Course Of Multiple Sclerosis Research Articles

Modern diagnostic potentials of studying structural and functional changes of the retina and the optic nerve in multiple sclerosis patients

Purpose: to study significant functional and structural changes in the retina and the intraocular section of the optic nerve in multiple sclerosis (MS) patients and analyze how they are interrelated with electrophysiological changes in the visual analyzer.Materials and methods. The study included 44 patients (88 eyes): group 1 (26 eyes) with MS duration ≤ 5 years and no history of optic neuritis (ON); group 2 (30 eyes) with MS duration from 6 to15 years and no history of ON; and group 3 (32 eyes) with MS duration ≤ 15 years with a history of ON. All patients underwent a complete ophthalmological examination and optical coherence tomography and had visually evoked potentials (VEP) and static automated perimetry registered.Results. A decrease in functional and structural parameters progressing with the duration of MS was revealed. In particular, best corrected visual acuity (BCVA) fell to 0.860 ± 0.075, the photosensitivity index MD maximally fell to -3.78 ± 0.95 dB, the strength of the P100 wave amplitude dropped to 7.84 ± 2.98 μV, the latency index of VEP rose to 124.21 ± 1.36 ms, the thickness of GCL + IPL fell to 65.69 ± 7.85 μm, and RNFL thickness averagely fell a low as to 80.25 ± 8.81 μm. When analyzing the topography of GCL + IPL decrease by sectors, the maximum value was revealed in the upper temporal segment (67.63 ± 7.89 μm). Sectoral changes in RNFL arranged in descending order of thickness showed the following sequence: lower upper nasal temporal. As the disease progressed, structural and functional changes were accompanied by an increase in the depth and a decrease in the thickness of the lamina cribrosa, with a maximum value revealed in the group with prior ON (239.00 ± 11.93 μm). Strong correlations were found in all study groups between (1) ave. GCL + IPL and ave. RNFL (r = 0.69; 0.64; 0.88, p < 0.03), (2) ave. GCL+IPL and BCVA (r = 0.86; 0.75; 0.78, p < 0.05), (3) MD and ave GCL + IPL (r = 0.52; 0.69; 0.71, p < 0.03), and (4) MD and ave. RNFL (r = 0.67; 0.61; 0.66, p < 0.05), as well as between the parameters of the lamina cribrosa and the markers under study.Conclusion. Significant functional and structural changes in the retina and the optic nerve were detected, correlating with the duration of the disease and with the clinical features of the course of multiple sclerosis. The presence of ON in history was accompanied by more pronounced changes, which can be considered as an important additional aggravating factor of the disease.

TRAF6 signaling in T cells is crucial for the pathogenicity of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an incurable chronic autoimmune disease affecting the central nervous system (CNS). Although IL-17-producing helper T (Th17) cells are thought to be one of the exacerbating factors in MS, the underlying pathogenic mechanism is incompletely understood. TNF receptor-associated factor 6 (TRAF6) deficient T cells exhibited enhanced Th17 cell differentiation, however, the physiological relevance of TRAF6 in T cells remains unknown. Here, we induced experimental autoimmune encephalomyelitis (EAE) in T cell-specific TRAF6 deficient (TRAF6ΔT) mice to investigate the role of TRAF6 in T cells during the course of MS using an EAE model. Although Th17 cell differentiation was enhanced in TRAF6ΔT mice, mutant mice were resistant to EAE. In contrast, TRAF6 loss did not affect regulatory T-cell differentiation. Consistent with the severity of EAE, a small number of infiltrating T cells and a small area of demyelination were observed in the CNS of TRAF6ΔT mice. Moreover, myelin oligodendrocyte glycoprotein-induced IL-17 production in TRAF6-deficient T cells was significantly suppressed. We further confirmed lower levels of CD69 and granulocyte-macrophage colony-stimulating factor in Th17 cells of TRAF6ΔT mice than in wild-type mice. In contrast, the expression of IL-10 and cytotoxic T-lymphocyte-associated protein 4 in T cells was significantly elevated in the absence of TRAF6 because of enhanced T-cell receptor signaling. Collectively, TRAF6 signaling in T cells contributes to the pathogenesis of EAE by regulating the pathogenicity and autoantigen reactivity of Th17 cells.

The role of ocrelizumab in recommendations and in the Polish therapeutic programme

Multiple sclerosis is a heterogeneous and chronic disease, and the primary goal of treatment is to prevent relapses and slow the progression of disability. Ocrelizumab is a generally well-tolerated disease-modifying therapy for multiple sclerosis, with high efficacy in the treatment of active relapsing forms, and a valuable treatment method for delaying the progression of the disease in patients with the primary progressive form. The activity of relapsing multiple sclerosis is defined on the basis of the clinical course of the disease or radiological findings assessed over a year. The occurrence of clinical relapses and/or activity on magnetic resonance imaging is taken into account. In line with the recommendations of the European Committee for Treatment and Research in Multiple Sclerosis and the European Academy of Neurology, as well as in accordance with the guidelines of the American Academy of Neurology, updated in 2021, depending on the disease activity in the early stage of multiple sclerosis, the choice of a disease-modifying drug should be motivated by higher efficacy. Recommendations for the treatment of multiple sclerosis in most countries in Europe and around the world are based on the above-mentioned guidelines. In Poland, recommendations for treatment modifying the course of multiple sclerosis were developed in 2023 by experts from the Multiple Sclerosis and Neuroimmunology Section of the Polish Neurological Society. Treatment based on the B.29 drug programme of the National Health Fund in Poland allows, from 1 July 2023, in addition to escalation, using the induction model based on highly effective therapies as first-line treatment.

The mechanism of action of anti-CD20 monoclonal antibodies used in the treatment of multiple sclerosis

CD20 is a transmembrane molecule located on the surface of a major population of cells belonging to the B lymphocyte lineage. Although the significance of this protein remains unknown, the presence of CD20 is a marker for mature circulating B cells. Monoclonal antibodies against CD20 are able to quickly and effectively eliminate circulating B lymphocytes. Four different anti-CD20 antibodies have been studied in the treatment of multiple sclerosis: rituximab, ocrelizumab, ofatumumab and ublituximab. Although all these monoclonal antibodies bind to the same protein, they have different molecular and pharmacological characteristics. One of the important differences between these molecules is the degree of humanisation of their molecular structure, as well as the mechanism of B cell removal. Phase III multicentre clinical trials conducted with each of these antibodies consistently confirmed that the elimination of B cells is an effective method of slowing down the progression of multiple sclerosis. Thus, B cells are considered as main group of immune cells involved in the development and course of multiple sclerosis. Numerous in vitro and in vivo data confirm the involvement of these cells in the pathogenesis of multiple sclerosis, despite the lack of evidence for the presence of pathogenic autoantibodies in this disease. Nevertheless, B cells represent a mixture of cell populations with different immunomodulatory properties. Therefore, future multiple sclerosis therapies should target the pathogenic groups of B lymphocytes, rather than non-selectively eliminating the entire population of these cells.

Longitudinal fibre-specific white matter damage predicts cognitive decline in multiple sclerosis.

During the course of multiple sclerosis, many patients experience cognitive deficits which are not simply driven by lesion number or location. By considering the full complexity of white matter structure at macro- and microstructural levels, our understanding of cognitive impairment in multiple sclerosis may increase substantially. Accordingly, this study aimed to investigate specific patterns of white matter degeneration, the evolution over time, the manifestation across different stages of the disease and their role in cognitive impairment using a novel fixel-based approach. Neuropsychological test scores and MRI scans including 30-direction diffusion-weighted images were collected from 327 multiple sclerosis patients (mean age = 48.34 years, 221 female) and 95 healthy controls (mean age = 45.70 years, 55 female). Of those, 233 patients and 61 healthy controls had similar follow-up assessments 5 years after. Patients scoring 1.5 or 2 standard deviations below healthy controls on at least two out of seven cognitive domains (from the Brief Repeatable Battery of Neuropsychological Tests, BRB-N) were classified as mildly cognitively impaired or cognitively impaired, respectively, or otherwise cognitively preserved. Fixel-based analysis of diffusion data was used to calculate fibre-specific measures (fibre density, reflecting microstructural diffuse axonal damage; fibre cross-section, reflecting macrostructural tract atrophy) within atlas-based white matter tracts at each visit. At baseline, all fixel-based measures were significantly worse in multiple sclerosis compared with healthy controls (P < 0.05). For both fibre density and fibre cross-section, a similar pattern was observed, with secondary progressive multiple sclerosis patients having the most severe damage, followed by primary progressive and relapsing-remitting multiple sclerosis. Similarly, damage was least severe in cognitively preserved (n = 177), more severe in mildly cognitively impaired (n = 63) and worst in cognitively impaired (n = 87; P < 0.05). Microstructural damage was most pronounced in the cingulum, while macrostructural alterations were most pronounced in the corticospinal tract, cingulum and superior longitudinal fasciculus. Over time, white matter alterations worsened most severely in progressive multiple sclerosis (P < 0.05), with white matter atrophy progression mainly seen in the corticospinal tract and microstructural axonal damage worsening in cingulum and superior longitudinal fasciculus. Cognitive decline at follow-up could be predicted by baseline fixel-based measures (R2 = 0.45, P < 0.001). Fixel-based approaches are sensitive to white matter degeneration patterns in multiple sclerosis and can have strong predictive value for cognitive impairment. Longitudinal deterioration was most marked in progressive multiple sclerosis, indicating that degeneration in white matter remains important to characterize further in this phenotype.

CONNECTION BETWEEN COMORBID PRIMARY HEADACHE, DEPRESSION AND ANXIETY IN PATIENTS WITH MULTIPLE SCLEROSIS

SUMMARY. Multiple sclerosis (MS) is a chronic autoimmune disorder of central nervous system that affects young people and progresses to physical disability. Among patient with MS risk of excessive anxiety and depression is quite common. One of the frequent comorbidities of MS is primary comorbid headache. Depression and anxiety might be more prominent on patients with pain comorbidity of MS. The aim – to show the prevalence and frequency of depression and anxiety in a population of patients with MS, with special attention to the group of patients with primary comorbid headache. Material and Methods. MS was confirmed according to the McDonald criteria 2017. Questionnaires Beck Depression Inventory (BDI) for assessment of depression and The Spielberger State-Trait Anxiety Inventory in Hanin`s interpretation (STAI), version for evaluation of reactive anxiety were used. Results. 130 patients with MS were examined with disease duration 8.63±7.49 years. 36.2 % of males (n=47) and 63.8 % of females (n=83) were included. Average score of patients with MS was 40.22±8.89 points that indicates moderate reactive anxiety. BDI score accounted for 14.15±7.58 points that interpretates as mild-to-moderate depression. Patients with MS and comorbid primary headache received the average points of the STAI in Hanin's interpretation – 42.41±7.49 (moderate anxiety); patients with MS without comorbid primary headache – 37.42±9.31 (low or moderate anxiety), but generally this difference did not show statistical significance (p=0.39). Among MS course scores of anxiety was similar between groups, depression score was the highest in group with primary progressive MS (PPMS). Conclusion. The average score of anxiety and depression showed moderate severity among patients with MS. There were not found significance between patients with primary headache comorbidity and without it, although scores between course disease subgroups showed higher points in patients with comorbid primary headache.

Clinical course of multiple sclerosis with comorbid endometriosis: A matched cohort study

BackgroundEndometriosis (EMS) is pain syndrome in which endometrial tissue grows outside the uterus. EMS is associated with an increased risk of multiple sclerosis (MS), a demyelinating disease of the central nervous system. ObjectiveTo characterize clinical phenotypes of a cohort of patients with both EMS and MS compared to a cohort of matched controls with only MS. MethodsWe retrospectively identified patients with EMS and MS at Beth Israel Deaconess Medical Center (BIDMC). We collected data on EMS treatments and analyzed differences in histories of gynecological cancer, smoking, fatigue, anxiety, depression, headache, and neuropathic pain compared to matched controls. We used Wilcoxon signed rank tests for paired samples to compare Expanded Disability Status Scores (EDSS) and timed 25-foot walk values (T25FW). ResultsUsing a case-control methodology, we found significantly increased EDSS (p < 0.001) and T25FW (p = 0.01) in the EMS-MS group compared to the MS group. More patients in the EMS-MS group had histories of smoking, anxiety, depression, and headaches, while more patients in the MS group had histories of fatigue and neuropathic pain. ConclusionWhen controlling for age, race, and MS therapy, those with EMS-MS experience more MS disability than controls, suggesting this population requires more monitoring and efficacious treatment.

A mixture model for differentiating longitudinal courses of multiple sclerosis

BackgroundMultiple sclerosis has a broad spectrum of clinical courses. Early identification of patients at greater risk of accumulating disability is essential. ObjectivesIdentify groups of patients with similar presentation through a mixture model and predict their trajectories over the years. MethodsRetrospective study of patients from 1994 to 2019. We performed a latent profile analysis followed by a latent transition analysis based on eight parameters: age, disease duration, EDSS, number of relapses, multi-topographic symptoms, motor impairment, sphincter impairment, and infratentorial lesions. ResultsWe included 629 patients, regardless of the phenotypical classification. We identified three distinct groups at the beginning and end of the follow-up. The three-classes model disclosed the “No disability regardless disease duration” (NDRDD) class with low EDSS and younger patients, the “Disability within a short disease duration” (DSDD) class with the worse disability besides short illness, and the “Disability within a long disease duration” (DLDD) class that achieved high EDSS over a long disease duration. EDSS, disease duration, and no sphincter impairment had the best entropy to distinguish classes at the initial presentation. Over time, the patients from NDRDD had a 52.1 % probability of changing to DLDD and 7.7 % of changing to DSDD. ConclusionsWe identified three groups of clinical presentations and their evolution over time based on considered prognostic factors. The most likely transition is from NDRDD to DLDD.

Impact of the therapy that changes the clinical course of multiple sclerosis using allogeneic mesenchymal stem cell transplantation on the immunological parameters of patients

Impact of the therapy that changes the clinical course of multiple sclerosis using allogeneic mesenchymal stem cell transplantation on the immunological parameters of patients

Serum Reactive Antibodies against the N-Methyl-D-Aspartate Receptor NR2 Subunit-Could They Act as Potential Biomarkers?

Synaptic dysfunction and disrupted communication between neuronal and glial cells play an essential role in the underlying mechanisms of multiple sclerosis (MS). Earlier studies have revealed the importance of glutamate receptors, particularly the N-methyl-D-aspartate (NMDA) receptor, in excitotoxicity, leading to abnormal synaptic transmission and damage of neurons. Our study aimed to determine whether antibodies to the NR2 subunit of NMDAR are detected in MS patients and evaluate the correlation between antibody presence and clinical outcome. Furthermore, our focus extended to examine a possible link between NR2 reactivity and anti-coagulant antibody levels as pro-inflammatory molecules associated with MS. A cross-sectional study was carried out, including 95 patients with MS and 61 age- and gender-matched healthy controls (HCs). The enzyme-linked immunosorbent assay was used to detect anti-NR2 antibodies in serum samples of participants along with IgG antibodies against factor (F)VIIa, thrombin, prothrombin, FXa, and plasmin. According to our results, significantly elevated levels of anti-NR2 antibodies were detected in MS patients compared to HCs (p < 0.05), and this holds true when we compared the Relapsing-Remitting MS course with HCs (p < 0.05). A monotonically increasing correlation was found between NR2 seropositivity and advanced disability (rs = 0.30; p < 0.01), anti-NR2 antibodies and disease worsening (rs = 0.24; p < 0.05), as well as between antibody activity against NR2 and thrombin (rs = 0.33; p < 0.01). The presence of anti-NR2 antibodies in MS patients was less associated with anti-plasmin IgG antibodies [OR:0.96 (95%CI: 0.92-0.99); p < 0.05]; however, such an association was not demonstrated when analyzing only RRMS patients. In view of our findings, NR2-reactive antibodies may play, paving the way for further research into their potential as biomarkers and therapeutic targets in MS.

Microglia activation in periplaque white matter in multiple sclerosis depends on age and lesion type, but does not correlate with oligodendroglial loss

Multiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of the CNS. The disease course in MS is highly variable and driven by a combination of relapse-driven disease activity and relapse-independent disease progression. The formation of new focal demyelinating lesions is associated with clinical relapses; however, the pathological mechanisms driving disease progression are less well understood. Current concepts suggest that ongoing focal and diffuse inflammation within the CNS in combination with an age-associated failure of compensatory and repair mechanisms contribute to disease progression. The aim of our study was to characterize the diffuse microglia activation in periplaque white matter (PPWM) of MS patients, to identify factors modulating its extent and to determine its potential correlation with loss or preservation of oligodendrocytes. We analyzed microglial and oligodendroglial numbers in PPWM in a cohort of 96 tissue blocks from 32 MS patients containing 100 lesions as well as a control cohort (n = 37). Microglia activation in PPWM was dependent on patient age, proximity to lesion, lesion type, and to a lesser degree on sex. Oligodendrocyte numbers were decreased in PPWM; however, increased microglia densities did not correlate with lower oligodendroglial cell counts, indicating that diffuse microglia activation is not sufficient to drive oligodendroglial loss in PPWM. In summary, our findings support the notion of the close relationship between focal and diffuse inflammation in MS and that age is an important modulator of MS pathology.

COMORBID MIGRAINE CHARACTERISTICS IN PATIENTS WITH MULTIPLE SCLEROSIS

Multiple Sclerosis (MS) is a chronic autoimmune disabling disease that is caused by autoimmune attack of myelin in the central nervous system [1]. Disease is not treatable and the progression depends on disease course and presence of comorbidity [2]. Among plenty of comorbid conditions that are present during MS duration, connection between primary headache and MS is well known but still poorly understood. Primary comorbid headache might be a cause of decreased quality of life of patients with MS. Mostly it depends on the type of primary headache and type of MS course (3).

Implementing Shared Decision-Making for Multiple Sclerosis: The MS-SUPPORT Tool

BackgroundDisease modifying therapies (DMTs) offer opportunities to improve the course of multiple sclerosis (MS), but decisions about treatment are difficult. People with multiple sclerosis (pwMS) want more involvement in decisions about DMTs, but new approaches are needed to support shared decision-making (SDM) because of the number of treatment options and the range of outcomes affected by treatment. We designed a patient-centered tool, MS-SUPPORT, to facilitate SDM for pwMS. We sought to evaluate the feasibility and impact of MS-SUPPORT on decisions about disease modifying treatments (DMTs), SDM processes, and quality-of-life. MethodsThis multisite randomized controlled trial compared the SDM intervention (MS-SUPPORT) to control (usual care) over a 12-month period. English-speaking adults with relapsing MS were eligible if they had an upcoming MS appointment and an email address. To evaluate clinician perspectives, participants’ MS clinicians were invited to participate. Patients were referred between November 11, 2019 and October 23, 2020 by their MS clinician or a patient advocacy organization (the Multiple Sclerosis Association of America). MS-SUPPORT is an online, interactive, evidence-based decision aid that was co-created with pwMS. It clarifies patient treatment goals and values and provides tailored information about MS, DMTs, and adherence. Viewed by patients before their clinic appointment, MS-SUPPORT generates a personalized summary of the patient's treatment goals and preferences, adherence, DMT use, and clinical situation to share with their MS clinician. Outcomes (DMT utilization, adherence, quality-of-life, and SDM) were assessed at enrollment, post-MS-SUPPORT, post-appointment, and quarterly for 1 year. ResultsParticipants included 501 adults with MS from across the USA (84.6% female, 83% white) and 34 of their MS clinicians (47% neurologists, 41% Nurse Practitioners, 12% Physician Assistants). Among the 203 patients who completed MS-SUPPORT, most (88.2%) reported they would recommend it to others and that it helped them talk to their doctor (85.2%), understand their options (82.3%) and the importance of taking DMTs as prescribed (82.3%). Among non-users of DMTs at baseline, the probability ratio of current DMT use consistently trended higher over one-year follow-up in the MS-SUPPORT group (1.30 [0.86-1.96]), as did the cumulative probability of starting a DMT within 6-months, with shorter time-to-start (46 vs 90 days, p=0.24). Among the 222 responses from 34 participating clinicians, more clinicians in the MS-SUPPORT group (vs control) trended towards recommending their patient start a DMT (9 of 108 (8%) vs 5 of 109 (5%), respectively, p=0.26). Adherence (no missed doses) to daily-dosed DMTs was higher in the MS-SUPPORT group (81.25% vs 56.41%, p=.026). Fewer patients forgot their doses (p=.046). The MS-SUPPORT group (vs control) reported 1.7 fewer days/month of poor mental health (p=0.02). ConclusionsMS-SUPPORT was strongly endorsed by patients and is feasible to use in clinical settings. MS-SUPPORT increased the short-term probability of taking and adhering to a DMT, and improved long-term mental health. Study limitations include selection bias, response bias, social desirability bias, and recall bias. Exploring approaches to reinforcement and monitoring its implementation in real-world settings should provide further insights into the value and utility of this new SDM tool.

Association between course of multiple sclerosis and polymorphisms of calcitriol receptor gene VDR FokI (rs2228570), BSMI (rs1544410), TaqI (rs731236), ApaI (rs7975232)

Objective. To evaluate the relationship between the frequency of exacerbations and the rate of progression of multiple sclerosis (MS) and polymorphisms of the calcitriol receptor gene VDR FokI (rs2228570), BSMI (rs1544410), TaqI (rs731236), ApaI (rs7975232).Material and methods. Ninety patients with relapsing-remitting MS took part in the study. All patients are Caucasians, were born and lived in the Altai region of the Russian Federation. Genotyping was performed by TaqMan probes.Results. A protective effect of the TT genotype VDR FokI (rs2228570) on the risk of increasing disability of more than 0.75 points per year according to the expanded disability scale was found (p = 0.034). The protective effect of the TT genotype of the TaqI polymorphism (rs731236) on exacerbations of MS more than once a year (p = 0.041) was also revealed. Associations of the MS course with other studied polymorphisms were not found.Conclusions. It can be assumed that the VDR FokI (rs2228570) and TaqI (rs731236) polymorphisms may influence the course of relapsing-remitting MS. The mechanisms of these influences may include the modulation of immune-inflammatory responses in the central nervous system, which are a key link in the MS pathogenesis.

Association of intestinal dysbiosis with susceptibility to multiple sclerosis: Evidence from different population studies (Review).

Understanding the relationship between microorganisms that live in our intestines and neuroinflammatory and neurodegenerative pathologies of the central nervous system (CNS) is essential, since they have been shown to have an immunomodulatory effect in neurological disorders, such as multiple sclerosis (MS). The gut microbiota can be affected by several environmental factors, including infections, physical and emotional stress and diet, the latter known as the main modulator of intestinal bacteria. An abrupt shift in the gut microbiota composition and function is known as dysbiosis, a state of local and systemic inflammation produced by pathogenic bacteria and its metabolites responsible for numerous neurological symptoms. It may also trigger neuronal damage in patients diagnosed with MS. Intestinal dysbiosis affects the permeability of the intestine, allowing chronic low-grade bacterial translocation from the intestine to the circulation, which may overstimulate immune cells and cells resident in the CNS, break immune tolerance and, in addition, alter the permeability of the blood-brain barrier (BBB). This way, toxins, inflammatory molecules and oxidative stress molecules can pass freely into the CNS and cause extensive damage to the brain. However, commensal bacteria, such as the Lactobacillus genus and Bacteroides fragilis, and their metabolites (with anti-inflammatory potential), produce neurotransmitters such as γ-aminobutyric acid, histamine, dopamine, norepinephrine, acetylcholine and serotonin, which are important for neurological regulation. In addition, reprogramming the gut microbiota of patients with MS with a healthy gut microbiota may help improve the integrity of the gut and BBB, by providing clinically protective anti-inflammatory effects and reducing the disease's degenerative progression. The present review provides valuable information about the relationship between gut microbiota and neuroinflammatory processes of the CNS. Most importantly, it highlights the importance of intestinal bacteria as an environmental factor that may mediate the clinical course of MS, or even predispose to the outbreak of this disease.

FRI432 An Interesting Case Of Primary Hypogonadism In A Patient With Multiple Sclerosis

Abstract Disclosure: S. Ahsun: None. P. Lekprasert: None. K.K. Win: None. Introduction: As per the recent data there is an association between low levels of testosterone in men and the risk for multiple sclerosis (MS). Most recent practice involves checking testosterone levels for male patients with newly developed MS and treating with testosterone supplementation if levels are low. CASE PRESENTATION: A 65-year-old male with medical history of multiple sclerosis, prediabetes, hypogonadism, squamous cell carcinoma of left ear, thyroid cancer (unknown type) status post total thyroidectomy and radioiodine therapy; presented to our endocrine office for an initial visit. Patient had been following with Endocrinologist at different state in the past and did not have much of his prior records since that practice closed. He has been on 150 mcg of levothyroxine and his TSH was stable at 1.2 (0.4-4.5 mIU/L). He also had a history of hypogonadism and had been on testosterone supplementation since the age around 50. Patient did not know the underlying cause for his hypogonadism. He has 3 biological children and the youngest one is 26 years old. He had been off of testosterone therapy for 3 months prior to our initial visit. We did some workup which showed total testosterone level of &amp;lt;20 (250-1100 ng/dL). Free testosterone 2.2 (46-224 pg/mL). FSH and LH levels were elevated at 27.1 (1.6-8 mIU/mL) and 17.3 (1.6-15.2 mIU/mL). Prolactin level was 5.1 (5.2-26.5) ng/mL. These labs were consistent with Primary hypogonadism. Repeat testing was done and the patient had redemonstration of very low testosterone levels. Further checking of the karyotype analysis revealed normal male karyotype testing. His physical exam showed normal sized testicles at 20 cc and no gynecomastia. Body hair distribution was normal but there was decreased shaving frequency with decreased muscle strength. Patient never had any chemotherapy or the radiation therapy to the pelvic area. No known history of chronic infection or trauma. Currently, he is on Ocrelizumab for Multiple Sclerosis. His testosterone level is now in the normal range with the testosterone therapy after the work up. CONCLUSION: As per the above case, our patient has an interesting presentation of primary hypogonadism with multiple sclerosis. He has no known reason for his primary testicular failure. We know that testosterone deficiency has been linked to development of MS and MS can lead to secondary hypogonadism. But Primary hypogonadism has not yet been seen with MS although autoimmunity can be postulated to lead to primary testicular failure in these patients, but more studies and investigation will need to be done to establish this cause and effect relationship. REFERENCE: Chitnis T. The role of testosterone in MS risk and course. Mult Scler. 2018 Jan;24(1):36-41. doi: 10.1177/1352458517737395. PMID: 29307293 Presentation: Friday, June 16, 2023

Modern neuroimaging criteria for diagnosing multiple sclerosis in children

The article presents a clinical case of multiple sclerosis (MS) in a 10-year-old female patient, the use of one of the advanced magnetic resonance imaging (MRI) techniques, namely proton magnetic resonance spectroscopy (1H-MRS), in the diagnosis of MS. MRI is an integral part of the diagnostic algorithm for patients with multiple sclerosis according to the McDonald criteria, which were last updated in 2017. In addition, MRI allows assessing the course of the disease, serving as a criterion for confirming the aggravation of the pathological process. Although the McDonald criteria are applied in adults, they are also used to diagnose MS in children, and MS in children has its own particularities. The McDonald criteria include traditional (conventional) MRI sequences: T2-weighted images, T1-weighted images, post-contrast T1-weighted images. With the rapid development of MRI, cutting-edge (advanced) MRI techniques have emerged that allow for a better understanding of changes in the brain matter in MS: brain volumetry, magnetization transfer imaging, cortical imaging, diffusion tensor imaging, 1H-MRS, susceptibility-weighted imaging. In particular, 1H-MRS allows us to assess the degree of white matter integrity by detecting increased resonance of myelin breakdown metabolites. The studies have shown that changes in MS have their own specificity, but there is no consensus on this issue. Currently, there are no agreed guidelines that would include advanced MRI techniques, but we believe they will allow us to better understand the course of MS and to predict the development of the disease. This approach will improve the management of MS in both adults and children and quality of their life.

Features of protein glycosylation in multiple sclerosis

The article presents an analytical review of the published data on the features of protein glycosylation in multiple sclerosis (MS). The search in the PubMed database with the keywords "multiple sclerosis, glycosylation", for the period of 2012-2022, resulted in 12 sources presenting the studies on N-glycosylated plasma proteins and immunoglobulins G in multiple sclerosis, clinically isolated syndrome, neuromyelitis optica spectrum disorders and meningitis of viral etiology in patients' cerebrospinal fluid and blood serum.&#x0D; The studies revealed specific changes in glycoproteins in multiple sclerosis. Glycome changes correlated with the age and sex of patients, with the clinical form of the disease, as well as with the degree of disability on the EDSS scale. These findings can contribute to the early diagnosis of MS, the definition of the form of the disease and its course prediction.&#x0D; Given the diversity of the glycome expression, the differences in its modifications in different environments (serum and blood plasma, cerebrospinal fluid), as well as the variety of approaches to its study (many quantitative and qualitative biochemical methods), there is a prospect of further search for markers and predictors of the course of multiple sclerosis.

Clinical markers for unfavorable course of multiple sclerosis

Objective. To study possible clinical markers associated with the unfavorable course of multiple sclerosis and its transition to a progressive subtype.&#x0D; Materials and methods. This prospective study included healthy volunteers and patients with relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS). For a comprehensive clinical evaluation, the participants completed the Timed 25-Foot Walk Test (T25-FW), Nine-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Fatigue test, and MSProDiscuss questionnaires. Then we compared the results between the groups.&#x0D; Results. We found significant differences between the groups in regard to most of the tests. Furthermore, we proposed a composite clinical score (CCS) based on T25-FW, SDMT, and 9-HPT results (for both hands).&#x0D; Discussion. Our CCS can be a useful clinical tool to determine the most likely course of multiple sclerosis at a certain timepoint.

Cognitive and Emotional Disorders during Multiple Sclerosis – Exogenous and Endogenous Conditions, Contemporary Methods of Treatment and Prevention

Multiple sclerosis (SM) is an autoimmune, demyelinating disease of the central nervous system. The disease affects patients of all ages, with a higher incidence in women. The etiopathogenesis of SM is not fully understood — it is believed that autoreactive lymphocytes play a key role in the development of the disease, although genetic predisposition and environmental factors also play a role. Diagnosis is based on the McDonald criteria, and the disease has different clinical presentations. Treatment is based on immunomodulation, aims to control the disease, and prevent recurrence. Frequent symptoms of the disease are motor, sensory, and cognitive disorders. Cognitive impairment, which is common in multiple sclerosis patients, has numerous consequences in everyday life (mental, social, economic) that significantly reduce the quality of life. Psycho-cognitive dysfunction, which can occur at any stage of the disease, is associated with changes in the central nervous system. Prevention of these disorders includes the early application of treatment methods that modify the natural course of the disease and the implication of pro-health behaviors, such as quitting smoking, proper diet and physical exercise. Pharmacological treatment shows limited effectiveness. Rehabilitation involving the use of compensatory strategies, remedial methods aimed at brain neuroplasticity and cognitive training shaping new functional networks of the brain is important. The aim of this work is to present the problem of cognitive and emotional disorders in the course of multiple sclerosis, with particular emphasis on endo- and exogenous conditions, together with modern methods of their treatment and prevention. (JNNN 2023;12(3):140–146)