Search Results (1,051)

(1) Background: Pain is a common symptom in patients with Amyotrophic Lateral Sclerosis (ALS). There are no evidence-based pharmacological treatments for pain in ALS; recommendations are based on guidelines for chronic non-oncological pain and clinical experience. The aim is to map the literature on how people with ALS experience pain, and how this affects their daily activities and social relationships. (2) Methods: This scoping review included studies concerning patients with spinal/bulbar ALS aged ≥ 18 years who experience pain, focusing on perception, characteristics, treatment, and impact on quality of life. Temporal and linguistic criteria were applied when searching the MEDLINE, CINAHL, and SCOPUS databases. (3) Results: The management of pain in these patients is complex and involves the use of anti-inflammatory drugs, analgesics, and opioids. Pain is associated with other conditions such as depression and anxiety, which contribute to a deterioration in the quality of life. Moreover, pain may also negatively influence patient compliance with prescribed treatment regimens and the quality of care they perceive themselves to be receiving. (4) Conclusions: It is of the most importance to identify effective ways to assess and treat this issue, with health care professionals taking an active role in this process. Full article

Background/objective: Amyotrophic lateral sclerosis (ALS) is a diagnosis that incorporates a heterogeneous set of neurodegenerative processes into a single progressive and uniformly fatal disease making the development of a uniformly applicable therapeutic difficult. Recent multinational ALS natural history incidence studies have identified systemic chronic activation of the innate immune system as a major risk factor for developing ALS. Persistent immune activation in patients with ALS leads to loss of muscle and lowering of serum creatinine. The goal of the current study was to test whether the slowing of nerve and muscle destruction in NP001-treated ALS patients compared with controls in phase 2 studies would lead to extension of survival. Methods: Phase 2 clinical studies with NP001, an intravenously administered form of the innate immune system regulator NaClO₂, are now reporting long-term survival benefits for drug recipients vs. placebo controls after only six months of intermittent treatment. As a prodrug, NP001 is converted by macrophages to taurine chloramine, a long-lived regulator of inflammation. We performed a pooled analysis of all patients who had completed the studies in two six-month NP001 phase 2 trials. Changes in respiratory vital capacity and the muscle mass product, creatinine, defined treated patients who, compared to placebo, had up to a year of extended survival. Conclusions: The observed longer survival in ALS patients with the greatest inflammation-associated muscle loss provides further evidence that ALS is a disease of ongoing innate immune dysfunction and that NP001 is a disease-modifying drug with sustained clinical activity. Full article

Background/Objectives: The aim of this study was to estimate the effect of a 6 months’ treatment course of the innate immune modulator NP001 (a pH-adjusted intravenous formulation of purified sodium chlorite), on disease progression, as measured by overall survival (OS) in patients with amyotrophic lateral sclerosis. Methods: Blinded survival data were retrospectively collected for 268 of the 273 patients who had participated in two phase 2 placebo-controlled clinical trials of NP001 (ClinicalTrials.gov: NCT01281631 and NCT02794857) and received at least one dose of either 1 mg/kg or 2 mg/kg of NP001 as chlorite based on actual body weight, or placebo. Kaplan–Meier methods were used on the intent-to-treat population to estimate survival probabilities. Results: In the overall population, the median OS was 4.8 months (2.7 years [95% CI: 2.3, 3.5] in the 2 mg/kg NP001group and 2.3 years [95% CI: 1.8, 2.9] in the placebo group). Hazard ratio (HR): 0.77 (95% CI: 0.57, 1.03), p = 0.073. Among patients aged ≤ 65 years, the median OS for the 2 mg/kg NP001 group was 10.8 months (3.3 years [95% CI: 2.4, 3.8] in the 2 mg/kg NP001 group and 2.4 years [95% CI: 1.7, 3.3] in the placebo group). HR: 0.69 (95% CI: 0.50, 0.95). No differences were observed in the 1 mg/kg NP001 group or in patients aged > 65 years. Conclusions: The findings from this study suggest that a 6 months’ treatment course of NP001 resulted in a 4.8-month increase in overall survival in patients with ALS. The findings from this study indicate that targeting inflammation associated with the innate immune system may provide a pathway for new therapeutic options for the treatment of ALS. Full article

This study used epigenomic methylation differential expression analysis to identify primary biomarkers in patients with amyotrophic lateral sclerosis (ALS). We combined electronic medical record datasets from MIMIC-IV (United States) and NHIRD (Taiwan) to explore ALS comorbidities in depth and discover any comorbidity-related biomarkers. We also applied word2vec to these two clinical diagnostic medical databases to measure similarities between ALS and other similar diseases and evaluated the statistical assessment of the odds ratio to discover significant comorbidities for ALS subjects. Important and representative DNA methylation biomarker candidates could be effectively selected by cross-comparing similar diseases to ALS, comorbidity-related genes, and differentially expressed methylation loci for ALS subjects. The screened epigenomic and comorbidity-related biomarkers were clustered based on their genetic functions. The candidate DNA methylation biomarkers associated with ALS were comprehensively discovered. Gene ontology annotations were then applied to analyze and cluster the candidate biomarkers into three different groups based on gene function annotations. The results showed that a potential testing kit for ALS detection can be composed of SOD3, CACNA1H, and ERBB4 for effective early screening of ALS using blood samples. By developing an effective DNA methylation biomarker screening mechanism, early detection and prophylactic treatment of high-risk ALS patients can be achieved. Full article

Physical–cognitive stimulation has emerged as a promising strategy for improving the quality of life of patients with amyotrophic lateral sclerosis (ALS). This case study reports on the use of immersive virtual reality (IVR) as a tool for multisensory stimulation in a woman with ALS (76 years old; 11 years since diagnosis; stage 2). The program consisted of IVR stimulation sessions (three sessions per week for 12 weeks). The results showed that the implementation of the program was feasible and safe (no adverse symptoms on the Simulator Sickness Questionnaire), as well as easy to execute (>80% on the System Usability Scale). Additionally, the participant reported improvements in aspects related to her mental health (44% depression and 20% anxiety) and improvements in her quality of life, and she also maintained her values in her functional capacity. This study presents novel and important findings by demonstrating the feasibility of implementing physical–cognitive stimulation programs with IVR in a person with ALS, allowing for multisensory stimulation with commercially available hardware and software and the generation of benefits in their health-related quality of life and mental health. Full article

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with sleep disturbance, namely insomnia and sleep-disordered breathing. This study aims to evaluate the overall sleep characteristics of ALS patients, their association with lung function tests, and possible predictive survival factors. We conducted a retrospective observation study among ALS patients monitored during a pulmonology consultation. Type one polysomnography (PSG) and lung function tests were performed once the patients presented with sleep-related symptoms, and the relationship between their parameters was assessed, as well as a survival analysis. We included 35 patients, with an overall diminished sleep efficiency, a partially conserved forced vital capacity (FVC), and low maximal inspiratory pressure (MIP). A positive correlation between FVC and REM sleep percentage was observed. A survival analysis showed that a normal rapid eye movement (REM) sleep percentage and respiratory disturbance index (RDI) ≥ 15/h were independent predictors of survival. We observed a trend for higher sleep quality in patients with conserved lung function. A better sleep quality was associated with a higher survival. Obstructive events (reduced or absence of airflow associated with continued or increased inspiratory effort) did not seem to impact survival. Full article

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. The heterogeneous nature of ALS at the clinical, genetic, and pathological levels makes it challenging to develop diagnostic and prognostic tools that fit all disease phenotypes. Limitations associated with the functional scales and the qualitative nature of mainstay electrophysiological testing prompt the investigation of more objective quantitative assessment. Biofluid biomarkers have the potential to fill that gap by providing evidence of a disease process potentially early in the disease, its progression, and its response to therapy. In contrast to other neurodegenerative diseases, no biomarker has yet been validated in clinical use for ALS. Several fluid biomarkers have been investigated in clinical studies in ALS. Biofluid biomarkers reflect the different pathophysiological processes, from protein aggregation to muscle denervation. This review takes a pathophysiologic approach to summarizing the findings of clinical studies utilizing quantitative biofluid biomarkers in ALS, discusses the utility and shortcomings of each biomarker, and highlights the superiority of neurofilaments as biomarkers of neurodegeneration over other candidate biomarkers. Full article

A Brain–Computer Interface (BCI) processes and converts brain signals to provide commands to output devices to carry out certain tasks. The main purpose of BCIs is to replace or restore the missing or damaged functions of disabled people, including in neuromuscular disorders like Amyotrophic Lateral Sclerosis (ALS), cerebral palsy, stroke, or spinal cord injury. Hence, a BCI does not use neuromuscular output pathways; it bypasses traditional neuromuscular pathways by directly interpreting brain signals to command devices. Scientists have used several techniques like electroencephalography (EEG) and intracortical and electrocorticographic (ECoG) techniques to collect brain signals that are used to control robotic arms, prosthetics, wheelchairs, and several other devices. A non-invasive method of EEG is used for collecting and monitoring the signals of the brain. Implementing EEG-based BCI technology in home automation systems may facilitate a wide range of tasks for people with disabilities. It is important to assist and empower individuals with paralysis to engage with existing home automation systems and gadgets in this particular situation. This paper proposes a home security system to control a door and a light using an EEG-based BCI. The system prototype consists of the EMOTIV Insight™ headset, Raspberry Pi 4, a servo motor to open/close the door, and an LED. The system can be very helpful for disabled people, including arm amputees who cannot close or open doors or use a remote control to turn on or turn off lights. The system includes an application made in Flutter to receive notifications on a smartphone related to the status of the door and the LEDs. The disabled person can control the door as well as the LED using his/her brain signals detected by the EMOTIV Insight™ headset. Full article

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknow etiology. Male sex is a well stablished risk factor, but other factors such as early and adult life expositions show contradictory evidence. Aim: to explore the link of clinical, sociodemographic, and occupational factors with ALS patients in Spain and the impact of these factors in functionality. Methods: A cross-sectional study was conducted with ALS patients and healthy controls. Registered variables were smoking, arterial hypertension, diabetes mellitus type 2, previous cancer to reproductive organs or breast, occupational exposure, and early life exposures. Functionality in ALS patients was compared according to each exposure. Results: The ALS group consisted of 59 participants and the control group of 90 participants. ALS patients showed a significant association with previous cancer (p = 0.011), occupational exposure (p < 0.001), and older siblings (p = 0.029). ALS patients presented significant differences in BMI according to hypertension and older-sibling factors. Moreover, respiratory function was affected in patients with previous cancer (p = 0.031). Conclusions: Occupational exposure and previous cancer to reproductive organs or breast could be linked to ALS patients. In addition, hypertension and previous cancer could affect their BMI and respiratory function. Other factors such as longer smoking periods and exposition to older siblings could also characterize ALS patients. Full article

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with progressive neurodegeneration, affecting both the cortical and the spinal component of the motor neuron circuitry in patients. The cellular and molecular basis of selective neuronal vulnerability is beginning to emerge. Yet, there are no effective cures for ALS, which affects more than 200,000 people worldwide each year. Recent studies highlight the importance of the glymphatic system and its proper function for the clearance of the cerebral spinal fluid, which is achieved mostly during the sleep period. Therefore, a potential link between problems with sleep and neurodegenerative diseases has been postulated. This paper discusses the present understanding of this potential correlation. Full article

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of motor neurons, with limited effective treatments. Recently, the exploration of natural products has unveiled their potential in exerting neuroprotective effects, offering a promising avenue for ALS therapy. In this study, the therapeutic effects of rutin, a natural flavonoid glycoside with neuroprotective properties, were evaluated in a superoxide dismutase 1 (SOD1)-G93A mouse model of ALS. We showed that rutin reduced the level of SOD1 aggregation and diminished glial cell activation in spinal cords and brainstems, resulting in significantly improved motor function and motor neuron restoration in SOD1-G93A mice. Our findings indicated that rutin’s multi-targeted approach to SOD1-related pathology makes it a promising candidate for the treatment of ALS. Full article

(1) Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease in which the patient suffers from an affection of both upper and lower motor neurons at the spinal and brainstem level, causing a progressive paralysis that leads to the patient’s demise. Gender is also considered a predisposing risk factor for developing the disease. A brief review of the pathophysiological mechanisms of the disease is also described in this work. Despite the fact that a cure for ALS is currently unknown, there exists a variety of pharmacological and non-pharmacological therapies that can help reduce the progression of the disease over a certain period of time and alleviate symptoms. (2) We aim to analyze these pharmacological and non-pharmacological therapies through a systematic review. A comprehensive, multidisciplinary approach to treatment is necessary. (3) Drugs such as riluzole, edaravone, and sodium phenylbutyrate, among others, have been investigated. Additionally, it is important to stay updated on research on new drugs, such as masitinib, from which very good results have been obtained. (4) Therapies aimed at psychological support, speech and language, and physical therapy for the patient are also available, which increase the quality of life of the patients. Full article

Microbes have inhabited the earth for hundreds of millions of years longer than humans. The microbiota–gut–brain axis (MGBA) represents a bidirectional communication pathway. These communications occur between the central nervous system (CNS), the enteric nervous system (ENS), and the emotional and cognitive centres of the brain. The field of research on the gut–brain axis has grown significantly during the past two decades. Signalling occurs between the gut microbiota and the brain through the neural, endocrine, immune, and humoral pathways. A substantial body of evidence indicates that the MGBA plays a pivotal role in various neurological diseases. These include Alzheimer’s disease (AD), autism spectrum disorder (ASD), Rett syndrome, attention deficit hyperactivity disorder (ADHD), non-Alzheimer’s neurodegeneration and dementias, fronto-temporal lobe dementia (FTLD), Wilson–Konovalov disease (WD), multisystem atrophy (MSA), Huntington’s chorea (HC), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), temporal lobe epilepsy (TLE), depression, and schizophrenia (SCZ). Furthermore, the bidirectional correlation between therapeutics and the gut–brain axis will be discussed. Conversely, the mood of delivery, exercise, psychotropic agents, stress, and neurologic drugs can influence the MGBA. By understanding the MGBA, it may be possible to facilitate research into microbial-based interventions and therapeutic strategies for neurological diseases. Full article

Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive and irreversible neurodegenerative disease with limited treatment options. Advances in regenerative medicine have opened up new treatment options. The primary and exploratory objectives of this retrospective cohort study were to evaluate the safety and efficacy of stem cells from human exfoliated deciduous teeth-conditioned media (SHED-CM). Methods: Safety assessments included adverse events, vital signs, and laboratory test changes before and after administration, and efficacy was measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), grip strength, and forced vital capacity in 24 patients with ALS treated at a single facility between 1 January 2022, and 30 November 2023. Results: While ALSFRS-R scores typically decline over time, the progression rate in this cohort was slower, suggesting a potential delay in disease progression. Alternatively, improvements in muscle strength and mobility were observed in some patients. Although adverse events were reported in only 3% of cases (no serious allergic reactions), the treatment-induced changes in vital signs and laboratory results were not clinically significant. Conclusions: The SHED-CM treatment is a safe and potentially effective therapeutic option for patients with ALS. Further research is needed to optimize the SHED-CM treatment; however, this study lays the groundwork for future exploration of regenerative therapies for ALS. Full article

This review offers an in-depth examination of amyotrophic lateral sclerosis (ALS), addressing its epidemiology, pathophysiology, clinical presentation, diagnostic techniques, and current as well as emerging treatments. The purpose is to condense key findings and illustrate the complexity of ALS, which is shaped by both genetic and environmental influences. We reviewed the literature to discuss recent advancements in understanding molecular mechanisms such as protein misfolding, mitochondrial dysfunction, oxidative stress, and axonal transport defects, which are critical for identifying potential therapeutic targets. Significant progress has been made in refining diagnostic criteria and identifying biomarkers, leading to earlier and more precise diagnoses. Although current drug treatments provide some benefits, there is a clear need for more effective therapies. Emerging treatments, such as gene therapy and stem cell therapy, show potential in modifying disease progression and improving the quality of life for ALS patients. The review emphasizes the importance of continued research to address challenges such as disease variability and the limited effectiveness of existing treatments. Future research should concentrate on further exploring the molecular foundations of ALS and developing new therapeutic approaches. The implications for clinical practice include ensuring the accessibility of new treatments and that healthcare systems are equipped to support ongoing research and patient care. Full article