-
Muscle & Nerve Jun 2020A brain-computer interface (BCI) is a device that detects signals from the brain and transforms them into useful commands. Researchers have developed BCIs that utilize... (Review)
Review
A brain-computer interface (BCI) is a device that detects signals from the brain and transforms them into useful commands. Researchers have developed BCIs that utilize different kinds of brain signals. These different BCI systems have differing characteristics, such as the amount of training required and the degree to which they are or are not invasive. Much of the research on BCIs to date has involved healthy individuals and evaluation of classification algorithms. Some BCIs have been shown to have potential benefit for users with minimal muscular function as a result of amyotrophic lateral sclerosis. However, there are still several challenges that need to be successfully addressed before BCIs can be clinically useful.
Topics: Amyotrophic Lateral Sclerosis; Brain; Brain-Computer Interfaces; Electroencephalography; Event-Related Potentials, P300; Humans
PubMed: 32034787
DOI: 10.1002/mus.26828 -
Amyotrophic Lateral Sclerosis &... Feb 2024While motor symptoms are well-known in ALS, non-motor symptoms are often under-reported and may have a significant impact on quality of life. In this study, we aimed to...
OBJECTIVE
While motor symptoms are well-known in ALS, non-motor symptoms are often under-reported and may have a significant impact on quality of life. In this study, we aimed to examine the nature and extent of non-motor symptoms in ALS.
METHODS
A 20-item questionnaire was developed covering the domains of autonomic function, sleep, pain, gastrointestinal disturbance, and emotional lability, posted online and shared on social media platforms to target people with ALS and controls.
RESULTS
A total of 1018 responses were received, of which 927 were complete from 506 people with ALS and 421 unaffected individuals. Cold limbs (p 1.66 × 10, painful limbs (p 6.14 × 10), and urinary urgency (p 4.70 × 10) were associated with ALS. People with ALS were more likely to report autonomic symptoms, pain, and psychiatric symptoms than controls (autonomic symptoms = 0.043, p 6.10 × 10, pain domain B = 0.18, p 3.72 × 10 and psychiatric domain = 0.173, p 1.32 × 10).
CONCLUSIONS
Non-motor symptoms in ALS are common. The identification and management of non-motor symptoms should be integrated into routine clinical care for people with ALS. Further research is warranted to investigate the relationship between non-motor symptoms and disease progression, as well as to develop targeted interventions to improve the quality of life for people with ALS.
Topics: Humans; Amyotrophic Lateral Sclerosis; Quality of Life; Pain; Disease Progression
PubMed: 37798838
DOI: 10.1080/21678421.2023.2263868 -
Biomolecules Mar 2024Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging,... (Review)
Review
Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD).
Topics: Humans; Biomarkers; Neurodegenerative Diseases; Alzheimer Disease; Amyotrophic Lateral Sclerosis; Parkinson Disease; Animals
PubMed: 38672416
DOI: 10.3390/biom14040398 -
Nature Communications Nov 2022Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, involving neuroinflammation and T cell infiltration in the central nervous system. However, the...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, involving neuroinflammation and T cell infiltration in the central nervous system. However, the contribution of T cell responses to the pathology of the disease is not fully understood. Here we show, by flow cytometric analysis of blood and cerebrospinal fluid (CSF) samples of a cohort of 89 newly diagnosed ALS patients in Stockholm, Sweden, that T cell phenotypes at the time of diagnosis are good predictors of disease outcome. High frequency of CD4FOXP3 effector T cells in blood and CSF is associated with poor survival, whereas high frequency of activated regulatory T (Treg) cells and high ratio between activated and resting Treg cells in blood are associated with better survival. Besides survival, phenotypic profiling of T cells could also predict disease progression rate. Single cell transcriptomics analysis of CSF samples shows clonally expanded CD4 and CD8 T cells in CSF, with characteristic gene expression patterns. In summary, T cell responses associate with and likely contribute to disease progression in ALS, supporting modulation of adaptive immunity as a viable therapeutic option.
Topics: Humans; Amyotrophic Lateral Sclerosis; CD8-Positive T-Lymphocytes; Neurodegenerative Diseases; T-Lymphocytes, Regulatory; Disease Progression
PubMed: 36347843
DOI: 10.1038/s41467-022-34526-9 -
Trends in Molecular Medicine Mar 2024Treatment of patients with amyotrophic lateral sclerosis (ALS) has entered a new era now that encouraging results about antisense oligonucleotides (ASOs) are becoming... (Review)
Review
Treatment of patients with amyotrophic lateral sclerosis (ALS) has entered a new era now that encouraging results about antisense oligonucleotides (ASOs) are becoming available and a first ASO therapy for ALS has been approved by the FDA. Moreover, there is hope not only that ALS can be stopped but also that symptoms can be reversed. Until now, degrading ASOs seemed to be successful mostly for rarer forms of familial ALS. However, the first attempts to correct mis-splicing events in sporadic ALS are underway, as well as a clinical trial examining interference with a genetic modifier. In this review, we discuss the current status of using ASOs in ALS and the possibilities and pitfalls of this therapeutic strategy.
Topics: Humans; Amyotrophic Lateral Sclerosis; Oligonucleotides, Antisense; RNA Splicing
PubMed: 38216448
DOI: 10.1016/j.molmed.2023.12.003 -
Biomolecules Oct 2023Amyotrophic lateral sclerosis (ALS) is a fatal condition characterized by the selective loss of motor neurons in the motor cortex, brainstem, and spinal cord. Muscle... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a fatal condition characterized by the selective loss of motor neurons in the motor cortex, brainstem, and spinal cord. Muscle involvement, muscle atrophy, and subsequent paralysis are among the main features of this disease, which is defined as a neuromuscular disorder. ALS is a persistently progressive disease, and as motor neurons continue to degenerate, individuals with ALS experience a gradual decline in their ability to perform daily activities. Ultimately, muscle function loss may result in paralysis, presenting significant challenges in mobility, communication, and self-care. While the majority of ALS research has traditionally focused on pathogenic pathways in the central nervous system, there has been a great interest in muscle research. These studies were carried out on patients and animal models in order to better understand the molecular mechanisms involved and to develop therapies aimed at improving muscle function. This review summarizes the features of ALS and discusses the role of muscle, as well as examines recent studies in the development of treatments.
Topics: Animals; Humans; Amyotrophic Lateral Sclerosis; Motor Neurons; Muscle, Skeletal; Muscular Atrophy; Paralysis
PubMed: 38002264
DOI: 10.3390/biom13111582 -
Journal of Neurology Dec 2023Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of both upper and lower motoneurons, leading to motor and... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of both upper and lower motoneurons, leading to motor and non-motor symptoms. Recent evidence suggests that ALS is indeed a multisystem disorder, associated with cognitive impairment, dysautonomia, pain and fatigue, excess of secretions, and sensory symptoms. To evaluate whether sensory neuropathy could broaden its spectrum, we systematically reviewed its presence and characteristics in ALS, extracting data on epidemiological, clinical, neurophysiological, neuropathological, and genetic features. Sensory neuropathy can be found in up to 20% of ALS patients, affecting both large and small fibers, although there is a great heterogeneity related to different techniques used for its detection (electromyography vs skin biopsy vs nerve biopsy). Moreover, the association between CIDP-like neuropathy and ALS needs to be better explored, although it could be interpreted as part of the neuroinflammatory process in the latter disease. Sensory neuropathy in ALS may be associated with a spinal onset and might be more frequent in SOD1 patients. Moreover, it seems mutually exclusive with cognitive impairment. No associations with sex and other genetic mutation were observed. All these data in the literature reveal the importance of actively looking for sensory neuropathy in ALS patients, and suggest including sensory neuropathy among ALS non-motor features, as it may explain sensory symptoms frequently reported throughout the course of the disease. Its early identification could help avoid diagnostic delays and improve patients' treatment and quality of life.
Topics: Humans; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Quality of Life; Motor Neurons; Electromyography
PubMed: 37610446
DOI: 10.1007/s00415-023-11954-1 -
Ageing Research Reviews Mar 2024Although sex differences in amyotrophic lateral sclerosis (ALS) have not been studied systematically, numerous clinical and preclinical studies have shown sex to be... (Review)
Review
Although sex differences in amyotrophic lateral sclerosis (ALS) have not been studied systematically, numerous clinical and preclinical studies have shown sex to be influential in disease prognosis. Moreover, with the development of advanced imaging tools, the difference between male and female brain in structure and function and their response to neurodegeneration are more definitive. As discussed in this review, ALS patients exhibit a sex bias pertaining to the features of the disease, and their clinical, pathological, (and pathophysiological) phenotypes. Several epidemiological studies have indicated that this sex disparity stems from various aetiologies, including sex-specific brain structure and neural functioning, genetic predisposition, age, gonadal hormones, susceptibility to traumatic brain injury (TBI)/head trauma and lifestyle factors.
Topics: Humans; Male; Female; Amyotrophic Lateral Sclerosis; Brain; Biology
PubMed: 38354985
DOI: 10.1016/j.arr.2024.102228 -
Translational Neurodegeneration Nov 2022Lipids, defined by low solubility in water and high solubility in nonpolar solvents, can be classified into fatty acids, glycerolipids, glycerophospholipids,... (Review)
Review
Lipids, defined by low solubility in water and high solubility in nonpolar solvents, can be classified into fatty acids, glycerolipids, glycerophospholipids, sphingolipids, and sterols. Lipids not only regulate integrity and fluidity of biological membranes, but also serve as energy storage and bioactive molecules for signaling. Causal mutations in SPTLC1 (serine palmitoyltransferase long chain subunit 1) gene within the lipogenic pathway have been identified in amyotrophic lateral sclerosis (ALS), a paralytic and fatal motor neuron disease. Furthermore, lipid dysmetabolism within the central nervous system and circulation is associated with ALS. Here, we aim to delineate the diverse roles of different lipid classes and understand how lipid dysmetabolism may contribute to ALS pathogenesis. Among the different lipids, accumulation of ceramides, arachidonic acid, and lysophosphatidylcholine is commonly emerging as detrimental to motor neurons. We end with exploring the potential ALS therapeutics by reducing these toxic lipids.
Topics: Humans; Amyotrophic Lateral Sclerosis; Translational Science, Biomedical; Motor Neurons; Motor Neuron Disease; Ceramides
PubMed: 36345044
DOI: 10.1186/s40035-022-00322-0 -
Neuroscience Research Dec 2023Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disease, still incurable. The disease is highly heterogenous both genetically and phenotypically.... (Review)
Review
Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disease, still incurable. The disease is highly heterogenous both genetically and phenotypically. Therefore, developing efficacious treatments is challenging in many aspects because it is difficult to predict the rate of disease progression and stratify the patients to minimize statistical variability in clinical studies. Moreover, there is a lack of sensitive measures of therapeutic effect to assess whether a pharmacological intervention ameliorates the disease. There is also urgency of markers that reflect a molecular mechanism dysregulated by ALS pathology and can be rescued when a treatment relieves the condition. Here, we summarize and discuss biomarkers tested in multicentered studies and across different laboratories like neurofilaments, the most used marker in ALS clinical studies, neuroinflammatory-related proteins, p75, p-Tau/t-Tau, and UCHL1. We also explore the applicability of muscle proteins and extracellular vesicles as potential biomarkers.
Topics: Humans; Amyotrophic Lateral Sclerosis; Prognosis; Biomarkers; Disease Progression
PubMed: 37689321
DOI: 10.1016/j.neures.2023.09.002