Anti-MOG Antibodies as Early Predictors for Conversion to Relapsing-Remitting Disease Course in Patients Suggestive of Multiple Sclerosis

2004 ◽  
pp. 163-166
Author(s):  
T. Berger ◽  
P. Rubner ◽  
R. Egg ◽  
E. Dilitz ◽  
D. Stadlbauer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Course ◽  
Early Predictors ◽  
Relapsing Remitting ◽  
Mog Antibodies

scholarly journals Machine Learning Use for Prognostic Purposes in Multiple Sclerosis

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 122
Author(s):  
Ruggiero Seccia ◽  
Silvia Romano ◽  
Marco Salvetti ◽  
Andrea Crisanti ◽  
Laura Palagi ◽  
...  
Keyword(s):  
Machine Learning ◽  
Multiple Sclerosis ◽  
High Impact ◽  
Prognostic Models ◽  
Early Prediction ◽  
Disease Course ◽  
Slow Progression ◽  
Relapsing Remitting ◽  
Long Time ◽  
Effective Drugs

The course of multiple sclerosis begins with a relapsing-remitting phase, which evolves into a secondarily progressive form over an extremely variable period, depending on many factors, each with a subtle influence. To date, no prognostic factors or risk score have been validated to predict disease course in single individuals. This is increasingly frustrating, since several treatments can prevent relapses and slow progression, even for a long time, although the possible adverse effects are relevant, in particular for the more effective drugs. An early prediction of disease course would allow differentiation of the treatment based on the expected aggressiveness of the disease, reserving high-impact therapies for patients at greater risk. To increase prognostic capacity, approaches based on machine learning (ML) algorithms are being attempted, given the failure of other approaches. Here we review recent studies that have used clinical data, alone or with other types of data, to derive prognostic models. Several algorithms that have been used and compared are described. Although no study has proposed a clinically usable model, knowledge is building up and in the future strong tools are likely to emerge.

scholarly journals Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mario Amatruda ◽  
Maria Petracca ◽  
Maureen Wentling ◽  
Benjamin Inbar ◽  
Kamilah Castro ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Disease Course ◽  
Primary Progressive ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
One Year ◽  
Multiple Sclerosis Patients

Abstract The disease course of patients with a confirmed diagnosis of primary progressive multiple sclerosis (PPMS) is uncertain. In an attempt to identify potential signaling pathways involved in the evolution of the disease, we conducted an exploratory unbiased lipidomic analysis of plasma from non-diseased controls (n = 8) and patients with primary progressive MS (PPMS, n = 19) and either a rapid (PPMS-P, n = 9) or slow (PPMS-NP, n = 10) disease course based on worsening disability and/or MRI-visible appearance of new T2 lesions over a one-year-assessment. Partial least squares-discriminant analysis of the MS/MSALL lipidomic dataset, identified lipids driving the clustering of the groups. Among these lipids, sphingomyelin-d18:1/14:0 and mono-hexosylceramide-d18:1/20:0 were differentially abundant in the plasma of PPMS patients compared to controls and their levels correlated with MRI signs of disease progression. Lyso-phosphatidic acid-18:2 (LPA-18:2) was the only lipid with significantly lower abundance in PPMS patients with a rapidly deteriorating disease course, and its levels inversely correlated with the severity of the neurological deficit. Decreased levels of LPA-18:2 were detected in patients with more rapid disease progression, regardless of therapy and these findings were validated in an independent cohort of secondary progressive (SPMS) patients, but not in a third cohorts of relapsing–remitting (RRMS) patients. Collectively, our analysis suggests that sphingomyelin-d18:1/14:0, mono-hexosylceramide-d18:1/20:0, and LPA-18:2 may represent important targets for future studies aimed at understanding disease progression in MS.

scholarly journals A metabolic perspective on CSF-mediated neurodegeneration in multiple sclerosis

Brain ◽  
2019 ◽  
Vol 142 (9) ◽  
pp. 2756-2774 ◽  
Author(s):  
Maureen Wentling ◽  
Carlos Lopez-Gomez ◽  
Hye-Jin Park ◽  
Mario Amatruda ◽  
Achilles Ntranos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuronal Damage ◽  
Morphological Changes ◽  
Progressive Multiple Sclerosis ◽  
Functional Screening ◽  
Disease Course ◽  
Post Translational Modification ◽  
Neurodegenerative Process ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients

Abstract Multiple sclerosis is an autoimmune demyelinating disorder of the CNS, characterized by inflammatory lesions and an underlying neurodegenerative process, which is more prominent in patients with progressive disease course. It has been proposed that mitochondrial dysfunction underlies neuronal damage, the precise mechanism by which this occurs remains uncertain. To investigate potential mechanisms of neurodegeneration, we conducted a functional screening of mitochondria in neurons exposed to the CSF of multiple sclerosis patients with a relapsing remitting (n = 15) or a progressive (secondary, n = 15 or primary, n = 14) disease course. Live-imaging of CSF-treated neurons, using a fluorescent mitochondrial tracer, identified mitochondrial elongation as a unique effect induced by the CSF from progressive patients. These morphological changes were associated with decreased activity of mitochondrial complexes I, III and IV and correlated with axonal damage. The effect of CSF treatment on the morphology of mitochondria was characterized by phosphorylation of serine 637 on the dynamin-related protein DRP1, a post-translational modification responsible for unopposed mitochondrial fusion in response to low glucose conditions. The effect of neuronal treatment with CSF from progressive patients was heat stable, thereby prompting us to conduct an unbiased exploratory lipidomic study that identified specific ceramide species as differentially abundant in the CSF of progressive patients compared to relapsing remitting multiple sclerosis. Treatment of neurons with medium supplemented with ceramides, induced a time-dependent increase of the transcripts levels of specific glucose and lactate transporters, which functionally resulted in progressively increased glucose uptake from the medium. Thus ceramide levels in the CSF of patients with progressive multiple sclerosis not only impaired mitochondrial respiration but also decreased the bioavailability of glucose by increasing its uptake. Importantly the neurotoxic effect of CSF treatment could be rescued by exogenous supplementation with glucose or lactate, presumably to compensate the inefficient fuel utilization. Together these data suggest a condition of ‘virtual hypoglycosis’ induced by the CSF of progressive patients in cultured neurons and suggest a critical temporal window of intervention for the rescue of the metabolic impairment of neuronal bioenergetics underlying neurodegeneration in multiple sclerosis patients.

Comparing a self report questionnaire with physician assessment for determining multiple sclerosis clinical disease course: a validation study

2007 ◽  
Vol 13 (8) ◽  
pp. 1033-1037 ◽  
Author(s):  
A.M. Bamer ◽  
K. Cetin ◽  
D. Amtmann ◽  
J.D. Bowen ◽  
K.L. Johnson
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Course ◽  
High School Education ◽  
Self Report ◽  
Kappa Statistics ◽  
Disease Course ◽  
Substantial Agreement ◽  
Patient Response ◽  
Relapsing Remitting ◽  
Subsequent Administration

Determining multiple sclerosis (MS) clinical course is important in research and clinical practice. However, many patients do not know their clinical course, limiting the option to use self-report in research studies including surveys. In order to address this, we developed a self-report item to be used in self-administered mailed surveys displaying graphically the courses of MS. The validity of this item was then evaluated by comparing physician-assessed disease clinical course to patient response on the self-report item on 94 of 99 consecutive patients seen in an MS specialty clinic. Kappa statistics were calculated comparing self-assessed versus physician-assessed MS clinical course for the four common MS clinical courses (κ=0.45) and for relapsing remitting versus other courses (κ=0.62) indicating substantial agreement. Subsequent administration of the item by mail to 1371 individuals with MS in Washington and Montana determined that while most individuals responded as intended to the item, persons with less than a high school education ( P=0.009) or over the age of 60 ( P = 0.002) were significantly more likely to leave the item blank. It appears that this item may be used to obtain a rough estimate of MS clinical course in research using self-report surveys where physician assessments are impractical. Multiple Sclerosis 2007; 13: 1033—1037. http://msj.sagepub.com

Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis

2011 ◽  
Vol 18 (1) ◽  
pp. 45-54 ◽  
Author(s):  
M Cossburn ◽  
G Ingram ◽  
C Hirst ◽  
Y Ben-Shlomo ◽  
TP Pickersgill ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Age At Onset ◽  
Disease Onset ◽  
Complete Recovery ◽  
Population Based ◽  
Disease Course ◽  
Index Event ◽  
Relapsing Remitting ◽  
Age Dependent

Background: Age at onset modifies prognosis in multiple sclerosis (MS) and may also exert an effect on the characteristics of disease ignition. Understanding how age influences presentation informs disease management and may allow differentiation of distinct clinical sub-groups. Objectives: To determine the nature of age-specific presentations of relapsing–remitting MS (RRMS) with respect to onset symptoms, gender ratios and index event outcomes. Methods: In a prospective, population-based sample of 1424 patients in South-East Wales we examined associations between age at onset, clinical features and outcome of the onset event, making specific comparisons between paediatric, adolescent and late-onset MS. Results: Age at onset varied significantly between sexes (Male 31.2, Female 29.3, p = 0.002), 0.7% had paediatric onset, 2.7% adolescent onset and 2.8% late-onset MS (>50 years). Optic neuritis was common in younger patients and declined after age 30. Lower limb motor, facial sensory, sexual and sphincteric symptoms rose with age independent of sex and disease course. F:M ratios were highest <16 years of age and declined with increasing age, with a male excess in those over 50. Probability of complete recovery from index event declined with age from 87.4% in the youngest group to 68% in the eldest ( p = 0.009). Conclusions: Age at disease onset in RRMS exerts a significant effect on gender ratios and presenting phenotype, and allows identification of specific clinical sub-groups. In addition, ability to recover from initial relapse declines with age, suggesting accumulation of disability in MS is an age-dependent response to relapse.

Pregnancy in women with MS: Impact on long-term disability accrual in a nationwide Danish Cohort

2021 ◽  
pp. 135245852110577
Author(s):  
Johanna Balslev Andersen ◽  
Malthe Faurschou Wandall-Holm ◽  
Per Kragh Andersen ◽  
Finn Sellebjerg ◽  
Melinda Magyari
Keyword(s):  
Multiple Sclerosis ◽  
Clinically Isolated Syndrome ◽  
Time Dependent ◽  
Disease Course ◽  
Expanded Disability Status Scale ◽  
Cox Models ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Edss Score

Background: Pregnancy is considered to influence the disease course in women with multiple sclerosis (MS). Objective: The aim of this study was to investigate the effect of pregnancy on long-term disability accrual in women with MS. Methods: The Danish Multiple Sclerosis Registry (DMSR) was used to identify women diagnosed with clinically isolated syndrome or relapsing-remitting MS. Cox models with pregnancy as a time-dependent exposure and propensity score (PS) models were used to evaluate time to reach confirmed Expanded Disability Status Scale (EDSS) score of 4 and 6. Results: A total of 425 women became parous and 840 remained nulliparous. When including pregnancy as a time-dependent exposure, a non-significant association with time to reach EDSS 4 (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.61–1.20) and EDSS 6 (HR 0.70, 95% CI 0.40–1.20) was found. Correspondingly, the PS model showed no association with pregnancy on time to reach EDSS 4 (HR 0.85, 95% CI 0.56–1.28). Conclusion: This study concludes that pregnancy does not affect long-term disability accumulation.

scholarly journals Recurrence of disease activity during pregnancy after cessation of fingolimod in multiple sclerosis

2017 ◽  
Vol 24 (7) ◽  
pp. 991-994 ◽  
Author(s):  
Ingrid Meinl ◽  
Joachim Havla ◽  
Reinhard Hohlfeld ◽  
Tania Kümpfel
Keyword(s):  
Multiple Sclerosis ◽  
At Risk ◽  
Disease Activity ◽  
Effective Treatment ◽  
Disease Course ◽  
Risk Of Recurrence ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Risk Of Relapse

Background: Fingolimod is an effective treatment for active relapsing–remitting multiple sclerosis (MS). Discontinuation of therapy may be followed by recurrence of disease activity. Thus, female MS patients may be at risk of relapse during pregnancy after stopping fingolimod. Objectives and methods: To report the disease course during pregnancy of five women who interrupted therapy with fingolimod for pregnancy. Results: All patients experienced relapses during pregnancy and/or postpartum after stopping fingolimod. Conclusion: The risk of recurrence of disease activity during pregnancy after stopping fingolimod may be substantial. This should be considered and discussed with MS patients who are planning to become pregnant.

scholarly journals Rationale and design of the brain magnetic resonance imaging protocol for FutureMS: a longitudinal multi-centre study of newly diagnosed patients with relapsing-remitting multiple sclerosis in Scotland

2021 ◽  
Author(s):  
Rozanna Meijboom ◽  
Stewart J Wiseman ◽  
Elizabeth N York ◽  
Mark E Bastin ◽  
Maria del C Valdés Hernández ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Disease Activity ◽  
Structural Mri ◽  
Structural Level ◽  
Disease Course ◽  
Resonance Imaging ◽  
Relapsing Remitting ◽  
G Ratio

ABSTRACTMultiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease. MS prevalence varies geographically, both between and within countries and is notably high in Scotland. Disease trajectory varies significantly between individuals and the causes for this are largely unclear. Biomarkers predictive of disease course are urgently needed to allow improved stratification for current disease modifying therapies and future targeted treatments aimed at neuroprotection and remyelination, and as endpoints for clinical trials. Magnetic resonance imaging (MRI) can detect disease activity and underlying neurological damage non-invasively in vivo at the micro and macro structural level. FutureMS is a prospective Scottish longitudinal multi-centre cohort study which focuses on deeply phenotyping and genotyping patients with recently diagnosed relapsing-remitting MS (RRMS) to identify predictors of disease activity and severity. Neuroimaging is a central component of the study and provides two main primary endpoints for disease activity and neurodegeneration. The aim of the current paper is to provide an overview of MRI data acquisition, management and processing in FutureMS.MRI is acquired at baseline (N=431) and 1-year follow-up, in Dundee, Glasgow and Edinburgh (3T Siemens) and in Aberdeen (3T Philips), and managed and processed in Edinburgh. The core structural MRI protocol comprises T1-weighted, T2-weighted, 2D/3D FLAIR and proton density images. The original study primary imaging outcome measures are new/enlarging white matter lesions (WML) assessed by neuroradiological visual read and reduction in brain volume over one year. Secondary imaging outcomes comprise WML volume as an additional quantitative structural MRI outcome measure, rim lesions on susceptibility-weighted imaging (SWI), and microstructural MRI measures, including diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics, relaxometry, magnetisation transfer (MT) ratio, MT saturation and derived g-ratio measures.FutureMS aims to reduce uncertainty around disease course and allow for targeted treatment in RRMS by exploring the role of conventional and advanced MRI measures as biomarkers of disease severity and progression in a large population of RRMS patients in Scotland.

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