International workshop on Cerebral Venous Thrombosis (ISCVT), 20 years later, what next ?

Posted in Saison 2017-2018

Introduction

Cerebral venous thrombosis (CVT), is a rare and long neglected variety varety of stroke which can be due to a multitude of causes such as head trauma, surgery, pregnancy and delivery and a host of medical conditions. Once thought to be frequently lethal, CVT has nowadays a good prognosis , provided that it is diagnosed and treated very early.

20 years ago, J Ferro, from Portugal lounched the first International Study on Cerebral Venous Thrombosis (ISCVT), which he chaired together with 3 of us coming from Mexico (FB), Nederland (JS) and France (MGB). The purpose of the present meeting is to summarize the progresses made in the last 20 years, to review the ongoing trials, and to discuss new potential diagnostic tools and therapeutic measures in order to further improve the acute and long term prognosis of patients suffering CVT.

Organizing Committee
  • Marie-Germaine Bousser
  • José Ferro
  • Fernando Barinagarrementeria
  • Jan Stam
  • Jonathan Coutinho
Sponsors

APHP     CERVCO   Logo lariboisire   Universite Paris Diderot

Program

Tuesday 17th October

Session 1

Moderator : Marie-Germaine Bousser

Session 2

Moderator : José Ferro

Session 3

Moderator : Jonathan Coutinho

Session 4

Moderator : Fernando Barinagarrementeria


Wednesday 18th October

Session 5

Moderator : Jan Stam

Session 6

Moderator : Isabelle Crassard

Session 7

Round table : Jan Stam, Jonathan COUTHINO, Fernando Barinagarrementeria, José Ferro, Marie-Germaine Bousser

Ongoing studies: endovascular treatment, duration of OAC?

What next ?

General discussion


Abstracts

Welcome speech by Marie-Germaine Bousser

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ISCVT 20 years by José Ferro

The objective of the International Study on Cerebral Vein and Dural Sinus Thrombosis ISCVT was to collect reliable prospective data on clinical presentation, causes and risk factors, prognostic factors, currently applied treatments, complications and outcomes of patients with cerebral sinus thrombosis. ISCVT included consecutive in - and out patients with proven CVST treated in the participating institutions, diagnosed by MRI/MRA, X-ray angiography, or post mortem. All surviving patients were followed up during at least 6 months after the diagnosis of CVST. The primary measure of outcome was the mRS at 6 months. ISCVT succeeded to include 624 adult CVT cases from 89 centers in 21 countries. The mean age was 39 years and the female/male ratio 2.9. The median follow up 16 months. We will briefly review how the study was organized and launched, the key ISCVT results, the study main limitations and implications for practice and future research

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Epidemology by Suzanne Silvis

The first calculations of the incidence of CVT were extrapolated from autopsy series and provided estimates of 0.1-0.2 cases per 100 000. Data from population-based studies conducted in the past few years in the Netherlands and Australia have shown that the current incidence of CVT among adults is about 1.3–1.6 per 100,000, and the incidence is probably even higher in Asia and the Middle East, given the higher rate of pregnancy and infection related cases in these countries. Although the increase in incidence might partly be explained by a shift in risk factors, improvements in imaging techniques — which result in the identification of less-severe cases — is probably the most important contributing factor.

Most adults with CVT are aged 30–40 years and less than 10% of these individuals are older than 65 years. In young and middle-aged adults, CVT is three times more common in women than in men. This heavily skewed sex ratio is the result of the sex-specific risk factors of oral contraceptives, pregnancy and puerperium. A large number of other risk factors — both transient and permanent — have been associated with CVT. Some of these risk factors – such as genetic thrombophilia – coincide with those for VTE, while others, like head trauma and regional infections are specific for CVT. Notably, the prevalence of different risk factors varies considerably between countries. Due to the rarity of CVT the number of controlled studies that have properly examined associations between potential risk factors and CVT is limited. Overall, an associated condition can be identified in about 85% of patients.

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CVT in low middle income countries by Fernando Barrinagarrementeria

Cerebral venous thrombosis (CVT)is an uncommon and frequently unrecognized type of stroke.

Regarding World Bank data or the current 2016 fiscal year, low-income economies are defined as those with a GNI per capita, calculated using the World Bank Atlas method, of $1,045 or less in 2014; middle-income economies are those with a GNI per capita of more than $1,045 but less than $12,736;

ISCVT was a multinational (21 countries), multicenter (89 centers), prospective observational study. According to World Bank definition, ISCVT included just 5 countries with medium income, all of them from upper middle income.

ISCVT recluted 624 patient but just 103 (17%) come from middle income countries. From this numbers conclusions from ISCVT could be representative from countries with high income and other life conditions. Unfortunately There is no population studies reporting the incidence of CVT and very few stroke registries include CVT cases but none of them come from low income countries.I will start with information from my country Mexico  In the Mexican registry of cerebrovascular disease, a multihospital prospective Mexican stroke registry, Among 2000 all-type acute stroke patients, 59 corresponding to had CVT (female:male ratio, 5:1; median age, 31 years). Puerperium (42%), contraceptive use (18%), and pregnancy (12%) were the main risk factors in women. In 67% of men, CVT was registered as idiopathic, but thrombophilia assessment was suboptimal.

Data from a single third level center in Mexico City showed some differences regarding ISCVT results mainly in risk factors or etiology of CVT. Among 415 patients seen in 23 years, mean age was 31 years with a clear female predominance (83%). Main risk factors or etiology included pregnancy or puerperium in 49%, thrombophilia in 26%, oral contraceptives in 7.5% and unknown 17%. The long term period of study explain the relatively low percentage of anticoagulation 48%, aspirin 48%, and 4.5% with no treatment. In last 15 years practically all patients received anticoagulation.

In this series with just 50% of anticoagulation rate acute mortality rate was 10.9%.

Information from Africa reveals that particular risk factors are related to CVT such as high frequency of infections and cases related to pregnancy and puerperium. Interestingly the frequency in the use of acute anticoagulation is close to 90% with good outcome in 75% and rate mortality between 7 and 10%

India has a long tradition reporting their series with CVT with emphasis in those cases related to pregnancy and puerperium. Analysis from recent series disclosed a lesser frequency of this association then previous years. Acute anticoagulation reached almost 95% with a mortality rate of 16%.

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Genetics by Pankaj Sharma

CVT is an understudied subtype of stroke. As is known to affect young (mainly female) patients its aetiological cause has been mainly linked to hormonal relationships. Notwithstanding this gender difference, the presence of this condition in a younger population opens up the tantalising possibility that there is a likely genetic susceptibility to CVT. Several investigators across the world have attempted to dissect such an aetiological basis but the relatively rarity of this condition means that no single investigator has had the capability to identify its genetic basis in a robust and reliable fashion. This talk will summarise the know data on CVT genetics and also present information about the ongoing international study to establish the largest genetic DNA bank in CVT in order to enable us to better understand the genetic basis of this important condition.

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Biomarkers in cerebral venous thrombosis by Turgut Tatlisumak

The term "biological marker" was introduced in 1950s. The widespread use of the term "biomarker" dates back to as early as 1980. In 1998, the National Institutes of Health Biomarkers Definitions Working Group defined a biomarker as "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.“ Usefulness of a biomarker depends on the precision it offers, usually evaluated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and sometimes positive or negative likelihood ratios (PLR and NLR, respectively).A biomarker for clinical use needs good sensitivity e.g. ≥0.9, and good specificity e.g. ≥0.9 although they should be chosen with the population in mind so positive predictive value and negative predictive value are more relevant. Biomarkers can be e.g. molecular or imaging biomarkers. Biomarkers can be classified in different ways: diagnostic (cardiac troponin in myocardial infarction), disease staging (brain natriuretic peptide for congestive heart failure), prognostic (cancer biomarkers), and response monitoring (HbA1c in diabetes). Further, biomarkers can stem from different tissues (blood, cerebrospinal fluid, urine, etc.) or may be noninvasive measurable (EEG or imaging biomarkers). Several molecules, mostly involved in coagulation system, have been studied in CVT patients mainly in rather small patient numbers and mostly delivered inconclusive or negative results in terms of acting as a biomarker. D-dimer, a fibrin-degradation product, released when plasmin breaks down fibrin treads in a clot and can reliably be measured from venous blood with quick and inexpensive methods in clinical settings, is the most commonly investigated. D-Dimer is routinely used in deep-vein thrombosis and pulmonary embolism suspect cases combined with clinical scores delivering good diagnostic precision. In CVT, D-Dimer seems to offer rather good precision in acute, but not in subacute/chronic cases and not in isolated headache/encephalopathy-type patients. Guidelines do not directly recommend replacing diagnostic imaging studies with D-Dimer measurements. Large, prospective, multicenter studies are needed for developing reliable biomarkers in diagnostics and other aspects of CVT.

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Pathogenesis of venous infarcts by Diana Aguiar de Sousa

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Isolated intracranial HT and sinus pathology by Jérôme Mawet

Almost 20 years ago, attention was drawn on the fact that cerebral venous thrombosis may present as an isolated intracranial hypertension, mimicking idiopathic isolated hypertension (IIH).

Today, radiological evidence of cerebral venous sinus stenosis in almost all patients with IIH and improvement of IIH after venous sinus stenting in case series suggest that the spectrum of cerebral venous disease is larger and not only relies on occlusion, but that cerebral venous stenosis may also be highly clinically relevant. This presentation will present the present data on venous disorders and intracranial hypertension and discuss the actual treatment recommendations.

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CVT in neonates by Luca Ramenghi

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Modern imaging of CVT at the acute phase by Jerome Hodel

The main topic of our research group is to develop advanced MR techniques in the field of neurodegenerative and inflammatory diseases.

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CVT and woman hormonal life by Isabelle Crassard and Geneviève Plu-Bureau

Cerebral venous thrombosis is three times more common among women than men. This sex ratio could be partly explained by specific female factors like oral contraceptives and to lesser extent pregnancy and post-partum. Combined hormonal contraceptives (CHC) increased the risk of CVT. The increase in thrombotic risk is the highest the first year of CHC use and 3rd generation (desogestrel or gestodene) or drospirenone or cyproterone acetate combined with ethinyl-estradiol CHC use are associated with an increased venous thrombotic risk as compared to 2nd generation (levonorgestrel combined with ethinyl-estradiol) CHC use. Moreover, the increased risk of venous thrombosis from CHC use may be synergic to that of biological thrombophilia. Despite a wide variety of clinical presentations, early diagnosis of CVT, mostly based on MRI/MRA, is essential but often difficult particularly during post-partum because of the numerous causes of headache that may occur after delivery. There are not specific clinical or radiological pattern of CVT during pregnancy and post-partum. The prognosis of CVT is however better in women with gender specific risk factors than in other causes of CVT, with a complete recovery in 80% of patients. Future pregnancy is possible, but contraception with estro-progestogens is definitely contra-indicated. Progestin-only contraceptive is an alternative for women with contraindication of estrogen use. By contrast with COC, low doses of both oral progestin contraceptives and intra-uterine levonorgestrel could be safe with respect to venous thrombotic risk.

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CVT and RCVS: is there a link? by Anne Ducros

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by severe headaches, often of the thunderclap type, and multifocal constriction of cerebral arteries, that resolve spontaneously in 1 to 3 months. More than half the cases of RCVS occur in special circumstances such as exposure to vasoactive substances or postpartum. A few patients with RCVS occurring in the setting of a CVT have been described, underscoring the fact that a patient with severe headaches might have two distinct underlying vascular disorders. Diagnosis relied on careful clinical analyses of the headache features and serial cerebral imaging.

Several hypotheses can be raised to explain the association of CVT and RCVS. It is difficult to imagine that a CVT could by itself trigger cerebral arterial constriction. Both conditions may share the same cause, e.g. postpartum or female hormonal treatments. Since RCVS has also been reported in the setting of abnormal intracranial pressure, intracranial hypertension due to CVT might trigger a RCVS. Conversely, post lumbar puncture syndrome might also be involved.

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Direct OAC and deep venous thrombosis: relevance for CVT? by Francesco Dentali

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Acute treatment: which heparin, which other medical treatment? by Jonathan Coutinho

Heparin is the mainstay for the treatment of acute CVT, based on data from two small randomized controlled trials. There is, however, no consensus on whether to use unfractionated heparin or low-molecular weight heparin. Surveys suggest that many physicians – especially neurologists – prefer unfractionated heparin, despite the fact that the available evidence seems to suggest that low-molecular weight heparin is the better choice. In patients with acute symptomatic seizures, anti-epileptic drugs should be administered as soon as possible to prevent recurrent seizures. Use of prophylactic anti-epileptic drugs in high risk patients has been advocated by some, but is controversial. Intracranial hypertension is very common in the acute phase of CVT. Acetazolamide has the potential to reduce intracranial pressure by lowering cerebral spinal fluid production, but is probably of limited value in the acute phase of CVT. The fact that cerebral edema in CVT is mostly vasogenic would suggest that the use of steroids may be beneficial. However, the available data on steroids in CVT – which is extremely limited – suggests that its use is associated with a worse outcome.

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Difficult situations for acute anti-coagulant treatment by Isabelle Crassard

The treatment of CVT at the acute phase is based on international recommendations. One of the most important of these treatments is heparin, regardless the clinical form of CVT . However, there are sometimes difficulties with it and this will be discussed in this presentation.

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Decompressive neurosurgery in cerebral venous thrombosis (CVT) by José Ferro

Decompressive neurosurgery (Hemicraniectomy or haematoma evacuation) are a life-saving intervention to prevent death in severe CVT patients with large hemispheric venous infarcts and hemorrhages. Due to the rarity of this clinical presentation of CVT no randomized controlled trials have been performed. In the literature several case reports, case series, two systematic reviews and two non-randomized controlled studies comparing decompressive surgery with no surgery, can be retrieved. From a literature review of case series (all retrospective), the average death rate among patients treated with decompressive surgery is 18.5%, the death or disability rate is 32.2%, the severe dependency rate is 3.4% and the complete recovery rate 30.7%. Despite the low numbers, the results of the two nonrandomized controlled studies demonstrate that decompressive surgery prevents death and does not result in an excess of severe disability. The recent ESO-EAN guidelines recommend using decompressive surgery for patients with acute CVT and parenchymal lesion(s) with impending herniation to prevent death (Quality of evidence – Low; Strength of recommendation – Strong). There is need to increase the evidence supporting and defining which patients benefit most from the intervention. The ongoing multicenter prospective registry DECOMPRESS-2 aims to include 100 patients, to describe vital and functional outcome of CVT patients treated by decompressive surgery, to identify subgroups of CVT patients who benefit most from this surgery and to describe patient-centered psychosocial outcomes (opinion on the benefit of surgery, depression/anxiety, Quality of Life, return to work, caregiver burden) after decompressive surgery in acute CVT.

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Recanalisation after CVT: dos it matter? by Antonio Arauz

The degree of recanalisation has been proposed as a posible prognostic marker after cerebral venous thrombosis. However, only a few studies have investigated the rates of recanalisation after CVT. In the majority of patients, partial or complete recanallization ca be demostrated with MRI. It is not known if MRI visualised recanalisation correlates with clinical outcome or recurrence. Combining the results of studies with repetitive imaging led to the suggestion that recanalisation only occurs within the first months and not after. Recanalisation in CVT occurs over time, until month 11 and complete recanalisation may influence functional outcome. The role of recanalisation on outcome and rerecurrence CVT need to be studied in future trials.

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Long term prognosis after CVT by Jukka Putaala

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Round table : Ongoing studies: endovascular treatment, duration of OAC? What next ?

Biographies

MGB 600Marie-Germaine Bousser

Marie-Germaine BOUSSER is emeritus Professor of Neurology at Paris Diderot University and former head of the Neurology department of Lariboisière Hospital in Paris. She is a headache and stroke specialist and was one of the Presidents of the International Headache Society and of the French headache society. She was one of the founders of the European Stroke Conference and she was the founder and first President of the French Stroke Society.

Cerebral venous thrombosis (CVT) has long been one of her favorite topics. She published in 1985 a series of 38 patients suffering from CVT in which she was one of the first to recommend the use of heparin treatment. In 1992, together with R. Ross Russell, she published a book on CVT. In the last 20 years, MG BOUSSER and her co-worker Isabelle CRASSARD gathered a cohort of over 500 patients with CVT about which they have written many articles on various aspects of this disorder.

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José FerroJosé Ferro

José M. Ferro was born in Lisbon on 22 October 1951. He graduated in 1975 and received his PhD in Medicine in 1987 from the the University of Lisbon. He was a post-doctoral fellow at the Department of Clinical Neurological Sciences, London, Canada.

He is currently Full Professor of Neurology and President of the “Conselho de Escola” of the School of Medicine at the University of Lisbon. He is Director of the Department of Neurosciences and Mental Health and Director of the Neurology Service at the Hospital de Santa Maria, Centro Hospitalar Lisboa Norte. He is the head of José Ferro Lab at the Instituto de Medicina Molecular, University of Lisbon.

He was President of the European Neurological Society, Chairman of the Stroke Portuguese Society and was recently elected for the Board of the Word Stroke Organisation in representation of the European Stroke Organisation. He was a member of the Program Committee of the European Stroke Conference. He is  also member of the Scientific Panel for Health of the Directorate-General for Research and Innovation, Directorate E – Health, of the European Commission.

He belongs to the Editorial Board of the journal Stroke, Journal of Neurology, European Stroke Journal and Cerebrovascular Diseases.

Has authored or co-authored 299 papers published in international journals and 60 book chapters.

Research in his main area of interest focuses on to cerebrovascular disease, in particular cerebral venous thrombosis, cognitive and psychiatric consequences of stroke, and stroke in young.

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Suzanne Silvis photoSuzanne Silvis

Suzanne Silvis obtained her MD from the VU University in Amsterdam in 2010 and will complete her Neurology residency at the Academic Medical Center in Amsterdam in 2018. During her residency, she started as a PhD candidate in stroke research under supervision of dr. Jonathan Coutinho. Her research concerns several aspects of cerebral venous thrombosis, with emphasis on risk factors for cerebral venous thrombosis.

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Fernando Barinagarrementeria photoFernando Barinagarrementeria

Dr Fernando Barinagarrementeria obtained his medical degree from the Universidad La Salle in Mexico City an was trained in neurology at the Institute of Neurology and Neurosurgery in Mexico City. Later he pursued specialized training in stroke medicine in Bordeaux under the mentorship of Professor Jean Marc Orgogozo.

Dr. Barinagarrementeria Founded the Stroke Clinic at National Institute of Neurology and Neurosurgery and was founder president of Mexican Stroke Association. Has been invited professor at University of Miami, Universidad de Navarra, University of Texas in San Antonio, University of Sao Paulo, Harvard Stroke Society, Hospital de Cruces, Bilbao, among others. Has been member of editorial board in Stroke, Journal of Stroke and cerebrovascular diseases and cerebrovascular Diseases.

He has authored more than 120 papers in peer-reviewed journals such as; The Lancet Neurology, Neurology, Stroke, Journal of Neurology, neurosurgery and psychiatry, International Journal of Stroke, Cerebrovascular Diseases, Journal of Stroke and Cerebrovascular Diseases and others. He is author of 4 books in Cerebrovascular diseases and other one of general neurology.

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Pankaj SharmaPankaj Sharma

Professor Pankaj Sharma is Director of the Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL). He was formally head of Imperial College Cerebrovascular Research Unit (ICCRU) at Imperial College London. He holds doctorates from both the Universities of Cambridge and London.  He is Editor-in-Chief of the Journal of the Royal Society of Medicine Cardiovascular Disease, Medical Director of Different Strokes, a UK national charity which seeks to support young stroke victims. A former Dept of Health Senior Fellow, British Heart Foundation Clinician Scientist at Cambridge University and Fulbright Scholar at Harvard Medical School, he has a long standing interest in the genetics of hypertension, cardio- and cerebrovascular disease.

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Turgut Tatlusimak photoTurgut Tatlisumak

Turgut Tatlisumak is professor of neurology at the University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden. He has long served as director of stroke center at the Department of Neurology, Helsinki University Central Hospital. He trained in neurology at the same department and completed a research fellowship at the University of Massachusetts Medical Center. He holds degrees in teaching and health administration. He is the founding chairman of Finnish National Telestroke Network. Turgut Tatlisumak has investigated almost all facades of stroke. He has edited or contributed to more than 10 books and published over 300 articles. He served as assistant editor and member of editorial board of Stroke, was the founding chief editor of Case Reports in Neurology, and member of editorial board to several other journals. He served as a peer reviewer to over 60 journals over 300 times. Dr Tatlisumak has been involved in over 50 multicenter trials serving at various positions including chairmanship of steering committees. He supervised 12 PhD, 10 master’s, and 35 MD theses. He has received several teaching and research awards. Dr Tatlisumak has served on executive committee of the Finnish Neurological Society and the Nordic Stroke Society. He is past treasurer of the European Stroke Organization. He is a fellow of AHA and ESO.

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Diana Aguiar de Sousa

Diana Aguiar de Sousa, MD, MSc, is Neurologist at Hospital de Santa Maria, in Lisbon, and invited assistant professor of Neuroanatomy at University of Lisbon. She graduated from the University of Lisbon (2004-2010) and completed her preclinical and residency training at Hospital Santa Maria. She is since 2013 clinical investigator at Instituto de Medicina Molecular and PhD student at University of Lisbon, under the guidance of Prof. José Ferro and Prof. Patrícia Canhão. She also completed with honours the Clinical Scholars Research Training Certificate Program from Harvard Medical School and a European Academy of Neurology Research Fellowship in acute stroke at Inselspital Bern, under supervision of Prof. Marcel Arnold and Prof. Simon Jung. She was awarded with a Young Investigator Award of the European Stroke Organization in 2016. She has authored over 40 presentations at scientific conferences, 15 peer reviewed papers and 5 book chapters. Her primary research interest is cerebral venous thrombosis.

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Jérôme HodelJérôme Hodel

Jerome Hodel, MD, PhD, Head of the Neuroradiology Department, Henri Mondor Hospital, Creteil, France

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Jonathan Coutinho photoJonathan Coutinho

Jonathan Coutinho became a board certified neurologist in 2014. After completing a post-doctorate fellowship at the University of Toronto, he became a staff neurologist at the Academic Medical Center in Amsterdam. He completed his PhD in 2014 on cerebral venous thrombosis. He is involved in several ongoing international studies on cerebral venous thrombosis, including the TO-ACT trial, EXCOA, DECOMPRESS-2 and RESPECT CVT. He has authored more than 30 papers on cerebral venous thrombosis.

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Jérôme MawetJérôme Mawet

Jerome Mawet is neurologist at the Emergency Headache Centre in Lariboisière, Paris, France.

He was board certified Neurologist in Liege, Belgium in 2008 and obtained the ESO European Master in Stroke Medicine at the Donau University, Krems, Austria in 2009. After a clinical fellowship in stroke in Lariboisiere, Paris, he joined in 2012 the team of the Emergency Headache Centre, a place which receives over 10000 admissions a year of patients with acute headache. In 2013-2014, he travelled to Boston, USA, for a one-year research fellowship on interaction between and stroke at the Harvard Medical School.

Because of his dual training in stroke and headache, he has special interest for vascular headache and for interaction between migraine and stroke.

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Luca Ramenghi photoLuca Ramenghi

Luca Antonio Ramenghi is the Medical Director of Neonatal Intensive Care Unit at Gaslini Children’s Hospital. His main scientific interest has been since the begining of his career the diagnosis of brain lesions acquired during the perinatal period, in term and preterm babies (intraventricular haemorrhage, cerebellar haemorrhage, perinatal arterial stroke and perinatal axphyxia). The first pubblication were based on the use of transfontanellar ultrasound and in the following years on brain MRI of neonates. He is member of the European Neonatal Brain Club, a group of researcher in this field pretty popular among neonatologists.

He is author of 115 international publications on Pub Med , author of 12 chapters of international books about neonatal neurology. He presented several times in different European courses, speeches on CSVT in neonates covering different aspects and, in particular, differences among preterm and term babies suffering such a disease.

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Isabelle Crassard

Isabelle Crassard is neurologist at the neurology department of Lariboisière Hospital in Paris. After a combined fellowship in neurology and angiohematology, she is particularly interested in disorders of coagulation associated with strokes and cerebral venous diseases. She worked with Marie-Germaine Bousser on the topics of cerebral venous thrombosis during the last 20 years.

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silhouette homme 150Geneviève Plu-Bureau

N.C

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Anne DUCROSAnne Ducros

Anne Ducros is Professor of Neurology at the University of Montpellier in France since September 2013 and Head of the Headache and Migraine Unit in the Department of Neurology of the Montpellier University Hospital. She obtained her M.D. in 1997 at the University of Montpellier and a Ph.D. in 1998 at the University Pierre et Marie Curie in Paris in the field of genetics of migraine. After having completed a stroke and headache fellowship, she participated in 2000 to the launching of the first French Emergency Headache Centre, in Lariboisière Hospital in Paris and co-headed this department for 13 years. Her main fields of research involve primary and secondary headaches in emergency settings, with a special interest for the links between headache and stroke. She is associate editor of Cephalalgia and president of the French Headache Society.

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Francesco DentaliFrancesco Dentali

N.C

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Jan STAMJan Stam

Jan Stam received his medical training at the University of Utrecht. After various attempts to postpone specialisation (such as training in tropical medicine, working in rural Angola and at the Jellinek Centre for Addiction Disorders in Amsterdam) he started his residency at the department of Neurology in Amsterdam (chair prof. H. van Crevel). In 1984 he was board certified as neurologist and in 1987 he obtained his doctorate, after defending his thesis: "A Cli¬nical and Electromyo¬graphic Stu¬dy of the Tendon Reflexes". In 1993 he was appointed Professor of Clinical Neurology at the Academic Medical Centre, University of Amsterdam. He was vice-chairman of the department of Neurology, director of the Neurology residency program and co-ordinated the Neurology training for medical students until his retirement in august 2014. Research interests: Cerebrovascular diseases, in particular cerebral venous thrombosis and cerebral small vessel disease.

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Antonio Arauz

Dr. Arauz obtained his medical degree from the National University of Mexico (UNAM) and his Master and PhD of Sciences from the same University. He also completed postgraduate training in Neurology and clinical fellowship of cerebrovascular diseases at the Instituto Nacional de Neurología in Mexico City. He is professor of Neurology at Facultad Mexicana de Medicina of the La Salle Univeristy and assistant professor of Neurology at UNAM. Dr. Arauz is the coordinator of the Stroke clinic and Vascular Neurology Program, at Instituto Nacional de Neurología y Neurocirugía Manuel Velsco Suárez in Mexico City.

Dr. Arauz was the country leader of following clinical trials: PREVAIL, PROFESS, SPS3, and co-investigator in the OPTIC Stroke Registry, the SOCRATES, and NAVIGATE ESUS international clinical trials. In his research, Dr. Arauz focuses primarily on the ischemic stroke in the young, especially in cervical artery dissection and cerebral venous thrombosis. He has authored more than 100 papers in peer-reviewed journals such as; The Lancet Neurology, Neurology, Stroke, Journal of Neurology, neurosurgery and psychiatry, International Journal of Stroke, Cerebrovascular Diseases, Journal of Stroke and Cerebrovascular Diseases and others.

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silhouette homme 150Jukka Putaala

N.C

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