scholarly journals Predictors and Conversion Rate of Clinically Isolated Syndrome to Clinically Definite Multiple Sclerosis: A Follow-up Study in Patients Living in the Southern Part of Iran

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.

2002 ◽  
Vol 8 (2) ◽  
pp. 115-118 ◽  
Author(s):  
A Ghezzi ◽  
C Pozzilli ◽  
M Liguori ◽  
M G Marrosu ◽  
N Milani ◽  
...  

Fifty-four subjects (36 females and 18 males) affected by clinically definite multiple sclerosis (MS) and with onset of the disease at 15 years of age or before were prospectively studied in five Italian MS centres. Female/male ratio was 4.7 in subjects with age ≥12 years, suggesting a role of hormonal changes in triggering MS onset. The mean follow-up duration was 10.9-5.6 years. The functional systems more frequently involved at onset were the pyramidal and brainstem (both in 28% of cases). The onset was monosymptomatic in 31 subjects (57%). The course was relapsing-remitting in 39 subjects (72%) and relapsing-progressive in 15 (28%). Disability was assessed by the Expanded Disability Status Scale (EDSS): the mean score after 8 years of follow up was 3.5 (-2.5). The score was <4 in 68% of cases, between 4 and 6 in 8% of cases, > 6 in 24% of cases. Disability after 8 years was highly predicted by disability in the first year (p=0.008). There was a tendency to a worse prognosis in relation to the number of relapses in the first 2 years (p=0.08). The outcome was not influenced by the characteristics of symptoms at onset, age and gender.


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.


2010 ◽  
Vol 16 (5) ◽  
pp. 576-580 ◽  
Author(s):  
María Díaz-Sánchez ◽  
S. Mayra Gómez-Moreno ◽  
M. Asunción Morales-Otal ◽  
Ana Ramos-González ◽  
Julián Benito-León

The MRI Barkhof—Tintoré criteria have proved to be highly specific for predicting conversion to clinically definite multiple sclerosis in patients with clinically isolated syndromes (CIS), but lacked an optimal sensitivity. In order to improve the accuracy of early multiple sclerosis diagnosis, new imaging criteria have been proposed by Swanton et al. We aimed to evaluate the accuracy of both MRI criteria for dissemination in space to predict conversion from CIS to clinically definite multiple sclerosis. We studied 79 CIS patients with baseline MRI performed within the first 3 months after onset. The sensitivity and specificity of both MRI criteria to predict conversion to clinically definite multiple sclerosis were analysed. The time to develop clinically definite multiple sclerosis from CIS onset, according to each imaging criteria, was studied by Kaplan—Meier survival curves. The overall conversion rate was 75.7% with a median follow-up of 57 months. Barkhof— Tintoré’s criteria showed a sensitivity of 71.9% and a specificity of 77.2%. Swanton’s criteria had a sensitivity of 91.2% and a specificity of 68.1%. Both MRI criteria identified CIS patients with higher risk and faster conversion to clinically definite multiple sclerosis. Swanton’s criteria are simpler and more sensitive than Barkhof—Tintoré‘s criteria, with a slight decrease in specificity. These results reinforce their use in multiple sclerosis diagnosis.


2013 ◽  
Vol 20 (4) ◽  
pp. 496-500 ◽  
Author(s):  
L Novakova ◽  
B Skoog ◽  
B Runmarker ◽  
S Ekholm ◽  
S Winblad ◽  
...  

The proportion of patients with clinically isolated syndrome (CIS) reported to convert to clinically definite multiple sclerosis varied between 30 and 75%. We studied the lifetime probability of remaining in the “CIS only” condition. The study was based on the longitudinally followed Gothenburg 1950–1964 incidence cohort ( n = 306). Survival analysis revealed that 17.8% of 236 attack onset patients remained “CIS only”. Patients with afferent (optic and sensory) symptoms had a better prognosis with approximately 30% of these patients remaining “CIS only”. Patients who had experienced no relapse during the first 25 years remained “CIS only” for the subsequent 25 years of follow-up.


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.


2017 ◽  
Vol 24 (7) ◽  
pp. 974-981 ◽  
Author(s):  
Roos M van der Vuurst de Vries ◽  
Jan JA van den Dorpel ◽  
Julia Y Mescheriakova ◽  
Tessel F Runia ◽  
Naghmeh Jafari ◽  
...  

Background: Fatigue is reported by more than 75% of multiple sclerosis (MS) patients. In an earlier study, we showed that fatigue is not only a common symptom in patients at time of clinically isolated syndrome (CIS; fatigued 46%) but also predicts subsequent diagnosis of clinically definite multiple sclerosis (CDMS). The course of fatigue after CIS is unknown. Objective: We aimed to explore the long-term course of fatigue after CIS. Methods: In this study, 235 CIS patients, aged 18–50 years, were prospectively followed. Patients filled in the Krupp’s Fatigue Severity Scale (FSS) and the Hospital Anxiety and Depression Scale (HADS) at baseline and annually. After reaching CDMS diagnosis, Expanded Disability Status Scale (EDSS) was obtained annually. Mixed-effects models were used to analyse longitudinal FSS measurements. Results: Fatigue at baseline was an independent predictor for CDMS diagnosis (hazard ratio (HR): 2.6, 95% confidence interval (CI): 1.6–4.4). The evolution of FSS was the same in CIS patients who remained monophasic and patients who were diagnosed with CDMS during follow-up. However, FSS increased by 0.86 units after reaching CDMS diagnosis ( p = 0.01). After this increase, the FSS course remained unaltered ( p = 0.44). Conclusion: Fatigue, which is often present at time of CIS, probably persists over time and increases after a second attack.


2015 ◽  
Vol 21 (8) ◽  
pp. 1013-1024 ◽  
Author(s):  
J Kuhle ◽  
G Disanto ◽  
R Dobson ◽  
R Adiutori ◽  
L Bianchi ◽  
...  

Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years’ follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71–2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52–2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04–3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98–0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.


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