-
Journal of Central Nervous System... 2024Appropriate treatment reduces the severity and duration of relapses in demyelinating diseases of Central Nervous System (CNS). If high-dose corticosteroids treatment...
BACKGROUND
Appropriate treatment reduces the severity and duration of relapses in demyelinating diseases of Central Nervous System (CNS). If high-dose corticosteroids treatment fails, therapeutic plasma exchange (TPE) is considered as a rescue treatment.
OBJECTIVES
This study aimed to investigate early clinical response and complications of TPE and prognostic factors in CNS demyelinating relapses.
DESIGN
This prospective observational study was designed in a tertiary center during one year.
METHODS
All adult patients diagnosed corticosteroid-resistant Multiple Sclerosis (MS), NeuroMyelitis Optica Spectrum Disorder (NMOSD), idiotypic Transverse Myelitis or Clinical Isolated Syndrome relapses, were eligible. Clinical response is defined based on Expanded Disability Status Scale (EDSS) at discharge. Clinical and laboratory complications recorded.
RESULTS
Seventy-two patients were analyzed which 58.3% patients were female. MS was diagnosed for 61.1% of cases. Thirty-five patients (48.6%) responded and the mean differences of EDSS significantly decreased 0.60 score (CI95%:0.44-.77). Electrolyte imbalances and thrombocytopenia occurred in 80.6% and 55.6% of cases respectively and 40.3% of patients had systemic reactions. However, 26.4% patients experienced moderate to severe complications. In patients with moderate to severe disability, responders were younger (MD: 8.42 years, CI95%: 1.67-15.17) and had lower EDSS score at admission (median:6, IQR: 5.5-6 against 7.5 IQR: 6.5-8). The risk of failure was higher in active progressive MS patients compared with RRMS patients (OR: 6.06, CI 95%:1.37-26.76). Patients with thrombocytopenia were hospitalized more than others (MD: 1.5 days, CI 95%: 0-3). Females were more prone to hypokalemia and systemic reactions (OR: 3.11, CI 95%:1.17-8.24 and OR: 6.67, CI 95%:2.14-20.81 respectively).
CONCLUSION
The most common indication of TPE was corticosteroid-resistant severe MS relapses. About half of the patients presented an early clinical response. Lower disability, younger age and RRMS diagnosis are prognostic factors of better response. One out of four patients experienced moderate to severe complications, mainly electrolyte imbalances and systemic reactions. Appropriate interventions against these complications should be considered during TPE, especially in females.
PubMed: 38903856
DOI: 10.1177/11795735241262738 -
Frontiers in Genetics 2024Charcot-Marie-Tooth disease type 4C (CMT4C) OMIM#601596 stands out as one of the most prevalent forms of recessive motor sensory neuropathy worldwide. This disorder...
INTRODUCTION
Charcot-Marie-Tooth disease type 4C (CMT4C) OMIM#601596 stands out as one of the most prevalent forms of recessive motor sensory neuropathy worldwide. This disorder results from biallelic pathogenic variants in the gene.
METHODS
Within a cohort comprising 700 unrelated Russian patients diagnosed with Charcot-Marie-Tooth disease, we conducted a gene panel analysis encompassing 21 genes associated with hereditary neuropathies. Among the cohort, 394 individuals exhibited demyelinating motor and sensory neuropathy.
RESULTS AND DISCUSSION
Notably, 10 cases of CMT4C were identified within this cohort. The prevalence of CMT4C among Russian demyelinating CMT patients lacking the duplication is estimated at 2.5%, significantly differing from observations in European populations. In total, 4 novel and 9 previously reported variants in the gene were identified. No accumulation of a major variant was detected. Three previously reported variants, c.2860C>T p. (Arg954*), p. (Arg658Cys) and c.279G>A p. (Lys93Lys), recurrently detected in unrelated families. Nucleotide alteration p. (Arg954*) is present in most of our patients (30%).
PubMed: 38903759
DOI: 10.3389/fgene.2024.1381915 -
Cureus May 2024We discuss a perplexing case of a 51-year-old female with a history of asthma and morbid obesity, presenting with acute bilateral vision loss of unknown etiology. The...
We discuss a perplexing case of a 51-year-old female with a history of asthma and morbid obesity, presenting with acute bilateral vision loss of unknown etiology. The patient's clinical course was marked by a constellation of symptoms, including blurry vision, eyeball pain, photophobia, headache, nausea, and dizziness, prompting a multidisciplinary approach for diagnostic evaluation. Despite a comprehensive workup and a temporal artery biopsy ruling out large vessel arteritis, the etiology of vision loss remained elusive until myelin oligodendrocyte glycoprotein (MOG) antibody testing returned positive, implicating myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). High-dose corticosteroid therapy was initiated. However, the patient had worsening visual symptoms and was started on plasmapheresis and subsequent administration of Rituximab to prevent relapses, along with a long-term steroid taper regimen. This case underscores the diagnostic challenge of optic neuritis, particularly in MOGAD. It emphasizes the importance of a thorough evaluation and multidisciplinary collaboration.
PubMed: 38903369
DOI: 10.7759/cureus.60612 -
Cureus May 2024Myelopathy manifests in childhood and can be clinically categorized according to the site of injury (which may result in spinal syndrome) or the source (which may be...
Myelopathy manifests in childhood and can be clinically categorized according to the site of injury (which may result in spinal syndrome) or the source (which may be nontraumatic or widely traumatic). Nontraumatic myelopathy can be caused by inflammatory, infectious, nutritional, metabolic, or ischemic factors. It may also be associated with systemic illnesses such as demyelinating disease, multiple sclerosis, or systemic lupus. Nonintentional harm is a significant factor to take into account in instances of traumatic myelopathy, which can frequently be linked to additional injuries. MRI and CT radiography help identify compressive myelopathy. We present the case of a 12-year-old girl who is right-hand dominant. She was in good health six months ago but recently began experiencing weakness in both of her lower limbs. An MRI of the brain revealed basilar invagination with stenosis of the foramen magnum, causing compressive myelopathy at the cranio-vertebral junction. The patient was operated on, followed by physiotherapy rehabilitation to improve functional independence and quality of life.
PubMed: 38903349
DOI: 10.7759/cureus.60785 -
Acta Medica Okayama Jun 2024The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol-disulfide...
The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol-disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients' sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol-disulfide homeostasis and ischaemia-modified albumin were measured.
We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol-disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol-disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol-disulfide homeostasis in multiple sclerosis patients.Topics: Humans; Oxidative Stress; Female; Male; Middle Aged; Sleep Wake Disorders; Adult; Multiple Sclerosis; Fatigue; Cognitive Dysfunction; Lipids; Homeostasis; Serum Albumin, Human; Disulfides; Sulfhydryl Compounds; Biomarkers
PubMed: 38902214
DOI: 10.18926/AMO/67201 -
Clinical Nutrition ESPEN Aug 2024Diet and inflammation may contribute to the development of multiple sclerosis (MS). The aim of this systematic review and meta-analysis was to assess the association... (Meta-Analysis)
Meta-Analysis
Diet and inflammation may contribute to the development of multiple sclerosis (MS). The aim of this systematic review and meta-analysis was to assess the association between proinflammatory diet, as estimated by the Dietary Inflammatory Index (DII®), and the likelihood of developing MS or other demyelinating autoimmune diseases. A systematic search was performed of search engines and databases (PubMed, ISI Web of Sciences, Scopus, and Embase) to identify relevant studies before 10th June 2023. The search identified 182 potential studies, from which 39 full-text articles were screened for relevance. Five articles with case-control design (n = 4,322, intervention group: 1714; control group: 2608) met the study inclusion criteria. The exposure variable was DII, with studies using two distinct models: quartile-based comparisons of DII and assessment of continuous DII. The meta-analysis of high versus low quartiles of DII with four effect sizes showed a significant association with MS/demyelinating autoimmune disease likelihood, with an odds ratio (OR) of 3.26 (95% confidence interval (CI) 1.16, 9.10). The meta-analysis of four studies with DII fit as a continuous variable showed a 31% increased likelihood of MS per unit increment; which was not statistically significant at the nominal alpha equals 0.05 (OR 1.31; 95% CI 0.95, 1.81). In conclusion, this systematic review and meta-analysis provides evidence of a positive association between higher DII scores with the likelihood of developing MS, highlighting that diet-induced inflammation could play a role in MS or other demyelinating autoimmune diseases risk.
Topics: Humans; Multiple Sclerosis; Diet; Inflammation; Demyelinating Diseases; Autoimmune Diseases; Risk Factors
PubMed: 38901931
DOI: 10.1016/j.clnesp.2024.04.022 -
Neurobiology of Disease Jun 2024Within the adult mouse subventricular zone (SVZ), neural stem cells (NSCs) produce neuroblasts and oligodendrocyte precursor cells (OPCs). T, the active thyroid hormone,...
Within the adult mouse subventricular zone (SVZ), neural stem cells (NSCs) produce neuroblasts and oligodendrocyte precursor cells (OPCs). T, the active thyroid hormone, influences renewal and commitment of SVZ progenitors. However, how regulators of T availability affect these processes is less understood. Using Mct8/Dio2 knockout mice, we investigated the role of MCT8, a TH transporter, and DIO2, the T-generating enzyme, in regulating adult SVZ-neurogliogenesis. Single-cell RNA-Seq revealed Mct8 expression in various SVZ cell types in WT mice, while Dio2 was enriched in neurons, astrocytes, and quiescent NSCs. The absence of both regulators in the knockout model dysregulated gene expression, increased the neuroblast/OPC ratio and hindered OPC differentiation. Immunostainings demonstrated compromised neuroblast migration reducing their supply to the olfactory bulbs, impairing interneuron differentiation and odor discrimination. These findings underscore the pivotal roles of MCT8 and DIO2 in neuro- and oligodendrogenesis, offering targets for therapeutic avenues in neurodegenerative and demyelinating diseases.
PubMed: 38901782
DOI: 10.1016/j.nbd.2024.106572 -
ELife Jun 2024Autoimmune diseases of the central nervous system (CNS) such as multiple sclerosis (MS) are only partially represented in current experimental models and the development...
Spontaneous human CD8 T cell and autoimmune encephalomyelitis-induced CD4/CD8 T cell lesions in the brain and spinal cord of HLA-DRB1*15-positive multiple sclerosis humanized immune system mice.
Autoimmune diseases of the central nervous system (CNS) such as multiple sclerosis (MS) are only partially represented in current experimental models and the development of humanized immune mice is crucial for better understanding of immunopathogenesis and testing of therapeutics. We describe a humanized mouse model with several key features of MS. Severely immunodeficient B2m-NOG mice were transplanted with peripheral blood mononuclear cells (PBMCs) from HLA-DRB1-typed MS and healthy (HI) donors and showed rapid engraftment by human T and B lymphocytes. Mice receiving cells from MS patients with recent/ongoing Epstein-Barr virus reactivation showed high B cell engraftment capacity. Both HLA-DRB1*15 (DR15) MS and DR15 HI mice, not HLA-DRB1*13 MS mice, developed human T cell infiltration of CNS borders and parenchyma. DR15 MS mice uniquely developed inflammatory lesions in brain and spinal cord gray matter, with spontaneous, hCD8 T cell lesions, and mixed hCD8/hCD4 T cell lesions in EAE immunized mice, with variation in localization and severity between different patient donors. Main limitations of this model for further development are poor monocyte engraftment and lack of demyelination, lymph node organization, and IgG responses. These results show that PBMC humanized mice represent promising research tools for investigating MS immunopathology in a patient-specific approach.
Topics: Animals; Humans; Multiple Sclerosis; Mice; HLA-DRB1 Chains; CD8-Positive T-Lymphocytes; Spinal Cord; Disease Models, Animal; Brain; Encephalomyelitis, Autoimmune, Experimental; CD4-Positive T-Lymphocytes; Female
PubMed: 38900149
DOI: 10.7554/eLife.88826 -
Brain and Behavior Jun 2024Gut microbiota alterations in multiple sclerosis (MS) patients have been reported in observational studies, but whether these associations are causal is unclear.
BACKGROUND
Gut microbiota alterations in multiple sclerosis (MS) patients have been reported in observational studies, but whether these associations are causal is unclear.
OBJECTIVE
We performed a Mendelian randomization study (MR) to assess the causal effects of gut microbiota on MS.
METHODS
Independent genetic variants associated with 211 gut microbiota phenotypes were selected as instrumental variables from the largest genome-wide association studies (GWAS) previously published by the MiBioGen study. GWAS data for MS were obtained from the International Multiple Sclerosis Genetics Consortium (IMSGC) for primary analysis and the FinnGen consortium for replication and collaborative analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy.
RESULTS
After inverse-variance-weighted and sensitivity analysis filtering, seven gut microbiota with potential causal effects on MS were identified from the IMSGC. Only five metabolites remained significant associations with MS when combined with the FinnGen consortium, including genus Anaerofilum id.2053 (odds ratio [OR] = 1.141, 95% confidence interval [CI]: 1.021-1.276, p = .021), Ruminococcus2 id.11374 (OR = 1.190, 95% CI: 1.007-1.406, p = .042), Ruminococcaceae UCG003 id.11361 (OR = 0.822, 95% CI: 0.688-0.982, p = .031), Ruminiclostridium5 id.11355 (OR = 0.724, 95% CI: 0.585-0.895, p = .003), Anaerotruncus id.2054 (OR = 0.772, 95% CI: 0.634-0.940, p = .010).
CONCLUSION
Our MR analysis reveals a potential causal relationship between gut microbiota and MS, offering promising avenues for advancing mechanistic understanding and clinical investigation of microbiota-mediated MS.
Topics: Humans; Mendelian Randomization Analysis; Multiple Sclerosis; Gastrointestinal Microbiome; Genome-Wide Association Study
PubMed: 38898610
DOI: 10.1002/brb3.3593