Interaction between riluzole treatment and dietary glycemic index in the disease progression of amyotrophic lateral sclerosis.

Objective: We examined whether riluzole treatment modifies the associations between the dietary glycemic index (GI) and load (GL) and disease progression in amyotrophic lateral sclerosis (ALS).

Methods: Sporadic ALS patients in the Multicenter Cohort Study of Oxidative Stress who completed a baseline food frequency questionnaire were included (n = 304). Interactions between baseline riluzole treatment and GI/GL on functional decline and tracheostomy-free survival were examined using linear regression and Cox proportional hazard models adjusted for covariates.

Blood glycated hemoglobin level is not associated with disease progression in amyotrophic lateral sclerosis.

Objective: A high glycemic index and high glycemic load diet has been associated with slower progression of amyotrophic lateral sclerosis (ALS), suggesting a benefit from high blood glucose levels. We examined the association between average blood glucose level and ALS progression in two independent cohorts.

Methods: Sporadic ALS patients enrolled in the ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS) who completed a 3-month follow-up visit and had available blood samples were included.

A microRNA diagnostic biomarker for amyotrophic lateral sclerosis.

Blood-based diagnostic biomarkers for amyotrophic lateral sclerosis will improve patient outcomes and positively impact novel drug development. Critical to the development of such biomarkers is robust method validation, optimization and replication with adequate sample sizes and neurological disease comparative blood samples. We sought to test an amyotrophic lateral sclerosis biomarker derived from diverse samples to determine if it is disease specific.

Reliability and consistency of the Japanese version of the Primary Lateral Sclerosis Functional Rating Scale.

Background: Primary lateral sclerosis (PLS) is an extremely rare condition; therefore, to date no clinical studies have been conducted. The Primary Lateral Sclerosis Functional Rating Scale (PLSFRS) was developed in the United States of America. The PLSFRS is a crucial assessment scale for international collaborative research and future clinical trials for PLS.

History of ALS and the competing theories on pathogenesis: IFCN handbook chapter.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the human motor system, first described in the 19th Century. The etiology of ALS appears to be multifactorial, with a complex interaction of genetic, epigenetic, and environmental factors underlying the onset of disease. Importantly, there are no known naturally occurring animal models, and transgenic mouse models fail to faithfully reproduce ALS as it manifests in patients.

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies as a candidate in PLS.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 30,000 people in the United States. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease.

Higher Glycemic Index and Glycemic Load Diet Is Associated with Slower Disease Progression in Amyotrophic Lateral Sclerosis.

Objective: High-caloric diets may slow the progression of amyotrophic lateral sclerosis; however, key macronutrients have not been identified. We examined whether dietary macronutrients are associated with the rate of progression and length of survival among the prospective cohort study participants.

Methods: Participants with a confirmed diagnosis of sporadic amyotrophic lateral sclerosis enrolled in the Multicenter Cohort Study of Oxidative Stress were included (n = 304).

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies as a candidate in PLS.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 30,000 people in the United States. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease.

Utilizing machine learning and lipidomics to distinguish primary lateral sclerosis from amyotrophic lateral sclerosis.

Introduction/aims: There are currently no imaging or blood diagnostic biomarkers that can differentiate amyotrophic lateral sclerosis (ALS) from primary lateral sclerosis (PLS) patients early in their disease courses. Our objective is to examine whether patients with PLS can be differentiated from ALS reliably by using plasma lipidome profile and supervised machine learning.

Methods: 40 ALS and 28 PLS patients derived from the Multicenter Cohort study of Oxidative Stress (COSMOS) and 28 healthy control volunteers (CTR) were included.

Early initiation of riluzole may improve absolute survival in amyotrophic lateral sclerosis.

Introduction/aims: Riluzole improves survival in amyotrophic lateral sclerosis (ALS), but optimal time and duration of treatment are unknown. The aim of this study was to examine if timing of riluzole initiation and duration of treatment modified its effect on survival.

Methods: Patients from the PRO-ACT dataset with information on ALS Functional Rating Scale, time from onset to enrollment (TFOE), and riluzole use were selected for analysis.

Clinicopathological correlates of pyramidal signs in multiple system atrophy.

Objective: Pyramidal signs are common but often under-recognized in multiple system atrophy (MSA). The clinicopathological correlates of pyramidal signs in MSA are not well characterized. The present study aims to understand the role of pyramidal signs in MSA.

Hastening the Diagnosis of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a chronic progressive neurodegenerative disease. Neurologists generally see patients as requested and as schedules allow. This practice is part of the reason it takes approximately 12 months from onset of new progressive weakness to receive a definitive diagnosis of ALS.

Phase 2B randomized controlled trial of NP001 in amyotrophic lateral sclerosis: Pre-specified and post hoc analyses.

Introduction/aims: ALS is a heterogeneous disease that may be complicated or in part driven by inflammation. NP001, a regulator of macrophage activation, was associated with slowing disease progression in those with higher levels of the plasma inflammatory marker C-reactive protein (CRP) in phase 2A studies in ALS. Here, we evaluate the effects of NP001 in a phase 2B trial, and perform a post hoc analysis with combined data from the preceding phase 2A trial.

Evaluating Personalized (N-of-1) Trials in Rare Diseases: How Much Experimentation Is Enough?

For rare diseases, conducting large, randomized trials of new treatments can be infeasible due to limited sample size, and it may answer the wrong scientific questions due to heterogeneity of treatment effects. Personalized (N-of-1) trials are multi-period crossover studies that aim to estimate individual treatment effects, thereby identifying the optimal treatments for individuals. This article examines the statistical design issues of evaluating a personalized (N-of-1) treatment program in people with amyotrophic lateral sclerosis (ALS).

Recruitment of Patients With Amyotrophic Lateral Sclerosis for Clinical Trials and Epidemiological Studies: Descriptive Study of the National ALS Registry's Research Notification Mechanism.

Background: Researchers face challenges in patient recruitment, especially for rare, fatal diseases such as amyotrophic lateral sclerosis (ALS). These challenges include obtaining sufficient statistical power as well as meeting eligibility requirements such as age, sex, and study proximity. Similarly, persons with ALS (PALS) face difficulty finding and enrolling in research studies for which they are eligible.

Metabolic Abnormalities, Dietary Risk Factors and Nutritional Management in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a devastating progressive neurodegenerative disease that affects motor neurons, leading to a relentless paralysis of skeletal muscles and eventual respiratory failure. Although a small percentage of patients may have a longer survival time (up to 10 years), in most cases, the median survival time is from 20 to 48 months. The pathogenesis and risk factors for ALS are still unclear: among the various aspects taken into consideration, metabolic abnormalities and nutritional factors have been the focus of recent interests.

Lipidomics study of plasma from patients suggest that ALS and PLS are part of a continuum of motor neuron disorders.

Motor neuron disorders (MND) include a group of pathologies that affect upper and/or lower motor neurons. Among them, amyotrophic lateral sclerosis (ALS) is characterized by progressive muscle weakness, with fatal outcomes only in a few years after diagnosis. On the other hand, primary lateral sclerosis (PLS), a more benign form of MND that only affects upper motor neurons, results in life-long progressive motor dysfunction.

Case-control study in ALS using the National ALS Registry: lead and agricultural chemicals are potential risk factors.

: 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. : P-ALS were recruited over 4 years.

Clinical care and therapeutic trials in PLS.

Primary lateral sclerosis (PLS) is an extremely rare central nervous system degenerative disorder characterized by slowly progressive upper motor neuron loss leading to severe limb and bulbar dysfunction and disability. Although not necessarily life-shortening, PLS disease burden is substantial and improved symptomatic treatments are a major unmet need, especially for the often refractory spasticity that is a core feature of the syndrome. In Section 1, we describe clinical care needs and emphasize a highly personalized approach that can be best attained through multidisciplinary management.

Better understanding the neurobiology of primary lateral sclerosis.

Primary lateral sclerosis (PLS) is a rare neurodegenerative disease characterized by progressive degeneration of upper motor neurons (UMNs). Recent studies shed new light onto the cellular events that are particularly important for UMN maintenance including intracellular trafficking, mitochondrial energy homeostasis and lipid metabolism. This review summarizes these advances including the role of Alsin as a gene linked to atypical forms of juvenile PLS, and discusses wider aspects of cellular pathology that have been observed in adult forms of PLS.