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Lancet (London, England) Oct 2022Amyotrophic lateral sclerosis is a fatal CNS neurodegenerative disease. Despite intensive research, current management of amyotrophic lateral sclerosis remains... (Review)
Review
Amyotrophic lateral sclerosis is a fatal CNS neurodegenerative disease. Despite intensive research, current management of amyotrophic lateral sclerosis remains suboptimal from diagnosis to prognosis. Recognition of the phenotypic heterogeneity of amyotrophic lateral sclerosis, global CNS dysfunction, genetic architecture, and development of novel diagnostic criteria is clarifying the spectrum of clinical presentation and facilitating diagnosis. Insights into the pathophysiology of amyotrophic lateral sclerosis, identification of disease biomarkers and modifiable risks, along with new predictive models, scales, and scoring systems, and a clinical trial pipeline of mechanism-based therapies, are changing the prognostic landscape. Although most recent advances have yet to translate into patient benefit, the idea of amyotrophic lateral sclerosis as a complex syndrome is already having tangible effects in the clinic. This Seminar will outline these insights and discuss the status of the management of amyotrophic lateral sclerosis for the general neurologist, along with future prospects that could improve care and outcomes for patients with amyotrophic lateral sclerosis.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Forecasting; Humans; Neurodegenerative Diseases; Prognosis
PubMed: 36116464
DOI: 10.1016/S0140-6736(22)01272-7 -
Nature Reviews. Disease Primers Oct 2017Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is characterized by the degeneration of both upper and lower motor neurons, which leads to... (Review)
Review
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is characterized by the degeneration of both upper and lower motor neurons, which leads to muscle weakness and eventual paralysis. Until recently, ALS was classified primarily within the neuromuscular domain, although new imaging and neuropathological data have indicated the involvement of the non-motor neuraxis in disease pathology. In most patients, the mechanisms underlying the development of ALS are poorly understood, although a subset of patients have familial disease and harbour mutations in genes that have various roles in neuronal function. Two possible disease-modifying therapies that can slow disease progression are available for ALS, but patient management is largely mediated by symptomatic therapies, such as the use of muscle relaxants for spasticity and speech therapy for dysarthria.
Topics: Amyotrophic Lateral Sclerosis; Humans
PubMed: 28980624
DOI: 10.1038/nrdp.2017.71 -
The Lancet. Neurology May 2022The diagnosis of amyotrophic lateral sclerosis can be challenging due to its heterogeneity in clinical presentation and overlap with other neurological disorders.... (Review)
Review
The diagnosis of amyotrophic lateral sclerosis can be challenging due to its heterogeneity in clinical presentation and overlap with other neurological disorders. Diagnosis early in the disease course can improve outcomes as timely interventions can slow disease progression. An evolving awareness of disease genotypes and phenotypes and new diagnostic criteria, such as the recent Gold Coast criteria, could expedite diagnosis. Improved prognosis, such as that achieved with the survival model from the European Network for the Cure of ALS, could inform the patient and their family about disease course and improve end-of-life planning. Novel staging and scoring systems can help monitor disease progression and might potentially serve as clinical trial outcomes. Lastly, new tools, such as fluid biomarkers, imaging modalities, and neuromuscular electrophysiological measurements, might increase diagnostic and prognostic accuracy.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Disease Progression; Electromyography; Humans; Prognosis
PubMed: 35334233
DOI: 10.1016/S1474-4422(21)00465-8 -
Deutsche Medizinische Wochenschrift... Dec 2021Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disorder which is characterized by progressive motor symptoms, such as muscle weakness, muscle atrophy... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disorder which is characterized by progressive motor symptoms, such as muscle weakness, muscle atrophy and spasticity. In Germany, 6000-8000 people are affected by ALS. Between 1200 and 1600 newly diagnosed patients are expected each year. Protein deposits in the cytoplasm of motor neurons are a molecular feature of ALS. The most common protein aggregates result from excessive deposition of TDP-43. Familial ALS is present in 5 to 10 % of all ALS patients. Common causal genes include C9orf72, SOD1, FUS, and TARDBP. Genetic factors may be involved even without a family history of ALS and may be underestimated. The disease course and progression are highly variable. Symptom severity and rate of progression are determined by the ALS Functional Scale (ALSFRS-R). Beyond clinical symptoms and the patient's perception of disease burden, measurement of slow vital capacity (SVC), peak cough flow (PCF), and body mass index (BMI) are used to underscore the indications for ventilatory and nutritional interventions, as well as palliative care. The validity of the biomarker neurofilament light chain (NF-L) for estimating prognosis is currently being investigated. ALS is not curable - however, various individual treatment options have to be considered for improving survival, symptom control and social participation. The care in specialized ALS centers is recommended to ensure optimal treatment regarding symptomatic medication, assistive devices, nutrition support and ventilation therapy. Optimal care is achieved by interdisciplinary collaboration of general practitioners, specialized physicians, neurologists and ALS experts being integrated in multiprofessional care networks.
Topics: Amyotrophic Lateral Sclerosis; Humans; Prognosis
PubMed: 34879411
DOI: 10.1055/a-1562-7882 -
Cold Spring Harbor Perspectives in... Aug 2017Amyotrophic lateral sclerosis (ALS) is primarily characterized by progressive loss of motor neurons, although there is marked phenotypic heterogeneity between cases.... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is primarily characterized by progressive loss of motor neurons, although there is marked phenotypic heterogeneity between cases. Typical, or "classical," ALS is associated with simultaneous upper motor neuron (UMN) and lower motor neuron (LMN) involvement at disease onset, whereas atypical forms, such as primary lateral sclerosis and progressive muscular atrophy, have early and predominant involvement in the UMN and LMN, respectively. The varying phenotypes can be so distinctive that they would seem to have differing biology. Because the same phenotypes can have multiple causes, including different gene mutations, there may be multiple molecular mechanisms causing ALS, implying that the disease is a syndrome. Conversely, multiple phenotypes can be caused by a single gene mutation; thus, a single molecular mechanism could be compatible with clinical heterogeneity. The pathogenic mechanism(s) in ALS remain unknown, but active propagation of the pathology neuroanatomically is likely a primary component.
Topics: Amyotrophic Lateral Sclerosis; Disease Progression; Extremities; Frontotemporal Dementia; Humans; Motor Neurons; Mutation; Phenotype
PubMed: 28003278
DOI: 10.1101/cshperspect.a024117 -
The New England Journal of Medicine Jul 2017
Review
Topics: Amyotrophic Lateral Sclerosis; Genetic Variation; Humans; Survival Analysis
PubMed: 28700839
DOI: 10.1056/NEJMra1603471 -
Lancet (London, England) Nov 2017Amyotrophic lateral sclerosis is characterised by the progressive loss of motor neurons in the brain and spinal cord. This neurodegenerative syndrome shares... (Review)
Review
Amyotrophic lateral sclerosis is characterised by the progressive loss of motor neurons in the brain and spinal cord. This neurodegenerative syndrome shares pathobiological features with frontotemporal dementia and, indeed, many patients show features of both diseases. Many different genes and pathophysiological processes contribute to the disease, and it will be necessary to understand this heterogeneity to find effective treatments. In this Seminar, we discuss clinical and diagnostic approaches as well as scientific advances in the research fields of genetics, disease modelling, biomarkers, and therapeutic strategies.
Topics: Amyotrophic Lateral Sclerosis; Cause of Death; Chronic Disease; DNA-Binding Proteins; Disease Progression; Female; Genetic Predisposition to Disease; Humans; Male; Survival Rate; TDP-43 Proteinopathies
PubMed: 28552366
DOI: 10.1016/S0140-6736(17)31287-4 -
The American Journal of Managed Care Aug 2018Amyotrophic lateral sclerosis (ALS) is a disease that results in the progressive deterioration and loss of function of the motor neurons in the brain and spinal cord,... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a disease that results in the progressive deterioration and loss of function of the motor neurons in the brain and spinal cord, leading to paralysis. ALS affects approximately 16,000 individuals, with a prognosis for survival of 2 to 5 years. There are 2 types of ALS differentiated by genetics: familial and sporadic (idiopathic). Diagnosis is determined by excluding other conditions and utilizing clinical examinations, laboratory tests, and nerve conduction/electromyography studies. Due to the collection of information from the participation of patients with ALS in registries, biomarkers and genes associated with ALS have been discovered. The best practices for the management of ALS include an interdisciplinary approach aimed at addressing the physical and psychological needs and desires of patients and their families and caregivers.
Topics: Activities of Daily Living; Amyotrophic Lateral Sclerosis; Disease Progression; Early Diagnosis; Genetic Markers; Humans; Quality of Life
PubMed: 30207670
DOI: No ID Found -
Handbook of Clinical Neurology 2023The scientific landscape surrounding amyotrophic lateral sclerosis has shifted immensely with a number of well-defined ALS disease-causing genes, each with related... (Review)
Review
The scientific landscape surrounding amyotrophic lateral sclerosis has shifted immensely with a number of well-defined ALS disease-causing genes, each with related phenotypical and cellular motor neuron processes that have come to light. Yet in spite of decades of research and clinical investigation, there is still no etiology for sporadic amyotrophic lateral sclerosis, and treatment options even for those with well-defined familial syndromes are still limited. This chapter provides a comprehensive review of the genetic basis of amyotrophic lateral sclerosis, highlighting factors that contribute to its heritability and phenotypic manifestations, and an overview of past, present, and upcoming therapeutic strategies.
Topics: Humans; Amyotrophic Lateral Sclerosis; Motor Neurons; Syndrome
PubMed: 37620070
DOI: 10.1016/B978-0-323-98817-9.00031-4 -
Handbook of Clinical Neurology 2016Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults and is characterized by neurodegeneration of motor neurons in the brain and spinal... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults and is characterized by neurodegeneration of motor neurons in the brain and spinal cord. The incidence of ALS is approximately 1-2.6 cases per 100 000 persons annually, whereas the prevalence is approximately 6 cases per 100 000. The average age of onset of ALS is currently 58-60 years and the average survival from onset to death is 3-4 years. Between October 19, 2010 and December 31, 2011, there were an estimated 12 187 prevalent cases diagnosed with definite ALS in the USA alone. Sporadic ALS (90-95%) constitutes the large majority of cases, while the remaining 5-10% are hereditary and termed familial ALS. Sporadic ALS is suspected to involve genetic susceptibility to environmental risk factors. The purpose of this review is to present a clinical overview of ALS and provide an epidemiologic summary of personal and environmental risk factors shown to be related to the risk of disease. A discussion of the most recent research initiatives is also included.
Topics: Amyotrophic Lateral Sclerosis; Female; Humans; Male; Middle Aged; Prevalence; Risk Factors
PubMed: 27637961
DOI: 10.1016/B978-0-12-802973-2.00013-6