Previous page Emmanuel FLAMAND ROZE Principal Investigator, MD, PhD, PU-PH, Sorbonne University, AP-HP
BiographyI have been deeply involved for more than 10 years, in the clinical care of patients with Parkinson disease and other movement disorders at the movement disorders clinic at the Salpêtrière hospital in Paris. At this very place, I also devised a program aimed at optimizing the transition of children and young adults living with chronic neurological illness from pediatric to adult departments. My main research areas of interest is neurodevelopmental movement disorders. I study the clinical aspects, genetic causes and neurophysiological mechanisms underpinning these disorders. I am also strongly involved in the study of experimental therapeutics and pilot studies to test them. I have published extensively on these topics (183 peer-reviewed papers). I received an award from the French Neurological Society for my work on myoclonus-dystonia, the “pilot project” award from the Dystonia Coalition for a project studying the role of the cerebellum in focal dystonia and the Breughel award for a project studying the agentivity in dystonic patients. Finally, I have a keen interest in teaching and has developed an innovative simulation-based medical education program (“The move”) to teach neurology semiology to medical students attending the Pierre et Marie Curie University in Paris. This program has already started in Dublin (Ireland) and is to be implemented in other French and European Universities. It was presented at the third meeting of the European Academy of Neurology in 2017 and received the excellence certificate of the PEPS jury (of the French ministry of education).
Positions and HonorsTraining and Faculty Appointments
- 1996 - 2002: Residency in Neurology and MD student, Assistance Publique - Hôpitaux de Paris
- 2002 - 2007: PhD student, CNRS - UMR7102
- 2004 - 2008: Fellowship in Neurology, Assistance publique-hopitaux de Paris
- 2008 - 2010: Medical Coordinator of the Centre for Clinical Research, Salpêtrière hospital, Paris, France
- 2010 - present: Consultant Neurologist, Movement Disorders Clinic, dep. Neurology, Salpêtrière Hospital, Paris
- 2010 - present: Researcher at the Brain and Spine Institute, Salpêtrière hospital, Paris
- 2015 - present: Professor of Neurology, Pierre et Marie Curie University, Paris
- 2008 award of the French neurological society for my work on myoclonus-dystonia
- 2010 award "pilot project" of the dystonia coalition for studying the role of cerebellum in focal dystonia.
- 2017 Breughel award for a project studying agentivity and in dystonic patients
- 2017 excellence certificate from the PEPS jury (ministry of education) for the teaching program “The move”
- 2016-present: member of the board of the "collège des enseignants de neurologie" (the leading board for the teaching of neurology in France)
- 2010 - present: Permanent member of the “cellule de préselection de l’inserm” for French medical research projects (weekly review and discussion of all clinical research projects (all medical specialties) sponsored by INSERM, which is the main institutional structure for medical research in France)
- 2010 - 2012 Member of the DGOS-INSERM committee (Ad hoc reviewer for research program)
- Principal Investigator 2011-2016: « Lateralization of motor control: the mirror movement paradigm »; Grant from Fondation pour la Recherche sur le Cerveau and Grant from Inserm-COSSEC
- Principal Investigator 2011-2015: « A randomized, controlled, double-blind, crossover trial of zonisamide in myoclonus-dystonia»; Grant from PHRC (AOR10029)
- Principal investigator 2011-2014: « Cerebellum and cortical plasticity: the case of focal dystonia »; Grant from Dystonia Coalition (NS065701)
- Principal Investigator 2014-2015: « Identification of new genes involved in paroxysmal kinesigenic dyskinesias »; Grant from Fondation Maladies Rares
- Principal Investigator 2015-2017: « A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood »; Grant from the Association Française de l’Hémiplégie Alternante
- Co-Principal investigator 2017-2019: «Identification of neuronal mecanisms of agency in dystonia»; Grant from AMADYS (prix Breughel 2017)
1. Mirror movementsFor the last seven years, I have been conducting a large research program on congenital mirror movements. We identified two (RAD51 and netrin-1) of the three main culprit genes for this disorder and clarify the genetic causes and pathophysiology of this disorder. We were also part of an international consortium that found out the role of a mirror movement gene (DCC) in another devlopmental disorder, namely corpus callosum agenesis. We finally took advantage of the mirror movement paradigm to get further insight into the development of the motor system and the mechanism involved in the lateralization of the motor control.
- Méneret A, Franz EA, Trouillard O, Oliver TC, Zagar Y, Robertson SP, Welniarz Q, MacKinlay Gardner RJ, Gallea C, Srour M, Depienne C, Jasoni CL, Dubacq C, Riant F, Lamy JC, Morel MP, Guérois R, Andreani J, Fouquet C, Doulazmi M, Vidailhet M, Rouleau GA, Brice A, Chédotal A, Dusart I, Roze E*, Markie D*. Mutations in the netrin-1 gene cause congenital mirror movements. Journal of Clinical investigation 2017;127:3923-36
- Welniarz Q, Morel MP, Pourchet O, Gallea C, Lamy JC, Cincotta M, Doulazmi M, Belle M, Méneret A, Trouillard O, Ruiz M, Brochard V, Meunier S, Trembleau A, Vidailhet M, Chédotal A,5 Dusart I, Roze E. Non cell-autonomous role of DCC in the guidance of the corticospnal tract at the midline. Scientific Reports 2017;7:410
- Marsh APL, Heron D, Edwards TJ, Quartier A, Galea C, Nava C, Rastetter A, Moutard ML, Anderson V, Bitoun P, Bunt J, Faudet A, Garel C, Gillies G, Gobius I, Guegan J, Heide S, Keren B, Lesne F, Lukic V, Mandelstam SA, Mcgillivray G, McIlroy A, Méneret A, Mignot C, Morcom LR, Odent S, Paolino A, Pope K, Riant F, Robinson G, Spencer-Smith M, Srour M, Stephenson SE, Tankard R, Trouillard O, Welniarz Q, Wood A, Brice A, Rouleau G, Attié-Bitach T, Delatycki MB, Mandel JL, Amor DJ, Roze E, Piton A, Bahlo M, Billette de Villemeur T, Sherr EH, Leventer RJ, Richards LJ, Lockhart PJ, Depienne C. Mutations in DCC cause isolated Agenesis of the Corpus Callosum with incomplete penetrance. Nature Genetics 2017;49:511-514
- Méneret A, Depienne C, Riant F, Trouillard O, Bouteiller D, Cincotta M, Bitoun P, Wickert J, Lagroua I, Westenberger A, Borgheresi A, Doummar D, Romano M, Rossi S, Defebvre L, De Meirleir L, Espay AJ, Fiori S, Klebe S, Quélin C, Rudnik-Schöneborn S, Plessis G, Dale RC, Sklower Brooks S, Dziezyc K, Pollak P, Golmard JL, Vidailhet M, Brice A, Roze E. Congenital mirror movements: mutational analysis of RAD51 and DCC in 26 cases. Neurology 2014; 3;82:1999-2002
- Gallea C, Popa T, Hubsch C, Valabregue R, Brochard V, Kundu P, Schmitt B, Bardinet E, Bertasi E, Flamand-roze C, Alexandre NPA, Delmaire C, Meneret A, Depienne C, Poupon C, Hertz-Pannier L, Cincotta M, Vidailhet M, Lehericy S, Meunier S, Roze E. RAD51 deficiency disrupts the corticospinal lateralization of the motor control. Brain 2013;136:3333-46
- Depienne C, Bouteiller D, Méneret A, Billot S, Groppa S, Klebbe S, Charbonnier-Beaupel F, Saraiva JP, Brueggemann N, Corvol JC, Bhatia K, Cincotta M, Brochard V, Flamand-Roze C, Carpentier W, Meunier S, Marie Y, Gaussen M, Stevanin G, Wehrle R, Vidailhet M, Klein C, Brice A, Roze E. RAD51 Haploinsufficiency causes congenital mirror movements in Humans. Am J Hum Genet 2012;90:301-307
- Depienne C, Cincotta M, Billot S, Bouteiller D, Groppa S, Brochard V, Flamand C, Hubsch C, Meunier S, Giovannelli F, Klebe S, Corvol JC, Vidailhet M, Brice A, Roze E. A novel DCC mutation and genetic heterogeneity in congenital mirror movements. Neurology 2011;76:260-4
2. Myoclonus dystoniaDuring the last decade, I was strongly involved in various major works clarifying the spectrum and pathophysiology of myoclonus dystonia. I published a seminal work describing the clinical and neurophysiological spectrum of this disorder, based on a very large series of patients that were studied in details. I also described rare genetic variants of the disease. I had a significant contribution in the understanding of the disorder by coordinating several experimental works on the pathophysiology that demonstrated the involvement of the cerebellum in this disorder and made it clear that this particular form of genetic dystonia has a pathogenesis, which is different from other genetic dystonias. Finally, I studied the therapeutic aspects: I was part of one of the first works describing the effect of deep brain stimulation and recently published a paper indicating that this effect may be sustained over at least ten tears. Finally, I conducted the first randomized controlled trial in this disorder, demonstrating that zonisamide is an effective treatment.
- Hainque E, Vidailhet M, Cozic N, Charbonnier-Beaupel F, Thobois S, Tranchant C, Brochard V, Glibert G, Drapier S, Mutez E, Doe De Maindreville A, Lebouvier T, Hubsch C, Degos B, Bonnet C, Grabli D, Legrand AP, Méneret A, Azulay JP, Bissery A, Zahr N, Clot F, Mallet A, Dupont S, Apartis E, Corvol JC, Roze E. A randomized, controlled, double-blind, crossover trial of zonisamide in myoclonus-dystonia. Neurology 2016;86:1729-35
- Popa T, Milani P, Richard A, Hubsch C, Brochard V, Tranchant C, Sadnicka A, Rothwell J, Vidailhet M, Meunier S, Roze E. The neurophysiologcal features of myoclonus dystonia and differentiation from other dystonias. JAMA Neurology 2014;71:612-9
- Hubsch C, Vidailhet M, Rivaud-Péchoux S, Pouget P, Brochard V, Degos B, Pelisson D, Golmard JL, Gaymard B, Roze E. Impaired saccadic adaptation in DYT11 dystonia. JNNP 2011;82:1103-6
- Roze E, Apartis E, Clot F, Dorison N, Thobois S, Guyant-Marechal L, Tranchant C, Damier P, Doummar D, Bahi-Buisson N, André-Obadia N, Maltete D, Echaniz-Laguna A, Pereon Y, Beaugendre Y, Dupont S, De Greslan T, Jedynak CP, Ponsot G, Dussaule JC, Brice A, Dürr A, Vidailhet M. Myoclonus dystonia: Clinical and electrophysiological pattern related to SGCE mutations. Neurology 2008; 70:1010-6.
3. Paroxysmal neurological disordersIn collaboration with other clinicians and geneticists, I have significantly contributed to our understanding of paroxysmal neurological disorders. In particular, we showed that PRRT2 was the main causative gene of paroxysmal kinesigenic dyskinesia in the European population and demonstrated that this gene was occasionnaly causing hemiplegic migraine. Recently, we also conducted a very innovative pilot therapeutic trial that provide data supporting the efficacy of triheptanoin on the paroxysmal movement disorders of patients with GLUT1 deficiency and developed a simple test to improve the diagnosis of this disorder.
- Gras D, Cousin C, Fung CW, Auvin S, Essid N, Hy Chung B, Da Costa L, Hainque E, Luton MP, Petit V, Vuillaumier-Barrot S, Boespflug-Tangy O, Roze E, Mochel F. A simple blood test expedites the diagnosis of GLUT1 deficiency syndrome. Annals of Neurology 2017;82:133-138
- Mochel F, Hainque E, Gras D, Adanyeguh IM, Caillet S, Héron B, Roubertie A, Kaphan E, Valabregue R, Rinaldi D, Vuillaumier S, Schiffmann R, Ottolenghi C, Hogrel JY, Servais L, Roze E. Triheptanoin dramatically reduces paroxysmal motor disorder in patients with GLUT1 deficiency. JNNP 2016;87:550-553
- Friedman J Méneret A, Chen DH, Touillard O, Vidailhet M, Raskind WH, Roze E. ADCY5 mutation carriers display pleiotropic paroxysmal day and nighttime dyskinesias. Mov disord 2016;31:147-148
- Meneret A, Grabli D, Depienne C, Gaudebout C, Picard F, Durr A, Lagroua I, Bouteiller D, Mignot C, Doummar D, Anheim M, Tranchant C, Burbaud P, Jedynak CP, Gras D, Steschenko D, Devos D, Billette de Villemeur T, Vidailhet M, Brice A, Roze E. PRRT2 mutations: a major cause of paroxysmal kinesigenic dyskinesia in the european population. Neurology 2012;79:170-4
- Riant F*, Roze E*, Barbance C, Méneret A, Guyant-Marechal L, Lucas C, Sabouraud P, Trebuchon A, Depienne C, and Tournier-Lasserve E. PRRT2 mutations cause hemiplegic migraines. Neurology 2012;79:2122-4
4. Unravelling the phenotype of rare movement disordersMy research directions have been driven by my clinical practice, which is focused in rare movement disorders, particularly in children from disorders. I have been thereby involved in various studies that clarified genotypic/phenotypic correlation of several rare movement disorders.
- Friedman J, Roze E, Abdenur JE, Chang R, Gasperini S, Saletti V, Wali GM, Eiroa H, Neville B, Felice A, Parascandalo R, Zafeiriou DI, Arrabal L, Dill P, Eichler FS, Echenne B, MD15, Gutierrez-Solana LG, Hoffmann GF, Hyland K, Kusmierska K, Tijssen MAJ, Lutz T, Mazzuca M, Penzien J, PollThe BT, Sykut-Cegielska J, Szymanska K, Thöny B, Blau N. Sepiapterin Reductase Deficiency: a treatable mimic of cerebral palsy. Annals of Neurology 2012 71:520-3
- Roze E, Bounolleau P, Ducreux D, Cochen V, Leu-Semenescu S, Beaugendre Y, Lavallard-Rousseau MC, Blancher A, Bourdain F, Dupont P, Carluer L, Verdure L, Vidailhet M, Apartis E. Propriospinal myoclonus revisited: clinical, neurophysiological and neuroradiological findings. Neurology 2009;72:1301-
- Ewenczyk C, Leroux A, Roubergue A, Laugel V, Afenjar A, Saudubray JM, Billette de Villemeur T, Beauvais P, Vidailhet M, Roze E. Recessive hereditary methemoglobinemia, type II: delineation of the clinical spectrum. Brain 2008;131:760-7
- Roze E, Paschke E, Lopez N, Eck T, Yoshida K, Maurell-Ollivier A, Doummar D, Caillaud C, Galanaud D, Billette de Villemeur T, Vidailhet M, Roubergue A. Dystonia and parkinsonism in GM1 type 3 gangliosidosis. Movement Disorders 2005;20:1366-9
5. Pathophysiology of writer'scramp and other focal dystoniaPart of my research work was focused on studying the pathophysiology of writer's cramp and other froms of focal dystonia. in collaboration with epidemiologist I evidenced several major risks factors for writing's cramp, which has potential implications for pathophysiology of focal dystonia. i was also involved in several projects supporting the role of a cerebellar dysfunction in dystonia, including writer's cramp.
- Gallea C, Balas M, Bertasi E, Valabregue R, Garcia-Lorenzo D, Coynel D, Bonnet C, Grabli D, Pélégrini-Issac, Doyon J, Benali H, Roze E, Vidailhet M, Lehericy S. Increased cortico-striatal connectivity during motor practice contributes to the consolidation of motor memory in writer's cramp patients. NeuroImage: Clinical 2015;8:180-92
- Hubsch C, Roze E, Popa T, Russo M, Balachandran A, Pradeep S, Mueller F, Quartarone A, Degos B, Vidailhet M, Kishore A, Meunier S. Defective cerebellar control of cortical plasticity in writer’s cramp. Brain 2013;136:2050-62
- Roze E, Soumaré A, Pironneau I, Sangla S, Cochen- De Cock V, Texeira A, Astorquiza A, Bonnet C, Bleton JP, Vidailhet M, Elbaz A. Case-control study of writer’s cramp. Brain 2009;132:756-64
- Vidailhet M, Grabli D, Roze E. Pathophysiology of dystonia. Cur opin Neurol 2009;22:406-13
6. Apomorphine and Parkinson diseaseI have been one of the pioneer neurologist that have used apomorphine in France and I have been strongly involved in the development of this approach in France (OPTIPUMP study – see below). I am currently the co-PI of the APOMORPHEE study that is a multicenter controlled trial testing the effect of Continuous apomorphine during the night on sleep disorders in insomniac patients with Parkinson's disease.
- Drapier S, Eusebio A, Degos B, Vérin M, Durif F, Azulay JP, Viallet F, Rouaud T, Moreau C, Defebvre L, Fraix V, Tranchant C, Andre K, Courbon CB, Roze E, Devos D. Quality of life in Parkinson’s disease improved by apomorphine pump: the OPTIPUMP study. Journal of Neurology 2016;263:1111-9.