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Neuro-degenerative Diseases 2019Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease. People with ALS demonstrate various speech problems.
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease. People with ALS demonstrate various speech problems.
SUMMARY
We aim to provide an overview of studies concerning the diagnosis of ALS based on the analysis of voice samples. The main focus is on the feasibility of the use of voice and speech assessment as an effective method to diagnose the disease, either in clinical or pre-clinical conditions, and to monitor the disease progression. Specifically, we aim to examine current knowledge on: (a) voice parameters and the data models that can, most effectively, provide robust results; (b) the feasibility of a semi-automatic or automatic diagnosis and outcomes; and (c) the factors that can improve or restrict the use of such systems in a real-world context. Key Messages: The studies already carried out on the possibility of diagnosis of ALS using the voice signal are still sparse but all point to the importance, feasibility and simplicity of this approach. Most cohorts are small which limits the statistical relevance and makes it difficult to infer broader conclusions. The set of features used, although diverse, is quite circumscribed. ALS is difficult to diagnose early because it may mimic several other neurological diseases. Promising results were found for the automatic detection of ALS from speech samples and this can be a feasible process even in pre-symptomatic stages. Improved guidelines must be set in order to establish a robust decision model.
Topics: Amyotrophic Lateral Sclerosis; Diagnosis, Computer-Assisted; Humans; Pattern Recognition, Automated; Speech Recognition Software; Voice; Voice Disorders
PubMed: 32126556
DOI: 10.1159/000506259 -
Frontiers in Neuroscience 2020Amyotrophic lateral sclerosis (ALS) is a rapidly progressive fatal neurodegenerative condition. There are no effective treatments. The only globally licensed...
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive fatal neurodegenerative condition. There are no effective treatments. The only globally licensed medication, that prolongs life by 2-3 months, was approved by the FDA in 1995. One reason for the absence of effective treatments is disease heterogeneity noting that ALS is clinically heterogeneous and can be considered to exist on a neuropathological spectrum with frontotemporal dementia. Despite this significant clinical heterogeneity, protein misfolding has been identified as a unifying pathological feature in these cases. Based on this shared pathophysiology, we carried out a systematic review and meta-analysis to assess the therapeutic efficacy of compounds that specifically target protein misfolding in preclinical studies of both ALS and FTD. Three databases: (i) PubMed, (ii) MEDLINE, and (iii) EMBASE were searched. All studies comparing the effect of treatments targeting protein misfolding in pre-clinical ALS or FTD models to a control group were retrieved. Systematic review identified 70 pre-clinical studies investigating the effects of therapies targeting protein misfolding on survival. Meta-analysis revealed that targeting protein misfolding did significantly improve survival compared to untreated controls ( < 0.001, df = 68, α = 0.05, CI 1.05-1.16), with no evidence of heterogeneity between studies ( = 0%). Further subgroup analyses, evaluating the effect of timing of these interventions, showed that, only treating prior to symptom onset ( = 33), significantly improved survival ( < 0.001, df = 31, α = 0.05, CI 1.08-1.29), although this likely reflects the inadequate sample size of later time points. Furthermore, arimoclomol was found to significantly reduce secondary outcome measures including: (i) histological outcomes, (ii) behavioral outcomes, and (iii) biochemical outcomes ( < 0.005). This analysis supports the hypothesis that protein misfolding plays an important role in the pathogenesis of ALS and FTD and that targeting protein misfolding, at least in pre-clinical models, can significantly improve survival, especially if such an intervention is administered prior to symptom onset.
PubMed: 32523508
DOI: 10.3389/fnins.2020.00511 -
Scientific Reports May 2024This network meta-analysis (NMA) aimed to compare the efficacy of five non-pharmacological interventions, including exercise intervention (EI), nutritional intervention... (Meta-Analysis)
Meta-Analysis
Efficacy of non-pharmacological interventions for individuals with amyotrophic lateral sclerosis: systematic review and network meta-analysis of randomized control trials.
This network meta-analysis (NMA) aimed to compare the efficacy of five non-pharmacological interventions, including exercise intervention (EI), nutritional intervention (NI), respiratory intervention (RI), psychological intervention (PSI), and integrated physical intervention (IPI), on functional status, quality of life, muscle strength, pulmonary function, and safety in patients with amyotrophic lateral sclerosis (ALS). We searched nine databases, PubMed, Cochrane, Embase, Scopus, Web of Science, CNKI, CBM, WFPD, and CSTJ, for randomized controlled trials of ALS patients. The primary outcome was the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score. Secondary outcomes were the McGill Quality of Life Questionnaire (McGill-QoL), Medical Research Council (MRC)-sum score, Forced Vital Capacity (FVC), and Fatigue Severity Scale (FSS) score. This NMA was conducted using random-effect models to calculate the standard mean difference (SMD) and 95% confidence interval (CI). All types of supplemental interventions had some benefit for patients with ALS. EI had a beneficial effect on the ALSFRS-R score (SMD: 1.01; 95% CI 0.50-1.51), FVC (SMD: 0.78; 95% CI 0.02-1.55), McGill-QoL (SMD: 0.71 95% CI 0.33-1.08), and MRC (SMD: 1.11; 95% CI 0.08-2.14). RI had a beneficial effect on the ALSFRS-R score (SMD: 0.83 95% CI 0.12-1.55). IPI had a beneficial effect on the ALSFRS-R score (SMD: 0.65 95% CI 0.06-1.24). NI had a beneficial effect on the McGill-QoL (SMD: 0.63 95% CI 0.02-1.23). The current study findings support a multimodal intervention strategy with an emphasis on EI for slowing disease progression in patients with ALS.
Topics: Amyotrophic Lateral Sclerosis; Humans; Randomized Controlled Trials as Topic; Quality of Life; Network Meta-Analysis; Exercise Therapy; Treatment Outcome; Muscle Strength
PubMed: 38762656
DOI: 10.1038/s41598-024-62213-w -
BMC Medicine Jun 2022The time of survival in patients with amyotrophic lateral sclerosis (ALS) varies greatly, and the genetic factors that contribute to the survival of ALS are not well... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The time of survival in patients with amyotrophic lateral sclerosis (ALS) varies greatly, and the genetic factors that contribute to the survival of ALS are not well studied. There is a lack of a comprehensive study to elucidate the role of genetic factors in the survival of ALS.
METHODS
The published studies were systematically searched and obtained from PubMed, EMBASE, and the Cochrane Library without any language restrictions from inception to Oct 27, 2021. A network meta-analysis for ALS causative/risk genes and a systematic review and pairwise meta-analysis for other genetic modifiers were conducted. The PROSPERO registration number: CRD42022311646.
RESULTS
A total of 29,764 potentially relevant references were identified, and 71 papers were eligible for analysis based on pre-decided criteria, including 35 articles in network meta-analysis for 9 ALS causative/risk genes, 17 articles in pairwise meta-analysis for four genetic modifiers, and 19 articles described in the systematic review. Variants in three genes, including ATXN2 (HR: 3.6), C9orf72 (HR: 1.6), and FUS (HR:1.8), were associated with short survival of ALS, but such association was not identified in SOD1, TARDBP, TBK1, NEK1, UBQLN2, and CCNF. In addition, UNC13A rs12608932 CC genotype and ZNF521B rs2275294 C allele also caused a shorter survival of ALS; however, APOE ε4 allele and KIFAP3 rs1541160 did not be found to have any effect on the survival of ALS.
CONCLUSIONS
Our study summarized and contrasted evidence for prognostic genetic factors in ALS and would help to understand ALS pathogenesis and guide clinical trials and drug development.
Topics: Adaptor Proteins, Signal Transducing; Alleles; Amyotrophic Lateral Sclerosis; Autophagy-Related Proteins; Genotype; Humans; Network Meta-Analysis
PubMed: 35754054
DOI: 10.1186/s12916-022-02411-3 -
The European Respiratory Journal Sep 2019Noninvasive ventilation (NIV) prolongs survival and quality of life in amyotrophic lateral sclerosis (ALS); however, its benefits depend upon the optimisation of both...
BACKGROUND
Noninvasive ventilation (NIV) prolongs survival and quality of life in amyotrophic lateral sclerosis (ALS); however, its benefits depend upon the optimisation of both ventilation and adherence. We aimed to identify factors associated with effective initiation and ongoing use of NIV in ALS to develop evidence-based guidance and identify areas for further research.
METHODS
We searched 11 electronic databases (January 1998 to May 2018) for all types of quantitative and qualitative studies. Supplementary grey literature searches were conducted. Records were screened against eligibility criteria, data were extracted from included studies and risk of bias was assessed. We present findings using a narrative synthesis.
RESULTS
We screened 2430 unique records and included 52 quantitative and six qualitative papers. Factors reported to be associated with NIV optimisation included coordinated multidisciplinary care, place of initiation, selection of interfaces, ventilator modes and settings appropriate for the individual patient, and adequate secretion management. The literature indicated that patients with significant bulbar dysfunction can still derive considerable benefit from NIV if their needs are met. Research emphasises that obstructive airway events, mask leak and uncontrolled secretions should be addressed by adjustments to the interface and machine settings, and the concomitant use of cough augmentation.
CONCLUSION
This review highlights that NIV optimisation requires an individualised approach to respiratory management tailored to the differing needs of each patient. Ultimately, this should lead to improved survival and quality of life. This review expands on recommendations in current international guidelines for NIV use in ALS and identifies areas for future research.
Topics: Amyotrophic Lateral Sclerosis; Caregivers; Cough; Evidence-Based Medicine; Humans; Lung; Monitoring, Ambulatory; Noninvasive Ventilation; Patient Compliance; Quality of Life; Reproducibility of Results; Respiratory Insufficiency; Risk; Treatment Outcome
PubMed: 31273038
DOI: 10.1183/13993003.00261-2019 -
CNS Neuroscience & Therapeutics Feb 2011Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease of adults which preferentially attacks the neuromotor system. Riluzole has been... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease of adults which preferentially attacks the neuromotor system. Riluzole has been used as the only approved treatment for amyotrophic lateral sclerosis since 1995, but its mechanism(s) of action in slowing the progression of this disease remain obscure. Searching PubMed for "riluzole" found 705 articles published between January 1996 and June 2009. A systematic review of this literature found that riluzole had a wide range of effects on factors influencing neural activity in general, and the neuromotor system in particular. These effects occurred over a large dose range (<1 μM to >1 mM). Reported neural effects of riluzole included (in approximate ascending order of dose range): inhibition of persistent Na(+) current = inhibition of repetitive firing < potentiation of calcium-dependent K(+) current < inhibition of neurotransmitter release < inhibition of fast Na(+) current < inhibition of voltage-gated Ca(2+) current = promotion of neuronal survival or growth factors < inhibition of voltage-gated K(+) current = modulation of two-pore K(+) current = modulation of ligand-gated neurotransmitter receptors = potentiation of glutamate transporters. Only the first four of these effects commonly occurred at clinically relevant concentrations of riluzole (plasma levels of 1-2 μM with three- to four-fold higher concentrations in brain tissue). Treatment of human ALS patients or transgenic rodent models of ALS with riluzole most commonly produced a modest but significant extension of lifespan. Riluzole treatment was well tolerated in humans and animals. In animals, despite in vitro evidence that riluzole may inhibit rhythmic motor behaviors, in vivo administration of riluzole produced relatively minor effects on normal respiration parameters, but inhibited hypoxia-induced gasping. This effect may have implications for the management of hypoventilation and sleep-disordered breathing during end-stage ALS in humans.
Topics: Adult; Aged; Amyotrophic Lateral Sclerosis; Animals; Brain; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Humans; Middle Aged; Motor Neurons; Neuroprotective Agents; Riluzole
PubMed: 20236142
DOI: 10.1111/j.1755-5949.2009.00116.x -
Amyotrophic Lateral Sclerosis &... Feb 2024Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with upper and lower motor neuron degeneration and necrosis, characterized by... (Review)
Review
OBJECTIVE
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with upper and lower motor neuron degeneration and necrosis, characterized by progressive muscle weakness, atrophy, and paralysis. The mutation-associated ALS has been classified as ALS6. We reported a case of ALS6 with de novo mutation and investigated retrospectively the characteristics of cases with mutation.
METHODS
We reported a male patient with a new heterozygous variant of the gene and comprehensively reviewed 173 ALS cases with mutation. The literature was reviewed from the PubMed MEDLINE electronic database (https://www.ncbi.nlm.nih.gov/pubmed) using "Amyotrophic Lateral Sclerosis and mutation" or " mutation" as key words from 1 January 2009 to 1 January 2022.
RESULTS
We report a case of ALS6 with a new mutation point (c.1225-1227delGGA) and comprehensively review 173 ALS cases with mutation. Though ALS6 is all with mutation, it is still a highly heterogenous subtype. The average onset age of ALS6 is 35.2 ± 1.3 years, which is much lower than the average onset age of ALS (60 years old). Juvenile FUS mutations have an aggressive progression of disease, with an average time from onset to death or tracheostomy of 18.2 ± 0.5 months. gene has the characteristics of early onset, faster progress, and shorter survival, especially in deletion mutation p.G504Wfs *12 and missense mutation of p.P525L.
CONCLUSIONS
ALS6 is a highly heterogenous subtype. Our study could allow clinicians to better understand the non-ALS typical symptoms, phenotypes, and pathophysiology of ALS6.
Topics: Humans; Male; Amyotrophic Lateral Sclerosis; Mutation; Mutation, Missense; Neurodegenerative Diseases; Retrospective Studies; RNA-Binding Protein FUS
PubMed: 37926865
DOI: 10.1080/21678421.2023.2272170 -
Frontiers in Neurology 2020Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive loss of motor neurons. Patients usually die 3-5 years after...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive loss of motor neurons. Patients usually die 3-5 years after diagnosis from respiratory failure. Several studies investigated the role of vitamin D as a biomarker or a therapeutic option for ALS patients. To clarify the scientific evidence, we performed a systematic review and different meta-analyses regarding the potential role of vitamin D in ALS. We performed a systematic review of clinical trials, cohorts, and case-control studies retrieved from PubMed, EMBASE, and Cochrane databases reporting vitamin D levels as a putative biomarker for ALS diagnosis or prognosis or the effect of vitamin D supplementation in ALS patients. Whenever possible, data were pooled using a random-effects model, with an assessment of heterogeneity. Out of 2,996 articles retrieved, we finally included 13 research articles, 12 observational studies (50% prospective), and 1 clinical trial. We found that ALS patients had slightly lower levels of vitamin D than controls (mean difference -6 ng/ml, 95% CI [-10.8; -1.3]), but important confounding factors were not considered in the studies analyzed. We found no relationship between vitamin D levels and ALS functional rate score-revised (ALSFRS-R), with highly heterogeneous results. Discordant results were reported in three studies regarding survival. Finally, five studies reported the effects of vitamin D supplementation with discordant results. Two of them showed a small improvement, whereas two others showed a deleterious effect on ALSFRS-R. One very small clinical trial with important methodological limitations showed some improvement in ALSFRS-R with high doses of vitamin D compared with normal doses. Our review did not find evidence to support the role of vitamin D on ALS diagnosis, prognosis, or treatment. Most studies had important limitations, mostly regarding the risk of bias for not considering confounding factors. Vitamin D supplementation should be offered to ALS patients to avoid other health issues related to vitamin D deficiency, but there is not enough evidence to support the use of vitamin D as a therapy for ALS.
PubMed: 32849187
DOI: 10.3389/fneur.2020.00697 -
The evolving role of surface electromyography in amyotrophic lateral sclerosis: A systematic review.Clinical Neurophysiology : Official... Apr 2020Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads to inexorable motor decline and a median survival of three years from symptom...
OBJECTIVE
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads to inexorable motor decline and a median survival of three years from symptom onset. Surface EMG represents a major technological advance that has been harnessed in the development of novel neurophysiological biomarkers. We have systematically reviewed the current application of surface EMG techniques in ALS.
METHODS
We searched PubMed to identify 42 studies focusing on surface EMG and its associated analytical methods in the diagnosis, prognosis and monitoring of ALS patients.
RESULTS
A wide variety of analytical techniques were identified, involving motor unit decomposition from high-density grids, motor unit number estimation and measurements of neuronal hyperexcitability or neuromuscular architecture. Some studies have proposed specific diagnostic and prognostic criteria however clinical calibration in large ALS cohorts is currently lacking. The most validated method to monitor disease is the motor unit number index (MUNIX), which has been implemented as an outcome measure in two ALS clinical trials.
CONCLUSION
Surface EMG offers significant practical and analytical flexibility compared to invasive techniques. To capitalise on this fully, emphasis must be placed upon the multi-disciplinary collaboration of clinicians, bioengineers, mathematicians and biostatisticians.
SIGNIFICANCE
Surface EMG techniques can enrich effective biomarker development in ALS.
Topics: Action Potentials; Amyotrophic Lateral Sclerosis; Biomarkers; Disease Progression; Electromyography; Humans; Motor Neurons; Muscle, Skeletal; Prognosis
PubMed: 32044239
DOI: 10.1016/j.clinph.2019.12.007 -
Global Spine Journal Feb 2019Systematic review.
STUDY DESIGN
Systematic review.
INTRODUCTION
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, ultimately resulting in paralysis and death. The condition is considered to be caused by a complex interaction between environmental and genetic factors. Although vast genetic research has deciphered many of the molecular factors in ALS pathogenesis, the environmental factors have remained largely unknown. Recent evidence suggests that participation in certain types of sporting activities are associated with increased risk for ALS.
OBJECTIVE
To test the hypothesis that competitive sports at the highest level that involve repetitive concussive head and cervical spinal trauma result in an increased risk of ALS compared with the general population or nonsport controls.
METHODS
Electronic databases from inception to November 22, 2017 and reference lists of key articles were searched to identify studies meeting inclusion criteria.
RESULTS
Sixteen studies met the inclusion criteria. Sports assessed (professional or nonprofessional) included soccer (n = 5), American football (n = 2), basketball (n = 1), cycling (n = 1), marathon or triathlon (n = 1), skating (n = 1), and general sports not specified (n = 11). Soccer and American football were considered sports involving repetitive concussive head and cervical spinal trauma. Professional sports prone to repetitive concussive head and cervical spinal trauma were associated with substantially greater effects (pooled rate ratio [RR] 8.52, 95% CI 5.18-14.0) compared with () nonprofessional sports prone to repetitive concussive head and cervical spinal trauma (pooled RR 0.60, 95% CI 0.12-3.06); () professional sports not prone to repetitive head and neck trauma (pooled RR 1.35, 95% CI 0.67-2.71); or () nonprofessional sports not prone to repetitive concussive head and cervical spinal trauma (pooled RR 1.17, 95% CI 0.79-1.71).
CONCLUSIONS
Our review suggests that increased susceptibility to ALS is significantly and independently associated with 2 factors: professional sports and sports prone to repetitive concussive head and cervical spinal trauma. Their combination resulted in an additive effect, further increasing this association to ALS.
PubMed: 30775214
DOI: 10.1177/2192568218813916