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ALS Therapy

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https://www.readbyqxmd.com/read/29448993/adjacent-level-spondylodiscitis-in-a-patient-with-thoracic-spondylodiscitis-a-case-report-and-review-of-the-literature
#1
K Farah, T Graillon, H Dufour, S Fuentes
INTRODUCTION: Adjacent level spondylodiscitis (ALS) after primary surgery for thoracic spondylodiscitis is a very rare condition. CASE REPORT: We report the case of a 76-year-old man with this pathology. A first posterior minimally invasive approach combined with anterior approach to the thoracic spine was safely performed for thoracic spondylodiscitis. More than a year later, exploration of recurrent symptoms with 18 FDG PET scan helped to diagnose ALS. Further surgery was performed...
February 12, 2018: Neuro-Chirurgie
https://www.readbyqxmd.com/read/29445154/interleukin-4-modulates-microglia-homeostasis-and-attenuates-the-early-slowly-progressive-phase-of-amyotrophic-lateral-sclerosis
#2
Chiara Rossi, Melania Cusimano, Martina Zambito, Annamaria Finardi, Alessia Capotondo, Jose Manuel Garcia-Manteiga, Giancarlo Comi, Roberto Furlan, Gianvito Martino, Luca Muzio
Microglia activation is a commonly pathological hallmark of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), a devastating disorder characterized by a selective motor neurons degeneration. Whether such activation might represent a causal event rather than a secondary epiphenomenon remains elusive. Here, we show that CNS-delivery of IL-4-via a lentiviral-mediated gene therapy strategy-skews microglia to proliferate, inducing these cells to adopt the phenotype of slowly proliferating cells...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29416499/a-metadata-analysis-of-oxidative-stress-etiology-in-preclinical-amyotrophic-lateral-sclerosis-benefits-of-antioxidant-therapy
#3
Leila Bond, Kamren Bernhardt, Priyank Madria, Katherine Sorrentino, Hailee Scelsi, Cassie S Mitchell
Oxidative stress, induced by an imbalance of free radicals, incites neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). In fact, a mutation in antioxidant enzyme superoxide dismutase 1 (SOD1) accounts for 20% of familial ALS cases. However, the variance among individual studies examining ALS oxidative stress clouds corresponding conclusions. Therefore, we construct a comprehensive, temporal view of oxidative stress and corresponding antioxidant therapy in preclinical ALS by mining published quantitative experimental data and performing metadata analysis of 41 studies...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29405033/therapy-in-amyotrophic-lateral-sclerosis-als-an-unexpected-evolving-scenario
#4
Vincenzo Silani
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease resulting in increasing disability, being uniformly fatal. Since its approval in the 1990s, riluzole remained for long time the unique treatment, offering modest survival benefit. Most recently a second drug has been approved by the US Food and Drug Administration for treatment of ALS: edaravone. Significant advances have been made in the symptomatic management of the disease but more effective drug therapy targeting disease progression is still dreadfully needed, the success appearing almost a miracle...
December 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/29399045/disease-modifying-and-symptomatic-treatment-of-amyotrophic-lateral-sclerosis
#5
REVIEW
Johannes Dorst, Albert C Ludolph, Annemarie Huebers
In this review, we summarize the most important recent developments in the treatment of amyotrophic lateral sclerosis (ALS). In terms of disease-modifying treatment options, several drugs such as dexpramipexole, pioglitazone, lithium, and many others have been tested in large multicenter trials, albeit with disappointing results. Therefore, riluzole remains the only directly disease-modifying drug. In addition, we discuss antisense oligonucleotides (ASOs) as a new and potentially causal treatment option. Progress in symptomatic treatments has been more important...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29399022/edematous-hyponatremia-treated-with-tolvaptan-in-a-patient-with-amyotrophic-lateral-sclerosis
#6
Gheun-Ho Kim
Amyotrophic lateral sclerosis (ALS) patients rarely present with either syndrome of inappropriate antidiuretic hormone secretion or generalized edema. Tolvaptan is a selective vasopressin V2 receptor antagonist that produces effective aquaresis, and its use in ALS patients has not been previously reported. A 50-year-old male ALS patient was admitted because of both generalized edema and dilutional hyponatremia. These manifestations were refractory to conventional diuretics and fluid therapy, but a very brisk diuresis was induced by tolvaptan administration...
December 2017: Electrolyte & Blood Pressure: E & BP
https://www.readbyqxmd.com/read/29385088/potential-role-of-humoral-il-6-cytokine-in-mediating-pro-inflammatory-endothelial-cell-response-in-amyotrophic-lateral-sclerosis
#7
REVIEW
Svitlana Garbuzova-Davis, Jared Ehrhart, Paul R Sanberg, Cesario V Borlongan
Amyotrophic lateral sclerosis (ALS) is a multifactorial disease with limited therapeutic options. Numerous intrinsic and extrinsic factors are involved in ALS motor neuron degeneration. One possible effector accelerating motor neuron death in ALS is damage to the blood-Central Nervous System barrier (B-CNS-B), mainly due to endothelial cell (EC) degeneration. Although mechanisms of EC damage in ALS are still unknown, vascular impairment may be initiated by various humoral inflammatory factors and other mediators...
January 31, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29384454/escape-from-homeostasis-spinal-microcircuits-and-progression-of-amyotrophic-lateral-sclerosis
#8
Robert M Brownstone, Camille Lancelin
In amyotrophic lateral sclerosis (ALS), loss of motoneuron function leads to weakness and ultimately respiratory failure and death. Regardless of the initial pathogenic factors, motoneuron loss follows a specific pattern: the largest α-motoneurons die prior to smaller α-motoneurons, and γ-motoneurons are spared. Here, we examine how homeostatic responses to this orderly progression could lead to local microcircuit dysfunction that in turn propagates motoneuron dysfunction and death. We first review motoneuron diversity and the principle of α-γ co-activation, and then discuss two specific spinal motoneuron microcircuits: those involving proprioceptive afferents, and those involving Renshaw cells...
January 31, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29375039/induced-pluripotent-stem-cells-in-modeling-and-cell-based-therapy-of-amyotrophic-lateral-sclerosis
#9
M Csobonyeiova, S Polak, A Nicodemou, L Danisovic
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by neuromuscular degeneration and the progressive loss of upper and lower motor neurons (MNs), causing weakness and paralysis. However, the underlying mechanisms of this disease are still unknown and there is no cure, or even treatment to stop or reverse its pathology. Consequently, most ALS patients die within 3 - 5 years after disease onset. While considerable progress has been made in studying animal models of ALS, they lack clinical suitability due to genetic differences...
October 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29367447/unraveling-als-due-to-sod1-mutation-through-the-combination-of-brain-and-cervical-cord-mri
#10
Federica Agosta, Edoardo Gioele Spinelli, Ivan V Marjanovic, Zorica Stevic, Elisabetta Pagani, Paola Valsasina, Biljana Salak-Djokic, Milena Jankovic, Dragana Lavrnic, Vladimir S Kostic, Massimo Filippi
OBJECTIVE: To explore structural and functional changes of the brain and cervical cord in patients with amyotrophic lateral sclerosis (ALS) due to mutation in the superoxide dismutase (SOD1) gene compared with sporadic ALS. METHODS: Twenty patients with SOD1 ALS, 11 with sporadic ALS, and 33 healthy controls underwent clinical evaluation and brain MRI. Cortical thickness analysis, diffusion tensor MRI of the corticospinal tracts (CST) and corpus callosum, and resting-state functional connectivity were performed...
January 24, 2018: Neurology
https://www.readbyqxmd.com/read/29352425/safety-and-efficacy-of-nanocurcumin-as-add-on-therapy-to-riluzole-in-patients-with-amyotrophic-lateral-sclerosis-a-pilot-randomized-clinical-trial
#11
Mona Ahmadi, Elmira Agah, Shahriar Nafissi, Mahmoud Reza Jaafari, Mohammad Hossein Harirchian, Payam Sarraf, Sara Faghihi-Kashani, Seyed Jalal Hosseini, Abdolreza Ghoreishi, Vajiheh Aghamollaii, Mostafa Hosseini, Abbas Tafakhori
The objective of present study was to assess the safety and efficacy of nanocurcumin as an anti-inflammatory and antioxidant agent in adults with amyotrophic lateral sclerosis (ALS). We conducted a 12-month, double-blind, randomized, placebo-controlled trial at a neurological referral center in Iran. Eligible patients with a definite or probable ALS diagnosis were randomly assigned to receive either nanocurcumin (80 mg daily) or placebo in a 1:1 ratio. A computerized random number generator was used to prepare the randomization list...
January 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29342921/rna-targeted-therapies-and-amyotrophic-lateral-sclerosis
#12
REVIEW
Stéphane Mathis, Gwendal Le Masson
Amyotrophic lateral sclerosis (ALS) is a fatal motor disease in adults. Its pathophysiology remains mysterious, but tremendous advances have been made with the discovery of the most frequent mutations of its more common familial form linked to the C9ORF72 gene. Although most cases are still considered sporadic, these genetic mutations have revealed the role of RNA production, processing and transport in ALS, and may be important players in all ALS forms. There are no disease-modifying treatments for adult human neurodegenerative diseases, including ALS...
January 15, 2018: Biomedicines
https://www.readbyqxmd.com/read/29334251/discussing-edaravone-with-the-als-patient-an-ethical-framework-from-a-u-s-perspective
#13
Crystal Jing Jing Yeo, Zachary Simmons
The recent approval of edaravone by the United States Food and Drug Administration has generated a mix of hope tempered by reality. The costs of the drug, both monetarily and with regard to intensity of treatment, are high. The benefits, while modest, will be viewed through a very different lens by individuals depending on their goals of care. By virtue of our training and experience, physicians are ideally suited to understand and explain new treatments to our patients. As healthcare providers with a fiduciary responsibility to our patients, we must make sure they are fully informed about both the costs and benefits of non-curative therapies such as edaravone, and be prepared to discuss these in the context of their goals of care and potential impact on quality of life...
January 15, 2018: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/29331073/cerebrospinal-fluid-macrophage-biomarkers-in-amyotrophic-lateral-sclerosis
#14
A G Thompson, E Gray, M-L Thézénas, P D Charles, S Evetts, M T Hu, K Talbot, R Fischer, B M Kessler, M R Turner
Objective The neurodegenerative disease amyotrophic lateral sclerosis (ALS) is a heterogeneous clinical syndrome involving multiple molecular pathways. The development of biomarkers for use in therapeutic trials is a priority. We sought to use a high-throughput proteomic method to identify novel biomarkers in individual cerebrospinal fluid samples. Methods Liquid chromatography-tandem mass spectrometry with label-free quantification was used to identify cerebrospinal fluid proteins using samples from a well-characterised longitudinal cohort comprising patients with ALS (n=43), the upper motor neuron variant primary lateral sclerosis (PLS, n=6), cross-sectional healthy (n=20) and disease controls (Parkinsons's n=20, ALS mimic disorders n=12)...
January 13, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29313812/pathogenic-commonalities-between-spinal-muscular-atrophy-and-amyotrophic-lateral-sclerosis-converging-roads-to-therapeutic-development
#15
REVIEW
Melissa Bowerman, Lyndsay M Murrray, Frédérique Scamps, Bernard L Schneider, Rashmi Kothary, Cédric Raoul
Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are the two most common motoneuron disorders, which share typical pathological hallmarks while remaining genetically distinct. Indeed, SMA is caused by deletions or mutations in the survival motor neuron 1 (SMN1) gene whilst ALS, albeit being mostly sporadic, can also be caused by mutations within genes, including superoxide dismutase 1 (SOD1), Fused in Sarcoma (FUS), TAR DNA-binding protein 43 (TDP-43) and chromosome 9 open reading frame 72 (C9ORF72)...
December 4, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29312526/amyotrophic-lateral-sclerosis-as-a-protein-level-non-genomic-disease-therapy-with-s2rm-exosome-released-molecules
#16
REVIEW
Greg Maguire
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease that leads to death. No effective treatments are currently available. Based on data from epidemiological, etiological, laboratory, and clinical studies, I offer a new way of thinking about ALS and its treatment. This paper describes a host of extrinsic factors, including the exposome, that disrupt the extracellular matrix and protein function such that a spreading, prion-like disease leads to neurodegeneration in the motor tracts...
November 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/29285622/effects-of-the-intensity-of-prehospital-treatment-on-short-term-outcomes-in-patients-with-acute-heart-failure-the-semica-2-study
#17
Òscar Miró, Melissa Hazlitt, Xavier Escalada, Pere Llorens, Víctor Gil, Francisco Javier Martín-Sánchez, Pia Harjola, Verónica Rico, Pablo Herrero-Puente, Javier Jacob, David C Cone, Martin Möckel, Michael Christ, Yonathan Freund, Salvatore di Somma, Said Laribi, Alexandre Mebazaa, Veli-Pekka Harjola
OBJECTIVE: Little is known about treatments provided by advanced life support (ALS) ambulance teams to patients with acute heart failure (AHF) during the prehospital phase, and their influence on short-term outcome. We evaluated the effect of prehospital care in consecutive patients diagnosed with AHF in Spanish emergency departments (EDs). METHODS: We selected patients from the EAHFE registry arriving at the ED by ALS ambulances with available follow-up data. We recorded specific prehospital ALS treatments (supplemental oxygen, diuretics, nitroglycerin, non-invasive ventilation) and patients were grouped according to whether they received low- (LIPHT; 0/1 treatments) or high-intensity prehospital therapy (HIPHT; > 1 treatment) for AHF...
December 28, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/29284475/existential-decision-making-in-a-fatal-progressive-disease-how-much-do-legal-and-medical-frameworks-matter
#18
Christian Weber, Barbara Fijalkowska, Katarzyna Ciecwierska, Anna Lindblad, Gisela Badura-Lotter, Peter M Andersen, Magdalena Kuźma-Kozakiewicz, Albert C Ludolph, Dorothée Lulé, Tomasz Pasierski, Niels Lynöe
BACKGROUND: Healthcare legislation in European countries is similar in many respects. Most importantly, the framework of informed consent determines that physicians have the duty to provide detailed information about available therapeutic options and that patients have the right to refuse measures that contradict their personal values. However, when it comes to end-of-life decision-making a number of differences exist in the more specific regulations of individual countries. These differences and how they might nevertheless impact patient's choices will be addressed in the current debate...
December 28, 2017: BMC Palliative Care
https://www.readbyqxmd.com/read/29258495/observational-study-of-patients-in-spain-with-amyotrophic-lateral-sclerosis-correlations-between-clinical-status-quality-of-life-and-dignity
#19
Yolanda Martínez-Campo, Christian Homedes, Ana Lazaro, Raquel Alarcón, David Campo, Mariona Riera, Raúl Domínguez, Mónica Povedano, Carlos Casasnovas
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that dramatically affects patients' quality of life (QoL) and dignity of life (DoL). We aimed to study the impact of ALS on QoL and DoL and how these evolve throughout the duration of the disease. METHODS: First, we performed an observational, descriptive study of 43 patients with ALS recruited from the ALS unit at our center and compared them with 20 healthy age- and sex-matched controls...
December 19, 2017: BMC Palliative Care
https://www.readbyqxmd.com/read/29249183/aav-gene-delivery-to-the-spinal-cord-serotypes-methods-candidate-diseases-and-clinical-trials
#20
Nathan Hardcastle, Nicholas M Boulis, Thais Federici
Adeno-associated viral (AAV) vector-mediated gene delivery to the spinal cord has finally entered the pathway towards regulatory approval. Phase 1 clinical trials using AAV gene therapy for pediatric disorders - spinal muscular atrophy (SMA) and giant axonal neuropathy (GAN) - are now underway. Areas covered: This review addresses the latest progress in the field of AAV gene delivery to the spinal cord, particularly focusing on the most prominent AAV serotypes and delivery methodologies to the spinal cord. Candidate diseases and scaling up experiments in large animals are also discussed...
December 18, 2017: Expert Opinion on Biological Therapy
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