Motor Neuron Diseases

The motor neuron disorders are a clinically diverse group of diseases that share a pathologic loss of the motor neurons. The most common adult-onset disorder is amyotrophic lateral sclerosis (ALS). Other forms include the spinal muscular atrophies, infectious motor neuronopathies, and rare focal forms of anterior horn cell loss.Overall, the incidence rate of ALS is believed to be 1.5 to 2.0 cases per 100,000 person-years, and the prevalence rate is 4 to 6 cases per 100,000 population. Other than in sparsely populated geographic clusters (eg, Guam and the Kii Peninsula of Japan), the incidence rate seems consistent across ethnic and geographic boundaries.

A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS

Journal of Personalized Medicine ◽

10.3390/jpm10030058 ◽

2020 ◽

Vol 10 (3) ◽

pp. 58 ◽

Cited By ~ 2

Author(s):

Owen Connolly ◽

Laura Le Gall ◽

Gavin McCluskey ◽

Colette G Donaghy ◽

William J Duddy ◽

...

Keyword(s):

Systematic Review ◽

Respiratory Failure ◽

Motor Neuron ◽

Motor Neurons ◽

Disease Duration ◽

Phenotype Correlation ◽

Motor Neuron Diseases ◽

Relationship Of ◽

Amyotrophic lateral sclerosis is a rare and fatal neurodegenerative disease characterised by progressive deterioration of upper and lower motor neurons that eventually culminates in severe muscle atrophy, respiratory failure and death. There is a concerning lack of understanding regarding the mechanisms that lead to the onset of ALS and as a result there are no reliable biomarkers that aid in the early detection of the disease nor is there an effective treatment. This review first considers the clinical phenotypes associated with ALS, and discusses the broad categorisation of ALS and ALS-mimic diseases into upper and lower motor neuron diseases, before focusing on the genetic aetiology of ALS and considering the potential relationship of mutations of different genes to variations in phenotype. For this purpose, a systematic review is conducted collating data from 107 original published clinical studies on monogenic forms of the disease, surveying the age and site of onset, disease duration and motor neuron involvement. The collected data highlight the complexity of the disease’s genotype–phenotype relationship, and thus the need for a nuanced approach to the development of clinical assays and therapeutics.

Ubiquitin-positive inclusion in anterior horn cells in subgroups of motor neuron diseases: A comparative study of adult-onset amyotrophic lateral sclerosis, juvenile amyotrophic lateral sclerosis and werdnig-hoffmann disease

Journal of the Neurological Sciences ◽

10.1016/0022-510x(93)90226-o ◽

1993 ◽

Vol 115 (2) ◽

pp. 208-213 ◽

Cited By ~ 25

Author(s):

Sadayuki Matsumoto ◽

Satoshi Goto ◽

Hirofumi Kusaka ◽

Terukuni Imai ◽

Nobuyuki Murakami ◽

...

Keyword(s):

Comparative Study ◽

Motor Neuron ◽

Anterior Horn ◽

Adult Onset ◽

Motor Neuron Diseases ◽

Anterior Horn Cells ◽

Juvenile Amyotrophic Lateral Sclerosis ◽

Lateral Sclerosis ◽

Werdnig Hoffmann

A review: Management of motor neuron diseases

IP Indian Journal of Neurosciences ◽

10.18231/j.ijn.2021.053 ◽

2022 ◽

Vol 7 (4) ◽

pp. 292-294

Author(s):

Aarti Chopra ◽

Ravi Kumar ◽

Girendra Kumar Gautam

Keyword(s):

Motor Neuron ◽

Motor Neurons ◽

Age At Onset ◽

Motor Neuron Diseases ◽

Progressive Degeneration ◽

Review Management ◽

The Central Nervous System ◽

Motor neuron diseases are a group of chronic sporadic and hereditary neurological disorders characterized by progressive degeneration of motor neurons. These might affect the upper motor neurons, lower motor neurons, or both. The prognosis of the motor neuron disease depends upon the age at onset and the area of the central nervous system affected. Amyotrophic lateral sclerosis (ALS) has been documented to be fatal within three years of onset. This activity focuses on amyotrophic lateral sclerosis as the prototype of MND, which affects both the upper and the lower motor neurons and discusses the role of inter-professional team in the differential diagnosis, evaluation, treatment, and prognostication. It also discusses various other phenotypes of MND with an emphasis on their distinguishing features in requisite detail.

Types of Motor Neuron Diseases

10.1093/med/9780199937837.003.0022 ◽

2017 ◽

Author(s):

Nimish Thakore ◽

Erik P Pioro

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neuron ◽

Motor Neuron Disease ◽

Motor Neurons ◽

Muscular Atrophy ◽

Motor Neuron Diseases ◽

The Subject ◽

Upper Motor Neurons ◽

Disorders of lower motor neurons (LMNs, or anterior horn cells) and upper motor neurons (UMNs), jointly termed motor neuron disorders (MNDs), are diverse and numerous. The prototypical MND, namely amyotrophic lateral sclerosis (ALS), a relentlessly progressive lethal disorder of adults, is the subject of another section and will not be discussed further here. Other MNDs include spinal muscular atrophy (SMA), of which there are four types: Kennedy’s disease, Brown-Violetto-Van Laere, and Fazio-Londe syndromes, lower motor neuron disorders as part of neurodegenerations and secondary motor neuron disease as part of malignancy, radiation and infection.

Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases

Neurology Research International ◽

10.1155/2012/498428 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 34

Author(s):

Asako Otomo ◽

Lei Pan ◽

Shinji Hadano

Keyword(s):

Motor Neuron ◽

Motor Neurons ◽

Protein Misfolding ◽

Disease Onset ◽

Ubiquitin Proteasome System ◽

Protective Role ◽

Motor Neuron Diseases ◽

Ubiquitin Proteasome ◽

Amyotrophic lateral sclerosis (ALS) is a heterogeneous group of incurable motor neuron diseases (MNDs) characterized by a selective loss of upper and lower motor neurons in the brain and spinal cord. Most cases of ALS are sporadic, while approximately 5–10% cases are familial. More than 16 causative genes for ALS/MNDs have been identified and their underlying pathogenesis, including oxidative stress, endoplasmic reticulum stress, excitotoxicity, mitochondrial dysfunction, neural inflammation, protein misfolding and accumulation, dysfunctional intracellular trafficking, abnormal RNA processing, and noncell-autonomous damage, has begun to emerge. It is currently believed that a complex interplay of multiple toxicity pathways is implicated in disease onset and progression. Among such mechanisms, ones that are associated with disturbances of protein homeostasis, the ubiquitin-proteasome system and autophagy, have recently been highlighted. Although it remains to be determined whether disease-associated protein aggregates have a toxic or protective role in the pathogenesis, the formation of them results from the imbalance between generation and degradation of misfolded proteins within neuronal cells. In this paper, we focus on the autophagy-lysosomal and endocytic degradation systems and implication of their dysfunction to the pathogenesis of ALS/MNDs. The autophagy-endolysosomal pathway could be a major target for the development of therapeutic agents for ALS/MNDs.

Cardiac Failure as an Unusual Presentation in a Patient with History of Amyotrophic Lateral Sclerosis

Case Reports in Neurological Medicine ◽

10.1155/2014/986139 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Mohammad Hasan Namazi ◽

Isa Khaheshi ◽

Habib Haybar ◽

Shooka Esmaeeli

Keyword(s):

Motor Neuron ◽

Motor Neurons ◽

Cardiac Failure ◽

Unusual Case ◽

Chief Complaint ◽

Pathogenetic Mechanism ◽

Motor Neuron Diseases ◽

History Of ◽

Amyotrophic lateral sclerosis (ALS) is the most well-known form of motor neuron diseases in which both upper and lower motor neurons are involved in this disease. We presented an unusual case of ALS whom had presented with chief complaint of dyspnea. Cardiac failure was diagnosed at the final stage of the ALS disease. The pathogenetic mechanism leading to an elevated occurrence of cardiomyopathy in ALS is not comprehensible. Dilated cardiomyopathy has been explained in some previous studies. Based on the collected data, it was hypothesized that cardiomyopathy is underdiagnosed in the ALS population, probably because symptoms are masqueraded as a result of the patients’ disability. It was suggested that in all motor neuron diseases a serial cardiological evaluation should be executed, including annual echocardiography.

Motor Neuron Diseases and Neuroprotective Peptides: A Closer Look to Neurons

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.723871 ◽

2021 ◽

Vol 13 ◽

Author(s):

Emanuela Zuccaro ◽

Diana Piol ◽

Manuela Basso ◽

Maria Pennuto

Keyword(s):

Motor Neuron ◽

Motor Neurons ◽

Muscular Atrophy ◽

Selective Vulnerability ◽

Therapeutic Interventions ◽

Motor Neuron Diseases ◽

Somatomedin C ◽

Beneficial Effects ◽

Pituitary Adenylate Cyclase ◽

Motor neurons (MNs) are specialized neurons responsible for muscle contraction that specifically degenerate in motor neuron diseases (MNDs), such as amyotrophic lateral sclerosis (ALS), spinal and bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). Distinct classes of MNs degenerate at different rates in disease, with a particular class named fast-fatigable MNs (FF-MNs) degenerating first. The etiology behind the selective vulnerability of FF-MNs is still largely under investigation. Among the different strategies to target MNs, the administration of protective neuropeptides is one of the potential therapeutic interventions. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with beneficial effects in many neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and more recently SBMA. Another neuropeptide that has a neurotrophic effect on MNs is insulin-like growth factor 1 (IGF-1), also known as somatomedin C. These two peptides are implicated in the activation of neuroprotective pathways exploitable in the amelioration of pathological outcomes related to MNDs.

Faculty Opinions recommendation of Therapeutic vaccine for acute and chronic motor neuron diseases: implications for amyotrophic lateral sclerosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1013340.190153 ◽

2003 ◽

Author(s):

Angela Vincent

Keyword(s):

Motor Neuron ◽

Therapeutic Vaccine ◽

Motor Neuron Diseases ◽

Lipidomics study of plasma from patients suggest that ALS and PLS are part of a continuum of motor neuron disorders

Scientific Reports ◽

10.1038/s41598-021-92112-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Estela Area-Gomez ◽

D. Larrea ◽

T. Yun ◽

Y. Xu ◽

J. Hupf ◽

...

Keyword(s):

Motor Neuron ◽

Motor Neurons ◽

Cell Structure ◽

Disease Onset ◽

Point Of View ◽

Motor Dysfunction ◽

Cellular Processes ◽

Progressive Muscle Weakness ◽

Human Pathology ◽

AbstractMotor neuron disorders (MND) include a group of pathologies that affect upper and/or lower motor neurons. Among them, amyotrophic lateral sclerosis (ALS) is characterized by progressive muscle weakness, with fatal outcomes only in a few years after diagnosis. On the other hand, primary lateral sclerosis (PLS), a more benign form of MND that only affects upper motor neurons, results in life-long progressive motor dysfunction. Although the outcomes are quite different, ALS and PLS present with similar symptoms at disease onset, to the degree that both disorders could be considered part of a continuum. These similarities and the lack of reliable biomarkers often result in delays in accurate diagnosis and/or treatment. In the nervous system, lipids exert a wide variety of functions, including roles in cell structure, synaptic transmission, and multiple metabolic processes. Thus, the study of the absolute and relative concentrations of a subset of lipids in human pathology can shed light into these cellular processes and unravel alterations in one or more pathways. In here, we report the lipid composition of longitudinal plasma samples from ALS and PLS patients initially, and after 2 years following enrollment in a clinical study. Our analysis revealed common aspects of these pathologies suggesting that, from the lipidomics point of view, PLS and ALS behave as part of a continuum of motor neuron disorders.

Poor Corticospinal Motor Neuron Health Is Associated with Increased Symptom Severity in the Acute Phase Following Repetitive Mild TBI and Predicts Early ALS Onset in Genetically Predisposed Rodents

Brain Sciences ◽

10.3390/brainsci11020160 ◽

2021 ◽

Vol 11 (2) ◽

pp. 160

Author(s):

Mor R. Alkaslasi ◽

Noell E. Cho ◽

Navpreet K. Dhillon ◽

Oksana Shelest ◽

Patricia S. Haro-Lopez ◽

...

Keyword(s):

Risk Factor ◽

Motor Neuron ◽

Motor Neurons ◽

Disease Onset ◽

Poor Health ◽

Disease Symptoms ◽

Established Risk Factor ◽

Early Injury ◽

Corticospinal Motor Neurons ◽

Traumatic brain injury (TBI) is a well-established risk factor for several neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease, however, a link between TBI and amyotrophic lateral sclerosis (ALS) has not been clearly elucidated. Using the SOD1G93A rat model known to recapitulate the human ALS condition, we found that exposure to mild, repetitive TBI lead ALS rats to experience earlier disease onset and shortened survival relative to their sham counterparts. Importantly, increased severity of early injury symptoms prior to the onset of ALS disease symptoms was linked to poor health of corticospinal motor neurons and predicted worsened outcome later in life. Whereas ALS rats with only mild behavioral injury deficits exhibited no observable changes in corticospinal motor neuron health and did not present with early onset or shortened survival, those with more severe injury-related deficits exhibited alterations in corticospinal motor neuron health and presented with significantly earlier onset and shortened lifespan. While these studies do not imply that TBI causes ALS, we provide experimental evidence that head injury is a risk factor for earlier disease onset in a genetically predisposed ALS population and is associated with poor health of corticospinal motor neurons.