Changes in saccadic intrusions over time as an objective biomarker to follow ALS disease progression.

: Saccadic Intrusions (SIs) are abnormal eye movements during gaze fixation. Studies have indicated the clinical relevance of SIs, especially of square wave jerks (SWJ) in ALS. We used a software-based platform to extract SIs as a part of an interventional drug trial.

Mutations in the tail and rod domains of the neurofilament heavy-chain gene increase the risk of ALS.

Objective: Neurofilament heavy-chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk.

Genetic diagnosis and detection rates using C9orf72 repeat expansion and a multi-gene panel in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. It is mostly sporadic, with the C9orf72 repeat expansion being the most common genetic cause. While the prevalence of C9orf72-ALS in patients from different populations has been studied, data regarding the yield of C9orf72 compared to an ALS gene panel testing is limited.

Quantitative sonographic assessment of muscle thickness and fasciculations distribution is a sensitive tool for neuromuscular disorders.

Introduction: Loss of muscle thickness can be demonstrated in a wide spectrum of neuromuscular disorders, while fasciculations are more frequent in amyotrophic lateral sclerosis (ALS). In the current study, we aimed to determine the sensitivity and specificity of quantitative sonographic assessment of muscle thickness and the presence of fasciculations for diagnosing various neuromuscular disorders.

Methods: The thickness and the presence of fasciculations in eight muscles were determined by sonography in patients with myopathy (22), polyneuropathy (36), ALS (91), and spinal muscular atrophy (SMA) (31) and compared to normative values determined in 65 heathy control subjects.

Pre-morbid Laboratory Tests, Diseases, and Medications in Amyotrophic Lateral Sclerosis in Israel.

Background: There is an unmet need for real-world data regarding laboratory results, co-morbidities, and medication use prior to the first symptoms of amyotrophic lateral sclerosis (ALS). Researchers must identify specific subpopulations at risk for developing ALS and understand pathogenic mechanisms preceding the clinical presentation of ALS as well as possible subclinical disease manifestations.

Objectives: To valuate the role of laboratory results, co-morbidities, and medication use prior to the first symptoms of patients with ALS in Israel so that specific subpopulations at risk for developing ALS can be identified and for possible subclinical disease manifestations.

Correlation between oculometric measures and clinical assessment in ALS patients participating in a phase IIb clinical drug trial.

Oculometric measures (OM) can be extracted from eye movements during presentation of visual stimuli. Studies have indicated the benefit of OM in assessment of neurological disorders, including Amyotrophic Lateral Sclerosis (ALS). We used a new software-based platform for the extraction of OM during patients' assessment.

Large-scale analyses of CAV1 and CAV2 suggest their expression is higher in post-mortem ALS brain tissue and affects survival.

Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in amyotrophic lateral sclerosis (ALS). Disease-associated variants have been identified within CAV1/2 enhancers, which reduce gene expression and lead to disruption of membrane lipid rafts.

Combination of ciprofloxacin/celecoxib as a novel therapeutic strategy for ALS.

Objective: This study aimed to evaluate the safety and tolerability of a fixed-dose co-formulation of ciprofloxacin and celecoxib (PrimeC) in patients with amyotrophic lateral sclerosis (ALS), and to examine its effects on disease progression and ALS-related biomarkers.

Methods: In this proof of concept, open-label, phase IIa study of PrimeC in 15 patients with ALS, participants were administered PrimeC thrice daily for 12 months. The primary endpoints were safety and tolerability.

FUS-P525L Juvenile Amyotrophic Lateral Sclerosis and Intellectual Disability: Evidence for Association and Oligogenic Inheritance.

Background And Objectives: Amyotrophic lateral sclerosis (ALS) is characterized by upper and lower motor neuron degeneration, with juvenile ALS (jALS) defined as disease with age at onset (AAO) before 25 years. We aimed to identify the genetic basis of 2 unrelated patients with jALS with very rapid deterioration and early age intellectual disability (ID) and to assess association of genetic findings with both phenotypes in a large cohort of patients with ALS and controls, and in the literature.

Methods: Exome sequencing was performed in 2 unrelated probands and their parents.

Longer-term follow-up of nusinersen efficacy and safety in adult patients with spinal muscular atrophy types 2 and 3.

The effectiveness of nusinersen treatment in patients with spinal muscular atrophy (SMA) was established in clinical trials only for pediatric patients. Few cohort studies confirmed its benefit in adults up to 22 months of treatment. We report a longer-term observation of nusinersen treatment effects and safety in a large cohort of adult patients.

Predicting functional impairment trajectories in amyotrophic lateral sclerosis: a probabilistic, multifactorial model of disease progression.

Objective: To employ Artificial Intelligence to model, predict and simulate the amyotrophic lateral sclerosis (ALS) progression over time in terms of variable interactions, functional impairments, and survival.

Methods: We employed demographic and clinical variables, including functional scores and the utilisation of support interventions, of 3940 ALS patients from four Italian and two Israeli registers to develop a new approach based on Dynamic Bayesian Networks (DBNs) that models the ALS evolution over time, in two distinct scenarios of variable availability. The method allows to simulate patients' disease trajectories and predict the probability of functional impairment and survival at different time points.

Common genetic basis of ALS patients and soccer players may contribute to disease risk.

Objective: The aim of the present study was to determine the prevalence of the ACSL A/G single nucleotide polymorphism among athletes and patients with amyotrophic lateral sclerosis (ALS). ALS is a progressive neurodegenerative disorder of motor neurons that leads to paralysis and death usually within 3-5 years from onset. Previous epidemiological studies reported a higher risk of ALS among soccer players.

The Sensitivity and Specificity of Split-Hand Index Using Muscle Sonography.

Background: The split-hand index (SHI) (first dorsal interosseous (FDI) × abductor pollicis brevis (APB)/abductor digiti minimi muscle (ADM)) has been suggested as a useful measure for amyotrophic lateral sclerosis (ALS) diagnosis, using electrophysiological and sonographic indices. In the present study, we aimed to explore the specificity of SHI derived by muscle ultrasound (MUS) for the diagnosis of ALS and spinal muscular atrophy (SMA).

Methods: Healthy controls ( = 65) were prospectively recruited at the Prosserman Family Neuromuscular clinic at Toronto General Hospital, from October to December 2018.

The Sensitivity of Quantitative Sonographic Assessment of Muscle Thickness for Amyotrophic Lateral Sclerosis Diagnosis.

Purpose: In the current proof-of-concept study, we aimed to examine the sensitivities and specificities of previously reported normal values for muscle ultrasound thickness in amyotrophic lateral sclerosis.

Methods: Muscle ultrasound was performed in 65 healthy control subjects and 91 amyotrophic lateral sclerosis patients using a standardized assessment of eight relaxed muscles and four contracted muscles. Normal values for muscle thickness were determined as values above the 5th percentile stratified by age and gender using the weighted average method.

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis.

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.

Objective: To identify the genetic variants associated with juvenile ALS.

Design, Setting, And Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation.

The Effect of SMN Gene Dosage on ALS Risk and Disease Severity.

Objective: The role of the survival of motor neuron (SMN) gene in amyotrophic lateral sclerosis (ALS) is unclear, with several conflicting reports. A decisive result on this topic is needed, given that treatment options are available now for SMN deficiency.

Methods: In this largest multicenter case control study to evaluate the effect of SMN1 and SMN2 copy numbers in ALS, we used whole genome sequencing data from Project MinE data freeze 2.

Fasciculation frequency at the biceps brachii and brachialis muscles is associated with amyotrophic lateral sclerosis disease burden and activity.

Introduction: Fasciculations are most commonly seen in the biceps brachii muscle in amyotrophic lateral sclerosis (ALS). In this study we have explored the association between fasciculation frequency in a single location-biceps brachii and brachialis muscles (BB), and disease burden and activity.

Methods: Sonographic muscle studies were performed in 90 ALS patients, 47 of whom were seen in subsequent follow-up.

The NEALS primary lateral sclerosis registry.

Primary lateral sclerosis (PLS) is a neurodegenerative disease characterized by progressive upper motor neuron dysfunction. Because PLS patients represent only 1 to 4% of patients with adult motor neuron diseases, there is limited information about the disease's natural history. The objective of this study was to establish a large multicenter retrospective longitudinal registry of PLS patients seen at Northeast ALS Consortium (NEALS) sites to better characterize the natural progression of PLS.

Split-hand phenomenon in motor neuron diseases: Sonographic assesment of muscle thickness.

Objective: To explore the diagnostic accuracy of the split-hand index (SHI) for amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) using sonographic assessment of muscle thickness.

Methods: We performed a prospective sonographic assessment of hand muscle thickness in 59 controls, 87 patients with ALS, and 33 patients with SMA. We determined the diagnostic accuracy of SHI for differentiating patients with ALS and SMA from controls.

Superiority of sonographic evaluation of contracted versus relaxed muscle thickness in motor neuron diseases.

Objective: To compare the correlations of relaxed and contracted limb muscle thickness with clinical scales in patients with amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).

Methods: Patients with ALS and SMA were prospectively recruited from December 2018 to November 2019. All patients underwent clinical assessment and sonographic muscle thickness measurement of eight relaxed muscles (biceps brachii, abductor pollicis brevis (APB), first dorsal interosseous, abductor digiti minimi, quadriceps, tibialis anterior, extensor digitorum brevis, and abductor hallucis brevis), and four contracted muscles (biceps brachii, APB, quadriceps, and tibialis anterior).