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.
Tuesday 17th October
9:30 - Registration
10:00 - Opening of the symposium
Moderator : Marie-Germaine Bousser
- Welcome speech by Marie-Germaine Bousser
- ISCVT 20 years by José Ferro
- Epidemiology by Suzanne Silvis
11:15 - 11:30 - coffee break
Moderator : José Ferro
- CVT in low middle income countries by Fernando Barinagarrementeria
- Genetics by Pankaj Sharma
- Biomarkers in cerebral venous thrombosis by Turgut Tatlisumak
1:00PM - 2:00PM - Buffet lunch
Moderator : Jonathan Coutinho
- Pathogenesis of venous infarcts by Diana Aguiar de Sousa
- Modern imaging of CVT at the acute phase by Jérôme Hodel
- Isolated intracranial HT and sinus pathology by Jérôme Mawet
3:30PM - 3:45PM - coffee break
Moderator : Fernando Barinagarrementeria
- CVT in neonates by Luca Ramenghi
- CVT and women hormonal life by Isabelle Crassard and Geneviève Plu-Bureau
- CVT and RCVS: is there a link? by Anne Ducros
5:30PM - End of the first day
Wednesday 18th October
9:15 - Registration
9:30 - Opening of the symposium
Moderator : Jan Stam
- Direct OAC and deep venous thrombosis : relevance for CVT? by Francesco Dentali
- Acute treatment : which heparin, which other medical treatment? by Jonathan Coutinho
- Difficult situations for acute anti-coagulant treatment by Isabelle Crassard
11:00 -11:15 - Coffee break
Moderator : Isabelle Crassard
- Decompressive surgery. When? How? by José Ferro
- Recanalisation after CVT: does it matter by Antonio Arauz
- Long term prognosis after CVT by Jukka Putaala
1:00PM - 2:00PM - Buffet lunch
Round table : Jan Stam, Jonathan COUTHINO, Fernando Barinagarrementeria, José Ferro, Marie-Germaine Bousser
2:00PM-4:30PM: Ongoing studies: endovascular treatment, duration of OAC?
What next ?
ISCVT 20 years by José Ferro
Epidemology by Suzanne Silvis
CVT in low middle income countries by Fernando Barrinagarrementeria
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.
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.
Pathogenesis of venous infarcts by Diana Aguiar de Sousa
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.
CVT in neonates by Luca Ramenghi
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.
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.
Direct OAC and deep venous thrombosis: relevance for CVT? by Francesco Dentali
Acute treatment: which heparin, which other medical treatment? by Jonathan Coutinho
Difficult situations for acute anti-coagulant treatment by Isabelle Crassard
Decompressive surgery. When? How? by José Ferro
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.
Long term prognosis after CVT by Jukka Putaala
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.
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.
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.
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.
Jonathan Coutinho is a staff neurologist at the Academic Medical Center, Amsterdam, the Netherlands. His main specialties are cerebral venous thrombosis and reperfusion therapy for acute ischemic stroke. In 2014 he completed his PhD on cerebral venous thrombosis and he has published more than 30 papers on this condition in the past years. He has given various invited lectures on cerebral venous thrombosis, including a state-of-the-art lecture for ISTH (Toronto, 2015), Karolinska stroke update (Stockholm, 2014) and the annual ESMINT congress (Nice, 2015). Jonathan Coutinho is a fellow of the European Stroke Organization and a member of the ESO guideline committee on cerebral venous thrombosis. Between 2014 and 2015 he spent 1 year as a post-doctorate research fellow at the Toronto Western Hospital, Canada.
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.
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.
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.
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.
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.