Prognosis Of Multiple Sclerosis Research Articles

Early Disease-Modifying Treatments for Presymptomatic Multiple Sclerosis.

Radiologically isolated syndrome (RIS) is the earliest stage in the disease continuum of multiple sclerosis (MS). RIS is discovered incidentally in individuals who are asymptomatic but have typical lesions in the brain and/or spinal cord suggestive of demyelination. The2009 and revised 2023 RIS criteria weredeveloped for diagnosis.Presymptomatic individuals who fulfill the 2009 RIS criteria by having 3-4 of 4 dissemination in spaceMcDonald 2005 MS criteria are still diagnosed with RIS using therevised 2023 RIS criteria.Inpresymptomatic individuals who do not fulfill the 2009 RIS criteria, the revised 2023 RIS criteria target to secure an accurate and timely diagnosis: In addition to (a) having one lesion in two of four locations (periventricular, juxtacortical/cortical, infratentorial, spinal cord), (b) two of three features (spinal cord lesion, cerebrospinal fluid (CSF)-restricted oligoclonal bands, and new T2 or gadolinium-enhancing lesion) should be fulfilled. Among laboratory biomarkers,CSF kappa-free light chain can also increase diagnostic accuracy. Once the diagnosis is confirmed, the established risk factors, including demographics, imaging, and laboratory biomarkers, should be evaluated for symptomatic MS transition and prognosis. Younger age, male sex, increased neurofilament-light chain, CSF abnormality, and the presence of infratentorial, spinal cord, or gadolinium-enhancing lesions on imaging are the main risk factors for transition to symptomatic MS. Two randomized clinical trials showed significant efficacy of disease-modifying treatments in delaying or preventing the development of the first clinical event in RIS. However, because some individuals remain as RIS, it is crucial to identify the individuals with a higher number of risk factors to optimize disease outcomes by early intervention while minimizing adverse events. Discussing each RIS case with an expert MS team is recommended because there is still a lack of clinical guidelines to improve care, counseling, and surveillance.

A 2-stage model of heterogenous treatment effects for brain atrophy in multiple sclerosis utilizing the MS PATHS research network

BackgroundTwo-stage models of heterogenous treatment effects (HTE) may advance personalized medicine in multiple sclerosis (MS). Brain atrophy is a relatively objective outcome measure that has strong relationships to MS prognosis and treatment effects and is enabled by standardized MRI. ObjectivesTo predict brain atrophy outcomes for patients initiating disease-modifying therapies (DMT) with different efficacies, considering the patients’ baseline brain atrophy risk measured via brain parenchymal fraction (BPF). MethodsAnalyses included patients enrolled in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network who started DMT and had complete baseline data and ≥ 6-month brain MRI follow-up. All brain MRIs were acquired using standardized acquisition sequences on Siemens 3T scanners. BPF change risk was derived by linear mixed effects models using baseline covariates. Model performance was assessed by predicted versus actual BPF change R2. Propensity score (PS) weighting was used to balance covariates between groups defined by DMT efficacy (high: natalizumab, alemtuzumab, ocrelizumab, and rituximab; moderate: dimethyl fumarate, fingolimod, and cladribine; low: teriflunomide, interferons, and glatiramer acetate). HTE models predicting 1 year change in BPF were built using a weighted linear mixed effects model with low-efficacy DMT as the reference. ResultsAnalyses included 581 high-, 183 moderate-, and 106 low-efficacy DMT-treated patients. The mean and median number of brain MRI observations per treatment period were 2.9 and 3.0, respectively. Risk model performance R2=0.55. After PS weighting, covariate standardized mean differences were <10 %, indicating excellent balance across measured variables. Changes in BPF between baseline and follow-up were found to be statistically significant (p < 0.001), suggesting a pathological change. Patients with low brain atrophy risk had a similar outcome regardless of DMT selection. In patients with high brain atrophy risk, high- and moderate-efficacy DMTs performed similarly, while a 2-fold worse BPF change was predicted for patients selecting low-efficacy DMTs (p < 0.001). Similar results were observed in a sensitivity analysis adjusting for pseudoatrophy effects in a sub-population of patients treated with natalizumab. ConclusionsThe relative benefit of selecting higher efficacy treatments may vary depending on patients’ baseline brain atrophy risk. Poor outcomes are predicted in individuals with high baseline risk who are treated with low-efficacy DMTs.

Emerging MRI and biofluid biomarkers in the diagnosis and prognosis of multiple sclerosis

Emerging MRI and biofluid biomarkers in the diagnosis and prognosis of multiple sclerosis

Serum NfL and GFAP are weak predictors of long-term multiple sclerosis prognosis: A 6-year follow-up

BackgroundSerum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising biomarkers that might be associated with clinical and radiological markers of multiple sclerosis (MS) severity. However, it is not known whether they can accurately identify patients at risk of disability progression in the medium and long term. ObjectivesWe wanted to determine the association between sNfL and sGFAP, Expanded Disability Status Scale score changes, and conversion to secondary progressive MS (SPMS) in a cohort of 133 patients with relapsing remitting MS. MethodsBlood samples were collected at inclusion to measure SNfL and sGFAP by single molecule array and their prognostic value was assessed using a linear mixed model. ResultsIn this cohort, 37 patients (27.8 % of 133) experienced disability progression and 12 patients (9.0 %) converted to SPMS during the follow-up (mean follow-up duration: 6.4 years). Only sNfL (p = 0.03) was associated with conversion to SPMS, and neither SNfL nor sGFAP was associated with disability progression. ConclusionSerum NfL and GFAP do not seem to accurately predict MS outcome in the long term. More studies are needed to determine how serum biomarkers, associated with other clinical and MRI biomarkers, might be used to improve MS prognostication.

Analysis of potential microRNA biomarkers for multiple sclerosis

Multiple sclerosis (MS) is a chronic demyelinating autoimmune neurodegenerative disorder for which no specific blood biomarker is available. MicroRNAs (miRNAs) have been investigated for their diagnostic potential in MS. However, MS-associated miRNAs are rarely replicated in different MS populations, thus impeding their use in clinical testing. Here, we evaluated the fold expression of seven reported MS miRNAs associated with MS incidence and clinical characteristics in 76 MS patients and 75 healthy control plasma samples. We found miR-23a-3p to be upregulated in relapsing-remitting MS (RRMS), while miR-326 was downregulated. MiR-150-5p and -320a-3p were significantly downregulated in secondary progressive MS (SPMS) patients compared to RRMS. High disability was associated with low miR-320a-3p, whereas low BDNF levels were associated with upregulation of miR-150-5p and downregulation of miR-326 expression in the total cohort. MiR-23a-3p and miR-326 showed significant diagnostic sensitivity, specificity, and accuracy for RRMS diagnosis. In addition, miR-150-5p and miR-320a-3p had comparable significant diagnostic test performance metrics distinguishing SPMS from RRMS. Therefore, there is potential for including miR-23a-3p and miR-326 in an RRMS diagnostic miRNA panel. Moreover, we have shown that miR-150-5p and miR-320a-3p could be novel RRMS conversion to SPMS biomarkers. The use of these miRNAs in MS diagnosis and prognosis warrants further investigation.

CD138 as a Specific CSF Biomarker of Multiple Sclerosis.

The aim of this study was to identify novel biomarkers for multiple sclerosis (MS) diagnosis and prognosis, addressing the critical need for specific and prognostically valuable markers in the field. We conducted an extensive proteomic investigation, combining analysis of (1) CSF proteome from symptomatic controls, fast and slow converters after clinically isolated syndromes, and patients with relapsing-remitting MS (n = 10 per group) using label-free quantitative proteomics and (2) oligodendrocyte secretome changes under proinflammatory or proapoptotic conditions using stable isotope labeling by amino acids in cell culture. Proteins exhibiting differential abundance in both proteomic analyses were combined with other putative MS biomarkers, yielding a comprehensive list of 87 proteins that underwent quantification through parallel reaction monitoring (PRM) in a novel cohort, comprising symptomatic controls, inflammatory neurologic disease controls, and patients with MS at various disease stages (n = 10 per group). The 11 proteins that passed this qualification step were subjected to a new PRM assay within an expanded cohort comprising 158 patients with either MS at different disease stages or other inflammatory or noninflammatory neurologic disease controls. This study unveiled a promising biomarker signature for MS, including previously established candidates, such as chitinase 3-like protein 1, chitinase 3-like protein 2, chitotriosidase, immunoglobulin kappa chain region C, neutrophil gelatinase-associated lipocalin, and CD27. In addition, we identified novel markers, namely cat eye syndrome critical region protein 1 (adenosine deaminase 2, a therapeutic target in multiple sclerosis) and syndecan-1, a proteoglycan, also known as plasma cell surface marker CD138 and acting as chitinase 3-like protein 1 receptor implicated in inflammation and cancer signaling. CD138 exhibited good diagnostic accuracy in distinguishing MS from inflammatory neurologic disorders (area under the curve [AUC] = 0.85, CI 0.75-0.95). CD138 immunostaining was also observed in the brains of patients with MS and cultured oligodendrocyte precursor cells but was absent in astrocytes. These findings identify CD138 as a specific CSF biomarker for MS and suggest the selective activation of the chitinase 3-like protein 1/CD138 pathway within the oligodendrocyte lineage in MS. They offer promising prospects for improving MS diagnosis and prognosis by providing much-needed specificity and clinical utility. This study provides Class II evidence that CD138 distinguishes multiple sclerosis from other inflammatory neurologic disorders with an AUC of 0.85 (95% CI 0.75-0.95).

Predicting clinical progression and cognitive decline in patients with relapsing-remitting multiple sclerosis: a 6-year follow-up study.

Cognitive impairment occurs from the earliest stages of multiple sclerosis (MS) and progresses over time. The introduction of disease modifying therapies (DMTs) has changed the prognosis for MS patients, offering a potential opportunity for improvement in the cognitive arena as well. 41 patients with relapsing-remitting multiple sclerosis (MS) were recruited to the study. Thirty patients were available for final follow-up and were included in the analysis. Baseline (BL) brain MRI including volumetry and neuropsychological tests were performed. Blood samples were collected at BL and follow-up (FU) and were tested for: vascular endothelial growth factor (VEGF), soluble vascular cell adhesion molecule-1 (sVCAM1), soluble platelet-endothelial CAM-1 (sPECAM1), and soluble intercellular CAM-1 (sICAM-1). Patients were invited for a final neuropsychological follow-up after a median of 6 years. Disease activity (relapses, EDSS increase, new/active brain lesions on MRI) was analysed between BL and FU. The study group deteriorated in the Rey-Osterrieth Complex Figure (ROCF) test (p = 0.001), but improved significantly in three other tests, i.e. semantic fluency test (p = 0.013), California Verbal Learning Test (CVLT, p = 0.016), and Word Comprehension Test (WCT, p < 0.001). EDSS increase correlated negatively with semantic fluency and WCT scores (r = -0.579, p = 0.001 and r = -0.391, p = 0.033, respectively). Improvements in semantic fluency test and WCT correlated positively with baseline deep grey matter, grey matter, and cortical volumes (p < 0.05, r > 0). Higher EDSS on FU correlated significantly negatively with baseline left and right pallidum, right caudate, right putamen, right accumbens, and cortical volume (p < 0.05, r < 0). No significant relationship was found between the number of relapses and EDSS on FU or neuropsychological deteriorations. Improvements in WCT and CVLT correlated positively with baseline sPECAM1 and sVCAM1 results, respectively (r > 0, p < 0.05). Deterioration in ROCF test correlated significantly with higher levels of baseline VEGF and sVCAM1 (p < 0.05). Brain volume is an important predictor of future EDSS and cognitive functions outcome. MS patients have a potential for improving in neuropsychological tests over time. It remains to be established whether this is related to successful disease modification with immunotherapy. Baseline volumetric measures are stronger predictors of cognitive performance than relapse activity, which yet again highlights the importance of atrophy in MS prognosis.

Gas6/TAM system as potential biomarker for multiple sclerosis prognosis.

The protein growth arrest-specific 6 (Gas6) and its tyrosine kinase receptors Tyro-3, Axl, and Mer (TAM) are ubiquitous proteins involved in regulating inflammation and apoptotic body clearance. Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system leading to progressive and irreversible disability if not diagnosed and treated promptly. Gas6 and TAM receptors have been associated with neuronal remyelination and stimulation of oligodendrocyte survival. However, few data are available regarding clinical correlation in MS patients. We aimed to evaluate soluble levels of these molecules in the cerebrospinal fluid (CSF) and serum at MS diagnosis and correlate them with short-term disease severity. In a prospective cohort study, we enrolled 64 patients with a diagnosis of clinical isolated syndrome (CIS), radiological isolated syndrome (RIS) and relapsing-remitting (RR) MS according to the McDonald 2017 Criteria. Before any treatment initiation, we sampled the serum and CSF, and collected clinical data: disease course, presence of gadolinium-enhancing lesions, and expanded disability status score (EDSS). At the last clinical follow-up, we assessed EDSS and calculated MS severity score (MSSS) and age-related MS severity (ARMSS). Gas6 and TAM receptors were determined using an ELISA kit (R&D Systems) and compared to neurofilament (NFLs) levels evaluated with SimplePlex™ fluorescence-based immunoassay. At diagnosis, serum sAxl was higher in patients receiving none or low-efficacy disease-modifying treatments (DMTs) versus patients with high-efficacy DMTs (p = 0.04). Higher CSF Gas6 and serum sAXL were associated with an EDSS<3 at diagnosis (p = 0.04; p = 0.037). Serum Gas6 correlates to a lower MSSS (r2 = -0.32, p = 0.01). Serum and CSF NFLs were confirmed as disability biomarkers in our cohort according to EDSS (p = 0.005; p = 0.002) and MSSS (r2= 0.27, p = 0.03; r2 = 0.39, p = 0.001). Results were corroborated using multivariate analysis. Our data suggest a protective role of Gas6 and its receptors in patients with MS and suitable severity disease biomarkers.

Complete Blood Count in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic disease that affects the central nervous system in primarily young adults. Although the exact etiology of MS is unknown, autoimmune mechanisms are thought to play a crucial role, especially with CD4+ T cells involved in the immune response. Inflammatory reactions involving T cells and macrophages are commonly observed in MS lesions. B lymphocytes, plasma cells, and antibodies also contribute to MS pathogenesis. Neutrophils, lymphocytes, monocytes, and platelets, key immune system components, play roles in inflammatory processes, but their association with MS prognosis remains inconclusive. Due to its heterogeneous nature, clinical manifestations of MS vary depending on the location of the affected central nervous system. While several potential biomarkers have been identified for MS diagnosis and monitoring, none have been universally accepted. Studies have examined complete blood count parameters in MS patients, including erythrocyte, platelet, and leukocyte populations. Changes in these parameters have been observed in MS patients compared to healthy controls and may be related to disease prognosis. For example, increased erythrocyte fragility and altered hemoglobin levels have been reported in MS patients. Leukocyte counts and ratios, such as the neutrophil/lymphocyte ratio, have shown associations with disease severity. Platelet activation and interaction with immune cells have also been implicated in MS pathophysiology. Nevertheless, further research is needed to fully understand the role of complete blood count parameters in MS. Identifying reliable biomarkers for early diagnosis and prognosis prediction would greatly enhance MS management. Moreover, these benefits could lead to substantial improvements in achieving complete recovery of patients, surpassing the focus on current symptomatic treatments.

The role of transcranial magnetic stimulation in multiple sclerosis prognosis

The role of transcranial magnetic stimulation in multiple sclerosis prognosis

Machine Learning Algorithms for Early Prediction of Multiple Sclerosis Progression: A Comparative Study

Multiple Sclerosis (MS) is a chronic autoimmune disease characterized by central nervous system (CNS) degeneration, leading to diverse neurological symptoms. Managing MS poses a challenge due to its unpredictable progression. This study focuses on early prediction of MS progression using machine learning (ML) algorithms, comparing the effectiveness of Random Forest, XGBoost, Decision Tree, and Logistic Regression. Clinical, genetic, and environmental factors were analyzed in a cohort of Mexican mestizo patients recently diagnosed with Clinically Isolated Syndrome (CIS). Data preprocessing addressed missing values, and feature selection tailored to the population’s characteristics was applied. The dataset was split into training and testing sets, maintaining stratification for CDMS and nonCDMS cases. Machine learning models were trained with optimized hyperparameters. Performance evaluation metrics, including accuracy, precision, recall, F1-score, and AUC-ROC, were employed. The Random Forest model exhibited superior performance (AUC: 0.93, accuracy: 87%), outperforming other models. Variable importance analysis identified top predictors, including Periventricular MRI, Age, Infratentorial MRI, and Oligoclonal Bands. The study’s clinical implications highlight ML’s potential in enhancing early MS prognosis, aiding timely interventions. The Random Forest model, with its robust performance, emerges as a valuable tool for identifying patients at risk. While the study contributes to predictive analytics in neurological disorders, limitations include cohort specificity and retrospective data use. Prospective studies and further exploration of data sources are recommended for broader applicability. This research demonstrates the efficacy of ML in early MS progression prediction, providing clinicians with a promising tool for personalized patient care. The findings contribute to advancing predictive healthcare analytics and emphasize the significance of tailored interventions in neurological disorders.

Dynamic changes in patient admission and their disabilities in multiple sclerosis and neuromyelitis optica: A Japanese nationwide administrative data study

BackgroundThe real-world data evidences how establishment of neuromyelitis optica (NMO) disease concept and development disease modifying therapy affect the patients with multiple sclerosis (MS) and NMO are lacking. The aim of this study is to clarify the diachronic trend of the severity and admissions of patients with MS and NMO. MethodsWe retrospectively investigated the trends in admissions, treatments, and disabilities in the patients with MS and NMO using the Japanese administrative data between 2012 and 2017. ResultsWe analyzed acute stage 9545 and 2035 admissions in each 6100 MS and 1555 NMO patients. The annual number of admission in MS significantly decreased in 6 years; however, those in NMO consistently increased. The patient proportion with lower disability was significantly increased in MS and NMO. These trends were especially observed in patients admitted to centralized hospitals with more active treatments, such as second-line disease modifying therapy for MS and plasmapheresis for NMO. Patients with NMO using DMT for MS diminished in 6 years. ConclusionA gradual improvement of disability in patients with MS and NMO was observed, probably due to advanced treatments, increased NMO awareness, and decreased misdiagnosis, which seems to be the key for better prognosis in MS and NMO.

Is it cost-effective to request IgM oligoclonal bands against lipids in daily practice as a biomarker for poor prognosis in multiple sclerosis?

Backgroundvarious prognostic factors of multiple sclerosis have been identified, including demographic, clinical, radiological, and laboratory factors. The aim was to analyze whether the presence of IgM oligoclonal bands against lipids is associated with disease progression. Methodsan individual-based, prospective, observational study was conducted at the Neurology Department of Hospital Universitari i Politècnic la Fe. Clinical, radiological, and laboratory variables were collected. Data analysis was divided into a descriptive phase and a subsequent analytical phase. Resultsa total of 116 patients were included. 81.9% of them had IgM oligoclonal bands against lipids, with phosphatidylcholine being the predominant type. A higher proportion of patients with IgM oligoclonal bands against lipids required treatment with a disease-modifying drug, started treatment at an earlier stage, showed poorer results in functional tests, and exhibited a higher increase in lesion burden, although these differences were not statistically significant. ConclusionsIn our study, the presence of IgM oligoclonal bands against lipids was not found to be associated with other poor prognostic variables.

The importance of the patient's perspective in decision-making in multiple sclerosis: Results of the OwnMS patient perspectives study.

Research is needed to identify the unmet disease education and communication needs of people with multiple sclerosis (PwMS) to support informed decision-making, enable self-management and maintain independence for PwMS for as long as possible. An Expert Steering Group co-developed two studies for PwMS aged 18 years and over: a qualitative, online, patient community activity and a quantitative anonymised online survey. The quantitative survey was conducted in the UK from 12 September 2019 to 18 November 2019 amongst PwMS recruited via the Multiple Sclerosis (MS) Trust newsletter and their closed Facebook group. Questions explored the goals, desires, and knowledge gaps of PwMS. Self-reported data from people with relapsing-remitting multiple sclerosis (RRMS) were collated and reviewed, and discussed by the Steering Group. This paper presents descriptive statistics of the quantitative survey findings. The sample consisted of 117 participants with RRMS. Most respondents (73%) had personal goals related to lifestyle and many (69%) were concerned about maintaining independence. More than half of respondents were worried about planning for the future in relation to income (56%), housing (40%) and most respondents also indicated MS had a negative impact on their lives, including their work life (73%) and social life (69%). Limited occupational support was forthcoming (17% were not provided with any support and only 27% report their work environment being adjusted to suit their needs). The ability to plan for the future and to understand the course of MS were highlighted as key priorities by respondents. A positive trend was observed between those who felt able to plan for the future and their knowledge of MS progression. The proportion of patients who report knowing a 'great deal' about MS prognosis and disability progression was low (16% and 9%, respectively), suggesting an increased role for clinical teams to provide information and education for PwMS. Communication between respondents and their clinical teams highlighted the role of specialist nurses for PwMS to provide holistic, informative support and demonstrated the level of comfort that PwMS have in discussing less clinical topics with these providers. This UK nationwide survey highlighted some of the unmet needs in disease education and communication in a subgroup of UK patients with RRMS, which can impact quality of life. Discussing goals and planning alongside prognosis and disability progression with MS care teams may enable people with RRMS not only to make informed treatment decisions, but also to self-manage and plan for the future, factors which are important to maintain independence.

Central vein sign and paramagnetic rim sign: From radiologically isolated syndrome to multiple sclerosis.

The widespread use of magnetic resonance imaging (MRI) has led to an increase in incidental findings in the central nervous system. Radiologically isolated syndrome (RIS) is a condition where imaging reveals lesions suggestive of demyelinating disease without any clinical episodes consistent with multiple sclerosis (MS). The prognosis for RIS patients is uncertain, with some remaining asymptomatic while others progress to MS. Several risk factors for disease progression have been identified, including male sex, younger age at diagnosis, and spinal cord lesions. This article reviews two promising biomarkers, the central vein sign (CVS) and the paramagnetic rim sign (PRS), and their potential role in the diagnosis and prognosis of MS and RIS. Both CVS and PRS have been shown to be accurate diagnostic markers in MS, with high sensitivity and specificity, and have been useful in distinguishing MS from other disorders. Further research is needed to validate these findings and determine the clinical utility of these biomarkers in routine practice.

The macular retinal ganglion cell layer as a biomarker for diagnosis and prognosis in multiple sclerosis: A deep learning approach.

The macular ganglion cell layer (mGCL) is a strong potential biomarker of axonal degeneration in multiple sclerosis (MS). For this reason, this study aims to develop a computer-aided method to facilitate diagnosis and prognosis in MS. This paper combines a cross-sectional study of 72 MS patients and 30 healthy control subjects for diagnosis and a 10-year longitudinal study of the same MS patients for the prediction of disability progression, during which the mGCL was measured using optical coherence tomography (OCT). Deep neural networks were used as an automatic classifier. For MS diagnosis, greatest accuracy (90.3%) was achieved using 17 features as inputs. The neural network architecture comprised the input layer, two hidden layers and the output layer with softmax activation. For the prediction of disability progression 8 years later, accuracy of 81.9% was achieved with a neural network comprising two hidden layers and 400 epochs. We present evidence that by applying deep learning techniques to clinical and mGCL thickness data it is possible to identify MS and predict the course of the disease. This approach potentially constitutes a non-invasive, low-cost, easy-to-implement and effective method.

Motherhood Experiences of Women With Multiple Sclerosis: A Thematic Meta-Synthesis.

The nature and unpredictable prognosis of multiple sclerosis (MS) make pregnancy and motherhood challenging experiences for women with the disease. Using the thematic synthesis method, we aimed to systematically interpret and synthesize data from qualitative research examining the motherhood experiences of women with MS. The analyses revealed three analytical themes: "Deciding to become a mother," "The journey during pregnancy, childbirth, and the postpartum period," and "Surviving as a mother with multiple sclerosis." For women with MS, being a mother, pregnancy, and the postpartum period were complex and challenging issues. During this period, most women felt lonely, thought that they were contradictory and inadequately informed by healthcare professionals and that they could not get enough social support. Despite all the difficulties, being a mother was a source of motivation for them. This meta-synthesis study provides healthcare professionals with an in-depth understanding of the experiences of women with MS with pregnancy, childbirth, postpartum period, and motherhood from their perspectives.

Lived experience of persons with multiple sclerosis: A qualitative interview study.

Multiple sclerosis (MS) is a chronic autoimmune disease with a substantial impact on quality of life and functional capability. The prognosis of MS has changed over time due to the development of increasingly effective therapies. As the knowledge and perceptions of persons living with chronic conditions increasingly have been acknowledged, it has become important to understand lived experiences with a focus on everyday events and experiences as a way of knowing and interpreting the world. Exploring context-specific lived experiences as a source of knowledge about the disease and care may contribute to more precision in designing care services. The aim of this study was to explore the lived experience of persons living with MS in a Swedish context. A qualitative interview study was conducted with both purposeful and random sampling strategies, resulting in 10 interviews. Data were analyzed using inductive thematic content analysis. The analysis generated 4 overarching themes with 12 subthemes, the 4 themes were: perspectives on life and health, influence on everyday life, relations with healthcare, and shared healthcare processes. The themes are concerned with the patients' own perspectives and context as well as medical and healthcare-related perspectives. Patterns of shared experiences were found, for example, in the diagnosis confirmation, future perspectives, and planning and coordination. More diverse experiences appeared concerning relations with others, one's individual requirements, symptoms and consequences, and knowledge building. The findings suggest a need for a more diverse and coproduced development of healthcare services to meet diverse needs in the population with greater acknowledgement of the person's lived experience, including consideration of the complexity of the disease, personal integrity, and different ways of knowing. Findings from this study will be further explored together with other quantitative and qualitative data.

Chemical exchange saturation transfer MRI detects myelin changes in cuprizone mouse model at 3T.

Chemical exchange saturation transfer (CEST) sensitively detects molecular alterations in the brain, such as relayed nuclear Overhauser effect (rNOE) CEST contrast at -3.5 ppm representing aliphatic protons in both lipids and proteins, and CEST contrast at 3.5 ppm correlating with amide proton in proteins. Myelin is rich in lipids and proteins, and therefore CEST can be explored as a biomarker for myelin pathology, which could contribute to the diagnosis and prognosis of multiple sclerosis (MS). In the current study, we investigate the specificity of aliphatic rNOE and the amide pool in myelin detection using the cuprizone (CPZ) mouse model, which recapitulates the demyelination and remyelination of MS. In this study, preclinical 3T MRI was performed in 19 male C57BL/6 mice. Mice in the normal control (NC) group (n = 9) were fed a normal diet for the whole course, while mice in the CPZ group (n = 10) were fed with CPZ for 10 weeks, followed by 4 weeks with a normal diet. The CEST contrast of rNOE (-3.5 ppm) and amide (3.5 ppm) in brain regions of the corpus callosum (CC) and the caudate putamen were compared. Statistical differences between the groups were calculated using two-way ANOVA. We observed significantly decreased rNOE (NC: 4.85% ± 0.09%/s vs. CPZ: 3.88% ± 0.18%/s, p = 0.007) and amide pool (NC: 3.20% ± 0.10%/s vs. CPZ: 2.46% ± 0.16%/s, p = 0.02) in the CC after 8 weeks on CPZ diet (p < 0.05). Moreover, the rNOE in the CPZ group recovered to a level comparable with the NC group at week 14 (p = 0.39), while amide remained at a level as low as that for the NC group (p = 0.051). Significant rNOE and amide changes, validated by immunohistochemistry results for demyelination and remyelination, demonstrate the huge potential of CEST for revealing myelin pathology, which has implications for MS identification at the clinical field strength of 3T.

The independent contribution of brain, spinal cord and gadolinium MRI in treatment decision in multiple sclerosis: A population-based retrospective study.

Spinal cord and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) can provide additional information to brain MRI to determine prognosis of multiple sclerosis (MS). However, the real-world impact of routine use of brain MRI with spinal cord and/or Gd sequences is unknown. Our aim was to evaluate the effect of brain, spinal cord and Gd MRI on treatment decisions in MS. In this 2015-2020 population-based study, we performed a retrospective analysis on MS patients resident in the Campania Region (South Italy), with disease modifying treatment (DMT) prescription (n=6,161). DMTs were classified as platform (dimethyl fumarate, glatiramer acetate, interferon-beta, peg-interferon-beta, teriflunomide), or high-efficacy (alemtuzumab, cladribine, fingolimod, natalizumab, ocrelizumab). We evaluated the association between binary MRI variables and switch from platform to high-efficacy DMT using multivariable logistic regression. The likelihood of switch from platform to high-efficacy DMT was 47% higher when including post-Gd acquisitions to brain and/or spinal cord MRI, 59% higher when including spinal cord acquisitions to brain MRI, and 132% higher when including any MRI compared with no MRI (all p<0.05). The likelihood of switch to high-efficacy DMT decreased over time from treatment start. Our results show that spinal cord and Gd MRI acquisitions can provide relevant information to influence subsequent treatment decisions, especially in early treatment phases, compared with stand-alone brain MRI.