Fast Facts: Diagnosing Amyotrophic Lateral Sclerosis

L. Jenkins, M. Turner

Description

A diagnosis of amyotrophic lateral sclerosis (also known as Lou Gehrig's disease or motor neuron disease) is a progressive neurodegenerative disorder that exerts a notorious life-shortening physical toll. Understandably, clinicians are keen to avoid a wrong diagnosis when there are such serious consequences, but any delay in diagnosis can result in unnecessary, and sometimes harmful, interventions, and prevents prompt implementation of much-needed physical and emotional support. Starting from the premise that ALS is not one disease but a syndrome, with a spectrum of upper and lower motor neuron involvement, this highly readable resource examines the causes of diagnostic delay and how to avoid them. With no diagnostic test to confirm the disease, no mandatory investigations and very few plausible 'ALS mimics', the authors take a pragmatic approach to what must always be a clinical diagnosis. With case presentations and teaching points to aid understanding, 'Fast Facts: ALS' will give clinicians the confidence to confirm or exclude a diagnosis of ALS, so that individuals facing this most challenging of conditions can receive rapid multidisciplinary support to maximize the quality of their remaining life. Contents: • Defining the syndrome • Epidemiology and pathophysiology • The first symptoms • Differential diagnosis • Investigations • Emerging diagnostic biomarkers

Informations

• Publié par: S. Karger AG
• Date de parution: 26 novembre 2019
• Nombre de lectures: 0
• EAN13: 9781912776122
• Langue: English
• Poids de l'ouvrage: 4 Mo

Extrait

Diagnosing Amyotrophic Lateral Sclerosis

Martin Turner MA MBBS P h D FRCP Professor of Clinical Neurology and Neuroscience Nuffield Department of Clinical Neurosciences University of Oxford; and Honorary Consultant Neurologist Oxford University Hospitals NHS Foundation Trust John Radcliffe Hospital, Oxford, UK

Liberty Jenkins MA MBC h B MRCP Neuromuscular and General Neurologist Director of ALS Clinic at Forbes Norris Center California Pacific Medical Center San Francisco California, USA
Declaration of Independence
This book is as balanced and as practical as we can make it.
Ideas for improvement are always welcome: [e-mail]
Fast Facts: Diagnosing Amyotrophic Lateral Sclerosis
First published 2020
Text 2020 Martin R Turner, Liberty Jenkins
2020 in this edition S. Karger Publishers Limited
S. Karger Publishers Limited, Elizabeth House, Queen Street,
Abingdon, Oxford OX14 3LN, UK. Tel: [phone]
Book orders can be placed by telephone [phone]) or email
( [e-mail] ), or via the website at: karger.com .
Fast Facts is a trademark of S. Karger Publishers Ltd.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the express permission of the publisher.
The rights of Martin R Turner and Liberty Jenkins to be identified as the authors of this work have been asserted in accordance with the Copyright, Designs Patents Act 1988 Sections 77 and 78.
The publisher and the authors have made every effort to ensure the accuracy of this book, but cannot accept responsibility for any errors or omissions.
For all drugs, please consult the product labeling approved in your country for prescribing information. Registered names, trademarks, etc. used in this book, even when not marked as such, are not to be considered unprotected by law.
A CIP record for this title is available from the British Library.
ISBN 978-1-912776-11-5
eISBN 978-1-912776-13-9
Turner MR (Martin R)
Fast Facts: Diagnosing Amyotrophic Lateral Sclerosis/
Martin R Turner, Liberty Jenkins
Cover image: A network of motor neurons in culture. Reproduced courtesy of Dr Emily Feneberg, Clinical Research Fellow, Oxford University Nuffield Department of Clinical Neurosciences, Oxford, UK.
Medical illustrations by Graeme Chambers.
Typesetting by Thomas Bohm, User Design, Illustration and Typesetting, UK.
Printed in the UK with Xpedient Print.
Made possible by an unrestricted educational grant from Mitsubishi Tanbe Pharma America. Mitsubishi Tanbe Pharma America did not have any influence on the content and all items were subject to independent peer and editorial review.
List of abbreviations
Introduction
Defining the syndrome
Epidemiology and pathophysiology
The first symptoms
Differential diagnosis
Investigations
Emerging diagnostic biomarkers
Useful resources
Index
List of abbreviations
ALS: amyotrophic lateral sclerosis
ALSFRS-R: revised ALS functional rating scale
BMAA: -methylamino- L -alanine
BVVL: Brown-Vialetto-Van Laere
CIDP: chronic inflammatory demyelinating polyneuropathy
CK: creatine kinase
CMAP: compound motor action potential
CSF: cerebrospinal fluid
CT: computed tomography
dHMN: distal hereditary motor neuropathy
DNA: deoxyribonucleic acid
DTI: diffusion tensor imaging
EMG: electromyography
FOSMN: facial-onset sensory and motor neuropathy
FTD: frontotemporal dementia
HRE: hexanucleotide repeat expansion (of C9orf72 )
HSP: hereditary spastic paraparesis
HTLV1: human T-cell lymphotrophic virus type 1
IBM: inclusion body myositis
LMN: lower motor neuron
MMN: multifocal motor neuropathy with conduction block
MMND: Madras motor neuron disease
MND: motor neuron disease
MRI: magnetic resonance imaging
MS: multiple sclerosis
MUP: motor unit potential
NCS: nerve conduction study
NfL: neurofilament light chain
PBA: pseudobulbar affect
PBP: progressive bulbar palsy
PET: positron emission tomography
PLS: primary lateral sclerosis
PMA: progressive muscular atrophy
pNfH: phosphorylated neurofilament heavy chain
RNA: ribonucleic acid
SBMA: spinobulbar muscular atrophy
SMA: spinal muscular atrophy
SNAP: sensory nerve action potential
TDP-43: transactive response DNA-binding protein with M r 43 kDa
UMN: upper motor neuron
VLCFA: very-long-chain fatty acid
Introduction
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects motor neurons. A diagnosis of ALS is one of the most devastating across the range of human illnesses. ALS is notorious for the physical toll and associated loss of personal independence it exerts, and the dramatically life-shortening outcome for most who develop it.
ALS has been historically classified as a neuromuscular disorder, based on the most obvious feature of progressive weakness that is frequently associated with muscle wasting. The modern understanding of ALS, however, is that of a much broader clinical syndrome, with brain pathology that may extend beyond traditional motor regions to involve cognitive and behavioral impairment, with dementia at its extreme.
Reaching an accurate diagnosis is important even in the absence of therapies to prevent progression. Advances in the multidisciplinary care of those with ALS over the past two decades have had a clear impact on survival. An accurate diagnosis provides a better understanding, and more effective communication, of the natural history of the condition. In turn, this facilitates an individual s autonomy and forward planning to maximize quality of life. In addition, a deeper understanding of the molecular basis of ALS, involving more sophisticated tools to capture disease activity, is accelerating prospects for more effective disease-modifying therapy.
Anxiety among physicians about wrongly labeling someone with any serious disease is understandable, but the adverse psychological consequences of diagnostic delay, even in the absence of reversing therapy, must also be recognized. ALS is usually an unmistakable clinical syndrome for which there are few credible mimics. It is currently a fundamentally clinical diagnosis and reliably so. Several objective biomarkers of limited sensitivity are available (e.g. electromyography), but to date there is no routine diagnostic test.
Diagnostic uncertainty arises from the heterogeneity of the clinical presentation and variable rate of symptom progression. This is apparent in the contrast between the survival of the disorder s two most recognizable faces, namely legendary Yankees baseball player Lou Gehrig (1903-1941) and world-renowned theoretical physicist Professor Stephen Hawking (1942-2018), who lived with the symptoms of ALS for 2 and 55 years, respectively (see Figure ).
This book will allow the clinician to more confidently confirm or exclude a diagnosis of ALS, so that individuals facing this most challenging of conditions can receive rapid multidisciplinary support to maximize the quality of their remaining life. Improved diagnostic confidence also means that the therapies in laboratory development today will be applied as early in the disease course as possible to the ALS cases of the future.

(a) American baseball player Lou Gehrig, when he was introduced as a new player for the New York Yankees in 1923. (b) Theoretical physicist Professor Stephen Hawking at NASA s StarChild Learning Center in 1974.
1 Defining the syndrome
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is on the long list of syndromes attributed to the pre-eminent French clinical anatomist Jean-Martin Charcot (1825-1893). However, descriptions of cases that are unmistakably ALS can be found in the literature half a century before Charcot s 1870s lectures on la scl rose amyotrophique . Many historical clinical descriptions of ALS are instantly recognizable and not easily mistaken for any other disorder ( Case report 1.1 ), yet it also remains surprisingly hard to define.
Differing nomenclature
ALS is a syndrome that arises from a neurodegenerative disorder of the motor system and its associated neuronal networks. 1 In the USA, ALS is more readily recognized by the term Lou Gehrig s disease, named after the Yankees baseball star of the 1930s who was known as the Iron Horse for his durability and high tally of home runs. In the UK, the term motor neuron disease is used synonymously with ALS, but confusingly it is sometimes also used as an umbrella term that includes other, unrelated, disorders of the motor neuron, such as Kennedy s disease (X-linked spinobulbar muscular atrophy).

CASE REPORT 1.1
Extract from 19th century case report, showing many of the characteristic clinical features of ALS 2
SA, age 39, dressmaker, admitted into Charing Cross Hospital, 18 January 1894. She had been seen on 1 May 1893 by Dr Bruce, who made the following notes:
Nervous debility in family. No previous illness of a serious nature, but for twelve months past her health had been failing. For the last five months she had been troubled with a feeling of cold in the right leg, from knee to toes, and a sense of weight in walking. The difficulty increased so that she dragged the right leg, which felt heavy and cold, and it commenced to waste. The right arm began to fail twenty-one days ago; gradually progre