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Scientific Reports Jun 2024Multiple sclerosis (MS) is a chronic and progressive neurological disorder, characterized by neuroinflammation and demyelination within the central nervous system (CNS)....
Multiple sclerosis (MS) is a chronic and progressive neurological disorder, characterized by neuroinflammation and demyelination within the central nervous system (CNS). The etiology and the pathogenesis of MS are still unknown. Till now, no satisfactory treatments, diagnostic and prognostic biomarkers are available for MS. Therefore, we aimed to investigate metabolic alterations in patients with MS compared to controls and across MS subtypes. Metabolic profiles of serum samples from patients with MS (n = 90) and healthy control (n = 30) were determined by Nuclear Magnetic Resonance (H-NMR) Spectroscopy using cryogenic probe. This approach was also utilized to identify significant differences between the metabolite profiles of the MS groups (primary progressive, secondary progressive, and relapsing-remitting) and the healthy controls. Concentrations of nine serum metabolites (adenosine triphosphate (ATP), tryptophan, formate, succinate, glutathione, inosine, histidine, pantothenate, and nicotinamide adenine dinucleotide (NAD)) were significantly higher in patients with MS compared to control. SPMS serum exhibited increased pantothenate and tryptophan than in PPMS. In addition, lysine, myo-inositol, and glutamate exhibited the highest discriminatory power (0.93, 95% CI 0.869-0.981; 0.92, 95% CI 0.859-0.969; 0.91, 95% CI 0.843-0.968 respectively) between healthy control and MS. Using NMR- based metabolomics, we identified a set of metabolites capable of classifying MS patients and controls. These findings confirmed untargeted metabolomics as a useful approach for the discovery of possible novel biomarkers that could aid in the diagnosis of the disease.
Topics: Humans; Biomarkers; Male; Female; Metabolomics; Adult; Middle Aged; Multiple Sclerosis; Disease Progression; Magnetic Resonance Spectroscopy; Metabolome; Case-Control Studies
PubMed: 38926483
DOI: 10.1038/s41598-024-64490-x -
Nature Communications Jun 2024B cells and T cells collaborate in multiple sclerosis (MS) pathogenesis. IgH mice possess a B cell repertoire skewed to recognize myelin oligodendrocyte glycoprotein...
B cells and T cells collaborate in multiple sclerosis (MS) pathogenesis. IgH mice possess a B cell repertoire skewed to recognize myelin oligodendrocyte glycoprotein (MOG). Here, we show that upon immunization with the T cell-obligate autoantigen, MOG, IgH mice develop rapid and exacerbated experimental autoimmune encephalomyelitis (EAE) relative to wildtype (WT) counterparts, characterized by aggregation of T and B cells in the IgH meninges and by CD4 T helper 17 (Th17) cells in the CNS. Production of the Th17 maintenance factor IL-23 is observed from IgH CNS-infiltrating and meningeal B cells, and in vivo blockade of IL-23p19 attenuates disease severity in IgH mice. In the CNS parenchyma and dura mater of IgH mice, we observe an increased frequency of CD4PD-1CXCR5 T cells that share numerous characteristics with the recently described T peripheral helper (Tph) cell subset. Further, CNS-infiltrating B and Tph cells from IgH mice show increased reactive oxygen species (ROS) production. Meningeal inflammation, Tph-like cell accumulation in the CNS and B/Tph cell production of ROS were all reduced upon p19 blockade. Altogether, MOG-specific B cells promote autoimmune inflammation of the CNS parenchyma and meninges in an IL-23-dependent manner.
Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; B-Lymphocytes; Myelin-Oligodendrocyte Glycoprotein; Mice; Autoimmunity; Interleukin-23; CD4-Positive T-Lymphocytes; Th17 Cells; Central Nervous System; Mice, Inbred C57BL; Female; Myelin Sheath; Meninges; Multiple Sclerosis
PubMed: 38926356
DOI: 10.1038/s41467-024-49259-0 -
BMJ Case Reports Jun 2024A primigravida in mid 30s presented to hospital at 30+2 weeks gestation, due to progressive neurological symptoms including ascending limb weakness and paraesthesia...
A primigravida in mid 30s presented to hospital at 30+2 weeks gestation, due to progressive neurological symptoms including ascending limb weakness and paraesthesia bilaterally as well as dysphagia, facial weakness and dysphasia.The patient was diagnosed with Guillain-Barré syndrome after physical examination and electromyography, which showed a patchy demyelinating sensorimotor polyneuropathy. The patient underwent a 5-day course of intravenous immunoglobulin, beginning the day after admission. Markers of severity including forced vital capacity improved thereafter until delivery.With limited evidence favouring one particular anaesthetic technique in parturients with Guillain-Barré syndrome, combined spinal epidural anaesthesia was preferred over general anaesthesia in order to avoid the potential for prolonged intubation postoperatively and to allow careful titration of neuraxial blockade. Delivery by caesarean section at 34+1 weeks due to pre-eclampsia was uncomplicated. Thereafter the patient's condition deteriorated, requiring a further 5-day course of intravenous immunoglobulin with symptoms gradually improving over a 6-month admission.
Topics: Humans; Female; Guillain-Barre Syndrome; Cesarean Section; Pregnancy; Anesthesia, Epidural; Adult; Anesthesia, Spinal; Immunoglobulins, Intravenous; Anesthesia, Obstetrical; Pregnancy Complications
PubMed: 38926128
DOI: 10.1136/bcr-2024-260285 -
Neurology(R) Neuroimmunology &... Sep 2024Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct CNS demyelinating disease. The rate of asymptomatic optic nerve enhancement on MRI...
BACKGROUND AND OBJECTIVES
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct CNS demyelinating disease. The rate of asymptomatic optic nerve enhancement on MRI has not been explored in patients with MOGAD. An improved understanding of this would guide clinical practice and assessment of treatment efficacy. We aimed to determine the frequency of asymptomatic optic nerve enhancement in MOGAD.
METHODS
This was a retrospective review of patients evaluated at Mayo Clinic with MOGAD between January 1, 2000, and August 1, 2021 (median follow-up 1.6 [range 1-19] years). MRI studies were reviewed by masked neuroradiologists. Scans performed within 30 days of ON attack were classified as attack scans. Images obtained for routine surveillance, before ON attack, or at the time of non-ON attack were classified as interattack scans.
RESULTS
Five hundred sixty-six MRIs (203 unique patients, 53% female) were included. Interattack MRIs represented 341 (60%) of the scans (median 36 days post-ON [range -1,032 to 6,001]). Of the interattack scans, 43 of 341 (13%), 30 unique patients, showed optic nerve enhancement. The enhancement was located at prior sites of ON in 35 of 43 (81%). Among the 8 patients with enhancement in new optic nerve areas, 6 had acute disseminated encephalomyelitis without an eye examination at the time of the MRI and 2 had preceding ON without imaging. Long-term visual outcomes showed no significant difference between those with and without asymptomatic enhancement, with improved visual acuity in most patients.
DISCUSSION
Asymptomatic optic nerve enhancement occurred in 13% of interattack MRIs, the majority in patients with prior ON and occurring at prior sites of optic nerve enhancement. New asymptomatic optic nerve enhancement in areas without prior ON was rare. These findings are important for understanding the natural history of MOGAD, the interpretation of symptoms or response to treatment, and the adjudication of attacks in clinical trials.
Topics: Humans; Female; Male; Adult; Myelin-Oligodendrocyte Glycoprotein; Retrospective Studies; Magnetic Resonance Imaging; Middle Aged; Young Adult; Optic Nerve; Adolescent; Aged; Child; Autoantibodies; Demyelinating Autoimmune Diseases, CNS; Child, Preschool; Asymptomatic Diseases; Aged, 80 and over
PubMed: 38924706
DOI: 10.1212/NXI.0000000000200277 -
CNS Neuroscience & Therapeutics Jun 2024To date, most existing models for predicting neuromyelitis optica spectrum disorder (NMOSD) are based primarily on clinical characteristics. Blood-based NMOSD severity...
Blood-based inflammatory protein biomarker panel for the prediction of relapse and severity in patients with neuromyelitis optica spectrum disorder: A prospective cohort study.
BACKGROUND
To date, most existing models for predicting neuromyelitis optica spectrum disorder (NMOSD) are based primarily on clinical characteristics. Blood-based NMOSD severity and prognostic predictive immune- and inflammation-related biomarkers are needed. We aimed to investigate the associations between plasma inflammatory biomarkers and relapse and attack severity in NMOSD.
METHODS
This two-step, single-center prospective cohort study included discovery and validation cohorts. We quantified 92 plasma inflammatory proteins by using Olink's proximity extension assay and identified differentially expressed proteins in the relapse group (relapse within 1 year of follow-up) and severe attack group. To define a new molecular prognostic model, we calculated the risk score of each patient based on the key protein signatures and validated the results in the validation cohort.
RESULTS
The relapse prediction model, including FGF-23, DNER, GDNF, and SLAMF1, predicted the 1-year relapse risk. The severe attack prediction model, including PD-L1 and MCP-2, predicted the severe clinical attack risk. Both the relapse and severe attack prediction models demonstrated good discriminative ability and high accuracy in the validation cohort.
CONCLUSIONS
Our discovered biomarker signature and prediction models may complement current clinical risk stratification approaches. These inflammatory biomarkers could contribute to the discovery of therapeutic interventions and prevent NMOSD progression.
Topics: Humans; Neuromyelitis Optica; Female; Biomarkers; Male; Adult; Prospective Studies; Recurrence; Middle Aged; Cohort Studies; Severity of Illness Index; Inflammation; Prognosis
PubMed: 38923840
DOI: 10.1111/cns.14811 -
La Medicina Del Lavoro Jun 2024Multiple sclerosis (MS), because of its early age at onset, greatly impacts the working lives of those affected by it in ways linked to different factors, both...
BACKGROUND
Multiple sclerosis (MS), because of its early age at onset, greatly impacts the working lives of those affected by it in ways linked to different factors, both professional and personal. It has been observed that only a small percentage (20-40%) of workers with MS retain their jobs after the diagnosis. When identifying factors determining job retention or loss in this setting, it is essential to consider the direct perspectives of people with MS (PwMS).
METHODS
A qualitative study, based on the conduction of two focus groups, was conducted to explore the personal experiences of PwMS who work.
RESULTS
The results show that there are numerous factors, both positive and negative, that can influence these people's ability to retain their jobs. The climate established in the workplace and the relationship between workers with MS and their colleagues were fundamentally important aspects, as was knowledge of the disease at the level of public opinion.
CONCLUSIONS
Managing work is a complex undertaking for people with a disabling condition like MS. There needs to be greater awareness of the employment rights of PwMS. Improving these knowledge-based aspects could undoubtedly improve the quality of the working lives of PwM.
Topics: Humans; Multiple Sclerosis; Female; Male; Qualitative Research; Adult; Middle Aged; Focus Groups; Disabled Persons; Employment; Workplace; Job Security
PubMed: 38922837
DOI: 10.23749/mdl.v115i3.15947 -
La Medicina Del Lavoro Jun 2024This study, conducted on a sample of Italian occupational physicians (OPs), aimed to gather data regarding professional activity and their needs in managing workers with...
BACKGROUND
This study, conducted on a sample of Italian occupational physicians (OPs), aimed to gather data regarding professional activity and their needs in managing workers with multiple sclerosis.
METHODS
A convenience sample of OPs recruited by e-mail invitation to the list of Italian Society of Occupational Medicine members was considered. A total of 220 OPs participated between July and October 2022. An ad hoc questionnaire was developed based on previous survey experiences. It investigated, among others, the characteristics of OP respondents, the evaluation of fitness for work issues, and the OP training and updating needs on multiple sclerosis and work.
RESULTS
Ninety-one percent of OPs had to assess the fitness for work of workers with multiple sclerosis during their activity. Sixty-four percent experienced particular difficulties in issuing a fitness for work judgment. Regarding the level of knowledge on multiple sclerosis, 54% judged it sufficient. The "Assessment of fitness for work for the specific task" and the "Role of the OPs in identifying reasonable accommodations" were the most interesting training topics regarding MS management in work contexts chosen by the respondents.
CONCLUSIONS
The interest in the work inclusion and job retention of people with disability, particularly the aspects linked to the Identification and implementation of reasonable accommodations, will require integration with the occupational safety and health protection system and will undoubtedly impact the OP's activities.
Topics: Humans; Italy; Multiple Sclerosis; Male; Female; Middle Aged; Adult; Occupational Medicine; Surveys and Questionnaires; Work Capacity Evaluation; Occupational Health Physicians
PubMed: 38922836
DOI: 10.23749/mdl.v115i3.16038 -
International Ophthalmology Jun 2024The aim of this study is to analyse whether optical coherence tomography angiography (angio-OCT, OCTA) measurements can be a useful tool to differentiate central nervous...
Optical coherence tomography angiography as a potential tool in differential diagnosis of multiple sclerosis and rheumatic disorders with central nervous system involvement.
PURPOSE
The aim of this study is to analyse whether optical coherence tomography angiography (angio-OCT, OCTA) measurements can be a useful tool to differentiate central nervous system (CNS) involvement in rheumatic disorders (RD) from multiple sclerosis (MS).
METHODS
A total of 85 patients- 41 with MS, 21 with RD with CNS involvement and 23 healthy controls were included in the study. All individuals underwent OCTA and the following parameters were measured in each eye separately: average foveal and parafoveal vessel density (VD), average foveal and parafoveal vessel length (VL) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as area, perimeter, and circularity of the foveal avascular zone.
RESULTS
OCTA showed a VD reduction in the foveal region of the SCP in eyes of RD patients when compared to MS patients (21.96 ± 3.39 vs.23.88 ± 3.05 (p = 0.003)). There have been no significant differences in any of the assessed parameters that is average VD and total average VL in the foveal area of the SCP as well as of the DCP in the general population comprising healthy controls, MS and RD groups (p > 0.05 for all).
CONCLUSIONS
Our results suggest that an OCTA finding of decreased VD in the foveal region of the SCP may be considered as a potentially useful biomarker of RD in comparison with MS patients.
Topics: Humans; Tomography, Optical Coherence; Male; Female; Multiple Sclerosis; Adult; Diagnosis, Differential; Fluorescein Angiography; Middle Aged; Retinal Vessels; Rheumatic Diseases; Fundus Oculi; Fovea Centralis
PubMed: 38922460
DOI: 10.1007/s10792-024-03217-3 -
Toxins May 2024As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to...
As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to treat both spasticity and neurogenic detrusor overactivity incontinence (NDOI) in patients with spinal cord injuries (SCIs) and multiple sclerosis (MS). We therefore identified patients followed at our institution by health data hub digging, using a specific procedure coding system in use in France, who have been treated at least once with detrusor and skeletal muscle BTIs within the same 1-month period, over the past 5 years (2017-2021). We analyzed 72 patients representing 319 CIs. Fifty (69%) were male, and the patients were mostly SCI (76%) and MS (18%) patients and were treated by a mean number of CIs of 4.4 ± 3.6 [1-14]. The mean cumulative dose was 442.1 ± 98.8 U, and 95% of CIs were performed within a 72 h timeframe. Among all CIs, five patients had symptoms evocative of distant spread but only one had a confirmed pathological jitter in single-fiber EMG. Eleven discontinued CIs for surgical alternatives: enterocystoplasty (five), tenotomy (three), intrathecal baclofen (two) and neurotomy (one). Concomitant BTIs for treating both spasticity and NDOI at the same time appeared safe when performed within a short delay and in compliance with actual knowledge for maximum doses.
Topics: Humans; Muscle Spasticity; Male; Female; Retrospective Studies; Middle Aged; Urinary Bladder, Overactive; Adult; Spinal Cord Injuries; Multiple Sclerosis; Neuromuscular Agents; Botulinum Toxins, Type A; Urinary Bladder, Neurogenic; Aged; Injections, Intramuscular; Treatment Outcome
PubMed: 38922146
DOI: 10.3390/toxins16060252 -
Current Issues in Molecular Biology Jun 2024Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system, the etiology of which is still unclear. Its hallmarks are... (Review)
Review
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system, the etiology of which is still unclear. Its hallmarks are inflammation and axonal damage. As a disease primarily impacting younger individuals, the social cost of MS is high. It has been proposed that environmental factors, smoking, and dietary habits acting on a genetic susceptibility play a role in MS. Recent studies indicate that diet can significantly influence the onset and progression of MS. This review delves into the impact of natural bioactive molecules on MS development and explores the dietary interventions that hold promise in managing the disease. Dietary patterns, including ketogenic and Mediterranean diets, are discussed. Theories about the potential mechanistic associations beneath the noted effects are also proposed. Several dietary components and patterns demonstrated the potential for a significant impact on MS. However, extensive prospective clinical trials are necessary to fully understand the role of natural bioactive molecules as disease modifiers in MS.
PubMed: 38921006
DOI: 10.3390/cimb46060335