Quantitative and Computational Spinal Imaging in Neurodegenerative Conditions and Acquired Spinal Disorders: Academic Advances and Clinical Prospects.

Quantitative spinal cord imaging has facilitated the objective appraisal of spinal cord pathology in a range of neurological conditions both in the academic and clinical setting. Diverse methodological approaches have been implemented, encompassing a range of morphometric, diffusivity, susceptibility, magnetization transfer, and spectroscopy techniques. Advances have been fueled both by new MRI platforms and acquisition protocols as well as novel analysis pipelines.

Enhanced Age-Dependent Motor Impairment in Males of Modeling Spinocerebellar Ataxia Type 1 Is Linked to Dysregulation of a Matrix Metalloproteinase.

Over the past two decades, has proven to be successful in modeling the polyglutamine (polyQ) (caused by CAG repeats) family of neurodegenerative disorders, including the faithful recapitulation of pathological features such as polyQ length-dependent formation of protein aggregates and progressive neuronal degeneration. In this study, pan-neuronal expression of human with long polyQ repeat of 82 amino acids was driven using an elav-GAL4 driver line. This would essentially model the polyQ disease spinocerebellar ataxia type 1 (SCA1).

Tracing ALS Degeneration: Insights from Spinal Cord and Cortex Transcriptomes.

Background/objectives: Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons. Key factors contributing to neuronal death include mitochondrial energy damage, oxidative stress, and excitotoxicity. The frontal cortex is crucial for action initiation, planning, and voluntary movements whereas the spinal cord facilitates communication with the brain, walking, and reflexes.

Hereditary Neuromuscular Disorders in Reproductive Medicine.

Neuromuscular disorders (NMDs) encompass a broad range of hereditary and acquired conditions that affect motor units, significantly impacting patients' quality of life and reproductive health. This narrative review aims to explore in detail the reproductive challenges associated with major hereditary NMDs, including Charcot-Marie-Tooth disease (CMT), dystrophinopathies, Myotonic Dystrophy (DM), Facioscapulohumeral Muscular Dystrophy (FSHD), Spinal Muscular Atrophy (SMA), Limb-Girdle Muscular Dystrophy (LGMD), and Amyotrophic Lateral Sclerosis (ALS). Specifically, it discusses the stages of diagnosis and genetic testing, recurrence risk estimation, options for preimplantation genetic testing (PGT) and prenatal diagnosis (PND), the reciprocal influence between pregnancy and disease, potential obstetric complications, and risks to the newborn.

SMN Deficiency Induces an Early Non-Atrophic Myopathy with Alterations in the Contractile and Excitatory Coupling Machinery of Skeletal Myofibers in the SMN∆7 Mouse Model of Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is caused by a deficiency of the ubiquitously expressed survival motor neuron (SMN) protein. The main pathological hallmark of SMA is the degeneration of lower motor neurons (MNs) with subsequent denervation and atrophy of skeletal muscle. However, increasing evidence indicates that low SMN levels not only are detrimental to the central nervous system (CNS) but also directly affect other peripheral tissues and organs, including skeletal muscle.

Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.

Pathological aggregation of a specific protein into insoluble aggregates is a common hallmark of various neurodegenerative diseases (NDDs). In the earlier literature, each NDD is characterized by the aggregation of one or two pathogenic proteins, which can serve as disease-specific biomarkers. The aggregation of these specific proteins is thought to be a major cause of or deleterious result in most NDDs.

Identification of Biochemical Determinants for Diagnosis and Prediction of Severity in 5q Spinal Muscular Atrophy Using H-Nuclear Magnetic Resonance Metabolic Profiling in Patient-Derived Biofluids.

This study explores the potential of H-NMR spectroscopy-based metabolic profiling in various biofluids as a diagnostic and predictive modality to assess disease severity in individuals with 5q spinal muscular atrophy. A total of 213 biosamples (urine, plasma, and CSF) from 153 treatment-naïve patients with SMA across five German centers were analyzed using H-NMR spectroscopy. Prediction models were developed using machine learning algorithms which enabled the patients with SMA to be grouped according to disease severity.

Gold Coast Criteria in ALS Diagnosis: A Real-World Experience.

Revised El Escorial (rEEC) and Awaji criteria are currently used for diagnosing and categorizing amyotrophic lateral sclerosis (ALS). However, they are complex; their sensitivity is still not optimal for research purposes, and they present high inter-rater variability in clinical practice. To address these points, in 2019, a new set of diagnostic criteria was proposed, namely the Gold Coast criteria (GCC), characterized by a dichotomous diagnostic categorization, i.

MicroRNAs as Biomarkers in Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by the loss of the survival motor neuron (SMN) protein, leading to degeneration of anterior motor neurons and resulting in progressive muscle weakness and atrophy. Given that SMA has a single, well-defined genetic cause, gene-targeted therapies have been developed, aiming to increase SMN production in SMA patients. The SMN protein is likely involved in the synthesis of microRNAs (miRNAs), and dysregulated miRNA expression is increasingly associated with the pathophysiology of SMA.

Exogenous α-Synuclein Induces Oxidative Damage to Dopaminergic Neurons Through p-NMDAR2B/Nur77.

Alpha-synuclein (α-syn) is a major pathological marker of Parkinson's disease (PD), and its abnormal expression and aggregation lead to dopaminergic neuron degeneration, in which oxidative stress plays an important role. However, the exact molecular mechanism by which α-syn causes PD remains unclear. In this study, exogenous α-syn, also known as α-syn preformed fibrils (α-syn PFFs), was used to construct in vivo and in vitro models of PD.

Impairments of inhibitory neurons in amyotrophic lateral sclerosis and frontotemporal dementia.

Amyotrophic lateral sclerosis and frontotemporal dementia are two fatal neurodegenerative disorders. They are part of a pathophysiological continuum, displaying clinical, neuropathological, and genetic overlaps. There is compelling evidence that neuronal circuit dysfunction is an early feature of both diseases.

Functional Outcome Measures to Optimize Drug Development in Spinal and Bulbar Muscular Atrophy: Results From a Meta-Analysis of the Global SBMA Dataset.

Background And Objectives: Spinal and bulbar muscular atrophy (SBMA) is a rare, slowly progressive, and debilitating disease without effective treatments available. Lack of reliable biomarkers and sensitive outcome measures makes clinical research conduct challenging. The primary objective of this study was to identify clinically meaningful and statistically sensitive outcome measures enabling the evaluation of therapeutic interventions in late-stage clinical trials.

STEED: A data mining tool for automated extraction of experimental parameters and risk of bias items from in vivo publications.

Background And Methods: Systematic reviews, i.e., research summaries that address focused questions in a structured and reproducible manner, are a cornerstone of evidence-based medicine and research.

A Case Series Examining Clinic, Laboratory, and Physical Function After Administration of Nusinersen in Adults With Spinal Muscular Atrophy, a Single-Center Study.

Spinal muscular atrophy is an incurable inherited disease caused by lower motor neuron death from mutations of the survival motor neuron genes. Intrathecal therapy with the antisense oligonucleotide, nusinersen, has been demonstrated to be beneficial in children with this disease, but the experience in adults, particularly ambulatory patients, is limited. We present a prospective observational case series from a single center using nusinersen therapy where we categorize 6 adult patients with spinal muscular atrophy into 2 functional categories: ambulatory (n = 3) or nonambulatory (n = 3).

Comparative Blood Profiling Based on ATR-FTIR Spectroscopy and Chemometrics for Differential Diagnosis of Patients with Amyotrophic Lateral Sclerosis-Pilot Study.

Amyotrophic lateral sclerosis (ALS) is a motor neurodegenerative disease characterized by poor prognosis. Currently, screening and diagnostic methods for ALS remain challenging, often leading to diagnosis at an advanced stage of the disease. This delay hinders the timely initiation of therapy, negatively impacting patient well-being.

Concomitant telomere attrition is associated with spinal muscular atrophy in highly inbred region of North India: unraveling the thread in Kashmir region.

Spinal muscular atrophy (SMA) is a rare genetic disorder that unequivocally results in the degeneration of motor neurons, leading to muscle weakness and atrophy. This condition is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which inevitably results in a deficiency of the SMN protein. In present study, we investigated the potential role of telomere attrition in SMA patients.

Efficacy of Nusinersen Treatment in Type 1, 2, and 3 Spinal Muscular Atrophy: Real-World Data from a Single-Center Study.

Background: Spinal muscular atrophy (SMA) is an inherited neuromuscular disease characterized by progressive muscle weakness and atrophy due to the absence of the survival motor neuron 1 () gene. SMA is classified into types 0 through 4 based on the age of symptom onset and the severity of motor function decline. Recent advances in SMA treatment, including nusinersen, onasemnogene abeparvovec, and risdiplam, have significantly improved the prognosis of SMA patients.

Development and validation of a one-step assay for genetic testing in spinal muscular atrophy MALDI-TOF MS.

Spinal muscular atrophy (SMA) is a fatal neuromuscular disorder primarily attributed to the homozygous deletion of the survival motor neuron 1 () gene, with disease severity closely correlated to the copy number variations (CNV) of . Conventional methodologies, however, fail to provide a comprehensive gene overview of and are often both time-intensive and costly. In this study, we present a novel one-step MALDI-TOF MS assay for SMA gene testing.

Muscle ultrasound aids diagnosis in amyotrophic lateral sclerosis.

Objective: There is a need for improved diagnostic tools in Amyotrophic Lateral Sclerosis (ALS). Our objective was to assess muscle ultrasound as a diagnostic tool in patients with ALS and determine a simplified screening protocol to aid implementation in clinical practice.

Methods: Ultrasound of bulbar and limb muscles was prospectively performed on all patients referred to a single centre with suspected ALS.