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International Journal of Environmental... Mar 2023Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease mediated by autoimmune reactions against myelin proteins and gangliosides in the grey and... (Review)
Review
INTRODUCTION
Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease mediated by autoimmune reactions against myelin proteins and gangliosides in the grey and white matter of the brain and spinal cord. It is considered one of the most common neurological diseases of non-traumatic origin in young people, especially in women. Recent studies point to a possible association between MS and gut microbiota. Intestinal dysbiosis has been observed, as well as an alteration of short-chain fatty acid-producing bacteria, although clinical data remain scarce and inconclusive.
OBJECTIVE
To conduct a systematic review on the relationship between gut microbiota and multiple sclerosis.
METHOD
The systematic review was conducted in the first quarter of 2022. The articles included were selected and compiled from different electronic databases: PubMed, Scopus, ScienceDirect, Proquest, Cochrane, and CINAHL. The keywords used in the search were: "multiple sclerosis", "gut microbiota", and "microbiome".
RESULTS
12 articles were selected for the systematic review. Among the studies that analysed alpha and beta diversity, only three found significant differences with respect to the control. In terms of taxonomy, the data are contradictory, but confirm an alteration of the microbiota marked by a decrease in Firmicutes, Lachnospiraceae, , , , , , , , and and an increase in Bacteroidetes, , , and . As for short-chain fatty acids, in general, a decrease in short-chain fatty acids, in particular butyrate, was observed.
CONCLUSIONS
Gut microbiota dysbiosis was found in multiple sclerosis patients compared to controls. Most of the altered bacteria are short-chain fatty acid (SCFA)-producing, which could explain the chronic inflammation that characterises this disease. Therefore, future studies should consider the characterisation and manipulation of the multiple sclerosis-associated microbiome as a focus of both diagnostic and therapeutic strategies.
Topics: Humans; Female; Adolescent; Dysbiosis; Neurodegenerative Diseases; Sclerosis; Microbiota; Fatty Acids, Volatile; Multiple Sclerosis; Bacteria
PubMed: 36901634
DOI: 10.3390/ijerph20054624 -
Journal of Clinical Medicine Feb 2023Critically sized nerve defects cause devastating life-long disabilities and require interposition for reconstruction. Additional local application of mesenchymal stem...
Critically sized nerve defects cause devastating life-long disabilities and require interposition for reconstruction. Additional local application of mesenchymal stem cells (MSCs) is considered promising to enhance peripheral nerve regeneration. To better understand the role of MSCs in peripheral nerve reconstruction, we performed a systematic review and meta-analysis of the effects of MSCs on critically sized segment nerve defects in preclinical studies. 5146 articles were screened following PRISMA guidelines using PubMed and Web of Science. A total of 27 preclinical studies (n = 722 rats) were included in the meta-analysis. The mean difference or the standardized mean difference with 95% confidence intervals for motor function, conduction velocity, and histomorphological parameters of nerve regeneration, as well as the degree of muscle atrophy, was compared in rats with critically sized defects and autologous nerve reconstruction treated with or without MSCs. The co-transplantation of MSCs increased the sciatic functional index (3.93, 95% CI 2.62 to 5.24, < 0.00001) and nerve conduction velocity recovery (1.49, 95% CI 1.13 to 1.84, = 0.009), decreased the atrophy of targeted muscles (gastrocnemius: 0.63, 95% CI 0.29 to 0.97 = 0.004; triceps surae: 0.08, 95% CI 0.06 to 0.10 = 0.71), and promoted the regeneration of injured axons (axon number: 1.10, 95% CI 0.78 to 1.42, < 0.00001; myelin sheath thickness: 0.15, 95% CI 0.12 to 0.17, = 0.28). Reconstruction of critically sized peripheral nerve defects is often hindered by impaired postoperative regeneration, especially in defects that require an autologous nerve graft. This meta-analysis indicates that additional application of MSC can enhance postoperative peripheral nerve regeneration in rats. Based on the promising results in vivo experiments, further studies are needed to demonstrate potential clinical benefits.
PubMed: 36835844
DOI: 10.3390/jcm12041306 -
Brain Sciences Jan 2023(1) Background: Multiple sclerosis (MS) is an immune system disease in which myelin in the nervous system is affected. This abnormal immune system mechanism causes... (Review)
Review
(1) Background: Multiple sclerosis (MS) is an immune system disease in which myelin in the nervous system is affected. This abnormal immune system mechanism causes physical disabilities and cognitive impairment. Functional magnetic resonance imaging (fMRI) is a common neuroimaging technique used in studying MS. Computational methods have recently been applied for disease detection, notably graph theory, which helps researchers understand the entire brain network and functional connectivity. (2) Methods: Relevant databases were searched to identify articles published since 2000 that applied graph theory to study functional brain connectivity in patients with MS based on fMRI. (3) Results: A total of 24 articles were included in the review. In recent years, the application of graph theory in the MS field received increased attention from computational scientists. The graph-theoretical approach was frequently combined with fMRI in studies of functional brain connectivity in MS. Lower EDSSs of MS stage were the criteria for most of the studies (4) Conclusions: This review provides insights into the role of graph theory as a computational method for studying functional brain connectivity in MS. Graph theory is useful in the detection and prediction of MS and can play a significant role in identifying cognitive impairment associated with MS.
PubMed: 36831789
DOI: 10.3390/brainsci13020246 -
Frontiers in Neuroendocrinology Apr 2023In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter...
In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter systems. Several parallels between progesterone and older generation progestin actions emerged, suggesting actions via progesterone receptors. However, existing results suggest a general lack of knowledge regarding the effects of currently used progestins in hormonal contraception regarding these cellular and molecular brain parameters. Human neuroimaging studies were reviewed with a focus on randomized placebo-controlled trials and cross-sectional studies controlling for progestin type. The prefrontal cortex, amygdala, salience network and hippocampus were identified as regions of interest for future preclinical studies. This review proposes a series of experiments to elucidate the cellular and molecular actions of contraceptive progestins in these areas and link these actions to behavioral markers of emotional and cognitive functioning. Emotional effects of contraceptive progestins appear to be related to 1) alterations in the serotonergic system, 2) direct/indirect modulations of inhibitory GABA-ergic signalling via effects on the allopregnanolone content of the brain, which differ between androgenic and anti-androgenic progestins. Cognitive effects of combined oral contraceptives appear to depend on the ethinylestradiol dose.
Topics: Animals; Humans; Progestins; Progesterone; Contraceptive Agents; Cross-Sectional Studies; Progesterone Congeners; Brain
PubMed: 36758768
DOI: 10.1016/j.yfrne.2023.101060 -
Acta Histochemica Jan 2023Epithelial membrane protein 2 (EMP2) is a cell surface protein composed of approximately 160 amino acids and encoded by the growth arrest-specific 3 (GAS3)/peripheral... (Review)
Review
OBJECTIVES
Epithelial membrane protein 2 (EMP2) is a cell surface protein composed of approximately 160 amino acids and encoded by the growth arrest-specific 3 (GAS3)/peripheral myelin protein 22 kDa (PMP22) gene family. Although EMP2 expression has been investigated in several diseases, much remains unknown regarding its mechanism of action and the extent of its role in pathogenesis. Our aim was to perform a systematic review on the involvement of EMP2 in disease processes and the current usage of anti-EMP2 therapies.
METHODS
A Boolean search of the English-language medical literature was performed. PubMed, Scopus, Cochrane, and Web of Science were used to identify relevant citations. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
52 studies met the inclusion criteria for qualitative analysis. Of those, 28 (53.8%) were human-only studies, 11 (21.2%) were animal-only studies, and 13 (25%) studies included both human and animal models. Furthermore, 34 (65.4%) studies focused on EMP2's role in neoplasms, while the remaining 18 (34.6%) articles evaluated its role in other pathologies.
CONCLUSION
Overall, the evidence suggests the mechanisms of action of EMP2 are context dependent. Promising results have been produced by utilizing EMP2 as a biomarker and therapeutic target. More studies are warranted to better understand the mechanism and comprehend the role of EMP2 in the pathogenesis of diseases.
Topics: Animals; Humans; Membrane Glycoproteins; Membrane Proteins
PubMed: 36455339
DOI: 10.1016/j.acthis.2022.151976 -
International Journal of Molecular... Nov 2022Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory... (Review)
Review
Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory infection. This narrative overview aims to summarise and discuss current knowledge and previous evidence regarding triggers and pathophysiology of GBS. A systematic search of the literature was carried out using suitable search terms. The most common subtypes of GBS are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). The most common triggers of GBS, in three quarters of cases, are previous infections. The most common infectious agents that cause GBS include , , and cytomegalovirus. is responsible for about a third of GBS cases. GBS due to is usually more severe than that due to other causes. Clinical presentation of GBS is highly dependent on the structure of pathogenic lipo-oligosaccharides (LOS) that trigger the innate immune system via Toll-like-receptor (TLR)-4 signalling. AIDP is due to demyelination, whereas in AMAN, structures of the axolemma are affected in the nodal or inter-nodal space. In conclusion, GBS is a neuro-immunological disorder caused by autoantibodies against components of the myelin sheath or axolemma. Molecular mimicry between surface structures of pathogens and components of myelin or the axon is one scenario that may explain the pathophysiology of GBS.
Topics: Humans; Amantadine; Autoantibodies; Axons; Campylobacter jejuni; Guillain-Barre Syndrome
PubMed: 36430700
DOI: 10.3390/ijms232214222 -
BMC Neurology Nov 2022Overlap syndromes of anti-NMDA receptor encephalitis and MOG-mediated demyelination have been reported. In this case we provide a long-term longitudinal follow-up of...
BACKGROUND
Overlap syndromes of anti-NMDA receptor encephalitis and MOG-mediated demyelination have been reported. In this case we provide a long-term longitudinal follow-up of clinical and imaging characteristics as well as of antibody dynamics.
CASE PRESENTATION
We report a 32-year-old male patient who presented with psychosis, decreased consciousness and movement disorders and was tested positive for anti-NMDA receptor antibodies. Forty-four months after symptom onset and diagnosis of autoimmune encephalitis, he suffered from relapse. At this time, the patient developed anti-MOG and anti-Caspr2 antibodies. Treatment with plasmapheresis, steroids and rituximab eventually led to substantial clinical and radiological improvement. Anti-Caspr2 antibodies persisted, anti-NMDA receptor antibodies decreased, while anti-MOG antibodies turned negative again.
CONCLUSION
We provide long-term longitudinal follow-up of a patient with anti-NMDA receptor encephalitis who developed triple antibody positivity at the time of relapse. Antibody dynamics were associated with clinical disease course.
Topics: Male; Humans; Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Myelin-Oligodendrocyte Glycoprotein; Follow-Up Studies; Autoantibodies; Neoplasm Recurrence, Local; Receptors, N-Methyl-D-Aspartate; Demyelinating Diseases
PubMed: 36384491
DOI: 10.1186/s12883-022-02974-x -
Multiple Sclerosis Journal -... 2022Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has various similarities with AQP4-IgG-seropositive Neuromyelitis Optica Spectrum Disorder...
BACKGROUND
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has various similarities with AQP4-IgG-seropositive Neuromyelitis Optica Spectrum Disorder (AQP4-IgG + NMOSD) in terms of clinical presentations, magnetic resonance imaging (MRI) findings, and response to treatment. But unlike AQP4-IgG + NMOSD, which is known to coexist with various autoimmune diseases and cancers, an association of MOGAD with these conditions is less clear.
METHODS
We conducted a systematic search in PubMed, Scopus, Web of Science, and Embase based on the preferred reporting items for systematic reviews and meta-analysis (PRISMA). Duplicates were removed using Mendeley 1.19.8 (USA production) and the citations were uploaded into Covidence systematic review platform for screening.
RESULTS
The most common autoimmune disease overlapping with MOGAD was anti-N-Methyl-D-Aspartate receptor encephalitis (anti-NMDAR-EN), followed by autoimmune thyroid disorders, and the most common autoantibody was antinuclear antibody (ANA), followed by AQP4-IgG (double-positive MOG-IgG and AQP4-IgG). A few sporadic cases of cancers and MOG-IgG-associated paraneoplastic encephalomyelitis were found.
CONCLUSION
Unlike AQP4-IgG + NMOSD, MOGAD lacks clustering of autoimmune diseases and autoantibodies associated with systemic and organ-specific autoimmunity. Other than anti-NMDAR-EN and perhaps AQP4-IgG + NMOSD, the evidence thus far does not support the need for routine screening of overlapping autoimmunity and neoplasms in patients with MOGAD.
PubMed: 36311694
DOI: 10.1177/20552173221128170 -
Developmental Cognitive Neuroscience Dec 2022Structural and functional brain alterations are found in adults with depression. It is not known whether these changes are a result of illness or exist prior to disorder... (Review)
Review
Structural and functional brain alterations are found in adults with depression. It is not known whether these changes are a result of illness or exist prior to disorder onset. Asymptomatic offspring of parents with depression offer a unique opportunity to research neural markers of familial risk to depression and clarify the temporal sequence between brain changes and disorder onset. We conducted a systematic review to investigate whether asymptomatic offspring at high familial risk have structural and functional brain changes like those reported in adults with depression. Our literature search resulted in 44 studies on 18,645 offspring ranging from 4 weeks to 25 years old. Reduced cortical thickness and white matter integrity, and altered striatal reward processing were the most consistent findings in high-risk offspring across ages. These alterations are also present in adults with depression, suggesting the existence of neural markers of familial risk for depression. Additional studies reproducing current results, streamlining fMRI data analyses, and investigating underexplored topics (i.e intracortical myelin, gyrification, subcortical shape) may be among the next steps required to improve our understanding of neural markers indexing the vulnerability to depression.
Topics: Adult; Humans; Depression; Genetic Predisposition to Disease; Reward; Magnetic Resonance Imaging; Brain
PubMed: 36242901
DOI: 10.1016/j.dcn.2022.101161 -
Frontiers in Neurology 2022Viral infections are a proposed possible cause of inflammatory central nervous system (CNS) demyelinating diseases, including multiple sclerosis (MS), neuromyelitis...
BACKGROUND
Viral infections are a proposed possible cause of inflammatory central nervous system (CNS) demyelinating diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). During the past 2 years, CNS demyelinating events associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported, but causality is unclear.
OBJECTIVE
To investigate the relationship between CNS demyelinating disease development and exacerbation with antecedent and/or concurrent SARS-CoV-2 infection.
METHODS
A systematic literature review of all publications describing either a new diagnosis or relapse of CNS demyelinating diseases (MS, NMOSD, MOGAD) in association with SARS-CoV-2 infection was performed utilizing PRISMA guidelines. Descriptive statistics were used for data analysis, using a case analysis approach.
RESULTS
Sixty-seven articles met the inclusion criteria for the study. Most of the reported cases of NMOSD ( = 13, 72.2% of reported cases) and MOGAD ( = 27, 96.5% of reported cases) were of new disease onset, presenting with typical clinical and radiographic features of these conditions, respectively. In contrast, reported MS cases varied amongst newly diagnosed cases ( = 10, 10.5% of reported cases), relapses ( = 63, 66.4%) and pseudo-relapses ( = 22, 23.2%). The median duration between COVID-19 infection and demyelinating event onset was 11.5 days (range 0-90 days) in NMOSD, 6 days (range-7 to +45 days) in MOGAD, and 13.5 days (range-21 to +180 days) in MS. Most cases received high-dose corticosteroids with a good clinical outcome.
CONCLUSION
Based upon available literature, the rate of CNS demyelinating events occurring in the setting of preceding or concurrent SARS-CoV-2 infection is relatively low considering the prevalence of SARS-CoV-2 infection. The clinical outcomes of new onset or relapsing MS, NMOSD, or MOGAD associated with antecedent or concurrent infection were mostly favorable. Larger prospective epidemiological studies are needed to better delineate the impact of COVID-19 on CNS demyelinating diseases.
PubMed: 36203986
DOI: 10.3389/fneur.2022.970383