Mohan Zhao, Na Wang, Yaoting Guo, Jingwen Li, Yue Yin, Yan Dong, Jiabin Zhu, Chao Peng, Tingting Xu, Jinsong Liu
Orphan nuclear receptor Nurr1 plays important roles in the progression of various diseases, including Parkinson's disease, neuroinflammation, Alzheimer's disease, and multiple sclerosis. It can recognize DNA as a monomer or heterodimer with retinoid X receptor α (RXRα). But the molecular mechanism of its transcriptional activity regulation is still largely unknown. Here we obtained a crystal structure of monomer Nurr1 (DNA- and ligand-binding domains, DBD and LBD) bound to NGFI-B response element...
December 6, 2022: Proceedings of the National Academy of Sciences of the United States of America
Bing Yang, Robert B Parker, Bernd Meibohm, Zaid H Temrikar, Ashish Srivastava, S Casey Laizure
Dimethyl fumarate (DMF) is a first-line prodrug for the treatment of relapsing-remitting multiple sclerosis (RRMS) that is completely metabolized to monomethyl fumarate (MMF), the active metabolite, before reaching the systemic circulation. Its metabolism has been proposed to be due to ubiquitous esterases in the intestines and other tissues, but the specific enzymes involved are unknown. We hypothesized based on its structure and extensive presystemic metabolism that DMF would be a carboxylesterase substrate subject to interaction with alcohol...
2022: PloS One
Miko Valori, Joonas Lehikoinen, Lilja Jansson, Jonna Clancy, Sofie A Lundgren, Satu Mustjoki, Pentti Tienari
Somatic mutations have a central role in cancer, but there are also a few rare autoimmune diseases in which somatic mutations play a major role. We have recently shown that nonsynonymous somatic mutations with low allele fractions are preferentially detectable in CD8+ cells and that the STAT3 gene is a promising target for screening. Here, we analyzed somatic mutations in the STAT3 SH2 domain in peripheral blood CD8+ cells in a set of 94 multiple sclerosis (MS) patients and 99 matched controls. PCR amplicons targeting the exons 20 and 21 of STAT3 were prepared and sequenced using the Illumina MiSeq instrument with 2x300bp reads...
2022: PloS One
C U Wickramasinghe, D M G Fernando, S Wijetunge, H R S D Sumanasekara
Multiple sclerosis (MS) is a debilitating, demyelinating disease of the central nervous system, with manifestations ranging from numbness and blindness to paralysis. Typical MS is a slowly progressive demyelinating disease, causing significant morbidity spanning over many years. In contrast, "Marburg's disease" is a rare variant of MS which demonstrates a malignant monophasic disease progression leading to death within weeks to months. We present a rapidly fatal demyelinating disease with the clinicopathological findings on par with the handful of reported cases of "Marburg's disease" in the literature...
November 28, 2022: Forensic Science, Medicine, and Pathology
Michela Ponzio, Maria Cristina Monti, Giulia Mallucci, Paola Borrelli, Sara Fusco, Andrea Tacchino, Giampaolo Brichetto, Livio Tronconi, Cristina Montomoli, Roberto Bergamaschi
BACKGROUND: Comorbid conditions are common in people with multiple sclerosis (pwMS). They can delay diagnosis and negatively impact the disease course, progression of disability, therapeutic management, and adherence to treatment. OBJECTIVE: To quantify the economic impact of comorbidity in multiple sclerosis (MS), based on cost-of-illness estimates made using a bottom-up approach. METHODS: A retrospective study was carried out in two northern Italian areas...
November 28, 2022: Neurological Sciences
Jean-Guillaume Letarouilly, Patrick Vermersch, René-Marc Flipo
Dealing with patients with both multiple sclerosis (MS) and inflammatory rheumatic disorders (IRD) is not uncommon for a rheumatologist, as there is a statistical association between spondyloarthritis and MS. As several central nervous system demyelinating events have been reported in patients treated with TNFi, the pre-existing demyelinating disease was considered a contraindication for TNFi. However, this contraindication is mainly based on a randomized controlled trial in MS and not on large epidemiologic studies...
November 28, 2022: Rheumatology
Anthony T Reder, Olaf Stuve, Stephanie K Tankou, Thomas P Leist
BACKGROUND: Multiple sclerosis (MS) is a neurological disorder marked by accumulating immune-mediated damage to the central nervous system. The dysregulated immune system in MS combined with immune effects of disease-modifying therapies (DMTs) used in MS treatment could alter responses to infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). Most of the literature on immune response to SARS-CoV-2 infection and COVID-19 vaccination, in both the general population and patients with MS on DMTs, has focused on humoral immunity...
November 28, 2022: Multiple Sclerosis: Clinical and Laboratory Research
David Payares-Garcia, Jorge Mateu, Wiebke Schick
Magnetic resonance imaging (MRI) plays an increasingly important role in the diagnosis and prognosis of neurodegenerative diseases. One field of extensive clinical use of MRI is the accurate and automated classification of degenerative disorders. Most of current classification studies either do not mirror medical practice where patients may exhibit early stages of the disease, comorbidities, or atypical variants, or they are not able to produce probabilistic predictions nor account for uncertainty. Also, the spatial heterogeneity of the brain alterations caused by neurodegenerative processes is not usually considered, despite the spatial configuration of the neuronal loss is a characteristic hallmark for each disorder...
November 28, 2022: Statistics in Medicine
D O Shabalina, A R Zulkaidarova, M A Khramchenko, S A Subocheva, M V Abros'kina, S V Prokopenko
OBJECTIVE: To evaluate the efficacy of remote rehabilitation for non-exacerbating patients with multiple sclerosis (MS). MATERIAL AND METHODS: A total of 17 patients, including 12 (70.6%) women and 5 (29.4%) men, with the established diagnosis of MS according to the 2017 McDonald criteria were enrolled in the study. The age varied from 26 to 70 years, the median age was 47 [34; 53] years. Patients with mild or moderate atactic disorders, mildly or moderately manifested central paresis with gait function and fine motor skills impairment were included in the group, median EDSS in which was 4 [3; 5...
2022: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Lita Araujo, Srikanth Kyatham, Kristen G Bzdek, Keiko Higuchi, Nupur Greene
Aim: Describe demographics, clinical characteristics, healthcare resource utilization (HCRU) and costs in people with multiple sclerosis (pwMS) switching to alemtuzumab from other disease-modifying therapies (DMTs). Patients & methods: Retrospective, observational study of IBM® MarketScan® claims database. PwMS previously treated with DMTs and initiating alemtuzumab (1 January 2013 to 31 December 2019) were identified. "Index" was date of alemtuzumab initiation (prescription filled)...
November 28, 2022: Journal of Comparative Effectiveness Research
Grigorios Kalaitzidis, Nicole Pellegrini, Natalia Nagy, Eleni Vasileiou, Henrik Ehrhardt, Abbey Reppen, Olwen C Murphy, Hussein Moussa, Angeliki Filippatou, Jeffrey Lambe, Anna DuVal, Nicholas Fioravante, Ohemaa Kwakyi, James Nguyen, Simidele Davis, Morgan Douglas, Alexandra Ramirez, Katie Ecoff, Alyssandra Valenzuela, Maria Reyes-Mantilla, Chen Hu, Kathryn C Fitzgerald, Elias S Sotirchos, Shiv Saidha, Peter A Calabresi
PURPOSE: To quantify the associations of myopia with longitudinal changes in retinal layer thicknesses in people with multiple sclerosis (PwMS) and healthy controls (HC). METHODS: A cohort of PwMS and HC with recorded refractive error (RE) prospectively scanned on Cirrus HD-OCT at the Johns Hopkins MS Center was assessed for inclusion. Exclusion criteria included OCT follow-up < 6 months, ocular comorbidities, incidental OCT pathologies, and inadequate scan quality...
November 28, 2022: Current Eye Research
Viktor Grut, Martin Biström, Jonatan Salzer, Pernilla Stridh, Anna Lindam, Lucia Alonso-Magdalena, Oluf Andersen, Daniel Jons, Martin Gunnarsson, Magnus Vrethem, Johan Hultdin, Peter Sundström
BACKGROUND: C-reactive protein (CRP) is a marker of systemic inflammation. Increased levels of CRP in young persons have been suggested to decrease the risk of multiple sclerosis (MS). OBJECTIVES: To assess CRP as a risk factor for MS. METHODS: Levels of CRP were measured with a high-sensitive immunoassay in biobank samples from 837 individuals who later developed MS and 984 matched controls. The risk of developing MS was analysed by conditional logistic regression on z -scored CRP values...
2022: Multiple Sclerosis Journal—Experimental, Translational and Clinical
Nazar Manko, Marina Starykovych, Nataliya Mitina, Kateryna Volianiuk, Lizhen Wang, Meng Jin, Kechun Liu, Rostyslav Panchuk, Olga Klyuchivska, Alexander Zaichenko, Yuriy Kit, Rostyslav Stoika
Recently, we detected a previously unknown Ser-Pro-Cys (SPC) tripeptide in the blood serum of multiple sclerosis patients. Its role as a biomarker of the autoimmune disease was suggested, although its origin and real biological activity remained unclear. Here, we created a biocompatible PEGylated comb-like polymer that was used as a platform for covalent immobilization of the SPC, which provided a possibility to explore the biological activity of this tripeptide. This macromolecular conjugate was synthesized via a reaction of the terminal epoxide group of the biocompatible copolymer of dimethyl maleate (DMM) and polyethylene glycol methyl ether methacrylate (PEGMA) with the amino group of the SPC tripeptide...
November 22, 2022: ACS Omega
Camryn R Rohringer, Isabella J Sewell, Shikha Gandhi, Jonah Isen, Benjamin Davidson, Melissa McSweeney, Walter Swardfager, Nadia Scantlebury, Richard H Swartz, Clement Hamani, Peter Giacobbe, Sean M Nestor, Yana Yunusova, Benjamin Lam, Michael L Schwartz, Nir Lipsman, Agessandro Abrahao, Jennifer S Rabin
Tremor is a debilitating symptom that can lead to functional impairment. Pharmacotherapy is often successful, but up to 50% of patients are resistant to medications or cannot tolerate side effects. Thalamotomy to the ventral intermediate nucleus of the thalamus is a surgical intervention for refractory tremor. Thalamotomy surgeries include radiofrequency and incisionless procedures, such as Gamma Knife radiosurgery and magnetic resonance-guided focused ultrasound. Cognitive changes following thalamotomy have been inconsistently reported across studies...
2022: Brain communications
Moisés Manuel Gallardo Pérez, Solón Javier Garcés Eisele
Multiple sclerosis (MS) is a demyelinating, autoimmune and inflammatory disease that affects the central nervous system (CNS) and is one of the leading causes of disability in young adults worldwide. There are different drugs for the treatment of MS that aim to modify the natural course of the disease and thus slow its progression. This group of drugs is known as disease modifying therapy (DMT). To evaluate the effectiveness of these drugs, mainly clinical and MRI parameters are used. In recent years, different studies have emerged that propose the use of biomarkers to improve the evaluation of the effectiveness of DMT and to provide individualized therapy...
December 2022: IBRO neuroscience reports
Andrés Felipe Herrera Ortiz, Santiago Aristizabal, Juan Guillermo Arámbula, Valeria Del Castillo, Juan Calderon, Nury Tatiana Rincón Cuenca, María José Abuchar, María Mónica Yepes, Angela Guarnizo
Multiple sclerosis is a frequent condition where the diagnosis relies on clinical presentation, neurologic examination, cerebro spinal fluid markers, and diagnostic imaging tests; however, atypical variants of the disease can lead to misdiagnosis in some scenarios. Herein, we describe a case of a 24-year-old patient with multiple sclerosis with megacystic plaques, in which appropriate interpretation of the imaging findings lead to a proper diagnosis and treatment.
February 2023: Radiology Case Reports
Hussain Hussain, Tamara Djurin, Jacqueline Rodriguez, Lia Daneelian, Sardar Sundi, Aya Fadel, Zahraa Saadoon
The trans-activation response DNA-binding protein of 43kDa (TDP-43) is involved in the pathogenesis of multiple brain disorders. As scientists are unraveling TDP-43 function and its impact on various diseases, we have begun to subcategorize them into TDP-43 proteinopathies. Furthermore, glial cell dysfunction contributes to various disorders, and TDP-43 is involved with glial cells via multiple pathways (direct or indirect) that aggravate the pathophysiology of such disorders. We are only now discovering and understanding the vast and diverse roles TDP-43 plays on neuronal cells and its effects on gliosis and neurodegenerative pathologies...
October 2022: Curēus
Erica Costantini, Eva Masciarelli, Laura Casorri, Marco Di Luigi, Marcella Reale
Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and axonal loss of the central nervous system (CNS). Despite its spread throughout the world, the mechanisms that determine its onset are still to be defined. Immunological, genetic, viral, and environmental factors and exposure to chemicals may trigger MS. Many studies have highlighted the anti-inflammatory and anti-oxidant effects of medicinal herbs, which make them a natural and complementary treatment for neurodegenerative diseases...
2022: Frontiers in Cellular Neuroscience
Christina Noll, Michael Hiltensperger, Lilian Aly, Rebecca Wicklein, Ali Maisam Afzali, Christian Mardin, Christiane Gasperi, Achim Berthele, Bernhard Hemmer, Thomas Korn, Benjamin Knier
BACKGROUND: Optical coherence tomography angiography (OCT-A) is a novel technique allowing non-invasive assessment of the retinal vasculature. During relapsing remitting multiple sclerosis (RRMS), retinal vessel loss occurs in eyes suffering from acute optic neuritis and recent data suggest that retinal vessel loss might also be evident in non-affected eyes. We investigated whether alterations of the retinal vasculature are linked to the intrathecal immunity and whether they allow prognostication of the future disease course...
2022: Frontiers in Immunology
Dirk T Ubbink, Olga C Damman, Brigit A de Jong
Multiple sclerosis (MS) is a chronic and progressive neurological disorder impacting physical, cognitive, and psychosocial health. The disease course, severity, and presence of symptoms differ within and between persons over time and are unpredictable. Given the preference-sensitive nature of many key decisions to be made, and the increasing numbers of disease-modifying therapies, shared decision-making (SDM) with patients seems to be key in offering optimum care and outcomes for people suffering from MS. In this paper, we describe our perspective on how to achieve SDM in patients with MS, following key SDM-elements from established SDM-frameworks...
2022: Frontiers in Neurology
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