Clinical trial NCT01590589: REGISTRY - an Observational Study of the European Huntington's Disease Network (EHDN)
Official title: REGISTRY - an Observational Study of the European Huntington's Disease Network (EHDN)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Huntington Disease
Huntington's Disease
Keywords: Huntington Disease
European HD Network
Cohort
REGISTRY
EHDN
Lead sponsor: European Huntington's Disease Network
Sponsor class: NETWORK
First posted: 2012-05-03
Enrollment: 10000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with manifest HD, unaffected individuals known to carry the HD mutation or at risk of carrying the HD mutation, and control research participants (e.g., spouses, siblings or offspring of HD mutation carriers known not to carry the HD mutation)

Brief summary: This is a multi-centre, multi-national, prospective, observational study of Huntington's disease (HD) with a control group of volunteers to:

* obtain natural history data on many HD mutation carriers and individuals who are part of an HD family
* relate phenotypical characteristics (genetic modifiers / wet and dry biomarkers)
* expedite identification and recruitment of participants for clinical trials
* develop and validate sensitive and reliable outcome measures for detecting onset and change over the natural course of premanifest and manifest HD which may also be potential outcome measures for use in future clinical trials and clinical care
* plan for future research studies

Detailed description: REGISTRY integrates prospectively and systematically collected clinical research data (e.g. phenotypical clinical features, family history, demographical characteristics) with access to biological specimens (e.g. blood, urine) obtained from individuals with manifest HD, unaffected individuals known to carry the HD mutation or at risk of carrying the HD mutation, and control research participants (e.g. spouses, siblings or offspring of HD mutation carriers known not to carry the HD mutation).

REGISTRY is an open-ended study and eligible subjects are assessed at annual study visits on the phenotypical characteristics of HD regardless of whether they display clinical symptoms and signs of the disease and of individuals who are part of an HD family (irrespective of their mutation carrier status). At each study visit, general clinical, motor function, behavior, cognitive, Health Economics, Quality of Life assessments are administered. In addition, participants are given the option to consent to the donation of biosamples for the purposes of mutation (CAG repeat length) testing and for research to identify biological modifiers and markers of HD. Biological specimens and phenotypical data are made available to qualified scientists whose projects are reviewed and approved by the Scientific and Bioethical Advisory Committee (SBAC) of EHDN. Successful applicants agree to accept the EHDN policies surrounding the use of the data/materials provided and publication of results (see data sharing and publication policies of EHDN, attached). Research projects should aim to advance scientific knowledge towards establishing clinically effective treatments that delay onset and/or slow the progression of the disease.

Eligibility criteria: REGISTRY-HD participants include those who are willing to participate in regular (annual) evaluations conducted by the investigators and have a diagnosis of HD, are HD mutation carriers (but who do not meet criteria for a diagnosis of HD) or persons at risk for HD (first and second degree relatives of people affected by HD), are non-HD mutation carrier relatives. Spouses of participants may take part as REGISTRY-CONTROLS.

Inclusion Criteria:

The following individuals may be eligible to participate

* Individuals, confirmed HD mutation carrier
* Manifest HD, without mutation (CAG) testing
* HD family member at-risk, without CAG testing
* HD family member, non-HD mutation carrier
* REGISTRY-CONTROL participants: companion/individual without HD history
* REGISTRY-COMPANION (any of the above).

Exclusion Criteria:

* Participants who are unable to understand the study protocol or unable to give informed consent, and have no legal representative.
* Participants with choreic movement disorder other than HD. (EHDN provides a Registry-like tool to record findings in patients affected with choreatic movement disorders other than HD under the label "Neuroacanthocytosis"; www.euro-hd.net/html/na/registry).

Primary outcomes:
measure: Phenotypical characteristics of HD
timeFrame: 13 years
Secondary outcomes:
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Universitätsklinik für Psychiatrie, Neuropsychiatrische Ambulanz
city: Innsbruck
country: Austria
facility: Universitätsklinik Innsbruck, Neurologie
city: Brussels
country: Belgium
facility: UCL-St Luc, Centre de génétique humaine
city: Gosselies
country: Belgium
facility: Institute of Pathology and Genetics (IPG)
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Gasthuisberg, Dienst Neurologie
city: Olomouc
country: Czechia
facility: Fakultní nemocnice Olomouc, Neurologická klinika
city: Praha 2
country: Czechia
facility: Centrum extrapyramidových onemocnění, Neurologická klinika, 1. LFUK
city: Copenhagen Ø
country: Denmark
facility: University Hospital of Copenhagen - Rigshospitalet, Dept. of Neurology
city: Helsinki
country: Finland
facility: The Family Federation of Finland Väestöliitto, Department of Medical Genetics
city: HUS
country: Finland
facility: Helsinki University Hospital, Dept. of Neurology
city: Kuopio
country: Finland
facility: Kuopio University Hospital, Neurology
city: Mariehamn
country: Finland
facility: Ålands Hälso- och Sjukvård, Långvårdsenheten
city: Oulu
country: Finland
facility: Oulu University Hospital (OUH), Dept. of Neurology
city: Tampere
country: Finland
facility: Suomen Terveystalo
city: Turku
country: Finland
facility: Turku University Hospital, Dept. of Neurology
city: Turku
country: Finland
facility: The Finnish Parkinson Association, Suvituuli
city: Amiens cedex
country: France
facility: CHU d'Amiens - Hôpital Nord, Service de Neurologie
city: Angers cedex 9
country: France
facility: CHU d'Angers, Service de Neurologie Charcot
city: Bordeaux cedex
country: France
facility: Hôpital Pellegrin, Service de Génétique Médicale (ESF 3e étage)
city: Clermont-Ferrand
country: France
facility: HU Clermont-Ferrand - Hôpital Gabriel Montpied, Service de Neurologie
city: Créteil cedex
country: France
facility: Hôpital Henri Mondor, Service de Neurologie
city: Lille cedex
country: France
facility: Clinique Neurologique Hôpital Roger Salengro CHRU, Neurologie et Pathologie du Mouvement
city: Marseille cedex 5
country: France
facility: CHU La Timone, Service de Neurologie (9e étage)
city: Paris
country: France
facility: Hôpital La Pitié Salpétrière, Génétique & Inserm U679
city: Rouen cedex
country: France
facility: CHU Rouen Charles Nicolle, Service de Neurologie
city: Strasbourg cedex
country: France
facility: Hôpital Civil, Service de Neurologie
city: Toulouse cedex 03
country: France
facility: Hôpital Purpan, INSERM U825, Pôle Neurosciences
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen, Neurologische Klinik
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Klinik und Poliklinik für Neurologie, Klinik für Psychiatrie und Psychotherapie
city: Bochum
country: Germany
facility: Ruhruniversität Bochum, Neurologie
city: Dinslaken
country: Germany
facility: Reha-Zentrum Dinslaken im Gesundheitszentrum Lang, Tagesklinik
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Klinik und Poliklinik für Neurologie
city: Erlangen
country: Germany
facility: Universtität Erlangen, Abteilung für Molekulare Neurologie
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Neurologie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Neurologische Abteilung
city: Hannover
country: Germany
facility: Neurologische Klinik mit Klinischer Neurophysiologie, Medizinische Hochschule Hannover
city: Heiligenhafen
country: Germany
facility: Psychatrium Gruppe AöR, Haus 2/1
city: Itzehoe
country: Germany
facility: Schwerpunktpraxis Huntington, Neurologie-Psychiatrie
city: Marburg
country: Germany
facility: Praxis
city: Marburg
country: Germany
facility: Universität Marburg, Neurologie
city: München
country: Germany
facility: Technische Universität München, Abteilung Neurologie
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Klinik und Poliklinik für Neurologie
city: Taufkirchen
country: Germany
facility: Isar-Amper-Klinikum - Klinik Taufkirchen (Vils)
city: Ulm
country: Germany
facility: University Hospital of Ulm, Dept. of Neurology
city: Bari
country: Italy
facility: University of Bari, Dept. of Neurological and Psychiatric Sciences
city: Bologna
country: Italy
facility: Università di Bologna, Dip. di Scienze Neurologiche - Clinica Neurologica
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia, Clinica Neurologica
city: Florence
country: Italy
facility: University of Florence, Dip. di Scienze Neurologiche e Psichiatriche
city: Genova
country: Italy
facility: Università di Genova, Dept. of Neurosciences
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neruologico Carlo Besta, SOSD Genetics of Neurodegenerative and Metabolic Diseases
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta, I Neurologia
city: Napoli
country: Italy
facility: Università di Napoli Federico II, Dip. Scienze Neurologiche Edificio 17
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitarie Pisana, Dip. di Neuroscienze - UO Neurologia
city: Pozzilli (IS)
country: Italy
facility: IRCCS Neuromed, U.O. Neurogenetica
city: Rome
country: Italy
facility: Azienda Ospedaliera S. Andrea, UOC Neurologia e Centro Neurologico Terapie Sperimentali CENTERS
city: Rome
country: Italy
facility: Università Cattolica del Sacro Cuore "A.Gemelli", Istituto di Neurologia / CNR, Istituto di Farmacologia Traslazionale
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente, Dept. of Neurology
city: Groningen
country: Netherlands
facility: UMC Groningen, Neurology
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre (LUMC), Neurology K5-Q
city: Maastricht
country: Netherlands
facility: MUMC, Dept. Neurology
city: Bergen
country: Norway
facility: NKS Olaviken Alderpsykiatriske sykehus, Poliklinikk og Huntington Klinikk
city: Oslo
country: Norway
facility: Rikshospitalet, Dept. of Medical Genetics
city: Oslo
country: Norway
facility: Ulleval University Hospital, Medical Genetics
city: Trondheim
country: Norway
facility: St. Olavs Hospital HF, Neurology
city: Gdansk
country: Poland
facility: Specialistic Hospital in Gdansk, Dept. of Neurology
city: Katowice
country: Poland
facility: Medical University of Silesia, Dept. of Neurology
city: Krakow
country: Poland
facility: Krakowska Akademia Neurologii
city: Poznan
country: Poland
facility: Poznan University of Medical Sciences, Dept. of Social Medicine
city: Warsaw
country: Poland
facility: Medical University of Warsaw, Dept. of Neurology
city: Warsaw
country: Poland
facility: Institute of Psychiatry and Neurology, First Dept. of Neurology
city: Coimbra
country: Portugal
facility: Hospital de Coimbra, Neurology Dept.
city: Lisbon
country: Portugal
facility: Hospital dos Capuchos, Centro Hospitalar Lisboa Central, Neurology Dept.
city: Lisbon
country: Portugal
facility: Hospital de Santa Maria, Centro de Estudos Egas Moniz, Neurology Dept.
city: Lisbon
country: Portugal
facility: Hospital Fernando Fonseca, Neurology Dept.
city: Porto
country: Portugal
facility: Hospital de São João, Neurology Dept.
city: Porto
country: Portugal
facility: Hospital Geral de Santo António, Neurology Dept.
city: Vila Real
country: Portugal
facility: Centro Hospitalar de Trás-os-Montes e Alto Douro, Neurology Dept.
city: Moscow
country: Russian Federation
facility: Huntington's Disease Society of Russia
city: Albacete
country: Spain
facility: Complejo Hospitalario Universitario de Albacete, Neurología
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina, Neurología
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebrón, Neurología, 3ª planta, consultas externas
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial, Neurología
city: Barcelona
country: Spain
facility: Hospital Bellvitge, Neurología
city: Burgos
country: Spain
facility: Hospital General Yagüe, Neurology
city: Cádiz
country: Spain
facility: Hospital Puerta del Mar, Neurología
city: Madrid
country: Spain
facility: Centro Ramón y Cajal, Neurología
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz, Neurology
city: Madrid
country: Spain
facility: Hospital Clínico de Madrid, Servicio de Neurología
city: Madrid
country: Spain
facility: Hospital de Fuenlabrada, Neurology
city: Murcia
country: Spain
facility: Hospital Virgen de la Arrixaca, Neurology
city: Oviedo
country: Spain
facility: Hospital Central de Oviedo, Neurología
city: Palma de Mallorca
country: Spain
facility: Hospital Son Dureta, Neurology
city: Pamplona
country: Spain
facility: Hospital Virgen del Camino, Medical Genetics
city: San Sebastián
country: Spain
facility: Hospital Donostia. Universidad del Pais Vasco, Neurociencias
city: Segovia
country: Spain
facility: Hospital General de Segovia, Neurología
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío, Servicio de Neurología
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena, Neurología
city: Terrassa - Barcelona
country: Spain
facility: Hospital Universitario Mutua de Terrassa, Neurologia - Investigación
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud, Neurology
city: Valencia
country: Spain
facility: Hospital La Fe, Consultas Externas de Neurología
city: Zaragoza
country: Spain
facility: Hospital Clinico Universario, Department of Neurology
city: Göteborg
country: Sweden
facility: Sahlgren University Hospital, Dept. of Clinical Genetics
city: Lund
country: Sweden
facility: Skåne Universitetssjukhus, Neurologiska kliniken
city: Stockholm
country: Sweden
facility: Neuroenheten Utsikten
city: Stockholm
country: Sweden
facility: Karolinska University Hospital - Huddinge Division, Neurology
city: Umeå
country: Sweden
facility: Norrlands Universitet Sjukhus, Dept. of Neurology
city: Uppsala
country: Sweden
facility: Uppsala University Hospital, Neurology
city: Bern
country: Switzerland
facility: Neurologische Klinik des Inselspitals, Praxis
city: Lausanne
country: Switzerland
facility: CHUV - Centre Hospitalier Universitaire Vaudois, Département de Neurologie
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Dept. of Neurology
city: Aberdeen
country: United Kingdom
facility: Clinical Genetics Centre, Ground Floor, Ashgrove House
city: Birmingham
country: United Kingdom
facility: The Barberry Centre, Dept. of Psychiatry
city: Blandford Forum
country: United Kingdom
facility: Blandford Hospital
city: Bristol
country: United Kingdom
facility: Frenchay Hospital, Neurology Dept.
city: Cambridge
country: United Kingdom
facility: Cambridge Centre for Brain Repair, Forvie Site
city: Cardiff
country: United Kingdom
facility: Cardiff University, Life Sciences Building
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School, Human Genetics Unit
city: Edinburgh
country: United Kingdom
facility: Molecular Medicine Centre, Western General Hospital, Dept. of Clinical Genetics
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Foundation Trust Hospital, Department of Neurology
city: Fife
country: United Kingdom
facility: Queen Margaret Hospital
city: Glasgow
country: United Kingdom
facility: Scottish Huntington Association, Units 105/106
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital, Neurology Dept.
city: Hull
country: United Kingdom
facility: Chapel Allerton Hospital, Yorkshire Regional Genetics Service
city: Leeds
country: United Kingdom
facility: Chapel Allerton Hospital
city: Leicester
country: United Kingdom
facility: Leicestershire Partnership NHS Trust, EMD South School, OSL house
city: Liverpool
country: United Kingdom
facility: The Walton Centre for Neurology and Neurosurgery
city: London
country: United Kingdom
facility: Guy's Hospital, Dept. of Neurology
city: London
country: United Kingdom
facility: The Royal Hospital for Neuro-disability, Research and Development
city: London
country: United Kingdom
facility: St George's Hospital Medical School, South West Thames Regional Genetics Unit
city: London
country: United Kingdom
facility: National Hospital for Neurology and Neurosurgery, Dept. for Neurology
city: Manchester
country: United Kingdom
facility: University of Manchester, Genetic Medicine, St. Mary's Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Institute of Human Genetics, International Centre for Life
city: Oxford
country: United Kingdom
facility: Churchill Hospital, Dept. of Clinical Genetics
city: Plymouth
country: United Kingdom
facility: Derriford Hospital, Dept. of Clinical Neuropsychology
city: Poole
country: United Kingdom
facility: Poole Hospital Foundation Trust, Brain Injury Service
city: Preston
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS Foundation Trust, Neurosciences Directorate, Royal Preston Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital, Dept. of Clinical Genetics
city: Southampton
country: United Kingdom
facility: Southampton General Hospital and University of Southampton, Neurology / Wellcome Trust Clinical Research Facility
city: Stoke-on-Trent
country: United Kingdom
facility: Bucknall Hospital, Neuropsychiatry Service
city: Swindon
country: United Kingdom
facility: Victoria Centre
Study officials:
affiliation: University Hospital of Ulm / Dept. of Neurology
name: Bernhard Landwehrmeyer, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rickards H, De Souza J, van Walsem M, van Duijn E, Simpson SA, Squitieri F, Landwehrmeyer B; European Huntington's Disease Network. Factor analysis of behavioural symptoms in Huntington's disease. J Neurol Neurosurg Psychiatry. 2011 Apr;82(4):411-2. doi: 10.1136/jnnp.2009.181149. Epub 2010 Apr 14.
citation: Orth M, Handley OJ, Schwenke C, Dunnett SB, Craufurd D, Ho AK, Wild E, Tabrizi SJ, Landwehrmeyer GB; Investigators of the European Huntington's Disease Network. Observing Huntington's Disease: the European Huntington's Disease Network's REGISTRY. PLoS Curr. 2010 Sep 28;2:RRN1184. doi: 10.1371/currents.RRN1184.
citation: Orth M; European Huntington's Disease Network; Handley OJ, Schwenke C, Dunnett S, Wild EJ, Tabrizi SJ, Landwehrmeyer GB. Observing Huntington's disease: the European Huntington's Disease Network's REGISTRY. J Neurol Neurosurg Psychiatry. 2011 Dec;82(12):1409-12. doi: 10.1136/jnnp.2010.209668. Epub 2010 Nov 19. No abstract available.
citation: Busse M, Al-Madfai DH, Kenkre J, Landwehrmeyer GB, Bentivoglio A, Rosser A; European Huntington's Disease Network. Utilisation of Healthcare and Associated Services in Huntington's disease: a data mining study. PLoS Curr. 2011 Jan 21;3:RRN1206. doi: 10.1371/currents.RRN1206.
citation: Lopez-Sendon JL, Royuela A, Trigo P, Orth M, Lange H, Reilmann R, Keylock J, Rickards H, Piacentini S, Squitieri F, Landwehrmeyer B, Witjes-Ane MN, Jurgens CK, Roos RA, Abraira V, de Yebenes JG; European HD Network. What is the impact of education on Huntington's disease? Mov Disord. 2011 Jul;26(8):1489-95. doi: 10.1002/mds.23385. Epub 2011 Mar 22.
citation: Ho AK, Hocaoglu MB; European Huntington's Disease Network Quality of Life Working Group. Impact of Huntington's across the entire disease spectrum: the phases and stages of disease from the patient perspective. Clin Genet. 2011 Sep;80(3):235-9. doi: 10.1111/j.1399-0004.2011.01748.x. Epub 2011 Aug 4.
citation: Quarrell OW, Handley O, O'Donovan K, Dumoulin C, Ramos-Arroyo M, Biunno I, Bauer P, Kline M, Landwehrmeyer GB; European Huntington's Disease Network. Discrepancies in reporting the CAG repeat lengths for Huntington's disease. Eur J Hum Genet. 2012 Jan;20(1):20-6. doi: 10.1038/ejhg.2011.136. Epub 2011 Aug 3.
citation: Saft C, Epplen JT, Wieczorek S, Landwehrmeyer GB, Roos RA, de Yebenes JG, Dose M, Tabrizi SJ, Craufurd D; REGISTRY Investigators of the European Huntington's Disease Network; Arning L. NMDA receptor gene variations as modifiers in Huntington disease: a replication study. PLoS Curr. 2011 Oct 4;3:RRN1247. doi: 10.1371/currents.RRN1247.
citation: Rickards H, De Souza J, Crooks J, van Walsem MR, van Duijn E, Landwehrmeyer B, Squitieri F, Simpson SA; European Huntington's Disease Network. Discriminant analysis of Beck Depression Inventory and Hamilton Rating Scale for Depression in Huntington's disease. J Neuropsychiatry Clin Neurosci. 2011 Fall;23(4):399-402. doi: 10.1176/jnp.23.4.jnp399.
citation: Lee JM, Ramos EM, Lee JH, Gillis T, Mysore JS, Hayden MR, Warby SC, Morrison P, Nance M, Ross CA, Margolis RL, Squitieri F, Orobello S, Di Donato S, Gomez-Tortosa E, Ayuso C, Suchowersky O, Trent RJ, McCusker E, Novelletto A, Frontali M, Jones R, Ashizawa T, Frank S, Saint-Hilaire MH, Hersch SM, Rosas HD, Lucente D, Harrison MB, Zanko A, Abramson RK, Marder K, Sequeiros J, Paulsen JS; PREDICT-HD study of the Huntington Study Group (HSG); Landwehrmeyer GB; REGISTRY study of the European Huntington's Disease Network; Myers RH; HD-MAPS Study Group; MacDonald ME, Gusella JF; COHORT study of the HSG. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion. Neurology. 2012 Mar 6;78(10):690-5. doi: 10.1212/WNL.0b013e318249f683. Epub 2012 Feb 8.
citation: Henley SM, Ridgway GR, Scahill RI, Kloppel S, Tabrizi SJ, Fox NC, Kassubek J; EHDN Imaging Working Group. Pitfalls in the use of voxel-based morphometry as a biomarker: examples from huntington disease. AJNR Am J Neuroradiol. 2010 Apr;31(4):711-9. doi: 10.3174/ajnr.A1939. Epub 2009 Dec 24.
citation: Aziz NA, Jurgens CK, Landwehrmeyer GB; EHDN Registry Study Group; van Roon-Mom WM, van Ommen GJ, Stijnen T, Roos RA. Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease. Neurology. 2009 Oct 20;73(16):1280-5. doi: 10.1212/WNL.0b013e3181bd1121. Epub 2009 Sep 23.
citation: Youssov K, Audureau E, Vandendriessche H, Morgado G, Layese R, Goizet C, Verny C, Bourhis ML, Bachoud-Levi AC. The burden of Huntington's disease: A prospective longitudinal study of patient/caregiver pairs. Parkinsonism Relat Disord. 2022 Oct;103:77-84. doi: 10.1016/j.parkreldis.2022.08.023. Epub 2022 Aug 24.
citation: McAllister B, Gusella JF, Landwehrmeyer GB, Lee JM, MacDonald ME, Orth M, Rosser AE, Williams NM, Holmans P, Jones L, Massey TH; REGISTRY Investigators of the European Huntington's Disease Network. Timing and Impact of Psychiatric, Cognitive, and Motor Abnormalities in Huntington Disease. Neurology. 2021 May 11;96(19):e2395-e2406. doi: 10.1212/WNL.0000000000011893. Epub 2021 Mar 25.
citation: Cubo E, Ramos-Arroyo MA, Martinez-Horta S, Martinez-Descalls A, Calvo S, Gil-Polo C; European HD Network. Clinical manifestations of intermediate allele carriers in Huntington disease. Neurology. 2016 Aug 9;87(6):571-8. doi: 10.1212/WNL.0000000000002944. Epub 2016 Jul 8.