Abstract Objective: To understand current genetic testing practices at Canadian ALS clinics. Methods: An online survey and phone interviews, with clinicians practicing in 27 ALS clinics in Canada, were employed to collect data. Quantitative and qualitative analyses were conducted. Results: Ninety-three percent (25/27) of ALS clinics in Canada are routinely ordering genetic testing for familial ALS

Abstract Objective: Hyaluronan, a glycosaminoglycan that forms a major constituent of the extracellular matrix, has been shown to be increased in the serum of patients with amyotrophic lateral sclerosis (ALS) with longer disease duration. We sought to determine whether measures of venous hyaluronan may serve as a predictive marker for disease progression in patients with ALS. Methods: Sixty-two patients

Abstract With the aim of shedding further light on the role of environmental factors in amyotrophic lateral sclerosis (ALS) etiology, we hereby conducted a historical narrative review to critically appraise the published reports on ALS geographical clusters using the modern interpretation of the Bradford Hill criteria for causation. Our research hypothesis was that the more criteria were met, the greater

(2021). Introduction. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration: Vol. 22, Assessments of Pulmonary Function in patients with Amyotrophic Lateral Sclerosis: Options and Applicability in both the clinical care and clinical trial settings, pp. 1-1.

(2021). Editorial to the supplement entitled “assessments of pulmonary function in patients with amyotrophic lateral sclerosis: options and applicability in both the clinical care and clinical trial settings”. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration: Vol. 22, Assessments of Pulmonary Function in patients with Amyotrophic Lateral Sclerosis: Options and Applicability in both the

Abstract Objective: To measure the correlation between single breath counting (SBC) and forced vital capacity (liters, FVCL) in amyotrophic lateral sclerosis (ALS) patients and to define the utility of SBC for determining when patients meet the threshold for initiation of noninvasive positive pressure ventilation (FVC < 50% predicted [FVCpred]). Methods: Both patient paced (SBCpp) or externally paced

Abstract In this study, we present and provide validation data for a tool that predicts forced vital capacity (FVC) from speech acoustics collected remotely via a mobile app without the need for any additional equipment (e.g. a spirometer). We trained a machine learning model on a sample of healthy participants and participants with amyotrophic lateral sclerosis (ALS) to learn a mapping from speech

Abstract Introduction: Vital capacity (VC) is routinely used for ALS clinical trial eligibility determinations, often to exclude patients unlikely to survive trial duration. However, spirometry has been limited by the COVID-19 pandemic. We developed a machine-learning survival model without the use of baseline VC and asked whether it could stratify clinical trial participants and a wider ALS clinic

Abstract Objective: To investigate the role of arterial blood gas (ABG) analysis parameters (blood carbon dioxide, pCO2; oxygen, pO2; carbonate, HCO3−; standard base excess, SBE) in monitoring respiratory function and ventilation compliance after noninvasive mechanical ventilation (NIV) adaptation, predicting survival in ALS patients. Methods: We selected the first ABG performed after NIV start in

Abstract Background: Although noninvasive ventilation (NIV) improves survival and quality of life (QOL) in ALS, use of NIV is suboptimal. Objective: To determine compliance with “early” NIV initiation, requisite for the feasibility of a large study of early NIV initiation, and examine factors impacting compliance. Methods: Seventy-three ALS participants with forced vital capacities (FVC) >50% were

Abstract Objective: To develop an ALS respiratory symptom scale (ARES) and evaluate how ARES compares to Medical Research Council Modified Dyspnea Scale (MRC), Borg dyspnea scale, and respiratory subscores from ALSFRS-R (ALSFRS-Resp) in detecting respiratory symptoms, correlation with pulmonary function and ALSFRS-R, and deterioration of pulmonary function and ALSFRS-R over time. Methods: The ARES

Abstract Background: There has been no comprehensive longitudinal study of pulmonary functions (PFTS) in ALS determining which measure is most sensitive to declines in respiratory muscle strength. Objective: To determine the longitudinal decline of PFTS in ALS and which measure supports Medicare criteria for NIV initiation first. Methods: Serial PFTs (maximum voluntary ventilation (MVV), maximum inspiratory

Abstract Objective: To study the association between ventilatory function and cognitive and behavioral impairment in ALS patients accounting for the effects of pertinent covariates. Methods: Four hundred and eighty-one patients were identified from the Mayo Clinic Florida ALS registry who had concurrent forced vital capacity (FVC) and cognitive and behavioral testing using the ALS Cognitive Behavioral

Abstract Objective To describe current practices and barriers and support needs in gastrostomy indication and decision-making amongst rehabilitation physicians of ALS care teams in the Netherlands. Methods: Cross-sectional online survey of rehabilitation physicians of ALS care teams in the Netherlands. Survey items covered current practices in timing of indication (i.e. indicators and criteria), goals

Abstract Objective: To assess the availability of health workers and medications for clinical management of amyotrophic lateral sclerosis (ALS) in African hospital centers. Availability and affordability analyses of disease-modifying treatments were performed. Methods: A multicenter observational study involving African hospitals was conducted. A standard questionnaire was developed based on the European

Abstract Introduction: Hyper-religiosity has been reported in patients affected by frontotemporal dementia (FTD) with asymmetrical, predominantly right-sided frontotemporal atrophy. Case report: We report a FTD patient carrying a double genetic variant (p.Cys139Arg and c.*78C > T) in the progranulin (GRN) gene who showed an unusual clinical phenotype characterized by hyper-religiosity behavior and

Abstract Objective: To estimate the prevalence of amyotrophic lateral sclerosis (ALS) in the United States for 2016 using data from the National ALS Registry (Registry). Established in 2009, the Registry collects data on ALS patients in the U.S. to better describe the epidemiology of ALS, examine risk factors such as environmental and occupational exposures, and characterize the demographics of those

Abstract Objective: To investigate changes in immune markers and frequencies throughout disease progression in patients with amyotrophic lateral sclerosis (ALS). Methods: In this longitudinal study, serial blood samples were collected from 21 patients with ALS over a time period of up to 16 months. Flow cytometry was used to quantitate CD14, HLA-DR, and CD16 marker expression on monocyte subpopulations

Abstract Objective: SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder characterized by progressive retrograde degeneration, or “dying-back” phenomenon, of the corticospinal tract’s longest axons. Neuroimaging studies mainly focus on white matter changes and, although previous studies

Abstract Objective Pain currently plays a subordinate role in the clinical care of patients with ALS. We aim to examine epidemiological and clinical characteristics of pain as well as its impact throughout the disease course. Methods During a longitudinal follow-up at three time points, 151 ALS patients from three German outpatient clinics completed the Brief Pain Inventory, ALS-Functional Rating Scale-Extension

Abstract A roundtable convened in July 2020 examined issues concerning respiratory support in amyotrophic lateral sclerosis (ALS), with reference to the potential for an early-phase orally administered medication that might either postpone the introduction of noninvasive ventilation (NIV) and/or enhance the benefits to be gained from it. Attention was also given to the impact of the COVID-19 pandemic

Abstract Objective: The presence of the hexanucleotide repeat expansion (HRE) in C9orf72 gene is associated to the ALS/FTD spectrum, but also to parkinsonisms. We here describe an Italian family with the father diagnosed with Parkinson disease (PD) at the age of 67 and the two daughters developing FTD and ALS at 45 years of age. We searched for C9orf72 HRE with possible genetic and epigenetic modifiers

Abstract Purpose: For patients diagnosed with ALS, dysphagia can result in aspiration, malnutrition, and mortality. The purpose of this study was to develop a clinical prediction model capable of identifying patients with ALS at imminent risk for developing swallowing complications. Methods: A retrospective cohort study using the Pooled Resource Open-Access ALS Clinical Trials Database (PRO-ACT) was

Abstract Objective: To assess the frequency and predictors of plateaus in ALS progression as assessed by the Medical Research Council (MRC) Scale. Methods: All patients attending the ALS Center of Turin, with a diagnosis between 2007 and 2014 were considered. At each visit, muscle strength was evaluated in several muscles and assessed using the MRC scale. Concomitant ALSFRSr scores were retrieved.

Abstract Objective: To evaluate how Amyotrophic Lateral Sclerosis (ALS) patients’ mortality rates change, based on different levels of forced vital capacity (FVC) and disease duration, providing a scheme of mortality rates of a real population of ALS patients to improve the design of future RCTs. Methods: One random spirometry for each ALS patient was selected during four time intervals from disease

Abstract Objective: Data on and increase of the incidence of amyotrophic lateral sclerosis (ALS) are conflicting and reflect the use of differing populations and designs. We investigated the incidence of ALS using data from a large population-based registry (SLALOM) in two three-year periods using the same diagnostic criteria and equal methods of case ascertainment. Methods: The registry is based in

Abstract Objective: To test two hypotheses: (1) partners of ALS patients have higher mortality due to outcomes related to psychological distress, and (2) parents and siblings of ALS patients have higher mortality due to diseases that co-occur with ALS. Methods: We performed a nationwide, register-based cohort study in Sweden. We included ALS-free partners, biological parents and full siblings (N = 11

Abstract Objective. Up to 50% of patients affected by amyotrophic lateral sclerosis (ALS) show behavioral changes within the spectrum of frontotemporal degeneration (FTD). Behavioral dysfunctions in ALS patients negatively impact on management, prognosis and survival. It is, thus, crucial to develop ALS-specific psychometric tools for early detecting alterations in behavior. This study aimed at investigating

Abstract Background: Amyotrophic lateral sclerosis (ALS) has a complex genetic origin, and how immune dysregulation may contribute to ALS etiology remain unclear. Given the roles played by apolipoprotein E (APOE) signaling in neuroinflammation and neurodegeneration, an improved knowledge of the association between APOE genotypes and ALS risk in Chinese population may help to understand the underlying

(2021). Inosine supplements only reach the CNS in molybdenum deficient humans and may cause astrocyte degeneration and bulbar–respiratory disease. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. Ahead of Print.

Abstract Objective:To determine if inflammation in proximity of the motor unit may contribute to neurodegeneration in amyotrophic lateral sclerosis (ALS). Methods: We identified all patients diagnosed in Sweden with concurrent ALS and multiple sclerosis (MS), myasthenia gravis (MG), inflammatory polyneuropathies (IP), or dermatopolymyositis (DMPM) during 1991–2014 according to the Swedish Patient Register

Abstract Introduction: The edaravone development program for amyotrophic lateral sclerosis (ALS) included trials MCI186-16 (Study 16) and MCI186-19 (Study 19). A cohort enrichment strategy was based on a Study 16 post hoc analysis and applied to Study 19 to elucidate a treatment effect in that study. To determine whether the Study 19 results could be generalized to a broader ALS population, we used

Abstract Objective: To study disease characteristics, progression and outcome in a group of motor neuron disease (MND) patients beginning with frontotemporal dementia (FTD) by comparing them with patients with the typical motor-onset. Methods: 849 patients recruited from tertiary centers were studied according to FTD-onset and motor-onset. We studied clinical data, functional decline and survival.

Abstract Objective: To evaluate the possible effect of reldesemtiv, a fast skeletal muscle troponin activator, on prescription and acceptance of durable medical equipment (DME) in the FORTITUDE-ALS trial. Methods: Health economic outcome information was collected in FORTITUDE-ALS (NCT03160898); sites recorded if and when DME, specifically manual or power wheelchairs, gastrostomy tubes, noninvasive

Abstract Mutations in myelin protein zero (MPZ) are associated with heterogeneous manifestations. In this study, we report clinical, electrophysiological, pathological, and muscle MRI findings from two relatives with MPZ Thr124Met variants, disclosing different phenotypes. The proband was a 73-year-old female with a 12-year-story of atrophy, weakness, and fasciculations in her proximal and distal lower

Abstract Amyotrophic lateral sclerosis (ALS) causes dysphagia and consequent poor nutrition. Sometimes enteral feeding is offered. Percutaneous endoscopic gastrostomy (PEG) is currently the technique of choice for enteral nutrition of these patients. This systematic review addresses the role of PEG and other enteral feeding techniques in maintaining ALS patients’ survival and quality of life and in

Abstract Vitamin C is one of the most common supplements taken by people with ALS. As an antioxidant, it has a plausible mechanism for slowing disease progression and there are some flawed pre-clinical studies and case reports suggesting benefit. However, a small human trial showed no benefit. Given this negative trial, we do not currently advise vitamin C as an ALS treatment.

Abstract Background: During the course of amyotrophic lateral sclerosis (ALS), patients and their families are faced with existential decisions concerning life-prolonging and -shortening measures. Correct anticipation of patient’s well-being and preferences is a prerequisite for patient-centered surrogate decision making. Methods: In Germany (N = 84), Poland (N = 77) and Sweden (N = 73) patient-caregiver

Abstract Objective: To test whether high-sensitivity cardiac troponin T (hs-cTnT) could act as a diagnostic or prognostic biomarker in ALS, comparing hs-cTnT to neurofilament light (NfL). Methods: We performed a case-control study, including 150 ALS patients, 28 ALS mimics, and 108 healthy controls, and a follow-up study of the ALS patients, during 2014–2020 in Stockholm, Sweden. We compared concentrations

Abstract Objective: To assess amyotrophic lateral sclerosis (ALS) prevalence and to analyze how this estimate vary according to the historical depth of data collection. Methods: Data from the PARALS register have been used. Crude prevalence ratio was estimated on 31 December 2015 for the period 2015–2013 and then repeated extending the time interval by 3 years each time. For each time interval, prevalence

Abstract Objective: To summarize applications of muscle magnetic resonance imaging (MRI) in cross-sectional assessment and longitudinal monitoring of motor neuron diseases and evaluate associations with clinical assessment techniques. Methods: PubMed and Scopus were searched for research published up to May 2021 relating to muscle MRI in motor neuron diseases, according to predefined inclusion and

Abstract Objective: Human endogenous retroviruses (HERVs) have been gradually confirmed to be involved in the onset and progression of motor neuron disease(MND). However, noninvasive detection of HERVs in the central nervous system is lacking. The aim of this study is to verify the relationship between the level of HERV-K env in neuronal extracellular vesicles in plasma and the onset and severity of

Abstract Objective: To identify occupational risk factors for ALS using well-characterized participants with ALS (P-ALS), sibling controls (S-controls), and matched population controls (P-controls) within the National ALS Registry. We also compared oxidative stress (OS) biomarkers between groups. Methods: P-ALS were recruited over 4 years. Demographic, socioeconomic, and medical data were ascertained

Abstract Forced vital capacity (FVC) is an essential respiratory measurement for assessment and monitoring of patients with Amyotrophic Lateral Sclerosis (ALS). Our clinic rapidly implemented remote assessment of FVC after COVID-19 related restrictions on respiratory testing were imposed, using mini-spirometers and video consultation. We sought to evaluate the patient's experiences of performing remote

Abstract Fused in sarcoma (FUS) is the most common causative gene in juvenile-onset amyotrophic lateral sclerosis (jALS). We presented a case of a 15-year-old Chinese girl with atypical and extremely rare bilateral abducens palsy was caused by a heterozygous c.1520del (p.Gly507Alafs*22) pathogenic frameshift mutation in the FUS gene revealed by whole-exome sequencing. This is the first jALS case presenting

Abstract Objectives: Mindfulness-based interventions seem to be effective in promoting QOL of ALS patients and caregivers, but most require substantial time. In the Langerian approach, mindfulness can be easily promoted with mental tasks and short lectures. This study aims to explore the impact of an ALS-specific online Langerian mindfulness training program on QOL of ALS patients. Methods: We developed

Abstract Objective: SQSTM1-variants associated with frontotemporal lobar degeneration have been described recently. In this study, we investigated a heterozygous in-frame duplication c.436_462dup p. (Pro146_Cys154dup) in the SQSTM1 gene in a family with a new phenotype characterized by a personality disorder and behavioral variant frontotemporal dementia (bvFTD). We review the literature on frontotemporal

Abstract ALSUntangled reviews alternative and off-label treatments for people with amyotrophic lateral sclerosis (ALS). Here we review melatonin. We show that it has plausible mechanisms, some positive (and some negative) pre-clinical studies, two cases in which cocktails of supplements including melatonin were associated with recovery of lost motor function, and a very small, flawed retrospective

Abstract Introduction: Motor neurone disease (MND) is characterized by rapidly progressive motor neurone degeneration which leads to muscle wasting. Mortality and morbidity are due to respiratory muscle failure which may be offset by ventilation. The aim of this observational study was to quantify the number and characteristics of patients living with MND choosing tracheostomy ventilation (TV) in the

Abstract C9ORF72 hexanucleotide expansion is the most common genetic cause of familial amyotrophic lateral sclerosis (ALS)/fronto-temporal dementia (FTD) disease spectrum. Even though three major mechanisms of disease pathogenesis have been proposed, we lack detailed understanding of the factors that influence disease onset and progression. We sought to characterize cerebrospinal fluid and sera of

Abstract Objective: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by motor neuron involvement. Although olfactory dysfunction has been described in ALS, clinicoradiological features associated with the olfactory dysfunction remain poorly understood. Methods: We enrolled 30 patients with ALS and age- and sex-matched 53 healthy controls (HCs). All participants

Abstract Background: Previous research has suggested that vigorous physical activity (VPA) during adolescence and early adulthood is associated with ALS. The National ALS Registry (Registry) collects physical activity data from persons with ALS. Objective: To examine the association between vigorous VPA and early onset ALS, defined as a diagnosis before age 60, among patients enrolled in the Registry

Abstract Objective: To investigate the impact of a novel heterozygous FUS mutation in the acceptor splice site of intron 14 (c.1542 − 1 g > t) on protein expression in Peripheral Blood Mononuclear Cells (PBMC) from a familial ALS patient. Methods: PBMC were isolated for mRNA analysis (cDNA synthesis, sequencing and one-step RT-PCR), Western Immunoblot (WI), and Immunofluorescence (IF). Results: cDNA

Abstract Introduction: Heterogeneity of amyotrophic lateral sclerosis (ALS) has been suggested in terms of epidemiology, phenotypes and genetics between geographic areas and populations. However, there is limited information in Latin America. We conducted a systematic review that aimed to describe the epidemiology, frequency of genetic mutations, clinical characteristics and survival of ALS patients

Abstract Objective: To assess patients Quality of life (QoL) and the burden of their caregivers during Covid-19 pandemic and specifically the impact of two-month lockdown period. Methods: In April 2020, a total of 60 patients and 59 caregivers were administered by phone scales assessing patients’ QoL (McGill QoL Questionnaire), general health status (EQ-5D-5L), and caregiver burden (Zarit Burden Interview)

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Most patients die of respiratory failure within 3 years of onset. In this study, we reported a female Chinese ALS patient with SOD1 c.404G > C, p.S135T mutation. The missense mutation was identified as “Likely pathogenic” according to the ACMG/AMP 2015 guideline. The patient presented with weakness and atrophy of lower

Abstract Objective: In 2010, the United States Agency for Toxic Substances and Disease Registry (ATSDR) created the National ALS Registry (Registry) to examine the epidemiology of ALS and potential risk factors. We are currently recruiting population-based controls for an epidemiologic case-control study to examine ALS environmental risk factors using this Registry. To date, we have recruited 181 non-diseased

Abstract The kinesin family member 5A (KIF5A) motor domain variants are typically associated with hereditary spastic paraplegia (HSP) or Charcot-Marie-Tooth 2 (CMT2), while KIF5A tail variants predispose to amyotrophic lateral sclerosis (ALS) and neonatal intractable myoclonus. Variants within the stalk domain of KIF5A are relatively rare. We describe a family of three patients with a complex HSP phenotype

Abstract Background: Assessing clinical progression in amyotrophic lateral sclerosis (ALS) remains a challenge. We evaluated the validity and predictive capabilities of the King’s and Milano-Torino Staging (MiToS) systems in a cohort of patients with ALS to demonstrate their benefit in clinical practice. Methodology: A cohort study was performed by including ALS incident cases in a referral center

Abstract Objective: Amyotrophic lateral sclerosis (ALS) is a mostly sporadic neurodegenerative disease. The role of environmental factors has been extensively investigated but associations remain controversial. Considering that a substantial proportion of adult life is spent at work, identifying occupations and work-related exposures is considered an effective way to detect factors that increase ALS