Involvement of the left uncinate fasciculus in the amyotrophic lateral sclerosis: an exploratory longitudinal multi-modal neuroimaging and neuropsychological study.

To investigate the microstructural integrity, tract volume analysis, and functional connectivity (FC) alterations of the left uncinate fasciculus (UF) in patients with amyotrophic lateral sclerosis (ALS) compared to healthy controls (HCs). Fourteen limb-onset ALS patients were recruited at baseline and ten at follow-up, along with 14 HCs. All participants underwent 3D T1-weighted, diffusion tensor imaging and kurtosis imaging (DTI/DKI), and resting-state functional MRI (rs-fMRI) using a 3 Tesla scanner with 64-channel coils.

The Neuroprotective Effect of the X Protein of Orthobornavirus Bornaense Type 1 in Amyotrophic Lateral Sclerosis.

In amyotrophic lateral sclerosis (ALS), early mitochondrial dysfunction may contribute to progressive motor neuron loss. Remarkably, the ectopic expression of the Orthobornavirus bornaense type 1 (BoDV-1) X protein in mitochondria blocks apoptosis and protects neurons from degeneration. Therefore, this study examines the neuroprotective effects of X protein in an ALS mouse model.

Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer's, Parkinson's, and ALS.

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression and limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, and genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene in these once-intractable conditions.

Advances and Challenges in Gene Therapy for Neurodegenerative Diseases: A Systematic Review.

This review explores recent advancements in gene therapy as a potential treatment for neurodegenerative diseases, focusing on intervention mechanisms, administration routes, and associated limitations. Following the PRISMA procedure guidelines, we systematically analyzed studies published since 2020 using the PICO framework to derive reliable conclusions. The efficacy of various gene therapies was evaluated for Parkinson's disease (n = 12), spinal muscular atrophy (n = 8), Huntington's disease (n = 3), Alzheimer's disease (n = 3), and amyotrophic lateral sclerosis (n = 6).

Immune mechanisms and shared immune targets in neurodegenerative diseases.

The immune system plays a major part in neurodegenerative diseases. In some, such as multiple sclerosis, it is the primary driver of the disease. In others, such as Alzheimer disease, amyotrophic lateral sclerosis and Parkinson disease, it has an amplifying role.

Evaluation of smartphone-based cough data in amyotrophic lateral sclerosis as a potential predictor of functional disability.

Objectives: Cough dysfunction is a feature of patients with amyotrophic lateral sclerosis (ALS). The cough sounds carry information about the respiratory system and bulbar involvement. Our goal was to explore the association between cough sound characteristics and the respiratory and bulbar functions in ALS.

Prognostic factors affecting ALS progression through disease tollgates.

Background And Objectives: Understanding factors affecting the timing of critical clinical events in ALS progression.

Methods: We captured ALS progression based on the timing of critical events (tollgates), by augmenting 6366 patients' data from the PRO-ACT database with tollgate-passed information using classification. Time trajectories of passing ALS tollgates after the first visit were derived using Kaplan-Meier analyses.

Inter-speaker acoustic differences of sustained vowels at varied dysarthria severities for amyotrophic lateral sclerosis.

We study inter-speaker acoustic differences during sustained vowel utterances at varied severities of Amyotrophic Lateral Sclerosis-induced dysarthria. Among source attributes, jitter and standard deviation of fundamental frequency exhibit enhanced inter-speaker differences among patients than healthy controls (HCs) at all severity levels. Though inter-speaker differences in vocal tract filter attributes at most severity levels are higher than those among HCs for close vowels /i/ and /u/, these are comparable with or lower than those among HCs for the relatively more open vowels /a/ and /o/.

Exercises and Brain Stimulation to Preserve Function in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.

Background And Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to the loss of motor function and muscle strength. Nonpharmacologic neuromodulative therapeutic approaches such as active exercise may contribute to preserve motor functions in ALS, but this hypothesis remains debated. The present meta-analysis first aimed to evaluate the effect of active exercise on function and muscle strength preservation.

Selective Muscle Involvement in Amyotrophic Lateral Sclerosis: Evidence Inferred from the Point of Motor Unit Firing Rates.

Introduction: The aim of the study is to determine the role of upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction as the primary initiator of distal-proximal and lateral-medial gradients of muscle involvement in amyotrophic lateral sclerosis (ALS).

Methods: Concentric needle electromyography recordings were performed in deltoid, abductor digiti minimi, and first dorsal interosseous (FDI) muscles in patients with ALS and controls during slight voluntary contraction needed to activate two motor units (MU). Five motor unit potential (MUP) pairs were recorded from each muscle.

The Causality Spectrum of Dropped Head Syndrome is Broad and Includes Myopathy, Neurodegenerative Disorders, and Varia.

Dropped head syndrome is a common complication of various neurological disorders. Most commonly, dropped head syndrome is due to primary or secondary myopathy. However, neurodegenerative diseases and various other conditions can also be complicated by dropped head syndrome.

Human iPSC-derived motor neuron innervation enhances the differentiation of muscle bundles engineered with benchtop fabrication techniques.

Engineered skeletal muscle tissues are critical tools for disease modeling, drug screening, and regenerative medicine, but are limited by insufficient maturation. Because innervation is a critical regulator of skeletal muscle development and regeneration in vivo, motor neurons are hypothesized to improve the maturity of engineered skeletal muscle tissues. Although motor neurons have been added to pre-engineered muscle constructs, the impact of motor neurons added prior to the onset of muscle differentiation has not been evaluated.

Postural Tremor Caused by Hirayama Disease Mimicking Essential Tremor.

Background: Postural tremor is a common clinical situation. Timely and accurate diagnosis is essential for effective treatment. However, clinicians often encounter difficulties distinguishing between essential tremor and other etiologies due to overlapping symptoms and atypical features.

Syringomyelia Mimicking as Bibrachial Variant of Motor Neuron Disease.

Introduction: Syringomyelia is a slowly progressive degenerative disorder of the spinal cord. Clinical features of syringomyelia vary from weakness in limbs to positive sensory symptoms and dissociative sensory loss. Thus, early and prompt diagnosis becomes crucial for reducing the morbidity associated with the disease.

Rethinking phase 2 trials in amyotrophic lateral sclerosis.

There is a long history in amyotrophic lateral sclerosis (ALS) of promoting therapies based on Phase 2 data, which then fail in Phase 3 trials. Experience suggests that studies of 6 months in duration are too short, especially with function-based outcome measures. Multiplicity poses a serious threat to data interpretation, and strategies to impute missing data may not be appropriate for ALS where progression is always expected.

Neuroprotective Effects of Dexamethasone in a Neuromelanin-Driven Parkinson's Disease Model.

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra that primarily affects movement control. Neuroinflammation plays a pivotal role in driving the disease's progression. The persistent inflammatory state in the brain exacerbates neuronal damage, creating a cycle that perpetuates the neurodegenerative process.

Semantic behavioral variant frontotemporal dementia and semantic dementia associated with mutations.

Frontotemporal dementia (FTD) is a highly heritable group of neurodegenerative disorders, characterized by varying clinical and pathological features. gene has been described worldwide within the FTD/ALS spectrum but its association with right and left temporal variant of FTD (tvFTD) is still unclear. This study aimed to reclassify a Sardinian FTD cohort according to proposed criteria for the semantic behavioral variant FTD (sbvFTD), explore mutations' association with tvFTD, and review related literature.

Antibody-Based PET Imaging of Misfolded Superoxide Dismutase 1 in an Amyotrophic Lateral Sclerosis Mouse Model.

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease characterized by motor neuron loss in the motor cortex, brain stem, and spinal cord. Mutations in the superoxide dismutase 1 (SOD1) gene, resulting in misfolding of its protein product, are a common cause of ALS. Currently, there is no approved ALS diagnostic tool.

Brain health: Pathway to primary prevention of neurodegenerative disorders of environmental origin.

While rising global rates of neurodegenerative disease encourage early diagnosis and therapeutic intervention to block clinical expression (secondary prevention), a more powerful approach is to identify and remove environmental factors that trigger long-latencybrain disease (primary prevention) by acting on a susceptible genotype or acting alone. The latter is illustrated by the post-World War II decline and disappearance of Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex (ALS/PDC), a prototypical often-familial neurodegenerative disease formerly present in very high incidence on the island of Guam. Lessons learned from 75 years of investigation on the etiology of ALS/PDC include: the importance of focusing field research on the disease epicenter and patients with early-onset disease; soliciting exposure history from patients, family, and community to guide multidisciplinary biomedical investigation; recognition that disease phenotype may vary with exposure history, and that familial brain disease may have a primarily environmental origin.

Attrition and discontinuation in amyotrophic lateral sclerosis clinical trials: a meta-analysis.

Objectives: Attrition due to adverse events and disease progression impacts the integrity and generalizability of clinical trials. The aim of this study is to provide evidence-based estimates of attrition for clinical trials in amyotrophic lateral sclerosis (ALS), and identify study-related predictors, through a comprehensive systematic review and meta-analysis.

Methods: We systematically reviewed the literature to identify all randomized, placebo-controlled clinical trials in ALS and determined the number of patients who discontinued the study per randomized arm.

Incidence and mortality of ALS: a 42-year population-based nationwide study.

Background And Aim: Recent studies have suggested that the incidence rate (IR) and the rate of death (MR) of amyotrophic lateral sclerosis (ALS) are increasing. Still, it remains unclear whether this is due to improved case ascertainment or represents a true increase. We examined the development in the incidence and mortality of ALS in Denmark for 42 years.

Exploring clinical chemistry markers in amyotrophic lateral sclerosis: insights into survival and disease trajectories.

Objective: Commonly measured clinical chemistry markers might be indicative of survival and disease progression in amyotrophic lateral sclerosis (ALS).

Methods: In a cohort study of 270 ALS patients diagnosed from April 2014 to May 2021 in Stockholm, Sweden, we examined the link between 29 clinical chemistry markers at diagnosis and mortality risk at 6 months, 1 year, and 3 years after diagnosis. Summary variables from exploratory factor analysis (EFA) assessed the markers' collective impact on survival.