Lewy Body Diseases and Multiple System Atrophy As ␣-Synucleinopathies
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Lewy Bodies in the Amygdala Increase of ␣-Synuclein Aggregates in Neurodegenerative Diseases with Tau-Based Inclusions
ORIGINAL CONTRIBUTION Lewy Bodies in the Amygdala Increase of ␣-Synuclein Aggregates in Neurodegenerative Diseases With Tau-Based Inclusions Anca Popescu, MD; Carol F. Lippa, MD; Virginia M.-Y. Lee, PhD; John Q. Trojanowski, MD, PhD Background: Increased attention has been given to Results: Lewy bodies were often abundant in classic Pick ␣-synuclein aggregation in nonsynucleinopathies be- disease, argyrophilic grain disease, Alzheimer disease, and cause ␣-synuclein–containing Lewy bodies (LBs) influ- dementia with LBs but not in cases with amygdala de- ence symptoms. However, the spectrum of disorders in generation lacking tau-based inclusions, control cases, which secondary inclusions are likely to occur has not preclinical disease carriers, or degenerative diseases lack- been defined. Amygdala neurons commonly develop large ing pathologic involvement of the amygdala. The ex- numbers of secondary LBs, making it a practical region posed ␣-synuclein epitopes were similar in all cases con- for studying this phenomenon. taining LBs. Objective: To characterize the spectrum of diseases as- Conclusions: Abnormal ␣-synuclein aggregation in the sociated with LB formation in the amygdala of neurode- amygdala is disease selective, but not restricted to dis- generative disease and control cases. orders of ␣-synuclein and -amyloid. Our data are com- patible with the notion that tau aggregates predispose neu- Design: An autopsy series of 101 neurodegenerative dis- ease and 34 aged control cases. Using immunohisto- rons to develop secondary LBs. chemistry studies, we examined the amygdala for ␣-synuclein aggregates. Arch Neurol. 2004;61:1915-1919 GGREGATION OF ␣-SY- of these subjects.7-9 It is unknown whether nuclein has a primary this curious finding is restricted to AD, or pathogenic role in spo- whether it is a more universal phenom- radic and familial autoso- enon. -
Diagnostic Clues in Multiple System Atrophy
DO I:10.4274/Tnd.82905 Case Report / Olgu Sunumu Diagnostic Clues in Multiple System Atrophy: A Case Report and Literature Review Multisistem Atrofi Tanısında İpuçları: Bir Olgu Sunumu ve Literatürün Gözden Geçirilmesi Mehmet Yücel, Oğuzhan Öz, Hakan Akgün, Semai Bek, Tayfun Kaşıkçı, İlter Uysal, Yaşar Kütükçü, Zeki Odabaşı Gülhane Military Medical Academy, Ankara, Turkey Sum mary Multiple system atrophy (MSA) is an adult-onset, sporadic, progressive neurodegenerative disease. Based on the consensus criteria, patients with MSA are clinically classified into cerebellar (MSA-C) and parkinsonian (MSA-P) subtypes. In addition to major diagnostic criteria including poor response to levodopa, and presence of pyramidal or cerebellar signs (ataxia) or autonomic failure, certain clinical features or ‘‘red flags’’ may raise the clinical suspicion for MSA. In our case report we present a 67-year-old female patient admitted to our hospital due to inability to walk, with poor response to levodopa therapy, whose neurological examination revealed severe Parkinsonism, ataxia and who fulfilled all criteria for MSA, as rarely seen in clinical practice.(Turkish Journal of Neurology 2013; 19:28-30) Key Words: Multiple system atrophy, autonomic failure, diagnostic criteria Özet Multisistem atrofi (MSA) erişkin dönemde başlayan, ilerleyici, nedeni bilinmeyen sporadik nörodejeneratif bir hastalıktır. MSA kabul görmüş tanı kriterlerine göre klinik olarak serebellar (MSA-C) ve parkinsoniyen (MSA-P) alt tiplerine ayrılmaktadır. Düşük levadopa yanıtı, piramidal, serebellar bulguların (ataksi) ya da otonomik bozukluk olması gibi majör tanı kriterlerininin yanında “red flags” olarak isimlendirilen belirgin klinik bulgular ya da uyarı işaretlerinin olması MSA tanısı için klinik şüpheyi oluşturmalıdır. Olgu sunumunda 67 yaşında yürüyememe şikayeti ile polikliniğimize müracaat eden ve levadopa tedavisine düşük yanıt gösteren ciddi parkinsonizm bulguları ile ataksi bulunan kadın hasta MSA tanı kriterlerini tam olarak karşıladığı ve klinik pratikte nadir görüldüğü için sunduk. -
Hereditary Ataxia Multigene Panel Testing
Lab Management Guidelines V1.0.2021 Hereditary Ataxia Multigene Panel Testing MOL.TS.310.A v1.0.2021 Introduction Hereditary Ataxia Multigene Panel testing is addressed by this guideline. Procedures addressed The inclusion of any procedure code in this table does not imply that the code is under management or requires prior authorization. Refer to the specific Health Plan's procedure code list for management requirements. Procedures addressed by this Procedure codes guideline Hereditary Ataxia Multigene Panel 81443 (including sequencing of at least 15 genes) Genomic Unity Ataxia Repeat Expansion 0216U and Sequence Analysis Genomic Unity Comprehensive Ataxia 0217U Repeat Expansion and Sequence Analysis Unlisted molecular pathology procedure 81479 What are hereditary ataxias Definition The hereditary ataxias are a group of genetic disorders. They are characterized by slowly progressive uncoordinated, unsteady movement and gait, and often poor coordination of hands, eye movements, and speech. Cerebellar atrophy is also frequently seen.1 Incidence and prevalence Prevalence estimates vary. The prevalence of autosomal dominant ataxias is approximately 1-5:100,000.1 One study in Norway estimated the prevalence of hereditary ataxia at 6.5 per 100,000 people.2 © 2020 eviCore healthcare. All Rights Reserved. 1 of 8 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com Lab Management Guidelines V1.0.2021 Symptoms Although hereditary ataxias are made up of multiple different conditions, they are characterized by slowly progressive uncoordinated, unsteady movement and gait, and often poor coordination of hands, eye movements, and speech. Cerebellar atrophy is also frequently seen.1 Cause Hereditary ataxias are caused by mutations in one of numerous genes. -
Multiple System Atrophy
Multiple System Atrophy U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health Multiple System Atrophy What is multiple system atrophy? ultiple system atrophy (MSA) is M a progressive neurodegenerative disorder characterized by a combination of symptoms that affect both the autonomic nervous system (the part of the nervous system that controls involuntary action such as blood pressure or digestion) and move- ment. The symptoms reflect the progressive loss of function and death of different types of nerve cells in the brain and spinal cord. Symptoms of autonomic failure that may be seen in MSA include fainting spells and prob- lems with heart rate, erectile dysfunction, and bladder control. Motor impairments (loss of or limited muscle control or movement, or limited mobility) may include tremor, rigidity, and/or loss of muscle coordination as well as difficulties with speech and gait (the way a person walks). Some of these features are similar to those seen in Parkinson’s disease, and early in the disease course it often may be difficult to distinguish these disorders. MSA is a rare disease, affecting potentially 15,000 to 50,000 Americans, including men and women and all racial groups. Symptoms tend to appear in a person’s 50s and advance rapidly over the course of 5 to 10 years, with progressive loss of motor function and 1 eventual confinement to bed. People with MSA often develop pneumonia in the later stages of the disease and may suddenly die from cardiac or respiratory issues. While some of the symptoms of MSA can be treated with medications, currently there are no drugs that are able to slow disease progression and there is no cure. -
When DLB, PD, and PSP Masquerade As MSA an Autopsy Study of 134 Patients
When DLB, PD, and PSP masquerade as MSA An autopsy study of 134 patients Shunsuke Koga, MD ABSTRACT Naoya Aoki, MD Objective: To determine ways to improve diagnostic accuracy of multiple system atrophy (MSA), Ryan J. Uitti, MD we assessed the diagnostic process in patients who came to autopsy with antemortem diagnosis Jay A. van Gerpen, MD of MSA by comparing clinical and pathologic features between those who proved to have MSA William P. Cheshire, MD and those who did not. We focus on likely explanations for misdiagnosis. Keith A. Josephs, MD Methods: This is a retrospective review of 134 consecutive patients with an antemortem clinical Zbigniew K. Wszolek, diagnosis of MSA who came to autopsy with neuropathologic evaluation of the brain. Of the 134 MD patients, 125 had adequate medical records for review. Clinical and pathologic features were J. William Langston, MD compared between patients with autopsy-confirmed MSA and those with other pathologic diag- Dennis W. Dickson, MD noses, including dementia with Lewy bodies (DLB), Parkinson disease (PD), and progressive supra- nuclear palsy (PSP). Correspondence to Results: Of the 134 patients with clinically diagnosed MSA, 83 (62%) had the correct diagnosis Dr. Dickson: at autopsy. Pathologically confirmed DLB was the most common misdiagnosis, followed by PSP [email protected] and PD. Despite meeting pathologic criteria for intermediate to high likelihood of DLB, several pa- tients with DLB did not have dementia and none had significant Alzheimer-type pathology. Auto- nomic failure was the leading cause of misdiagnosis in DLB and PD, and cerebellar ataxia was the leading cause of misdiagnosis in PSP. -
What You Need to Know
Multiple System Atrophy: What You Need to Know Publication Date: April 4, 2019 Authors: Daniel Claassen, MD, Allyson Mayeux, MD, and Annette Hoy, MD 2 Table of Contents Overview……………………………………………………………………………………………… 3 Differential Diagnosis…………………………………………………………………………… 9 Evaluation Methods……………………………………………………………………………… 12 Orthostatic Hypotension………………………………………………………………………. 14 Neurogenic Bladder………………………………………………………………………………. 20 MSA-P & MSA-C ..………………………………………………………………………………… 25 Dystonia………………………………………………………………………………………………… 29 Breathing Disorders………………………………………………………………………………… 34 REM Behavior Disorder…………………………………………………………………………… 39 Depression and Cognitive IMpairMent……………………………………………………. 43 Neuroprotective Diet…………………………………………………………………………….. 45 Constipation……………………………………………………………………………………………. 47 Advanced Planning: Advance Directives, Palliative Care, and Brain Donation…………………………………………………………………………………. 50 © Copyright MSA Coalition 2019. All Rights Reserved. www.multiplesystematrophy.org 3 Multiple System Atrophy Overview Multiple System Atrophy (MSA) is a rare neurodegenerative disorder that can cause different symptoms, such as impairments to balance and difficulty with movement, poor coordination, bladder dysfunction, sleep disturbances, and poor blood pressure control. The disease was first known as Shy-Drager Syndrome. At the moment, it is believed that MSA is "sporadic," meaning that there are no established genetic or environmental factors that cause the disease. A few reports have described families with MSA, but this finding is probably -
Cognitive and Psychiatric Disturbances in Parkinsonian Syndromes
Cognitive and Psychiatric Disturbances in Parkinsonian Syndromes Richard M. Zweig, MD*, Elizabeth A. Disbrow, PhD, Vijayakumar Javalkar, PhD KEYWORDS Parkinson Dementia with Lewy Bodies (DLB) Parkinsonian Progressive Supranuclear Palsy (PSP) Multiple System Atrophy (MSA) Corticobasal degeneration (CBD) KEY POINTS Executive dysfunction is often measurable in newly diagnosed Parkinson’s disease. Treatment with dopaminergic medications, particularly dopamine agonists, has been associated with hallucinations and impulse control disorder. While sharing many pathological features with Alzheimer’s disease, distinguishing clinical features of Dementia with Lewy bodies include episodic fluctuations of cognition, early hallucinations, and REM behavior disorder symptoms. Quetiapine appears to be effective for hallucinating patients, without worsening parkin- sonism at lower dosages. Clozapine is also effective. The promising 5-HT2A inverse agonist pimavanserin is awaiting FDA approval. The neuropsychiatric profile of progressive supranuclear palsy may closely resemble that of the frontotemporal lobar degenerations. INTRODUCTION As is the case with all of the neurodegenerative disorders, the subset comprising the parkinsonian syndromes of Parkinson disease, dementia with Lewy bodies, progres- sive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA) are considered proteinopathies. In these disorders, disease-associated proteins accumulate in the wrong cellular or extracellular compartments, and are often The authors have nothing to disclose. Department of Neurology, Louisiana State University Health Sciences Center - Shreveport, 1501 King’s Highway, Shreveport, LA 71103, USA * Corresponding author. E-mail address: [email protected] Neurol Clin 34 (2016) 235–246 http://dx.doi.org/10.1016/j.ncl.2015.08.010 neurologic.theclinics.com 0733-8619/16/$ – see front matter Ó 2016 Elsevier Inc. -
Head Drop and Camptocormia
EDITORIAL 1 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.73.1.1 on 1 July 2002. Downloaded from Head drop Table 2 Causes of ................................................................................... camptocormia Head drop and camptocormia Disorders Neuromuscular Motor neuron Amyotrophic lateral T Umapathi, V Chaudhry, D Cornblath, D Drachman, sclerosis17 18 J Griffin, R Kuncl Muscle IBM19 Nemaline myopathy20 ................................................................................... Facioscapulohumeral dystrophy The spectrum of bent spine disorders Parkinsonism Idiopathic21 Postencephalitic22 23 Villiusk encephalomyelitis24 ead ptosis (drop) results from Sodium valproate CASE A 25 weakness of the neck extensor, or toxicity An 80 year old man developed head pto- Idiopathic increased tone of the flexor mus- H sis insidiously over a period of few cles. It is characterised by marked anterior curvature or angulation of the weeks. A week before this he had an cervical spine and is associated with upper respiratory tract infection and also various neuromuscular (table 1) and experienced transient sharp pain over occasional nuclear sacs, target and tar- extrapyramidal disorders.12–15 Campto- the left and then the right shoulder. He getoid fibres as well as myopathic fea- cormia or the bent spine syndrome was had no diplopia, dysarthria, dysphagia, tures such as the presence of hyper- first described in hysterical soldiers in limb weakness, or fatiguability. Exam- trophic and split muscle fibres; a few 1915 by the French neurologist ination showed severe neck extensor necrotic, degenerating and regenerating Souques.16 Typically there is marked weakness, Medical Research Council fibres; increased internalised nuclei, and anterior curvature of the thoracolumbar (MRC) grade 2. Muscle strength was mild endomysial fibrosis. No type group- spine. -
Synuclein in PARK2-Mediated Parkinson's Disease
cells Review Interaction between Parkin and a-Synuclein in PARK2-Mediated Parkinson’s Disease Daniel Aghaie Madsen 1, Sissel Ida Schmidt 1, Morten Blaabjerg 1,2,3,4 and Morten Meyer 1,2,3,4,* 1 Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark; [email protected] (D.A.M.); [email protected] (S.I.S.); [email protected] (M.B.) 2 Department of Neurology, Odense University Hospital, 5000 Odense, Denmark 3 Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark 4 BRIDGE—Brain Research Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark * Correspondence: [email protected]; Tel.: +45-65503802 Abstract: Parkin and a-synuclein are two key proteins involved in the pathophysiology of Parkinson’s disease (PD). Neurotoxic alterations of a-synuclein that lead to the formation of toxic oligomers and fibrils contribute to PD through synaptic dysfunction, mitochondrial impairment, defective endoplasmic reticulum and Golgi function, and nuclear dysfunction. In half of the cases, the recessively inherited early-onset PD is caused by loss of function mutations in the PARK2 gene that encodes the E3-ubiquitin ligase, parkin. Parkin is involved in the clearance of misfolded and aggregated proteins by the ubiquitin-proteasome system and regulates mitophagy and mitochondrial biogenesis. PARK2-related PD is generally thought not to be associated with Lewy body formation although it is a neuropathological hallmark of PD. In this review article, we provide an overview of post-mortem neuropathological examinations of PARK2 patients and present the current knowledge of a functional interaction between parkin and a-synuclein in the regulation of protein aggregates including Lewy bodies. -
Principles-Of-Autonomic-Medicine-V
Principles of Autonomic Medicine v. 2.1 DISCLAIMERS This work was produced as an Official Duty Activity while the author was an employee of the United States Government. The text and original figures in this book are in the public domain and may be distributed or copied freely. Use of appropriate byline or credit is requested. For reproduction of copyrighted material, permission by the copyright holder is required. The views and opinions expressed here are those of the author and do not necessarily state or reflect those of the United States Government or any of its components. References in this book to specific commercial products, processes, services by trade name, trademark, manufacturer, or otherwise do not necessarily constitute or imply their endorsement, recommendation, or favoring by the United States Government or its employees. The appearance of external hyperlinks is provided with the intent of meeting the mission of the National Institute of Neurological Disorders and Stroke. Such appearance does not constitute an endorsement by the United States Government or any of its employees of the linked web sites or of the information, products or services contained at those sites. Neither the United States Government nor any of its employees, including the author, exercise any editorial control over the information that may be found on these external sites. Permission was obtained from the following for reproduction of pictures in this book. Other reproduced pictures were from -- 1 -- Principles of Autonomic Medicine v. 2.1 Wikipedia Commons or had no copyright. Tootsie Roll Industries, LLC (Tootsie Roll Pop, p. 26) Dr. Paul Greengard (portrait photo, p. -
Multiple System Atrophy Trust Founded by Sarah Matheson
Multiple System Atrophy Trust Founded by Sarah Matheson O T MUmultipleLTIPLE SYSTEMsystem A guide to A A GUIDE AatrophyTROPHY Multiple System Atrophy Trust Our Vision A world free of MSA Our Mission To find the cause, and ultimately, cure for MSA. Until that day we will do all we can to support people affected by MSA and will strive to ensure that they are not alone on their individual journeys. Our contact details are as follows: Telephone: 0333 323 4591 Email: [email protected] MSA Trust Nurse Specialists: Samantha Pavey (South East & East England) T: 0203 371 0003 E: [email protected] Katie Rigg (Scotland, Ireland and North England) T: 01434 381 932 E: [email protected] Jill Lyons (Wales & South West England) T: 01934 316 119 E: [email protected] Multiple System Atrophy Trust @MSAtrust 02 Multiple System Atrophy Trust Most people have never heard of multiple system atrophy (MSA). Many healthcare professionals are unfamiliar with the condition. It is rare, sometimes not recognised and, as you will probably know by now, often difficult to diagnose. The aim of this guide is to explain MSA. It includes information about the symptoms that may occur, what treatment options there are and tries to answer some frequently asked questions. We hope it will help support you and your family but if you have questions or want further advice, please contact us at the Multiple System Atrophy Trust (‘the Trust’). The Multiple System Atrophy Trust offers information, support and education and funds research into MSA. -
Multiple System Atrophy
Transverse Myelitis U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health Transverse Myelitis What is transverse myelitis? ransverse myelitis is a neurological disorder T caused by inflammation across both sides of one level, or segment, of the spinal cord. The term myelitis refers to inflammation of the spinal cord; transverse describes the position of the inflammation—across the width of the spinal cord. Attacks of inflammation can damage or destroy myelin, the fatty insulating substance that covers nerve cell fibers. This damage causes nervous system scars that interrupt communications between the nerves in the spinal cord and the rest of the body. Symptoms of transverse myelitis include a loss of spinal cord function over several hours to several weeks. What usually begins as a sudden onset of lower back pain, muscle weakness, or abnormal sensations in the toes and feet can rapidly progress to more severe symptoms, including paralysis, urinary reten- tion, and loss of bowel control. Although some individuals recover from transverse myelitis with minor or no residual problems, others suffer permanent impairments that affect their ability to perform ordinary tasks of daily living. Most individuals will have only one episode of transverse myelitis; a small percentage may have a recurrence. 1 The segment of the spinal cord at which the damage occurs determines which parts of the body are affected. Nerves in the cervical (neck) region control signals to the neck, arms, hands, and the muscles that control breathing (the diaphragm). Nerves in the thoracic (upper back) region relay signals to the torso and some parts of the arms.