DigiTRAC: Qualitative insights from knowledge users to inform the development of a Digital Toolkit for enhancing resilience among multiple sclerosis caregivers.

BACKGROUND: Resilience-promoting resources are critically needed to support positive caregiving experiences for multiple sclerosis (MS) caregivers. A digital toolkit offers a flexible way to access and use evidence-based resources that align with MS caregivers' interests and needs over time. OBJECTIVE: We explored the perspectives of key knowledge users regarding content areas, features, and other considerations to inform an MS caregiver resilience digital toolkit. METHODS: Twenty-two individuals completed a demographic survey as part of this study: 11 MS family caregivers, 7 representatives of organizations providing support services for people with MS and/or caregivers, and 4 clinicians. We conducted nine semi-structured individual interviews and two focus groups. Data were analyzed using content analysis. RESULTS: Participants recommended that a digital toolkit should include content focused on promoting MS caregivers' understanding of the disease, its trajectory and available management options, and enhancing caregiving skills and caregivers' ability to initiate and maintain behaviours to promote their own well-being. Features that allow for tracking and documenting care recipients' and caregivers' experiences, customization of engagement, and connectivity with other sources of support were also recommended. Participants suggested a digital toolkit should be delivered through an app with web browser capabilities accessible on smartphones, tablets, or laptops. They also acknowledged the need to consider how users' previous technology experiences and issues related to accessibility, usability, privacy and security could influence toolkit usage. CONCLUSION: These findings will guide future toolkit development and evaluation. More broadly, this study joins the chorus of voices calling for critical attention to the well-being of MS family caregivers.

Association between the Hopkins Falls grading scale and motor function tests in patients with multiple sclerosis.

Introduction: One of the main complications of multiple sclerosis (MS) is imbalance and walking problems that can lead to falls. This study investigated the association between a fall measurement scale called the Hopkins Falls Grading Scale (HFGS) and motor function tests in patients with MS. Material and Methods: This cross sectional study was conducted using convenience sampling on 85 patients referred to the MS Association of Mashhad, Iran, in 2023. The HFGS examined falls during the past year and divided them into 4 degrees, and the function test included the timed 25 foot walk (T25FW) test and the timed up and go (TUG) test. Kruskal-Wallis test and Spearman's correlation coefficient were used for data analysis. Results: A statistically significant association was obtained between HFGS and functional tests (T25FW and TUG) (for both P < 0.0001). A significant association was observed between the variables of age (P = 0.006), duration of the disease (P = 0.03), the use of mobility devices (P = 0.05), and HFGS. Conclusion: Considering the association between HFGS and motor function tests in MS patients, clinical experts should pay attention to patients who have slower movement and evaluate them in terms of falling status when performing motor function tests.

Coexistence of multiple sclerosis and systemic lupus erythematosus - a case report.

Purpose: Multiple sclerosis (MS) and systemic lupus erythematosus (SLE) are two autoimmune diseases that are relatively common, especially in women. However, it is extremely rare for them to coexist in a single patient (only 18 cases have been recorded worldwide). Both affect the nervous system and may manifest in identical ways. This creates significant difficulties, both in terms of diagnosis and choice of appropriate therapy. Case description: A 54-year-old female patient with quadriparesis, superficial sensory disturbance and gait and balance disorders was diagnosed with primary progressive MS according to McDonald's criteria. The magnetic resonance images were typical for MS. Previously, in 2013, she was diagnosed with SLE, treated successfully, and is currently in remission. After excluding neuropsychiatric lupus, ocrelizumab treatment was administered, with good clinical results. Comment: Adequate differentiation (magnetic resonance imaging, analysis of cerebrospinal fluid, clinical observation) as to whether the patient's symptoms are related to MS or to SLE nervous system involvement is the basis for proper diagnosis and treatment.

Multiple sclerosis relapse presenting as trigeminal neuralgia.

I present here a case of trigeminal neuralgia (TGN), which is a highly disabling disorder characterized by brief and recurrent shock-like episodes of facial pain. TGN occurs in 2% of people with MS. A 54-year-old woman diagnosed with multiple sclerosis (MS) in 2008 and who was in remission stopped taking her disease-modifying therapy (DMT) in 2018 due to a lack of relapses presented to our facility with excruciating right facial pain. Magnetic resonance imaging (MRI) of the brain with gadolinium showed enhancing plaque involving the proximal cisternal portion of the right trigeminal nerve on axial and sagittal sections. She was started on carbamazepine 300 mg 4 times a day. This case highlights the need for early diagnosis by MRI with gadolinium enhancement and prompt initiation of treatment helped her pain to subside and was able to return a week later to the MS clinic to be restarted on her prior DMT to prevent further MS relapses.

Early reduction of retinal thickness predicts physical and cognitive disability in newly diagnosed multiple sclerosis patients: results from a cross-sectional study.

INTRODUCTION: Retinal nerve fiber layer (RNFL) thickness is a promising biomarker of axonal loss and a potential outcome predictor in Multiple Sclerosis (MS). Cognitive impairment (CoI) exhibits a high prevalence in patients with MS (pwMS), even in the early phases of the disease. Our aim was to explore the role of RNFL thickness as a predictor of physical and cognitive disability in pwMS. METHODS: All newly diagnosed pwMS referred to the MS centre of the University-Hospital "Policlinico-San Marco" between 2015-2019 were evaluated at baseline and at 3 years. RNFL and ganglion cell layer (GCL) thickness for right (r.e.) and left eyes (l.e.) were measured with Optical Coherence Tomography (OCT). Disability level and cognitive profile were assessed, using the Expanded Disability Status Scale (EDSS) and the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, respectively. RESULTS: We consecutively enrolled 487 pwMS, including 68 (14.0%) with primary progressive MS (PPMS). At baseline, RNFL and GCL were bilaterally thinner in PPMS (r.e. 90.4 ± 12.7; l.e. 90.2 ± 13.5, and r.e. 80.1 ± 11.2; l.e. 80.3 ± 12.6, respectively) compared to relapsing-remitting MS (RRMS) (r.e. 94.6 ± 13.1; l.e. 94.3 ± 14.8, and r.e. 85.1 ± 9.5; l.e. 84.9 ± 9.3, respectively) (p < 0.01). Both groups exhibited reduced RNFL and GCL thickness, worse cognitive performance and higher EDSS scores at 3-years follow-up compared with baseline. RNFL thickness ≤ 88.0 µm was an independent predictor of CoI (OR = 5.32; 95% CI = 1.84-9.12; p = 0.02) and disability worsening (OR = 3.18; 95% CI = 1.21-10.33; p = 0.05). DISCUSSION: RNFL thickness, as a biomarker of neurodegeneration, could be considered a predictive biomarker of cognitive degeneration and physical disability in MS.

The meaning of health to persons aging with longstanding multiple sclerosis.

Understanding how persons aging with a chronic condition view their health is essential for planning and delivering person-centered care. The purpose of this study was to explore how persons aging with the chronic and disabling condition multiple sclerosis (MS) describe their health and how this has changed over time using data from Years 1 to 26 of an ongoing longitudinal survey study of health promotion and quality of life for persons with MS. The survey included measures of perceived meaning of health, self-rated health, health behaviors and quality of life outcomes. The sample included 168 persons with MS who returned the survey at Time 1 (1996) and again at Time 26 (2022). In 2022, participants had a mean age of 70.13 (SD = 8.19) and had been diagnosed with MS for an average of 34.47 years (SD = 6.27). Sixty percent of participants rated their overall health as good or excellent. Decreases in health self-ratings over time were not significant. Participants consistently agreed more strongly with items reflecting a wellness-oriented view of health than those reflecting a more clinical/biomedical model. At both time points, clinical definitions of health were negatively related and wellness definitions were positively related to reported frequency of health behaviors. Findings suggest that persons aging with the chronic condition of MS may be more responsive to health messages that emphasize function in daily living, carrying out normal responsibilities, and adjusting to changes in environment and demands. Patient or Public Contribution: Persons with MS provided study data, input on design, and construct measurement.

Multiple sclerosis in Central America and Caribbean countries: frequency and clinical characterization of an emergent disease.

Background: Multiple Sclerosis (MS) is a common neurological disease among white populations of European origin. Frequencies among Latin Americans continue to be studied, however, epidemiologic, and clinical characterization studies lack from Central American and Caribbean countries. Ethnicity in these countries is uniformly similar with a prevalent Mestizo population. Methods and results: Data from January 2014 to December 2019 from Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, Panama, Dominican Republic, and Aruba on demographic, clinical, MRI and phenotypic traits were determined in coordinated studies: ENHANCE, a population-based, retrospective, observational study on incidence and clinical characteristics, and from the subgroup with MS national registries (Aruba, Dominican Republic, Honduras, and Panama), data on prevalence, phenotypes and demographics. Expanded Disability Status Scale (EDSS), and therapeutic schemes were included. ENHANCE data from 758 patients disclosed 79.8% of Mestizo ethnicity; 72.4% female; median age at onset 31.0 years and 33.2 at diagnosis. The highest incidence rate was from Aruba, 2.3-3.5 × 100,000 inhabitants, and the lowest, 0.07-0.15 × 100,000, from Honduras. Crude prevalence rates per 100,000 inhabitants fluctuated from 27.3 (Aruba) to 1.0 (Honduras). Relapsing MS accounted for 87.4% of cases; EDSS <3.0 determined in 66.6% (mean disease duration: 9.1 years, SD ± 5.0); CSF oligoclonal bands 85.7%, and 87% of subjects hydroxyvitamin D deficient. Common initial therapies were interferon and fingolimod. Switching from interferon to fingolimod was the most common escalation step. The COVID-19 pandemic affected follow-up aspects of these studies. Conclusion: This is the first study providing data on frequencies and clinical characteristics from 8 countries from the Central American and Caribbean region, addressing MS as an emergent epidemiologic disorder. More studies from these areas are encouraged.

Localized Colitis Associated With Cholecystectomy in Multiple Sclerosis Patient Treated With Ocrelizumab.

Our understanding of multiple sclerosis (MS) has led to the development of new therapeutic strategies, including ocrelizumab, a third-generation humanized anti-CD20 antibody. Ocrelizumab is largely well tolerated with favorable effectiveness, however, it has been associated with reports of colitis presenting weeks to months following infusion. We present a case of severe localized colitis in the setting of recent surgery and chronic ocrelizumab use. High-dose IV hydrocortisone was initiated, and the patient showed gradual improvement. Repeat imaging after discharge showed near-complete resolution of the patient's condition. This case aims to increase awareness of possible postoperative severe localized colitis in MS patients on Ocrevus.

A new framework for understanding stress and disease: the developmental model of stress as applied to multiple sclerosis.

This paper proposes a new model of stress that integrates earlier models and adds insights from developmental psychology. Previous models describe the behavioral and physical effects of stress events, but have not explained the translation of experiences into stress itself. The Developmental Model of Stress shows how psychosocial developmental challenges in childhood create persistent negative beliefs and behaviors that increase threat perception and maladaptive stress responses. These developmental challenges produce early psychological and physiological predispositions for increased stress responses over time. Ongoing stress leads to dysregulation of physical stress-response systems (allostatic load), which is associated with multiple diseases. High allostatic load provides the necessary preconditions for the diathesis-stress model, which says the addition of an acute stressor to a weakened or predisposed system can lead to disease development. The paper also documents the evolving measurement of stress to better understand the stress-disease relationship, helping to resolve conflicting results between studies. The Developmental Model of Stress was combined with clinician insight and patient reports to build an integrative framework for understanding the role of stress in the development and progression of multiple sclerosis (MS). It includes the first mapping of maladaptive beliefs and behaviors arising from developmental challenges that are common to people with MS. An initial comparison shows these may be distinct from those of people with other chronic diseases. These beliefs and behaviors form the predisposing factors and contribute to the triggering factors, which are the acute stressors triggering disease onset. These often took two forms, a prolonged incident experienced as feeling trapped or stuck, and threat of a breach in a relationship. The reinforcing factors add the stress of a chronic disease with a poor prognosis and seemingly random symptom fluctuation, still managed with the same beliefs and behaviors developed in childhood, increasing physiological dysregulation and symptom severity. A pilot study is described in which these three categories of stress factors in MS were explicitly addressed. This study noted clinically important improvements in physical and mental well-being, providing preliminary support for the Developmental Model. Future research might expand on the pilot using a more robust sample and design.

25 Hydroxyvitamin D and Cytokine Profile in Patients With Relapsing-Remitting Multiple Sclerosis.

In experimental allergic encephalomyelitis, the severity of the deficiency is associated with the loss of axons, and it is likely that cytotoxic T-cells 8 (CD8 T) play an important role. In relapsing-remitting multiple sclerosis, there is a correlation between the inflammatory activity in the lesion and the transection of axons. To understand the pathological mechanisms, it is important to evaluate the changes in serum concentrations of pro- and anti-inflammatory cytokines during the disease course. A total of 46 patients and 40 healthy individuals participated in an open-label, prospective, case-control study from 2012 to 2014. The serum concentrations of cytokines were measured using enzyme-linked immunosorbent assay (ELISA). An immune imbalance was observed during relapse and remission phases compared to the control group. During relapse, the levels of interferon-gamma (IFN-γ) were significantly higher compared to those in remission (p=0.017). During remission, there was an improvement in the deficiency (p<0.001), and the anti-inflammatory cytokines transforming growth factor-beta (TGF-ß) and interleukin 4 (IL4) increased compared to those in relapse (p=0.006; p=0.009). A correlation was found between the serum concentrations of tumor necrosis factor-alpha (TNF-α) and Expanded Disability Status Scale (EDSS) during relapse (correlation coefficient: 0.301; significance (Sig.) (2-tailed 0.042). During the exacerbation, there was a moderate relationship between interleukin 17 (IL17) and 25-hydroxyvitamin D (25(OH)D) (P (p-value (probability value) = 0.02)). TNF-α, IFN-γ, IL17, and TGF-ß serum levels are criteria for evaluating immune inflammatory activity during relapse and remission periods.

Web scraping of user-simulated online nutrition information for people with multiple sclerosis.

BACKGROUND: People diagnosed with multiple sclerosis (MS) often seek to modify their diet guided by online advice, however this advice may not align with national dietary guidelines. The aim of this study was to simulate an online search for dietary advice conducted by a person with MS and evaluate the content. It was hypothesised that a variety of eating patterns are promoted for MS online and these dietary approaches can be contradictory. METHODS: An online search was simulated using Google Trends-informed search terms and Google and Bing search engines. URLs were extracted using R. Nutrition data were extracted including recommendations for diets, foods, supplements, and health professional consultation. Statistical analyses were conducted using R. RESULTS: 73 URLs from 49 websites were extracted, with only 14 results common to both search engines. Dietary recommendations included overall eating patterns (58 webpages, 79%), individual foods (55 webpages, 75%), and supplements (33 webpages, 45%). The most promoted eating pattern for MS was a balanced diet (33 recommendations, 48%), more likely by nonprofit organisations and health information websites (14 and 17 recommendations, 100% and 89%); lifestyle program websites were more likely to recommend restrictive diets (19 recommendations, 100%) (p<0.001). 52% pages advised consulting a health professional, most often a doctor or dietitian. CONCLUSION: A balanced diet is the most recommended eating pattern for MS online, though advice promoting restrictive diets persists.

Prevalence of elevated sNFL in a real-world setting: Results on 908 patients with different multiple sclerosis types and treatment conditions.

BACKGROUND: In the field of research for new validated surrogate biomarkers of treatment efficacy, disease activity and progression in Multiple Sclerosis (MS), serum neurofilament light-chain (sNFL) are actually the best candidate for MS patient monitoring. However, before they can be implemented in clinical practice, their usefulness as additional red flag routine measure must be demonstrated. To tackle the problem, this real-life cross-sectional study at the Regional Referring Center for Multiple Sclerosis (CRESM) aims to characterize sNFL levels and prevalence of elevated sNFL, according to our age-dependent cut-off values, in a large group of patients with different types of MS and treatment conditions. METHODS: 908 serum samples from as many MS patients being admitted at CRESM for diagnostic definition and/or during routinary treatment monitoring were consecutively collected between January 2019 and January 2020. sNFL levels were measured by single molecule array (Simoa™) technology on SR-X instrument using NF-light assays (Quanterix); results were interpreted using previously published cut-off values. RESULTS: Primary and Secondary Progressive MS (PPMS, SPMS) forms demonstrate higher levels and prevalence of elevated sNFL (PPMS= 32 %, SPMS= 21 %) compared to the Relapse and Remitting one (RRMS = 12 %). Besides, naïve samples of RRMS and PPMS subtypes showed higher prevalence of elevated sNFL (RRMS naïve= 31 %, PPMS naïve=67 %) compared to samples from patients treated for more than 12 months (RRMS treat>12m= 9 %, PPMS treat>12m= 19 %); treated SPMS patients demonstrated higher sNFL levels and a prevalence (22 %) of elevated sNFL compared to RRMS treated patients. Focusing on RRMS, no statistical difference was found between groups of patients treated for whatever time (up to or more than 60 months) and with either DMT type (high or low-efficacy DMT). Finally, RRMS patients treated with all DMTs for more than 12 months, with the exception of teriflunomide and alemtuzumab showed a prevalence of elevated sNFL in the range of 5-10 %. CONCLUSION: in a real-world setting comprising about 1000 MS patients, sNFL quantification was elevated in 5-to-67 % of patients, in different MS forms and treatment conditions. Elevated levels of sNFL must be considered a red-flag suggesting the need of a further clinical monitoring in any circumstance, as it can be indicative of new inflammation, ongoing degeneration or co-morbidities. This study supports the introduction of sNFL quantification in everyday patient management.

Impact of sex on clinical outcome in early Multiple Sclerosis.

BACKGROUND: Previous evidence suggests sex differences in the clinical course of relapsing remitting multiple sclerosis (RRMS), but comprehensive early-stage prospective studies are lacking. We aim to quantify the impact of sex on clinical outcomes in early-stage RRMS. METHODS: Utilizing prospective cohort data, we assessed the impact of biological sex on time-to-relapse, disability progression (Expanded Disability Status Scale [EDSS]), extremity function (Nine-Hole Peg Test, Timed-25-food walk test), cognition (Paced Auditory Serial Addition Test, Symbol Digit Modalities Test), quality-of-life (Hamburg Quality of Life Questionnaire in Multiple Sclerosis, Short-Form-36), fatigue (Fatigue Severity Scale, Fatigue Scale for Motor and Cognitive functions), and depression (Beck Depression Inventory-II) in clinically isolated syndrome (CIS) or RRMS patients. Inclusion was within 12 months of symptom onset. Linear, negative binomial, mixed, and Cox models estimated male vs. female effects at the four-year follow-up including baseline-to-follow-up course. RESULTS: We included 149 patients (65.1 % female). Eighty-five completed four-year follow-up. No sex differences in time-to-relapse emerged (HR = 0.91;95 %CI = 0.53-1.58). Males had no increased risk of EDSS worsening (OR = 0.75;95 %CI = 0.21-2.35) compared to females. Similarly, minor/no sex differences emerged in other outcomes. CONCLUSIONS: Four years after first manifestation, neither disease activity (disability progression and relapse rate) nor patient-reported outcomes showed sex-related disparities in this early-MS-cohort. GOV IDENTIFIER: NCT01371071.

Patterns of disease-modifying therapy utilization before, during, and after pregnancy and postpartum relapses in women with multiple sclerosis.

BACKGROUND: Pregnancy is a common consideration for people with multiple sclerosis (pwMS); MS onset is typically between 20 and 45 years of age, during potential child-bearing years. Pregnancy and postpartum care are a significant factor influencing disease-modifying therapy (DMT) selection for many pwMS. To date, few DMTs are considered safe to continue during pregnancy and real-world treatment patterns before, during, and after pregnancy remain uncharacterized. Evolving guidance is needed regarding how to optimize management of the pregnancy and postpartum periods considering the changing DMT landscape. This analysis in two large claims databases describes DMT utilization for the treatment of MS before, during, and after pregnancy and relapse patterns during pregnancy and postpartum. METHODS: In this retrospective, observational study, the US MarketScan Commercial and Medicaid claims database was assessed for female patients aged 18-55 years with ≥1 insurance claim submitted under the diagnosis code of MS from 01 January 2016-30 April 2021 and continuous enrollment eligibility from ≥6 months prior to pregnancy date (preconception) through 6 months of follow-up following delivery (postpartum period). Comorbid conditions were examined preconception and postpartum, including anxiety and depression. Moderate/severe relapse was defined as MS-related hospitalization, or an outpatient visit and one claim within 7 days of the visit with steroids or total plasma exchange. RESULTS: A total of 944 patients (mean [standard deviation] age, 32.4 [5.0] years) were eligible; 688 (73%) were commercially insured and 256 (27%) received Medicaid. Compared with commercially-insured patients, use of DMTs was lower among Medicaid patients at 6 months preconception (25.4% vs 40.4%; p < 0.001), with similar patterns observed both during pregnancy and postpartum. Overall, prevalence of DMT use declined sharply during pregnancy, from 36.3% of patients in the 6 months preconception to 17.9%, 5.3%, and 5.8% in trimesters 1, 2 and 3, respectively. Postpartum DMT utilization increased to 20.9% at 0-3 months and 24.4% at 4-6 months. Of all patients in the preconception period, the most frequently used DMTs were glatiramer acetate (14.3%), dimethyl fumarate (6.0%), interferon (5.2%), and natalizumab (4.9%). Due to small sample size, information was limited for anti-CD20s and alemtuzumab. The proportion of patients with any moderate/severe relapse declined over pregnancy (preconception, n = 82 [8.7%]; pregnancy, n = 25 [2.6%]), but increased postpartum (n = 94 [10.0%]). Of the 889 patients who stopped DMT during pregnancy, the risk of postpartum relapses was lower in the patients who resumed DMT postpartum (10/192) than in patients who did not (76/697) (5.2% vs 10.9%; odds ratio, 0.455 [95% confidence interval 0.216-0.860], p = 0.018). Cases of postpartum depression and anxiety were significantly lower in commercially-insured patients vs Medicaid patients (postpartum depression, 13.7% vs 27.0%, p < 0.01; postpartum anxiety, 16.3% vs 30.5%, p < 0.01). CONCLUSION: DMT utilization declined sharply during pregnancy; it gradually increased postpartum but remained below pre-pregnancy use. The proportion of pwMS experiencing a moderate/severe relapse and number of relapses declined over pregnancy but increased postpartum. Reinitiation of DMT during the postpartum period was associated with lower risk of relapses, supporting a role for early reinitiation of DMT postpartum. STUDY SUPPORTED BY: Biogen.

Evaluating the effect of dimethyl fumarate on subclinical biomarkers in a real-world patient cohort.

OBJECTIVE: Evaluate the real-world effect of dimethyl fumarate (DMF) on subclinical biomarkers in patients with relapsing-remitting multiple sclerosis (RRMS) and compare with results from clinical trials. METHODS: Magnetic resonance imaging (MRI) data from 102 RRMS patients were retrospectively collected and processed using icobrain to assess brain atrophy and to assist semi-manual lesion count. RESULTS: Mean (±SD) annualized percent brain volume change in the first 3 years after DMF-initiation were: -0.33 ± 0.68, -0.10 ± 0.60, and - 0.35 ± 0.71%/year, respectively. No new FLAIR lesions were detected in 73.7%, 77.3%, and 73.3% of the patients during years 1, 2, and 3. CONCLUSIONS: Results of this real-world study were consistent with previous DMF phase III clinical trials, supporting the generalizability of the effects observed in clinical trials to the real-world clinical setting.

Pathogenesis of multiple sclerosis: genetic, environmental and random mechanisms.

BACKGROUND: The pathogenesis of multiple sclerosis (MS) requires both genetic factors and environmental events. The question remains, however, whether these factors and events completely describe the MS disease process. This question was addressed using the Canadian MS data, which includes 29 478 individuals, estimated to represent 65-83% of all Canadian patients with MS. METHOD: The 'genetically-susceptible' subset of the population, (G), includes everyone who has any non-zero life-time chance of developing MS, under some environmental conditions. A 'sufficient' environmental exposure, for any genetically-susceptible individual, includes every set of environmental conditions, each of which is 'sufficient', by itself, to cause MS in that person. This analysis incorporates many epidemiological parameters, involved in MS pathogenesis, only some of which are directly observable, and establishes 'plausible' value ranges for each parameter. Those parameter value combinations (ie, solutions) that fall within these plausible ranges are then determined. RESULTS: Only a small proportion of the population (≤52%) has any possibility of developing MS, regardless of any environmental conditions that they could experience. Moreover, some of these genetically-susceptible individuals, despite their experiencing a 'sufficient' environmental exposure, will still not develop disease. CONCLUSIONS: This analysis explicitly includes all of those genetic factors and environmental events (including their interactions), which are necessary for MS pathogenesis, regardless of whether these factors, events and interactions are known, suspected or as yet unrecognised. Nevertheless, in addition, a 'truly' random mechanism also seems to play a critical role in disease pathogenesis. This observation provides empirical evidence, which undermines the widely-held deterministic view of nature. Moreover, both sexes seem to share a similar genetic and environmental disease basis. If so, then it is this random mechanism, which is primarily responsible for the currently-observed differences in MS disease expression between susceptible women and susceptible men.

[Optical coherence tomography in the diagnosis of multiple sclerosis]. / Opticheskaya kogerentnaya tomografiya v diagnostike rasseyannogo skleroza.

Multiple sclerosis (MS) is a chronic autoimmune-inflammatory and neurodegenerative disease. PURPOSE: This study explores the main structural changes in patients with MS and their relationships with the activity and type of disease course. MATERIAL AND METHODS: This prospective study included 159 patients (318 eyes) with an established diagnosis of MS: group (44 eyes; 13.84%) - relapsing-remitting type MS (RRMS) lasting up to 1 year without a history of optic neuritis (ON); group 2 (30 eyes; 9.43%) - RRMS up to 1 year with ON; group 3 (56 eyes; 17.61%) - RRMS lasting from 1 to 10 years without ON; group 4 (38 eyes; 11.95%) - RRMS from 1 to 10 years with ON; group 5 (49 eyes; 15.41%) - RRMS >10 years without ON; group 6 (37 eyes; 11.63%) - RRMS >10 years with ON; group 7 (34 eyes; 10.69%) - secondary progressive multiple sclerosis (SPMS) without ON; group 8 (30 eyes; 9.43%) - SPMS with ON. Patients underwent standard ophthalmological examinations, including optical coherence tomography. RESULTS: A decrease in structural parameters was diagnosed, progressing with the duration of the disease and the presence of ON: the minimum values of mGCL+IPL (65.83±9.14 µm) and mSNFL (76.37±14.77 µm) were detected in the group with SPMS with ON. High inverse correlations of EDSS with mGCL+IPL and mRNFL were demonstrated, with maximum in the group with the longest duration of MS without ON (-0.48 and -0.52 (p=0.01), respectively). CONCLUSION: Changes in the thickness of the structural parameters of the retina, measured by OCT, can be considered as a predictor of the course of MS.

Healthcare resource utilization and economic burden of multiple sclerosis in Chinese patients: results from a real-world survey.

Multiple sclerosis (MS) is uncommon in China and the standard of care is underdeveloped, with limited utilization of disease-modifying treatment (DMT). An understanding of real-world disease burden (including direct medical, non-medical, and indirect costs, such as loss of productivity), is currently lacking in this population. To investigate the overall burden of managing patients with MS in China, a cross-sectional survey of physicians and their consulting patients with MS was conducted in 2021. Physicians provided information on healthcare resource utilization (HCRU; consultations, hospitalizations, tests, medication) and associated costs. Patients provided data on changes in their life, productivity, and impairment of daily activities due to MS. Results were stratified by disease severity using generalized linear models, with a p value < 0.05 considered statistically significant. Patients with more severe disease had greater HCRU, including hospitalizations, consultations and tests/scans, and incurred higher direct and indirect costs and productivity loss, compared with those with milder disease. However, the use of DMT was higher in patients with mild disease severity. With the low uptake and limited efficacy of non-DMT drugs, Chinese patients with MS experience a high disease burden and significant unmet needs. Therapeutic interventions could help save downstream costs and lessen societal burden.

Neuropathic Pain Secondary to Multiple Sclerosis: A Narrative Review.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS). Neuropathic pain in MS is a debilitating symptom that significantly impairs the quality of life for a substantial proportion of MS patients. Neuropathic pain in MS stems primarily from demyelination, axonal loss, CNS inflammation, and direct damage to the myelin sheath, leading to pain manifestations such as ongoing extremity pain, Lhermitte's phenomenon, and trigeminal neuralgia (TN). The pathophysiological mechanisms behind MS-related neuropathic pain are explored in this review, highlighting central sensitization, neural dysfunction, spinal thalamic tract dysfunction, and inflammatory processes that exacerbate neuronal damage. Neuropathic pain in MS necessitates comprehensive assessment tools and neurophysiological tests to differentiate neuropathic pain from other MS symptoms accurately. Treatment strategies for MS-related neuropathic pain encompass pharmacological interventions, including anticonvulsants and antidepressants, and emerging therapies targeting specific inflammatory processes. The review advocates for a holistic approach to management, incorporating innovative treatments and multidisciplinary strategies to address both the physical symptoms and psychosocial aspects of this disorder. This comprehensive overview underscores the importance of ongoing research into targeted therapies to improve patient outcomes and enhance the quality of life for those affected by MS.

The hidden link: How oral and respiratory microbiomes affect multiple sclerosis.

BACKGROUND: Extensive research has explored the role of gut microbiota in multiple sclerosis (MS). However, the impact of microbial communities in the oral cavity and respiratory tract on MS is an emerging area of investigation. PURPOSE: We aimed to review the current literature related to the nasal, oral, and lung microbiota in people with MS (PwMS). METHODS: We conducted a narrative review of clinical and preclinical original studies on PubMed that explored the relationship between the bacterial or viral composition of the nasal, lung, and oral microbiota and MS. Additionally, to find relevant studies not retrieved initially, we also searched for references in related review papers, as well as the references cited within the included studies. RESULTS AND CONCLUSIONS: Thirteen studies were meticulously reviewed in three sections; oral microbiota (n = 8), nasal microbiota (n = 3), and lung microbiota (n = 2), highlighting considerable alterations in the oral and respiratory microbiome of PwMS compared to healthy controls (HCs). Genera like Aggregatibacter and Streptococcus were less abundant in the oral microbiota of PwMS compared to HCs, while Staphylococcus, Leptotrichia, Fusobacterium, and Bacteroides showed increased abundance in PwMS. Additionally, the presence of specific bacteria, including Streptococcus sanguinis, within the oral microbiota was suggested to influence Epstein-Barr virus reactivation, a well-established risk factor for MS. Studies related to the nasal microbiome indicated elevated levels of specific Staphylococcus aureus toxins, as well as nasal glial cell infection with human herpes virus (HHV)-6 in PwMS. Emerging research on lung microbiome in animal models demonstrated that manipulating the lung microbiome towards lipopolysaccharide-producing bacteria might suppress MS symptoms. These findings open avenues for potential therapeutic strategies. However, further research is crucial to fully understand the complex interactions between the microbiome and MS. This will help identify the most effective timing, bacterial strains, and modulation techniques.