DOCSLIB.ORG

Clinical Review Huntington's Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Clinical Review Huntington's Disease CLINICAL REVIEW For the full versions of these articles see bmj.com Huntington’s disease Marianne J U Novak,1 2 Sarah J Tabrizi1 3 1National Hospital for Neurology Huntington’s disease is a devastating inherited and Neurosurgery, London neurodegenerative disease characterised by progressive motor, WC1N 3BG cognitive, and psychiatric symptoms. Patients may present 2Wellcome Trust Centre for Neuroimaging, UCL Institute of with any of these symptoms, and familiarity with the pheno- Neurology, London WC1N 3BG type is therefore important. Chorea and loss of balance are 3Department of Neurodegenerative early symptoms that patients notice, although families often Disease, UCL Institute of Neurology notice cognitive or personality changes before this. Correspondence to: S Tabrizi [email protected] The disease occurs in all racial groups but is most common in people of northern European origin. Its prevalence in the Cite this as: BMJ 2010;340:c3109 Western hemisphere is 7-10/100 000.w1 The mean age of onset doi: 10.1136/bmj.c3109 of symptoms is 40 years, but juvenile onset (<20 years) and older onset (>70 years) forms are well recognised. The Hunt- ington’s Disease Association (HDA) has records of 6161 adults with symptomatic Huntington’s disease and 541 children with juvenile Huntington’s disease (in England and Wales) at the Fig 1 | Statistical parametric map showing grey matter volume loss in patient groups compared with controls. Pre-A and time of writing. This is a conservative estimate of prevalence pre-B are premanifest Huntington’s disease gene carriers with because it includes only those people in contact with the HDA, estimated time to clinical disease onset greater than and less and it suggests that the true prevalence of the disease is higher than 10.8 years, respectively. (This was estimated using CAG than previously thought.1 repeat length and age in a formula that has been well validated Although relatively uncommon, Huntington’s disease can and used extensively in research into Huntington’s diseasew10). be devastating for patients and their families. People who are at Stage 1 and stage 2 are patients with early manifest disease who risk of developing the disease because of a family history face have no functional impairment and mild functional impairment, difficult decisions about genetic testing. We review the features respectively. The figure shows progressive grey matter volume loss in the caudate and putamen (striatum) initially, followed of Huntington’s disease, recent advances in management, and by the cerebral cortex. Results are adjusted for age, sex, study advances in the practice and ethics of genetic testing that may site, and total intracranial volume and are corrected for multiple be relevant to a wide spectrum of health professionals. comparisons using family-wise error at P<0.05. Reproduced from Tabrizi et al,7 with permission from the Elsevier Publishing Group What are the clinical features of Huntington’s disease? The disease was originally named Huntington’s chorea after changes are initially seen most prominently in the striatum George Huntington, who wrote the first detailed description (part of the basal ganglia) and later become more widespread, in 1872. More recently, however, the name has changed to as shown in fig 1. Huntington’s disease to reflect the fact that chorea is not the Huntington’s disease progresses over 15-20 years. Char- only important manifestation of the disease. Many non-motor acteristic symptoms reflect a triad of motor, cognitive, and symptoms may be more disabling and distressing than the psychiatric manifestations of the disease (box 1). The onset motor symptoms.2-4 One study assessed the effect of cognitive of disease is currently defined as the point at which charac- and motor symptoms on the ability of 67 people with early teristic motor signs develop8; this is when a patient moves Huntington’s disease to carry out activities of daily living, and from being a “premanifest gene carrier” to having “manifest” found that cognitive impairment was associated with reduced disease. This distinction is somewhat arbitrary because most bmj.com archive functional ability independent of motor impairment.2 patients develop cognitive or psychiatric symptoms (or both) Ж Book review: Saturday Imaging and postmortem studies have shown that the during the prodromal (“premanifest”) period, often many (BMJ 2005;330:368) d isease is characterised by cerebral atrophy.5 6 Atrophic years before any motor signs are seen.7 9 w2 SUMMARY POINTS SOURCES AND SELECTION CRITERIA Huntington’s disease causes motor, cognitive, and psychiatric impairment This review is based on our experience of leading (SJT) Predictive and diagnostic genetic testing are available through specialist centres and working in (MJUN) the multidisciplinary Huntington’s disease clinic at the National Hospital for Neurology Genetic testing for the disease has many implications for patients and families and Neurosurgery, supported by an up to date literature The disease currently has no cure, but many therapeutic options exist to improve symptoms review performed using PubMed and a review of the Optimal care usually requires input from a multidisciplinary team Cochrane database. 34 BMJ | 3 JULY 2010 | VOLUME 341 CLINICAL REVIEW Box 1 | Common symptoms of Huntington’s disease Psychiatric symptoms Depression is one of the most common psychiatric symptoms Motor symptoms Chorea, dystonia, loss of postural reflexes, bradykinesia, rigidity and occurs as part of the disease, rather than merely as a response to diagnosis. A recent survey of 2835 patients with Cognitive symptoms Disorganisation as a result of difficulties with planning, initiating, and organising thoughts, the disease found that 40% had symptoms of depression, activities, and communication; perseveration; impulsivity; perceptual distortions; lack of and 50% reported having sought treatment for depression 10 insight; distractibility; difficulty in learning new information in the past. Other reported psychiatric symptoms include w3-w5 Psychiatric obsessive-compulsive symptoms and psychosis. Depression, obsessive-compulsive disorders, anxiety, irritability, apathy, hypersexuality It is important to recognise psychiatric symptoms in (uncommon), psychosis (uncommon) Huntington’s disease so that symptomatic treatment can Metabolic be offered. This may be difficult later in the disease because Weight loss, sleep disturbance diagnoses may be obscured by other features of the disease; Others depression, for example, may be difficult to detect in a patient Dysphasia (combination of motor and language difficulties), dysphagia (combination of who has altered facial expressions and tone of voice. Con- motor problems, impulsivity, and distractibility) versely, metabolic symptoms such as weight loss and sleep disturbance may be wrongly attributed to depression. Motor symptoms The motor symptoms of Huntington’s disease can be Suicide risk divided into two categories: added involuntary move- Patients with Huntington’s disease are more likely than mem- ments such as chorea, and impaired voluntary move- bers of the general population to commit suicide according ments, which cause limb incoordination and impaired to a meta-analysis of studies that reported mortality associ- hand function. These symptoms are worsened by loss ated with mental disorders (standardised mortality ratio of of postural reflexes. The pattern of symptoms tends to 290).w6 A survey of 4171 carriers of the Huntington’s gene change over time, with chorea declining and dystonia, with premanifest and manifest disease found that 17.5% rigidity, and bradykinesia becoming more marked. had suicidal thoughts at or around the time of assessment and 10% of those surveyed had made at least one suicide Cognitive symptoms attempt in the past.11 Suicidal ideation was highest in gene Cognitive impairment includes slowing of thought carriers who were nearing the threshold of being diagnosed processing and deterioration of executive functions with manifest disease (those with soft motor signs of Hunt- (high level cognitive processes that control other aspects ington’s disease), and in those who were beginning to lose of cognitive function). Typically, patients report difficulty their functional ability and independence (those with stage with multitasking, concentration, and short term memory. 2 disease). Risk factors for suicide in Huntington’s disease Thinking style becomes more concrete and less efficient, include depression and impulsivity.4 Some people with the and the planning, initiation, and organisation of time, disease also have suicidal thoughts in the absence of depres- thoughts, and activities become harder. People with sionw7: for some, thoughts of suicide seem to be a rational Huntington’s disease are often impulsive and develop response to their imminent loss of independence. psychomotor perseveration. Visuospatial perception can also deteriorate.4 9 Metabolic symptoms Huntington’s disease causes metabolic symptoms, which Linkage markers on chromosome 4 include catabolic weight loss, endocrine dysfunction, and sleep disturbance.12 Parent with Unaffected A B C D Huntington's parent disease Advanced disease By the time patients have endstage disease they are pro- Either A or B Neither C nor D foundly disabled. Communication may be severely limited carries mutant carries mutant and muteness is common, which can result in agitation HTT gene HTT gene and frustration. Huntington’s disease does not cause global Partner
Load more

Recommended publications
  • New Therapeutic Property of Dimebon As a Neuroprotective Agent
    Send Orders for Reprints to [email protected] Current Medicinal Chemistry, 2016, 23, 1-12 1 REVIEW ARTICLE New Therapeutic Property of Dimebon as a Neuroprotective Agent Aleksey Ustyugov1, Elena Shevtsova1, George E. Barreto2,3, Ghulam Md Ashraf 4, Sergey O. Bachurin1 and Gjumrakch Aliev1,5,6,* 1Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy Proezd 1, Cher- nogolovka, 142432, Russia; 2Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Uni- versidad Javeriana, Bogotá D.C., Colombia; 3Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile; 4King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Ara- bia; 5GALLY International Biomedical Research Consulting LLC., 7733 Louis Pasteur Drive, #330, San An- tonio, TX, 78229, USA; 6School of Health Science and Healthcare Administration, University of Atlanta, E. Johns Crossing, #175, Johns Creek, GA, 30097, USA Abstract: Dimebon (or Latrepirdine) was initially used as an anti-histamergic drug but later new therapeutic properties were rediscovered, adding to a growing body of “old” agents with prominent neuroprotective effects. In the present manuscript, we are focusing on our latest study on Dimebon with regard to brain’s pathological processes using in vivo protei- A R T I C L E H I S T O R Y nopathy models. In the study, neurodegenerative pathology has been attributed to a group of aggregate-prone proteins: hyperphosphorylated tau, fused in sarcoma and γ-synuclein , which Received: March 13, 2016 Revised: June 08, 2016 are involved in a number of neurological disorders. We have also presented our in vitro Accepted: July 24, 2016 model based on overexpression of an aberrant mutant form of transactive response DNA DOI: 10.2174/0929867323666160804 binding 43 kDa protein in cultured SH-SY5Y neuroblastoma cells.
    [Show full text]
  • Copyrighted Material
    Index Note: page numbers in italics refer to figures; those in bold to tables or boxes. abacavir 686 tolerability 536–537 children and adolescents 461 acamprosate vascular dementia 549 haematological 798, 805–807 alcohol dependence 397, 397, 402–403 see also donepezil; galantamine; hepatic impairment 636 eating disorders 669 rivastigmine HIV infection 680 re‐starting after non‐adherence 795 acetylcysteine (N‐acetylcysteine) learning disability 700 ACE inhibitors see angiotensin‐converting autism spectrum disorders 505 medication adherence and 788, 790 enzyme inhibitors obsessive compulsive disorder 364 Naranjo probability scale 811, 812 acetaldehyde 753 refractory schizophrenia 163 older people 525 acetaminophen, in dementia 564, 571 acetyl‐L‐carnitine 159 psychiatric see psychiatric adverse effects acetylcholinesterase (AChE) 529 activated partial thromboplastin time 805 renal impairment 647 acetylcholinesterase (AChE) acute intoxication see intoxication, acute see also teratogenicity inhibitors 529–543, 530–531 acute kidney injury 647 affective disorders adverse effects 537–538, 539 acutely disturbed behaviour 54–64 caffeine consumption 762 Alzheimer’s disease 529–543, 544, 576 intoxication with street drugs 56, 450 non‐psychotropics causing 808, atrial fibrillation 720 rapid tranquillisation 54–59 809, 810 clinical guidelines 544, 551, 551 acute mania see mania, acute stupor 107, 108, 109 combination therapy 536 addictions 385–457 see also bipolar disorder; depression; delirium 675 S‐adenosyl‐l‐methionine 275 mania dosing 535 ADHD
    [Show full text]
  • Scientific Advisory Board
    SCIENTIFIC ADVISORY BOARD ANNE B. YOUNG, MD, PHD CHAIR, SCIENTIFIC ADVISORY Board Chair Emerita, Department of Neurology Massachusetts General Hospital Distinguished Julieanne Dorn Professor of Neurology Harvard Medical School Royal College of Physicians, London American SCIENTIFICAcademy of Arts and Sciences ADVISORYNational Academy of MedicineBOARD ith funding from the Hereditary Disease Foundation and the National Institutes of Health, Anne WYoung has been involved in Huntington’s disease research for four decades. Anne participated in the Hereditary Disease Foundation’s Venezuela HD Project from 1981 until 2002 when the team could no longer return because of then Venezuelan President Hugo Chavez’s restrictions. In Venezuela, Anne focused on making accurate diagnoses, drawing blood for DNA, taking skin biopsies and helping collect tissue samples generously donated by the Venezuelan HD family members. Of the 20,000 neurological exams performed, Anne did many of them. Anne trained and mentored medical students and residents who joined the team. Anne and her late husband John B. (“Jack”) Penney, Jr. tested new models of how the basal ganglia controls movements. They based their theories on data from animal and postmortem human brain samples. They discovered, through clever experiments, how the basal ganglia are affected in Huntington’s and Parkinson’s diseases. The basal ganglia controls movement, reward, emotions and memory. Anne and Jack’s model suggested the design of therapies that would help both diseases. Anne was recruited in 1991 to Harvard Medical School and Massachusetts General Hospital as the hospital’s first female head of a department. She founded and designed the MassGeneral Institute for Neurodegenerative Diseases (MIND) in 2001 to accelerate the discovery of new and effective therapies for these disorders.
    [Show full text]
  • Press Release
    Press release Embargoed until 10.00 (GMT) Friday 9 May 2014 44 leading medical experts recognised for excellence in research 44 researchers from across the UK have been recognised for their contribution to the advancement of medical science by election to the Fellowship of the Academy of Medical Sciences. Academy Fellows are elected for excellence in medical research, for innovative application of scientific knowledge or for their conspicuous service to healthcare. The expertise of the new Fellows includes haematology, bioinformatics, immunology, psychiatry, biochemistry and health services provision. This year, fifteen (34%) of the new Fellows are women, compared to 23.2% of bioscience professors in the UK.* Professor Sir John Tooke PMedSci, President of the Academy of Medical Sciences said, “The Academy of Medical Sciences represents the excellence and diversity of medical science in the UK, and this is evident in the broad range of expertise demonstrated by this year’s new Fellows. They each bring a unique perspective which we will value immensely – from the industry experience of Fellows such as Professor Jackie Hunter to the policy knowledge of Baroness Finlay. Their election is a much deserved honour for the outstanding achievements they have shown throughout their careers. I know they will contribute greatly to the Academy, and I am delighted to welcome them all to the Fellowship.” Baroness Ilora Finlay of Landaff FMedSci is Professor of Palliative Medicine at Cardiff University, and a consultant at the Velindre Cancer Centre. In 2003, driven by her work with terminally ill lung cancer patients, she proposed a parliamentary bill to ban smoking in public buildings, and has worked with the government closely to advise on UK policies regarding organ donation, carbon monoxide poisoning, sunbed usage, bereavement in children and the care of prisoners.
    [Show full text]
  • 2009 Nhamcs Micro-Data File Documentation Page 1
    2009 NHAMCS MICRO-DATA FILE DOCUMENTATION PAGE 1 ABSTRACT This material provides documentation for users of the public use micro-data files of the 2009 National Hospital Ambulatory Medical Care Survey (NHAMCS). NHAMCS is a national probability sample survey of visits to hospital outpatient and emergency departments, conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention. The survey is a component of the National Health Care Surveys, which measure health care utilization across a variety of health care providers. There are two micro-data files produced from NHAMCS, one for outpatient department records and one for emergency department records. Section I of this documentation, “Description of the National Hospital Ambulatory Medical Care Survey,” includes information on the scope of the survey, the sample, field activities, data collection procedures, medical coding procedures, and population estimates. Section II provides detailed descriptions of the contents of each file’s data record by location. Section III contains marginal data for selected items on each file. The appendixes contain sampling errors, instructions and definitions for completing the Patient Record forms, and lists of codes used in the survey. PAGE 2 2009 NHAMCS MICRO-DATA FILE DOCUMENTATION SUMMARY OF CHANGES FOR 2009 The 2009 NHAMCS Emergency Department and Outpatient Department public use micro-data files are, for the most part, similar to the 2008 files, but there are some important changes. These are described in more detail below and reflect changes to the survey instrument, the Patient Record form. Emergency Departments 1. New or Modified Items a. In item 1, Patient Information, there is a new checkbox item “Arrival by Ambulance.” This replaces the 2008 item, “Mode of Arrival.” b.
    [Show full text]
  • Director's View: December 2020 Message from the Director And
    Director's view: December 2020 Message from the Director and Manager Welcome to the latest edition of the Institute’s termly newsletter, which is an update and highlights some of the many excellent activities at the Institute over the past 4 months. There have been many recent significant Institute achievements, some attracting major media attention (http://www.ucl.ac.uk/ion/news). It’s been nearly a year since the Covid-19 pandemic emerged around the world and made it very challenging for the fantastic work you all deliver in the Institute to continue as normal. We want to thank every single one of you who is helping us manage this unprecedented crisis and for the incredible innovation and collegiate spirit you have all shown. We have collectively adjusted to a “new normal” way of life, mastered the art of socialising with our friends and loved ones over Zoom, and gradually resumed most of our core work activities. IoN was part of the UCL pilots for re-opening buildings in June and we have since successfully re-opened all of them throughout the summer, thanks to your help and support. For more information please visit the Keeping safe on campus pages. There are a range of tools and initiatives available to all staff and students to help you cope during these difficult times, and to support you whilst working remotely. We have successfully restarted our planning for a new world-leading Translational Neuroscience Centre ; demolition of the old site on Gray’s Inn Road is well underway. As part of this major capital project, we are developing a number of new initiatives to improve laboratory support and ways of working.
    [Show full text]
  • Drug Delivery System for Use in the Treatment Or Diagnosis of Neurological Disorders
    (19) TZZ __T (11) EP 2 774 991 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 10.09.2014 Bulletin 2014/37 C12N 15/86 (2006.01) A61K 48/00 (2006.01) (21) Application number: 13001491.3 (22) Date of filing: 22.03.2013 (84) Designated Contracting States: • Manninga, Heiko AL AT BE BG CH CY CZ DE DK EE ES FI FR GB 37073 Göttingen (DE) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO •Götzke,Armin PL PT RO RS SE SI SK SM TR 97070 Würzburg (DE) Designated Extension States: • Glassmann, Alexander BA ME 50999 Köln (DE) (30) Priority: 06.03.2013 PCT/EP2013/000656 (74) Representative: von Renesse, Dorothea et al König-Szynka-Tilmann-von Renesse (71) Applicant: Life Science Inkubator Betriebs GmbH Patentanwälte Partnerschaft mbB & Co. KG Postfach 11 09 46 53175 Bonn (DE) 40509 Düsseldorf (DE) (72) Inventors: • Demina, Victoria 53175 Bonn (DE) (54) Drug delivery system for use in the treatment or diagnosis of neurological disorders (57) The invention relates to VLP derived from poly- ment or diagnosis of a neurological disease, in particular oma virus loaded with a drug (cargo) as a drug delivery multiple sclerosis, Parkinsons’s disease or Alzheimer’s system for transporting said drug into the CNS for treat- disease. EP 2 774 991 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 774 991 A1 Description FIELD OF THE INVENTION 5 [0001] The invention relates to the use of virus like particles (VLP) of the type of human polyoma virus for use as drug delivery system for the treatment or diagnosis of neurological disorders.
    [Show full text]
  • 2-The Putative Neurodegenerative Links.Pdf
    Progress in Neurobiology 91 (2010) 362–375 Contents lists available at ScienceDirect Progress in Neurobiology journal homepage: www.elsevier.com/locate/pneurobio The putative neurodegenerative links between depression and Alzheimer’s disease Suthicha Wuwongse a,b, Raymond Chuen-Chung Chang b,c,d,*, Andrew C.K. Law a,c,d,** a Department of Psychiatry, LKS Faculty of Medicine, Hong Kong b Laboratory of Neurodegenerative Diseases, Department of Anatomy, LKS Faculty of Medicine, Hong Kong c Research Centre of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, Hong Kong d State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong ARTICLE INFO ABSTRACT Article history: Alzheimer’s disease (AD) is the leading neurodegenerative cause of dementia in the elderly. Thus far, Received 11 September 2009 there is no curative treatment for this devastating condition, thereby creating significant social and Received in revised form 16 April 2010 medical burdens. AD is characterized by progressive cognitive decline along with various Accepted 27 April 2010 neuropsychiatric symptoms, including depression and psychosis. Depression is a common psychiatric disorder affecting individuals across the life span. Although the Keywords: ‘‘monoamine hypothesis’’ of depression has long been proposed, the pathologies and mechanisms for Alzheimer’s disease depressive disorders remain only partially understood. Pharmacotherapies targeting the monoaminer- Depression gic pathways have been the mainstay in treating depression. Additional therapeutic approaches focusing Neuroinflammation Brain-derived nerve growth factor other pathological mechanisms of depression are currently being explored. Neurodegeneration Interestingly, a number of proposed mechanisms for depression appear to be similar to those Cortisol implicated in neurodegenerative diseases, including AD.
    [Show full text]
  • Serotonergic System Antagonists Target Breast Tumor Initiating Cells and Synergize with Chemotherapy to Shrink Human Breast Tumor Xenografts
    www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 19), pp: 32101-32116 Research Paper Serotonergic system antagonists target breast tumor initiating cells and synergize with chemotherapy to shrink human breast tumor xenografts William D. Gwynne1, Robin M. Hallett1, Adele Girgis-Gabardo1, Bojana Bojovic1, Anna Dvorkin-Gheva2, Craig Aarts1, Kay Dias2, Anita Bane2 and John A. Hassell1,2 1Department of Biochemistry and Biomedical Sciences, McMaster University, Canada 2Department of Pathology and Molecular Medicine, McMaster University, Canada Correspondence to: John A. Hassell, email: [email protected] Keywords: breast cancer stem cells, tumor-initiating cells, serotonin antagonists, antidepressants, cytotoxic chemotherapy Received: November 25, 2016 Accepted: March 01, 2017 Published: March 29, 2017 Copyright: Gwynne et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Breast tumors comprise an infrequent tumor cell population, termed breast tumor initiating cells (BTIC), which sustain tumor growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC to provide more durable breast cancer remissions than are currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse BTIC resident in the mammary tumors of a HER2-overexpressing model
    [Show full text]
  • In This Issue Famous Neurologists Personal Perspectives
    ISSN 1473-9348 VOLUME 10 ISSUE 4 SEPTEMBER/OCTOBER 2010 ACNRwww.acnr.co.uk ADVANCES IN CLINICAL NEUROSCIENCE & REHABILITATION In this issue Gérard Said – Vasculitic Neuropathy Famous Neurologists J van Gijn – Joseph Babinski 1857-1932 Hugh Rickards – How Helpful is it to Global Outcome to Treat Abnormal Movements in Tourette’s Syndrome? Personal Perspectives Parkinson’s Disease: personal experience NEWS REVIEW > CONFERENCE REPORTS > BOOK REVIEWS > JOURNAL REVIEWS > EVENTS DIARY Make a lasting impression By initiating early Azilect monotherapy, you can maintain your patients’ overall motor performance.1,2 So make a lasting impression – initiate Azilect monotherapy early in the course of Parkinson’s disease.3 Simple and effective when it matters Azilect ® 1mg tablets in patients treated concomitantly with antidepressants/SNRIs and POM Marketing Authorisation Number: 1mg tablets (28 pack size) Prescribing information (Please refer to the Summary of Product rasagiline. Avoid concomitant use with fluoxetine or fluvoxamine. EU/1/04/304/003 Marketing Authorisation Holder: Teva Pharma Characteristics (SmPC) before prescribing) Presentation: Tablets Leave at least five weeks between discontinuation of fluoxetine and GmbH, Kandelstr 10, D-79199 Kirchzarten Germany Date last revised: containing 1mg rasagiline (as the mesilate). Indication: Treatment initiation of treatment with rasagiline. Leave at least 14 days between December 2009. Further information available from: Lundbeck of idiopathic Parkinson’s disease as monotherapy or as adjunct to discontinuation of rasagiline and initiation of treatment with fluoxetine Limited, Lundbeck House, Caldecotte Lake Business Park, Caldecotte, levodopa in patients with end of dose fluctuations. Dosage and or fluvoxamine. Administer potent CYP1A2 inhibitors with caution. Milton Keynes, MK7 8LG administration: Oral, 1mg once daily taken with or without food Co-administration with dextromethorphan or sympathomimetics and with or without levodopa.
    [Show full text]
  • 2 12/ 35 74Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 22 March 2012 (22.03.2012) 2 12/ 35 74 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 9/16 (2006.01) A61K 9/51 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 9/14 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/EP201 1/065959 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 14 September 201 1 (14.09.201 1) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, (25) Filing Language: English RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (26) Publication Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/382,653 14 September 2010 (14.09.2010) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, NANOLOGICA AB [SE/SE]; P.O Box 8182, S-104 20 ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, Stockholm (SE).
    [Show full text]
  • Compensation in Preclinical Huntington's Disease: Evidence from the Track-On HD Study
    EBioMedicine 2 (2015) 1420–1429 Contents lists available at ScienceDirect EBioMedicine journal homepage: www.ebiomedicine.com Research Article Compensation in Preclinical Huntington's Disease: Evidence From the Track-On HD Study Stefan Klöppel a,b,c,1,SarahGregoryd,1, Elisa Scheller a,b,e,LoraMinkovaa,b,e, Adeel Razi d,f, Alexandra Durr g,h, Raymund A.C. Roos i, Blair R. Leavitt j, Marina Papoutsi k,G.BernhardLandwehrmeyerl, Ralf Reilmann m,n, Beth Borowsky o, Hans Johnson p, James A. Mills q, Gail Owen k, Julie Stout r, Rachael I. Scahill k, Jeffrey D. Long q,s, Geraint Rees d,t,⁎,1, Sarah J. Tabrizi k,⁎⁎,1, the Track-On investigators a Albert-Ludwigs-University Freiburg, University Medical Center, Division Freiburg Brain Imaging, Freiburg, Germany b Albert-Ludwigs-University Freiburg, University Medical Center, Department of Psychiatry and Psychotherapy, Freiburg, Germany c Albert-Ludwigs-University Freiburg, University Medical Center, Department of Neurology, Freiburg, Germany d Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, UK e Albert-Ludwigs-University Freiburg, Department of Psychology, Laboratory for Biological and Personality Psychology, Freiburg, Germany f Department of Electronic Engineering, N.E.D University of Engineering & Technology, Karachi, Pakistan g APHP Department of Genetics, Groupe Hospitalier Pitié-Salpêtrière, UPMC Université Paris VI UMR_S1127, Paris France h Institut du Cerveau et de la Moelle, INSERM U1127, CNRS UMR7225, UPMC Université Paris VI UMR_S1127,
    [Show full text]