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Patrik Michel - Top 30 Publications

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke.

Background Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. Methods In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. Results A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. Conclusions Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE number, NCT00562289 .).

Time-resolved CT assessment of collaterals as imaging biomarkers to predict clinical outcomes in acute ischemic stroke.

Collateral circulation plays a pivotal role in the pathophysiology of acute ischemic stroke and is increasingly recognized as a promising biomarker for predicting the clinical outcome. However, there is no single established grading system. We designed a novel machine-learning software that allows non-invasive, objective, and quantitative assessment of collaterals according to their vascular territories. Our goal is to investigate the prognostic and predictive value of this collateral score for the prediction of acute stroke outcome.

Nonvitamin-K-antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: An updated systematic review and meta-analysis of randomized controlled trials.

Background In a previous systematic review and meta-analysis, we assessed the efficacy and safety of nonvitamin-K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and stroke or transient ischemic attack. Since then, new information became available. Aim The aim of the present work was to update the results of the previous systematic review and meta-analysis. Methods We searched PubMed until 24 August 2016 for randomized controlled trials using the following search items: "atrial fibrillation" and "anticoagulation" and "warfarin" and "previous stroke or transient ischemic attack." Eligible studies had to be phase III trials in patients with atrial fibrillation comparing warfarin with nonvitamin-K antagonist oral anticoagulants currently on the market or with the intention to be brought to the market in North America or Europe. The outcomes assessed in the efficacy analysis included stroke or systemic embolism, stroke, ischemic or unknown stroke, disabling or fatal stroke, hemorrhagic stroke, cardiovascular death, death from any cause, and myocardial infarction. The outcomes assessed in the safety analysis included major bleeding, intracranial bleeding, and major gastrointestinal bleeding. We performed fixed effects analyses on intention-to-treat basis. Results Among 183 potentially eligible articles, four were included in the meta-analysis. In 20,500 patients, compared to warfarin, nonvitamin-K antagonist oral anticoagulants were associated with a significant reduction of stroke/systemic embolism (relative risk reduction: 13.7%, absolute risk reduction: 0.78%, number needed to treat to prevent one event: 127), hemorrhagic stroke (relative risk reduction: 50.0%, absolute risk reduction: 0.63%, number needed to treat: 157), any stroke (relative risk reduction: 13.1%, absolute risk reduction: 0.7%, number needed to treat: 142), and intracranial hemorrhage (relative risk reduction: 46.1%, absolute risk reduction: 0.88%, number needed to treat: 113) over 1.8-2.8 years. Conclusions This updated meta-analysis in 20,500 atrial fibrillation patients with previous stroke or transient ischemic attack shows that compared to warfarin non-vitamin-K antagonist oral anticoagulants are associated with a significant reduction of stroke, stroke or systemic embolism, hemorrhagic stroke, and intracranial bleeding.

Spontaneous carotid and vertebral dissections.

Dissections of the cervical arteries account for approximately 15-20 % of all strokes in young patients. Clinically they present with laterocervical and/or hemicranial pain associated to a Horner syndrome in case of carotid dissection and a posterior cervical pain associated to headache in the occipital area in case of vertebral dissection. A multifactorial origin is often suggested, resulting from the combination of a weakness of the arterial wall, hereditary or not, of environmental factors such minor trauma or a previous infection and also of the presence of a certain number of vascular risk factors such as high blood pressure or migraines. The diagnosis is best established with MRI which shows specifically the intramural hematoma. Treatment includes anticoagulants or antiplatelets agents.

Perfusion imaging of acute ischemic stroke.

Multi-modal imaging in acute ischemic stroke includes structural imaging, perfusion imaging and angiographic assessment of brain arteries. Perfusion imaging discriminates brain tissue that is critically hypo-perfused but salvageable (ischemic penumbra) from irreversibly injured tissue (ischemic core). In acute reperfusion therapies (intravenous or endovascular), patients who have substantial penumbra and a small core (target mismatch pattern) are most likely to have a good clinical outcome. Patient selection based on multi-modal imaging is not proven mandatory for acute treatment in patients admitted within the established time-window. Multi-modal image-based patient selection may be promising tool to identify candidates for acute treatment beyond the established time-window.

Endovascular treatment for acute ischemic stroke.

The benefit of endovascular treatment (ET) after acute ischemic stroke has long been debated. Recent studies have demonstrated the clinical benefit of ET up to approximately 8 hours after stroke onset, mainly in association with intranenous thrombolysis. The positive effect is higher if ET is initiated early and performed by an experienced team. Current ET techniques include thrombectomy with clot removal using stentretriever technques or local thromboaspiration of the clot. ET seems to be so efficient that stroke care networks have to be organised to offer ET as quickly as possible in all patients who could benefit from this therapy.

Real-World Setting Comparison of Nonvitamin-K Antagonist Oral Anticoagulants Versus Vitamin-K Antagonists for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Evidence from the real-world setting complements evidence coming from randomized controlled trials. We aimed to summarize all available evidence from high-quality real-world observational studies about efficacy and safety of nonvitamin-K oral anticoagulants compared with vitamin-K antagonists in patients with atrial fibrillation.


Aducanumab reduces the burden of amyloid plaques in Alzheimer's disease, with significant improvement of clinical scores. Endovascular thrombectomy is recommended in patients with acute stroke with proximal occlusion of the anterior circulation. CGRP antagonists and botulinum toxin are effective in migraine. ZIKA virus infection has been linked to the Guillain-Barré syndrome. Edaravone has been approved for amyotrophic lateral sclerosis. Two monoclonal antibodies (ocrelizumab and daclizumab) and siponimod show positive results in multiple sclerosis. Thalamotomy of ventral intermediate nucleus (by gamma-knife or by magnetic resonance-guided focused ultrasound) is effective in drug-resistant essential tremor. The dose-dependent risk of foetal malformations associated with valproate and topiramate is confirmed.

Ischemic Amnesia: Causes and Outcome.

We aimed to describe the frequency and characteristics of acute ischemic stroke and transient ischemic attacks presenting predominantly with amnesia (ischemic amnesia) and to identify clinical clues for differentiating them from transient global amnesia (TGA).

Prevalence of Imaging Biomarkers to Guide the Planning of Acute Stroke Reperfusion Trials.

Imaging biomarkers are increasingly used as selection criteria for stroke clinical trials. The goal of our study was to determine the prevalence of commonly studied imaging biomarkers in different time windows after acute ischemic stroke onset to better facilitate the design of stroke clinical trials using such biomarkers for patient selection.

Prestroke CHA2DS2-VASc Score and Severity of Acute Stroke in Patients with Atrial Fibrillation: Findings from RAF Study.

The aim of this study was to investigate for a possible association between both prestroke CHA2DS2-VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF).

Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study.

This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation.

Sex Differences and Functional Outcome After Intravenous Thrombolysis.

Women have a worse outcome after stroke compared with men, although in intravenous thrombolysis (IVT)-treated patients, women seem to benefit more. Besides sex differences, age has also a possible effect on functional outcome. The interaction of sex on the functional outcome in IVT-treated patients in relation to age remains complex. The purpose of this study was to compare outcome after IVT between women and men with regard to age in a large multicenter European cohort reflecting daily clinical practice of acute stroke care.

Prehospital Scales for Large Vessel Occlusion: Closing in on a Moving Target.

Number needed to screen for acute revascularization trials in stroke: Prognostic and predictive imaging biomarkers.

Objective To systematically assess imaging biomarkers on CT-based multimodal imaging for their being predictive versus prognostic biomarkers for intravenous and endovascular (IA) revascularization therapy, and for their prevalence. Methods Our retrospective study included patients suspected of acute ischemic stroke with admission work-up including a non-contrast head CT, perfusion CT, and CT angiography. Modified Rankin scores at 90 days were used as outcomes. For each imaging biomarker, the effect size of the test of interaction between the presence of the biomarker and the treatment effect was calculated, allowing the inference of a total sample size. The total sample size required was combined with the prevalence of the biomarker to determine the number needed to screen. Results In the 0-4.5-h time window, the two predictive biomarkers associated with the smallest number needed to screen were perfusion CT penumbra ≥ 20% (404 NNS) and CT angiography collateral score ≥ 2 (581 NNS). In the 3-9-h time window, the four predictive biomarkers associated with the smallest number needed to screen were clot burden score (CBS) on CT angiography (1181 NNS), clot length ≥ 10 mm (1924 NNS), CBS and clot length ≥ 10 mm (1132 NNS), and CBS and perfusion CT penumbra ≥ 100% (1374 NNS). Perfusion CT ischemic core was a prognostic biomarker in both time windows. Interpretation Predictive biomarkers need to be differentiated from prognostic biomarkers when being considered to select patients for a trial, and their prevalence should be assessed to determine the number needed to screen and overall feasibility of the trials.

No Impact of Body Mass Index on Outcome in Stroke Patients Treated with IV Thrombolysis BMI and IV Thrombolysis Outcome.

The impact of excess body weight on prognosis after stroke is controversial. Many studies report higher survival rates in obese patients ("obesity paradox"). Recently, obesity has been linked to worse outcomes after intravenous (IV) thrombolysis, but the number and sample size of these studies were small. Here, we aimed to assess the relationship between body weight and stroke outcome after IV thrombolysis in a large cohort study.

CT-angiography source images indicate less fatal outcome despite coma of patients in the Basilar Artery International Cooperation Study.

Background Coma is associated with poor outcome in patients with basilar artery occlusion. Aims We sought to assess whether the posterior circulation Acute Stroke Prognosis Early CT Score and the Pons-Midbrain Index applied to CT angiography source images predict the outcome of comatose patients in the Basilar Artery International Cooperation Study. Methods Basilar Artery International Cooperation Study was a prospective, observational registry of patients with acute basilar artery occlusion with 48 recruiting centers worldwide. We applied posterior circulation Acute Stroke Prognosis Early CT Score and Pons-Midbrain Index to CT angiography source images of Basilar Artery International Cooperation Study patients who presented with coma. We calculated adjusted risk ratios to assess the association of dichotomized posterior circulation Acute Stroke Prognosis Early CT Score (≥8 vs. <8) and Pons-Midbrain Index (<3 vs. ≥3) with mortality and favourable outcome (modified Rankin Scale score 0-3) at one month. Results Of 619 patients in the Basilar Artery International Cooperation Study registry, CT angiography source images were available for review in 158 patients. Among these, 78 patients (49%) presented with coma. Compared to non-comatose patients, comatose patients were more likely to die (risk ratios 2.34; CI 95% 1.56-3.52) and less likely to have a favourable outcome (risk ratios 0.44; CI 95% 0.24-0.80). Among comatose patients, a Pons-Midbrain Index < 3 was related to reduced mortality (adjusted RR 0.66; 95% CI 0.46-0.96), but not to favourable outcome (adjusted RR 1.19; 95% CI 0.39-3.62). Posterior circulation Acute Stroke Prognosis Early CT Score dichotomized at ≥ 8 vs. <8 was not significantly associated with death (adjusted RR 0.70; 95% CI 0.46-1.05). Conclusion In comatose patients with basilar artery occlusion, the extent of brainstem ischemia appears to be related to mortality but not to favourable outcome.

Embolic Stroke of Undetermined Source and Detection of Atrial Fibrillation on Follow-Up: How Much Causality Is There?

There is increasing debate whether atrial fibrillation (AF) episodes during follow-up in patients with embolic stroke of undetermined source (ESUS) are causally associated with the event. AF-related strokes are more severe than strokes of other etiologies. In this context, we aimed to compare stroke severity between ESUS patients diagnosed with AF during follow-up and those who were not. We hypothesized that, if AF episodes detected during follow-up are indeed causally associated with the index event, stroke severity in the AF group should be higher than the non-AF group.

Sinking flap syndrome with abdominal pain: an atypical presentation.

A 53-year-old man developed significant mass effect secondary to an ischaemic stroke and was treated with decompressive craniectomy. During the first few days postsurgery he developed orthostatic vertigo with nausea. After a month, with increasing mobilisation and rehabilitation, he started reporting of severe abdominal pain. No aetiology could be found despite extensive local work up and the symptoms were resistant to any symptomatic treatment. Within days postcranioplasty there was a complete resolution of all the symptoms.

Intravenous Thrombolysis and Passes of Thrombectomy as Predictors for Endovascular Revascularization in Ischemic Stroke.

Patient selection for endovascular revascularization treatment (ERT) in acute ischemic stroke depends on the expected benefit-risk ratio. As rapid revascularization is a major determinant of good functional outcome, we aimed to identify its predictors after ERT.

Complete lingual palsy from bilateral Dejerine syndrome (bilateral medial medullary stroke).

Fatal subarachnoid hemorrhage following ischemia in vertebrobasilar dolichoectasia.

Vertebrobasilar dolichoectasia (VBD) is a chronic disorder with various cerebrovascular and compressive manifestations, involving subarachnoid hemorrhage (SAH). Occurrence of SAH shortly after worsening of clinical VBD symptoms has occasionally been reported. The goal of the study was to examine this association, in particular its pathophysiology, clinical precursor signs, time course, and outcome.To this end, in a retrospective multicenter study, we analyzed 20 patients with VBD and SAH in regard to preceding clinical symptoms, presence of vertebrobasilar thrombosis and ischemia, outcome and neuropathological correlates.Median age of the 7 female and 13 male patients was 70 years (interquartile range [IQR] 18.3 years). Fourteen patients (70%) presented with new or acutely worsening posterior fossa signs at a median of 3 days prior to SAH (IQR 2, range 0.5-14). A thrombus within the VBD was detected in 12 patients (60%). Thrombus formation was associated with clinical deterioration (χ = 4.38, P = 0.04) and ponto-cerebellar ischemia (χ = 8.09, P = 0.005). During follow-up after SAH, 13 patients (65%) died, after a median survival time of 24 hours (IQR 66.2, range 2-264 hours), with a significant association between proven ponto-cerebellar ischemia and case fatality (χ = 6.24, P = 0.01).The data establish an association between clinical deterioration in patients with VBD, vertebrobasilar ischemia, and subsequent SAH. Antithrombotic treatment after deterioration appears controversial and SAH outcome is frequently fatal. Our data also indicate a short window of 3 days that may allow for evaluating interventional treatment, preferably within randomized trials.

Repeated Intravenous Thrombolysis for Early Recurrent Stroke: Challenging the Exclusion Criterion.

Intravenous thrombolysis (IVT) within 4.5 hours from symptom onset improves functional outcome in patients with acute ischemic stroke. Its use in patients with previous stroke within the preceding 3 months is contraindicated because of the assumed higher risk of intracranial hemorrhage. In addition, tissue-type plasminogen activator may itself promote neurotoxicity and blood-brain barrier disruption. However, safety and effectiveness of repeated IVT is essentially unknown in patients with early (<3 months) recurrent stroke (ERS), because they were excluded from thrombolysis trials. This article reports the largest case series of repeated IVT in ERS.

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): clinical manifestations and multidisciplinary management.

Hereditary hemorrhagic telangiectasia (HHT), or Osler- Weber-Rendu syndrome, is a rare genetic disorder with autosomal dominant inheritance, characterized by recurrent epistaxis, mucocutaneous telangiectasia and visceral arteriovenous malformations (AVMs), which may lead to severe complications. The diagnosis of HHT is often delayed due to the rarity of the disease, and the variety of clinical manifestations. The management of HHT includes systematic screening for visceral AVMs at regular intervals, preventive interventions to reduce the risk of complications, and symptomatic measures. A multidisciplinary standardized program in specialised centers may improve the management of patients with HHT.

Eligibility and Predictors for Acute Revascularization Procedures in a Stroke Center.

Endovascular treatment (EVT) is a new standard of care for selected, large vessel occlusive strokes. We aimed to determine frequency of potentially eligible patients for intravenous thrombolysis (IVT) and EVT in comprehensive stroke centers. In addition, predictors of EVT eligibility were derived.

Large arterial occlusive strokes as a medical emergency: need to accurately predict clot location.

Endovascular treatment for acute ischemic stroke with a large intracranial occlusion was recently shown to be effective. Timely knowledge of the presence, site, and extent of arterial occlusions in the ischemic territory has the potential to influence patient selection for endovascular treatment. We aimed to find predictors of large vessel occlusive strokes, on the basis of available demographic, clinical, radiological, and laboratory data in the emergency setting.

Prediction of Large Vessel Occlusions in Acute Stroke: National Institute of Health Stroke Scale Is Hard to Beat.

Endovascular treatment for acute ischemic stroke with a large vessel occlusion was recently shown to be effective. We aimed to develop a score capable of predicting large vessel occlusion eligible for endovascular treatment in the early hospital management.


In 2015, cerebral stimulation becomes increasingly established in the treatment of pharmacoresistant epilepsy. Efficacy of endovascular treatment has been demonstrated for acute ischemic stroke. Deep brain stimulation at low frequency improves dysphagia and freezing of gait in Parkinson patients. Bimagrumab seems to increase muscular volume and force in patients with inclusion body myositis. In cluster-type headache, a transcutaneous vagal nerve stimulator is efficient in stopping acute attacks and also reducing their frequency. Initial steps have been undertaken towards modulating memory by stimulation of the proximal fornix. Teriflunomide is the first oral immunomodulatory drug for which efficacy has been shown in preventing conversion from clinical isolated syndrome to multiple sclerosis.

Intravenous Thrombolysis in Patients Dependent on the Daily Help of Others Before Stroke.

We compared outcome and complications in patients with stroke treated with intravenous thrombolysis (IVT) who could not live alone without help of another person before stroke (dependent patients) versus independent ones.