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Background: Multiple sclerosis is a chronic disease of the central nervous system characterized by inflammation, neurodegeneration, and failure of the central nervous system's repair mechanisms. The role of infectious agents against the background of genetic predisposition is currently considered a possible pathogenesis factor of this disease. Case presentation: We report the case of a 52-year-old white (Russian) female musician with 15-year history of relapsing–remitting multiple sclerosis who had repeatedly received conventional therapy without much benefit. In 2017, she was admitted to the outpatient department of the Institute of Virology, where she was treated with erythromycin and acyclovir (tablet forms), which were not applied in the traditional way but through the "device for transfer of information from the drug to the human body." The received effect led to suppression of the disease activity, a significant reduction in the symptoms of the disease, prevention of further increase in neurological manifestations of the disease, and improvement in the dynamics of the manifestation of the disease according to brain magnetic resonance imaging. Conclusion: The described case report is innovative and presents for the first time the results of a noninvasive approach to the treatment of a patient with multiple sclerosis in whom information about various medications was introduced into different parts of the body, including the brain. The results obtained may indicate a possible role of infectious agents in the genesis of multiple sclerosis. It indicates a potential impact on them by using a "device for transfer of information from the drug to the human body." The study was conducted in accordance with the principles of the Declaration of Helsinki. It was approved by the Institutional Review Board of the Research Institute of Virology of Uzbekistan (no. 12/8–1500, 1/3/2017). [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system, leading to a range of symptoms that impact physical, psychiatric, and cognitive functions. Cognitive dysfunction is prevalent among patients with MS (pwMS), affecting at least 65% of patients, and includes deficits in processing speed, attention, learning, memory, and executive function. Despite the significant impact on daily life, cognitive impairment in MS patients is often underrecognized in clinical settings. Methods: This systematic review and meta-analysis aimed to evaluate cognitive function using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery among pwMS patients and healthy controls (HCs). A comprehensive search of the Web of Science, PubMed, Scopus, and Cochrane Library databases was conducted on January 2024 following the PRISMA guidelines. Eligible studies included peer-reviewed research assessing the validity of the MACFIMS in adult MS patients. Data extraction and quality assessment were performed using standardized tools, and statistical analyses were conducted using R4.2.3. Results: Eight studies met the inclusion criteria, including a total of 1,481 pwMS and 1,072 HCs. The meta-analysis revealed significant cognitive deficits in pwMS patients compared to HCs across all the MACFIMS subtests, including language, spatial processing, new learning and memory, processing speed, and executive function. Processing speed and working memory were the most affected domains, with 36% of pwMS showing impairment on the Symbol Digit Modalities Test (SDMT). Subgroup analyses indicated that the Expanded Disability Status Scale (EDSS) score significantly influenced cognitive impairment, while disease duration had a limited impact. Conclusions: The MACFIMS effectively discriminates between pwMS patients and HCs, demonstrating its validity as a comprehensive cognitive assessment tool for MS. Routine cognitive screening, particularly for processing speed and working memory, is crucial for early detection and intervention. Future research should focus on the sensitivity and specificity of the MACFIMS across diverse MS subtypes and cultural contexts to enhance its global applicability in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system. The first presentation's possible triggers are still controversial among scientists. The objective of this study is to investigate and compare the potential social, environmental, and physical factors that may have contributed to the onset of MS before and during the Coronavirus Disease 2019 (COVID-19) pandemic. Methods: A questionnaire was designed in the MS research center of Sina Hospital and also distributed as an online Google Form on social media among Iranian MS patients. Demographic information, MS disease-related data, and possible patients reported MS triggers were recorded. They were containing stressful life events, COVID-19 and other infections, COVID-19 and other vaccines, pregnancy or labor, head trauma, surgery, and weight loss. Patients were divided into two groups regarding the time of MS diagnosis (before and during the COVID-19 pandemic). Results: Of 920 participants, 670 (72.8%) were female, and the mean age ± SD was 35.63 ± 8.1. The majority of patients (69.2%) had non-progressive forms of MS, and only 7.6% needed assistance for ambulation. 69% of participants were diagnosed with MS before the onset of the COVID-19 pandemic. There was a statistically significant difference between the most common first MS symptom before and after the beginning of the pandemic (visual type (n: 317 (49.9%)) before and sensory type (n: 170 (59.6%)) after the COVID-19 pandemic). A stressful life event was the most common patient-reported trigger of MS first presentation in both groups. (56.1% before and 54% after the COVID-19 pandemic). Comparing two groups, economic problems (AOR: 1.81; 95% ACI: 1.23–2.65) and job losses (AOR: 2.89; 95% ACI: 1.37–6.08) were significantly more common triggers for the initial presentation of MS after the pandemic, while the stress of occupational or educational exams (AOR: 0.52; 95% ACI: 0.34–0.79) was more prevalent before the pandemic. Conclusion: Patients believe that stressful life events are closely linked to triggering their first MS symptoms. Since the beginning of the COVID-19 pandemic, economic problems and job losses have increased; however, occupational or educational exams stress decreased. Caring for social stress by societies may affect MS development or delay MS onset. [ABSTRACT FROM AUTHOR]

Background: Diagnosing multiple sclerosis (MS) is challenging due to diverse symptoms and the absence of specific biomarkers. Concurrent autoimmune diseases (AID) or non-specific antibodies further complicate diagnosis, progression monitoring, and management. Data on AID prevalence in MS patients are sparse. This study aims to identify concurrent AIDs alongside MS. Methods: In this retrospective single-center study, we analyzed patient records at our university hospital from 2010 to 2017, focusing on cases suspected of inflammatory demyelinating disease. The 2017 McDonald criteria were applied. Additionally, we measured neurofilament light (NfL) levels from available CSF samples in our biobank. Results: We identified a total of 315 patients, of whom 66% were women. In total, 13.7% of all patients had concurrent AID, while 20.3% had isolated antibody findings without AID. The most common AID was autoimmune thyroiditis (8.9%), followed by chronic inflammatory skin diseases (1.6%), arthritis (1%), type 1 diabetes (1%), Sjögren's syndrome (0.6%), and inflammatory bowel diseases (0.6%). Cardiolipin antibodies were the most frequent isolated antibody finding (8.6%). Our data showed that, from the perspective of the initial demyelinating event, neither comorbid AID nor isolated antibodies significantly influenced relapses or MS progression over a median follow-up of 9 months. Standard CSF parameters and NfL levels were similar between the groups at the time of MS diagnosis. Conclusion: Our study shows that AIDs, particularly autoimmune thyroiditis, frequently occur at the onset of MS. The proportion of AIDs commonly treated with immunomodulatory therapy in our cohort was similar to that observed in the general population. Comorbid AID did not affect NfL levels, indicating similar disease activity. Future research should explore new AID emergence during the course of MS, especially considering the increased incidence of rheumatic diseases later in life. [ABSTRACT FROM AUTHOR]

Background: Immune dysregulation is a hallmark of autoimmune diseases of the central nervous system (CNS), characterized by an excessive immune response, and primary CNS tumors (pCNS-tumors) showing a highly immunosuppressive parenchymal microenvironment. Methods: Aiming to provide novel insights into the pathogenesis of CNS autoimmunity and cerebral tumor immunity, we analyzed the peripheral blood (PB) and cerebrospinal fluid (CSF) of 81 autoimmune limbic encephalitis (ALE), 148 relapsing–remitting multiple sclerosis (RRMS), 33 IDH-wildtype glioma, 9 primary diffuse large B cell lymphoma of the CNS (CNS-DLBCL), and 110 controls by flow cytometry (FC). Additionally, an in-depth immunophenotyping of the PB from an independent cohort of 20 RRMS and 18 IDH-wildtype glioblastoma patients compared to 19 controls was performed by FC combined with unsupervised computational approaches. Results: We identified alterations in peripheral and intrathecal adaptive immunity, mainly affecting the T cell (Tc) but also the B cell (Bc) compartment in ALE, RRMS, and pCNS-tumors compared to controls. ALE, RRMS, and pCNS-tumors featured higher expression of the T cell activation marker HLA-DR, which was even more pronounced in pCNS-tumors than in ALE or RRMS. Glioblastoma patients showed signs of T cell exhaustion that were not visible in RRMS patients. In-depth characterization of the PB revealed differences mainly in the T effector and memory compartment between RRMS and glioblastoma patients and similar alterations in the Bc compartment, including atypical Bc, CD19+CD20− double negative Bc, and plasma cells. PB and CSF mFC together with CSF routine parameters could reliably differentiate ALE and RRMS from pCNS-tumors facilitating early diagnosis and treatment. Conclusions: ALE, RRMS, and pCNS-tumors show distinct but partially overlapping changes mainly in HLA-DR+ Tc, memory Tc, exhausted Tc, and Bc subsets providing insights into disease pathogenesis. Moreover, mFC shows diagnostic potential facilitating early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Historical survey confirms that, over the latter part of the 20th century, autoimmune-based diseases, including multiple sclerosis (MS), have shown a worldwide increase in incidence and prevalence. Analytical population studies have established that the exponential rise in MS is not solely due to improvements in diagnosis and healthcare but relates to an increase in autoimmune risk factors. Harmful environmental exposures, including non-communicable social determinants of health, anthropogens and indigenous or transmissible microbes, constitute a group of causal determinants that have been closely linked with the global rise in MS cases. Exposure to environmental stressors has profound effects on the adaptive arm of the immune system and, in particular, the associated intrinsic process of immune ageing or immunosenescence (ISC). Stressor-related disturbances to the dynamics of ISC include immune cell-linked untimely or premature (p) alterations and an accelerated replicative (ar) change. A recognised immune-associated feature of MS is pISC and current evidence supports the presence of an arISC during the disease. Moreover, collated data illustrates the immune-associated alterations that characterise pISC and arISC are inducible by environmental stressors strongly implicated in causing duplicate changes in adaptive immune cells during MS. The close relationship between exposure to environmental risk factors and the induction of pISC and arISC during MS offers a valid mechanism through which pro-immunosenescent stressors may act and contribute to the recorded increase in the global rate and number of new cases of the disease. Confirmation of alterations to the dynamics of ISC during MS provides a rational and valuable therapeutic target for the use of senolytic drugs to either prevent accumulation and enhance ablation of less efficient untimely senescent adaptive immune cells or decelerate the dysregulated process of replicative proliferation. A range of senotherapeutics are available including kinase and transcriptase inhibitors, rapalogs, flavanols and genetically-engineered T cells and the use of selective treatments to control emerging and unspecified aspects of pISC and arISC are discussed. [ABSTRACT FROM AUTHOR]

Background: Several studies pointed out the importance of genetic risk factors such as parental consanguinity (PC) and familial multiple sclerosis (FMS) in the risk of MS. This study aimed to investigate the PC and FMS among people with MS (pwMS) in Isfahan, Iran. Methods: This case–control study was conducted on pwMS from the MS clinic of Kashani Hospital, Isfahan, Iran, in October 2023. A group of healthy controls (HC) were also recruited. Data on demographic and clinical characteristics and history of PC and FMS were collected from participants. The relationships between PC, FMS, and developing MS were assessed using multinomial logistic regression analysis. The odds ratio (OR) with a 95% confidence interval (CI) was computed. Results: A total number of 4264 pwMS and 400 HCs were included. The prevalence of PC and FMS among pwMS were 29.3% and 24%, respectively. Multinomial logistic regression adjusted for age and sex indicated that the odds of developing MS were significantly associated with a history of PC (OR = 3.03, 95% CI 2.23 to 4.13, p < 0.001) and FMS (OR = 5.42, 95% CI 3.51 to 8.38, p < 0.001). Conclusion: PC and FMS can increase the risk of developing MS. They should be considered along with other risk factors for developing MS. A comprehensive conclusion requires further research. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a complex chronic neuroinflammatory disease characterized by demyelination leading to neuronal dysfunction and neurodegeneration manifested by various neurological impairments. The endocannabinoid system (ECS) is a lipid signalling network, which plays multiple roles in the central nervous system and the periphery, including synaptic signal transmission and modulation of inflammation. The ECS has been identified as a potential target for the development of novel therapeutic interventions in MS patients. It remains unclear whether ECS-associated metabolites are changed in MS and could serve as biomarkers in blood or cerebrospinal fluid (CSF). In this retrospective study we applied targeted lipidomics to matching CSF and serum samples of 74 MS and 80 non-neuroinflammatory control patients. We found that MS-associated lipidomic changes overall did not coincide between CSF and serum. While glucocorticoids correlated positively, only the endocannabinoid (eCB) 2-arachidonoyl glycerol (2-AG) showed a weak positive correlation (r = 0.3, p < 0.05) between CSF and serum. Peptide endocannabinoids could be quantified for the first time in CSF but did not differ between MS and controls. MS patients showed elevated levels of prostaglandin E2 and steaorylethanolamide in serum, and 2-oleoylglycerol and cortisol in CSF. Sex-specific differences were found in CSF of MS patients showing increased levels of 2-AG and glucocorticoids in males only. Overall, arachidonic acid was elevated in CSF of males. Interestingly, CSF eCBs correlated positively with age only in the control patients due to the increased levels of eCBs in young relapsing-remitting MS patients. Our findings reveal significant discrepancies between CSF and serum, underscoring that measuring eCBs in blood matrices is not optimal for detecting MS-associated changes in the central nervous system. The identified sex and age-specific changes of analytes of the stress axis and ECS specifically in the CSF of MS patients supports the role of the ECS in MS and may be relevant for drug development strategies. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a disabling disease of the central nervous system. People living with MS often have co-existing sleep disorders and cognitive dysfunction. The objective of this study was to scrutinize the relationship between cognitive outcomes and sleep conditions in MS. Methods: This study followed the Joanna Briggs Institute's (JBI) and PRISMA guidelines. PubMed, Scopus, Embase, and Web of Science databases were searched and original studies delineating the relationship between sleep status and cognitive findings in MS patients‌ were included. The risk of bias was assessed using the JBI critical appraisal tools. Results: In the final review, out of 1635 screened records, 35 studies with 5321 participants were included. Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and polysomnography were the most common assessment tools for evaluation of sleep condition, and cognitive evaluations were conducted using the tests including Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test (CVLT), Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test (BVMT). Assessing the quality of studies showed no significant bias in most of the included articles. A link between sleep condition and cognitive abilities was suggested in the literature, especially with objective measurement of sleep condition; however, current evidence did not support a substantial association between self-reported sleep quality and processing speed and working memory in patients with MS. Discussion: Evidence proposes sleep is an independent factor associated with cognitive outcomes in MS. Given the limitations of the evidence such as the lack of well-designed prospective studies, these findings need to be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: Treatment decisions for persons with relapsing–remitting multiple sclerosis (RRMS) rely on clinical and radiological disease activity, the benefit-harm profile of drug therapy, and preferences of patients and physicians. However, there is limited evidence to support evidence-based personalized decision-making on how to adapt disease-modifying therapy treatments targeting no evidence of disease activity, while achieving better patient-relevant outcomes, fewer adverse events, and improved care. Serum neurofilament light chain (sNfL) is a sensitive measure of disease activity that captures and prognosticates disease worsening in RRMS. sNfL might therefore be instrumental for a patient-tailored treatment adaptation. We aim to assess whether 6-monthly sNfL monitoring in addition to usual care improves patient-relevant outcomes compared to usual care alone. Methods: Pragmatic multicenter, 1:1 randomized, platform trial embedded in the Swiss Multiple Sclerosis Cohort (SMSC). All patients with RRMS in the SMSC for ≥ 1 year are eligible. We plan to include 915 patients with RRMS, randomly allocated to two groups with different care strategies, one of them new (group A) and one of them usual care (group B). In group A, 6-monthly monitoring of sNfL will together with information on relapses, disability, and magnetic resonance imaging (MRI) inform personalized treatment decisions (e.g., escalation or de-escalation) supported by pre-specified algorithms. In group B, patients will receive usual care with their usual 6- or 12-monthly visits. Two primary outcomes will be used: (1) evidence of disease activity (EDA3: occurrence of relapses, disability worsening, or MRI activity) and (2) quality of life (MQoL-54) using 24-month follow-up. The new treatment strategy with sNfL will be considered superior to usual care if either more patients have no EDA3, or their health-related quality of life increases. Data collection will be embedded within the SMSC using established trial-level quality procedures. Discussion: MultiSCRIPT aims to be a platform where research and care are optimally combined to generate evidence to inform personalized decision-making in usual care. This approach aims to foster better personalized treatment and care strategies, at low cost and with rapid translation to clinical practice. Trial registration: ClinicalTrials.gov NCT06095271. Registered on October 23, 2023 [ABSTRACT FROM AUTHOR]

Background: Mirror movements (MM) are commonly caused by a defect of interhemispheric pathways also affected in multiple sclerosis (MS), particularly the corpus callosum. We investigated the prevalence of MM in MS in relation to functional and morphological callosal fiber integrity by transcranial magnetic stimulation (TMS), magnetic resonance imaging (MRI), as well as fatigue. Methods: In 21 patients with relapsing–remitting MS and 19 healthy controls, MM were assessed and graded (Woods and Teuber scale: MM 1—4) using a bedside test. Fatigue was evaluated using the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire. TMS measured ipsilateral silent period latency and duration. MRI assessed callosal atrophy by measuring the normalized corpus callosum area (nCCA), corpus callosum index (CCI), and lesion volume. Results: MS patients had significantly more often and pronounced MM compared to healthy controls (p = 0.0002) and nCCA was significantly lower (p = 0.045) in MRI studies. Patients with higher MM scores (MM > 1 vs. MM 0/1) showed significantly more fatigue (higher FSMC sum score, p = 0.04, motor score, p = 0.01). In TMS and MRI studies, no significant differences were found between patients with MM 0/1 and those with MM > 1 (ipsilateral silent period measurements, CCA, CCI and lesion volume). Conclusions: MM are common in MS and can easily be detected through bedside testing. As MM are associated with fatigue, they might indicate fatigue in MS. It is possible that other cerebral structures, in addition to the corpus callosum, may contribute to the origin of MM in MS. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a debilitating, non-traumatic disease that is common among young adults. Cultural factors, as background factors, can affect how patients adapt and their quality of life. This study aimed to explain the burden of cultural factors on Multiple sclerosis. Methods: This study was conducted with a qualitative approach and conventional content analysis among women with Multiple sclerosis in Mashhad. The data were collected through semi-structured interviews with women with MS. Fifteen patients with Multiple sclerosis were selected using purposeful sampling. The Graneheim and Lundman method was used to analyze the collected data. The transferability of the study was evaluated using the Guba and Lincoln criteria. MAXQADA 10 software was used to manage and analyze the data. Results: In explanation of the cultural factors of patients with Multiple sclerosis, one category (cultural tensions) and five subcategories (forced communication with spouse's family, definition of women's role in society, people's behavior, social beliefs and isolation of the patient) were extracted. Conclusion: The results obtained in this study show that female MS patients face various concerns. Overcoming these challenges require a change in the attitude of people in the society towards women with MS, which is important in the context of formulating practical policies to create a suitable culture. Adopted policies should aim to internalize the culture of changing society's views of female MS patients. Therefore, the authors argue that there is a need for cultural policies, followed by the systems implementing these policies to consider the challenges mentioned in this study as a priority for MS patients. [ABSTRACT FROM AUTHOR]

Cryptococcal infection of central nervous system commonly involves meningitis or meningoencephalitis, but rarely mimics inflammatory myelitis. We present short segment myelitis as a dominant manifestation caused by Cryptococcus neoformans in a patient with nephrotic syndrome under immunosuppressive therapy. This case report highlights Cryptococcus neoformans as a potential etiological factor for short segment myelitis in immunocompromised hosts. [ABSTRACT FROM AUTHOR]

Background: To investigate the safety (adverse events [AEs] and post-vaccination multiple sclerosis [MS] activity within 6 weeks), clinical efficacy (protection against coronavirus disease 2019 [COVID-19]), and vaccine-induced humoral immunogenicity (SARS-CoV-2 neutralizing antibody, anti-nucleocapsid IgG, and anti-spike IgG) of the Sinopharm (BBIBP-CorV) vaccine among people with MS (PwMS) receiving different disease-modifying therapies (DMTs). Methods: This prospective cohort study was conducted between November 2021 and May 2022. PwMS were followed for six months after the 2nd dose of vaccination. Antibody responses were measured 2–16 weeks after the 2nd dose injection. Multivariate logistic regression was employed to assess the impact of each DMT on dichotomous antibody responses, adjusting for age, sex, MS phenotype, expanded disability status scale, disease duration, and vaccination-antibody titration interval. Results: Among the 261 screened PwMS, 209 (aged 38.23 ± 9.73 years, female: 70.8%; relapsing-remitting MS: 80.4%) were included. The frequencies of experiencing non-serious AEs and post-vaccination MS activity were 66.0% and 4.8%, respectively. Breakthrough COVID-19 infection was observed in 14.8% of the PwMS. A subcohort of 125 PwMS was assessed for antibody responses. Positive neutralizing antibodies, anti-nucleocapsid IgG, and anti-spike IgG were detected in 36.8%, 35.2%, and 52.0% of the PwMS, respectively. Multivariate regression indicated a 96% (OR: 0.04 [95% CI: 0.00, 0.51], P = 0.013), 93% (OR: 0.07 [0.01, 0.64], P = 0.019), and 89% (OR: 0.11 [0.01, 0.96], P = 0.045) reduced odds of positive neutralizing antibody, anti-nucleocapsid IgG, and anti-spike IgG, respectively, among fingolimod-receivers. Additionally, anti-CD20s-receivers had 88% (OR: 0.12 [0.02, 0.85], P = 0.034) lower odds of being positive for anti-nucleocapsid IgG. Conclusions: BBIBP-CorV appeared to be well tolerated in PwMS, with promising clinical efficacy. However, a suboptimal humoral response was observed in PwMS receiving fingolimod and anti-CD20s. Future research should investigate the relationship between humoral responses and the frequency and severity of COVID-19 infection across various DMTs. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF) is a pleiotropic cytokine regulating many physiological and pathological immune-mediated processes. Specifically, it has been recognized as an essential pro-inflammatory cytokine implicated in multiple sclerosis (MS) pathogenesis and progression. MS is a chronic immune-mediated disease of the central nervous system, characterized by multifocal acute and chronic inflammatory demyelination in white and grey matter, along with neuroaxonal loss. A recent concept in the field of MS research is disability resulting from Progression Independent of Relapse Activity (PIRA). PIRA recognizes that disability accumulation since the early phase of the disease can occur independently of relapse activity overcoming the traditional dualistic view of MS as either a relapsing-inflammatory or a progressive-neurodegenerative disease. Several studies have demonstrated an upregulation in TNF expression in both acute and chronic active MS brain lesions. Additionally, elevated TNF levels have been observed in the serum and cerebrospinal fluid of MS patients. TNF appears to play a significant role in maintaining chronic intrathecal inflammation, promoting axonal damage neurodegeneration, and consequently contributing to disease progression and disability accumulation. In summary, this review highlights the current understanding of TNF and its receptors in MS progression, specifically focusing on the relatively unexplored PIRA condition. Further research in this area holds promise for potential therapeutic interventions targeting TNF to mitigate disability in MS patients. [ABSTRACT FROM AUTHOR]

Objective: To compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with multiple sclerosis (MS) referred to Royan Institute. Materials and methods: This retrospective study was carried out to evaluate all women diagnosed with MS and referred to Royan Institute for assessment and treatment of possible infertility between 2011 and 2022. The control group consisted of randomly selected healthy women with tubal factor infertility who were referred for treatment during the same time period and matched in terms of age. A comparison was made between groups in terms of ovarian reserve and infertility treatment outcomes. Additionally, patients with MS who met the criteria were monitored via telephone to evaluate the symptoms, disability and relapse rate both pre- and post-ART. Results: Over the course of a decade, the database documented a total of 60 cases diagnosed with MS. Upon examination of the records, it was found that in 27 patients only admission was done without any hormonal assessment or infertility treatment cycle and 5 patients proceeded with the intrauterine insemination cycle. Eventually, 28 women with MS underwent the ART cycle and all of them were treated with interferon beta, glatiramer acetate, or some oral disease modifying therapies. No statistically significant difference in terms of the basal levels of luteinizing hormone, follicle-stimulating hormone and anti-Müllerian hormone was found between the MS and control groups (P > 0.05). Two groups were comparable in terms of menstrual status. The study revealed that both groups exhibited similarities in terms of the controlled ovarian stimulation protocol and duration, the dosage of gonadotropin administered, as well as the ovarian response type, clinical pregnancy rate, and live birth rate (P > 0.05). After follow up, only 2 patients (9.5%) reported relapse of symptoms within one year after ART. Conclusion: The ovarian reserve and ovarian stimulation cycle and pregnancy outcomes following the ART cycle in MS patients were similar to the age-matched control group. The relapse rate of multiple sclerosis did not show a significant increase within a year following the ART cycle. [ABSTRACT FROM AUTHOR]

Background: Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson's Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans. Methods: In a case–control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer's disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating. Results: The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes. Conclusions and Relevance: Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a clinically and biologically heterogenous disease with currently unpredictable progression and relapse. After the development and success of neurofilament as a cerebrospinal fluid (CSF) biomarker, there is reinvigorated interest in identifying other markers of or contributors to disease. The objective of this study is to probe the predictive potential of a panel of brain-enriched proteins on MS disease progression and subtype. Methods: This study includes 40 individuals with MS and 14 headache controls. The MS cohort consists of 20 relapsing remitting (RR) and 20 primary progressive (PP) patients. The CSF of all individuals was analyzed for 63 brain enriched proteins using a method of liquid-chromatography tandem mass spectrometry. Wilcoxon rank sum test, Kruskal-Wallis one-way ANOVA, logistic regression, and Pearson correlation were used to refine the list of candidates by comparing relative protein concentrations as well as relation to known imaging and molecular biomarkers. Results: We report 30 proteins with some relevance to disease, clinical subtype, or severity. Strikingly, we observed widespread protein depletion in the disease CSF as compared to control. We identified numerous markers of relapsing disease, including KLK6 (kallikrein 6, OR = 0.367, p < 0.05), which may be driven by active disease as defined by MRI enhancing lesions. Other oligodendrocyte-enriched proteins also appeared at reduced levels in relapsing disease, namely CNDP1 (carnosine dipeptidase 1), LINGO1 (leucine rich repeat and Immunoglobin-like domain-containing protein 1), MAG (myelin associated glycoprotein), and MOG (myelin oligodendrocyte glycoprotein). Finally, we identified three proteins—CNDP1, APLP1 (amyloid beta precursor like protein 1), and OLFM1 (olfactomedin 1)—that were statistically different in relapsing vs. progressive disease raising the potential for use as an early biomarker to discriminate clinical subtype. Conclusions: We illustrate the utility of targeted mass spectrometry in generating potential targets for future biomarker studies and highlight reductions in brain-enriched proteins as markers of the relapsing remitting disease stage. [ABSTRACT FROM AUTHOR]

Background: Multiple Sclerosis (MS) represents the most common inflammatory neurological disease causing disability in early adulthood. Childhood and adolescence factors might be of relevance in the development of MS. We aimed to investigate the association between various factors (e.g., prematurity, breastfeeding, daycare attendance, weight history) and MS risk. Methods: Data from the baseline assessment of the German National Cohort (NAKO) were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between childhood and adolescence factors and risk of MS. Analyses stratified by sex were conducted. Results: Among a total of 204,273 participants, 858 reported an MS diagnosis. Male sex was associated with a decreased MS risk (HR 0.48; 95% CI 0.41–0.56), while overweight (HR 2.03; 95% CI 1.41–2.94) and obesity (HR 1.89; 95% CI 1.02–3.48) at 18 years of age compared to normal weight were associated with increased MS risk. Having been breastfed for ≤ 4 months was associated with a decreased MS risk in men (HR 0.59; 95% CI 0.40–0.86) compared to no breastfeeding. No association with MS risk was observed for the remaining factors. Conclusions: Apart from overweight and obesity at the age of 18 years, we did not observe considerable associations with MS risk. The proportion of cases that can be explained by childhood and adolescence factors examined in this study was low. Further investigations of the association between the onset of overweight and obesity in childhood and adolescence and its interaction with physical activity and MS risk seem worthwhile. [ABSTRACT FROM AUTHOR]

Background: Certain demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) exhibit serum autoantibodies against aquaporin-4 (αAQP4) and myelin oligodendrocyte glycoprotein (αMOG). The variability of the autoantibody presentation warrants further research into subtyping each case. Methods: To elucidate the relationship between astroglial and neuronal protein concentrations in the peripheral circulation with occurrence of these autoantibodies, 86 serum samples were analyzed using immunoassays. The protein concentration of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL) and tau protein was measured in 3 groups of subcategories of suspected NMOSD: αAQP4 positive (n = 20), αMOG positive (n = 32) and αMOG/αAQP4 seronegative (n = 34). Kruskal-Wallis analysis, univariate predictor analysis, and multivariate logistic regression with ROC curves were performed. Results: GFAP and NFL concentrations were significantly elevated in the αAQP4 positive group (p = 0.003; p = 0.042, respectively), and tau was elevated in the αMOG/αAQP4 seronegative group (p < 0.001). A logistic regression model to classify serostatus was able to separate αAQP4 seropositivity using GFAP + tau, and αMOG seropositivity using tau. The areas under the ROC curves (AUCs) were 0.77 and 0.72, respectively. Finally, a combined seropositivity versus negative status logistic regression model was generated, with AUC = 0.80. Conclusion: The 3 markers can univariately and multivariately classify with moderate accuracy the samples with seropositivity and seronegativity for αAQP4 and αMOG. [ABSTRACT FROM AUTHOR]

Background: Effective interventions for Multiple Sclerosis require timely treatment optimization which usually involves switching disease modifying therapies. The patterns of prescription and the reasons for changing treatment in people with MS, especially in low prevalence populations, are unknown. Objectives: To describe the persistence, reasons of DMT switches and prescription patterns in a cohort of Colombian people with MS. Methods: We conducted a retrospective observational study including patients with confirmed MS with at least one visit at our centre. We estimated the overall incidence rate of medication changes and assessed the persistence on medication with Kaplan–Meier survival estimates for individual medications and according to efficacy and mode of administration. The factors associated with changing medications were assessed using adjusted Cox proportional-hazards models. The reasons for switching medication changes were described, and the prescription patterns were assessed using network analysis, with measures of centrality. Results: Seven hundred one patients with MS were included. Mean age was 44.3 years, and 67.9% were female. Mean disease duration was 11.3 years and 84.5% had relapsing MS at onset, with median EDSS of 1.0. Treatment was started in 659 (94%) of the patients after a mean of 3 years after MS symptom onset. Among them, 39.5% maintained their initial DMT, 29.9% experienced a single DMT change, while 18.7% went through two, and 11.9% had three or more DMT changes until the final follow-up. The total number of treatment modifications reached 720, resulting in an incidence rate of 1.09 (95% confidence interval: 1.01–1.17) per patient per year The median time to change after the first DMT was 3.75 years, and was not different according to the mode of administration or efficacy classification. The main reasons for changing DMT were MS activity (relapses, 56.7%; MRI activity, 18.6%), followed by non-serious adverse events (15.3%) and disability (11.1%). Younger age at MS onset, care under our centre and insurer status were the main determinants of treatment change. Network analysis showed that interferons and fingolimod were the most influential DMTs. Conclusions: A majority of patients switch medications, mostly due to disease activity, and in association with age and insurer status. [ABSTRACT FROM AUTHOR]

Introduction: In Multiple Sclerosis (MS), patients´ characteristics and (bio)markers that reliably predict the individual disease prognosis at disease onset are lacking. Cohort studies allow a close follow-up of MS histories and a thorough phenotyping of patients. Therefore, a multicenter cohort study was initiated to implement a wide spectrum of data and (bio)markers in newly diagnosed patients. Methods: ProVal-MS (Prospective study to validate a multidimensional decision score that predicts treatment outcome at 24 months in untreated patients with clinically isolated syndrome or early Relapsing–Remitting-MS) is a prospective cohort study in patients with clinically isolated syndrome (CIS) or Relapsing–Remitting (RR)-MS (McDonald 2017 criteria), diagnosed within the last two years, conducted at five academic centers in Southern Germany. The collection of clinical, laboratory, imaging, and paraclinical data as well as biosamples is harmonized across centers. The primary goal is to validate (discrimination and calibration) the previously published DIFUTURE MS-Treatment Decision score (MS-TDS). The score supports clinical decision-making regarding the options of early (within 6 months after study baseline) platform medication (Interferon beta, glatiramer acetate, dimethyl/diroximel fumarate, teriflunomide), or no immediate treatment (> 6 months after baseline) of patients with early RR-MS and CIS by predicting the probability of new or enlarging lesions in cerebral magnetic resonance images (MRIs) between 6 and 24 months. Further objectives are refining the MS-TDS score and providing data to identify new markers reflecting disease course and severity. The project also provides a technical evaluation of the ProVal-MS cohort within the IT-infrastructure of the DIFUTURE consortium (Data Integration for Future Medicine) and assesses the efficacy of the data sharing techniques developed. Perspective: Clinical cohorts provide the infrastructure to discover and to validate relevant disease-specific findings. A successful validation of the MS-TDS will add a new clinical decision tool to the armamentarium of practicing MS neurologists from which newly diagnosed MS patients may take advantage. Trial registration ProVal-MS has been registered in the German Clinical Trials Register, 'Deutsches Register Klinischer Studien' (DRKS)—ID: DRKS00014034, date of registration: 21 December 2018; https://drks.de/search/en/trial/DRKS00014034 [ABSTRACT FROM AUTHOR]

Background: Observational studies have suggested an association between multiple sclerosis (MS) and cortical structure, but the results have been inconsistent. Objective: We used two-sample Mendelian randomization (MR) to assess the causal relationship between MS and cortical structure. Methods: MS data as the exposure trait, including 14,498 cases and 24,091 controls, were obtained from the International Multiple Sclerosis Genetics Consortium. Genome-wide association study (GWAS) data for cortical surface area (SAw/nw) and thickness (THw/nw) in 51,665 individuals of European ancestry were obtained from the ENIGMA Consortium. The inverse-variance weighted (IVW) method was used as the primary analysis for MR. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Enrichment analysis was performed on MR analyses filtered by sensitivity analysis. Results: After IVW and sensitivity analysis filtering, only six surviving MR results provided suggestive evidence supporting a causal relationship between MS and cortical structure, including lingual SAw (p =.0342, beta (se) = 5.7127 (2.6969)), parahippocampal SAw (p =.0224, beta (se) = 1.5577 (0.6822)), rostral middle frontal SAw (p =.0154, beta (se) = − 9.0301 (3.7281)), cuneus THw (p =.0418, beta (se) = − 0.0020 (0.0010)), lateral orbitofrontal THw (p =.0281, beta (se) = 0.0025 (0.0010)), and lateral orbitofrontal THnw (p =.0417, beta (se) = 0.0029 (0.0014)). Enrichment analysis suggested that leukocyte cell-related pathways, JAK-STAT signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and prolactin signaling pathway may be involved in the effect of MS on cortical morphology. Conclusion: Our results provide evidence supporting a causal relationship between MS and cortical structure. Enrichment analysis suggests that the pathways mediating brain morphology abnormalities in MS patients are mainly related to immune and inflammation-driven pathways. [ABSTRACT FROM AUTHOR]

Background: Up to 65% of people with multiple sclerosis (PwMS) develop cognitive deficits, which hampers their ability to work, participating in day-to-day life and ultimately reducing quality of life (QoL). Early cognitive symptoms are often less tangible to PwMS and their direct environment and are noticed only when symptoms and work functioning problems become more advanced, i.e., when (brain) damage is already advanced. Treatment of symptoms at a late stage can lead to cognitive impairment and unemployment, highlighting the need for preventative interventions in PwMS. Aims: This study aims to evaluate the (cost-) effectiveness of two innovative preventative interventions, aimed at postponing cognitive decline and work functioning problems, compared to enhanced usual care in improving health-related QoL (HRQoL). Methods: Randomised controlled trial including 270 PwMS with mild cognitive impairment, who have paid employment ≥ 12 h per week and are able to participate in physical exercise (Expanded Disability Status Scale < 6.0). Participants are randomised across three study arms: 1) 'strengthening the brain' – a lifestyle intervention combining personal fitness, mental coaching, dietary advice, and cognitive training; 2) 'strengthening the mind' – a work-focused intervention combining the capability approach and the participatory approach in one-on-one coaching by trained work coaches who have MS themselves; 3) Control group—receiving general information about cognitive impairment in MS and receiving care as usual. Intervention duration is four months, with short-term and long-term follow-up measurements at 10 and 16 months, respectively. The primary outcome measure of the Don't be late! intervention study will be HRQoL as measured with the 36-item Short Form. Secondary outcomes include cognition, work related outcomes, physical functioning, structural and functional brain changes, psychological functioning, and societal costs. Semi-structured interviews and focus groups with stakeholders will be organised to qualitatively reflect on the process and outcome of the interventions. Discussion: This study seeks to prevent (further) cognitive decline and job loss due to MS by introducing tailor-made interventions at an early stage of cognitive symptoms, thereby maintaining or improving HRQoL. Qualitative analyses will be performed to allow successful implementation into clinical practice. Trial registration: Retrospectively registered at ClinicalTrials.gov with reference number NCT06068582 on 10 October 2023. [ABSTRACT FROM AUTHOR]

Background: Diarrhoeal diseases are common among children in low- and middle-income countries and are major causes of morbidity and mortality. Cryptosporidium and Giardia are considered to be the main parasitic causes of diarrhoea in children. The aim of the present study was to determine the prevalence and associated factors of Cryptosporidium and Giardia infection in children under five years of age presenting at two health centres (Ndirande and Limbe) in Blantyre, Malawi. Methods: This cross-sectional study was performed from February to July 2019 and included 972 children under 5 years of age with diarrhoea. Stool samples were immediately tested after collection at enrolment with a rapid diagnostic test for Cryptosporidium and Giardia infection. Descriptive statistics were used to assess the prevalence of these protozoan parasitic infections, and differences in the basic demographic and anthroponotic variables (between children with diarrhoea and parasite infection, being either Cryptosporidium and Giardia or both versus children with diarrhoea but no RDT confirmed parasite infection) were assessed. Their association with Cryptosporidium and Giardia infection was analysed using simple logistic regressions. Results: Of the children recruited, 88 (9.1%) tested positive for Cryptosporidium and 184 (18.9%) for Giardia. Children with only a Giardia infection or a coinfection (of both parasites) were significantly older (mean age 24–26 months) compared to children with only a Cryptosporidium infection (mean age 13 months) or no parasitic infection (mean age 14 months). No significant differences were found with respect to gender, body temperature, stunting or wasting between the different groups of children with moderate to severe diarrhoea. Children attending the Ndirande health centre had almost two times higher odds of testing positive for both infections than those attending Limbe health centre. Conclusion: Cryptosporidium and Giardia infections are highly prevalent in children < 5 years with moderate to severe diarrhoea attending the Limbe and Ndirande health centres in Blantyre, Malawi. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Since MS does not have a definitive cure, individuals affected by it need to adapt and coordinate with their chronic illness in order to fulfill their duties and responsibilities. The first step in helping patients to better care for and manage their illness is to engage in self-care behaviors. This study was conducted with the aim of design and validation of a questionnaire on the factors influencing self-care behaviors in patients with Multiple sclerosis. Methods: This cross-sectional study was conducted on Multiple sclerosis patients in Iran in 2023. The age range of patients varied between 22 and 52 years. Having MS disease, passing one year of the disease duration, living in Mashhad city, having informed consent to participate in the study and not completing the questionnaire were the entry and exit criteria of the study. Results: This study was conducted on 500 patients with multiple sclerosis. Based on the results of psychometrics (face, content and construct validity), the number of questions was reduced from 120 to 47 questions and 73 questions were eliminated. Finally, the questionnaire was approved with 47 questions and 4 subscales of understanding the symptoms of the disease (9 questions), tendency to conscious and targeted care (21 questions), laziness in care (8 questions) and tendency to receive therapy services (9 questions). Cronbach's alpha and McDonald's omega index for all questionnaire questions were 0.877 and 0.881, respectively. Conclusions: Based on the results of this questionnaire, 47 questions and 4 subscales can be used to measure the factors influencing the adoption of self-care behaviour's in patients with multiple sclerosis. [ABSTRACT FROM AUTHOR]

Background: Impaired brain energy metabolism has been observed in many neurodegenerative diseases, including Parkinson's disease (PD) and multiple sclerosis (MS). In both diseases, mitochondrial dysfunction and energetic impairment can lead to neuronal dysfunction and death. CNM-Au8® is a suspension of faceted, clean-surfaced gold nanocrystals that catalytically improves energetic metabolism in CNS cells, supporting neuroprotection and remyelination as demonstrated in multiple independent preclinical models. The objective of the Phase 2 REPAIR-MS and REPAIR-PD clinical trials was to investigate the effects of CNM-Au8, administered orally once daily for twelve or more weeks, on brain phosphorous-containing energy metabolite levels in participants with diagnoses of relapsing MS or idiopathic PD, respectively. Results: Brain metabolites were measured using 7-Tesla 31P-MRS in two disease cohorts, 11 participants with stable relapsing MS and 13 participants with PD (n = 24 evaluable post-baseline scans). Compared to pre-treatment baseline, the mean NAD+/NADH ratio in the brain, a measure of energetic capacity, was significantly increased by 10.4% after 12 + weeks of treatment with CNM-Au8 (0.584 units, SD: 1.3; p = 0.037, paired t-test) in prespecified analyses of the combined treatment cohorts. Each disease cohort concordantly demonstrated increases in the NAD+/NADH ratio but did not reach significance individually (p = 0.11 and p = 0.14, PD and MS cohorts, respectively). Significant treatment effects were also observed for secondary and exploratory imaging outcomes, including β-ATP and phosphorylation potential across both cohorts. Conclusions: Our results demonstrate brain target engagement of CNM-Au8 as a direct modulator of brain energy metabolism, and support the further investigation of CNM-Au8 as a potential disease modifying drug for PD and MS. [ABSTRACT FROM AUTHOR]

Background: The Female Sexual Function Index (FSFI) is a widely recognized tool for assessing sexual dysfunction (SD). However, its validation for Spanish women suffering from multiple sclerosis (MS) has not yet been conducted. Aim: The study aimed to examine the psychometric properties of the 19-item Spanish version of the FSFI (svFSFI) in women with relapsing MS. Method: A total of 137 women with relapsing MS from three Spanish centers participated in the study and completed the svFSFI. The psychometric properties of the questionnaire were evaluated. The prevalence of SD in the study cohort was determined, and its association with clinical and sociodemographic variables was analyzed using bi- and multivariate regression analyses. Results: The svFSFI demonstrated excellent test-retest reliability and substantial-to-excellent internal consistency in the context of relapsing MS. There was significant convergent validity in the intercorrelations of domains. Discriminant validity showed differences in SD between women with high and low neurological disability, as measured by the Expanded Disability Status Scale (EDSS) scores. An exploratory factor analysis indicated a five-factor structure for the svFSFI. The prevalence of SD in the MS cohort was found to be 42.6%, with the 'desire' and 'arousal' domains being the most affected. Factors such as EDSS score, fatigue, depression, and having a stable partner were found to influence the total svFSFI score. Conclusion: The study validates the svFSFI as a reliable and valid instrument for evaluating sexual dysfunction in Spanish women with MS. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal (GI) symptoms affect more than 80% of individuals with relapsing-remitting multiple sclerosis (RRMS). Ginger is widely known for its GI relieving properties. Therefore, we investigated the effect of ginger supplementation on common GI symptoms in RRMS patients. Methods: This study was a 12-week double-blind parallel randomized controlled trial with a 3-week run-in period. The intervention (n = 26) and control (n = 26) groups received 500 mg ginger and placebo (as corn) supplements 3 times a day along with main meals, respectively. At the beginning and end of the trial, the frequency and severity of constipation, dysphagia, abdominal pain, diarrhea, bloating, belching, flatulence, heartburn, anorexia, and nausea were assessed using the visual analogue scale ranging from 0 to 100 mm. Totally, 49 participants completed the study. However, data analysis was performed on all 52 participants based on the intention-to-treat principle. Results: In comparison with placebo, ginger supplementation resulted in significant or near-significant reductions in the frequency (-23.63 ± 5.36 vs. 14.81 ± 2.78, P < 0.001) and severity (-24.15 ± 5.10 vs. 11.39 ± 3.23, P < 0.001) of constipation, the frequency (-12.41 ± 3.75 vs. 3.75 ± 1.82, P < 0.001) and severity (-13.43 ± 4.91 vs. 6.88 ± 2.69, P = 0.001) of nausea, the frequency (-9.31 ± 4.44 vs. 1.56 ± 4.05, P = 0.098) and severity (-11.57 ± 5.09 vs. 3.97 ± 3.99, P = 0.047) of bloating, and the severity of abdominal pain (-5.69 ± 3.66 vs. 3.43 ± 3.26, P = 0.069). Conclusion: Ginger consumption can improve constipation, nausea, bloating, and abdominal pain in patients with RRMS. Trial Registration: This trial was prospectively registered at the Iranian Registry of Clinical Trials (www.irct.ir) under the registration number IRCT20180818040827N3 on 06/10/2021. [ABSTRACT FROM AUTHOR]

Background: Multimodal agility-based exercise training (MAT) is a group-based exercise training framework for persons with multiple sclerosis (pwMS) with a potential to impact fatigue and fatigability. In a mixed-methods design, this study evaluated the feasibility of implementing MAT in an inpatient rehabilitation setting and the feasibility of a randomized controlled trial (RCT) study protocol with 'traditional' strength and endurance training (SET) as an active control condition. Secondarily, preliminary outcome data was acquired. Methods: PwMS with low to moderate disability and self-reported fatigue were randomly allocated to either MAT or SET when starting inpatient rehabilitation (4–6 weeks). The MAT-participants exercised in a group following a MAT-manual (sessions were gym- (5x/week) and pool-based (3x/week)). SET-participants exercised individually 5x/week on a cycle ergometer, and 3x/week on strength training machines. Feasibility assessments focused on processes, resources, management, time, and scientific domains. Assessed clinical outcomes at admission and discharge included perceived fatigue, motor and cognitive fatigability, cognitive performance, motor function, and balance confidence. Perceived fatigue was reassessed 1, 4, and 12 weeks after discharge. Feasibility was determined regarding predetermined progression criteria. Results: Twenty-two participants were randomized. Both groups performed the minimum number of sessions (> 18), and retention was adequate (73–91%). SET-participants performed more sessions than MAT-participants (30.8 vs. 22.7) and stayed longer in the facility (34.2 vs. 31.6 days). Non-eligibility of admitted pwMS was high (74% non-eligible), mainly due to high EDSS and inability to attend pool-based sessions. Consequently, recruitment (1.8/month) was slower than the predetermined progression criterium. Baseline assessments took longer than required (only 50% completed within 3 days). Short-term fatigue reduction was similar for both groups. Motor fatigability also improved in both groups, whereas cognitive fatigability deteriorated. In MAT, average improvement in walking endurance (43.9 m) exceeded minimal important change values for individuals (> 26.9 m). Conclusions: Progressing to a definitive RCT necessitates adaptation of eligibility criteria. In the present design it will also be difficult to attain similar dosing of interventions. A multicenter RCT focused only on gym-based MAT might be another option to assess the effect of MAT. The primary outcome measure should be able to measure change in perceived fatigue more robustly. Trial registration: German Clinical Trials Register: DRKS00023943, date of registration: 23 September 2021. [ABSTRACT FROM AUTHOR]

Background: Motor impairments are very common in neurological diseases such as multiple sclerosis. Noninvasive brain stimulation could influence the motor function of patients. Objective: The aim of this meta-analysis was to evaluate the effectiveness of transcranial direct current stimulation (tDCS) on balance and gait ability in patients with multiple sclerosis. Additionally, a secondary aim was to compare the influence of the stimulation location of tDCS on current effectiveness. Methods: A search was conducted for randomized controlled trials published up to May 2023 comparing the application of tDCS versus a sham or control group. The primary outcome variables were balance and gait ability. Results: Eleven studies were included in the qualitative analysis, and ten were included in the quantitative analysis, which included 230 patients with multiple sclerosis. The average effect of tDCS on gait functionality was superior to that of the control group (SMD = -0.71; 95% CI, -1.05 to -0.37). However, the overall results of the tDCS vs. sham effect on static balance did not show significant differences between groups (MD = 1.26, 95% CI, -1.31 to 3.82). No significant differences were found when different locations of tDCS were compared. Conclusions: These results reveal that tDCS is an effective treatment for improving gait ability with a low quality of evidence. However, the application of tDCS has no effect on static balance in patients with multiple sclerosis with very low quality of evidence. Similarly, there seems to be no difference regarding the stimulation area with tDCS. [ABSTRACT FROM AUTHOR]

Background: Gait impairment is a relevant problem in persons with multiple sclerosis (pwMS). The Multiple Sclerosis Walking Scale 12 (MSWS-12) is a valid Patient Reported Outcome Measure (PROM) to evaluate walking ability in pwMS. The aim of this study was to provide a linguistically valid translation of MSWS-12 into German language (MSWS-12/D) and to evaluate its psychometric properties. Methods: The MSWS-12 was translated in a process modified from guidelines for the cross-cultural adaption of PROMs, and a pre-test was applied in a small sample of 20 pwMS to evaluate comprehensibility and acceptance. Psychometric properties (floor and ceiling effects, internal consistency, construct validity) were then assessed in 124 pwMS seen at academic MS centers. Construct validity was evaluated against Expanded Disability Status Scale (EDSS) and maximum gait speed in the Timed 25-Foot Walk (T25FW). Results: Although the sample covered a wide spectrum of symptom severity, the majority had rather low levels of disability (EDSS median 2.0) and 6.5% scored EDSS of 0. In this sample, MSWS-12/D showed floor effects (36% with score 0) and for internal consistency, a Cronbach's alpha of 0.98 was calculated. MSWS-12/D score showed a relevant correlation to EDSS (ρ = 0.73) and T25FW speed (r=-0.72). Conclusion: We provide MSWS-12/D as a linguistically valid German version of MSWS-12. Psychometric properties (acceptance, floor and ceiling effects, internal consistency and construct validity) in pwMS were similar to those described for the original version. This indicates that MSWS-12/D can be applied as equivalent to the original version in German speaking pwMS. Results support the relevance of PROMs to capture patient perception of walking ability in addition to performance-based assessments such as maximum walking speed or maximum walking distance. [ABSTRACT FROM AUTHOR]

Background: Muscle strength and dexterity impairments are common among patients with multiple sclerosis (MS) producing limitations in activities of daily living related to the upper limb (UL). This study aimed to evaluate the effectiveness of serious games specifically developed for the MYO Armband® capture sensor in improving forearm and wrist mobility, UL muscle strength, dexterity, fatigue, functionality, quality of life, satisfaction, adverse effects and compliance. Methods: A double-blinded (allocation concealment was performed by a blinded investigator and by blinding for assessors) randomised controlled trial was conducted. The sample was randomised into two groups: an experimental group that received treatment based on UL serious games designed by the research team and controlled by the MYO Armband® gesture capture sensor, along with conventional rehabilitation and a control group that received the same conventional rehabilitation for the UL. Both groups received two 60-min sessions per week over an eight-week period. Wrist range of motion (goniometry), grip muscle strength (Jamar® dynamometer), coordination and gross UL dexterity (Box and Block Test), fatigue (Fatigue Severity Scale), functionality (ABILHAND), quality of life (Multiple Sclerosis Impact Scale-29), adverse effects (Simulator Sickness Questionnaire, SSQ), perceived workload (NASA-Task load index), satisfaction (Client Satisfaction Questionnaire-8 (CSQ-8), Satisfaction with Technology Scale, System Usability Scale (SUS) and QUEST 2.0) and compliance (attendance) were assessed in both groups pre-treatment, post-treatment and during a follow-up period of 2 weeks without receiving any treatment. Results: Significant differences were observed in the experimental group compared to the control group in the assessment of forearm supination (p =.004) and grip strength (p =.004). Adverse effects were minimal (SSQ: 7/100 points) and perceived workload was low (NASA-Task Load Index: 25/100 points) in the experimental group. The MYO Armband® technology proved to be useful for the participants (SUS: 80.66/100) and the satisfaction scales received high scores (QUEST 2.0: 59.4/70 points; Satisfaction with Technology: 84.36/100 points). There were significant differences between the groups in terms of attendance percentage (p =.029). Conclusions: An experimental protocol using MYO Armband®-based serious games designed for UL rehabilitation showed improvements in active wrist range of motion and handgrip strength in patients with MS, with high satisfaction, minimal adverse effects and workload and excellent compliance. Trial registration number: This randomised controlled trial has been registered at ClinicalTrials.gov Identifier: NCT04171908. [ABSTRACT FROM AUTHOR]

Background: Recent data suggest that myelin may be altered by physiological events occurring outside of the central nervous system, which may cause changes to cognition and behavior. Similarly, peripheral infection by non-neurotropic viruses is also known to evoke changes to cognition and behavior. Methods: Mice were inoculated with saline or influenza A virus. Bulk RNA-seq, lipidomics, RT-qPCR, flow cytometry, immunostaining, and western blots were used to determine the effect of infection on OL viability, protein expression and changes to the lipidome. To determine if microglia mediated infection-induced changes to OL homeostasis, mice were treated with GW2580, an inhibitor of microglia activation. Additionally, conditioned medium experiments using primary glial cell cultures were also used to test whether secreted factors from microglia could suppress OL gene expression. Results: Transcriptomic and RT-qPCR analyses revealed temporal downregulation of OL-specific transcripts with concurrent upregulation of markers characteristic of cellular stress. OLs isolated from infected mice had reduced cellular expression of myelin proteins compared with those from saline-inoculated controls. In contrast, the expression of these proteins within myelin was not different between groups. Similarly, histological and immunoblotting analysis performed on various brain regions indicated that infection did not alter OL viability, but increased expression of a cellular stress marker. Shot-gun lipidomic analysis revealed that infection altered the lipid profile within the prefrontal cortex as well as in purified brain myelin and that these changes persisted after recovery from infection. Treatment with GW2580 during infection suppressed the expression of genes associated with glial activation and partially restored OL-specific transcripts to baseline levels. Finally, conditioned medium from activated microglia reduced OL-gene expression in primary OLs without altering their viability. Conclusions: These findings show that peripheral respiratory viral infection with IAV is capable of altering OL homeostasis and indicate that microglia activation is likely involved in the process. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease that leads to irreversible damage to the brain and spinal cord. The goal of so-called "immune reconstitution therapies" (IRTs) is to achieve long-term disease remission by eliminating a pathogenic immune repertoire through intense short-term immune cell depletion. B cells are major targets for effective immunotherapy in MS. Objectives: The aim of this study was to analyze the gene expression pattern of B cells before and during IRT (i.e., before B-cell depletion and after B-cell repopulation) to better understand the therapeutic effects and to identify biomarker candidates of the clinical response to therapy. Methods: B cells were obtained from blood samples of patients with relapsing–remitting MS (n = 50), patients with primary progressive MS (n = 13) as well as healthy controls (n = 28). The patients with relapsing MS received either monthly infusions of natalizumab (n = 29) or a pulsed IRT with alemtuzumab (n = 15) or cladribine (n = 6). B-cell subpopulation frequencies were determined by flow cytometry, and transcriptome profiling was performed using Clariom D arrays. Differentially expressed genes (DEGs) between the patient groups and controls were examined with regard to their functions and interactions. We also tested for differences in gene expression between patients with and without relapse following alemtuzumab administration. Results: Patients treated with alemtuzumab or cladribine showed on average a > 20% lower proportion of memory B cells as compared to before IRT. This was paralleled by profound transcriptome shifts, with > 6000 significant DEGs after adjustment for multiple comparisons. The top DEGs were found to regulate apoptosis, cell adhesion and RNA processing, and the most highly connected nodes in the network of encoded proteins were ESR2, PHB and RC3H1. Higher mRNA levels of BCL2, IL13RA1 and SLC38A11 were seen in patients with relapse despite IRT, though these differences did not pass the false discovery rate correction. Conclusions: We show that B cells circulating in the blood of patients with MS undergoing IRT present a distinct gene expression signature, and we delineated the associated biological processes and gene interactions. Moreover, we identified genes whose expression may be an indicator of relapse risk, but further studies are needed to verify their potential value as biomarkers. [ABSTRACT FROM AUTHOR]

Background: As a modulator of the sphingosine 1-phosphate receptor, siponimod is administered as a therapeutic intervention for multiple sclerosis. A previous phase 3 study first reported siponimod-associated macular edema. Since that report, there were only few relevant reports in clinical settings. Here, we report a case of secondary progressive multiple sclerosis developed macular edema after siponimod treatment. We also review the progress of sphingosine 1-phosphate receptor modulators, elaborate on accepted mechanisms in treating multiple sclerosis, and discuss the causation of siponimod-associated macular edema. Case presentation: A 38-year-old Chinese female patient with secondary progressive multiple sclerosis, who had recurrent numbness of the limbs and right leg fatigue, developed mild macular edema following 4 months of siponimod treatment. The macular edema resolved after discontinuing the medication, and did not recur after resuming siponimod. Conclusion: Although siponimod-associated macular edema may be rare, mild, transitory, and manageable, it cannot be ignored and requires ongoing vigilance. [ABSTRACT FROM AUTHOR]

Introduction: Balance disorders are common in people with Multiple Sclerosis (PwMS) and, together with other impairments and disabilities, often prevent PwMS from performing their daily living activities. Besides clinical scales and performance tests, robotic platforms can provide more sensitive, specific, and objective monitoring. Validated technologies have been adopted as gold standard, but innovative robotic solutions would represent an opportunity to detect balance impairment in PwMS. Aim: Study's aim was to compare postural assessment of 46 PwMS with a relapsing–remitting form during static tasks performed with the novel robotic platform hunova® and the gold standard EquiTest®, Methods: Pearson's r was run on Center of Pressure (COP)-related parameters and global static balance measures computed from hunova® and EquiTest® in eyes-open (EO) and eyes-closed (EC) conditions. In addition, agreeableness level toward the use of both devices was tested through numeric rating scale. Results: Considering COP-related parameters, correlations were significant for all measures (p <.001). Interestingly, in EO, a strong correlation was shown for sway area (r =.770), while Medio-Lateral (ML) and Anterior–Posterior (AP) oscillation range, path length, ML and AP speed, ML and AP root mean square distance had a relatively strong association (.454 ≤ r ≤.576). In EC, except for ML oscillation range showing a relatively strong correlation (r =.532), other parameters were strongly associated (.603 ≤ r ≤.782). Correlations between global balance indexes of hunova® and EquiTest® revealed a relatively strong association between the Somatosensory Score in EquiTest® and the Somatosensory Index in hunova® (r = −.488). While in EO Static Balance Index from hunova® was highly correlated with Equilibrium score of EquiTest® (r =.416), Static Balance Index had a relatively strong association with both the Equilibrium (r =.482) and Strategy Score (r =.583) of EquiTest® in EC. Results from agreeableness rating scale revealed that hunova® was highly appreciated compared to EquiTest® (p =.044). Conclusions: hunova® represents an innovative adjunct to standard robotic balance evaluation for PwMS. This confirms that combining traditional and robotic assessments can more accurately detect balance impairments in MS. [ABSTRACT FROM AUTHOR]

Background: Primary progressive multiple sclerosis (PPMS) is characterised by gradual worsening of disability from symptom onset. Knowledge about the natural course of PPMS remains limited. Methods: PPMS patients from the German NeuroTransData (NTD) MS registry with data from 56 outpatient practices were employed for retrospective cross-sectional and longitudinal analyses. The cross-sectional analysis included a contemporary PPMS cohort with a documented visit within the last 2 years before index date (1 Jan 2021). The longitudinal analysis included a disease modifying therapy (DMT)-naïve population and focused on the evolution of expanded disability status scale (EDSS) from the first available assessment at or after diagnosis within the NTD registry to index date. Outcome measures were estimated median time from first EDSS assessment to first 24-week confirmed EDSS ≥ 4 and ≥ 7. Besides EDSS change, the proportion of patients on disability pension were described over time. Results: The cross-sectional analysis included 481 PPMS patients (59.9% female, mean [standard deviation, SD] age 60.5 [11.5] years, mean [SD] EDSS 4.9 [2.1]). Estimated median time from first EDSS assessment after diagnosis to reach 24-week confirmed EDSS ≥ 4 for DMT-naïve patients was 6.9 years. Median time to EDSS ≥ 7 was 9.7 years for 25% of the population. Over a decade mean (SD) EDSS scores increased from 4.6 (2.1) to 5.7 (2.0); the proportion of patients on disability pension increased from 18.9% to 33.3%. Conclusions: This study provides first insights into the German NTD real-world cohort of PPMS patients. Findings confirm the steadily deteriorating course of PPMS accompanied by increasingly limited quality of life. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) leads to demyelination and neurodegeneration with autoimmune responses in central nervous system. Patients begin with a relapsing–remitting (RR) course, and more than 80% of them may advance to secondary progressive MS (SPMS), which is characteristic for the gradual decline of neurological functions without demonstrated treating method to prevent. This study aims to investigate the contribution of peripheral CD8 + T cells during the conversion from RRMS to SPMS, as well as reveal potential diagnostic signature in distinguishing SPMS. Methods: Single-cell RNA sequencing was employed to reveal the heterogeneity of CD8 + T cells between SPMS and RRMS. In addition, flow cytometry was used to further characterized CD8 + T cell dynamic changes in patients. T cell receptor sequencing was performed to detect the clonal expansion of MS. Using Tbx21 siRNA, T-bet was confirmed to manipulate GzmB expression. The correlation between GzmB + CD8 + T cell subsets and clinical characteristics of MS and their potential diagnostic value for SPMS were evaluated by generalized linear regression models and receiver operating characteristic (ROC) curve respectively. Results: Other than diminished naïve CD8 + T cell, elevating of activated CD8 + T cell subsets were observed in SPMS patients. Meanwhile, this aberrant amplified peripheral CD8 + T cells not only exhibited terminal differentiated effector (EMRA) phenotype with GzmB expression, but also possessed distinct trajectory from clonal expansion. In addition, T-bet acted as a key transcriptional factor that elicited GzmB expression in CD8 + TEMRA cells of patients with SPMS. Finally, the expression of GzmB in CD8 + T cells was positively correlated with disability and progression of MS, and could effectively distinguish SPMS from RRMS with a high accuracy. Conclusions: Our study mapped peripheral immune cells of RRMS and SPMS patients and provided an evidence for the involvement of GzmB + CD8 + TEMRA cells in the progression of MS, which could be used as a diagnostic biomarker for distinguishing SPMS from RRMS. [ABSTRACT FROM AUTHOR]

Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive lung disease caused by variants in the SLC34A2 gene encoding the sodium-dependent phosphate transport protein 2B, NaPi-2b. PAM is characterized by deposition of calcium phosphate crystals in the alveoli. Onset and clinical course vary considerably; some patients remain asymptomatic while others develop severe respiratory failure with a significant symptom burden and compromised survival. It is likely that PAM is under-reported due to lack of recognition, misdiagnosis, and mild clinical presentation. Most patients are genetically uncharacterized as the diagnostic confirmation of PAM has traditionally not included a genetic analysis. Genetic testing may in the future be the preferred tool for diagnostics instead of invasive methods. This systematic review aims to provide an overview of the growing knowledge of PAM genetics. Rare variants in SLC34A2 are found in almost all genetically tested patients. So far, 34 allelic variants have been identified in at least 68 patients. A majority of these are present in the homozygous state; however, a few are found in the compound heterozygous form. Most of the allelic variants involve only a single nucleotide. Half of the variants are either nonsense or frameshifts, resulting in premature termination of the protein or decay of the mRNA. There is currently no cure for PAM, and the only effective treatment is lung transplantation. Management is mainly symptomatic, but an improved understanding of the underlying pathophysiology will hopefully result in development of targeted treatment options. More standardized data on PAM patients, including a genetic diagnosis covering larger international populations, would support the design and implementation of clinical studies to the benefit of patients. Further genetic characterization and understanding of how the molecular changes influence disease phenotype will hopefully allow earlier diagnosis and treatment of the disease in the future. [ABSTRACT FROM AUTHOR]

Background: Teriflunomide, the active metabolite of leflunomide, is a disease-modifying therapy drug used for the treatment of multiple sclerosis (MS), yet the complications associated with this drug remain not fully understood. Here we present the rare case of a 28-year-old female MS patient who developed subacute cutaneous lupus erythematosus (SCLE) following teriflunomide treatment. Though SCLE has been reported to be associated with leflunomide, the current report represents the first documented evidence demonstrating SCLE as a potential teriflunomide treatment-related complication. Additionally, a literature review on the leflunomide-induced SCLE was conducted to emphasize the association of SCLE with teriflunomide, specifically amongst the female demographic with a preexisting autoimmune diathesis. Case presentation: A 28-year-old female first presented with MS symptoms in the left upper limb along with blurred vision in the left eye. Medical and family histories were unremarkable. The patient exhibited positive serum biomarkers including ANA, Ro/SSA, La/SSB, and Ro-52 antibodies. Relapsing–remitting MS was diagnosed according to the 2017 McDonald's diagnostic criteria, and remission was achieved upon intravenous administration of methylprednisolone followed by teriflunomide sequential therapy. Three months post-teriflunomide treatment, the patient developed multiple facial cutaneous lesions. SCLE was subsequently diagnosed and was attributed to treatment-related complication. Interventions include oral administration of hydroxychloroquine and tofacitinib citrate effectively resolved cutaneous lesions. Discontinuation of hydroxychloroquine and tofacitinib citrate treatment led to recurring SCLE symptoms under continuous teriflunomide treatment. Full remission of facial annular plaques was achieved after re-treatment with hydroxychloroquine and tofacitinib citrate. The patient's clinical condition remained stable in long-term outpatient follow-ups. Conclusions: As teriflunomide has become a standard disease-modifying therapy for MS, the current case report highlights the importance of monitoring treatment-related complications, specifically in relation to SCLE symptoms. [ABSTRACT FROM AUTHOR]

Background and objectives: Recent literature on multiple sclerosis (MS) demonstrates the growing implementation of optical coherence tomography–angiography (OCT-A) to discover potential qualitative and quantitative changes in the retina and optic nerve. In this review, we analyze OCT-A studies in patients with MS and examine its utility as a surrogate or precursor to changes in central nervous system tissue. Methods: PubMed and EMBASE were systematically searched to identify articles that applied OCT-A to evaluate the retinal microvasculature measurements in patients with MS. Quantitative data synthesis was performed on all measurements which were evaluated in at least two unique studies with the same OCT-A devices, software, and study population compared to controls. A fixed-effects or random-effects model was applied for the meta-analysis based on the heterogeneity level. Results: The study selection process yielded the inclusion of 18 studies with a total of 1552 evaluated eyes in 673 MS-associated optic neuritis (MSON) eyes, 741 MS without optic neuritis (MSNON eyes), and 138 eyes without specification for the presence of optic neuritis (ON) in addition to 1107 healthy control (HC) eyes. Results indicated that MS cases had significantly decreased whole image superficial capillary plexus (SCP) vessel density when compared to healthy control subjects in the analyses conducted on Optovue and Topcon studies (both P < 0.0001). Likewise, the whole image vessel densities of deep capillary plexus (DCP) and radial peripapillary capillary (RPC) were significantly lower in MS cases compared to HC (all P < 0.05). Regarding optic disc area quadrants, MSON eyes had significantly decreased mean RPC vessel density compared to MSNON eyes in all quadrants except for the inferior (all P < 0.05). Results of the analysis of studies that used prototype Axsun machine revealed that MSON and MSNON eyes both had significantly lower ONH flow index compared to HC (both P < 0.0001). Conclusions: This systematic review and meta-analysis of the studies reporting OCT-A measurements of people with MS confirmed the tendency of MS eyes to exhibit reduced vessel density in the macular and optic disc areas, mainly in SCP, DCP, and RPC vessel densities. [ABSTRACT FROM AUTHOR]

Background: Balance training interventions with a gradual progression of difficulty and highly challenging tasks designed specifically for people with multiple sclerosis (MS) are rare. The objective was to adapt a balance training intervention originally developed for Parkinson's disease through a co-design process and then conduct a pilot trial in MS to evaluate the feasibility of a large, full-scale study. Methods: Twelve people with MS with mild to moderate overall MS-disability were included in this single-group feasibility trial. Participants received one-hour training sessions twice or three times weekly for 10 weeks. The assessment included tests of physical and cognitive functioning and patient-reported quality of life-related outcomes. Data on feasibility aspects were collected at baseline and follow-up assessments and three times during the intervention period to inform the recruitment process, as well as to monitor retention and inclusion rates, study procedures, intervention delivery, and dynamic changes in the selected potential outcome measures. Progression criteria were used to determine whether to proceed to a full-scale trial. Descriptive statistics were used to present the data. Results: Out of six progression criteria, only retention and attendance at training sessions were not met. Reasons reported for not completing the intervention period mainly depended on external circumstances beyond the control of the study. In contrast, study procedures, intervention delivery, and intervention content (progression, adjustment, and control of challenge level of exercises) were considered feasible for a future, full-scale trial. The Mini-BESTest, which was used for the assessment of balance control, was considered suitable as the primary outcome in a full-scale trial with no ceiling or floor effects. Further, the Mini-BESTest showed a positive trend in outcome response with a median difference of 3.5 points between baseline and follow-up assessments. The power calculation performed suggests a feasible number of participants for recruitment. Conclusions: Overall trial aspects and intervention delivery were deemed feasible for a full-scale trial, but adjustments are needed to increase retention and attendance. [ABSTRACT FROM AUTHOR]

Background: This study was conducted with the aim of identifying the burden of psychosocial factors on the worsening symptoms of multiple sclerosis. Methods: This as conducted with a qualitative approach and conventional content analysis among patients with Multiple sclerosis in Mashhad. Data were collected through semi-structured interviews with patients with Multiple sclerosis. Twenty-one patients with Multiple sclerosis were selected through purposive sampling and snowball sampling. The data were analyzed using Graneheim and Lundman method. Guba and Lincoln's criteria were used for evaluating research transferability. The data collection and management was performed by using the MAXQADA 10 software. Results: In explanation of the psychosocial factors of patients with Multiple sclerosis, one category (psychosocial tensions) and three subcategories of stress (physical symptoms, emotional symptoms, and behavioral symptoms), agitation (family disorder, treatment-related concerns, and social relationship concerns), and stigmatization (social stigma and internalized stigma) were extracted. Conclusion: The results of this study show that patients with Multiple sclerosis are faced with concerns such as stress, agitation, and fear of stigma, and need support and understanding from the family and community to overcome these concerns. Society must base its health policies on addressing the challenges faced by patients. Accordingly, the authors argue that health policies, and consequently, healthcare systems, need to address patients' ongoing challenges as a priority in caring for patients with Multiple sclerosis. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) has two pathophysiological processes, one inflammatory and the other degenerative. We investigated the relationship between active lesions on magnetic resonance imaging showing the inflammatory phase in MS patients and serum parameters that can be used as inflammatory biomarkers. Thus, we aim to detect the inflammatory period in clinical and radiological follow-up and to reveal the period in which disease-modifying treatments are effective with serum parameters. Methods: One hundred eighty-six MS patients presented to our hospital between January 2016 and November 2021 and 94 age- and sex-matched healthy volunteers were recruited for our study. While 99 patients had active lesions on magnetic resonance imaging, 87 patients did not have any active lesions. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) were determined. The SII (systemic immune inflammatory index) value was calculated according to the platelet X neutrophil/lymphocyte ratio formula. Results: NLR, MLR, PLR and SII values were found to be statistically significantly higher in MS patients than in the control group. The NLR, MLR, PLR and SII were higher in the active group with gadolonium than in the group without active lesions. In addition, the cutoff values that we can use to determine the presence of active lesions were 1.53, 0.18, 117.15, and 434.45 for NLR, MLR PLR and SII, respectively. Conclusions: We found that all parameters correlated with radiological activity. In addition, we showed that we can detect the inflammatory period with high sensitivity and specificity with the cutoff value used for SII and PLR. Among these easily accessible and inexpensive evaluations, we concluded that SII, including the values in the PLR formula, can come to the fore. [ABSTRACT FROM AUTHOR]

Background: Impaired cerebrospinal fluid (CSF) homeostasis is central to the pathogenesis of idiopathic intracranial hypertension (IIH), although the precise mechanisms involved are still not completely understood. The aim of the current study was to assess the CSF/serum ratio of neurofilament light chain levels (QNfL) as a potential indicator of functional CSF outflow obstruction in IIH patients. Methods: NfL levels were measured by single molecule array in CSF and serum samples of 87 IIH patients and in three control groups, consisting of 52 multiple sclerosis (MS) patients with an acute relapse, 21 patients with an axonal polyneuropathy (PNP), and 41 neurologically healthy controls (HC). QNfL was calculated as the ratio of CSF and serum NfL levels. Similarly, we also assessed the CSF/serum ratio of glial fibrillary acidic protein (QGFAP) levels to validate the QNfL data. Routine CSF parameters including the CSF/serum albumin ratio (QAlb) were determined in all groups. Lumbar puncture opening pressure of IIH patients was measured by manometry. Results: CSF-NfL levels (r = 0.29, p = 0.008) and QNfL (0.40, p = 0.0009), but not serum NfL (S-NfL) levels, were associated with lumbar puncture opening pressure in IIH patients. CSF-NfL levels were increased in IIH patients, MS patients, and PNP patients, whereas sNfL levels were normal in IIH, but elevated in MS and PNP. Remarkably, QNfL (p < 0.0001) as well as QGFAP (p < 0.01) were only increased in IIH patients. QNfL was positively correlated with CSF-NfL levels (r = 0.51, p = 0.0012) and negatively correlated with S-NfL levels (r = − 0.51, p = 0.0012) in HC, while it was only positively associated with CSF-NfL levels in IIH patients (r = 0.71, p < 0.0001). An increase in blood-CSF barrier permeability assessed by QAlb did not lead to a decrease in QNfL in any cohort. Conclusions: The observed elevation of QNfL in IIH patients, which was associated with lumbar puncture opening pressure, indicates a reduced NfL transition from the CSF to serum compartment. This supports the hypothesis of a pressure-dependent CSF outflow obstruction to be critically involved in IIH pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis is a chronic immune-mediated disease of the brain and spinal cord resulting in physical and cognitive impairment in young adults. It is hypothesized that a disrupted bacterial and viral gut microbiota is a part of the pathogenesis mediating disease impact through an altered gut microbiota-brain axis. The aim of this study is to explore the characteristics of gut microbiota in multiple sclerosis and to associate it with disease variables, as the etiology of the disease remains only partially known. Methods: Here, in a case-control setting involving 148 Danish cases with multiple sclerosis and 148 matched healthy control subjects, we performed shotgun sequencing of fecal microbial DNA and associated bacterial and viral microbiota findings with plasma cytokines, blood cell gene expression profiles, and disease activity. Results: We found 61 bacterial species that were differentially abundant when comparing all multiple sclerosis cases with healthy controls, among which 31 species were enriched in cases. A cluster of inflammation markers composed of blood leukocytes, CRP, and blood cell gene expression of IL17A and IL6 was positively associated with a cluster of multiple sclerosis-related species. Bacterial species that were more abundant in cases with disease-active treatment-naïve multiple sclerosis were positively linked to a group of plasma cytokines including IL-22, IL-17A, IFN-β, IL-33, and TNF-α. The bacterial species richness of treatment-naïve multiple sclerosis cases was associated with number of relapses over a follow-up period of 2 years. However, in non-disease-active cases, we identified two bacterial species, Faecalibacterium prausnitzii and Gordonibacter urolithinfaciens, whose absolute abundance was enriched. These bacteria are known to produce anti-inflammatory metabolites including butyrate and urolithin. In addition, cases with multiple sclerosis had a higher viral species diversity and a higher abundance of Caudovirales bacteriophages. Conclusions: Considerable aberrations are present in the gut microbiota of patients with multiple sclerosis that are directly associated with blood biomarkers of inflammation, and in treatment-naïve cases bacterial richness is positively associated with disease activity. Yet, the finding of two symbiotic bacterial species in non-disease-active cases that produce favorable immune-modulating compounds provides a rationale for testing these bacteria as adjunct therapeutics in future clinical trials. [ABSTRACT FROM AUTHOR]