Impact Of Amyotrophic Lateral Sclerosis Research Articles

Development of a novel patient reported outcome measure for health-related quality of life in amyotrophic lateral sclerosis (PROQuALS): study protocol

BackgroundPatient reported outcome measures (PROMs) can be used to assess the impact of health conditions upon an individual’s health-related quality of life (HRQoL). Whilst PROMs have been used to quantify the HRQoL impact of amyotrophic lateral sclerosis (ALS), existing instruments may not fully capture what matters to people living with ALS (plwALS) or be appropriate to be used directly to inform the cost-effectiveness of new treatments. This highlights a need for a new condition-specific PROM that can both capture what’s important to plwALS and be used in economic evaluation. This study has two key aims: 1) to produce a novel PROM for measuring HRQoL in plwALS (PROQuALS). 2) to value a set of items from the novel PROM to generate an associated preference-weighted measure (PWM) that will enable utility values to be generated.MethodsA mixed-methods study design will be conducted across three stages. Stage 1 involves concept elicitation and the generation of draft PROM content from a robust and comprehensive systematic review of HRQoL in ALS, with input from plwALS. Stage 2 consists of cognitive debriefing of the draft PROM content to ascertain its content validity (Stage 2a), followed by a psychometric survey (Stage 2b) to assess statistical performance. Evidence from Stage 2 will be used to make decisions on the final content and format of the novel PROM. Stage 3 will involve valuation and econometric modeling using health economics methods to generate preference weights, so a PWM derived from the novel PROM can be used in the cost-effectiveness analyses of treatments. Patient and clinical advisory groups will have critical, collaborative input throughout the project.DiscussionThe novel PROM will be designed to comprehensively assess important aspects of HRQoL to plwALS and to quantify HRQoL in terms of subjective impact. The PROQuALS measure will be available for use in research and healthcare settings. The associated PWM component will extend and enable the use of PROQuALS in cost-effective analyses of new treatments for ALS.Trial registrationNot applicable.

PCR15 Impact of Amyotrophic Lateral Sclerosis on Work and Daily Living: Results from a Real-World Survey

PCR15 Impact of Amyotrophic Lateral Sclerosis on Work and Daily Living: Results from a Real-World Survey

Running and swimming prevent the deregulation of the BDNF/TrkB neurotrophic signalling at the neuromuscular junction in mice with amyotrophic lateral sclerosis.

Nerve-induced muscle contraction regulates the BDNF/TrkB neurotrophic signalling to retrogradely modulate neurotransmission and protect the neuromuscular junctions and motoneurons. In muscles with amyotrophic lateral sclerosis, this pathway is strongly misbalanced and neuromuscular junctions are destabilized, which may directly cause the motoneuron degeneration and muscular atrophy observed in this disease. Here, we sought to demonstrate (1) that physical exercise, whose recommendation has been controversial in amyotrophic lateral sclerosis, would be a good option for its therapy, because it normalizes and improves the altered neurotrophin pathway and (2) a plausible molecular mechanism underlying its positive effect. SOD1-G93A mice were trained following either running or swimming-based protocols since the beginning of the symptomatic phase (day 70 of age) until day 115. Next, the full BDNF pathway, including receptors, downstream kinases and proteins related with neurotransmission, was characterized and motoneuron survival was analysed. The results establish that amyotrophic lateral sclerosis-induced damaging molecular changes in the BDNF/TrkB pathway are reduced, prevented or even overcompensated by precisely defined exercise protocols that modulate TrkB isoforms and neurotransmission regulatory proteins and reduce motoneuron death. Altogether, the maintenance of the BDNF/TrkB signalling and the downstream pathway, particularly after the swimming protocol, adds new molecular evidence of the benefits of physical exercise to reduce the impact of amyotrophic lateral sclerosis. These results are encouraging since they reveal an improvement even starting the therapy after the onset of the disease.

Report by the Spanish Foundation for the Brain on the social impact of amyotrophic lateral sclerosis and other neuromuscular disorders

IntroductionA thorough knowledge of the socioeconomic scope of neuromuscular disease is essential for managing resources and raising social awareness. DevelopmentOur group reviewed current data on the epidemiology, mortality and dependence rates, and socioeconomic impact of amyotrophic lateral sclerosis and neuromuscular diseases in Spain. We also recorded how neurological care for these patients is organised. ConclusionsNeuromuscular disorders are a very heterogeneous group of diseases, and some are very rare. These disorders account for between 2.8% and 18% of the total motives for a neurological consultation. In Spain, prevalence and incidence figures for amyotrophic lateral sclerosis are similar to those in other countries; however, figures for patients with other neuromuscular diseases are not known. Since the diseases are chronic, progressive, and debilitating, they cause considerable disability and dependence, which in turn directly affects healthcare and social costs associated with the disease. The costs generated by one patient with amyotrophic lateral sclerosis or Duchenne disease have been calculated at about 50000 euros per year. Neuromuscular disease shows aetiological, diagnostic, and prognostic complexity, and it requires multidisciplinary management. Follow-up for these patients should be entrusted to specialised units.

Impact of Amyotrophic Lateral Sclerosis on Slow Tonic Myofiber Composition in Human Extraocular Muscles.

To analyze the proportion and cross-sectional area of myofibers containing myosin heavy chain slow-twitch (MyHCI) and myosin heavy chain slow tonic (MyHCsto) in extraocular muscles of autopsied amyotrophic lateral sclerosis (ALS) patients with either spinal or bulbar site of disease onset. Whole-muscle cross sections from the middle portion of the medial rectus were labeled with antibodies against MyHCI or MyHCsto and laminin. Myofibers labeled with the MyHC antibodies (MyHCI+sto) and the total number of myofibers were quantified in the orbital and global layer of 6 control individuals and 18 ALS patients. The cross-sectional area of myofibers labeled for either MyHC was quantified in 130 to 472 fibers/individual in the orbital and in 180 to 573 fibers/individual in the global layer of each specimen. The proportion of MyHCI+sto myofibers was significantly smaller in the orbital and global layer of ALS compared to control individuals. MyHCI+sto myofibers were significantly smaller in the global layer than in the orbital layer of ALS, whereas they were of similar size in control subjects. The decreased proportion of MyHCI+sto fibers correlated significantly with the age of death, but not disease duration, in patients who had the bulbar-onset variant of ALS but not in patients with spinal variant. ALS, regardless of site of onset, involves a loss of myofibers containing MyHCI+sto. Only in bulbar-onset cases did aging seem to play a role in the pathophysiological processes underlying the loss of MyHCI+sto fibers.

Informe de la Fundación Del Cerebro sobre el impacto social de la esclerosis lateral amiotrófica y las enfermedades neuromusculares

IntroductionA thorough knowledge of the socioeconomic scope of neuromuscular disease is essential for managing resources and raising social awareness. DevelopmentOur group reviewed current data on the epidemiology, mortality and dependence rates, and socioeconomic impact of amyotrophic lateral sclerosis and neuromuscular diseases in Spain. We also recorded how neurological care for these patients is organised. ConclusionsNeuromuscular disorders are a very heterogeneous group of diseases, and some are very rare. These disorders account for between 2.8% and 18% of the total motives for a neurological consultation. In Spain, prevalence and incidence figures for amyotrophic lateral sclerosis are similar to those in other countries; however, figures for patients with other neuromuscular diseases are not known. Since the diseases are chronic, progressive, and debilitating, they cause considerable disability and dependence, which in turn directly affects healthcare and social costs associated with the disease. The costs generated by one patient with amyotrophic lateral sclerosis or Duchenne disease have been calculated at about 50 000 euros per year. Neuromuscular disease shows aetiological, diagnostic, and prognostic complexity, and it requires multidisciplinary management. Follow-up for these patients should be entrusted to specialised units.

Different Impact of ALS on Laminin Isoforms in Human Extraocular Muscles versus Limb Muscles

To determine the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the laminin isoform composition of the basement membranes (BMs) in EOMs and limb muscles from donors with ALS. Muscle samples collected at autopsy from ALS donors and from transgenic mice overexpressing human superoxide dismutase type I mutations (D90A or G93A), and age-matched controls were analyzed with immunohistochemistry using antibodies against laminin chain (Ln)α2, Lnα4, Lnα5, Lnβ1, Lnβ2, and Lnγ1. Neuromuscular junctions (NMJs) were identified with α-bungarotoxin. Lnα2, the hallmark chain of skeletal muscle, and Lnβ2 were absent or partially absent from the BMs in a variable number of muscle fibers in most of the ALS EOMs. Three ALS donors showed dramatic decrease in the levels of these chains around their muscle fibers and NMJs. Changes in Lnα2 were not age related and were also present in EOMs of ALS mouse models. Lnα4 was preserved in the majority of NMJs in EOMs but absent in the majority of NMJs in limb muscle of ALS. The BMs around muscle fibers, NMJs, nerves, and blood vessels of the majority of EOMs of ALS donors had rather normal appearance and laminin composition, but heterogeneity was observed among EOM samples of individual ALS donors and between ALS donors. The present study showed distinct impact of ALS on EOMs compared with limb muscles. The EOMs maintained a normal laminin composition in their NMJs, which may be instrumental for the fact that they are not typically affected in ALS.