Performance of the 2017 and 2010 Revised McDonald Criteria in Predicting MS Diagnosis After a Clinically Isolated Syndrome

Background and ObjectivesTo compare the performance of the 2017 revisions to the McDonald criteria with the 2010 McDonald criteria in establishing MS diagnosis and predicting prognosis in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS).MethodsCSF examination, brain and spinal cord MRI obtained ≤5 months from CIS onset, and a follow-up brain MRI acquired within 15 months from CIS onset were evaluated in 785 CIS patients from 9 European centers. Date of second clinical attack and of reaching Expanded Disability Status Score (EDSS) ≥ 3.0, if they occurred, were also collected. Performance of the 2017 and 2010 McDonald criteria for dissemination in space (DIS), time (DIT) (including oligoclonal bands assessment) and DIS + DIT for predicting a second clinical attack (clinically definite [CD] MS) and EDSS ≥ 3.0 at follow-up was evaluated. Time to MS diagnosis for the different criteria was also estimated.ResultsAt follow-up (median = 69.1 months), 406/785 CIS patients developed CDMS. At 36 months, the 2017 DIS + DIT criteria had higher sensitivity (0.83 vs 0.66), lower specificity (0.39 vs 0.60) and similar area under the curve values (0.61 vs 0.63). Median time to MS diagnosis was shorter with the 2017 vs the 2010 or CDMS criteria (2017 revision = 3.2; 2010 revision = 13.0; CDMS = 58.5 months). The 2 sets of criteria similarly predicted EDSS ≥ 3.0 milestone. Three periventricular lesions improved specificity in patients ≥45 years.DiscussionThe 2017 McDonald criteria showed higher sensitivity, lower specificity and similar accuracy in predicting CDMS compared to 2010 McDonald criteria, while shortening time to diagnosis of MS.Classification of EvidenceThis study provides Class II evidence that the 2017 McDonald Criteria more accurately distinguish CDMS in patients early after a CIS when compared to the 2010 McDonald criteria.

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Early predictors of multiple sclerosis after a typical clinically isolated syndrome

Multiple Sclerosis Journal ◽

10.1177/1352458514533397 ◽

2014 ◽

Vol 20 (13) ◽

pp. 1721-1726 ◽

Cited By ~ 24

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.

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

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286419898083 ◽

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.

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Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study

Multiple Sclerosis Journal ◽

10.1177/1352458514568827 ◽

2015 ◽

Vol 21 (8) ◽

pp. 1013-1024 ◽

Cited By ~ 143

Author(s):

J Kuhle ◽

G Disanto ◽

R Dobson ◽

R Adiutori ◽

L Bianchi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinically Isolated Syndrome ◽

Nuclear Antigen ◽

Oligoclonal Bands ◽

Serum Samples ◽

T2 Lesions ◽

Definite Multiple Sclerosis ◽

Epstein Barr ◽

Csf Oligoclonal Bands

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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Improved performance of the 2017 McDonald criteria for diagnosis of multiple sclerosis in children in a real-life cohort

Multiple Sclerosis Journal ◽

10.1177/1352458519863781 ◽

2019 ◽

Vol 26 (11) ◽

pp. 1372-1380 ◽

Cited By ~ 4

Author(s):

Yael Hacohen ◽

Wallace Brownlee ◽

Kshitij Mankad ◽

Wui K ‘Kling’ Chong ◽

Alan Thompson ◽

...

Keyword(s):

Multiple Sclerosis ◽

Real Life ◽

Oligoclonal Bands ◽

Resonance Imaging ◽

Multi Centre Study ◽

Mcdonald Criteria ◽

Improved Performance ◽

Magnetic Resonance Imaging Mri ◽

Criteria For Diagnosis ◽

Higher Sensitivity

Objective: To compare the performance of the 2017 McDonald criteria with that of the 2010 criteria for the diagnosis of multiple sclerosis (MS) in children in the clinical setting. Methods: In this retrospective, multi-centre study, we identified children who presented with symptoms suggestive of a clinically isolated syndrome (CIS) and were followed up for at least 2 years or until their second attack. Results: Of 156 children with CIS followed up for a median of 4.17 years, 94 (60.3%) were diagnosed with MS. In all, 83 (88.3%) of these fulfilled the 2010 dissemination in space (DIS) criteria at onset. Three additional children fulfilled the 2017 DIS criteria because of the inclusion of symptomatic lesions. Of the 59 children with MS who underwent post-gadolinium magnetic resonance imaging (MRI), 44 (74.6%) fulfilled the 2010 dissemination in time (DIT) criteria at baseline. When the presence of oligoclonal bands (OCBs) was used to substitute DIT, an additional 35 children (79/94, 84.0%) were diagnosed with MS according to the 2017 criteria. The 2017 criteria had higher accuracy (87.2% vs 66.7%), higher sensitivity (84.0% vs 46.8%), but reduced specificity (91.9% vs 96.8%) when compared to the 2010 criteria. Conclusion: The improved performance of the 2017 criteria when compared to the 2010 criteria was predominantly due to the inclusion of intrathecal OCBs.

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

Multiple Sclerosis Journal ◽

10.1177/1352458516667565 ◽

2016 ◽

Vol 23 (7) ◽

pp. 1031-1034 ◽

Cited By ~ 15

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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Predictive factors for multiple sclerosis in patients with clinically isolated spinal cord syndrome

Multiple Sclerosis Journal ◽

10.1177/1352458510386999 ◽

2010 ◽

Vol 17 (3) ◽

pp. 312-318 ◽

Cited By ~ 26

Author(s):

Aurélie Ruet ◽

Mathilde SA Deloire ◽

Jean-Christophe Ouallet ◽

Sandrine Molinier ◽

Bruno Brochet

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Brain Mri ◽

Predictive Values ◽

Logistic Analysis ◽

Mcdonald Criteria ◽

Clinical Magnetic Resonance Imaging ◽

Clinical Episode ◽

Intrathecal Igg Synthesis ◽

Periventricular Lesions

Objectives: To identify predictors of conversion to definite multiple sclerosis (MS) in patients with a cord clinically isolated syndrome. Methods: The predictive values for conversion to MS of clinical, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) variables in 114 patients with acute partial myelitis confirmed by a spinal cord lesion on MRI were studied. Other causes of cord syndromes were excluded. Results: MS was diagnosed in 78 patients (86%) during 4.0 ± 1.9 years of follow-up. Some 67 of these patients had a second clinical episode. The diagnosis of isolated myelitis was maintained for 36 patients, 78% of whom (28 cases) were followed for at least 2 years, comparable to the MS patients. Age, bladder involvement, ≥2 cord lesions on MRI, ≥9 brain lesions, ≥3 periventricular lesions and intrathecal IgG synthesis predicted conversion to clinically definite MS. Multivariate logistic analysis identified three predictors of MS diagnosis: age ≤40 years, inflammatory CSF and ≥3 periventricular lesions on brain MRI. Conclusion: Two out of three baseline factors (age, periventricular lesions and inflammatory CSF) predicted conversion to MS with better accuracy than the revised McDonald criteria for dissemination in space.

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No evidence of disease activity is associated with reduced rate of axonal retinal atrophy in MS

Neurology ◽

10.1212/wnl.0000000000004736 ◽

2017 ◽

Vol 89 (24) ◽

pp. 2469-2475 ◽

Cited By ~ 20

Author(s):

Marco Pisa ◽

Simone Guerrieri ◽

Giovanni Di Maggio ◽

Stefania Medaglini ◽

Lucia Moiola ◽

...

Keyword(s):

Disease Activity ◽

Operating Characteristic ◽

Characteristic Curve ◽

Brain Mri ◽

Area Under The Curve ◽

Fiber Layer ◽

Additional Tool ◽

Disability Status ◽

Reduced Rate

Objective:To explore, in a longitudinal study, the usefulness of optical coherence tomography (OCT) in monitoring people with multiple sclerosis (MS) by testing the association between retinal nerve fiber layer (RNFL) thinning and clinical and brain MRI criteria of no evidence of disease activity (NEDA).Methods:OCT, visual evoked potentials (VEPs), and disability, using the Expanded Disability Status Scale (EDSS), were tested at baseline and after 2 years in 72 patients, 63 with routine yearly brain MRI.Results:Longitudinal mean binocular RNFL thinning, in absence of optic neuritis during follow-up, was correlated with EDSS worsening, also controlling for baseline EDSS, RNFL, disease duration, and MS subtype (Spearman ρ −0.462, p < 0.001; partial correlation coefficient −0.437, p < 0.001). At follow-up, patients classified as NEDA (20; 31.7%) had RNFL loss of −0.93 μm ± 1.35 SD, while patients with active disease had −2.83 μm ± 2 SD thinning (t test; p < 0.001). At logistic regression, mean RNFL reduction correctly classified 76.2% of patients as NEDA at 2 years (R2 0.355; p = 0.003). A cutoff of −1.25 μm RNFL loss classified NEDA status with specificity 81.4% and sensitivity 80% (receiver operating characteristic curve: area under the curve 0.8; p < 0.001). No significant longitudinal correlations were found between changes in RNFL and in VEP latencies or scores.Conclusions:NEDA is associated with a relatively preserved RNFL over 2 years. A greater neuroretinal loss was detected even in patients with clinical evidence of disease activity independently from changes in brain MRI lesions, prompting further validation of OCT as an additional tool in MS monitoring.

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The Usefulness of Gadolinium-Enhanced Images on a Follow-up Magnetic Resonance Image in Suspected Multiple Sclerosis

Canadian Association of Radiologists Journal ◽

10.1016/j.carj.2012.07.003 ◽

2013 ◽

Vol 64 (4) ◽

pp. 358-362 ◽

Cited By ~ 1

Author(s):

Fraser G.A. Moore ◽

Mark Levental

Keyword(s):

Multiple Sclerosis ◽

Magnetic Resonance ◽

Primary Outcome ◽

Brain Mri ◽

Brain Magnetic Resonance Imaging ◽

Clinically Isolated Syndrome ◽

Space And Time ◽

Scan Time ◽

Number Of Patients

Purpose Multiple sclerosis diagnostic criteria include the presence of gadolinium-enhancing lesions when determining dissemination in space and time. Gadolinium is expensive, increases scan time and patient discomfort, and can, rarely, cause serious adverse effects. Our objective was to determine the usefulness of including gadolinium-enhanced images as part of a follow-up brain magnetic resonance imaging (MRI) in patients with a clinically isolated syndrome. Methods Consecutive patients seen between 2008 and 2010 with a clinically isolated syndrome suggestive of multiple sclerosis were prospectively enrolled, had a non–gadolinium-enhanced brain MRI, and consented to a follow-up gadolinium-enhanced brain MRI. The primary outcome was a comparison of the number of patients diagnosed with multiple sclerosis compared with the number who would have been diagnosed without the gadolinium-enhanced images. Results Twenty-one patients enrolled, and 2 withdrew. Follow-up MRIs were performed a median of 241 days after the initial MRI. Eleven patients met the primary outcome and were diagnosed with multiple sclerosis: 6 as a result of a second clinical attack and 5 by using imaging criteria for dissemination in space and time. If the gadolinium-enhanced images had not been obtained, then there would have been no change in the primary outcome. Conclusions In Canadian centers with similar MRI waiting times to those in our study, the routine use of gadolinium as part of a follow-up MRI in patients with suspected multiple sclerosis may not be clinically useful. Gadolinium-enhanced images could still be obtained on an as-needed basis for specific clinical indications.

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Predicting Aggressive Multiple Sclerosis With Intrathecal IgM Synthesis Among Patients With a Clinically Isolated Syndrome

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000001047 ◽

2021 ◽

Vol 8 (5) ◽

pp. e1047

Author(s):

Enric Monreal ◽

Susana Sainz de la Maza ◽

Lucienne Costa-Frossard ◽

Paulette Walo-Delgado ◽

Javier Zamora ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Onset ◽

Clinically Isolated Syndrome ◽

Oligoclonal Bands ◽

Expanded Disability Status Scale ◽

Disability Status ◽

Patients At Risk ◽

Worse Prognosis

ObjectiveTo determine the best method to measure intrathecal immunoglobulin (Ig) M synthesis (ITMS), a biomarker of worse prognosis in multiple sclerosis (MS). We compared the ability for predicting a poor evolution of 4 methods assessing ITMS (IgM oligoclonal bands [OCMBs], lipid-specific OCMBs [LS-OCMBs], Reibergram, and IgM index) in patients with a clinically isolated syndrome (CIS).MethodsProspective study with consecutive patients performed at a referral MS center. We used unadjusted and multivariate Cox regressions for predicting a second relapse, Expanded Disability Status Scale (EDSS) scores of 4 and 6, and development of secondary progressive MS (SPMS).ResultsA total of 193 patients were included, with a median (interquartile range) age of 31 (25–38) years and a median follow-up of 12.9 years. Among all methods, only OCMB, LS-OCMB, and Reibergram significantly identified patients at risk of some of the pre-established outcomes, being LS-OCMB the technique with the strongest associations. Adjusted hazard ratio (aHR) of LS-OCMB for predicting a second relapse was 2.50 (95% CI 1.72–3.64, p < 0.001). The risk of reaching EDSS scores of 4 and 6 and SPMS was significantly higher among patients with LS-OCMB (aHR 2.96, 95% CI 1.54–5.71, p = 0.001; aHR 4.96, 95% CI 2.22–11.07, p < 0.001; and aHR 2.31, 95% CI 1.08–4.93, p = 0.03, respectively).ConclusionsITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB.Classification of EvidenceThis study provides Class II evidence that lipid-specific IgM oligoclonal bands can predict progression from CIS to MS and a worse disease course over a follow-up of at least 2 years.

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Reiber’s Diagram for Kappa Free Light Chains: The New Standard for Assessing Intrathecal Synthesis?

Diagnostics ◽

10.3390/diagnostics9040194 ◽

2019 ◽

Vol 9 (4) ◽

pp. 194 ◽

Cited By ~ 2

Author(s):

Philipp Schwenkenbecher ◽

Franz Felix Konen ◽

Ulrich Wurster ◽

Torsten Witte ◽

Stefan Gingele ◽

...

Keyword(s):

Linear Function ◽

Oligoclonal Bands ◽

Light Chains ◽

Hyperbolic Function ◽

Free Light Chains ◽

Mcdonald Criteria ◽

Relapsing Multiple Sclerosis ◽

Automated Determination

Oligoclonal bands are the gold standard for determination of an intrathecal immunoglobulin G synthesis and were recently included in the McDonald criteria of 2017 to diagnose relapsing multiple sclerosis (MS) as a substitute for dissemination in time. Intrathecally produced kappa free light chains (KFLC) are a novel promising biomarker with similar characteristics and the advantage for automated determination. However, different approaches exist to determine the intrathecal KFLC fraction. The most common method is to calculate the CSF/serum KFLC quotient with reference to the albumin CSF/serum quotient (QKappa/QAlb) the so-called KFLC index. Recently, Reiber developed a theoretically and empirically founded hyperbolic function similar to his traditional hyperbolic function for the immunoglobulins A, G, M. Our study included a total of 168 patients with either MS according to the McDonald criteria of 2017, clinically isolated syndrome (CIS) with conversion to MS during follow-up, or stable CIS. Positive oligoclonal bands were compared with the KFLC index, Reiber’s KFLC diagram, Presslauer’s KFLC exponential curve, and Senel’s linear curve for KFLC. Reiber’s diagram detected an intrathecal production of KFLC in 98/100 patients with MS, only one patient fewer than oligoclonal bands positivity (99/100). By using the KFLC index ≥ 5.9, Presslauer’s KFLC exponential function, and Senel’s linear curve two more patients would not have been identified (96/100). For the group of patients who converted from CIS to MS similar results were obtained for both the oligoclonal bands and the Reiber graph (21/24, 88%). The KFLC index ≥ 5.9, Presslauer’s method, and Senel’s linear function each identified two patients fewer (19/24, 79%). In patients with stable CIS, 11/44 patients (25%) displayed oligoclonal bands in contrast to 9/44 patients (20%) with elevated KFLC by using Reiber’s diagram and Presslauer’s method, 8/44 patients (18%) with elevated KFLC as detected by Senel’s linear function, and 7/44 patients (16%) with KFLC index ≥ 5.9. In conclusion, Reiber’s KFLC diagram shows a great diagnostic performance to detect an intrathecal KFLC production in patients with MS.

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