Maximal and Minimal Motor Conduction Velocity in Amyotrophic Lateral Sclerosis and X-Linked Bulbospinal Muscular Atrophy Measured by Harayama’s Collision Method

Neurofilaments: light, medium, and heavy (abbreviated as NF-L, NF-M, and NF-H, respectively), which belong to Type IV intermediate filament family (IF), are neuron-specific cytoskeletal components. Neurofilaments are axonal structural components and integral components of synapses, which are important for neuronal electric signal transmissions along the axons and post-translational modification. Abnormal assembly of neurofilaments is found in several human neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), infantile spinal muscular atrophy (SMA), and hereditary sensory-motor neuropathy (HSMN). In addition, those pathological neurofilament accumulations are known in α-synuclein in Parkinson’s disease (PD), Aβ and tau in Alzheimer’s disease (AD), polyglutamine in CAG trinucleotide repeat disorders, superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP43), neuronal FUS proteins, optineurin (OPTN), ubiquilin 2 (UBQLN2), and dipeptide repeat protein (DRP) in amyotrophic lateral sclerosis (ALS). When axon damage occurs in central nervous disorders, neurofilament proteins are released and delivered into cerebrospinal fluid (CSF), which are then circulated into blood. New quantitative analyses and assay techniques are well-developed for the detection of neurofilament proteins, particularly NF-L and the phosphorylated NF-H (pNF-H) in CSF and serum. This review discusses the potential of using peripheral blood NF quantities and evaluating the severity of damage in the nervous system. Intermediate filaments could be promising biomarkers for evaluating disease progression in different nervous system disorders.

Download Full-text

Utility of Transcranial Magnetic Simulation in Studying Upper Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis

Brain Sciences ◽

10.3390/brainsci11070906 ◽

2021 ◽

Vol 11 (7) ◽

pp. 906

Author(s):

Nimeshan Geevasinga ◽

Mehdi Van den Bos ◽

Parvathi Menon ◽

Steve Vucic

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neurons ◽

Cortical Excitability ◽

Muscular Atrophy ◽

Close Relationship ◽

Bulbar Onset ◽

Als Patients ◽

Transcranial Magnetic Simulation ◽

Cortical Dysfunction ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is characterised by progressive dysfunction of the upper and lower motor neurons. The disease can evolve over time from focal limb or bulbar onset to involvement of other regions. There is some clinical heterogeneity in ALS with various phenotypes of the disease described, from primary lateral sclerosis, progressive muscular atrophy and flail arm/leg phenotypes. Whilst the majority of ALS patients are sporadic in nature, recent advances have highlighted genetic forms of the disease. Given the close relationship between ALS and frontotemporal dementia, the importance of cortical dysfunction has gained prominence. Transcranial magnetic stimulation (TMS) is a noninvasive neurophysiological tool to explore the function of the motor cortex and thereby cortical excitability. In this review, we highlight the utility of TMS and explore cortical excitability in ALS diagnosis, pathogenesis and insights gained from genetic and variant forms of the disease.

Download Full-text

Motor Unit Number Estimation in Neuromuscular Disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100008568 ◽

2008 ◽

Vol 35 (2) ◽

pp. 153-159 ◽

Cited By ~ 22

Author(s):

Omid Rashidipour ◽

K. Ming Chan

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Unit ◽

Neuromuscular Disease ◽

Muscular Atrophy ◽

Neuromuscular Diseases ◽

Neuronal Loss ◽

Response To Treatment ◽

Motor Unit Number Estimation ◽

Electrophysiological Method ◽

Lateral Sclerosis

Motor unit number estimation (MUNE) is an electrophysiological method designed to quantify motor unit loss in target muscles of interest. Most of the techniques are noninvasive and are therefore well suited for longitudinal monitoring. In this brief review, we describe the more commonly used techniques and their applications in amyotrophic lateral sclerosis, poliomyelitis, spinal muscular atrophy and hereditary sensorimotor neuropathies. Findings in some of these studies offer important pathophysiological insights. Since conventional electrophysiologic methods are not sensible measures of motor neuronal loss, MUNE could play a potentially important role in the diagnosis, monitoring of disease progression and response to treatment in neuromuscular diseases in which motor unit loss is a major feature.

Download Full-text

Use of sugammadex in a patient with progressive muscular atrophy and in a patient with amyotrophic lateral sclerosis

Medicine ◽

10.1097/md.0000000000007339 ◽

2017 ◽

Vol 96 (25) ◽

pp. e7339

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Muscular Atrophy ◽

Lateral Sclerosis ◽

Progressive Muscular Atrophy

Download Full-text

Differential motor neuron involvement in progressive muscular atrophy: a comparative study with amyotrophic lateral sclerosis

BMJ Open ◽

10.1136/bmjopen-2014-005213 ◽

2014 ◽

Vol 4 (5) ◽

pp. e005213 ◽

Cited By ~ 31

Author(s):

Yuichi Riku ◽

Naoki Atsuta ◽

Mari Yoshida ◽

Shinsui Tatsumi ◽

Yasushi Iwasaki ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Comparative Study ◽

Motor Neuron ◽

Muscular Atrophy ◽

Lateral Sclerosis ◽

Progressive Muscular Atrophy

Download Full-text

Multi-Study Proteomic and Bioinformatic Identification of Molecular Overlap between Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA)

Brain Sciences ◽

10.3390/brainsci8120212 ◽

2018 ◽

Vol 8 (12) ◽

pp. 212 ◽

Cited By ~ 4

Author(s):

Darija Šoltić ◽

Melissa Bowerman ◽

Joanne Stock ◽

Hannah Shorrock ◽

Thomas Gillingwater ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Spinal Muscular Atrophy ◽

Calcium Binding ◽

Bioinformatics Analysis ◽

Muscular Atrophy ◽

Molecular Pathways ◽

Motor Neuron Degeneration ◽

Neuron Degeneration ◽

Therapeutic Development ◽

Lateral Sclerosis

Unravelling the complex molecular pathways responsible for motor neuron degeneration in amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) remains a persistent challenge. Interest is growing in the potential molecular similarities between these two diseases, with the hope of better understanding disease pathology for the guidance of therapeutic development. The aim of this study was to conduct a comparative analysis of published proteomic studies of ALS and SMA, seeking commonly dysregulated molecules to be prioritized as future therapeutic targets. Fifteen proteins were found to be differentially expressed in two or more proteomic studies of both ALS and SMA, and bioinformatics analysis identified over-representation of proteins known to associate in vesicles and molecular pathways, including metabolism of proteins and vesicle-mediated transport—both of which converge on endoplasmic reticulum (ER)-Golgi trafficking processes. Calreticulin, a calcium-binding chaperone found in the ER, was associated with both pathways and we independently confirm that its expression was decreased in spinal cords from SMA and increased in spinal cords from ALS mice. Together, these findings offer significant insights into potential common targets that may help to guide the development of new therapies for both diseases.

Download Full-text

Diffusion-Tensor MR Imaging of Corticospinal Tract in Amyotrophic Lateral Sclerosis and Progressive Muscular Atrophy

Radiology ◽

10.1148/radiol.2371041506 ◽

2005 ◽

Vol 237 (1) ◽

pp. 258-264 ◽

Cited By ~ 109

Author(s):

Mirco Cosottini ◽

Marco Giannelli ◽

Gabriele Siciliano ◽

Guido Lazzarotti ◽

Maria Chiara Michelassi ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Mr Imaging ◽

Corticospinal Tract ◽

Diffusion Tensor ◽

Muscular Atrophy ◽

Diffusion Tensor Mr Imaging ◽

Lateral Sclerosis ◽

Progressive Muscular Atrophy

Download Full-text

The motor neurone disorders

10.1093/med/9780198569381.003.0524 ◽

2011 ◽

Author(s):

Pamela Shaw

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Muscular Atrophy ◽

Motor Neurone ◽

System Control ◽

Loss Of Function ◽

The United Kingdom ◽

System Degeneration ◽

Motor Neurones ◽

Related Group ◽

Lateral Sclerosis

The motor neurone diseases are a group of disorders in which there is selective loss of function of upper and/or lower motor neurones in the motor cortex, brainstem, and spinal cord resulting in impairment in the nervous system control of voluntary movement. The term ‘motor neurone disease’, often abbreviated to ‘MND’, is used differently in different countries. In the United Kingdom it is used as an umbrella term to cover the related group of neurodegenerative disorders including amyotrophic lateral sclerosis, the commonest variant, as well as progressive muscular atrophy, primary lateral sclerosis, and progressive bulbar palsy. However, in many other countries amyotrophic lateral sclerosis, referred to as ALS, has been adopted as the umbrella term for this group of clinical variants of motor system degeneration. There is a tendency now internationally to use the ALS/MND abbreviation to cover this group of conditions. Careful diagnosis within the motor neurone diseases is essential for advising about prognosis, potential genetic implications, and for identifying those with acquired lower motor neurone syndromes who may benefit for the administration of immunomodulatory therapy.

Download Full-text

Beyond the Traditional Clinical Trials for Amyotrophic Lateral Sclerosis and The Future Impact of Gene Therapy

Journal of Neuromuscular Diseases ◽

10.3233/jnd-200531 ◽

2021 ◽

Vol 8 (1) ◽

pp. 25-38

Author(s):

Marisa Cappella ◽

Pierre-François Pradat ◽

Giorgia Querin ◽

Maria Grazia Biferi

Keyword(s):

Gene Therapy ◽

Clinical Trials ◽

Amyotrophic Lateral Sclerosis ◽

Muscular Atrophy ◽

Monogenic Disease ◽

Sporadic Als ◽

Pathological Mechanism ◽

Huge Impact ◽

Als Patients ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating and incurable motor neuron (MN) disorder affecting both upper and lower MNs. Despite impressive advances in the understanding of the disease’s pathological mechanism, classical pharmacological clinical trials failed to provide an efficient cure for ALS over the past twenty years. Two different gene therapy approaches were recently approved for the monogenic disease Spinal muscular atrophy, characterized by degeneration of lower MNs. This milestone suggests that gene therapy-based therapeutic solutions could be effective for the treatment of ALS. This review summarizes the possible reasons for the failure of traditional clinical trials for ALS. It provides then a focus on the advent of gene therapy approaches for hereditary forms of ALS. Specifically, it describes clinical use of antisense oligonucleotides in three familial forms of ALS, caused by mutations in SOD1, C9orf72 and FUS genes, respectively.. Clinical and pre-clinical studies based on AAV-mediated gene therapy approaches for both familial and sporadic ALS cases are presented as well. Overall, this overview highlights the potential of gene therapy as a transforming technology that will have a huge impact on treatment perspective for ALS patients and on the design of future clinical trials.

Download Full-text