DOCSLIB.ORG

Corticobasal Syndrome: Clinical, Neuropsychological, Imaging

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Corticobasal Syndrome: Clinical, Neuropsychological, Imaging CORTICOBASAL SYNDROME: CLINICAL, NEUROPSYCHOLOGICAL, IMAGING, GENETIC AND PATHOLOGICAL FEATURES by Mario Masellis A thesis submitted in conformity with the requirements for the degree of Doctorate of Philosophy in the Graduate Department of Institute of Medical Sciences, University of Toronto © Copyright by Mario Masellis (2012) Library and Archives Bibliothèque et Canada Archives Canada Published Heritage Direction du Branch Patrimoine de l'édition 395 Wellington Street 395, rue Wellington Ottawa ON K1A 0N4 Ottawa ON K1A 0N4 Canada Canada Your file Votre référence ISBN: 978-0-494-97827-6 Our file Notre référence ISBN: 978-0-494-97827-6 NOTICE: AVIS: The author has granted a non- L'auteur a accordé une licence non exclusive exclusive license allowing Library and permettant à la Bibliothèque et Archives Archives Canada to reproduce, Canada de reproduire, publier, archiver, publish, archive, preserve, conserve, sauvegarder, conserver, transmettre au public communicate to the public by par télécommunication ou par l'Internet, prêter, telecommunication or on the Internet, distribuer et vendre des thèses partout dans le loan, distrbute and sell theses monde, à des fins commerciales ou autres, sur worldwide, for commercial or non- support microforme, papier, électronique et/ou commercial purposes, in microform, autres formats. paper, electronic and/or any other formats. The author retains copyright L'auteur conserve la propriété du droit d'auteur ownership and moral rights in this et des droits moraux qui protege cette thèse. Ni thesis. Neither the thesis nor la thèse ni des extraits substantiels de celle-ci substantial extracts from it may be ne doivent être imprimés ou autrement printed or otherwise reproduced reproduits sans son autorisation. without the author's permission. In compliance with the Canadian Conformément à la loi canadienne sur la Privacy Act some supporting forms protection de la vie privée, quelques may have been removed from this formulaires secondaires ont été enlevés de thesis. cette thèse. While these forms may be included Bien que ces formulaires aient inclus dans in the document page count, their la pagination, il n'y aura aucun contenu removal does not represent any loss manquant. of content from the thesis. Corticobasal Syndrome: Clinical, Neuropsychological, Imaging, Genetic and Pathological Features Doctorate of Philosophy 2012 Mario Masellis Graduate Department of Institute of Medical Sciences, University of Toronto ABSTRACT Corticobasal Syndrome (CBS) is a rare movement and cognitive disorder. There is significant heterogeneity observed in it clinical presentation, neuroimaging, pathology and genetics. Understanding this heterogeneity is a priority and may help to shed light on underlying pathogenic mechanisms. We first demonstrated that truncating mutations in the progranulin gene (PGRN) can cause familial CBS associated with frontotemporal lobar degeneration (FTLD)- ubiquitin pathology. This study identified a mutation in PGRN (Intervening Sequence 7+1 guanine > adenine [IVS7+1G>A]) that segregated with CBS in a family. The mutation was predicted to result in a shortened messenger RNA (mRNA) sequence and the absence of the mutant PGRN allele was confirmed in the reverse transcriptase-polymerase chain reaction (RT- PCR) product, which supported the model of haploinsufficiency for PGRN-linked disease. In a second familial study, clinical, radiological, genetic, and pathological studies were performed to contrast clinical features of the affected members. Sequencing PGRN revealed a novel, heterozygous cytosine-adenine dinucleotide deletion in exon 11 (g.2988_2989delCA, P439_R440fsX6). The proband`s clinical diagnosis was frontotemporal dementia and parkinsonism (FTDP). The proband‟s brother with the same mutation presented initially as a progressive non-fluent aphasia (PNFA), and later evolved into a CBS. Pathological analysis ii revealed Frontotemporal Lobar Degeneration-Ubiquitin (FTLD-U)/ TAR DNA-binding protein 43 (TDP43) positive pathology. The next studies shift away from pathogenic mechanisms to focus on brain-behavioural correlations and phenotypic heterogeneity in a prospective sample of 31 CBS cases. We provide the first direct correlative analysis between the severity of ideomotor apraxia, a common sign in CBS, and cerebral SPECT perfusion imaging. Reductions in perfusion within the left inferior parietal lobule (t=5.7, p=0.03, Family-Wise Error [FWE] corrected), including the left angular gyrus (t=5.7, p=0.02, FWE corrected), were associated with more severe ideomotor apraxia. We stratified the sample into CBS presenting with early motor features (CBS-M; n=9) or early dementia (CBS-D; n=22), which identified that CBS-M were more likely to have cortical sensory loss than CBS-D (p=0.005). In contrast, the presence of aphasia was found to be more common and severe in CBS-D compared to CBS-M (p=0.02). CBS-M patients had significantly reduced perfusion in the right supplementary and premotor areas compared to CBS-D (p<0.05). iii ACKNOWLEDGEMENTS I would like to first and foremost thank my supervisor, Dr. Sandra Black, for her support and mentorship over the many years that I have known her. I first met Dr. Black (a.k.a. Sandy) back in 2001 when I began my residency program in psychiatry. I attended many of her cognitive neurology clinics as an intern and it was this initial exposure to the field of neurology and neurodegenerative disease that made me decide to transfer into the neurology residency program. The commitment and passion that she displayed towards treating patients and their families afflicted with these devastating diseases was truly an inspiration for me. She taught me that every patient has something unique to offer not only in terms of developing my clinical skills, but also importantly in terms of asking novel questions about the diseases and their heterogeneous presentations that could be assessed using the scientific method and valuable data gathered from clinical and neuroimaging studies. In 2004, I had an opportunity to do my fourth year project course in her lab, which further stimulated me to pursue a career in research and enroll in the Ph.D. program following completion of my residency. Needless to say, my experiences in her lab have been outstanding. As a result of this training, I have learned a new research method, applied neuroimaging, which I now can add to my repertoire of techniques to use in my clinical and genetic studies. Sandy‟s enthusiasm for research is incredible and her passion to understand and to investigate novel therapies to treat these devastating disorders has also stimulated me to pursue a career as a clinician-scientist. I would also like to thank Sandy for her support of my research ideas, which have led to several peer-reviewed funding projects during and beyond my training. Thank you Sandy for your ongoing support and I look forward to collaborating with you on many interesting projects to come! iv I would also like to thank Dr. James Kennedy (a.k.a. Jim) for his mentorship over many years and also for his contribution to and participation on my program advisory committee. Jim stimulated my initial interest in scientific research in the mid-1990s when I completed a M.Sc. in his laboratory. My thesis was on pharmacogenetics and I am pleased to say that I continue this very interesting line of research using the combination of my genetic, clinical and neuroimaging training. I would also like to thank Dr. Robert Chen for his commitment and contributions that he has made as a member of my program advisory committee. I appreciate the efforts of Dr. Antonio Strafella for reading my thesis under tight time lines and also for being present at my final program advisory committee meeting to participate as an additional examiner. I would like to thank my friends and colleagues: Dr. Brad MacIntosh, Dr. Kie Honjo, Dr. Galit Kleiner-Fisman, Dr. Ekaterina Rogaeva, Dr. Anthony E. Lang, Dr. Eric Roy, Isabelle Guimont, Philip Francis, and Gregory Szilagyi. Their technical and thought-stimulating advice and suggestions have helped to bring me to this point today. I would also like to thank Kayla Sherborn for her impeccable organizational skills in helping to assemble components of this thesis. I would like to thank my in-laws for their support over the last few years and also for their assistance in making home life more manageable. I would like to thank my parents for providing me with the opportunities to pursue higher level education and for providing the right environment for me to succeed. I greatly appreciate their continued support and inspiration and I v am indebted to them for their patience especially over the last few years during the preparation of this thesis. Last but not least, I would like to thank my beautiful wife, Paola Masellis, for her incredible patience and support that she has provided since the first day that I met her and over the course of the last few years during the completion of this thesis. We have been through a lot together, especially in recent years, and I am indebted to her kindness, love, and caring attitude. With the completion of this thesis, I look forward to many good times ahead and many more years of positive and happy life experiences together with her. Thanks for all that you do! vi TABLE OF CONTENTS TITLE PAGE i ABSTRACT ii ACKNOWLEDGEMENTS iv TABLE OF CONTENTS vii LIST OF TABLES xi LIST OF FIGURES xiii ABBREVIATIONS xvii CONTRIBUTIONS xxv 1.0: GENERAL INTRODUCTION 1 1.1 Corticobasal Degeneration: Historical
Load more

Recommended publications
  • Criteria for the Diagnosis of Corticobasal Degeneration
    VIEWS & REVIEWS Criteria for the diagnosis of corticobasal degeneration Melissa J. Armstrong, ABSTRACT MD Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) Irene Litvan, MD no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An Anthony E. Lang, MD international consortium of behavioral neurology, neuropsychology, and movement disorders special- Thomas H. Bak, MD ists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses Kailash P. Bhatia, MD (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from pub- Barbara Borroni, MD lished reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal Adam L. Boxer, MD, syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary PhD progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features Dennis W. Dickson, MD of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing Murray Grossman, MD a comprehensive description of CBD and correcting common misconceptions. Clinical CBD pheno- Mark Hallett, MD types and features were combined to create 2 sets of criteria: more specific clinical research criteria Keith A. Josephs, MD for probable CBD and broader criteria for possibleCBDthataremoreinclusivebuthaveahigher Andrew Kertesz, MD chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and grad- Suzee E. Lee, MD ual progression for at least 1 year, age at onset $50 years, no similar family history or known tau Bruce L. Miller, MD mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS Stephen G.
    [Show full text]
  • What Every Social Worker Physical Therapist Occupational
    What Every Social Worker Physical Therapist Occupational Therapist Speech-Language Pathologist Should Know About Progressive Supranuclear Palsy (PSP) Corticobasal Degeneration (CBD) Multiple System Atrophy (MSA) A Comprehensive Guide to Signs, Symptoms, and Management Strategies DISEASE SUMMARIES at a glance Progressive Supranuclear Palsy (PSP) • Rare neurodegenerative disease, the most common parkinsonian disorder after Parkinson’s disease (PD) • Originally described in 1964 as Steele-Richardson-Olszewski syndrome • Often mistakenly diagnosed as PD due to the similar early symptoms • Symptoms include early postural instability, supranuclear gaze palsy (paralysis of voluntary vertical gaze with preserved reflexive eye movements), and levodopa-nonresponsive parkinsonism • Onset of symptoms is typically symmetric • Pathologically classified as a tauopathy (abnormal accumulation in the brain of the protein tau) • Five to seven cases per 100,000 people • Slightly more common in men • Average age of onset is 60–65 years, but can occur as early as age 40 • Life expectancy is five to seven years following symptom onset • No cure or effective medication management Signs and Symptoms • Early onset gait and balance problems • Clumsy, slow, or shuffling gait 2 • Lack of coordination • Slowed or absent balance reactions and postural instability • Frequent falls (primarily backward) • Slowed movements • Rigidity (generally axial) • Vertical gaze palsy • Loss of downward gaze is usually first • Abnormal eyelid control • Decreased blinking with “staring”
    [Show full text]
  • Corticobasal Syndrome: a Pract Neurol: First Published As 10.1136/Practneurol-2020-002835 on 23 July 2021
    Review Corticobasal syndrome: a Pract Neurol: first published as 10.1136/practneurol-2020-002835 on 23 July 2021. Downloaded from practical guide Duncan Wilson ,1,2 Campbell Le Heron,1,2 Tim Anderson 1,2,3 1Neurology Department, ABSTRACT We diagnosed corticobasal syndrome Christchurch Hospital, Corticobasal syndrome is a disorder of movement, referred her to physiotherapy and occupa- Christchurch, New Zealand 2New Zealand Brain Research cognition and behaviour with several possible tional therapy. An MR scan of brain showed Institute, Christchurch, New underlying pathologies, including corticobasal only mild involutional changes consistent Zealand 3 degeneration. It presents insidiously and is slowly with age but no perirolandic atrophy. Department of Medicine, Her condition progressed over the University of Otago, progressive. Clinicians should consider the diagnosis Christchurch, Christchurch, New in people presenting with any combination of next 4 years. She lost vertical eye move- Zealand extrapyramidal features (with poor response to ments and her alien limb became very pronounced. Her speech deteriorated to Correspondence to levodopa), apraxia or other parietal signs, aphasia Dr Tim Anderson, New Zealand and alien- limb phenomena. Neuroimaging showing ‘yes’ and ‘no’, although she could still Brain Research Institute, asymmetrical perirolandic cortical changes supports comprehend. She became more rigid Christchurch, New Zealand; tim. the diagnosis, while advanced neuroimaging with worsening dystonia particularly of anderson@ otago. ac. nz may give insight into the underlying pathology. neck extension, and her postural reflexes Accepted 2 March 2021 Identifying corticobasal syndrome carries some became impaired. We gave an unsuccessful Published Online First trial of levodopa and sought speech and 13 August 2021 management implications (especially if protein- based treatments arise in the future) and prognostic language involvement; botulinum injec- significance.
    [Show full text]
  • An Evolution of the Diagnostic Criteria for Tauopathies
    Tauopathies An Evolution of the Diagnostic Criteria for Tauopathies Despite the complexity of dementias, and the overlap of one diagnosis with another, new methods are appearing to help distinguish different conditions. Furthermore, increased knowledge of tauopathies and TDP-43 proteinopathies (now frequently called tardopathies), and of the genetic mutations associated with them, is helping specialists and physicians learn more about dementias, and their root problems in the central nervous system. By Marie-Pierre Thibodeau, MD; Howard Chertkow, MD, FRCPC; and Gabriel C. Léger, MDCM, FRCPC linicians have approached demen- many of the neurodegenerative diseases moting vital axonal transport.3,5 Tau Ctias based on crude clinical sub- that cause dementia. These can now be abnormalities, in the form of hyper- groupings (e.g., cortical vs. subcorti- classified not just based on the clinical phosphorylated insoluble inclusions, cal), or based on the clinical syndrome phenotype, but also on the type of pro- have been noted in many different enti- approach and accepted criteria for clin- tein that accumulates in tissue, and ties (Table 1).3 Although a number of ical entities. Progress in immunohis- might ultimately be the target of specif- mutations within the gene coding for tolochemical methods in recent years ic therapies. Dementia can result from tau (MAPT, or microtubule associated has led to a better understanding of the accumulation of amyloid,1 produc- protein tau) have been linked to tau- ing Alzheimer’s disease (AD: an amy- related diseases, the primary cause of loidopathy); synuclein,2 producing the most tauopathies remains unknown.5 Marie-Pierre Thibodeau, MD synucleinopathies Parkinson’s disease A few comments on tau biochem- Resident in Geriatric Medicine, (PD) and dementia with Lewy bodies; istry.
    [Show full text]
  • Can Multiple System Atrophy Clinically Be Misdiagnosed As Corticobasal
    Current Journal Clinical Note of Neurology Curr J Neurol 2021; 20(2): 115-7 Can multiple system atrophy clinically Received: 10 Dec. 2020 be misdiagnosed as corticobasal Accepted: 07 Feb. 2021 syndrome in the early stages? Yasaman Saeedi1, Maziar Emamikhah1, Ali Shoeibi2, Mohammad Rohani1 1 Department of Neurology, Hazrat Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, Iran 2 Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Keywords is challenging, especially at early stages when the Multiple System Atrophy; Corticobasal Degeneration; manifestations overlap. We report three probable Corticobasal Syndrome; Atypical Parkinsonism; MSA cases, with unusual presentation (asymmetric Asymmetric Parkinsonism; Hand Dystonia parkinsonism, severe limb dystonia, and prominent myoclonus) initially diagnosed as CBS. Case 1: This was a 57-year-old woman; her problems started 10 years ago with jerky tremor Multiple system atrophy (MSA), an atypical of left hand. Her movements gradually got slower parkinsonian syndrome (APS) and without response to levodopa. During the last synucleinopathy, usually presents with early 2 years, she had not been able to walk autonomic dysfunction, symmetrical levodopa- independently and been suffering from a fixed unresponsive parkinsonism, and cerebellar posture in the left hand, making it immobile and symptoms. Myoclonus, speech disturbance, useless. She had a history of RBD and nocturnal rapid-eye-movement sleep behavior disorder stridor for years and urinary incontinence since (RBD), stridor and dystonia are other features. the last year. Her family history was negative. Cognition is not impaired in majority.1 Examination revealed normal cognition, Corticobasal degeneration (CBD), another APS, anarthria, slow saccadic eye movements, severe is characterized by cognitive and asymmetrical jaw-closing dystonia, dystonic posture of hands motor symptoms.
    [Show full text]
  • Predicting Amyloid Status in Corticobasal Syndrome Using
    Sha et al. Alzheimer's Research & Therapy (2015) 7:8 DOI 10.1186/s13195-014-0093-y RESEARCH Open Access Predicting amyloid status in corticobasal syndrome using modified clinical criteria, magnetic resonance imaging and fluorodeoxyglucose positron emission tomography Sharon J Sha1*, Pia M Ghosh2,3, Suzee E Lee2, Chiara Corbetta-Rastelli2,3, Willian J Jagust2,3,4, John Kornak5, Katherine P Rankin2, Lea T Grinberg2, Harry V Vinters7,8, Mario F Mendez7, Dennis W Dickson6, William W Seeley2, Marilu Gorno-Tempini2, Joel Kramer2, Bruce L Miller2, Adam L Boxer2 and Gil D Rabinovici2,3,4 Abstract Introduction: Group comparisons demonstrate greater visuospatial and memory deficits and temporoparietal-predominant degeneration on neuroimaging in patients with corticobasal syndrome (CBS) found to have Alzheimer’sdisease (AD) pathology versus those with underlying frontotemporal lobar degeneration (FTLD). The value of these features in predicting underlying AD pathology in individual patients is unknown. The goal of this study is to evaluate the utility of modified clinical criteria and visual interpretations of magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) for predicting amyloid deposition (as a surrogate of Alzheimer’sdisease neuropathology) in patients presenting with CBS. Methods: In total, 25 patients meeting CBS core criteria underwent amyloid (Pittsburgh compound B; PIB) PET scans. Clinical records, MRI, and FDG scans were reviewed blinded to PIB results. Modified clinical criteria were used to classify CBS patients as temporoparietal variant CBS (tpvCBS) or frontal variant CBS (fvCBS). MRI and FDG-PET were classified based on the predominant atrophy/hypometabolism pattern (frontal or temporoparietal). Results: A total of 9 out of 13 patients classified as tpvCBS were PIB+, compared to 2out of 12 patients classified as fvCBS (P < 0.01, sensitivity 82%, specificity 71% for PIB+ status).
    [Show full text]
  • Progressive Supranuclear Palsy and Corticobasal Degeneration: Pathophysiology and Treatment Options Ruth Lamb, Bsc, MRCP1,* Jonathan D
    Curr Treat Options Neurol (2016) 18: 42 DOI 10.1007/s11940-016-0422-5 Movement Disorders (A Videnovich, Section Editor) Progressive Supranuclear Palsy and Corticobasal Degeneration: Pathophysiology and Treatment Options Ruth Lamb, BSc, MRCP1,* Jonathan D. Rohrer, MRCP, PhD2 Andrew J. Lees, FRCP, FMedSci3 Huw R. Morris, FRCP, PhD1 Address *,1Department of Clinical Neuroscience, UCL Institute of Neurology, Queen Square, London, UK Email: [email protected] 2Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK 3Department of Molecular Neuroscience, Queen Square Brain Bank for Neurological Disorders, University College London, London, UK Published online: 15 August 2016 * The Author(s) 2016. This article is published with open access at Springerlink.com This article is part of the Topical Collection on Movement Disorders Keywords Atypical Parkinsonism I Progressive supranuclear palsy I Steele-Richardson-Olszewski syndrome I Richardson’ssyndromeI Corticobasal degeneration I Corticobasal syndrome I Movement disorders I Neurodegenerative diseases I Parkinson-plus syndromes I Treatment I Tauopathies I Tau protein Opinion statement There are currently no disease-modifying treatments for progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD), and no approved pharmacological or therapeutic treatments that are effective in controlling their symptoms. The use of most pharmacological treatment options are based on experience in other disorders or from non-randomized historical controls, case series, or expert opinion. Levodopa may provide some improvement in symptoms of Parkinsonism (specifically bradyki- nesia and rigidity) in PSP and CBD; however, evidence is conflicting and where present, benefits are often negligible and short lived. In fact, Bpoor^ response to levodopa forms part of the NINDS-SPSP criteria for the diagnosis of PSP and consensus criteria for the diagnosis of CBD (Lang Mov Disord.
    [Show full text]
  • The Significant Characteristics of Corticobasal Syndrome
    Mini-Review Page 1 of 6 The significant characteristics of corticobasal syndrome Theodore P. Parthimos1, Kleopatra H. Schulpis2 13rd Age Day Care Center IASIS, Glyfada, Greece; 2Institute of Child Health, Research Center, “Aghia Sophia” Children’s Hospital, Athens, Greece Contributions: (I) Conception and design: All authors; (II) Administrative support: All authors; (III) Provision of study materials or patients: All authors; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Theodore P. Parthimos. 3rd Age Day Care Center IASIS, 32 Ierou Lochou Street, Athens, 17237, Greece. Email: [email protected]. Abstract: Corticobasal syndrome (CBS) is a rare neurodegenerative disorder. Mutation in the microtubule associated protein tau (MAPT) has been presented in patients with CBS. Also, a mutation in the gene that encodes progranulin (PGRN) is frequently observed in CBS patients. Patients with this syndrome present predominantly dementia findings. This syndrome is associated with various clinical and laboratory characteristics which give the opportunity to differentiate among the other dementia syndromes. The aim of this study was to described symptoms and signs of the CBS and its confirmation with mutation analysis of the related genes. Patients with CBS commonly present Parkinsonism like syndrome/ Parkinson disease findings such as akinesia, rigidity and dystonia. Myoclonus, limb apraxia and alien limb phenomena are also included in the clinical presentation of the disease. Most patients also complained because of agraphia, difficulties in spontaneous speech and both single-word and sentence repetition inability. Magnetic resonance imaging (MRI) present damage to the primary motor cortex, inferior parietal, left supplementary motor area and basal ganglia.
    [Show full text]
  • Corticobasal Syndrome
    Dement Neuropsychol 2016 December;10(4):267-275 Views & Reviews Corticobasal syndrome A diagnostic conundrum Jacy Bezerra Parmera1, Roberta Diehl Rodriguez1,2, Adalberto Studart Neto1, Ricardo Nitrini1, Sonia Maria Dozzi Brucki1 ABSTRACT. Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome of great interest to movement disorder specialists and behavioral neurologists. Although originally considered a primary motor disorder, it is now also recognized as a cognitive disorder, usually presenting cognitive deficits before the onset of motor symptoms. The term CBS denotes the clinical phenotype and is associated with a heterogeneous spectrum of pathologies. Given that disease-modifying agents are targeting the pathologic process, new diagnostic methods and biomarkers are being developed to predict the underlying pathology. The heterogeneity of this syndrome in terms of clinical, radiological, neuropsychological and pathological aspects poses the main challenge for evaluation. Key words: corticobasal syndrome, corticobasal degeneration, dementia, atypical parkinsonism. O ENIGMÁTICO DIAGNÓSTICO DA SÍNDROME CORTICOBASAL RESUMO. A síndrome corticobasal é classificada dentro do grupo das síndromes parkinsonianas atípicas, e atualmente desperta interesse em neurologistas especialistas em distúrbios do movimento e neurologia cognitiva e comportamental. Inicialmente considerada como uma síndrome tipicamente motora, hoje se reconhece a importância dos achados cognitivos na apresentação, podendo ocorrer mesmo na ausência de alterações motoras. Tal designação refere-se à síndrome clínica e é associada a várias patologias subjacentes. Tendo em vista que drogas modificadoras da doença estão focando na patologia de base, novos métodos diagnósticos de imagem e outros biomarcadores estão sendo desenvolvidos para predizer o processo patológico específico antemortem. A heterogeneidade clínica e patológica desta entidade, portanto, é o maior desafio a ser desvendado.
    [Show full text]
  • Unravelling Genetic Factors Underlying Corticobasal Syndrome: a Systematic Review
    cells Review Unravelling Genetic Factors Underlying Corticobasal Syndrome: A Systematic Review Federica Arienti 1 , Giulia Lazzeri 1, Maria Vizziello 1, Edoardo Monfrini 1 , Nereo Bresolin 2, Maria Cristina Saetti 1, Marina Picillo 3, Giulia Franco 2 and Alessio Di Fonzo 2,* 1 Dino Ferrari Center, Department of Pathophysiology and Transplantation, Neuroscience Section, University of Milan, 20122 Milan, Italy; [email protected] (F.A.); [email protected] (G.L.); [email protected] (M.V.); [email protected] (E.M.); [email protected] (M.C.S.) 2 Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurology Unit, 20122 Milan, Italy; [email protected] (N.B.); [email protected] (G.F.) 3 Center for Neurodegenerative Diseases, Department of Medicine, Surgery and Dentistry, Neuroscience Section, University of Salerno, 84084 Salerno, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-025-503-3807 Abstract: Corticobasal syndrome (CBS) is an atypical parkinsonian presentation characterized by heterogeneous clinical features and different underlying neuropathology. Most CBS cases are spo- radic; nevertheless, reports of families and isolated individuals with genetically determined CBS have been reported. In this systematic review, we analyze the demographical, clinical, radiological, and anatomopathological features of genetically confirmed cases of CBS. A systematic search was performed using the PubMed, EMBASE, and Cochrane Library databases, included all publications in English from 1 January 1999 through 1 August 2020. We found forty publications with fifty-eight eligible cases. A second search for publications dealing with genetic risk factors for CBS led to the review of eight additional articles.
    [Show full text]
  • Clinical and Pathologic Features of Cognitive-Predominant Corticobasal Degeneration Nobutaka Sakae, Octavio A
    Published Ahead of Print on June 9, 2020 as 10.1212/WNL.0000000000009734 ARTICLE OPEN ACCESS Clinical and pathologic features of cognitive- predominant corticobasal degeneration Nobutaka Sakae, MD, PhD, Octavio A. Santos, PhD, Otto Pedraza, PhD, Irene Litvan, MD, Correspondence Melissa E. Murray, PhD, Ranjan Duara, MD, Ryan J. Uitti, MD, Zbigniew K. Wszolek, MD, Dr. Dickson Neill R. Graff-Radford, MBBS, Keith A. Josephs, MD, MST, MSc, and Dennis W. Dickson, MD [email protected] Neurology® 2020;95:1-11. doi:10.1212/WNL.0000000000009734 Abstract Objective To describe clinical and pathologic characteristics of corticobasal degeneration (CBD) with cognitive predominant problems during the disease course. Methods In a series of autopsy-confirmed cases of CBD, we identified patients with cognitive rather than motor predominant features (CBD-Cog), including 5 patients thought to have Alzheimer disease (AD) and 10 patients thought to have behavioral variant frontotemporal dementia (FTD). We compared clinical and pathologic features of CBD-Cog with those from a series of 31 patients with corticobasal syndrome (CBD-CBS). For pathologic comparisons between CBD-Cog and CBD-CBS, we used semiquantitative scoring of neuronal and glial lesion types in multiple brain regions and quantitative assessments of tau burden from image analysis. Results Five of 15 patients with CBD-Cog never had significant motor problems during their disease course. The most common cognitive abnormalities in CBD-Cog were executive and visuo- spatial dysfunction. The frequency of language problems did not differ between CBD-Cog and CBD-CBS. Argyrophilic grain disease, which is a medial temporal tauopathy associated with mild cognitive impairment, was more frequent in CBD-Cog.
    [Show full text]
  • Clinicopathologic Correlations and Neuroimaging Biomarkers in Primary Progressive Aphasia
    ADVERTIMENT. Lʼaccés als continguts dʼaquesta tesi queda condicionat a lʼacceptació de les condicions dʼús establertes per la següent llicència Creative Commons: http://cat.creativecommons.org/?page_id=184 ADVERTENCIA. El acceso a los contenidos de esta tesis queda condicionado a la aceptación de las condiciones de uso establecidas por la siguiente licencia Creative Commons: http://es.creativecommons.org/blog/licencias/ WARNING. The access to the contents of this doctoral thesis it is limited to the acceptance of the use conditions set by the following Creative Commons license: https://creativecommons.org/licenses/?lang=en Clinicopathologic correlations and neuroimaging biomarkers in primary progressive aphasia Doctoral student Miguel Ángel Santos Santos Directors Maria Luisa Gorno-Tempini Juan Fortea Ormaechea Antonio Escartín Siquer Programa de doctorat en Medicina con el Real Decreto 1393 Departament de Medicina. Facultat de Medicina. Universidad Autònoma de Barcelona. 2017 CERTIFICATE OF DIRECTION Maria Luisa Gorno-Tempini, Doctor in Neuroscience by University College London and Professor of Neurology at the University of California San Francisco, Juan Fortea Ormaechea, Doctor in Medicine by the Universidad de Barcelona and specialist in Neurology at the Hospital Sant Pau Memory Unit, and Antonio Escartín Siquer, Doctor in Medicine by the Universidad Autonoma de Barcelona and Professor of Neurology in the Department of Medicine at the Universidad Autonoma de Barcelona, CERTIFY: That the thesis titled “Clinicopathologic correlations
    [Show full text]