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Neurology Aug 2023Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder affecting upper and lower motor neurons. Due to its rarity and rapidly progressive nature,...
BACKGROUND AND OBJECTIVES
Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder affecting upper and lower motor neurons. Due to its rarity and rapidly progressive nature, studying the epidemiology of ALS is challenging, and a comprehensive picture of the global burden of this disease is lacking. The objective of this systematic review was to describe the global incidence and prevalence of ALS.
METHODS
We searched MEDLINE, Embase, Global Health, PsycInfo, Cochrane Library, and CINAHL to identify articles published between January 1, 2010, and May 6, 2021. Studies that were population based and reported estimates of prevalence, incidence, and/or mortality of ALS were eligible for inclusion. This study focuses on the incidence and prevalence. Quality assessment was performed using a tool developed to evaluate methodology relevant to prevalence and incidence studies. This review was registered with PROSPERO, CRD42021250559.
RESULTS
This search generated 6,238 articles, of which 140 were selected for data extraction and quality assessment. Of these, 85 articles reported on the incidence and 61 on the prevalence of ALS. Incidence ranged from 0.26 per 100,000 person-years in Ecuador to 23.46 per 100,000 person-years in Japan. Point prevalence ranged from 1.57 per 100,000 in Iran to 11.80 per 100,000 in the United States. Many articles identified cases with ALS from multiple data sources.
DISCUSSION
There is variation in reported incidence and prevalence estimates of ALS across the world. While registries are an important and powerful tool to quantify disease burden, such resources are not available everywhere. This results in gaps in reporting of the global epidemiology of ALS, as highlighted by the degree of variation (and quality) in estimates of incidence and prevalence reported in this review.
Topics: Amyotrophic Lateral Sclerosis; Incidence; Prevalence; Humans; Africa; Asia; Europe; North America; South America; Oceania
PubMed: 37308302
DOI: 10.1212/WNL.0000000000207474 -
Chest Aug 2023Respiratory failure is a significant concern in neuromuscular diseases (NMDs). This CHEST guideline examines the literature on the respiratory management of patients...
BACKGROUND
Respiratory failure is a significant concern in neuromuscular diseases (NMDs). This CHEST guideline examines the literature on the respiratory management of patients with NMD to provide evidence-based recommendations.
STUDY DESIGN AND METHODS
An expert panel conducted a systematic review addressing the respiratory management of NMD and applied the Grading of Recommendations, Assessment, Development, and Evaluations approach for assessing the certainty of the evidence and formulating and grading recommendations. A modified Delphi technique was used to reach a consensus on the recommendations.
RESULTS
Based on 128 studies, the panel generated 15 graded recommendations, one good practice statement, and one consensus-based statement.
INTERPRETATION
Evidence of best practices for respiratory management in NMD is limited and is based primarily on observational data in amyotrophic lateral sclerosis. The panel found that pulmonary function testing every 6 months may be beneficial and may be used to initiate noninvasive ventilation (NIV) when clinically indicated. An individualized approach to NIV settings may benefit patients with chronic respiratory failure and sleep-disordered breathing related to NMD. When resources allow, polysomnography or overnight oximetry can help to guide the initiation of NIV. The panel provided guidelines for mouthpiece ventilation, transition to home mechanical ventilation, salivary secretion management, and airway clearance therapies. The guideline panel emphasizes that NMD pathologic characteristics represent a diverse group of disorders with differing rates of decline in lung function. The clinician's role is to add evaluation at the bedside to shared decision-making with patients and families, including respect for patient preferences and treatment goals, considerations of quality of life, and appropriate use of available resources in decision-making.
Topics: Humans; Quality of Life; Respiration, Artificial; Noninvasive Ventilation; Respiratory Insufficiency; Physicians
PubMed: 36921894
DOI: 10.1016/j.chest.2023.03.011 -
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 -
Sleep Medicine Jul 2023This study explores the polysomnographic differences between amyotrophic lateral sclerosis (ALS) patients and healthy controls. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study explores the polysomnographic differences between amyotrophic lateral sclerosis (ALS) patients and healthy controls.
METHODS
An electronic literature search was conducted in MEDLINE, EMBASE, All EBM databases, Web of Science, and CNKI from inception to Oct 2022.
RESULTS
Meta-analyses revealed significant reductions in sleep efficiency, total sleep time, N2%, slow wave sleep percentage, minimum SpO, and mean SpO, and increases in wake time after sleep onset and N1%, sleep latency, rapid eye movement sleep latency, time spent with SpO < 90%, oxygen desaturation index, and apnea hypopnea index in ALS patients compared with controls. Sensitivity analyses showed that some heterogeneity was explained by excluding patients taking medications impacting sleep, whether studies employed an adaptation night, and the use of different PSG scoring rules.
CONCLUSIONS
Significant polysomnographic abnormalities are present in ALS. Our findings underscore the need for a comprehensive PSG assessment of sleep changes in ALS patients. When performing PSG examinations in ALS, whether the patients are taking medication impacting sleep and the scoring system used should be considered.
Topics: Humans; Amyotrophic Lateral Sclerosis; Polysomnography; Sleep; Sleep, REM; Sleep Latency
PubMed: 37163838
DOI: 10.1016/j.sleep.2023.04.014 -
Genes Apr 2024Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS.
METHODS
Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939.
RESULTS
Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival.
DISCUSSION
Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls.
Topics: Amyotrophic Lateral Sclerosis; Humans; Neurofilament Proteins; Biomarkers; Intermediate Filaments; Prognosis
PubMed: 38674431
DOI: 10.3390/genes15040496 -
Noninvasive mechanical ventilation assistance in amyotrophic lateral sclerosis: a systematic review.Sao Paulo Medical Journal = Revista... 2023Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS), and morbidity is related to poor quality of life (QOL)....
BACKGROUND
Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS), and morbidity is related to poor quality of life (QOL). Non-invasive ventilation (NIV) may be associated with prolonged survival and QOL in patients with ALS.
OBJECTIVES
To assess whether NIV is effective and safe for patients with ALS in terms of survival and QOL, alerting the health system.
DESIGN AND SETTING
Systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting standards using population, intervention, comparison, and outcome strategies.
METHODS
The Cochrane Library, CENTRAL, MEDLINE, LILACS, EMBASE, and CRD databases were searched based on the eligibility criteria for all types of studies on NIV use in patients with ALS published up to January 2022. Data were extracted from the included studies, and the findings were presented using a narrative synthesis.
RESULTS
Of the 120 papers identified, only 14 were related to systematic reviews. After thorough reading, only one meta-analysis was considered eligible. In the second stage, 248 studies were included; however, only one systematic review was included. The results demonstrated that NIV provided relief from the symptoms of chronic hypoventilation, increased survival, and improved QOL compared to standard care. These results varied according to clinical phenotype.
CONCLUSIONS
NIV in patients with ALS improves the outcome and can delay the indication for tracheostomy, reducing expenditure on hospitalization and occupancy of intensive care unit beds.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO database: CRD42021279910 - https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=279910.
Topics: Humans; Amyotrophic Lateral Sclerosis; Noninvasive Ventilation; Quality of Life; Respiration, Artificial; Respiratory Insufficiency
PubMed: 37436254
DOI: 10.1590/1516-3180.2022.0470.R1.100423 -
Amyotrophic Lateral Sclerosis &... Aug 2023This review sought to gain a comprehensive, up-to-date understanding of the epidemiology and cost and healthcare resource use (HCRU) burden of amyotrophic lateral...
This review sought to gain a comprehensive, up-to-date understanding of the epidemiology and cost and healthcare resource use (HCRU) burden of amyotrophic lateral sclerosis (ALS) in the US, at a patient and national level. A targeted literature review (TLR) to identify epidemiological evidence (prevalence, incidence, mortality, survival), and systematic literature review (SLR) to identify cost and HCRU data published since January 2016, were performed. MEDLINE databases and Embase searches were conducted in January 2021. Key congresses (2019-2020) and bibliographies of relevant SLRs were hand-searched. Two high-quality SLRs were reviewed for additional cost data published between January 2001-2015. Registry and database studies were prioritized for epidemiological evidence. To allow comparison between studies in this publication, only evidence from the US was considered, with costs inflated to the 2020/2021 cost-year and converted to US dollars. Eight studies from the epidemiology TLR, and eighteen from the cost and HCRU SLR, were extracted. Reported ALS incidence in the US was ∼1.5 per 100,000 person-years, and point prevalence ranged from 3.84-5.56 per 100,000 population. Total US national costs spanned ∼$212 million-∼$1.4 billion USD/year, and variably consisted of direct costs associated with HCRU and indirect costs. : The national cost of ∼$1.02 billion USD/year (estimated using a prevalence of 16,055 cases) best aligns with prevalence estimates found in the TLR (equating to ∼13,000-18,000 cases). However, large-scale, population-based studies are necessary to precisely assess US epidemiology of ALS and capture all costs needed to inform cost-effectiveness models and resource planning.
Topics: Humans; United States; Amyotrophic Lateral Sclerosis; Financial Stress; Prevalence; Registries; Databases, Factual; Cost of Illness; Health Care Costs
PubMed: 36748473
DOI: 10.1080/21678421.2023.2165947 -
The Cochrane Database of Systematic... Aug 2023Maintaining adequate nutrition is critical for people with amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND). Enteral tube feeding is offered... (Review)
Review
BACKGROUND
Maintaining adequate nutrition is critical for people with amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND). Enteral tube feeding is offered to people experiencing difficulty swallowing (dysphagia) to prevent weight loss and aspiration pneumonia. Among the types of enteral tube feeding, percutaneous endoscopic gastrostomy (PEG) is the typical procedure offered to people with ALS and will be mainly discussed here.
OBJECTIVES
To examine the effectiveness of percutaneous endoscopic gastrostomy or other enteral tube feeding in people with ALS, compared to oral feeds without enteral tube feeding on: 1. survival; 2. nutritional status; 3. quality of life. To examine the incidence of minor and major complications of percutaneous endoscopic gastrostomy (PEG) and other enteral tube feeding procedures in people with ALS.
SEARCH METHODS
On 3 January 2020 and 6 February 2021, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE. Embase, ClinicalTrials.gov and WHO ICTRP. We screened the results to identify randomized controlled studies on enteral tube feeding in ALS. We reviewed all references from the search in published articles to identify any additional references.
SELECTION CRITERIA
We included randomized controlled trials (RCTs), quasi-RCTs, and cross-over trials evaluating the effectiveness and complications of PEG or other enteral tube feeding placement in ALS.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We found no RCTs or quasi-RCTs comparing the effectiveness of enteral tube feeding versus oral feeds without enteral tube feeding.
AUTHORS' CONCLUSIONS
There are no RCTs or quasi-RCTs to indicate whether enteral tube feeding is effective compared to continuation of oral feeding for any of the outcome measures. Such RCTs are very unlikely to be performed for ethical reasons. RCTs evaluating the effect of different enteral tube insertion techniques and timings of tube placement on survival and quality of life of people with ALS dysphagia are feasible and warranted.
Topics: Humans; Amyotrophic Lateral Sclerosis; Deglutition Disorders; Enteral Nutrition; Intubation, Gastrointestinal; Motor Neuron Disease
PubMed: 37579081
DOI: 10.1002/14651858.CD004030.pub4 -
Neurological Sciences : Official... Oct 2023The study aims to increase understanding of edaravone's efficacy and safety as an amyotrophic lateral sclerosis (ALS) treatment and provide significant insights... (Meta-Analysis)
Meta-Analysis Review
AIM
The study aims to increase understanding of edaravone's efficacy and safety as an amyotrophic lateral sclerosis (ALS) treatment and provide significant insights regarding this field's future research.
METHODS
We conducted a comprehensive search of the Embase, PubMed, Cochrane Library, Web of Science, and Scopus databases for randomized controlled trials and observational studies up until September 2022. We evaluated the studies' quality using the Cochrane risk of bias tool and the National Institutes of Health tool.
RESULTS
We included 11 studies with 2845 ALS patients. We found that edaravone improved the survival rate at 18, 24, and 30 months (risk ratio (RR) = 1.03, 95% confidence interval (CI) [1.02 to 1.24], P = 0.02), (RR = 1.22, 95% CI [1.06 to 1.41], P = 0.007), and (RR = 1.17, 95% CI [1.01 to 1.34], P = 0.03), respectively. However, the administration of edaravone did not result in any significant difference in adverse effects or efficacy outcomes between the two groups, as indicated by a P value greater than 0.05.
CONCLUSION
Edaravone improves survival rates of ALS patients at 18, 24, and 30 months with no adverse effects. However, edaravone does not affect functional outcomes. In order to ensure the validity of our findings and assess the results in accordance with the disease stage, it is essential to carry out additional prospective, rigorous, and high-quality clinical trials. The current study offers preliminary indications regarding the effectiveness and safety of edaravone. However, further comprehensive research is required to establish the generalizability and sustainability of the findings.
Topics: United States; Humans; Edaravone; Amyotrophic Lateral Sclerosis; Prospective Studies; Quality of Life; Severity of Illness Index
PubMed: 37249667
DOI: 10.1007/s10072-023-06869-8 -
Acta Neurologica Belgica Jun 2024The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings.... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings. This study aims to evaluate the effectiveness and long-term efficacy of edaravone.
METHODS
The OVID Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched for articles published between January 1, 2000, and May 1, 2023. Two investigators independently screened the retrieved articles for randomized controlled trials (RCTs), cohort studies, or single-arm trials that evaluated the effect of edaravone on amyotrophic lateral sclerosis (ALS). The risk of bias was evaluated using the revised Cochrane Risk-of-Bias (RoB 2.0) tool for randomized controlled trials (RCTs) and the Risk-of-Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies. The primary outcome was the ALSFRS-R score assessed at month 6, with secondary outcomes including the ALSFRS-R scores evaluated at months 9, 12, and 18, forced vital capacity (FVC), and adverse events. The certainty of evidence was assessed using the GRADE approach.
RESULTS
The analysis included 16 studies with a total of 4828 participants. Among these, four were randomized controlled trials (RCTs) and 12 were observational studies. Of the RCTs, four were rated as having a low risk of bias, while six of the observational studies were rated as having a low risk of bias. Edaravone was associated with slightly slower progression in the reduction of ALSFRS-R score at month 6 compared to placebo (mean difference 1.01, 95%CI -0.87 to 3.09, p = 0.293), as shown by evidence from RCTs. However, observational studies did not show any benefit of adding edaravone to routine practice (mean difference 1.85, 95%CI -2.05 to 5.75, p = 0.352). The change from baseline in ALSFRS-R score was -2.1, -4.04, -7.5, -6.82, and -7.9 at months 3, 6, 9, 12, and 18, respectively. The GRADE assessment indicated moderate certainty for evidence from RCTs, while evidence from observational studies had very low certainty.
CONCLUSION
Due to the limited number of studies and confounding issues in observational studies, further examination of the added benefits of edaravone to routine practice is necessary through RCTs, particularly regarding its long-term efficacy.
Topics: Edaravone; Humans; Amyotrophic Lateral Sclerosis; Free Radical Scavengers; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38347315
DOI: 10.1007/s13760-024-02476-2