Prognostic value of oligoclonal IgG bands in Japanese clinically isolated syndrome converting to clinically definite multiple sclerosis

2017 ◽  
Vol 307 ◽  
pp. 1-6 ◽  
Author(s):  
Masako Kinoshita ◽  
Masako Daifu ◽  
Keiko Tanaka ◽  
Masami Tanaka
2021 ◽  
Vol 11 (11) ◽  
pp. 1444
Author(s):  
Mattia Fonderico ◽  
Emilio Portaccio ◽  
Lorenzo Razzolini ◽  
Luisa Pastò ◽  
Angelo Bellinvia ◽  
...  

The presence of intrathecal IgM synthesis (ITMS) has been associated with an aggressive multiple sclerosis (MS) clinical course. In the present systematic review, we aimed at assessing the prevalence of ITMS among different MS phenotypes. Moreover, we aimed at quantifying the risk of a second relapse in ITMS positive and oligoclonal IgG bands (OCGBs)-positive patients. We selected clinical studies reporting the ITMS prevalence assessed as oligoclonal IgM Bands (OCMBs), lipid-specific OCMBs (LS-OCMBs), and/or as an intrathecal IgM production > 0% (IgMLoc, Reiber formula). The overall prevalence of ITMS was higher in relapsing-remitting (RR) than clinically isolated syndrome (CIS) patients (40.1% versus 23.8%, p < 0.00001), while was in line with that detected in primary progressive MS (PPMS, 26.7%). Almost all patients (98%) with ITMS had also OCGBs. The risk of having a second relapse was higher in OCGBs positive patients (HR = 2.18, p = 0.007) but much higher in ITMS positive patients (HR = 3.62, p = 0.0005). This study revealed that the prevalence of ITMS is higher in RRMS patients. It suggests that the risk of having a second relapse, previously ascribed to OCGBs, may, to a certain extent, be related to the presence of intrathecal IgM.


2017 ◽  
Vol 3 (4) ◽  
pp. 205521731773280 ◽  
Author(s):  
Mark S Freedman ◽  
Thomas P Leist ◽  
Giancarlo Comi ◽  
Bruce AC Cree ◽  
Patricia K Coyle ◽  
...  

Background Multiple sclerosis (MS) diagnostic criteria have changed since the ORACLE-MS study was conducted; 223 of 616 patients (36.2%) would have met the diagnosis of MS vs clinically isolated syndrome (CIS) using the newer criteria. Objective The objective of this paper is to assess the effect of cladribine tablets in patients with a first clinical demyelinating attack fulfilling newer criteria (McDonald 2010) for MS vs CIS. Methods A post hoc analysis for subgroups of patients retrospectively classified as fulfilling or not fulfilling newer criteria at the first clinical demyelinating attack was conducted. Results Cladribine tablets 3.5 mg/kg ( n = 68) reduced the risk of next attack or three-month confirmed Expanded Disability Status Scale (EDSS) worsening by 74% vs placebo ( n = 72); p = 0.0009 in patients meeting newer criteria for MS at baseline. Cladribine tablets 5.25 mg/kg ( n = 83) reduced the risk of next attack or three-month confirmed EDSS worsening by 37%, but nominal significance was not reached ( p = 0.14). In patients who were still CIS after applying newer criteria, cladribine tablets 3.5 mg/kg ( n = 138) reduced the risk of conversion to clinically definite multiple sclerosis (CDMS) by 63% vs placebo ( n = 134); p = 0.0003. Cladribine tablets 5.25 mg/kg ( n = 121) reduced the risk of conversion by 75% vs placebo ( n = 134); p < 0.0001. Conclusions Regardless of the criteria used to define CIS or MS, 3.5 mg/kg cladribine tablets are effective in patients with a first clinical demyelinating attack. ClinicalTrials.gov registration: The ORACLE-MS study (NCT00725985).


2009 ◽  
Vol 11 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Deborah M. Miller ◽  
Craig Kollman ◽  
Andrea Kalajian ◽  
Paul W. O'Connor ◽  
R. Philip Kinkel

A secondary analysis was undertaken to compare patient-reported outcomes (PROs) of individuals who did and did not convert to clinically definite multiple sclerosis (CDMS) approximately 5 years after their first clinically isolated syndrome (CIS). Patients included in the analysis were participating in a long-term extension (called CHAMPIONS) of the Controlled High-Risk Avonex® Multiple Sclerosis Prevention Study (CHAMPS). The Multiple Sclerosis Quality of Life Inventory (MSQLI), a battery including the Short Form Health Status Survey (SF-36) and nine disease-specific scales, was administered to participants 5 years after their initial symptoms suggestive of MS (randomization into the CHAMPS study). Of 203 CHAMPIONS patients, 188 (93%) completed the MSQLI at enrollment into this extension study. Of these, 79 (42%) converted to CDMS. Statistically significant differences (P &lt; .001) between those who did and did not convert to CDMS were found for 4 of the 11 MSQLI scales: the SF-36 Physical Component Summary, the Modified Fatigue Impact Scale, the Pain Effects Scale, and the Bladder Control Scale. Trends not meeting our criteria for statistical significance (P &gt; .001 but &lt; .01) were observed for the SF-36 Mental Component Summary, the Perceived Deficits Questionnaire, and the Mental Health Inventory. SF-36 scores for patients not converting to CDMS over 5 years were similar to those reported for age-matched normal controls. No other demographic or disease-related factors were associated with these PROs. When stratified by Expanded Disability Status Scale score, patients who converted to CDMS demonstrated statistically significant differences on the same four scales defined above that differentiated those who did and did not convert to CDMS. These data show that individuals who have CDMS but limited disability demonstrate clear evidence of diminished health-related quality of life.


2008 ◽  
Vol 14 (8) ◽  
pp. 1026-1030 ◽  
Author(s):  
F Di Pauli ◽  
M Reindl ◽  
R Ehling ◽  
F Schautzer ◽  
C Gneiss ◽  
...  

Background Cigarette smoking increases the risk for development of multiple sclerosis and modifies the clinical course of the disease. In this study, we determined whether smoking is a risk factor for early conversion to clinically definite multiple sclerosis after a clinically isolated syndrome. Methods We included 129 patients with a clinically isolated syndrome, disseminated white-matter lesions on brain magnetic resonance imaging, and positive oligoclonal bands in the cerebrospinal fluid. The patients’ smoking status was obtained at the time of the clinically isolated syndrome. Results During a follow-up time of 36 months, 75% of smokers but only 51% of non-smokers developed clinically definite multiple sclerosis, and smokers had a significantly shorter time interval to their first relapse. The hazard ratio for progression to clinically definite multiple sclerosis was 1.8 (95% confidence interval, 1.2–2.8) for smokers compared with non-smokers ( P = 0.008). Conclusions Smoking is associated with an increased risk for early conversion to clinically definite multiple sclerosis after a clinically isolated syndrome, and our results suggest that smoking is an independent but modifiable risk factor for disease progression of multiple sclerosis. Therefore, it should be considered in the counseling of patients with a clinically isolated syndrome.


2020 ◽  
Vol 6 (1) ◽  
pp. 9-15
Author(s):  
Sadegh Izadi ◽  
◽  
Meysam Ahmadi ◽  
Maryam Poursadeghfard ◽  
◽  
...  

Background: Clinical course of Clinically Isolated Syndrome (CIS) is variable, and identifying patients who will eventually develop Multiple Sclerosis (MS) is essential. Objectives: To assess the conversion rate of CIS to Clinically Definite Multiple Sclerosis (CDMS) and its predictors in southern Iran. Materials & Methods: A total of 143 CIS patients registered to Fars Multiple Sclerosis Society (FMSS) were enrolled in the study from 2006 until 2012, and all of them were followed for 5 years. Also, their demographic and MRI data were recorded. The obtained data were analyzed by univariate and multivariable Cox regression models in SPSS v. 17. P<0.05 was considered statistically significant. Results: About 26.6% of patients progressed to MS after a mean duration of 3.4±1.1 years. The conversion rate was 27.6% in patients presented with optic neuritis, and 25.6% in patients presented with spinal cord problems. Although it was not statistically significant (P=0.23), the mean age of the patients who converted to MS was lower at the onset of the presentation (27.6 vs. 29.4 years). In patients who had 3 or more MRI lesions, the conversion rate was 49.2%; however, it was only 9.8% in subjects who had fewer than 3 lesions (OR=8.95, 95% CI=3.69–21.7, P <0.001). Women had higher conversion rate though it was not statistically significant (OR=2.09, 95% CI=0.57–7.64, P=0.26). Conclusion: Our results supported this supposition that the number of MRI lesions at baseline can be used as a predictor of CIS conversion to MS.


2021 ◽  
Vol 12 ◽  
Author(s):  
Klaus Berek ◽  
Gabriel Bsteh ◽  
Michael Auer ◽  
Franziska Di Pauli ◽  
Anne Zinganell ◽  
...  

BackgroundReports on typical routine cerebrospinal fluid (CSF) findings are outdated owing to novel reference limits (RL) and revised diagnostic criteria of Multiple Sclerosis (MS).ObjectiveTo assess routine CSF parameters in MS patients and the frequency of pathologic findings by applying novel RL.MethodsCSF white blood cells (WBC), CSF total protein (CSF-TP), CSF/serum albumin quotient (Qalb), intrathecal synthesis of immunoglobulins (Ig) A, M and G, oligoclonal IgG bands (OCB) were determined in patients with clinically isolated syndrome (CIS) and MS.ResultsOf 541 patients 54% showed CSF pleocytosis with a WBC count up to 40/μl. CSF cytology revealed lymphocytes, monocytes and neutrophils in 99%, 41% and 9% of patients. CSF-TP and Qalb were increased in 19% and 7% applying age-corrected RL as opposed to 34% and 26% with conventional RL. Quantitative intrathecal IgG, IgA and IgM synthesis were present in 65%, 14% and 21%; OCB in 95% of patients. WBC were higher in relapsing than progressive MS and predicted, together with monocytes, the conversion from CIS to clinically definite MS. Intrathecal IgG fraction was highest in secondary progressive MS.ConclusionsCSF profile in MS varies across disease courses. Blood-CSF-barrier dysfunction and intrathecal IgA/IgM synthesis are less frequent when the novel RL are applied.


2018 ◽  
Vol 25 (7) ◽  
pp. 958-967 ◽  
Author(s):  
Roos M van der Vuurst de Vries ◽  
Yu Yi M Wong ◽  
Julia Y Mescheriakova ◽  
E Daniëlle van Pelt ◽  
Tessel F Runia ◽  
...  

Background: A promising biomarker for axonal damage early in the disease course of multiple sclerosis (MS) is neurofilament light chain (NfL). It is unknown whether NfL has the same predictive value for MS diagnosis in children as in adults. Objective: To explore the predictive value of NfL levels in cerebrospinal fluid (CSF) for MS diagnosis in paediatric and adult clinically isolated syndrome (CIS) patients. Methods: A total of 88 adult and 65 paediatric patients with a first attack of demyelination were included and followed (mean follow up-time in adults: 62.8 months (standard deviation (SD) ±38.7 months) and 43.8 months (SD ±27.1 months) in children). Thirty control patients were also included. Lumbar puncture was done within 6 months after onset of symptoms. NfL was determined in CSF using enzyme-linked immunosorbent assay (ELISA). COX regression analyses were used to calculate hazard ratios (HR) for clinically definite multiple sclerosis (CDMS) diagnosis. Results: After adjustments for age, oligoclonal bands (OCB), and asymptomatic T2 lesions on baseline magnetic resonance imaging (MRI), increased NfL levels in both paediatric and adult CIS patients were associated with a shorter time to CDMS diagnosis (children HR = 3.7; p = 0.007, adults HR = 2.1; p = 0.032). For CIS patients with a future CDMS diagnosis, children showed higher NfL levels than adults (geometric mean 4888 vs 2156 pg/mL; p = 0.007). Conclusion: CSF NfL levels are associated with CDMS diagnosis in children and adults with CIS. This makes NfL a promising predictive marker for disease course with potential value in clinical practice.


2012 ◽  
Vol 4 ◽  
pp. JCNSD.S8755 ◽  
Author(s):  
Oscar Fernández

Glatiramer acetate (GA) represents one of the most common disease-modifying therapies for multiple sclerosis. GA is currently approved for patients at high risk of developing clinically definite multiple sclerosis (CDMS) after having experienced a well-defined first clinical episode (clinically isolated syndrome or CIS) and for patients with relapsing-remitting multiple sclerosis (RRMS). GA's efficacy and effectiveness to reduce relapse frequency have been proved in placebo-controlled and observational studies. Comparative trials have also confirmed the lack of significant differences over other choices of treatment in the management of relapse frequency, and long-term studies have supported its effect at extended periods of time. Additionally, RRMS patients with suboptimal response to interferon β may benefit from reduced relapse rate after switching to GA, and those with clinically isolated syndrome may benefit from delayed conversion to CDMS. All these results, together with its proven long-term safety and positive effect on patients’ daily living, support the favorable risk-benefit of GA for multiple sclerosis treatment.


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