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Alternating Hemiplegia Alexis Arzimanoglou Patient driven research: Alternating Hemiplegia Alexis Arzimanoglou Hôpital Robert Debré CENTRE THEMATIQUE Service de neurologie pédiatrique et de maladies DE RECHERCHE ET DE SOINS métaboliques I.D.E.E. Institute for children and adolescents with epilepsy HOSPICES CIVILS DE LYON ALTERNATING HEMIPLEGIA: A rare and strange neurological disorder Major Clinical Features: • Onset in infancy (< 18 months) • Repeated episodes of hemiplegia on either side • Episodes of bilateral paralysis • Associated paroxysmal events (dystonic, chorea, …) • Abnormal ocular movements • Epileptic seizures • Appearance of fixed chronic features • Sleep interrupts paralytic attacks (that may last several hours) Differential diagnosis: 1.Epilepsy 2.Migraine : hemiplegic, basilar 3.Paroxysmal dyskinesias 4.Vascular disorders:,malformations; multiple emboli; Osler- Weber-Rendu disease; cutis marmorata 5.Hematologic disorders: homocystinuria; thrombophilia 6.Metabolic diseases: MELAS and other mitochondrial diseases; urea cycle diseases 7.Others: including paroxysmal torticollis of infancy, demyelinating diseases, relapsing encephalitides In summary: A rare and difficult to diagnose disorder of early childhood; It is the association of signs and symptoms that allows diagnosis of Alternating Hemiplegia; No biological marker All investigations normal The absolute need for a multicenter - multicountry collaboration TheThe EuropeanEuropean NetworkNetwork forfor ResearchResearch onon AHCAHC (ENRAH)(ENRAH) Network of Centers of Expertise Research Groups Patient Organisations Coordination, Vienna, A The benefits Participants Alexis Arzimanoglou, MD, Paris, France Andreas Moser, MES, MBA,Vienna, Austria Arn M.J.M. van den Maagdenberg, PhD, Leden, NL Facilitate Brian G R Neville, Prof., London, UK Carme Fons , MD, Barcelona, Spain exchange of Claudio Zucca , M.D.,Bosisio Parini , Italy Dilsad Türkdogan, M.D., Istanbul, Turkey ideas & Dominique Ponceline , St. G. Arpajon, France Emilio Fernandez-Alvarez, Prof , Barcelona, Spain development of Francis P. Crawley, Prof. , Brussels, Belgium Friedrich Ebinger, Dr., Heidelberg, Germany new ideas Georg Spiel, Univ. Doz. Dr. , Klagenfurt, Austria Giuseppe Gobbi , Dr. , Bologna, Italy Inês Carrilho, MD, Porto, Portugal between experts Laura A.E.M. Laan, MD, PhD, Leden, The Netherlands M. Valeriani , Dr. Rome, Italy from several Melania Gianotta, MD, Bologna, Italy Mirjana Toullec ,Saint Germain En Laye , France European Paul Casaer, Prof., Leuven, Belgium Philip Hirst , Dr., Warfield Bracknell Berks , UK Rosaria Vavassori , Verderio Superiore , Italy countries Sona Nevsimalova, Dr., Prague, Czech Republic Tsveta Schyns, PhD , Vienna, Austria The benefits Financial support for young researchers; Work closer with the patient associations The creation of an impressive database: a web-based European registry INTERNATIONALINTERNATIONAL REGISTRYREGISTRY OFOF AHCAHC PATIENTSPATIENTS -- EUROPEEUROPE European Registry on AHC cases Restricted Information www.enrah.net Public Coded standardized data Patients Data Files and Human Samples at the National Clinical Centers Confidential People with AHC and their Families, GPs, Following neurologists e n r a h THE QUESTIONNAIRE EUROPEAN NETWORK FOR RESEARCH ON General information ALTERNATING HEMIPLEGIA Recruitment date Diagnosis date Patient CODE Patient Birth Date Pregnancy (O= normal; 1= abnormal; 88=unknown) Delivery (0=eutocic; 1= dystocic. 88=unknown) (or 0=vaginal delivery 1= section caesarea ?) First or second degree consanguineity (0=no; 1=yes; 88=unknown) Any history of migraine in the family* (0=no; 1=yes; 88=unknown) Any history of epilepsy in the family* (0=no; 1=yes; 88=unknown) Any history of other paroxysmal disease in the family* (0=no; 1=yes; 88=unknown) Any history of other neurological disease in the family* (0=no; 1=yes; 88=unknown) Any history of mortality in childhood in the family* (0=no; 1=yes; 88=unknown) Any history of comorbidity in the family* (0=no; 1=yes; 88=unknown) *at least with grand parents e n r a h THE QUESTIONNAIRE EUROPEAN NETWORK FOR RESEARCH ON General information ALTERNATING HEMIPLEGIA PAROXYSMAL EVENTS (0=no 1=yes; 88=unknown) Onset<18 mths (0=no 1=yes; 88=unknown) Premonitory signs (0=no 1=yes; 88=unknown) Tonic/dystonic attack (0=no 1=yes; 88=unknown) Plegic attack (0=no 1=yes; 88=unknown) Abnormal ocular movement (0=no 1=yes; 88=unknown) Epilepsy (0=no 1=yes; 88=unknown) Status epilepticus (0=no 1=yes; 88=unknown) Headache (0=no 1=yes; 88=unknown) Neurovegetative disorders (0=no 1=yes; 88=unknown) ( orautonomic disturbances) Breathing difficulties (0=no 1=yes; 88=unknown) Pain (0=no 1=yes; 88=unknown) Disappearance of symptoms with sleep (0=no 1=yes; 88=unknown) e n r a h THE QUESTIONNAIRE EUROPEAN NETWORK FOR RESEARCH ON General information ALTERNATING HEMIPLEGIA NON PAROXYSMAL FEATURES (0=no; 1=mild; 2=moderate; 3=severe 88=unknown) Gross Motor problems (0=no; 1=mild; 2=moderate; 3=severe 88=unknown) Fine motor problems (0=no; 1=mild; 2=moderate; 3=severe 88=unknown) Pyramidal signs (0=no; 1=mild; 2=moderate; 3=severe 88=unknown) Dystonia (0=no; 1=mild; 2=moderate; 3=severe 88=unknown) Myoclonus (0=no; 1=mild; 2=moderate; 3=severe 88=unknown) Chorea (0=no; 1=mild; 2=moderate; 3=severe 88=unknown) Tremor (0=no; 1=mild; 2=moderate;3=severe 88=unknown) Complex Movement Disorder (0=no; 1=mild; 2=moderate; 3=severe 88=unknown) Muscle Tone (0=normal; 1= hypertonia; 2= hypotonia) Cognitive impairment (0=no; 1=mild; 2=moderate; 3=severe 88=unknown) Language disorder (0=no; 1=mild; 2=moderate; 3=severe 88=unknown) Behavioural disorders (0=no; 1=mild; 2=moderate; 3=severe 88=unknown) School attendance (0=normal without help; 1=normal with help; 2=special course) Working employment (0=no; 1=autonomous ; 2=with assistance; 88=unknown) e n r a h EUROPEAN NETWORK FOR RESEARCH ON FOLLOW UP AT 2 YRS ALTERNATING HEMIPLEGIA (from 0 yrs to 2 yrs) date: PAROXYSMAL features TONIC OR DYSTONIC ATTACKS (0=no; 1=yes ) Semeiology (0=simple; 1= mixed) Limb involvement (0=one; 1= >1 same side; 2=>1 different side) Consciousness (0= normal; 1= altered) Frequency (0=<1/year; 1=monthly; 2=weekly; 3=daily) Length (0=<1hour; 1=1-6 hours; 2=6-12 hours; 3=12-24 hours, 4=>24 hours) Trigger events (0=no; 1= yes) Most effective drugs for acute attack (0=no; 1=yes) ( or any effective drug…?) Most effective drugs to prevent the attack (0=no; 1=yes) ( or any effective drug…?) Other effective measures (0=no; 1=yes)*link to the open window e n r a h THE QUESTIONNAIRE EUROPEAN NETWORK FOR RESEARCH ON General information ALTERNATING HEMIPLEGIA OTHER INFORMATION: A huge amount of clinical data collected Direct benefits • Better define the severity spectrum of the disorder, atypical forms, co-morbidities, …; • Have some hints on global natural evolution; • Be prepared for genotype-phenotype correlations … Acetazolamide Gabapentin Tiagabine Alprazolam Haloperidol Topiramate Baclofen Lamotrigine Trazodone Barbexaclone L-dopa + carbidopa Triexyphenidyl Biperiden Levetiracetam Tript-OH Bromocriptine Lorazepam Valproate Methoclopramide Buspirone Methysergide Carbamazepine Niaprazine Chloral Hidrate Nimodipine Ciproterone- ethinylestradiol Nitrazepam Oxcarbazepine Clobazam Phenitoine Clonazepam Phenobarbital Clonidine Pimozide Diazepam Piracetam Dihydroergotamine Pregabaline Ergotamine Primidone Ethosuximide Propanolol Felbamate Sertraline Flunarizine Sulthiame Fluoxetine Sumatriptan LABORATORY INVESTIGATION (0=normal; 1=not normal; 99=not NEURORADIOLOGICAL AND done) NEUROPHYSIOLOGICAL INVESTIGATION (0=normal;1=not normal; 99=not Base screening * done) Lactate CT scan Pyruvate MRI scan CPK fMRI scan Ammonium interictal SPECT lysosomal enzyme ictal SPECT Amino acids MRI spectroscopy Organic acids Ictal EEG (during epileptic seizure) VLFA ictal EEG (during motor attack) CDG interictal EEG Purine, pirimidyne VEP Antiphospholipid ABR Ana Blink reflex Liquor (standard EMG examination) SEP LCR neurotrasmitter ENG LCR pyruvate Angiogram LCR lactate LCR amino acids Muscle Biopsy ECG Mitochondrial chain analysis Echocardiogram Skin Biopsy Olygosaccarid e n r a h THE QUESTIONNAIRE EUROPEAN NETWORK FOR RESEARCH ON General information ALTERNATING HEMIPLEGIA OTHER INFORMATION: A huge amount of data to collect on drugs and investigations already performed Indirect benefits • Eventually identify the most pertinent investigations to perform; • Identify what drugs have been used by others, eventually build-up a controlled trials • Reduce costs; The difficulties and limits 1.The creation of a database for rare disorders is an unavoidable step for the development of new projects but not a research project proper; 2. This would be possible in parallel but a substantial funding would be necessary. A critique !! Although it is easy to understand some of the reasons … obtaining funding for such projects on rare (but they are many) disorders remains a very complex procedure both at a European and at a local level. MERCI !!!! 1. Projects like ENRAH enormously facilitate close collaboration between clinicians, geneticists, basic scientists …at a European level. 2. Such a collaboration represents the unique pathway for a competent collaboration with US centers, for the benefit of the patients..
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