Arzimanoglou - EURORDIS
Transcript of Arzimanoglou - EURORDIS
Patient driven research:Alternating Hemiplegia
Alexis Arzimanoglou
Hôpital Robert DebréService de neurologie pédiatrique et de maladies
métaboliques
CENTRE THEMATIQUE DE RECHERCHE ET DE SOINS
I.D.E.E.Institute for children and adolescents
with epilepsyHOSPICES CIVILS DE LYON
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.Epilepsy2.Migraine : hemiplegic, basilar
3.Paroxysmal dyskinesias4.Vascular disorders:,malformations; multiple emboli; Osler-
Weber-Rendu disease; cutis marmorata5.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 European Network for The European Network for Research on AHC (ENRAH)Research on AHC (ENRAH)
Network of Centers of ExpertiseNetwork of Centers of ExpertiseResearch GroupsResearch GroupsPatient OrganisationsPatient Organisations
Coordination, Vienna, ACoordination, Vienna, A
Facilitate exchange of ideas & development of new ideas between experts from several European countries
The benefits
Participants
Alexis Arzimanoglou, MD, Paris, France Andreas Moser, MES, MBA,Vienna, Austria
Arn M.J.M. van den Maagdenberg, PhD, Leden, NL
Brian G R Neville, Prof., London, UKCarme Fons , MD, Barcelona, SpainClaudio Zucca , M.D.,Bosisio Parini , ItalyDilsad Türkdogan, M.D., Istanbul, TurkeyDominique Ponceline , St. G. Arpajon, FranceEmilio Fernandez-Alvarez, Prof , Barcelona, SpainFrancis P. Crawley, Prof. , Brussels, BelgiumFriedrich Ebinger, Dr., Heidelberg, GermanyGeorg Spiel, Univ. Doz. Dr. , Klagenfurt, AustriaGiuseppe Gobbi , Dr. , Bologna, ItalyInês Carrilho, MD, Porto, PortugalLaura A.E.M. Laan, MD, PhD, Leden, The NetherlandsM. Valeriani , Dr. Rome, ItalyMelania Gianotta, MD, Bologna, ItalyMirjana Toullec ,Saint Germain En Laye , FrancePaul Casaer, Prof., Leuven, BelgiumPhilip Hirst , Dr., Warfield Bracknell Berks , UKRosaria Vavassori , Verderio Superiore , ItalySona Nevsimalova, Dr., Prague, Czech RepublicTsveta Schyns, PhD , Vienna, Austria
The creation of an impressive database:a web-based European registry
The benefits Financial support for young researchers;
Work closer with the patient associations
People with AHC and their Families, GPs, Following neurologists
Patients Data Files and Human Samples at the National Clinical CentersConfidential
European Registryon AHC cases
Restricted
Coded standardized data
Information www.enrah.netPublic
INTERNATIONAL REGISTRY OF AHC PATIENTSINTERNATIONAL REGISTRY OF AHC PATIENTS-- EUROPEEUROPE
e n r a hEUROPEAN NETWORK FOR RESEARCH ONALTERNATING HEMIPLEGIA
THE QUESTIONNAIREGeneral information
*at least with grand parents
Any history of comorbidity 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 other neurological disease 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 epilepsy in the family* (0=no; 1=yes; 88=unknown)Any history of migraine in the family* (0=no; 1=yes; 88=unknown)First or second degree consanguineity (0=no; 1=yes; 88=unknown)Delivery (0=eutocic; 1= dystocic. 88=unknown) (or 0=vaginal delivery 1= section caesarea ?)
Pregnancy (O= normal; 1= abnormal; 88=unknown)Patient Birth Date Patient CODEDiagnosis dateRecruitment date
e n r a hEUROPEAN NETWORK FOR RESEARCH ONALTERNATING HEMIPLEGIA
THE QUESTIONNAIREGeneral information
Disappearance of symptoms with sleep (0=no 1=yes; 88=unknown)
Pain (0=no 1=yes; 88=unknown)
Breathing difficulties (0=no 1=yes; 88=unknown)
Neurovegetative disorders (0=no 1=yes; 88=unknown) ( orautonomic disturbances)
Headache (0=no 1=yes; 88=unknown)
Status epilepticus (0=no 1=yes; 88=unknown)
Epilepsy (0=no 1=yes; 88=unknown)
Abnormal ocular movement (0=no 1=yes; 88=unknown)
Plegic attack (0=no 1=yes; 88=unknown)
Tonic/dystonic attack (0=no 1=yes; 88=unknown)
Premonitory signs (0=no 1=yes; 88=unknown)
Onset<18 mths (0=no 1=yes; 88=unknown)
PAROXYSMAL EVENTS (0=no 1=yes; 88=unknown)
e n r a hEUROPEAN NETWORK FOR RESEARCH ONALTERNATING HEMIPLEGIA
THE QUESTIONNAIREGeneral information
Working employment (0=no; 1=autonomous ; 2=with assistance; 88=unknown)
School attendance (0=normal without help; 1=normal with help; 2=special course)
Behavioural disorders (0=no; 1=mild; 2=moderate; 3=severe 88=unknown)
Language disorder (0=no; 1=mild; 2=moderate; 3=severe 88=unknown)
Cognitive impairment (0=no; 1=mild; 2=moderate; 3=severe 88=unknown)
Muscle Tone (0=normal; 1= hypertonia; 2= hypotonia)
Complex Movement Disorder (0=no; 1=mild; 2=moderate; 3=severe 88=unknown)
Tremor (0=no; 1=mild; 2=moderate;3=severe 88=unknown)
Chorea (0=no; 1=mild; 2=moderate; 3=severe 88=unknown)
Myoclonus (0=no; 1=mild; 2=moderate; 3=severe 88=unknown)
Dystonia (0=no; 1=mild; 2=moderate; 3=severe 88=unknown)
Pyramidal signs (0=no; 1=mild; 2=moderate; 3=severe 88=unknown)
Fine motor problems (0=no; 1=mild; 2=moderate; 3=severe 88=unknown)
Gross Motor problems (0=no; 1=mild; 2=moderate; 3=severe 88=unknown)
NON PAROXYSMAL FEATURES (0=no; 1=mild; 2=moderate; 3=severe 88=unknown)
e n r a hEUROPEAN NETWORK FOR RESEARCH ONALTERNATING HEMIPLEGIA
FOLLOW UP AT 2 YRS(from 0 yrs to 2 yrs)
date:
Other effective measures (0=no; 1=yes)*link to the open windowMost effective drugs to prevent the attack (0=no; 1=yes) ( or any effective drug…?)Most effective drugs for acute attack (0=no; 1=yes) ( or any effective drug…?)Trigger events (0=no; 1= yes)Length (0=<1hour; 1=1-6 hours; 2=6-12 hours; 3=12-24 hours, 4=>24 hours)Frequency (0=<1/year; 1=monthly; 2=weekly; 3=daily)Consciousness (0= normal; 1= altered)Limb involvement (0=one; 1= >1 same side; 2=>1 different side)Semeiology (0=simple; 1= mixed)TONIC OR DYSTONIC ATTACKS (0=no; 1=yes )
PAROXYSMAL features
e n r a hEUROPEAN NETWORK FOR RESEARCH ONALTERNATING HEMIPLEGIA
THE QUESTIONNAIREGeneral information
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 …
Fluoxetine
Flunarizine
Felbamate
Ethosuximide
Ergotamine
Dihydroergotamine
Diazepam
Clonidine
Clonazepam
Clobazam
Ciproterone-ethinylestradiol
Chloral Hidrate
Carbamazepine
Buspirone
Bromocriptine
Biperiden
Barbexaclone
Baclofen
Alprazolam
Acetazolamide
Sumatriptan
Sulthiame
Sertraline
Propanolol
Primidone
Pregabaline
Piracetam
Pimozide
Phenobarbital
Phenitoine
Oxcarbazepine
Nitrazepam
Nimodipine
Niaprazine
Methysergide
Methoclopramide
Lorazepam
Levetiracetam
L-dopa + carbidopa
Lamotrigine
Haloperidol
Gabapentin
Valproate
Tript-OH
Triexyphenidyl
Trazodone
Topiramate
Tiagabine
Olygosaccarid
Skin Biopsy
Mitochondrial chain analysis
Muscle Biopsy
LCR amino acids
LCR lactate
LCR pyruvate
LCR neurotrasmitter
Liquor (standard examination)
Ana
Antiphospholipid
Purine, pirimidyne
CDG
VLFA
Organic acids
Amino acids
lysosomal enzyme
Ammonium
CPK
Pyruvate
Lactate
Base screening *
LABORATORY INVESTIGATION(0=normal; 1=not normal; 99=not
done)
Echocardiogram
ECG
Angiogram
ENG
SEP
EMG
Blink reflex
ABR
VEP
interictal EEG
ictal EEG (during motor attack)
Ictal EEG (during epileptic seizure)
MRI spectroscopy
ictal SPECT
interictal SPECT
fMRI scan
MRI scan
CT scan
(0=normal;1=not normal; 99=not done)
NEURORADIOLOGICAL AND NEUROPHYSIOLOGICAL INVESTIGATION
e n r a hEUROPEAN NETWORK FOR RESEARCH ONALTERNATING HEMIPLEGIA
THE QUESTIONNAIREGeneral information
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;
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.
The difficulties and limits
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.