What do we currently know about the clinically isolated syndrome suggestive of multiple sclerosis? An update

2020 ◽  
Vol 31 (3) ◽  
pp. 335-349
Author(s):  
Tomasz Grzegorski ◽  
Jacek Losy
Keyword(s):  
Multiple Sclerosis ◽  
Predictive Factors ◽  
Clinically Isolated Syndrome ◽  
Clinical Image ◽  
Double Blind ◽  
Beneficial Effects ◽  
Mcdonald Criteria ◽  
Clinical Episode ◽  
The Central Nervous System ◽  
Large Groups

AbstractMultiple sclerosis (MS) is a chronic, demyelinating, not fully understood disease of the central nervous system. The first demyelinating clinical episode is called clinically isolated syndrome (CIS) suggestive of MS. Although the most common manifestations of CIS are long tracts dysfunction and unilateral optic neuritis, it can also include isolated brainstem syndromes, cerebellar involvement, and polysymptomatic clinical image. Recently, the frequency of CIS diagnosis has decreased due to the more sensitive and less specific 2017 McDonald criteria compared with the revisions from 2010. Not all patients with CIS develop MS. The risk of conversion can be estimated based on many predictive factors including epidemiological, ethnical, clinical, biochemical, radiological, immunogenetic, and other markers. The management of CIS is nowadays widely discussed among clinicians and neuroscientists. To date, interferons, glatiramer acetate, teriflunomide, cladribine, and some other agents have been evaluated in randomized, placebo-controlled, double-blind studies relying on large groups of patients with the first demyelinating event. All of these drugs were shown to have beneficial effects in patients with CIS and might be used routinely in the future. The goal of this article is to explore the most relevant topics regarding CIS as well as to provide the most recent information in the field. The review presents CIS definition, classification, clinical image, predictive factors, and management. What is more, this is one of very few reviews summarizing the topic in the light of the 2017 McDonald criteria.

Early predictors of multiple sclerosis after a typical clinically isolated syndrome

2014 ◽  
Vol 20 (13) ◽  
pp. 1721-1726 ◽  
Author(s):  
Aurélie Ruet ◽  
Georgina Arrambide ◽  
Bruno Brochet ◽  
Cristina Auger ◽  
Eva Simon ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
At Risk ◽  
High Specificity ◽  
Clinically Isolated Syndrome ◽  
Oligoclonal Bands ◽  
Mcdonald Criteria ◽  
Early Predictors ◽  
Patients At Risk ◽  
Magnetic Resonance Imaging Mri ◽  
Periventricular Lesions

Background: The 2010 McDonald criteria allow diagnosing multiple sclerosis (MS) with one magnetic resonance imaging (MRI) scan. Nevertheless, not all patients at risk fulfil criteria at baseline. Other predictive factors (PFs) are: age ≤40 years, positive oligoclonal bands (OBs), and ≥3 periventricular lesions. Objective: The purpose of this study was to evaluate the 2010 McDonald criteria performance and to assess other PFs in patients without dissemination in space (DIS). Methods: Patients with clinically isolated syndrome (CIS) underwent baseline MRI and OB determination with clinical and radiological follow-up. Adjusted hazard ratios (aHRs) for clinically definite MS were estimated for DIS, dissemination in time (DIT), and DIS+DIT. Diagnostic properties at two years were calculated. In cases without DIS, combinations of ≥2 PFs were assessed. Results: A total of 652 patients were recruited; aHRs were 3.8 (2.5–5.8) for DIS, 4.2 (1.9–9.2) for DIT, and 8.6 (5.4–13.8) for DIS+DIT. Sensitivities were 69.6%, 42.3%, and 36.4%, and specificities were 67.3%, 87.9%, and 90.2%, respectively. In patients without DIS, aHRs varied between 2.7–5.5 and specificities ranged from 73.5–89.7% for PF combinations. Conclusion: The high specificity of the 2010 McDonald criteria is confirmed. In patients without DIS, PF combinations could be helpful in identifying those at risk for MS.

scholarly journals The STING-IFN-β-Dependent Axis Is Markedly Low in Patients with Relapsing-Remitting Multiple Sclerosis

2020 ◽  
Vol 21 (23) ◽  
pp. 9249
Author(s):  
Lars Masanneck ◽  
Susann Eichler ◽  
Anna Vogelsang ◽  
Melanie Korsen ◽  
Heinz Wiendl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Type I ◽  
Autoimmune Encephalomyelitis ◽  
Beneficial Effects ◽  
Endogenous Production ◽  
Relapsing Remitting ◽  
Peripheral Lymphoid Tissue ◽  
The Central Nervous System ◽  
Peripheral Immune Cells ◽  
Relapsing Remitting Multiple Sclerosis

Cyclic GMP-AMP-synthase is a sensor of endogenous nucleic acids, which subsequently elicits a stimulator of interferon genes (STING)-dependent type I interferon (IFN) response defending us against viruses and other intracellular pathogens. This pathway can drive pathological inflammation, as documented for type I interferonopathies. In contrast, specific STING activation and subsequent IFN-β release have shown beneficial effects on experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Although less severe cases of relapse-remitting MS (RRMS) are treated with IFN-β, there is little information correlating aberrant type I IFN signaling and the pathologic conditions of MS. We hypothesized that there is a link between STING activation and the endogenous production of IFN-β during neuroinflammation. Gene expression analysis in EAE mice showed that Sting level decreased in the peripheral lymphoid tissue, while its level increased within the central nervous system over the course of the disease. Similar patterns could be verified in peripheral immune cells during the acute phases of RRMS in comparison to remitting phases and appropriately matched healthy controls. Our study is the first to provide evidence that the STING/IFN-β-axis is downregulated in RRMS patients, meriting further intensified research to understand its role in the pathophysiology of MS and potential translational applications.

scholarly journals Application of the 2017 McDonald criteria in a Chinese population with clinically isolated syndrome

2020 ◽  
Vol 13 ◽  
pp. 175628641989808
Author(s):  
Yang Zheng* ◽  
Chun-Hong Shen* ◽  
Sa Wang ◽  
Fan Yang ◽  
Meng-Ting Cai ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Diagnostic Performance ◽  
Age Of Onset ◽  
Asian Population ◽  
Tertiary Hospital ◽  
Clinically Isolated Syndrome ◽  
Chinese Patients ◽  
Mcdonald Criteria ◽  
Lower Specificity ◽  
Higher Sensitivity

Background: Diagnostic criteria for multiple sclerosis have evolved over time, with the most recent being the 2017 McDonald criteria. Evidence is lacking regarding the validity of the 2017 McDonald criteria among the Asian population. Therefore, this study aims to evaluate the diagnostic performance of the 2017 McDonald criteria in Chinese patients with clinically isolated syndrome (CIS). Methods: A total of 93 patients with initial findings suggestive of CIS in a tertiary hospital in China from 2012 to 2017 were included in this retrospective study. Baseline and follow-up data were reviewed. Diagnostic performance (sensitivity, specificity, accuracy), was assessed and survival analysis was performed for the 2017 and 2010 McDonald criteria respectively. Results: Among the 93 Chinese patients with CIS, 57 were female (61.3%) and the median (interquartile range) age of onset was 37 (31.3–41.8) years. The 2017 McDonald criteria displayed a higher sensitivity (75.0% versus 14.6%, p < 0.0001), lower specificity (47.1% versus 100.0%, p < 0.05) but an overall higher accuracy (67.7% versus 36.9%, p < 0.0001) when compared with the 2010 iteration. The novel criteria allow for a better detection of MS at baseline (40.8% versus 9.9%, p < 0.0001). Conclusion: The 2017 McDonald criteria had a higher sensitivity but lower specificity than the 2010 iteration. Overall it facilitated an earlier and more accurate diagnosis of multiple sclerosis in Chinese patients with CIS.

ANALYSIS OF THE TOPIC STUDY USING 2010 MCDONALD CRITERIA

2015 ◽  
Vol 86 (11) ◽  
pp. e4.27-e4
Author(s):  
David Rog ◽  
Jerry Wolinsky ◽  
Philippe Truffinet ◽  
Karthinathan Thangavelu ◽  
Aaron Miller
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Resonance Imaging ◽  
Mcdonald Criteria ◽  
Clinical Episode ◽  
Magnetic Resonance Imaging Lesion ◽  
Consistent Treatment ◽  
Post Hoc ◽  
Reduced Risk ◽  
Risk Of Relapse

IntroductionTOPIC (NCT00622700) was designed to evaluate teriflunomide in patients with a first clinical episode suggestive of multiple sclerosis (MS). Teriflunomide 14 mg reduced risk of relapse determining conversion to clinically definite MS by 42.6%, and of new relapse or magnetic resonance imaging lesion by 34.9% vs placebo. After study initiation, the 2005 McDonald criteria were revised, potentially allowing earlier MS diagnosis.MethodsThe 2010 McDonald criteria were applied retrospectively. Patients who received teriflunomide 14 mg or placebo for ≤108 weeks were grouped according to fulfilment of 2010 criteria at baseline. Time to MS was analysed for those not fulfilling the 2010 criteria at baseline. Additional post hoc analyses will evaluate differences in outcomes based on baseline radiological characteristics of reclassified patients.ResultsPatients receiving teriflunomide 14mg (n=214) or placebo (n=197) were analysed. For those not meeting the 2010 criteria (n=163), probability of conversion to MS was 54.1% (14 mg) and 74.4% (placebo). Teriflunomide 14mg reduced the probability of conversion to MS by 39.1% vs placebo. Data regarding time to MS based upon baseline radiological characteristics will be presented.ConclusionsTeriflunomide demonstrates a consistent treatment effect in patients with MS diagnosed according to differing diagnostic criteria. (Study supported by Genzyme, a Sanofi company).

MOG-Ab prevalence in optic neuritis and clinical predictive factors for diagnosis

2019 ◽  
Vol 104 (6) ◽  
pp. 842-845 ◽  
Author(s):  
Jean-Baptiste Ducloyer ◽  
Angelique Caignard ◽  
Ramzi Aidaoui ◽  
Yolaine Ollivier ◽  
Guillaume Plubeau ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Neuritis ◽  
Prospective Study ◽  
Predictive Factors ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Clinically Isolated Syndrome ◽  
Predictive Values ◽  
Bilateral Involvement ◽  
Optic Disc Swelling ◽  
Male Sex

ObjectiveWhat is the proportion of antibodies to myelin oligodendrocyte glycoprotein (MOG-Ab) in optic neuritis (ON) in adults and what would be the ON presentation for which MOG-Ab should be tested?MethodsMulticentric prospective study conducted during 1 year on all patients diagnosed with acute ON in all ophthalmological units in hospitals in a region in western France.ResultsSixty-five patients were included. MOG-Ab prevalence was 14% (9/65) during an acute ON and 13% (7/55) after exclusion of patients already diagnosed with multiple sclerosis (MS) (8) or MOG+ON (2). Compared with MS and clinically isolated syndrome, MOG+ON had no female preponderance (67% of men in case of MOG+ON and 22% of men in case of MS and clinically isolated syndrome, p<0.05) were more often bilateral (44% vs 3%, p<0.005) and associated with optic disc swelling (ODS) (78% vs 14%, p<0.001). To predict MOG+ON, the positive predictive values (PPVs) of male sex, ODS and bilateral involvement were 29% (95% CI 9% to 48%), 41% (95% CI 18% to 65%) and 40% (95% CI 10% to 70%), respectively, while the negative predictive values (NPV) were 93% (95% CI 86% to 100%), 96% (95% CI 90% to 100%) and 91% (95% CI 83% to 99%), respectively. The combined factor ‘ODS or bilateral or recurrent ON’ was the best compromise between PPV (31% (95% CI 14% to 48%)) and NPV (100% (95% CI 100% to 100%)).ConclusionAmong ON episodes, MOG-Ab were found in 14% of cases. MOG+ON occurred without female preponderance and was significantly associated with ODS and/or bilateral ON. Testing MOG-Ab only in patients presenting with ODS or bilateral or recurrent ON would limit MOG-Ab tests to fewer than half of all patients without the risk of missing any MOG+ON cases.

A randomized placebo-controlled cross-over study using a low frequency magnetic field in the treatment of fatigue in multiple sclerosis

2011 ◽  
Vol 18 (1) ◽  
pp. 82-89 ◽  
Author(s):  
Maria Laura Lopes de Carvalho ◽  
Roberta Motta ◽  
Giovanna Konrad ◽  
Mario Alberto Battaglia ◽  
Giampaolo Brichetto
Keyword(s):  
Magnetic Field ◽  
Multiple Sclerosis ◽  
Therapy Group ◽  
Treatment Protocol ◽  
Low Frequency ◽  
Rehabilitation Centre ◽  
Double Blind ◽  
Beneficial Effects ◽  
Frequency Magnetic Field ◽  
The Impact

Background: Fatigue is one of the most common disabling symptoms in multiple sclerosis (MS). There is growing evidence in the literature for beneficial effects of magnetic fields on different MS symptoms and this has been reported to be beneficial in patients with MS, especially those with fatigue. Objectives: The aim of the study was to assess the effects on primary fatigue with a pulsed systemic low frequency magnetic field by means of clinical scales in a population of MS subjects. Methods: Randomized double-blind cross-over trial with 50 MS subjects with primary fatigue who were recruited among those followed as outpatients at the AISM Rehabilitation Centre, Genova, Italy. Subjects were randomized into two groups: magnetic field group and sham therapy group and evaluated with the Modified Fatigue Impact Scale (MFIS), the Fatigue Severity Scale (FSS), VAS and Time Walking Test 10 meter (TWT10m.) at the time points of the study. Each group received both sham therapy and magnetic field therapy with a wash-out period of 5 months. Subjects were treated for 24 min per session, three times per week, for 8 weeks. Statistical analysis was performed using multivariate analysis. Results: Results showed a statistically significant improvement in MFIS Physical Score for T0 − T1 ( p < 0.05) for TIME but not for TREATMENT and TIME*TREATMENT factors. No statistically significant differences were found for all other parameters considered in the study. Conclusions: Exposure to a low frequency magnetic field, within the parameters of this treatment protocol, has no advantage over sham exposure in reducing the impact of fatigue.

scholarly journals Evaluation of Demographic, Clinical and Beyond Clinical Characteristics in Patients with Multiple Sclerosis in Rafsanjan City, Iran

2017 ◽  
Vol 2 (2) ◽  
pp. 63
Author(s):  
Amir Moghaddamahmadi ◽  
Pouria Yazdian-Anari ◽  
Siamak Kazemisufi ◽  
Alireza Vakilian ◽  
Aliasghar Ranjbartotoei ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Characteristics ◽  
Demographic Data ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Female Ratio ◽  
Mcdonald Criteria ◽  
Male Female Ratio ◽  
The Central Nervous System ◽  
The Mean

Background and objectives: Multiple sclerosis is a chronic and progressive autoimmune disease of the central nervous system that causes motor and sensory impairment and physical disability in patients. This study was conducted to determine the demographic, clinical, and beyond clinical characteristics in patients with multiple sclerosis to help identify common disabilities and better understand of the specific needs of these ones.Materials and methods: This descriptive cross-sectional study was carried out on 50 MS patients in Rafsanjan, Iran. A definitive diagnosis has been done according to neurologist and McDonald criteria. The neurologist conducted examinations. The demographic data were recorded using questionnaire. MRI images were analyzed with the help of radiologist and all data were analyzed using SPSS software.Results: The mean age was 33.81±8.38 years and male/female ratio was 7/42. According to data, 66.7% of the patients were suffering from relapsing-remitting type (RR) disease, and most lesions on MRI in these patients were observed in pyramidal and JuxtaCortical areas. The mean EDSS scores of patients was 1.46. The duration of disease and the number of attacks had a significant correlation with educational level (P<0.05); age was significantly associated with pyramidal, mental and sphincter symptoms (P<0.05).Conclusion: These results suggest that the prevalence of MS in women is higher than in men, especially among housekeeper women. Relapsing and remitting disease showed higher frequency.

scholarly journals Periventricular lesions and MS diagnostic criteria in young adults with typical clinically isolated syndromes

2016 ◽  
Vol 23 (7) ◽  
pp. 1031-1034 ◽  
Author(s):  
Wallace J Brownlee ◽  
Katherine A Miszkiel ◽  
Daniel R Altmann ◽  
Olga Ciccarelli ◽  
David H Miller
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Clinically Isolated Syndrome ◽  
Resonance Imaging ◽  
Mcdonald Criteria ◽  
Specificity And Sensitivity ◽  
Magnetic Resonance Imaging Mri ◽  
Periventricular Lesions ◽  
Periventricular Lesion

In patients who present with a clinically isolated syndrome (CIS), whose features are suggestive of multiple sclerosis (MS), fulfilling McDonald 2010 magnetic resonance imaging (MRI) criteria for dissemination in space (DIS) and dissemination in time (DIT) enables a diagnosis of MS. While ⩾1 periventricular lesion is included in the 2010 DIS criteria, earlier McDonald criteria required ⩾3 periventricular lesions to confirm DIS and recent Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS)-recommended DIS criteria also require ⩾3 lesions. We investigated the effect of varying the required number of periventricular lesions and found that the best combination of specificity and sensitivity for clinically definite MS was seen for ⩾1 periventricular lesion using both the McDonald 2010 and MAGNIMS 2016 criteria.

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