and 3 accurately predicted transfer to PAC facilities, especially in medical patients on day 3. To confirm and refine these results, PACD scores’ value to guide discharge planning interventions and subsequent impact on hospital stay warrants further investigation. Trial registration ClinialTrials.gov Identifier, NCT01768494.

Published
2018
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12. Humoral Immune Response after the Third SARS-CoV-2 mRNA Vaccination in CD20 Depleted People with Multiple Sclerosis

Author

Lutz Achtnichts, Barbara Jakopp, Michael Oberle, Krassen Nedeltchev, Christoph Andreas Fux, Johann Sellner, and Oliver Findling

Subjects
SARS-CoV-2, B cell depletion, humoral immune response, vaccination, COVID-19, Medicine
Abstract

CD20 depletion is a risk factor for unfavorable outcomes of COVID-19 in people with MS (pwMS). Evidence suggests that protective IgG response to mRNA-based vaccines in B cell-depleted individuals is limited. We studied the seroconversion after the third mRNA SARS-CoV-2 vaccine in B cell-depleted pwMS with limited or no IgG response after the standard immunization. Sixteen pwMS treated with ocrelizumab or rituximab received a third homologous SARS-CoV-2 mRNA vaccine, either the Moderna mRNA-1273 or Pfizer-BioNTech’s BNT162b2 vaccine. We quantified the response of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 four weeks later. An antibody titer of 100 AU/mL or more was considered clinically relevant. The median time between the last infusion of the anti-CD20 treatment and the third vaccination was 22.9 weeks (range 15.1–31.3). After the third vaccination, one out of 16 patients showed an IgG titer deemed clinically relevant. Only the seroconverted patient had measurable B-cell counts at the time of the third vaccination. The development of a humoral immune response remains rare in pwMS on anti-CD20 therapy, even after third dose of the homologous SARS-CoV-2 mRNA vaccine. It remains to be determined whether T-cell responses can compensate for the lack of seroconversion and provide sufficient protection against CoV-2 infections.

Published
2021
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13. Long-term evaluation of NEDA-3 status in relapsing-remitting multiple sclerosis patients after switching from natalizumab to fingolimod

Author

Lara Diem, Krassen Nedeltchev, Timo Kahles, Lutz Achtnichts, and Oliver Findling

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: Natalizumab significantly reduces the disease activity in patients with relapsing-remitting multiple sclerosis but due to the risk of progressive multifocal leukoencephalopathy it is often discontinued. Fingolimod is seen as an alternative, but there are no long-term analyses of the efficacy of fingolimod in this setting using the no evidence of disease activity (NEDA)-3 criteria. We provide an assessment of patients who discontinued natalizumab and switched to fingolimod or other treatments by evaluating the proportion of patients who fulfil NEDA-3 criteria after prolonged follow-up periods. Methods: We conducted a retrospective observational study of multiple sclerosis patients, who were treated with continuous natalizumab or who had switched to fingolimod or other treatments after natalizumab discontinuation. We assessed NEDA-3 status, annual relapse rate and determined the odds ratio between disease course after treatment switch and other patient and treatment characteristics. Results: A total of 61 patients on continuous natalizumab treatment and 53 patients who switched from natalizumab to fingolimod or other treatments were accompanied for up to 5 years. While the proportion of natalizumab patients fulfilling NEDA-3 criteria remained stable at 90% during the entire follow-up period, the proportion of patients switching to fingolimod or other therapies dropped to 76.7% in the first year after discontinuation, and to 50% in the years thereafter. While the median Expanded Disability Status Scale remained stable and the percentage of relapsing patients did not change significantly, recurring magnetic resonance imaging activity was found in up to 42% of the patients after switching from natalizumab to other treatments. New disease activity was significantly correlated with extended treatment gap between natalizumab discontinuation and the start of a new therapy. Discussion: Patients remain clinically stable after discontinuing natalizumab and switching to other therapies. However, when considering NEDA-3 criteria, a considerable proportion of patients show disease reactivation. Careful monitoring and early evaluation of alternatives is necessary after switching from natalizumab to other treatments.

Published
2018
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14. A comparison of balance control during stance and gait in patients with inflammatory and non-inflammatory polyneuropathy.

Author

Oliver Findling, Rens van der Logt, Krassen Nedeltchev, Lutz Achtnichts, and John H J Allum

Subjects
Medicine, Science
Abstract

We compared changes in balance control due to chronic inflammatory demyelinating polyneuropathy (CIDP) and non-inflammatory (non-inf) polyneuropathy (PNP) to each other and with respect to healthy controls (HCs). Differences in patients' subjective impressions of balance capabilities were also compared.Balance control of 11 CIDP patients (mean age 61.1±(sd) 11, 8 male) and 10 non-inf PNP patients (mean age 68.5±11.7, all male) was examined and compared to that of 18 age- and gender-matched healthy controls. Balance control during stance and gait tasks was measured as trunk sway angles and angular velocities with body-worn gyroscopes. Patients' subjective impressions of balance were obtained using the Dizziness Handicap Inventory (DHI). The Neuropathy Impairment Score in the Lower Limbs (NIS-LL) was used to measure clinical disease status.Non-inf PNP patients had slightly lower NIS-LL (13.5±7.2 vs. 17.9±15.1) and DHI scores (22.6±17.1 vs 27.6±16.3). Gait tasks showed a significant decrease in gait speed with respect to HCs for both patient groups but reduced trunk sway for non-inf PNP patients. Trunk sway during tandem walking and walking on the heels was greater for both groups than that of HCs. Sway during 2-legged stance tasks with eyes closed on a firm or foam surface was also greater than for HCs.Compared to HCs both groups of patients have significantly greater sway for most stance and gait tasks accompanied by reduced gait speed. As for HCs, non-inf PNP patients reduced trunk sway with slower gait speed. In CIDP patients this compensatory strategy was absent, possibly due to a greater deficit of efferent and motor nerve fibers. An interpretation of these findings is that CIDP patients have reduced ability to decrease trunk sway with slower gait speed and is possibly associated with an increased risk of falls.

Published
2018
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15. Interdisciplinary decision-making and treatment of intracranial aneurysms in the era of complementary microsurgical and endovascular techniques

Author

Serge Marbacher, Michael Diepers, Timo Kahles, Krassen Nedeltchev, Luca Remonda, and Javier Fandino

Subjects
clipping, Coiling, hybrid operating room, intracranial aneurysm, Medicine
Abstract

Rupture of an intracranial aneurysm is a life-threatening event. Only one third of intracranial aneurysms rupture during a patient’s lifetime. Accurate markers that predict which intracranial aneurysms rupture and which do not are currently lacking in routine clinical practice. Therefore, the treatment decision is a careful balance between the natural history of the intracranial aneurysm and the risk of intervention based on aneurysm- and patient-specific risk factors. Many of these risk factors are also used to determine the modality of intervention. In this review, the authors discuss the interdisciplinary decision-making process and treatment approach in the era of complementary techniques for intracranial aneurysm obliteration.

Published
2016
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16. The Swiss Multiple Sclerosis Cohort-Study (SMSC): A Prospective Swiss Wide Investigation of Key Phases in Disease Evolution and New Treatment Options.

Author

Giulio Disanto, Pascal Benkert, Johannes Lorscheider, Stefanie Mueller, Jochen Vehoff, Chiara Zecca, Simon Ramseier, Lutz Achtnichts, Oliver Findling, Krassen Nedeltchev, Ernst-Wilhelm Radue, Till Sprenger, Christoph Stippich, Tobias Derfuss, Jean-François Louvion, Christian P Kamm, Heinrich P Mattle, Christoph Lotter, Renaud Du Pasquier, Myriam Schluep, Caroline Pot, Patrice H Lalive, Özgür Yaldizli, Claudio Gobbi, Ludwig Kappos, Jens Kuhle, and SMSC Scientific Board

Subjects
Medicine, Science
Abstract

The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed at building a prospective cohort of MS patients with standardized collection of demographic, clinical, MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response. The Swiss MS Cohort (SMSC) is a prospective observational study performed across seven Swiss MS centers including patients with MS, clinically isolated syndrome (CIS), radiologically isolated syndrome or neuromyelitis optica. Neurological and radiological assessments and biological samples are collected every 6-12 months. We recruited 872 patients (clinically isolated syndrome [CIS] 5.5%, relapsing-remitting MS [RRMS] 85.8%, primary progressive MS [PPMS] 3.5%, secondary progressive MS [SPMS] 5.2%) between June 2012 and July 2015. We performed 2,286 visits (median follow-up 398 days) and collected 2,274 serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain MRI scans. 158 relapses occurred and expanded disability status scale (EDSS) scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS patients were treated with fingolimod (33.4%), natalizumab (24.5%) or injectable DMDs (13.6%). The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects.

Published
2016
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17. Rivaroxaban vs Vitamin K Antagonist in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease

Author

Laetitia, Albano, Catherine, Albert, Joachim, Alexandre, Ayham, Al-Zoebi, Cedric, Annweiler, Johann, Auer, Sanjeet, Balgobin, Joachim, Beige, Ahmed, Berami, Jean-Baptiste, Berneau, Patrick, Biggar, Ralf, Birkemeyer, Christina, Bondke, Renate, Bonin-Schnabel, Hendrik, Bonnemeier, Marc, Bouiller, Anne-Sophie, Boureau, Johannes, Brachmann, Jörg, Brosche, Sebastien, Caudmont, Guillaume, Cayla, Vianney, Charpy, Joel, Constans, Jean-Baptiste, Dally, Guillaume, De Geeter, Fédéric, Debelle, Eric, Decoulx, Nicolas, Delarche, Georg, Delle Karth, Pascal, Delsart, Michael, Derndorfer, Laurent, Desprets, Jean-Guillaume, Dillinger, Camille, Dubart, Katrin, Eberhard, Sabine, Eichinger-Hasenauer, Volker, Eissing, Christiane, Erley, Jean-Baptiste, Esteve, Emile, Ferrari, Virginie, Fossey-Diaz, Stéphane, Fromentin, Karim, Gallouj, Estelle, Gandjbakhch, Anne-Sophie, Garnier, Laure, Gilis, Bertrand, Gondouin, Franziska, Grundmann, Isabelle, Gueffet, Sebastian, Haaß, Didier, Haguenhauer, Thierry, Hannedouche, Georg, Häusler Karl, Gerd-Ulrich, Heinz, Philipp, Herold, Klaus, Hertting, Etienne, Hoffer, Joachim, Hoyer, Burkhard, Hügl, Sybille, Jänsch, Georges, Jean-Louis, Michael, Jeserich, Werner, Jung, Samuel, Kassis, Bernd-Thomas, Kellner, Marcus, Ketteler, Thomas, Kielstein Jan, René, Koning, Fabian, Krämer, Jean-Marie, Krzesinski, Ulrich, Lammers, Jean-Marie, Lefebvre, Eric, Legrand, Matthias, Leschke, Bernhard-Paul, Lodde, Christian, Maalouli, Christian, Mahnkopf, Sebastien, Mailliez, Jacques, Mansourati, Eloi, Marijon, Christian, Meyer, Detlev, Moll, Gilles, Montalescot, Serge, Motte, Vincent, Mouquet, Krassen, Nedeltchev, Anna, Neykova, Jörg, Nothroff, Raphael, Poyet, Roland, Prondzinsky, Ursula, Rauch-Kröhnert, Frank, Richard, Werner, Rieker, Andrea, Rocco, Thomas, Rostock, Daniel, Scherr, Axel, Schlitt, Hans, Schmidt-Gürtler, Norbert, Schön, Johannes, Schwab, Carsten, Schwencke, Peter, Schwimmbeck, G, Schwinger Robert H., Andreas, Schwittay, Igor, Sibon, Ulrike, Spengler, Alexander, Stadelmann, Clemens, Steinwender, Reinhard, Stöhring, Jean-Claude, Stolear, Guillaume, Taldir, Jean-Michel, Tartière, Serge, Treille, Pierre, Tremolieres, Zead, Tubail, Xavier, Warling, Morgane, Wetzstein, Adrian, Zaman, Claudia, Zemmrich, Kreutz, Reinhold, Deray, Gilbert, Floege, Jürgen, Gwechenberger, Marianne, Hahn, Kai, Luft, Andreas R., Persson, Pontus, Axthelm, Christoph, Beer, Juerg Hans, Bergler-Klein, Jutta, Lellouche, Nicolas, Taggeselle, Jens, Coleman, Craig I., and Beyer-Westendorf, Jan

Published
2024
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18. Rivaroxaban vs Vitamin K Antagonist in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease

Author

Kreutz, Reinhold, primary, Deray, Gilbert, additional, Floege, Jürgen, additional, Gwechenberger, Marianne, additional, Hahn, Kai, additional, Luft, Andreas R., additional, Persson, Pontus, additional, Axthelm, Christoph, additional, Beer, Juerg Hans, additional, Bergler-Klein, Jutta, additional, Lellouche, Nicolas, additional, Taggeselle, Jens, additional, Coleman, Craig I., additional, Beyer-Westendorf, Jan, additional, Laetitia, Albano, additional, Catherine, Albert, additional, Joachim, Alexandre, additional, Ayham, Al-Zoebi, additional, Cedric, Annweiler, additional, Johann, Auer, additional, Sanjeet, Balgobin, additional, Joachim, Beige, additional, Ahmed, Berami, additional, Jean-Baptiste, Berneau, additional, Patrick, Biggar, additional, Ralf, Birkemeyer, additional, Christina, Bondke, additional, Renate, Bonin-Schnabel, additional, Hendrik, Bonnemeier, additional, Marc, Bouiller, additional, Anne-Sophie, Boureau, additional, Johannes, Brachmann, additional, Jörg, Brosche, additional, Sebastien, Caudmont, additional, Guillaume, Cayla, additional, Vianney, Charpy, additional, Joel, Constans, additional, Jean-Baptiste, Dally, additional, Guillaume, De Geeter, additional, Fédéric, Debelle, additional, Eric, Decoulx, additional, Nicolas, Delarche, additional, Georg, Delle Karth, additional, Pascal, Delsart, additional, Michael, Derndorfer, additional, Laurent, Desprets, additional, Jean-Guillaume, Dillinger, additional, Camille, Dubart, additional, Katrin, Eberhard, additional, Sabine, Eichinger-Hasenauer, additional, Volker, Eissing, additional, Christiane, Erley, additional, Jean-Baptiste, Esteve, additional, Emile, Ferrari, additional, Virginie, Fossey-Diaz, additional, Stéphane, Fromentin, additional, Karim, Gallouj, additional, Estelle, Gandjbakhch, additional, Anne-Sophie, Garnier, additional, Laure, Gilis, additional, Bertrand, Gondouin, additional, Franziska, Grundmann, additional, Isabelle, Gueffet, additional, Sebastian, Haaß, additional, Didier, Haguenhauer, additional, Thierry, Hannedouche, additional, Georg, Häusler Karl, additional, Gerd-Ulrich, Heinz, additional, Philipp, Herold, additional, Klaus, Hertting, additional, Etienne, Hoffer, additional, Joachim, Hoyer, additional, Burkhard, Hügl, additional, Sybille, Jänsch, additional, Georges, Jean-Louis, additional, Michael, Jeserich, additional, Werner, Jung, additional, Samuel, Kassis, additional, Bernd-Thomas, Kellner, additional, Marcus, Ketteler, additional, Thomas, Kielstein Jan, additional, René, Koning, additional, Fabian, Krämer, additional, Jean-Marie, Krzesinski, additional, Ulrich, Lammers, additional, Jean-Marie, Lefebvre, additional, Eric, Legrand, additional, Matthias, Leschke, additional, Bernhard-Paul, Lodde, additional, Christian, Maalouli, additional, Christian, Mahnkopf, additional, Sebastien, Mailliez, additional, Jacques, Mansourati, additional, Eloi, Marijon, additional, Christian, Meyer, additional, Detlev, Moll, additional, Gilles, Montalescot, additional, Serge, Motte, additional, Vincent, Mouquet, additional, Krassen, Nedeltchev, additional, Anna, Neykova, additional, Jörg, Nothroff, additional, Raphael, Poyet, additional, Roland, Prondzinsky, additional, Ursula, Rauch-Kröhnert, additional, Frank, Richard, additional, Werner, Rieker, additional, Andrea, Rocco, additional, Thomas, Rostock, additional, Daniel, Scherr, additional, Axel, Schlitt, additional, Hans, Schmidt-Gürtler, additional, Norbert, Schön, additional, Johannes, Schwab, additional, Carsten, Schwencke, additional, Peter, Schwimmbeck, additional, G, Schwinger Robert H., additional, Andreas, Schwittay, additional, Igor, Sibon, additional, Ulrike, Spengler, additional, Alexander, Stadelmann, additional, Clemens, Steinwender, additional, Reinhard, Stöhring, additional, Jean-Claude, Stolear, additional, Guillaume, Taldir, additional, Jean-Michel, Tartière, additional, Serge, Treille, additional, Pierre, Tremolieres, additional, Zead, Tubail, additional, Xavier, Warling, additional, Morgane, Wetzstein, additional, Adrian, Zaman, additional, and Claudia, Zemmrich, additional

Published
2024
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19. Sex Differences in Outcomes of Intravenous Thrombolysis in Acute Ischemic Stroke Patients with Preadmission Use of Antiplatelets

Author

Roberta Noseda, Federico Rea, Alberto Pagnamenta, Pamela Agazzi, Giovanni Bianco, Shairin Sihabdeen, David Seiffge, Patrik Michel, Krassen Nedeltchev, Leo Bonati, Georg Kägi, Julien Niederhauser, Thomas Nyffeler, Andreas Luft, Susanne Wegener, Ludwig Schelosky, Friedrich Medlin, Biljana Rodic, Nils Peters, Susanne Renaud, Marie-Luise Mono, Emmanuel Carrera, Urs Fischer, Alessandro Ceschi, Carlo Walter Cereda, Noseda, R, Rea, F, Pagnamenta, A, Agazzi, P, Bianco, G, Sihabdeen, S, Seiffge, D, Michel, P, Nedeltchev, K, Bonati, L, Kägi, G, Niederhauser, J, Nyffeler, T, Luft, A, Wegener, S, Schelosky, L, Medlin, F, Rodic, B, Peters, N, Renaud, S, Mono, M, Carrera, E, Fischer, U, Ceschi, A, and Cereda, C

Subjects
Psychiatry and Mental health, ischemic stroke, sex, intravenous thrombolysis, Pharmacology (medical), Neurology (clinical), antiplatelet
Abstract

Aim: To compare safety and functional outcomes of intravenous thrombolysis (IVT) between females and males with acute ischaemic stroke (AIS) in relation to preadmission use of antiplatelets. Methods: Multicentre cohort study of patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry, presenting with AIS and receiving IVT. Primary safety outcome was in-hospital symptomatic intracerebral haemorrhage (sICH). Primary functional outcome was functional independence at 3 months after discharge. Multivariable logistic regression models were fitted to assess the association between sex and each outcome according to preadmission use of antiplatelets. Results: The study included 4996 patients (42.51 % females, older than males, median age 79 vs 71 years, p < 0.0001). Comparable proportions of females (39.92 %) and males (40.39 %) used antiplatelets before admission (p = 0.74). In total, 3.06 % females and 2.47 % males developed in-hospital sICH (p = 0.19), with similar odds (adjusted odds ratio, [AOR] 0.93, 95 % confidence interval, [CI] 0.63–1.39). No interaction was found between sex and preadmission use of either single or dual antiplatelets in relation to in-hospital sICH (p = 0.94 and p = 0.23). Males had higher odds of functional independence at 3 months (AOR 1.34, 95 % CI 1.09–1.65), regardless of preadmission use of antiplatelets (interaction between sex and preadmission use of either single or dual antiplatelets p = 0.41 and p = 0.58). Conclusion: No sex differences were observed in the safety of IVT regarding preadmission use of antiplatelets. Males showed more favourable 3-month functional independence than females; however, this sex difference was apparently not explained by a sex-specific mechanism related to preadmission use of antiplatelets.

Published
2023

20. Effect of admission time on provision of acute stroke treatment at stroke units and stroke centers—An analysis of the Swiss Stroke Registry

Author

Valerian L Altersberger, Patrick R Wright, Sabine A Schaedelin, Gian Marco De Marchis, Henrik Gensicke, Stefan T Engelter, Marios Psychogios, Timo Kahles, Martina Goeldlin, Thomas R Meinel, Pasquale Mordasini, Johannes Kaesmacher, Alexander von Hessling, Jochen Vehoff, Johannes Weber, Susanne Wegener, Stephan Salmen, Rolf Sturzenegger, Friedrich Medlin, Christian Berger, Ludwig Schelosky, Susanne Renaud, Julien Niederhauser, Christophe Bonvin, Michael Schaerer, Marie-Luise Mono, Biljana Rodic, Guido Schwegler, Nils Peters, Manuel Bolognese, Andreas R Luft, Carlo W Cereda, Georg Kägi, Patrick Michel, Emmanuel Carrera, Marcel Arnold, Urs Fischer, Krassen Nedeltchev, and Leo H Bonati

Subjects
Original Research Articles, Neurology (clinical), 610 Medicine & health, Cardiology and Cardiovascular Medicine
Abstract

Introduction: Rapid treatment of acute ischemic stroke (AIS) depends on sufficient staffing which differs between Stroke Centers and Stroke Units in Switzerland. We studied the effect of admission time on performance measures of AIS treatment and related temporal trends over time. Patients and methods: We compared treatment rates, door-to-image-time, door-to-needle-time, and door-to-groin-puncture-time in stroke patients admitted during office hours (Monday–Friday 8:00–17:59) and non-office hours at all certified Stroke Centers and Stroke Units in Switzerland, as well as secular trends thereof between 2014 and 2019, using data from the Swiss Stroke Registry. Secondary outcomes were modified Rankin Scale and mortality at 3 months. Results: Data were eligible for analysis in 31,788 (90.2%) of 35,261 patients. Treatment rates for IVT/EVT were higher during non-office hours compared with office hours in Stroke Centers (40.8 vs 36.5%) and Stroke Units (21.8 vs 18.5%). Door-to-image-time and door-to-needle-time increased significantly during non-office hours. Median (IQR) door-to-groin-puncture-time at Stroke Centers was longer during non-office hours compared to office hours (84 (59–116) vs 95 (66–130) minutes). Admission during non-office hours was independently associated with worse functional outcome (1.11 [95%CI: 1.04–1.18]) and increased mortality (1.13 [95%CI: 1.01–1.27]). From 2014 to 2019, median door-to-groin-puncture-time improved and the treatment rate for wake-up strokes increased. Discussion and Conclusion: Despite differences in staffing, patient admission during non-office hours delayed IVT to a similar, modest degree at Stroke Centers and Stroke Units. A larger delay of EVT was observed during non-office hours, but Stroke Centers sped up delivery of EVT over time. Patients admitted during non-office hours had worse functional outcomes, which was not explained by treatment delays.

Published
2022

21. Abstract TP150: Outcome Of Patients With Lacunar Strokes In The Era Of Thrombectomy

Author

Yael van der Geest, Giulio Disanto, Giovanni Bianco, Shairin Sihabdeen, Marco Pileggi, Davide Strambo, Patrik Michel, Timo Kahles, Krassen Nedeltchev, Urs Fischer, Leo Bonati, Georg Kaegi, Jose Bernardo Escribano, Emmanuel Carrera, Thomas Nyffeler, Manuel Bolognese, Susanne Wegener, Andreas Luft, Friedrich Medlin, Susanne Renaud, Marie-Luise Mono, Luca Remonda, Paolo Machi, Marios Psychogios, Johannes Kaesmacher, Joanna M Wardlaw, and Carlo W Cereda

Subjects
Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: Endovascular treatment (EVT), in particular mechanical thrombectomy, has dramatically improved the clinical outcome of patients with large vessels occlusion (LVO) of the anterior circulation. In contrast, the benefits of EVT cannot be applied to lacunar strokes (LS). The absence of a LVO in LS has been historically associated with a more favorable outcome, but in the new era of EVT, this assumption may not be correct anymore. We aimed to test the general assumption that LS have a better prognosis than other stroke subtypes, and analyze the outcome of LS treated with IVT as compared to strokes with LVO treated with IVT and/or mechanical thrombectomy in the multicentric Swiss Stroke Registry. Methods: retrospective propensity score matching analysis of patients from the Swiss stroke registry (SSR) with lacunar stroke treated with thrombolysis versus LVO of the medial cerebral artery treated with EVT (with or without thrombolysis). Primary endpoint was a shift analysis of mRs at 90 days after stroke. Secondary outcomes were favorable functional outcome (mRS 0-1), independence (mRS 0-2), survival with high disability (mRS 3-5) and mortality (mRS 6) at 90 days. Results: From 13'227 patients, the propensity score method matched (sex, age, NIHSS, time to treatment, prior anticoagulation, pre-stroke modified Rankin Score, mRs) 538 patients (269 in each group. There was no difference between groups in mRs shift analysis at 90 days after stroke (OR=0.99, 95%CI=0.73-1.35, p=0.952). There was also no significant difference in mRS 0-1 (59.9% vs 55.8% respectively; OR=0.79, 95%CI=0.55-1.16, p=0.75). LS+IVT patients showed a non-significant trend towards mRS 3-5 (OR=1.23, 95%CI=0.78-1.94, p=0.38), while patients treated with EVT had a slightly, non-significant, higher mortality (6.3% vs 1.9%, p=0.38). Conclusions: Lacunar strokes - which cannot directly benefit from thrombectomy therapy - when treated with IVT and matched on key prognostic variables, seem to have similar outcomes as LVO strokes treated with EVT. This observation confirms that lacunar stroke is not a benign entity and therefore suggests that reperfusion therapy should be addressed with the same intensity as LVO stroke.

Published
2023

22. Spike-microstates correlate with interictal epileptogenic discharges: a marker for hidden epileptic activity

Author

Vincent Rochas, Markus Gschwind, Krassen Nedeltchev, and Margitta Seeck

Subjects
Cellular and Molecular Neuroscience, Psychiatry and Mental health, Neurology, Biological Psychiatry
Abstract

Objectively estimating disease severity and treatment success is a main problem in outpatient managing of epilepsy. Self-reported seizures diaries are well-known to underestimate the actual seizure count, and repeated EEGs might not show interictal epileptiform discharges (IEDs), although patients suffer from seizures. In this prospective study, we investigate the potential of microstate analysis to monitor epilepsy patients independently of their IED count. From our databank of candidates for epilepsy surgery, we included 18 patients who underwent controlled resting EEG sessions (with eyes closed, 30 min), at around the same time of the day, during at least four days (range: 4–8 days; mean: 5). Nine patients with temporal foci, six with extratemporal foci, and three with generalized epilepsy were included. Each patient’s IEDs were marked and the topographic voltage maps of the IED peaks were averaged, and an individual average spike topography (AST) was created. The AST was then backfitted to each timepoint of the whole EEG resulting in the Spike-Microstate (SMS). The presence of the SMS in the residual EEG outside of the short IEDs epochs was determined for each recording session in each patient and correlated with the occurrence of the IEDs across all recording session, as well as with the drug charge of each day. Overall, SMS was much more represented in the routine EEG than the IEDs: they were identified 262 times more often than IEDs. The SMS time coverage correlated significantly with the IED occurrence rate (rho = 0.56; P < 0.001). If only patients with focal epilepsy were considered, this correlation was even higher rho = 0.69 (P < 0.001). Drug charge per day did not correlate with SMS. In this proof-of-concept study, the time coverage of SMS correlated strongly with the occurrence rate of the IEDs, they can be retrieved in the scalp EEG at a much higher occurrence rate. We conclude that SMS, once obtained for a given patient, are a more abundant marker of hidden epileptic activity than IEDs, in particular in focal epilepsy, and can be used also in absence of IEDs. Future larger studies are needed to verify its potential as monitoring tool and to determine cut-off values when drug protection becomes imperfect.

Published
2023

23. Correlation of disability with quality of life in patients with multiple sclerosis treated with natalizumab: primary results and post hoc analysis of the TYSabri ImPROvement study (PROTYS)

Author

Lutz Achtnichts, Chiara Zecca, Oliver Findling, Christian P Kamm, Stefanie Mueller, Jens Kuhle, Andreas Lutterotti, Claudio Gobbi, Camille Viviani, Emanuela Villiger-Borter, and Krassen Nedeltchev

Subjects
Neurology, 610 Medicine & health, Neurology (clinical), 610 Medizin und Gesundheit
Abstract

BackgroundIn patients with multiple sclerosis (MS), relapses and disability progression have been associated with decreased health-related quality of life (HRQoL).MethodsPROTYS, a prospective, multicentre, single-arm, observational study in seven Swiss MS centres, evaluated correlations between change in disability status (measured through the Expanded Disability Status Scale (EDSS)) and HRQoL changes (measured through the global Multiple Sclerosis International Quality of Life (MusiQoL) index questionnaire) in 35 patients with relapsing remitting MS on natalizumab for 1 year. In addition, several other scales were also used, such as: Multiple Sclerosis Intimacy and Sexuality Questionnaire-19, EuroQoL-5 Dimension, and Fatigue Scale of Motor and Cognitive Function. A post hoc analysis further assessed the association between HRQoL changes after 1 year and the MusiQoL subscores and other patient-reported outcome (PRO) measures.ResultsAt 1 year, patients were categorised into ‘EDSS improved’ (6/35), ‘EDSS stable’ (28/35) and ‘EDSS worsened’ (1/35). Mean disability scores decreased for ‘EDSS improved’ and ‘EDSS stable’ but increased for ‘EDSS worsened’. Mean MusiQoL index score for ‘EDSS improved’ increased from 61.2 at baseline to 66.3 at 1 year, while the ‘EDSS stable’ group increased from 67.9 to 70.8. No meaningful statistical relationship was observed between EDSS group and changes in MusiQoL score. For the post hoc analysis, patients were categorised in ‘MusiQoL improved’ (n=21) and ‘MusiQoL worsened’ (n=14) groups. MusiQoL subscores for ‘symptoms,’ ‘psychological well-being’ and ‘activities of daily living’, as well as scores for several related PRO measures, correlated with improvement of the MusiQoL global index. There was no correlation between the changes in MusiQoL global index and EDSS score.ConclusionsNatalizumab treatment for 1 year resulted in either improved or stable EDSS status in most patients, and although no significant relationship was observed between global HRQoL change and EDSS change, several domains of HRQoL seemed to improve with natalizumab treatment.Trial registration numberNCT02386566.

Published
2023

24. Carotid plaque surface echogenicity predicts cerebrovascular events: An Echographic Multicentric Swiss Study

Author

Roman F Sztajzel, Stefan T Engelter, Leo H Bonati, Marie‐Luise Mono, Agnieska Slezak, Rebekka Kurmann, Krassen Nedeltchev, Henrik Gensicke, Christopher Traenka, Ralf W Baumgartner, Christophe Bonvin, Lorenz Hirt, Friedrich Medlin, Annika Burow, Georg Kägi, Monika Kapauer, Jochen Vehoff, Karl O Lovblad, Francois Curtin, and Philippe A Lyrer

Subjects
Pilot Projects, 610 Medicine & health, Constriction, Pathologic, Plaque, Atherosclerotic, Stroke, Ischemic Attack, Transient, Risk Factors, Humans, Carotid Stenosis/diagnostic imaging, Ischemic Attack, Transient/diagnostic imaging, Switzerland/epidemiology, Plaque, Atherosclerotic/diagnostic imaging, Stroke/diagnostic imaging, Ultrasonography, carotid plaque echogenicity, carotid plaque surface, degree of stenosis, duplex ultrasound, stroke, Radiology, Nuclear Medicine and imaging, Carotid Stenosis, Neurology (clinical), Switzerland
Abstract

BACKGROUND AND PURPOSE To determine the prognostic value for ischemic stroke or transitory ischemic attack (TIA) of plaque surface echogenicity alone or combined to degree of stenosis in a Swiss multicenter cohort METHODS: Patients with ≥60% asymptomatic or ≥50% symptomatic carotid stenosis were included. Grey-scale based colour mapping was obtained of the whole plaque and of its surface defined as the regions between the lumen and respectively 0-0.5, 0-1, 0-1.5, and 0-2 mm of the outer border of the plaque. Red, yellow and green colour represented low, intermediate or high echogenicity. Proportion of red color on surface (PRCS) reflecting low echogenictiy was considered alone or combined to degree of stenosis (Risk index, RI). RESULTS We included 205 asymptomatic and 54 symptomatic patients. During follow-up (median/mean 24/27.7 months) 27 patients experienced stroke or TIA. In the asymptomatic group, RI ≥0.25 and PRCS ≥79% predicted stroke or TIA with a hazard ratio (HR) of respectively 8.7 p = 0.0001 and 10.2 p < 0.0001. In the symptomatic group RI ≥0.25 and PRCS ≥81% predicted stroke or TIA occurrence with a HR of respectively 6.1 p = 0.006 and 8.9 p = 0.001. The best surface parameter was located at 0-0.5mm. Among variables including age, sex, degree of stenosis, stenosis progression, RI, PRCS, grey median scale values and clinical baseline status, only PRCS independently prognosticated stroke (p = 0.005). CONCLUSION In this pilot study including patients with at least moderate degree of carotid stenosis, PRCS (0-0.5mm) alone or combined to degree of stenosis strongly predicted occurrence of subsequent cerebrovascular events.

Published
2022

25. Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial

Author

Urs Fischer, Johannes Kaesmacher, Daniel Strbian, Omer Eker, Christoph Cognard, Patricia S Plattner, Lukas Bütikofer, Pasquale Mordasini, Sandro Deppeler, Vitor M Pereira, Jean François Albucher, Jean Darcourt, Romain Bourcier, Guillon Benoit, Chrysanthi Papagiannaki, Ozlem Ozkul-Wermester, Gerli Sibolt, Marjaana Tiainen, Benjamin Gory, Sébastien Richard, Jan Liman, Marielle Sophie Ernst, Marion Boulanger, Charlotte Barbier, Laura Mechtouff, Liqun Zhang, Gaultier Marnat, Igor Sibon, Omid Nikoubashman, Arno Reich, Arturo Consoli, Bertrand Lapergue, Marc Ribo, Alejandro Tomasello, Suzana Saleme, Francisco Macian, Solène Moulin, Paolo Pagano, Guillaume Saliou, Emmanuel Carrera, Kevin Janot, María Hernández-Pérez, Raoul Pop, Lucie Della Schiava, Andreas R Luft, Michel Piotin, Jean Christophe Gentric, Aleksandra Pikula, Waltraud Pfeilschifter, Marcel Arnold, Adnan H Siddiqui, Michael T Froehler, Anthony J Furlan, René Chapot, Martin Wiesmann, Paolo Machi, Hans-Christoph Diener, Zsolt Kulcsar, Leo H Bonati, Claudio L Bassetti, Mikael Mazighi, David S Liebeskind, Jeffrey L Saver, Jan Gralla, Angelika Alonso, Caroline Arquizan, Xavier Barreau, Rémy Beaujeux, Daniel Behme, Tobias Boeckh-Behrens, Christian Boehme, Martí Boix, Grégoire Boulouis, Nicolas Bricout, Nicolas Broc, Carlo W. Cereda, Emmanuel Chabert, Tae-Hee Cho, Alessandro Cianfoni, Vincent Costalat, Christian Denier, Frederico Di Maria, Richard du Mesnil de Rochemont, Patricia Fearon, Anna Ferrier, Sebastian Fischer, Maxime Gauberti, Marie Gaudron, Laetitia Gimenez, Christoph Globas, Michael Görtler, Mayank Goyal, Ruediger Hilker-Roggendorf, Michael D. Hill, Vi Tuan Hua, Lisa Humbertjean, Olav Jansen, Simon Jung, Georg Kägi, Michael E. Kelly, Ilka Kleffner, Michael Knoflach, Krassen Nedeltchev, Lars Udo Krause, Kimmo Lappalainen, Margaux Lefebvre, Joe Leyon, Liang Liao, Jean-Sebastien Liegey, Christian Loehr, Patrik Michel, Stefania Nannoni, Patrick Nicholson, Lorena Nico, Michael Obadia, Julien Ognard, Ayokunle Ogungbemi, Jean-Marc Olivot, Simon Escalard, Marco Pasi, Lissa Peeling, Jane Perez, Martina Petersen, Eike Piechowiak, Roberto Raposo, Silja Räty, Sarah C. Reitz, Sebastià Remollo, Luca Remonda, Ian Rennie, Manuel Requena, Alexander Riabikin, Roberto Riva, Aymeric Rouchaud, Andrea Rosi, Marta Rubiera, Laurent Spelle, Marlena Schnieder, Joanna D. Schaafsma, Tilman Schubert, Jörg B. Schulz, Mohammed Siddiqui, Sébastien Soize, Michael Sonnberger, Emmanuel Touze, Aude Triquenot, Guillaume Turc, Lucy Vieira, Wagih Ben Hassen, Judith N. Wagner, Katrin Wasser, Johannes Weber, Holger Wenz, David Weisenburger-Lile, Fritz Wodarg, Valérie Wolff, Silke Wunderlich, University of Bern, Bern University Hospital [Berne] (Inselspital), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Service de neuroradiologie [Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Toulouse [Toulouse], Département de Neuro-Radiologie [Bordeaux] (DNR - Bordeaux), CHU Bordeaux [Bordeaux], University of Toronto, Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Radiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service de neurologie [Rouen], Helsinki University Hospital [Finland] (HUS), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], University Medical Center Göttingen (UMG), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Interférométrie, In situ et Instrumentation pour la Microscopie Electronique (CEMES-I3EM), Centre d'élaboration de matériaux et d'études structurales (CEMES), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Hôpital Foch [Suresnes], Institut de Ciencies del Cosmos (ICCUB), Universitat de Barcelona (UB), Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Environnement, Bioénergie, Microalgues et Plantes (EBMP), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Département de Neuroradiologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Lille, University hospital of Zurich [Zurich], Fondation Ophtalmologique Adolphe de Rothschild [Paris], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toronto Western Hospital, Frankfurt University Hospital, University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Case Western Reserve University [Cleveland], Alfried Krupp Krankenhaus [Essen], Geneva University Hospitals and Geneva University, Institute of Medical Informatics, Biometrics and Epidemiology [ Essen, Germany] (IMIBE), University Hospital Basel [Basel], University of Basel (Unibas), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), University of California (UC), SWIFT DIRECT Collaborators: Angelika Alonso, Caroline Arquizan, Xavier Barreau, Rémy Beaujeux, Daniel Behme, Tobias Boeckh-Behrens, Christian Boehme, Martí Boix, Grégoire Boulouis, Nicolas Bricout, Nicolas Broc, Carlo W Cereda, Emmanuel Chabert, Tae-Hee Cho, Alessandro Cianfoni, Vincent Costalat, Christian Denier, Frederico Di Maria, Richard du Mesnil de Rochemont, Patricia Fearon, Anna Ferrier, Sebastian Fischer, Maxime Gauberti, Marie Gaudron, Laetitia Gimenez, Christoph Globas, Michael Görtler, Mayank Goyal, Ruediger Hilker-Roggendorf, Michael D Hill, Vi Tuan Hua, Lisa Humbertjean, Olav Jansen, Simon Jung, Georg Kägi, Michael E Kelly, Ilka Kleffner, Michael Knoflach, Krassen Nedeltchev, Lars Udo Krause, Kimmo Lappalainen, Margaux Lefebvre, Joe Leyon, Liang Liao, Jean-Sebastien Liegey, Christian Loehr, Patrik Michel, Stefania Nannoni, Patrick Nicholson, Lorena Nico, Michael Obadia, Julien Ognard, Ayokunle Ogungbemi, Jean-Marc Olivot, Simon Escalard, Marco Pasi, Lissa Peeling, Jane Perez, Martina Petersen, Eike Piechowiak, Roberto Raposo, Silja Räty, Sarah C Reitz, Sebastià Remollo, Luca Remonda, Ian Rennie, Manuel Requena, Alexander Riabikin, Roberto Riva, Aymeric Rouchaud, Andrea Rosi, Marta Rubiera, Laurent Spelle, Marlena Schnieder, Joanna D Schaafsma, Tilman Schubert, Jörg B Schulz, Mohammed Siddiqui, Sébastien Soize, Michael Sonnberger, Emmanuel Touze, Aude Triquenot, Guillaume Turc, Lucy Vieira, Wagih Ben Hassen, Judith N Wagner, Katrin Wasser, Johannes Weber, Holger Wenz, David Weisenburger-Lile, Fritz Wodarg, Valérie Wolff, Silke Wunderlich., Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), St George’s University Hospitals, Vall d'Hebron University Hospital [Barcelona], and CarMeN, laboratoire

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], General Medicine, 610 Medicine & health
Abstract

Background Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. Methods In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0.9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. Findings Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7 .3%, 95% CI -16.6 to 2.1, lower limit of one-sided 95% CI -15.1%, crossing the non-inferiority margin of - 12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy ( risk difference -1.0%, 95% CI -4.8 to 2 .7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [ 91%] of 201 vs 199 [96%] of 207, risk difference -5.1%, 95% CI -10.2 to 0. 0, p=0.047). Interpretation Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

Published
2022

26. Oral disease modifying therapies - A game changer for treatment decision in untreated patients with RRMS and CIS? - A swiss single center cross-sectional study

Author

Sebastian Finkener, Lutz Achtnichts, Michaela Cervenakova, Krassen Nedeltchev, and Oliver Findling

Subjects
Neurology, Neurology (clinical), General Medicine, 610 Medicine & health
Abstract

Several disease-modifying therapies (DMTs) show efficacy in relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS). However, there is still a relevant proportion of patients who remain untreated. We provide real-world data on untreated and treated patients and we report whether and how the introduction of oral DMTs changed the treatment decision. Furthermore, we discuss possible reasons for not receiving DMTs.We conducted a retrospective cross-sectional study and analysed demographic and clinical data of patients with RRMS and CIS at our MS center. Comparison was made between untreated and treated patients in 2010 (before the introduction of oral DMTs) and in 2014 (after the introduction of oral DMTs). Furthermore, we analysed reasons for the decision against DMTs in patients who never received DMTs and patients who discontinued DMTs.We analysed datasets of 344 MS patients in 2010 and 253 in 2014. There were more untreated patients in CIS than in RRMS. In RRMS, the proportion of untreated patients decreased significantly between 2010 and 2014 from 23.6% to 11.1%, while the use of oral medications increased significantly from1% to more than 50% in 2014. In CIS, there was no significant change in untreated patients between 2010 and 2014 (61.1% in 2010 to 52.6% in 2014). Untreated patients with RRMS were significantly older and had lower ARR than treated patients. Patients who never received DMT had lower EDSS compared to patients that had been treated before. The main reasons for the decision against DMT were "belief in a benign course" and "fear of adverse effects". Treatment discontinuation was caused mainly by the adverse effects.In our data a relevant proportion of patients with RRMS and CIS did not receive any DMT. We hypothesize that in patients with RRMS the introduction of oral DMTs translated to a higher rate of treatment, whereas in CIS there no change was observed. This could be due to limited therapeutic options in CIS. There is more information needed regarding the treatment recommendation for older patients and patients with mild course of the disease.

Published
2022

27. Early versus Late initiation of direct oral Anticoagulants in post-ischaemic stroke patients with atrial fibrillatioN (ELAN): Protocol for an international, multicentre, randomised-controlled, two-arm, open, assessor-blinded trial

Author

Urs Fischer, Sven Trelle, Mattia Branca, Georgia Salanti, Maurizio Paciaroni, Cecilia Ferrari, Stefanie Abend, Seraina Beyeler, Daniel Strbian, Götz Thomalla, George Ntaios, Leo H Bonati, Patrik Michel, Krassen Nedeltchev, Thomas Gattringer, Else Charlotte Sandset, Peter Kelly, Robin Lemmens, Masatoshi Koga, Padmavathy N Sylaja, Diana Aguiar de Sousa, Natan M Bornstein, Zuzana Gdovinova, David J Seiffge, Jan Gralla, Thomas Horvath, Jesse Dawson, Neurologian yksikkö, HUS Neurocenter, and University of Helsinki

Subjects
HSJ NEU, Doac, 3112 Neurosciences, Atrial fibrillation, THERAPY, GUIDE, 3124 Neurology and psychiatry, Acute Ischaemic Stroke, Anticoagulation, Study Protocol, Acute ischaemic stroke, 3121 General medicine, internal medicine and other clinical medicine, Atrial Fibrillation, timing, Neurology (clinical), Timing, ACUTE ISCHEMIC-STROKE, Cardiology and Cardiovascular Medicine, 610 Medicine & health, 360 Social problems & social services
Abstract

Rationale: Direct oral anticoagulants (DOAC) are highly effective in preventing ischaemic strokes in people with atrial fibrillation (AF). However, it is unclear how soon they should be started after acute ischaemic stroke (AIS). Early initiation may reduce early risk of recurrence but might increase the risk of haemorrhagic complications. Aim: To estimate the safety and efficacy of early initiation of DOACs compared to late guideline-based initiation in people with AIS related to AF. Methods and design: An international, multicentre, randomised (1:1) controlled, two-arm, open, assessor-blinded trial is being conducted. Early treatment is defined as DOAC initiation within 48 h of a minor or moderate stroke, or at day 6–7 following major stroke. Late treatment is defined as DOAC initiation after day 3–4 following minor stroke, after day 6–7 following moderate stroke and after day 12–14 following major stroke. Severity of stroke is defined according to imaging assessment of infarct size. Sample size: ELAN will randomise 2000 participants 1:1 to early versus late initiation of DOACs. This assumes a risk difference of 0.5% favouring the early arm, allowing an upper limit of the 95% confidence interval up to 1.5% based on the Miettinen & Nurminen formula. Outcomes: The primary outcome is a composite of symptomatic intracranial haemorrhage, major extracranial bleeding, recurrent ischaemic stroke, systemic embolism or vascular death at 30 ± 3 days after randomisation. Secondary outcomes include the individual components of the primary outcome at 30 ± 3 and 90 ± 7 days and functional status at 90 ± 7 days. Discussion: ELAN will estimate whether there is a clinically important difference in safety and efficacy outcomes following early anticoagulation with a DOAC compared to late guideline-based treatment in neuroimaging-selected people with an AIS due to AF.

Published
2022

28. Ischaemic stroke despite antiplatelet therapy: Causes and outcomes

Author

Norbert Silimon, Boudewijn Drop, Leander Clénin, Krassen Nedeltchev, Timo Kahles, Alexander A Tarnutzer, Mira Katan, Leo Bonati, Stephan Salmen, Sylvan Albert, Alexander Salerno, Emmanuel Carrera, Christian Berger, Nils Peters, Friedrich Medlin, Carlo Cereda, Manuel Bolognese, Georg Kägi, Susanne Renaud, Julien Niederhauser, Christophe Bonvin, Michael Schärer, Marie-Luise Mono, Andreas Luft, Biljana Rodic-Tatic, Urs Fischer, Simon Jung, Marcel Arnold, Thomas Meinel, and David Seiffge

Subjects
Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

Background: Ischaemic stroke may occur despite antiplatelet therapy (APT). We aimed to investigate frequency, potential causes and outcomes in patients with ischaemic stroke despite APT. Methods: In this cohort study, we enrolled patients with imaging-confirmed ischaemic stroke from the Swiss Stroke Registry (01/2014-07/2022). We determined the frequency of prior APT, assessed stroke aetiology (modified TOAST classification) and determined the association of prior APT with unfavourable functional outcome (modified Rankin Scale score 3–6) and recurrent ischaemic stroke at 3 months using regression models. Results: Among 53,352 patients, 27,484 (51.5%) had no prior antithrombotic treatment, 17,760 (33.3%) were on APT, 7039 (13.2%) on anticoagulation and 1069 (2.0%) were on APT + anticoagulation. In patients with a history of ischaemic stroke/TIA ( n = 11,948; 22.4%), 2401 (20.1%) had no prior antithrombotic therapy, 6594 (55.2%) were on APT, 2489 (20.8%) on anticoagulation and 464 (3.9%) on APT + anticoagulation. Amongst patients with ischaemic stroke despite APT, aetiology was large artery atherosclerosis in 19.8% ( n = 3416), cardiac embolism in 23.6% ( n = 4059), small vessel disease in 11.7% ( n = 2011), other causes in 7.4% ( n = 1267), more than one cause in 6.3% ( n = 1078) and unknown cause in 31.3% ( n = 5388). Prior APT was not independently associated with unfavourable outcome (aOR = 1.06; 95% CI: 0.98–1.14; p = 0.135) or death (aOR = 1.10; 95% CI: 0.99–1.21; p = 0.059) at 3-months but with increased odds of recurrent stroke (6.0% vs 4.3%; aOR 1.26; 95% CI: 1.11–1.44; p Conclusions: One-third of ischaemic strokes occurred despite APT and 20% of patients with a history of ischaemic stroke had no antithrombotic therapy when having stroke recurrence. Aetiology of breakthrough strokes despite APT is heterogeneous and these patients are at increased risk of recurrent stroke.

Published
2023

29. Endovascular Treatment for Acute Ischemic Stroke With or Without General Anesthesia: A Matched Comparison

Author

Benjamin Wagner, Johannes Lorscheider, Andrea Wiencierz, Kristine Blackham, Marios Psychogios, Daniel Bolliger, Gian Marco De Marchis, Stefan T. Engelter, Philippe Lyrer, Patrick R. Wright, Urs Fischer, Pasquale Mordasini, Stefania Nannoni, Francesco Puccinelli, Timo Kahles, Giovanni Bianco, Emmanuel Carrera, Andreas R. Luft, Carlo W. Cereda, Georg Kägi, Johannes Weber, Krassen Nedeltchev, Patrik Michel, Jan Gralla, Marcel Arnold, Leo H. Bonati, Javier Anon, Sandra Clarke, Michael Diepers, Philipp Gruber, Eileen Martin, Luca Remonda, Andreas Schweikert, Vedrana Zupa., Valerian Altersberger, Alex Brehm, Tolga Dittrich, Amgad El Mekabaty, Joachim Fladt, Urs Fisch, Henrik Gensicke, Lisa Hert, Sabrina Manuzzi, Marina Maurer, Louisa Meya, Nils Peters, Alexandros Polymeris, Sebastian Thilemann, Christopher Traenka, Ioannes Tsogkas, Anaelle Zietz, Martina Goeldlin, Mirjam Heldner, Simon Jung, Johannes Kaesmacher, Basel Mamaari, Thomas Meinel, Madlaine Mueller, Hakan Sarykaya, David Seiffge, Bernhard Siepen, Jan Vynkier, Ashraf Eskandari, Vasiliki Pantazou, Davide Strambo, Jane Frangi, Shairin Sihabdeen, Jochen Vehoff, Mira Katan, Achim Mueller, and Susanne Wegener

Subjects
Advanced and Specialized Nursing, Stroke, Treatment Outcome, Endovascular Procedures, Humans, Neurology (clinical), Anesthesia, General, Cardiology and Cardiovascular Medicine, Intracranial Hemorrhages, United States, Brain Ischemia, Ischemic Stroke
Abstract

Background: Endovascular treatment in large artery occlusion stroke reduces disability. However, the impact of anesthesia type on clinical outcomes remains uncertain. Methods: We compared consecutive patients in the Swiss Stroke Registry with anterior circulation stroke receiving endovascular treatment with or without general anesthesia (GA). The primary outcome was disability on the modified Rankin Scale after 3 months, analyzed with ordered logistic regression. Secondary outcomes included dependency or death (modified Rankin Scale score ≥ 3), National Institutes of Health Stroke Scale after 24 hours, symptomatic intracranial hemorrhage with ≥ 4 points worsening on National Institutes of Health Stroke Scale within 7 days, and mortality. Coarsened exact matching and propensity score matching were performed to adjust for indication bias. Results: One thousand two hundred eighty-four patients (GA: n=851, non-GA: n=433) from 8 Stroke Centers were included. Patients treated with GA had higher modified Rankin Scale scores after 3 months than patients treated without GA, in the unmatched (odds ratio [OR], 1.75 [1.42–2.16]; P P =0.020), and the propensity score matching analysis (n=568; OR, 1.61 [1.20–2.15]; P =0.001). In the coarsened exact matching analysis, there were no significant differences in National Institutes of Health Stroke Scale after 1 day (estimated coefficient 2.61 [0.59–4.64]), symptomatic intracranial hemorrhage (OR, 1.06 [0.30–3.75]), dependency or death (OR, 1.42 [0.91–2.23]), or mortality (OR, 1.65 [0.94–2.89]). In the propensity score matching analysis, National Institutes of Health Stroke Scale after 24 hours (estimated coefficient, 3.40 [1.76–5.04]), dependency or death (OR, 1.49 [1.07–2.07]), and mortality (OR, 1.65 [1.11–2.45]) were higher in the GA group, whereas symptomatic intracranial hemorrhage did not differ significantly (OR, 1.77 [0.73–4.29]). Conclusions: This large study showed worse functional outcome after endovascular treatment of anterior circulation stroke with GA than without GA in a real-world setting. This finding appears to be independent of known differences in patient characteristics between groups.

Published
2022

30. Ischemic stroke in COVID-19 patients: Mechanisms, treatment, and outcomes in a consecutive Swiss Stroke Registry analysis

Author

Ludwig Schelosky, Valerian L Altersberger, Nils Peters, Christophe Bonvin, Marcel Arnold, Marie-Luise Mono, Stefan T. Engelter, Lehel-Barna Lakatos, Shadi Taheri, Georg Kägi, Giovanni Bianco, Santi Galletta, Andrea von Reding, Carlo W. Cereda, Emmanuel Carrera, Davide Strambo, Manuel Bolognese, Krassen Nedeltchev, Guido Schwegler, Alexander A. Tarnutzer, Florian Lindheimer, Morin Beyeler, Christian Berger, Urs Fischer, Andreas R. Luft, Rolf Sturzenegger, Biljana Rodic, Federico Massini, Gian Marco De Marchis, Leo H. Bonati, Markus Baumgärtner, Patrik Michel, Albert Sylvan, Friedrich Medlin, Pamela N Correia, Timo Kahles, Stephan Salmen, and Swiss Stroke Registry Investigators

Subjects
medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, 610 Medicine & health, Revascularization, Asymptomatic, COVID-19, Humans, Ischemic Stroke, Registries, SARS-CoV-2, Stroke/epidemiology, Stroke/therapy, Switzerland/epidemiology, Treatment Outcome, ischemic stroke, Internal medicine, medicine, Stroke, business.industry, medicine.disease, Neurology, Radiological weapon, Concomitant, Propensity score matching, Etiology, Neurology (clinical), medicine.symptom, business, 610 Medizin und Gesundheit, Switzerland
Abstract

Most case series of patients with ischemic stroke (IS) and COVID-19 are limited to selected centers or lack 3-month outcomes. The aim of this study was to describe the frequency, clinical and radiological features, and 3-month outcomes of patients with IS and COVID-19 in a nationwide stroke registry. From the Swiss Stroke Registry (SSR), we included all consecutive IS patients ≥18 years admitted to Swiss Stroke Centers or Stroke Units during the first wave of COVID-19 (25 February to 8 June 2020). We compared baseline features, etiology, and 3-month outcome of SARS-CoV-2 polymerase chain reaction-positive (PCR+) IS patients to SARS-CoV-2 PCR- and/or asymptomatic non-tested IS patients. Of the 2341 IS patients registered in the SSR during the study period, 36 (1.5%) had confirmed COVID-19 infection, of which 33 were within 1 month before or after stroke onset. In multivariate analysis, COVID+ patients had more lesions in multiple vascular territories (OR 2.35, 95% CI 1.08-5.14, p = 0.032) and fewer cryptogenic strokes (OR 0.37, 95% CI 0.14-0.99, p = 0.049). COVID-19 was judged the likely principal cause of stroke in 8 patients (24%), a contributing/triggering factor in 12 (36%), and likely not contributing to stroke in 13 patients (40%). There was a strong trend towards worse functional outcome in COVID+ patients after propensity score (PS) adjustment for age, stroke severity, and revascularization treatments (PS-adjusted common OR for shift towards higher modified Rankin Scale (mRS) = 1.85, 95% CI 0.96-3.58, p = 0.07). In this nationwide analysis of consecutive ischemic strokes, concomitant COVID-19 was relatively rare. COVID+ patients more often had multi-territory stroke and less often cryptogenic stroke, and their 3-month functional outcome tended to be worse.

Published
2022

31. Mechanical thrombectomy using the new Tigertriever in acute ischemic stroke patients – A Swiss prospective multicenter study

Author

Timo Kahles, Luca Remonda, Michael Diepers, Jatta Berberat, Alexander von Hessling, David S Liebeskind, Krassen Nedeltchev, Philipp Gruber, Johannes Weber, and Javier Anon

Subjects
Male, medicine.medical_specialty, business.industry, Middle Aged, medicine.disease, Stroke, Mechanical thrombectomy, Multicenter study, Internal medicine, medicine, Cardiology, Feasibility Studies, Humans, Female, Patient Safety, Prospective Studies, Registries, business, Acute ischemic stroke, Switzerland, Aged, Ischemic Stroke, Thrombectomy, Large vessel occlusion
Abstract

Purpose Tigertriever is a novel operator-adjustable clot retriever designed to enhance the operator's options to control the interaction of retriever and clot. The aim of this study was to assess the feasibility, safety and efficacy of the Tigertriever device system. Methods Prospective multi-center registry study at three comprehensive stroke centers in Switzerland from 2017 to 2019 of patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO) using Tigertriever as a first-line device. Results 30 AIS patients (median age 72.5 years (IQR 64–79), 50% women) with a median NIHSS on admission of 11 (IQR 6-13) and a median ASPECT score of 9 (IQR 7–10) were treated with the new Tigertriever and included in this study. The first-pass effect was 24% (n = 7). A good recanalization (eTICI 2 b/2c/3) was achieved in 94% of the cases. Median mRS at 90 days was 1 (IQR 1–2). Conclusion This study demonstrated feasibility, safety and effectiveness of the Tigertriever in AIS patients with LVO with a high reperfusion rate.

Published
2020

32. Abstract WP75: Sex Differences In The Outcomes Of Intravenous Thrombolysis In Acute Ischemic Stroke Patients With Preadmission Use Of Antiplatelet Agents: A Population-based Study In The Swiss Stroke Registry

Author

Roberta Noseda, Federico Rea, Alberto Pagnamenta, Giovanni Bianco, Shairin Sihabdeen, pamela agazzi, David Seiffge, Patrik Michel, Krassen Nedeltchev, Leo Bonati, Georg Kägi, Julien Niederhauser, Thomas Nyffeler, Andreas Luft, Ludwig Schelosky, Friedrich Medlin, Biljana Rodic, Nils Peters, Susanne Renaud, Marie-Luise Mono, Emmanuel Carrera, Urs Fischer, Professor Alessandro Ceschi, and Carlo W Cereda

Subjects
Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: This study aimed to evaluate whether patient sex modifies the association between preadmission use of antiplatelet agents (APAs) and safety and efficacy outcomes of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS). Methods: Cohort study from the Swiss Stroke Registry of consecutive patients with AIS treated with IVT stratified according to sex and assessed for preadmission use of APAs in multivariate logistic regression models. The primary safety outcome was in-hospital symptomatic intracerebral haemorrhage (sICH). The primary efficacy outcome was functional independence (FI) at 3 months after discharge. Secondary efficacy outcomes included favourable functional outcome (FFO), modified Rankin Scale score shift analysis, survival with high disability or death at 3 months. Results: Study cohort included 4996 patients, 2124 women (43%) and 2872 men (57%). Women were older than men (79 vs 71 years, P P =0.74). Preadmission use of dual APAs was associated with higher odds of in-hospital sICH (adjOR 2.89, 95%CI 1.15-7.29), with a statistically significant trend from single to dual APAs ( P =0.02). No interaction was found between preadmission use of either single or dual APAs and patient sex ( P =0.89 and P =0.21, respectively). Men had significantly higher chances of 3-month FI (adjOR 1.34, 95%CI 1.09-1.65), better outcomes across all levels of disability and mortality (adjOR 0.86, 95%CI 0.75-0.99). We found no sex differences in FFO and severe disability or death at 3 months after discharge (adjOR 1.15, 95%CI 0.96-1.36 and adjOR 1.11, 95%CI 0.79-1.55, respectively). We found no interaction between patient sex and preadmission use of either single or dual APAs for any of the secondary efficacy outcomes. Conclusions: Female sex was associated with more unfavourable 3-month efficacy outcomes than male sex after IVT. Even though preadmission use of dual APAs was associated with increased odds of in-hospital sICH, sex-gender differences in 3-month efficacy outcomes apparently were not explained by a sex-specific mechanism related to preadmission use of APAs.

Published
2022

33. F28 Novel mutations and findings in a cohort of McLeod neuroacanthocytosis, an X-linked HD phenocopy

Author

Ernst Walther, Andreas Hermann, Beat M. Frey, Carsten Buhmann, Stefan Evers, Franz Marxreiter, Krassen Nedeltchev, Federica Montagnese, Wolfgang Löscher, Peter Reilich, Hans H. Jung, Wolfgang von Kalckreuth, Beate Schlotter-Weigel, Armin Orth, Carsten Saft, Maja Patricia Mattle-Greminger, Adrian Danek, Beate Mayer, Manfred Hoenig, Zacharias Kohl, and Kevin Peikert

Subjects
Phenocopy, business.industry, Disease, medicine.disease, Bioinformatics, Genotype-phenotype distinction, Chronic granulomatous disease, Neuroacanthocytosis, Cohort, medicine, McLeod syndrome, medicine.symptom, business, Myopathy
Abstract

Background McLeod syndrome (MLS) is an ultra-rare neurodegenerative X-linked disease caused by mutations in the XK gene, classified as one of the core neuroacanthocytosis syndromes. Together with the clinically very similar chorea-acanthocytosis it belongs to the heterogeneous group of ‘Huntington’s disease (HD) phenocopies’. Aims To characterize a cohort of HD phenocopies with the genetically confirmed diagnosis of McLeod syndrome. Methods This is a retrospective and prospective analysis of genotype and phenotype of sixteen McLeod cases. Results We longitudinally characterized the second largest cohort known to date. We identified novel XK mutations as well as deletions that extend into the PRRG1 gene (novel) and describe two contiguous gene deletion cases of MLS with X-linked chronic granulomatous disease (deletion also effecting the CYBB gene). This study confirms core features of MLS such as late onset hyperkinetic movements in association with neuro/myopathy, neuropsychiatric impairment, cardiac involvement, hyperCKemia. Novel aspects in this MLS series seem obstructive sleep apnea and epileptic seizure onset in childhood. Conclusions Our study expands the limited knowledge on the variable course, the various clinical manifestations and the genetic spectrum of a hereditary HD phenocopy syndrome.

Published
2021

35. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Author

Alison Halliday, Richard Bulbulia, Leo H Bonati, Johanna Chester, Andrea Cradduck-Bamford, Richard Peto, Hongchao Pan, John Potter, Hans Henning Eckstein, Barbara Farrell, Marcus Flather, Averil Mansfield, Boby Mihaylova, Kazim Rahimi, David Simpson, Dafydd Thomas, Peter Sandercock, Richard Gray, Andrew Molyneux, Cliff P Shearman, Peter Rothwell, Anna Belli, Will Herrington, Parminder Judge, Peter Leopold, Marion Mafham, Michael Gough, Piergiorgio Cao, Sumaira MacDonald, Vasha Bari, Clive Berry, S Bradshaw, Wojciech Brudlo, Alison Clarke, Robin Cox, Susan Fathers, Kamran Gaba, Mo Gray, Elizabeth Hayter, Constance Holliday, Rijo Kurien, Michael Lay, Steffi le Conte, Jessica McManus, Zahra Madgwick, Dylan Morris, Andrew Munday, Sandra Pickworth, Wiktor Ostasz, Michiel Poorthuis, Sue Richards, Louisa Teixeira, Sergey Tochlin, Lynda Tully, Carol Wallis, Monique Willet, Alan Young, Renato Casana, Chiara Malloggi, Andrea Odero Jr, Vincenzo Silani, Gianfranco Parati, Giuseppe Malchiodi, Giovanni Malferrari, Francesco Strozzi, Nicola Tusini, Enrico Vecchiati, Gioacchino Coppi, Antonio Lauricella, Roberto Moratto, Roberto Silingardi, Jessica Veronesi, Andrea Zini, Emanuele Ferrero, Michelangelo Ferri, Andrea Gaggiano, Carmelo Labate, Franco Nessi, Daniele Psacharopulo, Andrea Viazzo, Giovanni Malacrida, Daniela Mazzaccaro, Giovanni Meola, Alfredo Modafferi, Giovanni Nano, Maria Teresa Occhiuto, Paolo Righini, Silvia Stegher, Stefano Chiarandini, Filippo Griselli, Sandro Lepidi, Fabio Pozzi Mucelli, Marcello Naccarato, Mario D'Oria, Barbara Ziani, Andrea Stella, Mortalla Dieng, Gianluca Faggioli, Mauro Gargiulo, Sergio Palermo, Rodolfo Pini, Giovanni Maria Puddu, Andrea Vacirca, Domenico Angiletta, Claudio Desantis, Davide Marinazzo, Giovanni Mastrangelo, Guido Regina, Raffaele Pulli, Paolo Bianchi, Lea Cireni, Elisabetta Coppi, Rocco Pizzirusso, Filippo Scalise, Giovanni Sorropago, Valerio Tolva, Valeria Caso, Enrico Cieri, Paola DeRango, Luca Farchioni, Giacomo Isernia, Massimo Lenti, Gian Battista Parlani, Guglielmo Pupo, Grazia Pula, Gioele Simonte, Fabio Verzini, Federico Carimati, Maria Luisa Delodovici, Federico Fontana, Gabriele Piffaretti, Matteo Tozzi, Efrem Civilini, Giorgio Poletto, Bernhard Reimers, Barbara Praquin, Sonia Ronchey, Laura Capoccia, Wassim Mansour, Enrico Sbarigia, Francesco Speziale, Pasqualino Sirignano, Danilo Toni, Roberto Galeotti, Vincenzo Gasbarro, Francesco Mascoli, Tiberio Rocca, Elpiniki Tsolaki, Giulia Bernardini, Ester DeMarco, Alessia Giaquinta, Francesco Patti, Massimiliano Veroux, Pierfrancesco Veroux, Carla Virgilio, Nicola Mangialardi, Matteo Orrico, Vincenzo Di Lazzaro, Nunzio Montelione, Francesco Spinelli, Francesco Stilo, Carlo Cernetti, Sandro Irsara, Giuseppe Maccarrone, Diego Tonello, Adriana Visonà, Beniamino Zalunardo, Emiliano Chisci, Stefano Michelagnoli, Nicola Troisi, Maela Masato, Massimo Dei Negri, Andrea Pacchioni, Salvatore Saccà, Giovanni Amatucci, Alfredo Cannizzaro, Federico Accrocca, Cesare Ambrogi, Renzo Barbazza, Giustino Marcucci, Andrea Siani, Guido Bajardi, Giovanni Savettieri, Angelo Argentieri, Riccardo Corbetta, Attilio Odero, Pietro Quaretti, Federico Z Thyrion, Alessandro Cappelli, Domenico Benevento, Gianmarco De Donato, Maria Agnese Mele, Giancarlo Palasciano, Daniela Pieragalli, Alessandro Rossi, Carlo Setacci, Francesco Setacci, Domenico Palombo, Maria Cecilia Perfumo, Edoardo Martelli, Aldo Paolucci, Santi Trimarchi, Viviana Grassi, Luigi Grimaldi, Giuliana La Rosa, Domenico Mirabella, Matteo Scialabba, Leonildo Sichel, Costantino L D'Angelo, Gian Franco Fadda, Holta Kasemi, Mario Marino, Francesco Burzotta, Francesco Alberto Codispoti, Angela Ferrante, Giovanni Tinelli, Yamume Tshomba, Claudio Vincenzoni, Deborah Amis, Dawn Anderson, Martin Catterson, Mike Clarke, Michelle Davis, Anand Dixit, Alexander Dyker, Gary Ford, Ralph Jackson, Sreevalsan Kappadath, David Lambert, Tim Lees, Stephen Louw, James McCaslin, Noala Parr, Rebecca Robson, Gerard Stansby, Lucy Wales, Vera Wealleans, Lesley Wilson, Michael Wyatt, Hardeep Baht, Ibrahim Balogun, Ilse Burger, Tracy Cosier, Linda Cowie, Gunaratnam Gunathilagan, David Hargroves, Robert Insall, Sally Jones, Hannah Rudenko, Natasha Schumacher, Jawaharlal Senaratne, George Thomas, Audrey Thomson, Tom Webb, Ellen Brown, Bernard Esisi, Ali Mehrzad, Shane MacSweeney, Norman McConachie, Alison Southam, Wayne Sunman, Ahmed Abdul-Hamiq, Jenny Bryce, Ian Chetter, Duncan Ettles, Raghuram Lakshminarayan, Kim Mitchelson, Christopher Rhymes, Graham Robinson, Paul Scott, Alison Vickers, Ray Ashleigh, Stephen Butterfield, Ed Gamble, Jonathan Ghosh, Charles N McCollum, Mark Welch, Sarah Welsh, Leszek Wolowczyk, Mary Donnelly, Stephen D'Souza, Anselm A Egun, Bindu Gregary, Thomas Joseph, Christine Kelly, Shuja Punekar, M Asad Rahi, Sonia Raj, Dare Seriki, George Thomson, James Brown, Ragunath Durairajan, Iris Grunwald, Paul Guyler, Paula Harman, Matthew Jakeways, Christopher Khuoge, Ashish Kundu, Thayalini Loganathan, Nisha Menon, Raji O Prabakaran, Devesh Sinha, Vicky Thompson, Sharon Tysoe, Dennis Briley, Chris Darby, Linda Hands, Dominic Howard, Wilhelm Kuker, Ursula Schulz, Rachel Teal, David Barer, Andrew Brown, Susan Crawford, Paul Dunlop, Ramesh Krishnamurthy, Nikhil Majmudar, Duncan Mitchell, Min P Myint, Richard O'Brien, Janice O'Connell, Naweed Sattar, Shanmugam Vetrivel, Jonathan Beard, Trevor Cleveland, Peter Gaines, John Humphreys, Alison Jenkins, Craig King, Daniel Kusuma, Ralph Lindert, Robbie Lonsdale, Raj Nair, Shah Nawaz, Faith Okhuoya, Douglas Turner, Graham Venables, Paul Dorman, Andrea Hughes, Deborah Jones, David Mendelow, Helen Rodgers, Aidas Raudoniitis, Peter Enevoldson, Hans Nahser, Imelda O'Brien, Francesco Torella, Dave Watling, Richard White, Pauline Brown, Dipankar Dutta, Lorraine Emerson, Paula Hilltout, Sachin Kulkarni, Jackie Morrison, Keith Poskitt, Fiona Slim, Sarah Smith, Amanda Tyler, Joanne Waldron, Mark Whyman, Milda Bajoriene, Lucy Baker, Amanda Colston, Bekky Eliot-Jones, Gita Gramizadeh, Catherine Lewis-Clarke, Laura McCafferty, Deborah Oliver, Debbie Palmer, Abhijeet Patil, Suzannah Pegler, Gopi Ramadurai, Aisling Roberts, Tracey Sargent, Shivaprasad Siddegowda, Ravi Singh-Ranger, Akintunde Williams, Lucy Williams, Steve Windebank, Tadas Zuromskis, Lanka Alwis, Jane Angus, Asaipillai Asokanathan, Caroline Fornolles, Diana Hardy, Sophy Hunte, Frances Justin, Duke Phiri, Marie Mitabouana-Kibou, Lakshmanan Sekaran, Sakthivel Sethuraman, Margaret L Tate, Joyce Akyea-Mensah, Stephen Ball, Angela Chrisopoulou, Elizabeth Keene, Alison Phair, Steven Rogers, John V Smyth, Colin Bicknell, Jeremy Chataway, Nicholas Cheshire, Andrew Clifton, Caroline Eley, Richard Gibbs, Mohammad Hamady, Beth Hazel, Alex James, Michael Jenkins, Nyma Khanom, Austin Lacey, Maz Mireskandari, Joanna O'Reilly, Antony Pereira, Tina Sachs, John Wolfe, Philip Davey, Gill Rogers, Gemma Smith, Gareth Tervit, Ian Nichol, Andrew Parry, Gavin Young, Simon Ashley, James Barwell, Francis Dix, Azlisham M Nor, Chris Parry, Angela Birt, Paul Davies, Jim George, Anne Graham, Leon Jonker, Nicci Kelsall, Caroline Potts, Toni Wilson, Jamie Crinnion, Larissa Cuenoud, Nikola Aleksic, Srdan Babic, Nenad Ilijevski, Đorde Radak, Dragan Sagic, Slobodan Tanaskovic, Momcilo Colic, Vladimir Cvetic, Lazar Davidovic, Dejana R Jovanovic, Igor Koncar, Perica Mutavdžic, Miloš Sladojevic, Ivan Tomic, Eike S Debus, Ulrich Grzyska, Dagmar Otto, Götz Thomalla, Jessica Barlinn, Johannes Gerber, Kathrin Haase, Christian Hartmann, Stefan Ludwig, Volker Pütz, Christian Reeps, Christine Schmidt, Norbert Weiss, Sebastian Werth, Simon Winzer, Janine Gemper, Albrecht Günther, Bianka Heiling, Elisabeth Jochmann, Panagiota Karvouniari, Carsten Klingner, Thomas Mayer, Julia Schubert, Friederike Schulze-Hartung, Jürgen Zanow, Yvonne Bausback, Franka Borger, Spiridon Botsios, Daniela Branzan, Sven Bräunlich, Henryk Hölzer, Janin Lenzer, Christopher Piorkowski, Nadine Richter, Johannes Schuster, Dierk Scheinert, Andrej Schmidt, Holger Staab, Matthias Ulrich, Martin Werner, Hermann Berger, Gábor Biró, Hans-Henning Eckstein, Michael Kallmayer, Kornelia Kreiser, Alexander Zimmermann, Bärbel Berekoven, Klaus Frerker, Vera Gordon, Giovanni Torsello, Sebastian Arnold, Cora Dienel, Martin Storck, Bernhard Biermaier, Hans Martin Gissler, Christof Klötzsch, Tomas Pfeiffer, Ralph Schneider, Leander Söhl, Michael Wennrich, Angelika Alonso, Michael Keese, Christoph Groden, Andreas Cöster, Andreas Engelhardt, Christoph-Maria Ratusinski, Bengt Berg, Martin Delle, Johan Formgren, Peter Gillgren, Lotta Jarl, Torbjörn B Kall, Peter Konrad, Niklas Nyman, Claes Skiöldebrand, Johnny Steuer, Rabbe Takolander, Jonas Malmstedt, Stefan Acosta, Katarina Björses, Kerstin Brandt, Nuno Dias, Anders Gottsäter, Jan Holst, Thorarinn Kristmundsson, Tobias Kühme, Tilo Kölbel, Bengt Lindblad, Mats Lindh, Martin Malina, Tomas Ohrlander, Tim Resch, Viola Rönnle, Björn Sonesson, Margareta Warvsten, Zbigniew Zdanowski, Erik Campbell, Per Kjellin, Hans Lindgren, Johan Nyberg, Björn Petersen, Gunnar Plate, Håkan Pärsson, Peter Qvarfordt, Pavel Ignatenko, Andrey Karpenko, Vladimir Starodubtsev, Mikhail A Chernyavsky, Maria S Golovkova, Boris B Komakha, Nikolay N Zherdev, Andrey Belyasnik, Pavel Chechulov, Dmitry Kandyba, Igor Stepanishchev, Csaba Csobay-Novák, Edit Dósa, László Entz, Balázs Nemes, Zoltán Szeberin, Pál Barzó, Mihaly Bodosi, Eniko Fákó, Béla Fülöp, Tamás Németh, Szilárd Pazdernyik, Krisztina Skoba, Erika Vörös, Eleni Chatzinikou, Athanasios Giannoukas, Christos Karathanos, Stylianos Koutsias, Georgios Kouvelos, Miltiadis Matsagkas, Styliani Ralli, Christos Rountas, Nikolaos Rousas, Konstantinos Spanos, Elias Brountzos, John D Kakisis, Andreas Lazaris, Konstantinos G Moulakakis, Leonidas Stefanis, Georgios Tsivgoulis, Spyros Vasdekis, Constantine N Antonopoulos, Ion Bellenis, Dimitrios Maras, Antonios Polydorou, Victoria Polydorou, Antonios Tavernarakis, Nikolaos Ioannou, Maria Terzoudi, Miltos Lazarides, Michalis Mantatzis, Kostas Vadikolias, Lukasz Dzieciuchowicz, Marcin Gabriel, Zbigniew Krasinski, Grzegorz Oszkinis, Fryderyk Pukacki, Maciej Slowinski, Michal-Goran Stanišic, Ryszard Staniszewski, Jolanta Tomczak, Maciej Zielinski, Piotr Myrcha, Dorota Rózanski, Stanislaw Drelichowski, Wojciech Iwanowski, Katarzyna Koncewicz, Pawel Bialek, Zbigniew Biejat, Wojciech Czepel, Anna Czlonkowska, Anatol Dowzenko, Julia Jedrzejewska, Adam Kobayashi, Jerzy Leszczynski, Andrzej Malek, Jerzy Polanski, Robert Proczka, Maciej Skorski, Mieczyslaw Szostek, Piotr Andziak, Maciej Dratwicki, Robert Gil, Miroslaw Nowicki, Jaroslaw Pniewski, Jaroslaw Rzezak, Piotr Seweryniak, Pawel Dabek, Michal Juszynski, Grzegorz Madycki, Bartosz Pacewski, Witold Raciborski, Piotr Slowinski, Walerian Staszkiewicz, Martin Bombic, Vladimír Chlouba, Jirí Fiedler, Karel Hes, Petr Koštál, Jindrich Sova, Zdenek Kríž, Mojmír Prívara, Michal Reif, Robert Staffa, Robert Vlachovský, Bohuslav Vojtíšek, Tomáš Hrbác, Martin Kuliha, Václav Procházka, Martin Roubec, David Školoudík, David Netuka, Anna Šteklácová, Vladimír Beneš III, Pavel Buchvald, Ladislav Endrych, Miroslav Šercl, Walter Campos Jr, Ivan B Casella, Nelson de Luccia, André E V Estenssoro, Calógero Presti, Pedro Puech-Leão, Celso R B Neves, Erasmo S da Silva, Cid J Sitrângulo Jr, José A T Monteiro, Gisela Tinone, Marcelo Bellini Dalio, Edwaldo E Joviliano, Octávio M Pontes Neto, Mauricio Serra Ribeiro, Patrick Cras, Jeroen M H Hendriks, Mieke Hoppenbrouwers, Patrick Lauwers, Caroline Loos, Laetitia Yperzeele, Mia Geenens, Dimitri Hemelsoet, Isabelle van Herzeele, Frank Vermassen, Parla Astarci, Frank Hammer, Valérie Lacroix, André Peeters, Robert Verhelst, Silvana Cirelli, Pol Dormal, Annelies Grimonprez, Bart Lambrecht, Philipe Lerut, Eddy Thues, Guy De Koster, Quentin Desiron, Alain Maertens de Noordhout, Danielle Malmendier, Mireille Massoz, Georges Saad, Marc Bosiers, Joren Callaert, Koen Deloose, Estrella Blanco Cañibano, Beatriz García Fresnillo, Mercedes Guerra Requena, Pilar C Morata Barrado, Miguel Muela Méndez, Antonio Yusta Izquierdo, Fernando Aparici Robles, Paula Blanes Orti, Luis García Dominguez, Rafael Martínez López, Manuel Miralles Hernández, José I Tembl Ferrairo, Ángel Chamorro, Juan Macho, Víctor Obach, Vincent Riambau, Luis San Román, Frank J Ahlhelm, Kristine Blackham, Stefan Engelter, Thomas Eugster, Henrik Gensicke, Lorenz Gürke, Philippe Lyrer, Luigi Mariani, Marina Maurer, Edin Mujagic, Mandy Müller, Marios Psychogios, Peter Stierli, Christoph Stippich, Christopher Traenka, Thomas Wolff, Benjamin Wagner, Martina M Wiegert, Sandra Clarke, Michael Diepers, Ernst Gröchenig, Philipp Gruber, Andrej Isaak, Timo Kahles, Regula Marti, Krassen Nedeltchev, Luca Remonda, Nadir Tissira, Martina Valença Falcão, Gert J de Borst, Rob H Lo, Frans L Moll, Raechel Toorop, Bart H van der Worp, Evert J Vonken, Jaap L Kappelle, Ommid Jahrome, Floris Vos, Wouter Schuiling, Hendrik van Overhagen, Rudolf W M Keunen, Bob Knippenberg, Jan J Wever, Jan W Lardenoije, Michel Reijnen, Luuk Smeets, Steven van Sterkenburg, Gustav Fraedrich, Elke Gizewski, Ingrid Gruber, Michael Knoflach, Stefan Kiechl, Barbara Rantner, Timur Abdulamit, Patrice Bergeron, Raymond Padovani, Jean-Christophe Trastour, Jean-Marie Cardon, Anne Le Gallou-Wittenberg, Eric Allaire, Jean-Pierre Becquemin, Frédéric Cochennec-Paliwoda, Pascal Desgranges, Hassan Hosseini, Hicham Kobeiter, Jean Marzelle, Mohammed A Almekhlafi, Simerpreet Bal, Phillip A Barber, Shelagh B Coutts, Andrew M Demchuk, Muneer Eesa, Michelle Gillies, Mayank Goyal, Michael D Hill, Mark E Hudon, Anitha Jambula, Carol Kenney, Gary Klein, Marie McClelland, Alim Mitha, Bijoy K Menon, William F Morrish, Steven Peters, Karla J Ryckborst, Greg Samis, Supriya Save, Eric E Smith, Peter Stys, Suresh Subramaniam, Garnette R Sutherland, Tim Watson, John H Wong, L Zimmel, Vojko Flis, Jože Matela, Kazimir Miksic, Franko Milotic, Božidar Mrdja, Barbara Stirn, Erih Tetickovic, Mladen Gasparini, Anton Grad, Ingrid Kompara, Zoren Miloševic, Veronika Palmiste, Toomas Toomsoo, Balzhan Aidashova, Nursultan Kospanov, Roman Lyssenko, Daulet Mussagaliev, Rafi Beyar, Aaron Hoffman, Tony Karram, Arthur Kerner, Eugenia Nikolsky, Samy Nitecki, Silva Andonova, Chavdar Bachvarov, Vesko Petrov, Ivan Cvjetko, Vinko Vidjak, Damir Halužan, Mladen Petrunic, Bao Liu, Chang-Wei Liu, Daniel Bartko, Peter Beno, František Rusnák, Kamil Zelenák, Masayuki Ezura, Takashi Inoue, Naoto Kimura, Ryushi Kondo, Yasushi Matsumoto, Hiroaki Shimizu, Hidenori Endo, Eisuke Furui, Søren Bakke, Kristen Krohg-Sørensen, Terje Nome, Mona Skjelland, Bjørn Tennøe, João Albuquerque e Castro, Gonçalo Alves, Frederico Bastos Gonçalves, José de Aragão Morais, Ana C Garcia, Hugo Valentim, Leonor Vasconcelos, Fernando Belcastro, Fernando Cura, Patricio Zaefferer, Foad Abd-Allah, Mohamed H Eldessoki, Hussein Heshmat Kassem, Haytham Soliman Gharieb, Mary P Colgan, Syed N Haider, Joe Harbison, Prakash Madhavan, Dermot Moore, Gregor Shanik, Viviane Kazan, Munier Nazzal, Vicki Ramsey-Williams, ACST-2 Collaborative Group, Group, ACST-2 Collaborative, Halliday A., Bulbulia R., Bonati L.H., Chester J., Cradduck-Bamford A., Peto R., Pan H., Potter J., Henning Eckstein H., Farrell B., Flather M., Mansfield A., Mihaylova B., Rahimi K., Simpson D., Thomas D., Sandercock P., Gray R., Molyneux A., Shearman C.P., Rothwell P., Belli A., Herrington W., Judge P., Leopold P., Mafham M., Gough M., Cao P., MacDonald S., Bari V., Berry C., Bradshaw S., Brudlo W., Clarke A., Cox R., Fathers S., Gaba K., Gray M., Hayter E., Holliday C., Kurien R., Lay M., le Conte S., McManus J., Madgwick Z., Morris D., Munday A., Pickworth S., Ostasz W., Poorthuis M., Richards S., Teixeira L., Tochlin S., Tully L., Wallis C., Willet M., Young A., Casana R., Malloggi C., Odero A., Silani V., Parati G., Malchiodi G., Malferrari G., Strozzi F., Tusini N., Vecchiati E., Coppi G., Lauricella A., Moratto R., Silingardi R., Veronesi J., Zini A., Ferrero E., Ferri M., Gaggiano A., Labate C., Nessi F., Psacharopulo D., Viazzo A., Malacrida G., Mazzaccaro D., Meola G., Modafferi A., Nano G., Occhiuto M.T., Righini P., Stegher S., Chiarandini S., Griselli F., Lepidi S., Pozzi Mucelli F., Naccarato M., D'Oria M., Ziani B., Stella A., Dieng M., Faggioli G., Gargiulo M., Palermo S., Pini R., Puddu G.M., Vacirca A., Angiletta D., Desantis C., Marinazzo D., Mastrangelo G., Regina G., Pulli R., Bianchi P., Cireni L., Coppi E., Pizzirusso R., Scalise F., Sorropago G., Tolva V., Caso V., Cieri E., DeRango P., Farchioni L., Isernia G., Lenti M., Parlani G.B., Pupo G., Pula G., Simonte G., Verzini F., Carimati F., Delodovici M.L., Fontana F., Piffaretti G., Tozzi M., Civilini E., Poletto G., Reimers B., Praquin B., Ronchey S., Capoccia L., Mansour W., Sbarigia E., Speziale F., Sirignano P., Toni D., Galeotti R., Gasbarro V., Mascoli F., Rocca T., Tsolaki E., Bernardini G., DeMarco E., Giaquinta A., Patti F., Veroux M., Veroux P., Virgilio C., Mangialardi N., Orrico M., Di Lazzaro V., Montelione N., Spinelli F., Stilo F., Cernetti C., Irsara S., Maccarrone G., Tonello D., Visona A., Zalunardo B., Chisci E., Michelagnoli S., Troisi N., Masato M., Dei Negri M., Pacchioni A., Sacca S., Amatucci G., Cannizzaro A., Accrocca F., Ambrogi C., Barbazza R., Marcucci G., Siani A., Bajardi G., Savettieri G., Argentieri A., Corbetta R., Quaretti P., Thyrion F.Z., Cappelli A., Benevento D., De Donato G., Mele M.A., Palasciano G., Pieragalli D., Rossi A., Setacci C., Setacci F., Palombo D., Perfumo M.C., Martelli E., Paolucci A., Trimarchi S., Grassi V., Grimaldi L., La Rosa G., Mirabella D., Scialabba M., Sichel L., D'Angelo C.L., Fadda G.F., Kasemi H., Marino M., Burzotta F., Codispoti F.A., Ferrante A., Tinelli G., Tshomba Y., Vincenzoni C., Amis D., Anderson D., Catterson M., Clarke M., Davis M., Dixit A., Dyker A., Ford G., Jackson R., Kappadath S., Lambert D., Lees T., Louw S., McCaslin J., Parr N., Robson R., Stansby G., Wales L., Wealleans V., Wilson L., Wyatt M., Baht H., Balogun I., Burger I., Cosier T., Cowie L., Gunathilagan G., Hargroves D., Insall R., Jones S., Rudenko H., Schumacher N., Senaratne J., Thomas G., Thomson A., Webb T., Brown E., Esisi B., Mehrzad A., MacSweeney S., McConachie N., Southam A., Sunman W., Abdul-Hamiq A., Bryce J., Chetter I., Ettles D., Lakshminarayan R., Mitchelson K., Rhymes C., Robinson G., Scott P., Vickers A., Ashleigh R., Butterfield S., Gamble E., Ghosh J., McCollum C.N., Welch M., Welsh S., Wolowczyk L., Donnelly M., D'Souza S., Egun A.A., Gregary B., Joseph T., Kelly C., Punekar S., Rahi M.A., Raj S., Seriki D., Thomson G., Brown J., Durairajan R., Grunwald I., Guyler P., Harman P., Jakeways M., Khuoge C., Kundu A., Loganathan T., Menon N., Prabakaran R.O., Sinha D., Thompson V., Tysoe S., Briley D., Darby C., Hands L., Howard D., Kuker W., Schulz U., Teal R., Barer D., Brown A., Crawford S., Dunlop P., Krishnamurthy R., Majmudar N., Mitchell D., Myint M.P., O'Brien R., O'Connell J., Sattar N., Vetrivel S., Beard J., Cleveland T., Gaines P., Humphreys J., Jenkins A., King C., Kusuma D., Lindert R., Lonsdale R., Nair R., Nawaz S., Okhuoya F., Turner D., Venables G., Dorman P., Hughes A., Jones D., Mendelow D., Rodgers H., Raudoniitis A., Enevoldson P., Nahser H., O'Brien I., Torella F., Watling D., White R., Brown P., Dutta D., Emerson L., Hilltout P., Kulkarni S., Morrison J., Poskitt K., Slim F., Smith S., Tyler A., Waldron J., Whyman M., Bajoriene M., Baker L., Colston A., Eliot-Jones B., Gramizadeh G., Lewis-Clarke C., McCafferty L., Oliver D., Palmer D., Patil A., Pegler S., Ramadurai G., Roberts A., Sargent T., Siddegowda S., Singh-Ranger R., Williams A., Williams L., Windebank S., Zuromskis T., Alwis L., Angus J., Asokanathan A., Fornolles C., Hardy D., Hunte S., Justin F., Phiri D., Mitabouana-Kibou M., Sekaran L., Sethuraman S., Tate M.L., Akyea-Mensah J., Ball S., Chrisopoulou A., Keene E., Phair A., Rogers S., Smyth J.V., Bicknell C., Chataway J., Cheshire N., Clifton A., Eley C., Gibbs R., Hamady M., Hazel B., James A., Jenkins M., Khanom N., Lacey A., Mireskandari M., O'Reilly J., Pereira A., Sachs T., Wolfe J., Davey P., Rogers G., Smith G., Tervit G., Nichol I., Parry A., Young G., Ashley S., Barwell J., Dix F., Nor A.M., Parry C., Birt A., Davies P., George J., Graham A., Jonker L., Kelsall N., Potts C., Wilson T., Crinnion J., Cuenoud L., Aleksic N., Babic S., Ilijevski N., Radak, Sagic D., Tanaskovic S., Colic M., Cvetic V., Davidovic L., Jovanovic D.R., Koncar I., Mutavdzic P., Sladojevic M., Tomic I., Debus E.S., Grzyska U., Otto D., Thomalla G., Barlinn J., Gerber J., Haase K., Hartmann C., Ludwig S., Putz V., Reeps C., Schmidt C., Weiss N., Werth S., Winzer S., Gemper J., Gunther A., Heiling B., Jochmann E., Karvouniari P., Klingner C., Mayer T., Schubert J., Schulze-Hartung F., Zanow J., Bausback Y., Borger F., Botsios S., Branzan D., Braunlich S., Holzer H., Lenzer J., Piorkowski C., Richter N., Schuster J., Scheinert D., Schmidt A., Staab H., Ulrich M., Werner M., Berger H., Biro G., Eckstein H.-H., Kallmayer M., Kreiser K., Zimmermann A., Berekoven B., Frerker K., Gordon V., Torsello G., Arnold S., Dienel C., Storck M., Biermaier B., Gissler H.M., Klotzsch C., Pfeiffer T., Schneider R., Sohl L., Wennrich M., Alonso A., Keese M., Groden C., Coster A., Engelhardt A., Ratusinski C.-M., Berg B., Delle M., Formgren J., Gillgren P., Jarl L., Kall T.B., Konrad P., Nyman N., Skioldebrand C., Steuer J., Takolander R., Malmstedt J., Acosta S., Bjorses K., Brandt K., Dias N., Gottsater A., Holst J., Kristmundsson T., Kuhme T., Kolbel T., Lindblad B., Lindh M., Malina M., Ohrlander T., Resch T., Ronnle V., Sonesson B., Warvsten M., Zdanowski Z., Campbell E., Kjellin P., Lindgren H., Nyberg J., Petersen B., Plate G., Parsson H., Qvarfordt P., Ignatenko P., Karpenko A., Starodubtsev V., Chernyavsky M.A., Golovkova M.S., Komakha B.B., Zherdev N.N., Belyasnik A., Chechulov P., Kandyba D., Stepanishchev I., Csobay-Novak C., Dosa E., Entz L., Nemes B., Szeberin Z., Barzo P., Bodosi M., Fako E., Fulop B., Nemeth T., Pazdernyik S., Skoba K., Voros E., Chatzinikou E., Giannoukas A., Karathanos C., Koutsias S., Kouvelos G., Matsagkas M., Ralli S., Rountas C., Rousas N., Spanos K., Brountzos E., Kakisis J.D., Lazaris A., Moulakakis K.G., Stefanis L., Tsivgoulis G., Vasdekis S., Antonopoulos C.N., Bellenis I., Maras D., Polydorou A., Polydorou V., Tavernarakis A., Ioannou N., Terzoudi M., Lazarides M., Mantatzis M., Vadikolias K., Dzieciuchowicz L., Gabriel M., Krasinski Z., Oszkinis G., Pukacki F., Slowinski M., Stanisic M.-G., Staniszewski R., Tomczak J., Zielinski M., Myrcha P., Rozanski D., Drelichowski S., Iwanowski W., Koncewicz K., Bialek P., Biejat Z., Czepel W., Czlonkowska A., Dowzenko A., Jedrzejewska J., Kobayashi A., Leszczynski J., Malek A., Polanski J., Proczka R., Skorski M., Szostek M., Andziak P., Dratwicki M., Gil R., Nowicki M., Pniewski J., Rzezak J., Seweryniak P., Dabek P., Juszynski M., Madycki G., Pacewski B., Raciborski W., Slowinski P., Staszkiewicz W., Bombic M., Chlouba V., Fiedler J., Hes K., Kostal P., Sova J., Kriz Z., Privara M., Reif M., Staffa R., Vlachovsky R., Vojtisek B., Hrbac T., Kuliha M., Prochazka V., Roubec M., Skoloudik D., Netuka D., Steklacova A., Benes III V., Buchvald P., Endrych L., Sercl M., Campos W., Casella I.B., de Luccia N., Estenssoro A.E.V., Presti C., Puech-Leao P., Neves C.R.B., da Silva E.S., Sitrangulo C.J., Monteiro J.A.T., Tinone G., Bellini Dalio M., Joviliano E.E., Pontes Neto O.M., Serra Ribeiro M., Cras P., Hendriks J.M.H., Hoppenbrouwers M., Lauwers P., Loos C., Yperzeele L., Geenens M., Hemelsoet D., van Herzeele I., Vermassen F., Astarci P., Hammer F., Lacroix V., Peeters A., Verhelst R., Cirelli S., Dormal P., Grimonprez A., Lambrecht B., Lerut P., Thues E., De Koster G., Desiron Q., Maertens de Noordhout A., Malmendier D., Massoz M., Saad G., Bosiers M., Callaert J., Deloose K., Blanco Canibano E., Garcia Fresnillo B., Guerra Requena M., Morata Barrado P.C., Muela Mendez M., Yusta Izquierdo A., Aparici Robles F., Blanes Orti P., Garcia Dominguez L., Martinez Lopez R., Miralles Hernandez M., Tembl Ferrairo J.I., Chamorro A., Macho J., Obach V., Riambau V., San Roman L., Ahlhelm F.J., Blackham K., Engelter S., Eugster T., Gensicke H., Gurke L., Lyrer P., Mariani L., Maurer M., Mujagic E., Muller M., Psychogios M., Stierli P., Stippich C., Traenka C., Wolff T., Wagner B., Wiegert M.M., Clarke S., Diepers M., Grochenig E., Gruber P., Isaak A., Kahles T., Marti R., Nedeltchev K., Remonda L., Tissira N., Valenca Falcao M., de Borst G.J., Lo R.H., Moll F.L., Toorop R., van der Worp B.H., Vonken E.J., Kappelle J.L., Jahrome O., Vos F., Schuiling W., van Overhagen H., Keunen R.W.M., Knippenberg B., Wever J.J., Lardenoije J.W., Reijnen M., Smeets L., van Sterkenburg S., Fraedrich G., Gizewski E., Gruber I., Knoflach M., Kiechl S., Rantner B., Abdulamit T., Bergeron P., Padovani R., Trastour J.-C., Cardon J.-M., Le Gallou-Wittenberg A., Allaire E., Becquemin J.-P., Cochennec-Paliwoda F., Desgranges P., Hosseini H., Kobeiter H., Marzelle J., Almekhlafi M.A., Bal S., Barber P.A., Coutts S.B., Demchuk A.M., Eesa M., Gillies M., Goyal M., Hill M.D., Hudon M.E., Jambula A., Kenney C., Klein G., McClelland M., Mitha A., Menon B.K., Morrish W.F., Peters S., Ryckborst K.J., Samis G., Save S., Smith E.E., Stys P., Subramaniam S., Sutherland G.R., Watson T., Wong J.H., Zimmel L., Flis V., Matela J., Miksic K., Milotic F., Mrdja B., Stirn B., Tetickovic E., Gasparini M., Grad A., Kompara I., Milosevic Z., Palmiste V., Toomsoo T., Aidashova B., Kospanov N., Lyssenko R., Mussagaliev D., Beyar R., Hoffman A., Karram T., Kerner A., Nikolsky E., Nitecki S., Andonova S., Bachvarov C., Petrov V., Cvjetko I., Vidjak V., Haluzan D., Petrunic M., Liu B., Liu C.-W., Bartko D., Beno P., Rusnak F., Zelenak K., Ezura M., Inoue T., Kimura N., Kondo R., Matsumoto Y., Shimizu H., Endo H., Furui E., Bakke S., Krohg-Sorensen K., Nome T., Skjelland M., Tennoe B., Albuquerque e Castro J., Alves G., Bastos Goncalves F., de Aragao Morais J., Garcia A.C., Valentim H., Vasconcelos L., Belcastro F., Cura F., Zaefferer P., Abd-Allah F., Eldessoki M.H., Heshmat Kassem H., Soliman Gharieb H., Colgan M.P., Haider S.N., Harbison J., Madhavan P., Moore D., Shanik G., Kazan V., Nazzal M., Ramsey-Williams V., and Gargiulo M

Subjects
Male, medicine.medical_specialty, Time Factors, Time Factor, medicine.medical_treatment, Carotid Stenosi, MEDLINE, Carotid endarterectomy, Rate ratio, Risk Assessment, Asymptomatic, law.invention, Randomized controlled trial, law, Risk Factors, carotid artery stenting (CAS), carotid endarterectomy (CEA), Stent, medicine, Humans, Carotid Stenosis, Stroke, Endarterectomy, Aged, Endarterectomy, Carotid, business.industry, carotid artery, Risk Factor, Articles, General Medicine, trial, medicine.disease, Settore MED/22 - CHIRURGIA VASCOLARE, Surgery, Stenosis, Treatment Outcome, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Female, Stents, Human medicine, medicine.symptom, business, Human
Abstract

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

Published
2021

37. Outcome of endovascular therapy in stroke with large vessel occlusion and mild symptoms

Author

Timo Kahles, Henrik Gensicke, Leo H. Bonati, Mandy D. Müller, Marcel Arnold, Georg Kägi, Stefania Nannoni, Giulio Disanto, Urs Fischer, Alessandro Cianfoni, Claudio Staedler, Krassen Nedeltchev, Carlo W. Cereda, Giovanni Bianco, Sebastian Thilemann, Emmanuel Carrera, Andreas R. Luft, Mirjam Rachel Heldner, Johannes Kaesmacher, Simon Jung, Patrik Michel, Concetta Manno, University of Zurich, and Cereda, Carlo W

Subjects
Male, medicine.medical_specialty, Stroke/epidemiology/surgery, 610 Medicine & health, Endovascular therapy, Severity of Illness Index, Brain Ischemia, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, Internal medicine, Severity of illness, Clinical endpoint, Humans, Medicine, cardiovascular diseases, Registries, 030212 general & internal medicine, Stroke, Aged, Retrospective Studies, Brain Ischemia/epidemiology/surgery, business.industry, Endovascular Procedures, Retrospective cohort study, Odds ratio, Middle Aged, medicine.disease, Confidence interval, 10040 Clinic for Neurology, ddc:616.8, 2728 Neurology (clinical), Mild symptoms, Treatment Outcome, cardiovascular system, Cardiology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Large vessel occlusion
Abstract

ObjectiveTo compare outcomes after endovascular therapy (EVT) and IV thrombolysis (IVT) in patients with stroke with emergent large vessel occlusion (LVO) and mild neurologic deficits.MethodsThis was a retrospective analysis of patients from the Swiss Stroke Registry with admission NIH Stroke Scale score ≤5 and LVO treated by EVT (± IVT) vs IVT alone. The primary endpoint was favorable functional outcome (modified Rankin Scale [mRS] score 0–1) at 3 months. Secondary outcomes were independence (mRS score 0–2), mRS score (ordinal shift analysis), and survival with high disability (mRS score 4–5). Safety endpoints were mortality and symptomatic hemorrhage.ResultsOf 11,356 patients, 312 met the criteria and propensity score method matched 108 in each group. A comparably large proportion of patients with EVT and IVT had favorable outcome (63% vs 65.7% respectively; odds ratio 0.94, 95% confidence interval 0.51–1.72; p = 0.840). Patients with EVT showed a nonsignificant trend toward higher mRS score at 3 months (p = 0.717), while the proportion of surviving patients with high disability was comparably very low in both groups (p = 0.419). Mortality was slightly higher among those with EVT (9.3% vs 2.8%; p = 0.06), and symptomatic intracranial hemorrhage was a rare event in both groups (2.8% vs 0%; p = 0.997).ConclusionsIn acute ischemic stroke, EVT and IVT appear similarly effective in achieving favorable outcome at 3 months for patients with LVO and mild neurologic symptoms. EVT might be marginally inferior to IVT regarding outcome across all levels of disability and mortality. Further studies are required to determine whether certain subgroups of patients with LVO and mild symptoms benefit from EVT.Classification of evidenceThis study provides Class III evidence that patients with LVO and mild symptoms receiving either EVT or IVT had similar favorable functional outcomes at 3 months.

Published
2019

38. NOACs in Anesthesiology

Author

Christian Kern, Wolfgang Korte, François Mach, Donat R. Spahn, Jürg-Hans Beer, Alain Borgeat, Pierre-Guy Chassot, Krassen Nedeltchev, University of Zurich, and Spahn, Donat R

Subjects
medicine.medical_specialty, Perioperative management, 10216 Institute of Anesthesiology, business.industry, 2720 Hematology, Renal function, 610 Medicine & health, Review Article, Hematology, Plasma levels, 030204 cardiovascular system & hematology, Discontinuation, 03 medical and health sciences, 0302 clinical medicine, Anesthesia, Anesthesiology, 2723 Immunology and Allergy, Immunology and Allergy, Medicine, Elective surgery, business, 030215 immunology
Abstract

Background: Due to increasing use of new oral anticoagulants (NOACs), clinicians are faced more and more frequently with clinical issues related to these drugs. Objective: The objective of this publication is to make practical suggestions for the perioperative management of NOACs as well as for their handling in overdoses and bleedings. Recommendations: In elective surgery and creatinine clearance ≥ 50 ml/min, a NOAC should be discontinued 24-36 h before the intervention, and even earlier in case of reduced kidney function. In emergency interventions that cannot be delayed, the management is dependent on the NOAC plasma levels. With levels ≤ 30 ng/ml, surgery can be performed. With levels >30 ng/ml, reversal agents should be considered. In low bleeding risk surgery, NOACs can be re-started 24 h after the intervention, which is prolonged to 48-72 h after surgery with high bleeding risk. In case of NOAC overdose and minor bleedings, temporary discontinuation and supportive care are usually sufficient to control the situation. In severe or life-threatening bleedings, nonspecific and specific reversal agents should be considered.

Published
2019

39. Akute Revaskularisation beim ischämischen Hirnschlag

Author

Marcel Arnold, Patrik Michel, Thilman Schubert, Susanne Wegener, Michael Diepers, David Bervini, Guido Schwegler, Emmanuel Carrera, Carlo Cereda, Thomas Nyffeler, Stephan G. Wetzel, Stefan T. Engelter, Yvan Gasche, Henrik Gensicke, Jean-Daniel Rouvé, Christophe Bonvin, Pasquale Mordasini, Georg Kägi, and Krassen Nedeltchev

Abstract

Von der Schweizerischen Hirnschlag Gesellschaft und ihren Partnergesellschaften unter Berucksichtigung der neuen wissenschaftlichen Daten uberarbeitete Schweizer Leitlinien.

Published
2021

40. Revascularisation aiguë en cas d’accident vasculaire cérébral ischémique

Author

Marcel Arnold, Krassen Nedeltchev, Carlo W. Cereda, Christophe Bonvin, David Bervini, Emmanuel Carrera, Georg Kägi, Thomas Nyffeler, Stephan G. Wetzel, Henrik Gensicke, Guido Schwegler, Jean-Daniel Rouvé, Thilman Schubert, Susanne Wegener, Michael Diepers, Pasquale Mordasini, Patrik Michel, Stefan T. Engelter, and Yvan Gasche

Abstract

Lignes directrices suisses revisees de la Societe Cerebrovasculaire Suisse et ses societes partenaires suite aux nouvelles donnees scientifiques.

Published
2021

41. Prähospitalphase beim akuten Hirnschlag

Author

Susanne Renaud, Urs Fischer, Julien Niederhäuser, Marcel Arnold, Krassen Nedeltchev, David Schurter, Paul Imboden, Christophe Bonvin, Georg Kägi, Patrik Michel, Emmanuel Carrera, A. Luft, Carlo Cereda, Patrick Arni, Stefan T. Engelter, Gian Marco De Marchis, and Olivier Nyenhuis

Abstract

Die Akutbehandlung des Hirnschlags hat enorme Fortschritte gemacht. Zur Organisation der Prahospitalphase hat die Schweizerische Hirnschlag Gesellschaft mit ihren Partnergesellschaften diese Guideline erarbeitet.

Published
2021

42. Phase préhospitalière en cas d’accident vasculaire cérébral aigu

Author

Urs Fischer, Patrik Michel, Gian Marco De Marchis, Christophe Bonvin, Patrick Arni, Stefan T. Engelter, Emmanuel Carrera, Andreas R. Luft, Julien Niederhäuser, Krassen Nedeltchev, Paul Imboden, Olivier Nyenhuis, Carlo W. Cereda, David Schurter, Susanne Renaud, Marcel Arnold, and Georg Kägi

Abstract

Le traitement aigu de l’accident vasculaire cerebral a fait d’enormes progres. Pour l'organisation de la phase prehospitaliere, la Societe Cerebrovasculaire Suisse et ses societes partenaires ont elabore les presentes recommandations.

Published
2021

43. Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD):an open-label, randomised, non-inferiority trial

Author

Stefan T Engelter, Christopher Traenka, Henrik Gensicke, Sabine A Schaedelin, Andreas R Luft, Barbara Goeggel Simonetti, Urs Fischer, Patrik Michel, Gaia Sirimarco, Georg Kägi, Jochen Vehoff, Krassen Nedeltchev, Timo Kahles, Lars Kellert, Sverre Rosenbaum, Regina von Rennenberg, Roman Sztajzel, Stephen L Leib, Simon Jung, Jan Gralla, Nicole Bruni, David Seiffge, Katharina Feil, Alexandros A Polymeris, Levke Steiner, Janne Hamann, Leo H Bonati, Alex Brehm, Gian Marco De Marchis, Nils Peters, Christoph Stippich, Christian H Nolte, Hanne Christensen, Susanne Wegener, Marios-Nikos Psychogios, Marcel Arnold, Philippe Lyrer, Valerian Altersberger, Thomas Fabbro, Urs Fisch, Joachim Fladt, Lisa Hert, Philippe A Lyrer, Marina Maurer, Alexandros Polymeris, Sabine Schaedelin, Sebastian Thilemann, Benjamin Wagner, Mirjam Heldner, David J Seiffge, Hubertus Mueller, Lukas Sveikata, Pamela Correia, Ashraf Eskandari, Ivo Meyer, Stefania Nannoni, Suzette Remillard, Alexandros Zachariadis, Georg Kaegi, Anna Mueller, Hebun J Erdur, and Jan F Scheitz

Subjects
Adult, Male, medicine.medical_specialty, medicine.drug_class, Denmark, Population, Carotid Artery, Internal, Dissection, 030204 cardiovascular system & hematology, Phenprocoumon, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Germany, medicine, Clinical endpoint, Humans, education, Stroke, Vertebral Artery Dissection, education.field_of_study, Acenocoumarol, Aspirin, business.industry, Warfarin, Anticoagulants, Vitamin K antagonist, Middle Aged, medicine.disease, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Platelet Aggregation Inhibitors, Switzerland, medicine.drug
Abstract

Background: Cervical artery dissection is a major cause of stroke in young people (aged

Published
2021

44. Abstract P407: Etiology And Outcomes Of Non-traumatic Intracerebral Hemorrhage - Data From The Swiss Stroke Registry

Author

Emmanuel Carrera, Stefan T. Engelter, Susanne Renaud, Philippe Lyrer, Madlaine Mueller, Christophe Bonvin, Marcel Arnold, Achim Mueller, Stephan Salmen, Susanne Wegener, Javier Fandino, Werner J. Z’Graggen, Ludwig Schelosky, Leo H. Bonati, Nils Peters, David J. Seiffge, Christian Berger, Georg Kaegi, Carlo W. Cereda, Julien Niederhaeuser, Rolf Sturzenegger, Alexandros A Polymeris, Martina Goeldlin, Krassen Nedeltchev, Bernhard Siepen, Manuel Bolognese, Tomas Dobrocky, Biljana Rodic, Timo Kahles, Marie-Luise Mono, Bastian Volbers, David Bervini, Friedrich Medlin, Urs Fischer, and Davide Strambo

Subjects
Advanced and Specialized Nursing, Intracerebral hemorrhage, Stroke registry, Pediatrics, medicine.medical_specialty, business.industry, medicine.disease, nervous system diseases, Non traumatic, medicine, Etiology, cardiovascular diseases, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Amyloid angiopathy
Abstract

Background: We determined the frequency of different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their association with clinical characteristics and outcomes. Methods: We analyzed data from consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014-2019). Etiology of ICH was determined according to prespecified, mutually exclusive categories. We assessed prevalence of ICH etiologies, their association with clinical characteristics, functional independence (modified Rankin Scale 0-2), mortality, recurrent ICH and ischemic stroke at 3 months. Results: We included 2584 patients (median age 72y, IQR 64-82, 46.6% female, median NIHSS 10; IQR 3-15). 2037 patients (80%) had hypertension and 553 (22.3%) were on anticoagulants. Distribution of etiologies was as follows: Hypertension (n=1216 patients; 47.1% of all / 56.3% of patients with hypertension), unknown etiology (n=542, 21.0%), antithrombotic therapy (n=225, 8.7% of all / 38% of patients on anticoagulants), cerebral amyloid angiopathy (CAA, n=211, 8.2%), macro-vascular (n=121, 4.7%), other determined etiologies (n=269, 10.4%). Patients with hypertensive ICH had significantly higher NIHSS (median 9; IQR 4-16) and blood pressure levels (median systolic 176; IQR 156-195) on admission. Patients with CAA had significantly lower NIHSS at baseline (median 5; IQR 2-12). Three month follow-up was available for 2109/2584 patients (81.6%). 820 (38.9%) were functionally independent, 658 have died (31.2%). Hypertensive ICH was associated with an increased rate of functional independence (aOR =1.42, 95%CI 1.06-1.90, p=0.02). 5.2% of patients had a cerebrovascular event within 3 months. CAA was associated with a high risk of recurrent ICH (HR 6.95, 95%CI 3.05-15.84, p Conclusions: In Swiss Stroke Units and Centers, one of two patients has ICH from a different cause than hypertension. The rate of functionally independent patients at 3 months seems higher than mortality. Absolute and relative risks of recurrent ICH and ischemic stroke after recent ICH differ among underlying etiologies.

Published
2021

45. Acute revascularization in ischemic stroke: Updated Swiss guidelines

Author

Emmanuel Carrera, Henrik Gensicke, Jean-Daniel Rouvé, Susanne Wegener, Patrik Michel, Christophe Bonvin, Thomas Nyffeler, Pasquale Mordasini, Tilman Schubert, Georg Kägi, Krassen Nedeltchev, David Bervini, Guido Schwegler, Marcel Arnold, Stefan T. Engelter, Yvan Gasche, Carlo Cereda, Stephan G. Wetzel, Michael Diepers, and University of Zurich

Subjects
medicine.medical_specialty, thrombolysis, medicine.medical_treatment, Neurosciences. Biological psychiatry. Neuropsychiatry, 610 Medicine & health, Guidelines, Revascularization, Endovascular therapy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, 10043 Clinic for Neuroradiology, Internal medicine, medicine, 030212 general & internal medicine, guidelines, Acute ischemic stroke, Stroke, Thrombectomy, ddc:617, business.industry, Thrombolysis, Swiss, medicine.disease, ddc:616.8, thrombectomy, Ischemic stroke, Cardiology, revascularization, business, 030217 neurology & neurosurgery, RC321-571
Abstract

In acute ischemic stroke, intravenous thrombolysis (IVT) and acute endovascular therapy (EVT) have been shown to reduce long-term disability in randomized trials. International guidelines are partially not up to date and may not address situations for which there is limited scientific evidence. The goals of the present guidelines are to summarize the current scientific data for acute revascularization treatments to make sure that all Swiss Centers apply a similar, evidence, or consensus-based treatment standard. A multidisciplinary working group of the Swiss Stroke Society (SSS) searched and reviewed the literature on new randomized controlled trials (RCTs), large case series, meta-analyses, and other guidelines since the previous recommendations in 2009 to elaborate the consensus guidelines. The new RCTs have confirmed the effectiveness of IVT in various populations up to 4.5 h and proven the benefit of acute EVT up to approximately 8 h. For patients with unknown onset (including wake-up stroke), IVT and EVT can be effective up to 24 h after last proof of good health if patients are selected with advanced neuroimaging. Multiple case series and meta-analyses allow narrowing down the indications and relative and absolute contraindications to optimize the benefit&ndash, risk ratio of acute revascularization.

Published
2021

46. Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation

Author

Davide Strambo, Giovanni Bianco, Timo Kahles, Ludwig Schelosky, Mira Katan, Elisabeth Dirren, Christian Berger, David J. Seiffge, Roland Backhaus, Marcel Arnold, Mattia Branca, Patrik Michel, Julien Niederhäuser, Carlo W. Cereda, Stefan T. Engelter, Marie-Luise Mono, Emmanuel Carrera, Georg Kägi, Susanne Renaud, Urs Fischer, Christophe Bonvin, Biljana Rodic, Johannes Kaesmacher, Sylvan Albert, Krassen Nedeltchev, Gian Marco De Marchis, Pasquale Mordasini, Friedrich Medlin, Mirjam Rachel Heldner, Leo H. Bonati, Simon Jung, Stephan Salmen, Manuel Bolognese, Michael Schaerer, Alexander A. Tarnutzer, Jan Gralla, Thomas Raphael Meinel, Jochen Vehoff, Investigators of the Swiss Stroke Registry, Lyrer, P., Peters, N., Polymeris, A., Thilemann, S., Altersberger, V., Blackham, K., Dittrich, T., El Mekabaty, A., Fladt, J., Fisch, U., Gensicke, H., Hert, L., Manuzzi, S., Psychogios, M., Maurer, M., Traenka, C., Tsogkas, I., Wagner, B., Zietz, A., Brehm, A., Meya, L., Sarikaya, H., Goeldlin, M., Vynckier, J., Mamaari, B., Siepen, B., Mueller, M., Eskandari, A., Pantazou, V., Wegener, S., Mueller, A., Schütz, V., Pokorny, T., Luft, A., Albert, S., Sturzenegger, R., Humm, A., Cuendet, D., Accolla, E., Annoni, J.M., Foucras, S., Minkner, K.K., Olivier, P., Kelemen, P., Brodo, G., Cordier, M., Jurgutiene, V., Sotomayor, G.T., and Fisch, L.

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, 610 Medicine & health, macromolecular substances, Anticoagulants, Anticoagulation, DOAC, Ischaemic Stroke, Thrombectomy, Thrombolysis, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, Interquartile range, Internal medicine, Atrial Fibrillation, medicine, cardiovascular diseases, Research Articles, Ischemic Stroke, business.industry, Confounding, Atrial fibrillation, Odds ratio, medicine.disease, Confidence interval, ddc:616.8, 030104 developmental biology, Neurology, Cardiology, Neurology (clinical), business, 030217 neurology & neurosurgery, Research Article, Cohort study
Abstract

OBJECTIVE The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes. METHODS This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months. RESULTS Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p

Published
2021

47. Lipoprotein(a) is associated with large artery atherosclerosis stroke aetiology and stroke recurrence among patients below the age of 60 years: results from the BIOSIGNAL study

Author

George Ntaios, Alejandro Bustamante, Corinne Inauen, Georg Kägi, Gian Marco De Marchis, Leo H. Bonati, Arnold von Eckardstein, Marcel Arnold, Katharina Spanaus, Juliane Schweizer, Carlo W. Cereda, Thomas Pokorny, Timo Kahles, Alexander Benedikt Leichtle, Valerie Schütz, Markus F. F. Arnold, Christian Foerch, Laura P. Westphal, Mira Katan, Andreas R. Luft, Mandy D. Müller, Krassen Nedeltchev, Joan Montaner, Christos T. Nakas, Urs Fischer, Antonela Bicvic, University of Zurich, Arnold, Markus, and Arnold, Marcel

Subjects
medicine.medical_specialty, 610 Medicine & health, 030204 cardiovascular system & hematology, 2705 Cardiology and Cardiovascular Medicine, Brain Ischemia, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Risk Factors, Internal medicine, 540 Chemistry, Medicine, Humans, Prospective Studies, Risk factor, Stroke, 10038 Institute of Clinical Chemistry, biology, business.industry, Hazard ratio, Atrial fibrillation, Lipoprotein(a), Odds ratio, Arteries, Middle Aged, medicine.disease, Atherosclerosis, 10040 Clinic for Neurology, Cohort, biology.protein, Cardiology, 10023 Institute of Intensive Care Medicine, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Cohort study
Abstract

Aims Lipoprotein(a) [Lp(a)] is a recognized causal risk factor for atherosclerotic cardiovascular disease but its role for acute ischaemic stroke (AIS) is controversial. In this study, we evaluated the association of Lp(a) with large artery atherosclerosis (LAA) stroke and risk of recurrent cerebrovascular events in AIS patients. Methods and results For this analysis of the prospective, observational, multicentre BIOSIGNAL cohort study we measured Lp(a) levels in plasma samples of 1733 primarily Caucasian (98.6%) AIS patients, collected within 24 h after symptom onset. Primary outcomes were LAA stroke aetiology and recurrent cerebrovascular events (ischaemic stroke or transient ischaemic attack) within 1 year. We showed that Lp(a) levels are independently associated with LAA stroke aetiology [adjusted odds ratio 1.48, 95% confidence interval (CI) 1.14-1.90, per unit log10Lp(a) increase] and identified age as a potent effect modifier (Pinteraction =0.031) of this association. The adjusted odds ratio for LAA stroke in patients aged Conclusion Elevated Lp(a) was independently associated with LAA stroke aetiology and risk of recurrent cerebrovascular events among primarily Caucasian individuals aged

Published
2020

48. Comparison of different carotid stent designs in endovascular therapy of severe carotid artery stenosis

Author

Michael Diepers, Luca Remonda, Timo Kahles, Philipp Gruber, Krassen Nedeltchev, Jatta Berberat, and Javier Anon

Subjects
medicine.medical_specialty, medicine.medical_treatment, Carotid arteries, atherosclerotic, Neurosciences. Biological psychiatry. Neuropsychiatry, 030204 cardiovascular system & hematology, Endovascular therapy, 03 medical and health sciences, 0302 clinical medicine, carotid stenting, medicine, cardiovascular diseases, Thrombus, Stroke, business.industry, carotid artery, stent design, medicine.disease, stroke, hybrid carotid stent system, Stenosis, Embolism, Radiology, Carotid stenting, business, Stent design, 030217 neurology & neurosurgery, RC321-571, Double-layer micromesh stent
Abstract

One of the major periprocedural risks of carotid artery stenting is embolism caused either by plaque debris or by local thrombus forming. Double-layer micromesh stent design has shown to lower the chance of debris embolism but might have a slightly higher risk of local thrombus forming. Thus, we compared two different stent designs regarding safety and outcome profile in elective patients with high-grade carotid artery stenosis using a self-expanding, double-layer micromesh carotid stent system (DLCS) or a self-expanding hybrid carotid stent system (HCS). A single-center, open-label, retrospective cohort study of 67 consecutive, elective patients with high-grade symptomatic and asymptomatic carotid stenosis was executed at a comprehensive stroke center. Outcome measures were reocclusion rate, periprocedural symptomatic ischemic events, as well as other periprocedural complications, and recurrent stroke and mortality at 30 days&rsquo, follow-up. Thirty-two patients (24% women, median age 75 years (interquartile range (IQR) 71&ndash, 80) were treated with DLCS, and 35 patients (29% women, median age 71 years (IQR 63&ndash, 76) years) with HCS. In both groups, pretreatment carotid stenosis degree was similar (median NASCET of 80%). Successful deployment was achieved in all cases without technical failure, and both groups did not differ in reocclusion rates, recurrent stroke, and mortality within 30 days. DCLS and HCS revealed to have similar safety and outcome profile in elective patients with high-grade symptomatic as well as asymptomatic carotid artery stenosis.

Published
2020
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49. Drug-Coated Balloon Treatment in Symptomatic Intracranial High Grade Stenosis : A Retrospective Study of 33 Patients

Author

Javier Anon, Timo Kahles, Michael Diepers, Jatta Berberat, Krassen Nedeltchev, Luca Remonda, and Philipp Gruber

Subjects
medicine.medical_specialty, Percutaneous, Constriction, Pathologic, Balloon, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Restenosis, Interquartile range, medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Retrospective Studies, business.industry, Retrospective cohort study, medicine.disease, Intracranial Arteriosclerosis, Surgery, Stenosis, Pharmaceutical Preparations, Neurology (clinical), business, Complication, 030217 neurology & neurosurgery, Angioplasty, Balloon, Cohort study
Abstract

Endovascular therapy (EVT) represents an alternative treatment modality for symptomatic intracranial high-grade atherosclerotic stenosis (sICAS); however, periprocedural complication rates as well as midterm restenosis rates represent relevant limitations of EVT. Drug-coated balloon percutaneous transluminal angioplasty (DCB-PTA) may overcome some of these shortcomings. The aim of this study was to assess feasibility and safety as well as the stroke recurrence rate in 33 patients. A retrospective, monocentric cohort study of sICAS patients treated with DCB-PTA. Outcome measures were the periprocedural intracranial complication rate, the recurrent stroke rate and mortality during follow-up. This cohort study included 33 patients with 35 sICAS treated with DCB-PTA. The median age was 72 years (interquartile range, IQR 66–77 years); median clinical and mean radiological follow-up time was 9 months (IQR 3–22 months). Median preprocedural degree of stenosis (WASID) was 80% (IQR 73–80%) and median postprocedural residual stenosis degree (WASID) was 50% (IQR 33–60%). Intracranial periprocedural complications occurred in 2 (6%) patients. The overall restenosis rate was 15% (n = 5). In four patients a symptomatic ischemic re-event occurred within 7 months after the initial treatment. None of the patients died. This DCB-PTA cohort study showed a relatively low intracranial complication rate of 6% with a symptomatic recurrence rate of 12%. Larger trials are needed to validate these promising observations.

Published
2020

50. Abstract WP225: Fetal-Type Posterior Cerebral Artery: A Not So Benign Anatomical Variant?

Author

Timo Kahles, Luca Remonda, Oliver Findling, Nadir Tissira, Nico Strecker, Philipp Gruber, Marta Kubacka, Krassen Nedeltchev, and Carlos Garcia Esperon

Subjects
Advanced and Specialized Nursing, Cerebral circulation, Fetus, business.industry, medicine.artery, medicine, Neurology (clinical), Posterior cerebral artery, Anatomy, Cardiology and Cardiovascular Medicine, medicine.disease, business, Stroke
Abstract

Introduction: The fetal-type of the posterior cerebral artery (ftPCA) is a remnant of the embryonic cerebral vasculature and describes a predominant supply of the PCA territory by a branch of the internal carotid artery. It is usually considered a benign anatomical variant with a prevalence ranging between 3% and 40%. Given the larger supply of the brain parenchyma by the anterior circulation in this variant, ftPCA is often associated with a hypoplastic basilar artery and thus a reduced vertebrobasilar blood flow. Hypothesis: Attenuated blood flow through the vertebrobasilar system in patients with a ftPCA is associated with an increased risk of infratentorial ischemic stroke. Methods: We prospectively analyzed 625 consecutive acute stroke patients from our comprehensive stroke center. Cerebral MRI was used to identify stroke location. PCA territory blood supply was classified in 5 subcategories using CT or MRI angiography: 1) total ftPCA (i.e. complete supply via PCOM); 2) predominant ftPCA; 3) balanced PCA (supply via PCOM and P1); 4) predominant P1, and 5) complete P1 supply. Variants 1) and 2) were considered ftPCA for further analysis. We compared the frequencies of anterior, posterior, infratentorial, and multiple territories strokes between patients with and without ftPCA. Results: There were 215 patients (34%) with ftPCA. Patients with ftPCA were significantly more likely to suffer from an infratentorial stroke than those without the ftPCA variant (20% vs 12.2%, P = 0.009). In contrast, anterior, posterior, and multiple territories stroke did not differ between groups. When posterior territory strokes were attributed to the corresponding P1 or PCOM supply, there was no difference in the frequency of vertebrobasilar stroke (i.e. infratentorial plus P1-PCA) between patients with and without ftPCA (P=0.864). Mean cross sectional area of the basilar artery was significantly lower in patients with ftPCA compared to those without ftPCA (6.6mm2 vs. 9.7mm2, P Conclusion: Fetal-type PCA is associated with a higher frequency of infratentorial stroke and a lower cross sectional area of the basilar artery. Possibly, hemodynamic factors influence infratentorial stroke risk in patients with ftPCA.

Published
2020

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