Spinal cord gray matter atrophy is associated with disability in spinal muscular atrophy.

Background: With the approval of disease-modifying treatments for 5q-spinal muscular atrophy (SMA), there is an increasing need for biomarkers for disease course and therapeutic response monitoring. Radially sampled Averaged Magnetization Inversion Recovery Acquisitions (rAMIRA) MR-imaging enables spinal cord (SC) gray matter (GM) delineation and quantification in vivo. This study aims to assess SC GM atrophy in patients with 5q-SMA and its associations with clinical disability.

Safety and tolerability of tegoprubart in patients with amyotrophic lateral sclerosis: A Phase 2A clinical trial.

Background: The interaction of CD40L and its receptor CD40 on activated T cells and B cells respectively control pro-inflammatory activation in the pathophysiology of autoimmunity and transplant rejection. Previous studies have implicated signaling pathways involving CD40L (interchangeably referred to as CD154), as well as adaptive and innate immune cell activation, in the induction of neuroinflammation in neurodegenerative diseases. This study aimed to assess the safety, tolerability, and impact on pro-inflammatory biomarker profiles of an anti CD40L antibody, tegoprubart, in individuals with amyotrophic lateral sclerosis (ALS).

Safety, tolerability, and efficacy of fasudil in amyotrophic lateral sclerosis (ROCK-ALS): a phase 2, randomised, double-blind, placebo-controlled trial.

Background: Fasudil is a small molecule inhibitor of Rho-associated kinase (ROCK) and is approved for the treatment of subarachnoid haemorrhage. In preclinical studies, fasudil has been shown to attenuate neurodegeneration, modulate neuroinflammation, and foster axonal regeneration. We aimed to investigate the safety, tolerability, and efficacy of fasudil in patients with amyotrophic lateral sclerosis.

The Lateral Corticospinal Tract Sign: An MRI Marker for Amyotrophic Lateral Sclerosis.

Background Radially sampled averaged magnetization inversion-recovery acquisition (rAMIRA) imaging shows hyperintensity in the lateral corticospinal tract (CST) in patients with motor neuron diseases. Purpose To systematically determine the accuracy of the lateral corticospinal tract sign for detecting patients with amyotrophic lateral sclerosis (ALS) at rAMIRA MRI. Materials and Methods This study included prospectively acquired data from participants in ALS and other motor neuron disease imaging studies at the University Hospital Basel, Switzerland.

A novel digital tool for detection and monitoring of amyotrophic lateral sclerosis motor impairment and progression via keystroke dynamics.

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition leading to progressive muscle weakness, atrophy, and ultimately death. Traditional ALS clinical evaluations often depend on subjective metrics, making accurate disease detection and monitoring disease trajectory challenging. To address these limitations, we developed the nQiALS toolkit, a machine learning-powered system that leverages smartphone typing dynamics to detect and track motor impairment in people with ALS.

Multicenter expanded access program for access to investigational products for amyotrophic lateral sclerosis.

Introduction/aims: Expanded access (EA) is a Food and Drug Administration-regulated pathway to provide access to investigational products (IPs) to individuals with serious diseases who are ineligible for clinical trials. The aim of this report is to share the design and operations of a multicenter, multidrug EA program for amyotrophic lateral sclerosis (ALS) across nine US centers.

Methods: A central coordination center was established to design and conduct the program.

The Effects of Interactive Context on Acoustic Characteristics of Speech in People With Dysarthria: A Preliminary Study.

Purpose: The current study compared temporal and spectral acoustic contrast between vowel segments produced by speakers with dysarthria across three speech tasks-interactive, solo habitual, and solo clear.

Method: Nine speakers with dysarthria secondary to amyotrophic lateral sclerosis participated in the study. Each speaker was paired with a typical interlocutor over videoconferencing software.

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.

Neurophysiological and imaging biomarkers of lower motor neuron dysfunction in motor neuron diseases/amyotrophic lateral sclerosis: IFCN handbook chapter.

This chapter discusses comprehensive neurophysiological biomarkers utilised in motor neuron disease (MND) and, in particular, its commonest form, amyotrophic lateral sclerosis (ALS). These encompass the conventional techniques including nerve conduction studies (NCS), needle and high-density surface electromyography (EMG) and H-reflex studies as well as novel techniques. In the last two decades, new methods of assessing the loss of motor units in a muscle have been developed, that are more convenient than earlier methods of motor unit number estimation (MUNE),and may use either electrical stimulation (e.

European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD).

Background: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS).

Methods: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel.

Cervical and thoracic spinal cord gray matter atrophy is associated with disability in patients with amyotrophic lateral sclerosis.

Background And Purpose: In amyotrophic lateral sclerosis (ALS), there is an unmet need for more precise patient characterization through quantitative, ideally operator-independent, assessments of disease extent and severity. Radially sampled averaged magnetization inversion recovery acquisitions (rAMIRA) magnetic resonance imaging enables gray matter (GM) and white matter (WM) area quantitation in the cervical and thoracic spinal cord (SC) with optimized contrast. We aimed to investigate rAMIRA-derived SC GM and SC WM areas and their association with clinical phenotype and disability in ALS.

5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2.

Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland.

Comparison of Vowel and Sentence Intelligibility in People With Dysarthria Secondary to Amyotrophic Lateral Sclerosis.

Purpose: In this study, we examined the utility of vowel intelligibility testing for assessing the impact of dysarthria on speech characteristics in people with amyotrophic lateral sclerosis (ALS). We tested the sensitivity and specificity of overall vowel identification, as well as that of vowel-specific identification, to dysarthria presence and severity. We additionally examined the relationship between vowel intelligibility and sentence intelligibility.

Digital markers of motor speech impairments in spontaneous speech of patients with ALS-FTD spectrum disorders.

Objective: To evaluate automated digital speech measures, derived from spontaneous speech (picture descriptions), in assessing bulbar motor impairments in patients with ALS-FTD spectrum disorders (ALS-FTSD).

Methods: Automated vowel algorithms were employed to extract two vowel acoustic measures: vowel space area (VSA), and mean second formant slope (F2 slope). Vowel measures were compared between ALS with and without clinical bulbar symptoms (ALS + bulbar (n = 49, ALSFRS-r bulbar subscore: x¯ = 9.

Amyotrophic lateral sclerosis: exploring pathophysiology in the context of treatment.

Amyotrophic lateral sclerosis (ALS) is a complex, neurodegenerative disorder in which alterations in structural, physiological, and metabolic parameters act synergistically. Over the last decade there has been a considerable focus on developing drugs to slow the progression of the disease. Despite this, only four disease-modifying therapies are approved in North America.

Neuroprognostication for Patients with Amyotrophic Lateral Sclerosis: An Updated, Evidence-Based Review.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder that presents and progresses in various ways, making prognostication difficult. Several paradigms exist for providers to elucidate prognosis in a way that addresses not only the amount of time a patient has to live, but also a patient's quality of their life moving forward. Prognostication, with regard to both survivability and quality of life, is impacted by several features that include, but are not limited to, patient demographics, clinical features on presentation, and over time, access to therapy, and access to multidisciplinary clinics.

Oral Edaravone - Introducing a Flexible Treatment Option for Amyotrophic Lateral Sclerosis.

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease. While pharmacotherapy options remain limited, the Food and Drug Administration (FDA) approved intravenous (IV) and oral edaravone for the treatment of ALS in 2017 and 2022, respectively. With the addition of oral edaravone, patients with ALS may exclusively use oral medications.

The natural history of ALS: Baseline characteristics from a multicenter clinical cohort.

Background: Amyotrophic lateral sclerosis (ALS) is a rare disease with urgent need for improved treatment. Despite the acceleration of research in recent years, there is a need to understand the full natural history of the disease. As only 40% of people living with ALS are eligible for typical clinical trials, clinical trial datasets may not generalize to the full ALS population.