Cadasil 20 years later, what next?

Publié dans Saison 2013-2014


En 1993 à Paris, des équipes clinique et génétique dirigées respectivement par Marie-Germaine BOUSSER et Elisabeth TOURNIER-LASSERVE décrivirent une nouvelle maladie qui touchait une famille française dont l’étude approfondie de 57 membres adultes permit de localiser le gène responsable sur le chromosome 19 et d’en définir les caractéristiques essentielles : affection autosomique dominante des artères cérébrales responsable chez l’adulte jeune d’infarctus cérébraux et d’ atteinte de la substance blanche, d’où l’acronyme CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). En moins de trois ans, l’étude de 33 autres familles françaises aboutit à la découverte du gène responsable, Notch 3, connu chez la drosophile mais pas encore chez l’homme. Une nouvelle voie de recherche fondamentale s’ouvrit alors pour comprendre comment des mutations d’un tel gène pouvaient aboutir à des infarctus cérébraux chez l’homme. Parallèlement, plus de mille familles atteintes de CADASIL ont été identifiées à travers le monde et plus de mille articles ont été publiés sur le sujet. Pour marquer le vingtième anniversaire de la description de la maladie, un workshop aura lieu les 19 et 20 Septembre 2013 à la Fondation Singer-Polignac. Il réunira les meilleurs spécialistes mondiaux de CADASIL et des autres maladies de petites artères cérébrales, du gène Notch 3, et du couplage neuro-vasculaire, afin d’envisager de nouvelles pistes de recherche permettant de déboucher sur d’ éventuelles voies thérapeutiques.

In 1993 in Paris, our clinical and genetic teams, headed respectively by MG Bousser and E. Tournier-Lasserve, identified a new disease affecting a French family. The extensive study of 57 adults members of this family led to the localization of the responsible gene on chromosome 19 and to the description of the main characteristics of the disease : autosomal dominant small artery disease of the brain with subcortical infarcts and white matter involvement, hence the proposed acronym : CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy). In less than 3 years, the study of 33 french families led to the identification of the responsible gene : Notch 3, so far known in the drosophila, but not in humans. A new basic science research field was thus opened to understand how mutations of this gene could induce cerebral infarcts in humans. More than 1000 CADASIL families have now been identified worldwide, and over 1000 scientific articles have been published on this topic. To celebrate the 20th anniversary of the disease description, a workshop will take place on September 19-20 2013 at Fondation Singer Polignac in Paris. The best specialists of CADASIL, of other small artery diseases of the brain, of Notch 3 and of neurovascular coupling will participate, aiming at developing new research projects and opening therapeutic avenues.


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Thursday 19th septembre2013

Session 1 - CADASIL 20 years later

Moderators : Marie Germaine Bousser and Elisabeth Tournier-Lasserve



Moderators : Bo Norrving and Anne Joutel






Moderators : Léonardo Pantoni and Hugues Chabriat






Moderators : Christophe Tzourio and Joël Menard




Friday 20th september 2013



Moderators : Mike Moskowitz and Jean-Louis Mas



Moderators : Jan Torleif Pedersen and Stéphanie Debette



Session 7 – CADASIL: WHAT NEXT ?

Moderators : Constantino Iadecola and Marie-Germaine Bousser



 General discussion : What next ? with Costantino Iadecola and Marie-Germaine Bousser


Présentations : (texte & vidéo)

Opening speech by Marie Germaine Bousser



CADASIL : main clinical features and natural history by Hugues Chabriat


The main clinical manifestations of CADASIL include migraine with aura, ischemic stroke, mood disturbances, gait problems and cognitive decline from executive dysfunction to severe dementia. The onset of symptoms and clinical course of the disease appear extremely variable among affected subjects although the clinical severity increased globally with age. Gender and vascular risk factors seem to modulate the clinical expression of the disease. Recently, a large follow-up study allowed determining the most important predictors of disability and dementia, outside age, during the course the disease. Better knowledge of the natural history of the disease, of the determinants of the phenotype variability and of the progression of disability are crucial for preparing future therapeutic trials in this disorder.



CADASIL : lessons from neuroimaging by Hugues Chabriat and Marco Düring


CADASIL is responsible for multiple types of signal abnormalities as seen on cerebral MRI examination. Hyperintensities on T2-weighted or FLAIR MRI are the earliest manifestations of the disease. Recent experimental and imaging data suggest that different mechanisms may promote the development of these lesions, the extent of which appears widely variable during the course of the disease. Lacunar infarctions are often associated with white-matter hyperintensities but occur usually later. Their number was found strongly related to the acceleration of cerebral atrophy observed in the disease. A recent longitudinal study on incident lacunes suggests that the appearance of lacunes is intimately related to the location of white-matter hyperintensities. Other cerebral tissue modifications such as microbleeds, dilated perivascular spaces or microstructural tissue changes as measured using water diffusion can be also observed. During the recent decade, the relationships between these different MRI markers and the clinical presentation of CADASIL have been analyzed and their potential predictive value and usefulness for clinical trials were recently evaluated.

The imaging markers in CADASIL are also close to those usually detected in other types of small vessel disease. Therefore, data obtained in CADASIL are unique to understand the pathophysiology of subcortical ischemic vascular cognitive decline in general. Recently, studies showed that ischemic lesions in strategic white matter tracts drive the typical cognitive symptoms in CADASIL. Interestingly, lacunes have distant effects on connected cortical regions and the impact of subcortical regions on cognitive performance seems to be mediated by the occurrence of cortical alterations. In addition, there is an interplay between white matter integrity, cognitive and gait performances, providing a basis for the frequent observation that gait and cognition decline in parallel in small vessel diseases.




CADASIL, molecular genetics and genetic counseling by Elisabeth Tournier-Lasserve


CADASIL was initially described as an autosomal dominant vascular leukoencephalopathy linked to chromosome 19 and characterized by the presence of a specific Granular Osmiophilic Material (GOM) within the membrane of arterial vascular smooth cells. In 1996, all families fulfilling those criteria were shown to harbor highly stereotyped mutations leading to an odd number of cysteine residues within one of the 23 exons encoding EGF-like motifs of the NOTCH3 receptor.

More than 3000 index cases with a small artery disease of unknown etiology have now been screened for NOTCH3 mutations in our diagnostic lab, allowing diagnosis and genetic counseling of this condition in both familial and sporadic cases. Fifteen per cent of these patients have typical CADASIL mutations.

Interestingly, 2 % of these index patients show missense mutations which do not affect the number of cysteine residues but are absent from all existing databases, raising the question of their pathogenicity. In addition, several index patients and their relatives were shown to carry mutations leading to a premature stop codon and a NOTCH3 haploinsufficiency whose pathogenicity is so far unknown. A combination of skin biopsy electronic microscopy analysis, mRNA analysis and familial segregation analysis have been used to clarify the pathogenicity of these mutations and avoid a misdiagnosis of CADASIL.



Neuropathology of CADASIL and other small artery diseases of the brain (SADB) by Hannu Kalimo


The three main small vessel diseases (SVD) are (1) the soul of this workshop, CADASIL, (2) arteriolosclerosis (AloS; “Binswanger´s disease”) and (3) cerebral amyloid angiopathy (CAA). CADASIL (CAD) and AloS share several features: Both affect mainly white matter (WM) or deep gray matter (GM) arterioles, whereas cortical arterioles are relatively spared. In CAD and AloS the arteriolar smooth muscle cells (SMC) degenerate, in CAD associated with the pathognomonic accumulation of granular osmiophilic material (GOM) on or close to the degenerating SMCs, which become replaced by collagen with consequent thickening of the walls, stenosis and subsequent lacunar ischemic infarcts. Intracerebral hemorrhages (ICH) in CAD and AloS are relatively rare, since the thickened walls appear to withstand the burden, unless hypertension (rel. uncommon in CAD but frequent in AloS) bring on extra destructive force. CAA, most commonly due to A deposition, affects almost exclusively cortical arterioles with parieto-occipital predilection. The replacement of SMCs by deposits of A renders the arteriolar walls quite fragile and, thus, large ICHs are common in CAA, mainly of lobar type corresponding to the CAA distribution. In addition there are several other SVDs, which will be shortly discussed in the presentation.



Introduction to Cadasil and other hereditary SABDC by Léonardo Pantoni and Hugues Chabriat


CADASIL, mechanisms of disease by Anne Joutel


Among the important advances in the field of small vessel disease (SVD) of the brain has been the identification of genes involved in mendelian forms of SVD. CADASIL, with an autosomal dominant mode of transmission, is an archetypal SVD that emerges as the most common heritable cause of stroke and vascular dementia worldwide. The disease is caused by highly stereotyped missense mutations that alter the number of cysteine residues in the extracellular domain of Notch3, a transmembrane receptor that undergoes a series of proteolytic cleavages upon ligand binding that release the extracellular domain (Notch3ECD) and ultimately enable the intracellular domain to translocate to the nucleus, where it acts as a transcriptional activator. Notch3 is predominantly expressed in smooth muscle cells and is critical for the maturation and function of small vessels of the brain. CADASIL mutations differentially affect Notch3 transcriptional activity, however, it is still highly debated whether this may contribute to the disease process. On the other hand, all CADASIL-associated Notch3 mutations are associated with early accumulation of Notch3ECD at the plasma membrane of smooth muscle cells, in extracellular deposits called Granular Osmiophilic Material. Importantly, recent studies lend support to a Notch3ECD cascade hypothesis in CADASIL disease pathology, which posits that aggregation/accumulation of Notch3ECD is a central event, promoting the abnormal recruitment of functionally important extracellular matrix proteins that may ultimately cause multifactorial toxicity. Finally, a unique collection of mouse models, including one (TgPAC-Notch3R169C) that recapitulates the preclinical stage of the disease, has been generated. Analysis of these mice provides compelling evidence for cerebrovascular dysfunction and microcirculatory failure as the earliest consequences of pathogenic mutant Notch3, culminating in progressive hypoperfusion and white matter damages.



CADASIL SADB and migraine by Katharina Eikermann-Haerter


Migraine is associated with acquired and genetic vasculopathies in epidemiological, genetic and neuroimaging studies. Migraine is an established independent risk factor for ischemic stroke and ischemic heart disease, while arterial dissections, arterio-venous malformations and reversible cerebral vasoconstriction syndromes are associated with migraine as well. Migraine is also part of the phenotype of genetic vasculopathies, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) or retinal vasculopathy with cerebral leukodystrophy (RVCL). Possible mechanisms for the clinical association between migraine and vasculopathies include shared genetic factors, vascular endothelial dysfunction, or neuronal mechanisms. Recent studies suggest that excitatory mechanisms implicated in migraine pathophysiology (spreading depolarization) increase cerebral vulnerability to ischemia. Spreading depolarization can be triggered by cerebral hypoperfusion. Upon ischemia, CADASIL mutant mice develop high-frequent spreading depolarizations that exacerbate the metabolic mismatch and worsen outcomes. These findings suggest spreading depolarization as a potential mechanism underlying the migraine-stroke continuum in CADASIL, and perhaps linking migraine and other small artery diseases of the brain as well.



Hypertension and ageing related SADB by Bo Norrving


In the early literature reports on SADB hypertension was considered a characteristic feature, and even considered mandatory for the development of lacunar infarcts. However, later studies have shown that the prevalence of hypertension is similar in lacunar and non-lacunar infarcts. Many patients with SADB are not hypertensive.

For silent cerebral infarcts (mostly caused by SADB) and white matter hyperintensities of presumed ischemic origin, hypertension along with age have been the most consistent risk factors across studies. Recent studies using MRI have shown that high blood pressure affects brain morphometrics already in early mid-age.

In most studies a simplistic definition of hypertension has been used. However, blood pressure vaiability appears to equally important as blood pressure levels in the relation to stroke. Also, the genetical co-variance between hypertension and SADB is a resaech area that is currently being explored. Whereas many pathophysiological links between hypertension and SADB remains to be further studied, the practical importance of control of hypertension in the population should be widely recognized as hypertension remains the single most important modifiable risk factor for stroke.




Hypertension and ageing : Lessons from experimental models by Franck Faraci


Hypertension is one of the greatest risk factors for cerebrovascular disease and stroke and a leading cause of cognitive impairment. The impact of hypertension on the cerebral circulation is diverse with effects along all the vascular tree as well as cells that interact with the vasculature. This presentation will summarize recent findings related to mechanisms by which hypertension, and particularly angiotensin II, promotes large and small vessel disease in brain including interacting oxidative- and inflammatory-related mechanisms. In addition, it will highlight recent insight into the cell specific impact of nuclear receptor peroxisome proliferator-activated receptor- (PPAR). PPAR in vascular muscle facilitates nitric oxide-mediated signaling while inhibiting rho kinase and components of the renin-angiotensin system that promote vessel disease. PPAR in endothelium protects against oxidative stress and vascular aging. Because recent findings suggest that the renin-angiotensin system plays an important role in vascular aging, finding from experimental models of hypertension have broad implications for large and small vessel disease.



GWAs of SADB MRI hyperintensities by Stéphanie Debette


MRI-markers of cerebral small vessel disease, comprising white matter hyperintensities (WMH) and lacunar brain infarcts, are highly prevalent in the general population. Besides being associated with progressive functional decline, and portending an increased risk of stroke, MRI-markers of cerebral small vessel disease are powerful predictors of cognitive decline and dementia. Identifying genetic determinants of MRI-SVD may reveal key biological pathways underlying this disorder. We will review evidence for a genetic predisposition to MRI-markers of cerebral small vessel disease and will present results of recent genome-wide association studies performed on these phenotypes. In a meta-analysis of genome-wide association studies for WMH burden in 9,361 individuals of European descent from 7 community-based cohorts, the most significant association was with single nucleotide variants in one locus on chromosome 17q25. This result has been largely replicated in various independent studies and may provide novel insights into the pathogenesis of cerebral WMH.




The neurovascular unit : neurovascular coupling in health and disease by Costantino Iadecola


The brain is uniquely dependent on a well-regulated delivery of oxygen and glucose through the blood supply. The neurovascular unit, comprised of endothelial cells, smooth muscle cells/pericytes, astrocytes, perivascular cells, and neurons, is responsible for matching local cerebral perfusion to the metabolic needs of the brain (neurovascular coupling). Cognitive function is highly dependent on adequate cerebral perfusion, and alterations in neurovascular coupling have emerged as a key factor both in vascular causes of cognitive impairment and in dementia on neurodegenerative bases, such as Alzheimer’s disease. Clinical-pathological studies support the notion that vascular lesions aggravate the deleterious effects of neurodegenerative pathology by reducing the threshold for cognitive impairment and accelerating the pace of the dementia. In the absence of mechanism-based approaches to counteract vascular or neurodegenerative dementia, targeting vascular risk factors offers the opportunity to mitigate the impact of one of the most disabling human afflictions.


Pericytes in neurovascular coupling in health and disease David Attwell


Brain blood flow is regulated to ensure adequate power for neuronal computation. Blood flow is increased to areas where neurons are active, and this increase underlies non-invasive brain imaging using BOLD fMRI. Blood flow is controlled at the arteriole level by smooth muscle, but there is controversy over whether it is also regulated by pericytes at the capillary level. I will demonstrate that neuronal activity and the excitatory neurotransmitter glutamate evoke an outward membrane current in pericytes and dilate capillaries, and that this dilation is caused by active relaxation of pericytes rather than a passive expansion of capillaries downstream of arteriole relaxation. Glutamate-evoked dilation is mediated by prostaglandin E2, but requires nitric oxide release to suppress synthesis of the vasoconstrictor 20-HETE. In vivo, when sensory input to the neocortex releases glutamate and increases blood flow, capillaries dilate first, followed by arterioles. Capillary dilation is estimated to generate ~89% of the increase of blood flow occurring. Capillaries also have a role in pathology. Ischaemia was previously shown to lead to a contraction of pericytes. I will report that this is followed by their death, which is expected to produce an irreversible constriction of capillaries. Pericyte death is reduced by block of glutamate receptors or calcium removal, and increases with reperfusion, but is not blocked by scavenging of reactive oxygen species. These data establish, for the first time, pericytes as major regulators of cerebral blood flow, and initiators of the BOLD fMRI response. They also focus attention on prevention of pericyte death as a therapeutic strategy to reduce the long-lasting blood flow decrease which contributes to neuronal death after stroke.



Potassium channels and neurovascular coupling by Mark Nelson


CADASIL mouse model (Tg-Notch3R169C) recapitulates the salient preclinical features of the disease. Indicative of cerebrovascular dysfunction, this model exhibited compromised cerebral blood flow autoregulation and decreased constrictions of isolated pial arteries to intravascular pressure (Joutel et al., JCI, 2010). We examined the consequences of CADASIL-causing mutation R169C on the function of intracerebral arterioles. Elevation of intravascular pressure to 20 mm Hg constricted isolated arterioles from control and CADASIL mice to a similar extent. However, above 30 mm Hg, CADASIL arterioles constricted significantly less than control. At 40 mm Hg, CADASIL arterioles were 38% less constricted, and the smooth muscle membrane potential was 10 mV hyperpolarized compared to control. We hypothesized that this difference was due to increased activity of voltage-dependent potassium (Kv) channels. Using patch-clamp technique, we found that Kv current density was 30% greater in myocytes from CADASIL arterioles than in control, and activation of epidermal growth factor receptor that causes Kv channel endocytosis restored myogenic tone in CADASIL arterioles. These results support the concept that the CADASIL mutation decreases pressure-induced vasoconstriction through upregulation of smooth muscle Kv channels.



Novel hereditary SADB by Elisabeth Tournier-Lasserve and Dominique Hervé


CADASIL is the most common hereditary SADB but represents only part of this group of diseases. Indeed, only 15% of the patients with WM lesions suggestive of a SADB and referred for molecular screening of NOTCH3 are mutated. A few additional hereditary SADB have been characterized genetically including hereditary cerebral amyloid angiopathies (APP), COL4A1 angiopathy, HERNS syndrome (TREX), Coats + syndrome (CTC1) and CARASIL (HTRA1) but the number of affected families is very limited, which strongly suggests that genetic heterogeneity of this group of diseases is much higher than expected. To pursue the dismantlement of hereditary SADB and identify the genes involved in these conditions, we use a systematic approach combining detailed clinico-radiological characterization of each family and state of the art next generation molecular tools. Several novel SADB have been identified using this strategy and will be discussed at the symposium.



CADASIL cohorts and methodology of clinical trials by Hugues Chabriat

[Abstract NC]


Exome and genome sequencing by Elisabeth Tournier-Lasserve

[Abstract NC]

[vidéo NC]


New epidemiology/statistics approaches for multifactorial diseases by Stéphanie Debette


In recent years the identification of genetic variants associated with complex diseases has been revolutionized by the advent of high-throughput technologies and large international collaborative projects. Genome-wide association studies (GWAS) have enabled the discovery of thousands of novel genetic associations with many diseases and traits, mostly in previously unsuspected regions. More recently, next generation sequencing has become accessible for relatively large samples, thus considerably expanding the spectrum of genetic variation that can be explored in association with complex diseases. We will review the main methodological aspects of these approaches, current limitations, as well as expected applications. Examples drawn from cerebrovascular disorders, as well as lessons learnt from other complex diseases, will be presented.



Imaging of neurovascular coupling in human by Habib Benali

[Abstract NC]


Micro infarctus, a new SADB MRI marker ? by Joanna Wardlaw

Microinfarcts, a new small artery disease of the brain marker: Microinfarcts are tiny ‘infarcts’ that have been recognised with increasing frequency on pathological examination in older people and those with dementia. Recent high field MR studies suggest that they may also occasionally be visible on MRI with sensitive sequences. They appear to share arteriolar pathologies with small vessel disease lesions that are more clearly seen on structural MR imaging such as lacunes and white matter hyperintensities. The exact nature of microinfarcts and their relationship to overt small vessel disease imaging features is unclear and will be discussed.



Potential therapeutic avenues ? by Anne Joutel and Mark Nelson

[Abstract NC]



Portrait Marie-Germaine BOUSSERMarie-Germaine BOUSSER

Est actuellement attachée dans le Service de Neurologie de l’Hôpital Lariboisière à Paris et Professeur émérite de Neurologie à l’Université Paris-Diderot

Elle a consacré l’essentiel de ses travaux de recherche et de son activité clinique à la pathologie vasculaire cérébrale et aux céphalées.

Elle a notamment :

  • montré l’efficacité de l’aspirine dans la prévention secondaire des infarctus cérébraux
  • identifié une nouvelle maladie génétique autosomique dominante des petites artères cérébrales (CADASIL) responsable de migraine avec aura, d’infarctus cérébraux et de démence
  • contribué à une meilleure connaissance d’autres affections vasculaires cérébrales dont elle est une référence internationale, notamment les thromboses veineuses cérébrales, le syndrome de vasoconstriction cérébrale réversible et les dissections artérielles cervicales
  • contribué à une meilleure connaissance de la génétique et des traitements de la migraine.

Elle a publié plus de 500 articles originaux et écrit plusieurs livres , principalement sur la migraine , les accidents vasculaires cérébraux et l’aspirine.


Marie-Germaine BOUSSER is presently consultant in the Lariboisière hospital Neurology department in Paris and Emeritus professor at Université Paris-Diderot

Her research and clinical activities have been mostly devoted to cerebrovascular diseases and headache.

In particular , she has

  • shown the efficacy of aspirin in stroke secondary prevention
  • identified a new variety of autosomal dominant small artery disease of the brain for which she has coined the acronym CADASIL
  • contributed to a better understanding and treatment of other causes of stroke of which she is a world expert such as cerebral venous thrombosis, cervical artery dissections, reversible cerebral vasoconstriction syndrome
  • contributed to a better understanding and treatment of migraine

She has published over 500 articles in peer review journals and several books mostly on migraine, stroke and aspirin



Portrait Elisabeth Tournier-LasserveElisabeth Tournier-Lasserve

Elisabeth Tournier-Lasserve obtained her MD in Paris and after her specialization in Neurology, she spent 3 years in Bob Lazzarini’s Molecular Neuro-Genetics lab at the National Institute for Health in Bethesda, USA. Back to Europe she started her own research lab and did major contributions in the field of hereditary neuro-vascular disorders.

She is currently Professor of Medical Genetics at University Paris7

Denis Diderot, director of INSERM U740 Research Genetics of Vascular disorders and of the Genetics Diagnostic facility of Lariboisière Hospital, France.

CADASIL was initially described as an autosomal dominant vascular leukoencephalopathy linked to chromosome 19 and characterized by the presence of a specific Granular Osmiophilic Material (GOM) within the membrane of arterial vascular smooth cells. In 1996, all families fulfilling those criteria were shown to harbor highly stereotyped mutations leading to an odd number of cysteine residues within one of the 23 exons encoding EGF-like motifs of the NOTCH3 receptor.

More than 3000 index cases with a small artery disease of unknown etiology have now been screened for NOTCH3 mutations in our diagnostic lab, allowing diagnosis and genetic counseling of this condition in both familial and sporadic cases. Fifteen per cent of these patients have typical CADASIL mutations.

Interestingly, 2 % of these index patients show missense mutations which do not affect the number of cysteine residues but are absent from all existing databases, raising the question of their pathogenicity. In addition, several index patients and their relatives were shown to carry mutations leading to a premature stop codon and a NOTCH3 haploinsufficiency whose pathogenicity is so far unknown. A combination of skin biopsy electronic microscopy analysis, mRNA analysis and familial segregation analysis have been used to clarify the pathogenicity of these mutations and avoid a misdiagnosis of CADASIL.

CADASIL is the most common hereditary SADB but represents only part of this group of diseases. Indeed, only 15% of the patients with WM lesions suggestive of a SADB and referred for molecular screening of NOTCH3 are mutated. A few additional hereditary SADB have been characterized genetically including hereditary cerebral amyloid angiopathies (APP), COL4A1 angiopathy, HERNS syndrome (TREX), Coats + syndrome (CTC1) and CARASIL (HTRA1) but the number of affected families is very limited, which strongly suggests that genetic heterogeneity of this group of diseases is much higher than expected. To pursue the dismantlement of hereditary SADB and identify the genes involved in these conditions, we use a systematic approach combining detailed clinico-radiological characterization of each family and state of the art next generation molecular tools. Several novel SADB have been identified using this strategy and will be discussed at the symposium.




Hugues Chabriat

Hugues Chabriat MD PhD is currently tenured Professor of Neurology at University Paris VII – Denis Diderot and the head of the Neurology department at Hôpital Lariboisière within the Assistance Publique des Hôpitaux de Paris (France). He is also the head of the national referral centre for rare vascular diseases of the brain and retina in France. He has long been studying the clinical aspects and neuroimaging features of hereditary or age-related small vessel disease of the brain. He has a strong expertise in the clinical aspects and neuroimaging features of these diseases and performed multiple clinical and imaging studies in this field, particularly in CADASIL. Today, his researches particularly focus on the natural history of CADASIL, on the relationships between cerebral lesions and the occurrence of cognitive deficit and disability in small vessel disease, on the development of imaging biomarkers for future clinical trials in these disorders and on the dismantlement of hereditary forms of microangiopathies in collaboration with the geneticists.


Marco Düring

Studied medicine in Freiburg, Heidelberg and Bern. Doctoral thesis on the protein biochemistry of amyloid beta protein at the Center for Molecular Biology Heidelberg in the lab of Konrad Beyreuther. Now resident at the Department of Neurology and Junior Group Leader at the Institute for Stroke and Dementia Research. Research focus is the pathophysiology of small vessel disease and mechanisms of post-stroke dementia, mainly using neuroimaging techniques.


Portrait Bo NorrvingBo Norrving

Bo Norrving is professor in neurology at Lund University, Sweden. His research activities have focused on stroke epidemiology, stroke syndromes, small vessel disease, ultrasound, neuroimaging, clinical genetics, clinical trials and organisation of stroke services. He was corresponding author of the Swedish Aspirin Low-Dose Trial (SALT) published in The Lancet 1991 as the first trial to demonstrate the benefit of low dose aspirin therapy for the prevention of stroke. He was a pioneer in introducing assessment of cerebral hemodynamics by blood flow techniques, clinical syndromes of cerebellar stroke and lacunar infarcts, the importance of silent small vessel disease in the brain, and the recognition of dissection as a major cause of stroke in the young. He is chair of the steering committee of SIFAP, the world’s largest study on stroke in the young, and a member of safety and endpoint committees of several seminal clinical trials. He is a founder of Riks-Stroke, the world’s 1st national stroke registry. He is Senior Consulting Editor of Stroke, Associate Editor of Neuroepidemiology, and member of several editorial boards. He was the President of the World Stroke Organisation between 2008 and 2012 and continues as the representative of the society at the WHO and the UN. He chairs the Cerebrovascular Committee for the revision of the International Classification of Disease (ICD 11) at the WHO.




Anne Joutel

Anne JOUTEL has been trained in clinical neurology at Paris Hospitals, she received the MD degree from the University of Paris 7, in 1996. She studied Neurogenetics at Faculty of Medicine Necker Enfants Malades and she received the PhD degree from the University of Paris 6, in 1996. In 1998, she was recruited to INSERM as Research officer and then promoted to Senior Research Officer in 2005.

Dr. Joutel’s research focuses on the pathogenesis of Small vessel Disease of the brain. A major area of interest deals with the mechanisms linking Notch3 mutations to the functional and anatomic features in CADASIL. Dr. Joutel has published more that 60 papers in peer reviewed journals, which have been cited >6,000 times.



Portrait Hannu KalimoHannu Kalimo

I was born in 1944. M.D. in 1969, Ph.D. in 1974 and pathology specialist in 1976 at Univ. of Turku, Turku, Finland at the same Univ. and Dept of Pathology as Prof. Patrick Sourander, before he moved to Sweden. I received my neuropathology training in Dr. Julio Garcia´s (Baltimore, USA) and Prof. Yngve Olsson´s (Uppsala, Sweden) laboratories, which training entitled me to Finnish neuropathology specialty in 1979. I continued my research on cerebrovascular pathology in collaboration with Proff. Bo Siesjö´s and Barbro Johansson´s teams (Lund, Sweden) thru 1980´s. I became Prof. Sourander´s successor at the Univ. of Göteborg, Sweden for 1984-86, and thereafter prof. Olsson´s successor at the Univ. of Uppsala, Sweden (2002-2005) and finally successor of prof. Matti Haltia at Univ. of Helsinki, Finland (2003-2011). In the CADASIL territory I have been the pathologist in the Finnish CADASIL-team since early 1990´s. Now I am - since the fall of 2011 - a retiree from diagnostic work, but have not yet fully withdrawn from research to my grandpa-carpenter´s workshop…


Portrait Leonardo PantoniLeonardo Pantoni

Dr. Leonardo Pantoni, MD, PhD, studied medicine at the University of Florence and graduated in 1989. He was trained in neurology at the School of Neurology of the same University under the guide of Domenico Inzitari and became certified neurologist in 1993. From August 1993 to July 1995 he held a research fellowship in neuropathology at the Henry Ford Hospital in Detroit, Michigan, under the tutelage of Julio H. Garcia. In 1999 he received his PhD degree in Neuroscience. He is currently staff neurologist at the NEUROFARBA Department of the University of Florence where he is also professor at the School of Neurology. In October 2010 he attained the title of Associate Professor.

During all these years, dr. Pantoni has been interested in clinical neurology, mainly in the field of cerebrovascular diseases, and has focused his research on vascular dementia, small vessel diseases, and cerebral white matter changes of which he has explored definitions, radiological and pathological correlates, and therapeutic approaches. He has also a specific interest in experimental brain ischemia as it relates to the study of white matter lesions and cognitive changes and in CADASIL, a hereditary small vessel disease of the brain. From 2001 to present, he has been the deputy coordinator and publication coordinator of the European multicenter study LADIS (Leukoaraiosis and Disability in the Elderly, principal investigator Domenico Inzitari).

Dr. Pantoni is first co-editor of the book The Matter of White Matter. Clinical and pathophysiological aspects of white matter disease related to cognitive decline and vascular dementia, the first ever-published textbook entirely dedicated to the issue of age-related white matter changes. From 1996 to 2003 he has acted as scientific secretary of the European Task Force on Age-Related White Matter Changes, a multi-national association of the most prominent European experts on the topic. In July 2003, he was elected member of the Board of Directors of the International Psychogeriatric Association and in 2007 he was re-elected for a second term (2007-2011). He has also acted as the chairman of the publication committee of this association. Dr. Pantoni has been one the two chairmen of the 2005 congress of the International Society for Vascular Behavioural and Cognitive Disorders (VAS-COG) of which he is among the founding members, and, since 2009, member of the Executive Committee. In 2010, he became fellow of the European Stroke Organization.

Over the last years, Dr. Pantoni has served as reviewer for many international journals among which: New England Journal of Medicine, The Lancet, JAMA, Annals of Neurology, Brain, Lancet Neurology, Stroke, Journal of Cerebral Blood Flow and Metabolism, Neurology, Hypertension, Neurobiology of Aging. He is member of the Editorial Board of Cerebrovascular Diseases, Acta Neurologica Scandinavica and International Journal of Alzheimer Disease and permanent member of the scientific committee of the European Stroke Conference. In 2010, he has been nominated Section Editor (Vascular Cognitive Impairment) of the journal Stroke.

More recently, he has become member of the scientific committee of the International Stroke Conference (chair for the Vascular Cognitive Impairment category).

Dr. Pantoni has currently over 170 publications indexed in Pubmed and a Hirsh Index (HI) = 41



Portrait Christof HaffnerChristof Haffner

Studied biology and received Ph.D. in Clinical Biochemistry from the University of Würzburg. Completed Postdocs at the Dep. of Cell Biology, Yale University, New Haven and at the Dep. of Biochemistry, University of Halle/Saale. Held a senior scientist position at the Dep. of Metabolic Biochemistry, Ludwig-Maximilians-University Munich. Since 2009 senior scientist at the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University Munich. Finished his habilitation in biochemistry in 2013. His research interests are molecular and cellular mechanisms underlying small vessel disease.


Portrait Dominique HervéDominique Hervé

Dominique Hervé is a board-certified neurologist specialized in stroke medicine. He is responsible for running the national referral center for rare vascular diseases of the brain and retina (CERVCO) based at Lariboisiere hospital (Paris, France). He has a long track and expertise in the management of cerebrovascular diseases particularly in rare vascular disorders. His researches particularly focus on the clinical and radiological aspects of Moya-Moya disease, on the description of the various phenotypes related to SVD and to Moya-Moya disease and on the dismantlement of SVD using family studies and genetic tools.


Portrait Christophe TzourioChristophe Tzourio

Christophe Tzourio, MD, PhD, was initially trained as a vascular neurologist. After a training in epidemiology and a PhD thesis on genetic modeling in Alzheimer’s disease he became full time researcher with the INSERM (National Institute of Health and Medical Research). He is currently professor of epidemiology at the university of Bordeaux and head of a research unit in neuroepidemiology. He is principal investigator of an ongoing population-based cohort study in more than 9000 elderly individuals, the 3C study, which has for main aim to assess the importance of vascular factors in dementia. He is also PI of an ongoing blood pressure lowering trial aiming at reducing the burden of silent cerebral infarcts. He has published >200 original papers which have been cited >9000 times in international peer-reviewed journals. He is ranked in the top 1% of scientists (Highly Cited Scientist) by the ISI in both 'Clinical Medicine' and 'Neuroscience'. He has a special interest for the study of the consequences of blood pressure on the brain, particularly MRI brain lesions and dementia.



Portrait Joël MenardJoël Menard

Maitrise d’Investigation Clinique à Mc Gill (Montréal) en 1966 et Doctorat en Médecine à Paris en 1970

Professeur de Médecine Interne en 1973 à la Faculté de Médecine Broussais-Hôtel –Dieu de Paris

Chef de Service d’Hypertension artérielle à l’Hôpital Saint- Joseph de Paris (1975-1981) et à l’Hôpital Broussais (1981-1986)

Directeur de la recherche clinique et du développement international de Ciba-Geigy à Bâle (1986-1989)

Chef du Centre de Médecine Préventive Cardiovasculaire de l’Hôpital Broussais à Paris (1990-1997)

Président des Conférences Nationales de Santé françaises (1996 et 1997)

Directeur Général de la Santé, Ministère de la Santé (1997-1999)

Professeur de Santé Publique à la Faculté de Médecine René-Descartes de Paris (Paris 5), puis Professeur Émérite en 2009

Délégué à la Recherche Clinique de l’Assistance Publique-Hôpitaux de Paris (2000-2006)

Plan Alzheimer (Préparation, 2007) et Président du Conseil Scientifique de la Fondation Plan-Alzheimer (2008-2013)



Portrait Franck FaraciFranck Faraci

Dr Faraci's laboratory focuses on the biology of the cerebral circulation. Current emphasis is on the impact of cardiovascular risk factors using models of cerebrovascular disease and aging. The laboratory uses integrated molecular techniques with physiological and pharmacological approaches to examine mechanisms that regulate structure and function of the vessel wall. The work relies heavily on the use of genetically altered mice including more advanced models with cell-specific genetic manipulations. Much of this effort is aimed toward defining mechanisms that promote or protect against large and small vessel disease. Major areas of study currently include the interaction of oxidant- and immune-related mechanisms. The role of the renin-angiotensin system and the nuclear receptor peroxisome proliferator-activated receptors are a current focus. A better understanding of such mechanisms may provide insight into approaches that could stop or delay the progression of large and small vessel disease that eventually lead to stroke and contribute to the vascular component of cognitive impairment. 



Portrait Stéphanie DebetteStéphanie Debette

Stéphanie Debette trained as a neurologist and completed a stroke fellowship in Lille University Hospital, France. In parallel, she obtained a master degree in statistical genetics and a PhD in Epidemiology (Inserm Unit U744, Lille). After a brief research fellowship in clinical neuroscience at St George’s University of London, UK, she worked as a post-doctoral research fellow in the department of neurology of Boston University School of Medicine, USA, in the neurology research group of the Framingham Heart Study. In 2010 she obtained a Chair of Excellence from the French National Research Agency to set up a research team on the epidemiology and genetic epidemiology of structural and vascular brain aging, in close collaboration with Inserm Unit U708, France. Since 2012, Dr. Debette is an Associate Professor of Epidemiology and Neurology at Paris 7 University, Lariboisière Hospital and Inserm Unit U740, Paris, France, and an Adjunct Associate Professor in the Department of Neurology, Boston University School of Medicine, Boston, USA. Her main area of interest is the epidemiology and genetic epidemiology of cerebrovascular and cognitive disorders, with a focus on MRI-markers of cerebral small vessel disease.



Portrait Mike MoskowitzMike Moskowitz

Dr. Moskowitz received his M.D. from Tufts University, Boston. Following postdoctoral training at the Massachusetts Institute of Technology, Cambridge, he came to the MGH in 1975 where he is currently professor of Neurology.

The Moskowitz laboratory has a long-standing interest in mechanisms regulating cerebral blood vessel function with a particular focus on interactions between neurons, glial and vascular cells. Such studies are relevant to the pathophysiology of stroke, migraine, and traumatic brain injury. In the past, his laboratory discovered the sensory innervation to the Circle of Willis and the triggering of the trigeminovascular innervation by intense neuronal and glial activity.

His laboratory also was the first to identify the neuronal 5HT receptor subtypes for abortive anti-migraine drugs. More recent research projects relate to matrix metalloproteases (MMPs) and their upregulation on vascular permeability following cortical spreading depression. In addition to MMPs, his laboratory has a long-standing interest in tissue mediators of brain injury including nitric oxide and has studied its Janus effect on vascular function and cell death.

For this project, his laboratory developed unique expertise in physiological monitoring in genetically engineered mice including techniques to evaluate cerebrovascular physiology in fully instrumented animals. His laboratory used these methods to examine the relevance of specific cell types and pathways important in cerebral ischemia such as the contribution of the endothelium and brain parenchyma to stroke protection by NO and the statins. Experiments over the past decade have examined caspases as mediators of cell demise and the role of death receptors in ischemic brain injury. His laboratory is now examining the molecular consequences of cortical spreading depression as a potential mechanism to understand drug activity and as mechanism linking the pathophysiologic relationship between migraine and stroke.


  • Moskowitz MA, Lo EH. Neurogenesis and apoptotic cell death. Stroke 2003.
  • Chiarugi A, Moskowitz MA. Poly(ADP-ribose) polymerase-1 activity promotes NF-kB-driven transcription and microglial activation: implication for neurodegenerative disorders. J Neurochem. 2003
  • Atochin DN, Clark J, Demchenko IT, Moskowitz MA, and Huang PL. Rapid cerebral ischemic preconditioning in mice deficient in endothelial and neuronal nitric oxide synthases. Stroke 2003
  • Teramoto T, Qiu J, Plumier JC, Moskowitz MA. EGF amplifies the replacement of parvalbumin-expressing striatal interneurons after ischemia. J Clin Invest. 2003
  • Lo EH, Dalkara T, Moskowitz MA. Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci. 2003
  • Finklestein SP, Fisher M, Furland AJ, Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Special Report. Stroke 1999.
  • Yoshimura S, Teramoto T, Whalen MJ, Irizarry MC, Takagi Y, Qiu J, Harada J, Waeber C, Breakefield XO, Moskowitz MA. FGF-2 regulates neurogenesis and degeneration in the dentate gyrus after traumatic brain injury in mice. J Clin Invest. 2003
  • Wada K, Sugimori H, Bhide PG, Moskowitz MA, Finklestein SP. Effect of basic fibroblast growth factor treatment on brain progenitor cells after permanent focal ischemia in rats. Stroke 2003
  • Frenkel D, Huang Z, Maron R, Koldzic DN, Hancock WW, Moskowitz MA, Weiner HL. Nasal vaccination with myelin oligodendrocyte glycoprotein reduces stroke size by inducing IL-10-producing CD4+T cells. J Immunol. 2003
  • Lo EH, Broderick JP, Moskowitz MA. Advances in stroke 2003: tPA and proteolysis in the neurovascular unit. Stroke 2004
  • Harada J, Foley M, Moskowitz MA, Waeber C. Sphingosine-1-phosphate induces proliferation and morphological changes of neural progenitor cells. J Neurochem. 2004
  • Plesnila N, Zhu C, Culmsee C, GrÖger M, Moskowitz MA, Blomgren K. Nuclear translocation of apoptosis-inducing factor after focal cerebral ischemia. J Cereb Blood Flow Metab. 2004
  • Qiu J, Takagi Y, Harada J, Rodriques N, Moskowitz MA, Scadden DT, Cheng T. Regenerative response in ischemic brain restricted by p21cip1/waf1. J Exp Med. 2004
  • Qiu J, Nishimura M, Wang Y, Sims JR, Qiu S, Savitz SI, Salomone S, Moskowitz MA.  Early release of HMGB-1 from neurons after the onset of ischemia. J Cereb Blood Flow Metab. 2008
  • Breckwoldt MO, Chen JW, Stangenberg L, Aikawa E, Rodriguez E, Qiu S, Moskowitz MA, Weissleder R. Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc Natl Acad Sci (USA) 2008
  • Dalkara T, Nozari A, Moskowitz MA.  Migraine aura pathophysiology: the role of blood vessel and microembolisation. Lancet Neurol. 2010
  • Moskowitz MA, Lo EH, Iadacola C. The science of stroke: mechanisms in search of treatments.  Neuron 2010
  • Nozari A, Dilekoz, E., Sukhotinksy, I, Stein, T, Eikermann-Haerter, K., Liu, C., Wang, Y., Frosch, MP, Waeber, C, Ayata, C, Moskowitz, MA.  Microemboli may link spreading depression migraine aura, and patent foramen ovale, Annals Neurol. 2010
  • Qiu J, Xu J, Zheng Y, Wei Y, Zhu X, Lo, EH, Moskowitz MA, Sims JR. High-mobility group box 1 promotes metalloproteinase-9 upregulation through Toll-like receptor 4 after cerebral ischemia.  Stroke 2010
  • Moskowitz MA, Waeber C. Remote ischemic preconditioning: making the brain more tolerant, safely and inexpensively. Circulation 2011
  • Eikermann-Haerter K, Yuzawa I, Qin T, Wang Y, Baek K, Kim YR, Hoffmann U, Dilekoz E, Waeber C, Ferrari MD, van den Maagdenberg AM, Moskowitz MA, Ayata C. Enhanced subcortical spreading depression in familial hemiplegic migraine type 1 mutant mice. J Neurosci. 2011
  • Terpolilli N, Moskowitz MA, Plesnila N. Nitric oxide: considerations for the treatment of ischemic stroke.  J Cereb Blood Flow Metab. 2012
  • Pietrobon D, Moskowitz MA. Pathophysiology of migraine.  In: D Julius and DE Clapham eds), Annual Review of Physiology, 2013



Portrait Jean-Louis MasJean-Louis Mas

Professor of Neurology, Paris Descartes University; Head of the Neurology Department and Stroke Unit of Sainte-Anne Hospital, Paris; Head of the research team « Stroke: determinants of prognosis and imaging », INSERM UMR 894, Centre of Psychiatry and Neurosciences (CPN), Paris.

Other responsabilities: Deputy director of the CPN, INSERM, U894; Member of the management committee of the Paris Descartes Faculty of Medicine; Past president of the French Neuro-Vascular Society; Chair of the national committee for special education in cerebrovascular disease; Member of the board of directors of Sainte-Anne hospital; Member of the board of directors of the Department Hospitalo-Universitaire Neuro-Vasc-Paris Sorbonne. Chair of the guidelines committee of the European Stroke Organisation; Member of the programme and scientific committees of the European Stroke Conference; Past member of the board of directors of the World Stroke Organisation.



Portrait Costantino IadecolaCostantino Iadecola

Costantino Iadecola, M.D., is the Anne Parrish Titzell Professor of Neurology and Director of the Brain and Mind Research Institute at Weill Cornell Medical College, New York, USA. Dr. Iadecola is a clinician-scientist who works on the cellular and molecular mechanisms of neurovascular function, and on the overlap between stroke and dementia. Dr. Iadecola has published over 240 journal articles and plays a leadership role in several international networks for stroke and dementia research. He is a recipient of the Javits Award from the National Institutes of Health, the Willis Award, the highest honor in stroke research bestowed by the American Heart Association, and of the Zenith Fellow Award from the Alzheimer’s Association. He is on several editorial boards, including the Annals of Neurology, and serves in various editorial capacities for Stroke, Hypertension, Circulation, and the Journal of Neuroscience.


Portrait David AttwellDavid Attwell

David Attwell did a first degree in physics and a PhD on the electrophysiology of nerve and muscle cells (with Julian Jack) in Oxford, before spending 2 years in Berkeley studying the retina with Frank Werblin. On returning to the UK, he moved to the Department of Physiology at University College London, where he has remained ever since. He has worked on a wide range of subjects including the properties of glial cells, glutamate transporters, stroke, the formation of myelin by oligodendrocytes, how neuronal computation is powered and the control of cerebral blood flow. He was made a Fellow of the Royal Society in 2001.



Portrait Mark NelsonMark Nelson

University Distinguished Professor and Chair, University of Vermont

Professor, Institute of Cardiovascular Sciences, University of Manchester, UK

Visiting Professor, Pharmacology, University of Oxford, Oxford.

A major goal of the research in Dr. Nelson's laboratory is to understand the control of smooth muscle and endothelial cell function by ion channels and calcium signaling. In particular we are interested in understanding the mechanisms by which computationally active neurons in the brain control local cerebral blood flow (CBF) ("neurovascular coupling") in health and disease (e.g. small vessel disease including CADASIL), using optical techniques to measure calcium signaling and arteriolar diameter in the neurovascular unit (neurons, astrocytes, arteriolar smooth muscle and endothelium) in brain slices as well as CBF in vivo, electrophysiological techniques to measure membrane currents and membrane potential of astrocytes, smooth muscle and endothelial cells from parenchymal arterioles. Arteriolar diameter is also measured in isolated pressurized parenchymal arterioles. An objective is to understand the basic mechanisms for ion channel control of local cerebral blood flow and blood brain barrier permeability, and using this information to elucidate pathologies and possible new therapeutic interventions.


Portrait Jan Torleif PedersenJan Torleif Pedersen

Research Fellow, Head Neurodegeneration, H. Lundbeck A/S, DK-2500 Valby, Denmark, Cette adresse e-mail est protégée contre les robots spammeurs. Vous devez activer le JavaScript pour la visualiser. Jan Torleif is a biophysicist by training earning a masters degree in biochemistry and chemical engineering from the technical university of Denmark (DTU). Jan since pursued his interest in protein structure earning a PhD in biophysics from the university of Bath in the United Kingdom. As a research associate at the Center for Advanced Research in Biotechnology (CARB), In Rckville, Maryland USA, Jan developed theoretical methods for the understanding of protein structure and dynamics. Applying theoretical methods to the understanding of biological systems has always been a key pursuit and in particular the application of these to drug discovery and neuroscience research. In the past 12 years Jan Torleif has build an innovative program within neurodegeneration at Lundbeck in Copenhagen, focusing on Alzheimer’s disease, Vascular dementias and other neurodegenerative disorders. Current research focusses on developing next generation therapies, which will provide disease modification for progressive neurodegenerative disorders.



Portrait Katharina Eikermann-HaerterKatharina Eikermann-Haerter

Dr Eikermann-Haerter, MD, is a principal investigator at the Massachusetts General Hospital, Department of Radiology, on pathophysiology of migraine and stroke. She receives peer-reviewed funding, and publishes in leading scientific journals in the areas of neuroscience and cardiovascular medicine. Her accomplishments have been acknowledged by numerous prestigious awards, such as the Harold Wolff - John Graham Award from the American Academy of Neurology. Her work demonstrates that spreading depression can produce migraine aura-like symptoms, and increase the vulnerability to stroke. Other important studies revealed mechanisms that can explain the female preponderance in migraine.



PortraitHabib BenaliHabib Benali

Habib Benali is the director of the unit 678, Laboratory of Functional Imaging of the French National of Health and Medical Research (INSERM) and Paris 6 University (UPMC) since 2008. He is the co-director of the International Laboratory of Neuroimaging and Modelisation of the INSERM-UPMC and Montreal University since 2007. His current research group interests are in human brain mapping and functional connectivity analysis using multimodal analysis of electromagnetic and hemodynamic processes in the brain and spinal cord. He developped biomathematical models to better understand the mechanisms of brain signals (BOLD fMRI, MRS, EEG, optical imaging) and functional and anatomical connectivity (fMRI and EEG functional connectivity, dynamic functional connectivity and anatomical connectivity using diffusion imaging). He proposed macroscopic models of the spatial extent of the anatomical networks and their functional dynamics. Together with members of my his research team in Paris, he will use his experience to assist investigators collaborated in analyzing and interpreting functional and anatomical brain data of healty subjects and patients.


Dynamical models of the brain activity

Over the recent years increasingly accurate quantitative neuroimaging data have been produced and published. This raises several questions: (1) How can this type of data be incorporated to assist with modeling of brain activity? (2) Which new hypotheses for interpreting functional imaging data can we formulate? Recent advances in multimodal simultaneous recordings will progressively help to better determine different underlying mechanisms of brain activity. Biophysical models have been recognized to be powerful tools to cross-correlate different types of information: introducing non observable variables, these models are able to link the measured data with hidden physiological parameters. We proposed a biophysical model at the mesoscopic level, which segregates neuronal and glial activities in terms of the excitation/inhibition balance, metabolism and CBF activation.



Portrait Joanna WardlawJoanna Wardlaw

JM Wardlaw is an expert in stroke, particularly neuroimaging of large and small vessel ischaemic stroke. She was European Editor of Stroke from 2005 to 2012. She has worked on thrombolytic treatment for stroke since 1989, most recently publishing the third International Stroke Trial which demonstrated the benefits of rt-PA for a much wider range of patients than previously thought. She has worked on cerebral small vessel disease since 2000, including research to determine the underlying mechanism(s) and hence to optimise prevention and treatment.