scholarly journals Clinical Significance of Myelin Oligodendrocyte Glycoprotein Autoantibodies in Patients with Typical MS Lesions on MRI

2021 ◽  
Vol 7 (4) ◽  
pp. 205521732110487
Author(s):  
Pietro Zara ◽  
Valentina Floris ◽  
Eoin P. Flanagan ◽  
A. Sebastian Lopez-Chiriboga ◽  
Brian G. Weinshenker ◽  
...  
Keyword(s):  
Myelin Oligodendrocyte Glycoprotein ◽  
Disease Course ◽  
Targeted Agents ◽  
High Efficacy ◽  
T2 Lesions ◽  
Igg Synthesis ◽  
Relapsing Remitting ◽  
Intrathecal Igg Synthesis ◽  
Age Range ◽  
Over Time

Background Myelin-oligodendrocyte-glycoprotein (MOG)-IgG-positivity in patients with typical MS lesions on MRI may lead to diagnostic/therapeutic uncertainty. Objective and Methods We reviewed reports of cases with MS phenotype on MRI and MOG-IgG-positivity published in Pubmed between 01/2012–06/2021. Results Sixteen patients were included (median age [range], 37,5 [25–66] years; 60% female). Three patients initially tested negative for MOG-IgG. Disease course was: relapsing-remitting, 10; or progressive, 6. Intrathecal IgG-synthesis was common (79%). Low and high-efficacy MS-targeted agents prevented relapses in 30% and 100%, respectively. None of the patients showed resolution of MRI T2-lesions over time. Conclusions MOG-IgG-positivity is unlikely to alter the expected treatment response and outcomes in patients with otherwise typical MS phenotype on MRI.

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.

Peripheral imbalanced TFH/TFR ratio correlates with intrathecal IgG synthesis in multiple sclerosis at clinical onset

2018 ◽  
Vol 25 (7) ◽  
pp. 918-926 ◽  
Author(s):  
Marco Puthenparampil ◽  
Antonio Zito ◽  
Giorgia Pantano ◽  
Lisa Federle ◽  
Erica Stropparo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Oligoclonal Bands ◽  
T Helper ◽  
Germinal Center Reaction ◽  
Clinical Onset ◽  
Follicular Helper ◽  
Igg Synthesis ◽  
Relapsing Remitting ◽  
Intrathecal Igg Synthesis ◽  
Relapsing Remitting Multiple Sclerosis

Background: Alteration of T-follicular helper (TFH) and regulatory (TFR) subpopulations may contribute to the development of auto-reactive B-cell. Objective: To investigate whether changes in TFH and TFR subsets are associated with abnormal IgG synthesis in blood and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. Methods: Paired blood and CSF samples were obtained from 31 untreated relapsing-remitting multiple sclerosis (RRMS) patients at diagnosis. Peripheral blood TFH (CD3+CD4+CXCR5+CD25–CD127+), TFR (CD3+CD4+CXCR5+CD25+CD127dim), conventional T-Helper (TH, CD3+CD4+CXCR5–CD25–CD127+), and regulatory T-cells (T-Reg, CD3+CD4+CXCR5–CD25+CD127dim) were analyzed in all RRMS patients and in 13 healthy controls (HCs). Qualitative and quantitative intrathecal IgG synthesis was evaluated in RRMS patients, who were then further subclassified according to the presence of IgG oligoclonal bands in blood and/or CSF. Results: Compared to HC, RRMS had lower TFR percentage ( p < 0.01) and higher TFH/TFR ratio ( p < 0.001). In RRMS, TFH/TFR ratio correlated with both qualitative ( r = 0.56, p < 0.005) and quantitative intrathecal IgG synthesis (IgG Index: r = 0.78; IgGLoc: r = 0.79; IgGIF: r = 0.76, all p < 0.001). Patients with the highest TFH/TFR ratios had higher percentages of circulating B-cells (36.1 ± 35.2%, p < 0.05). Conclusion: In RRMS, increased TFH/TFR ratio associates with abnormal IgG production in blood and CSF, suggesting that antibody-producing cells, derived from deregulated peripheral germinal center reaction, colonize the CNS.

Measurement Invariance of the Serbian Version of the Satisfaction With Life Scale Across Age, Gender, and Time

2019 ◽  
Vol 35 (4) ◽  
pp. 555-563 ◽  
Author(s):  
Veljko Jovanović
Keyword(s):  
Life Satisfaction ◽  
Factor Analysis ◽  
Confirmatory Factor Analysis ◽  
Satisfaction With Life ◽  
Satisfaction With Life Scale ◽  
Confirmatory Factor ◽  
Life Scale ◽  
Serbian Version ◽  
Age Range ◽  
Over Time

Abstract. The present research aimed at examining measurement invariance of the Serbian version of the Satisfaction with Life Scale (SWLS) across age, gender, and time. A total sample in Study 1 consisted of 2,595 participants from Serbia, with a mean age of 23.79 years (age range: 14–55 years). The final sample in Study 2 included 333 Serbian undergraduate students ( Mage = 20.81; age range: 20–27 years), who completed the SWLS over periods of 6 and 18 months after the initial assessment. Confirmatory factor analysis (CFA) supported the modified unidimensional model of the SWLS, with correlated residuals of items 4 and 5 tapping past satisfaction. The results of the multigroup confirmatory factor analysis supported the full scalar invariance across gender and over time and partial scalar invariance across age. Latent mean comparisons revealed that women reported higher life satisfaction than men. Additionally, adolescents reported higher life satisfaction than students and adults, with adults showing the lowest life satisfaction. Our findings indicate that the SWLS allows meaningful comparisons in life satisfaction across age, gender, and over time.

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 A clinical staging proposal of the disease course over time in non-severe patients with coronavirus disease 2019

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yiting Lin ◽  
Yiqun Wu ◽  
Ping Zhong ◽  
Bingbo Hou ◽  
Jielan Liu ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Clinical Signs ◽  
Clinical Staging ◽  
Disease Course ◽  
Prodromal Phase ◽  
The Third ◽  
Convalescent Phase ◽  
Secondary Damage ◽  
Remission Phase ◽  
Over Time

AbstractInformation on the clinical staging of coronavirus disease 2019 (COVID-19) is still limited. This study aimed to propose a clinical staging proposal of the disease course in non-severe patients with COVID-19. In this retrospective study, 108 non-severe patients with COVID-19 were grouped according to the duration from symptoms onset to hospital admission: ≤ 1 week, > 1 to 2 weeks, > 2 to 3 weeks, > 3 to 5 weeks, respectively. The dynamic changes of clinical signs were profiled across the four groups. A clinical staging proposal of the disease course over time was proposed from the perspective of the interaction between the virus and host. The prodromal phase, characterized by pneumonia, significant lymphopenia, and slightly elevated inflammatory markers, occurred in the first week after symptoms onset. In the second week, all the hematological and inflammatory markers were at the peak or bottom. Meanwhile, progressive pneumonia as well as the secondary damage of other organs (e.g. cardiac damage, coagulopathy, etc.) was significant during this period, making the disease progress into the apparent manifestation phase. In the third week, the improvement of the majority of clinical signs accompanied by a relatively high degree of inflammatory response defined the remission phase. After 3 weeks, patients were in the convalescent phase, in which all the indicators were maintained at a relatively normal level. We concluded that the disease course over time in non-severe patients with COVID-19 could be divided into four phases: the prodromal phase (in the first week), the apparent manifestation phase (in the second week), the remission phase (in the third week), and the convalescent phase (after 3 weeks), respectively. In clinical practice, tailored therapies should be considered seriously in different stages of the disease course.

Development of Autoimmune Thyroid Disease in Multiple Sclerosis Patients Post-Alemtuzumab Improves Treatment Response

2020 ◽  
Vol 105 (9) ◽  
pp. e3392-e3399 ◽  
Author(s):  
Alina Sovetkina ◽  
Rans Nadir ◽  
Antonio Scalfari ◽  
Francesca Tona ◽  
Kevin Murphy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Graves Disease ◽  
Autoimmune Thyroid ◽  
Tertiary Referral Center ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Edss Score ◽  
Multiple Sclerosis Patients

Abstract Context Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20% and 40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect. Objective The objective of this work is to determine whether MS disease progression following alemtuzumab treatment differs in patients who develop AITD compared to those who do not. Design, Setting, and Patients A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 was conducted at a tertiary referral center. Main Outcome Measures Thyroid status, new relapses, Expanded Disability Status Scale (EDSS) score change, and disability progression following alemtuzumab were evaluated. Results Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [interquartile range]; AITD: –0.25 [–1 to 0.5] vs non-AITD: 0 [1-0]. P = .007]. Multivariable regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (P = .011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (P = .023). There was no difference in the number of new focal T2 lesions and contrast-enhancing magnetic resonance imaging lesions developed following alemtuzumab between the 2 groups. Conclusion Graves disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.

No evidence of disease activity in multiple sclerosis: Implications on cognition and brain atrophy

2015 ◽  
Vol 22 (1) ◽  
pp. 64-72 ◽  
Author(s):  
Alfredo Damasceno ◽  
Benito Pereira Damasceno ◽  
Fernando Cendes
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Atrophy ◽  
Repeated Measures ◽  
Positive Impact ◽  
Cognitive Domains ◽  
Cortical Thinning ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Volume Decrease

Background: The concept of no evidence of disease activity (NEDA) has emerged as an important outcome measure for multiple sclerosis (MS). However, it is not known if maintaining NEDA has a positive impact on cognition or brain atrophy. Objective: To evaluate NEDA status after two years, addressing its implications on cognition and brain atrophy. Methods: Forty-two relapsing–remitting MS patients and 30 controls underwent MRI (3T) and cognitive evaluation (BRB-N). Forty patients performed additional evaluations, after 12 and 24 months. NEDA was defined as the absence of clinical (relapses/disability progression) and MRI activity (new T2/gadolinium-enhancing lesions). Repeated measures and multivariate analyses were performed to assess the contribution of NEDA criteria to GM atrophy. Results: After two years, 30.8% of the cohort had NEDA. From these, 58.3% still had worsening in ⩾2 cognitive domains. Patients with MRI activity had more cortical thinning and slightly more thalamus volume decrease. Absence of new/enlarging T2 lesions was the only predictor of cortical thinning, subcortical GM and thalamic atrophy rates. Conclusions: NEDA status was achieved in a small proportion of our cohort, and did not preclude cognitive deterioration. Absence of MRI activity and especially of new/enlarging T2 lesions was associated with less cortical and subcortical GM atrophy.

scholarly journals Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study

2018 ◽  
Vol 25 (6) ◽  
pp. 819-827 ◽  
Author(s):  
Gavin Giovannoni ◽  
Per Soelberg Sorensen ◽  
Stuart Cook ◽  
Kottil W Rammohan ◽  
Peter Rieckmann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
High Disease Activity ◽  
Study Entry ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Study Population ◽  
Magnetic Resonance Imaging Mri ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

Background: In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Objective: Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population. Methods: Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions). Results: In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population. Conclusion: Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.

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