scholarly journals Adipsin, MIP-1b, and IL-8 as CSF Biomarker Panels for ALS Diagnosis

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Maria Teresa Gonzalez-Garza ◽  
Hector Ramon Martinez ◽  
Delia E. Cruz-Vega ◽  
Martin Hernandez-Torre ◽  
Jorge E. Moreno-Cuevas
Keyword(s):  
Motor Neurons ◽  
Rating Scales ◽  
Neurodegenerative Disorder ◽  
Panel Analysis ◽  
Therapeutic Approaches ◽  
Reliable Diagnosis ◽  
Als Patients ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is an aggressive neurodegenerative disorder that selectively attacks motor neurons in the brain and spinal cord. Despite important advances in the knowledge of the etiology and progression of the disease, there are still no solid grounds in which a clinician could make an early objective and reliable diagnosis from which patients could benefit. Diagnosis is difficult and basically made by clinical rating scales (ALSRs and El Escorial). The possible finding of biomarkers to aid in the early diagnosis and rate of disease progression could serve for future innovative therapeutic approaches. Recently, it has been suggested that ALS has an important immune component that could represent either the cause or the consequence of the disease. In this report, we analyzed 19 different cytokines and growth factors in the cerebrospinal fluid of 77 ALS patients and 13 controls by decision tree and PanelomiX program. Results showed an increase of Adipsin, MIP-1b, and IL-6, associated with a decrease of IL-8 thresholds, related with ALS patients. This biomarker panel analysis could represent an important aid for diagnosis of ALS alongside the clinical and neurophysiological criteria.

Potential skin involvement in ALS: revisiting Charcot’s observation – a review of skin abnormalities in ALS

2017 ◽  
Vol 28 (5) ◽  
pp. 551-572 ◽  
Author(s):  
Bastien Paré ◽  
François Gros-Louis
Keyword(s):  
Motor Neurons ◽  
Skin Changes ◽  
Embryonic Origin ◽  
Skin Abnormalities ◽  
Als Patients ◽  
The 19Th Century ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons of the brain and spinal cord, leading to progressive paralysis and death. Interestingly, many skin changes have been reported in ALS patients, but never as yet fully explained. These observations could be due to the common embryonic origin of the skin and neural tissue known as the ectodermal germ layer. Following the first observation in ALS patients’ skin by Dr Charcot in the 19th century, in the absence of bedsores unlike other bedridden patients, other morphological and molecular changes have been observed. Thus, the skin could be of interest in the study of ALS and other neurodegenerative diseases. This review summarizes skin changes reported in the literature over the years and discusses about a novelin vitroALS tissue-engineered skin model, derived from patients, for the study of ALS.

scholarly journals Death Receptors in the Selective Degeneration of Motoneurons in Amyotrophic Lateral Sclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Julianne Aebischer ◽  
Nathalie Bernard-Marissal ◽  
Brigitte Pettmann ◽  
Cédric Raoul
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Immune Cells ◽  
Microglial Activation ◽  
Death Receptors ◽  
Strong Body ◽  
Als Patients ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Lateral Sclerosis

While studies on death receptors have long been restricted to immune cells, the last decade has provided a strong body of evidence for their implication in neuronal death and hence neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). ALS is a fatal paralytic disorder that primarily affects motoneurons in the brain and spinal cord. A neuroinflammatory process, associated with astrocyte and microglial activation as well as infiltration of immune cells, accompanies motoneuron degeneration and supports the contribution of non-cell-autonomous mechanisms in the disease. Hallmarks of Fas, TNFR, LT-βR, and p75NTR signaling have been observed in both animal models and ALS patients. This review summarizes to date knowledge of the role of death receptors in ALS and the link existing between the selective loss of motoneurons and neuroinflammation. It further suggests how this recent evidence could be included in an ultimate multiapproach to treat patients.

scholarly journals Utility of phrenic nerve ultrasound in amyotrophic lateral sclerosis

2020 ◽  
Author(s):  
Cezar Thomas Suratos ◽  
Naoko Takamatsu ◽  
Hiroki Yamazaki ◽  
Yusuke Osaki ◽  
Tatsuya Fukumoto ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Phrenic Nerve ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Pulmonary Function Tests ◽  
Cross Sectional ◽  
The Right ◽  
Als Patients ◽  
Lateral Sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the upper and lower motor neurons causing progressive weakness. It eventually involves the diaphragm which leads to respiratory paralysis and subsequently death. Phrenic nerve (PN) conduction studies and diaphragm ultrasound has been studied and correlated with pulmonary function tests in ALS patients. However, PN ultrasonography has not been employed in ALS. This study aims to sonographically evaluate the morphologic appearance of the PN of ALS patients. Thirty-eight ALS patients and 28 normal controls referred to the neurophysiology laboratory of two institutions were retrospectively included in the study. Baseline demographic and clinical variables such as disease duration, ALS Functional Rating Scale-Revised score, and ALS region of onset were collected. Ultrasound was used to evaluate the PN cross-sectional area (CSA) of ALS and control subjects. The mean PN CSA of ALS patients were 1.08 ± 0.39 mm on the right and 1.02 ± 0.34 mm on the left. The PN CSA of ALS patients were significantly decreased compared to controls (p value < 0.00001). The PN CSA of ALS patients was not correlated to any of the demographic and clinical parameters tested. This study demonstrates that ALS patients have a smaller PN size compared to controls using ultrasonography.

scholarly journals Pain in Amyotrophic Lateral Sclerosis: A Neglected Aspect of Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Chalonda R. Handy ◽  
Christina Krudy ◽  
Nicholas Boulis ◽  
Thais Federici
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Viral Vectors ◽  
Neurodegenerative Disorder ◽  
Respiratory Dysfunction ◽  
Clostridial Neurotoxins ◽  
Reduction Of Pain ◽  
Als Patients ◽  
Number Of Individuals ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive loss of motor neurons, muscle wasting, and respiratory dysfunction. With disease progression, secondary symptoms arise creating new problematic conditions for ALS patients. Amongst these is pain. Although not a primary consequence of disease, pain occurs in a substantial number of individuals. Yet, studies investigating its pathomechanistic properties in the ALS patient are lacking. Therefore, more exploratory efforts into its scope, severity, impact, and treatment should be initiated. Several studies investigating the use of Clostridial neurotoxins for the reduction of pain in ALS patients suggest the potential for a neural specific approach involving focal drug delivery. Gene therapy represents a way to accomplish this. Therefore, the use of viral vectors to express transgenes that modulate the nociceptive cascade could prove to be an effective way to achieve meaningful benefit in conditions of pain in ALS.

Role of transition metals in the pathogenesis of amyotrophic lateral sclerosis

2008 ◽  
Vol 36 (6) ◽  
pp. 1322-1328 ◽  
Author(s):  
Willianne I.M. Vonk ◽  
Leo W.J. Klomp
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Transition Metals ◽  
Motor Neurons ◽  
Neurodegenerative Disorder ◽  
Sod1 Gene ◽  
Brain And Spinal Cord ◽  
Lateral Sclerosis

ALS (amyotrophic lateral sclerosis) is a devastating progressive neurodegenerative disorder resulting in selective degeneration of motor neurons in brain and spinal cord and muscle atrophy. In approx. 2% of all cases, the disease is caused by a mutation in the Cu,Zn-superoxide dismutase (SOD1) gene. The transition metals zinc and copper regulate SOD1 protein stability and activity, and disbalance of the homoeostasis of these metals has therefore been implicated in the pathogenesis of ALS. Recent data strengthen the hypothesis that these transition metals are excellent potential targets to develop an effective therapy for ALS.

scholarly journals Implications of Selective Autophagy Dysfunction for ALS Pathology

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 381 ◽  
Author(s):  
Emiliano Vicencio ◽  
Sebastián Beltrán ◽  
Luis Labrador ◽  
Patricio Manque ◽  
Melissa Nassif ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Neurodegenerative Disorder ◽  
Cellular Mechanisms ◽  
Selective Autophagy ◽  
Neurodegenerative Process ◽  
Sporadic Cases ◽  
Protein Components ◽  
Als Patients ◽  
Brain And Spinal Cord

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder that progressively affects motor neurons in the brain and spinal cord. Due to the biological complexity of the disease, its etiology remains unknown. Several cellular mechanisms involved in the neurodegenerative process in ALS have been found, including the loss of RNA and protein homeostasis, as well as mitochondrial dysfunction. Insoluble protein aggregates, damaged mitochondria, and stress granules, which contain RNA and protein components, are recognized and degraded by the autophagy machinery in a process known as selective autophagy. Autophagy is a highly dynamic process whose dysregulation has now been associated with neurodegenerative diseases, including ALS, by numerous studies. In ALS, the autophagy process has been found deregulated in both familial and sporadic cases of the disease. Likewise, mutations in genes coding for proteins involved in the autophagy machinery have been reported in ALS patients, including selective autophagy receptors. In this review, we focus on the role of selective autophagy in ALS pathology.

Ice Bucket At First…and then? – Psychopathology in Amyotrophic Lateral Sclerosis Patients and their Caregivers, a Review

2016 ◽  
Vol 33 (S1) ◽  
pp. S529-S529
Author(s):  
A.R. Figueiredo ◽  
V. Espírito Santo ◽  
R. Almendra ◽  
A. Costa
Keyword(s):  
Social Support ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Neurodegenerative Disorder ◽  
Psychological Adaptation ◽  
Well Being ◽  
Negative Effect ◽  
Competing Interest ◽  
Als Patients ◽  
Lateral Sclerosis

IntroductionAmyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder that affects motor neurons in the cerebral cortex, brainstem and spinal cord. The progressive loss of motor function creates profound changes on patient's lives and their caregivers.ObjectiveAssessment of eventual existence of psychopathology in ALS patients and their caregivers.MethodsLiterature review using the terms: ALS, Amyotrophic Lateral Sclerosis, psychopathology, psychiatric disorder; depression; anxiety, caregivers.ResultsModerate depressive or anxious symptoms are often observed. The results are not consistent, some studies showing that major depression is less common that in general population, others that is mildly increased. Some studies show that depressive symptoms are related to poorer QoL and with faster disease progression, others suggests no correlations. Coping strategies, cognitive appraisal and social support are important factors to psychological adaptation to ALS. After the diagnosis, high levels of anxiety can be observed. Psychopathological features are observed at this time, and generally depression does not increase as death approaches. Beyond loss of physical functions, it seems that patients’ neurobehavioral symptoms, such as aggressiveness, disinhibition and impulsivity, cognitive impairment, and also lack of social support have a negative effect on caregivers’ mental health. Concordance between patient and caregiver distress was found.ConclusionsIt is important to assess potential psychological distress in ALS patients and their caregivers, given that cope with disease can affect its course. Caregivers’ needs should be addressed, to benefit their well-being and consequently patients’ QoL. There are few studies about psychopharmacotherapy and/or psychotherapy in these patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Alok Kumar ◽  
Devlina Ghosh ◽  
R. L. Singh
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Neurodegenerative Disorders ◽  
Metabolic Profile ◽  
Body Fluids ◽  
Fast Progression ◽  
Progression Of Disease ◽  
Als Patients ◽  
The Brain ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is one of the most common motor neurodegenerative disorders, primarily affecting upper and lower motor neurons in the brain, brainstem, and spinal cord, resulting in paralysis due to muscle weakness and atrophy. The majority of patients die within 3–5 years of symptom onset as a consequence of respiratory failure. Due to relatively fast progression of the disease, early diagnosis is essential. Metabolomics offer a unique opportunity to understand the spatiotemporal metabolic crosstalks through the assessment of body fluids and tissue. So far, one of the most challenging issues related to ALS is to understand the variation of metabolites in body fluids and CNS with the progression of disease. In this paper we will review the changes in metabolic profile in response to disease progression condition and also see the therapeutic implication of various drugs in ALS patients.

scholarly journals Toxic Damage to Motor Neurons

2021 ◽  
Vol 15 (4) ◽  
pp. 410-421
Author(s):  
M. N. Zakharova ◽  
I. S. Bakulin ◽  
A. A. Abramova
Keyword(s):  
Motor Neurons ◽  
Specific Treatment ◽  
Toxic Substances ◽  
Toxic Damage ◽  
Increased Risk ◽  
Genetic And Environmental Factors ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Lateral Sclerosis

Abstract—Amyotrophic lateral sclerosis (ALS) is a multifactor disease in the development of which both genetic and environmental factors play a role. Specifically, the effects of organic and inorganic toxic substances can result in an increased risk of ALS development and the acceleration of disease progression. It was described that some toxins can induce potentially curable ALS-like syndromes. In this case, the specific treatment for the prevention of the effects of the toxic factor may result in positive clinical dynamics. In this article, we review the main types of toxins that can damage motor neurons in the brain and spinal cord leading to the development of the clinical manifestation of ALS, briefly present historical data on studies on the role of toxic substances, and describe the main mechanisms of the pathogenesis of motor neuron disease associated with their action.

scholarly journals Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2687
Author(s):  
Ali Yousefian-Jazi ◽  
YunHee Seol ◽  
Jieun Kim ◽  
Hannah L. Ryu ◽  
Junghee Lee ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Genetic Variants ◽  
Diagnostic Tests ◽  
Neurodegenerative Disorder ◽  
Therapeutic Approaches ◽  
Causative Gene ◽  
Disease Mechanisms ◽  
Disease Modifying ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease and a neurodegenerative disorder, affecting the upper and/or lower motor neurons. Notably, it invariably leads to death within a few years of onset. Although most ALS cases are sporadic, familial amyotrophic lateral sclerosis (fALS) forms 10% of the cases. In 1993, the first causative gene (SOD1) of fALS was identified. With rapid advances in genetics, over fifty potentially causative or disease-modifying genes have been found in ALS so far. Accordingly, routine diagnostic tests should encompass the oldest and most frequently mutated ALS genes as well as several new important genetic variants in ALS. Herein, we discuss current literatures on the four newly identified ALS-associated genes (CYLD, S1R, GLT8D1, and KIF5A) and the previously well-known ALS genes including SOD1, TARDBP, FUS, and C9orf72. Moreover, we review the pathogenic implications and disease mechanisms of these genes. Elucidation of the cellular and molecular functions of the mutated genes will bring substantial insights for the development of therapeutic approaches to treat ALS.

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