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      New insights into the treatment of meningoencephalomyelitis of unknown origin since 2009: A review of 671 cases

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          Abstract

          “Meningoencephalomyelitis of unknown origin” (MUO)—a collective term for a group of clinically-indistinguishable (but pathologically distinct) autoimmune diseases of the CNS—has become increasingly commonly recognized throughout the world. In the 1960s−1980s the focus was primarily on the pathological description of these conditions and, largely anecdotally, their response to glucocorticoids. The subsequent availability of magnetic resonance imaging for companion animals led to a focus on imaging characteristics and response of MUO to various immunosuppressive medications. Previous reviews have not found clear evidence of superiority of any specific treatment regimen. Here, we review outcomes in a further 671 dogs treated with various combinations of glucocorticoids and immunosuppressive drugs and reported since 2009, aiming to determine whether recommendations can be drawn from the material published during more recent decades. We observe that: (i) there is more complete information on outcome of MUO-affected dogs solely receiving glucocorticoids and these reports provide evidence to undermine the dogma that MUO inevitably requires treatment with glucocorticoids plus an immunosuppressive drug; (ii) there is far more information on the pharmacokinetics of cytarabine delivered by a variety of routes, revealing that previous dosing and duration of administration in dogs with MUO may not have been optimal; and, (iii) there is a large number of cases that could be available for entry into multi-institutional randomized controlled trials. Finally, we suggest new research avenues that might aid future clinical trials in MUO through improved understanding of etiological triggers and individual patterns of immune response, such as the impact of the gut microbiome, the potential of CSF flow cytometry, and the establishment of robust clinical scores for evaluation of treatment success.

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          Most cited references117

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          Multi-omics approaches to disease

          High-throughput technologies have revolutionized medical research. The advent of genotyping arrays enabled large-scale genome-wide association studies and methods for examining global transcript levels, which gave rise to the field of “integrative genetics”. Other omics technologies, such as proteomics and metabolomics, are now often incorporated into the everyday methodology of biological researchers. In this review, we provide an overview of such omics technologies and focus on methods for their integration across multiple omics layers. As compared to studies of a single omics type, multi-omics offers the opportunity to understand the flow of information that underlies disease.
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            Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis

            Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system of unknown etiology. We tested the hypothesis that MS is caused by Epstein-Barr virus (EBV) in a cohort comprising more than 10 million young adults on active duty in the US military, 955 of whom were diagnosed with MS during their period of service. Risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion. These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.
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              Multiple sclerosis

              Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. This disorder is a heterogeneous, multifactorial, immune-mediated disease that is influenced by both genetic and environmental factors. In most patients, reversible episodes of neurological dysfunction lasting several days or weeks characterize the initial stages of the disease (that is, clinically isolated syndrome and relapsing-remitting MS). Over time, irreversible clinical and cognitive deficits develop. A minority of patients have a progressive disease course from the onset. The pathological hallmark of MS is the formation of demyelinating lesions in the brain and spinal cord, which can be associated with neuro-axonal damage. Focal lesions are thought to be caused by the infiltration of immune cells, including T cells, B cells and myeloid cells, into the central nervous system parenchyma, with associated injury. MS is associated with a substantial burden on society owing to the high cost of the available treatments and poorer employment prospects and job retention for patients and their caregivers.
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                Author and article information

                Contributors
                Journal
                Front Vet Sci
                Front Vet Sci
                Front. Vet. Sci.
                Frontiers in Veterinary Science
                Frontiers Media S.A.
                2297-1769
                15 March 2023
                2023
                : 10
                : 1114798
                Affiliations
                [1] 1Department of Small Animal Clinical Sciences, Texas A&M University , College Station, TX, United States
                [2] 2Bristol Vet Specialists, CVS Referrals & Bristol Translational Health Sciences, University of Bristol , Bristol, United Kingdom
                Author notes

                Edited by: R. Timothy Bentley, Purdue University, United States

                Reviewed by: Hanne Gredal, University of Copenhagen, Denmark; Rita Goncalves, University of Liverpool, United Kingdom

                *Correspondence: Nick Jeffery njeffery@ 123456cvm.tamu.edu

                This article was submitted to Veterinary Neurology and Neurosurgery, a section of the journal Frontiers in Veterinary Science

                Article
                10.3389/fvets.2023.1114798
                10050685
                37008358
                f744e7c3-0b07-4df5-914b-4cc2f7529695
                Copyright © 2023 Jeffery and Granger.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 December 2022
                : 17 February 2023
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 117, Pages: 14, Words: 12617
                Funding
                Figure 1 originates from work by NG and Prof. Linda Wooldridge funded by the Langford Trust.
                Categories
                Veterinary Science
                Review

                meningoencephalomyelitis,dog,therapy,glucocorticoid,cytarabine

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