MRI Criteria For Dissemination Research Articles

The diagnostic workup of children with the radiologically isolated syndrome differs by age and by sex.

Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown. To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests. We analyzed children (≤ 18y) with RIS enrolled in an international longitudinal study. Index scans met 2010/2017 multiple sclerosis (MS) MRI criteria for dissemination in space (DIS). We used Fisher's exact test and multivariable logistic regression (covariates = age, sex, MRI date, MRI indication, 2005 MRI DIS criteria met, and race). We included 103 children with RIS (67% girls, median age = 14.9y). Children ≥ 12y were more likely than children < 12y to have CSF obtained (58% vs. 21%, adjusted odds ratio [AOR] = 4.9, p = 0.03). Pre-2017, girls were more likely than boys to have CSF obtained (n = 70, 79% vs. 52%, AOR = 4.6, p = 0.01), but not more recently (n = 30, 75% vs. 80%, AOR = 0.2, p = 0.1; p = 0.004 for interaction). Spinal MRIs were obtained sooner in children ≥ 12y (median 11d vs. 159d, p = 0.03). Younger children with RIS may be at continued risk for misdiagnosis and misclassification of MS risk. Consensus guidelines are needed.

Oligoclonal Bands in Spinal Fluid Improve the Specificity of Different MRI Criteria for Dissemination in Space to Predict a First Clinical Event in Children with the Radiologically Isolated Syndrome (S51.002)

Oligoclonal Bands in Spinal Fluid Improve the Specificity of Different MRI Criteria for Dissemination in Space to Predict a First Clinical Event in Children with the Radiologically Isolated Syndrome (S51.002)

Editors' Note

Editors' Note: Regarding “The contemporary spectrum of multiple sclerosis misdiagnosis: A multicenter study,” Dalla Costa et al. express concerns about the interpretation of results because of the number of patients screened, the clinical and paraclinical characteristics of the misdiagnosed patients, and the lack of specification of fulfilled multiple sclerosis (MS) criteria through which the diagnosis was made. Solomon et al., authors of the study, explain that the study was not designed to assess the frequency of MS misdiagnosis or its specific causes. They add that application of MS diagnostic criteria to a neurologic syndrome not typical for MS contributed to misdiagnosis in 65% of cases, and that in 60% of cases, using MRI criteria for dissemination in space in a patient with nonspecific symptoms contributed to misdiagnosis. Commenting on “Early start of DOAC after ischemic stroke: Risk of intracranial hemorrhage and recurrent events,” Prof. Kawada argues that larger patient cohorts more accurately estimate the risk of intracranial hemorrhage (ICH) from direct, non–vitamin K antagonist oral anticoagulants (DOACs). Seiffge et al., authors of the study, agree but point out that they looked at symptomatic ICH only and a well-designed randomized clinical trial is necessary to address timing of DOAC after ischemic stroke due to nonvalvular atrial fibrillation. —Chafic Karam, MD, and Robert C. Griggs, MD Editors' Note: Regarding “The contemporary spectrum of multiple sclerosis misdiagnosis: A multicenter study,” Dalla Costa et al. express concerns about the interpretation of results because of the number of patients screened, the clinical and paraclinical characteristics of the misdiagnosed patients, and the lack of specification of fulfilled multiple sclerosis (MS) criteria through which the diagnosis was made. Solomon et al., authors of the study, explain that the study was not designed to assess the frequency of MS misdiagnosis or its specific causes.

Author response: The contemporary spectrum of multiple sclerosis misdiagnosis: A multicenter study.

We appreciate the comments of Dalla Costa et al. on our Contemporary Issues article.1 As discussed, this study was not designed to assess the frequency of multiple sclerosis (MS) misdiagnosis or its specific causes.1 We catalogued the diagnoses ultimately assigned to patients mistaken as having MS and reported the evaluation of the MS specialists who determined that a misdiagnosis had occurred according to their analysis of what led to misdiagnosis. Accepting this limitation, application of MS diagnostic criteria to a neurologic syndrome not typical for MS contributed to misdiagnosis in 65% of cases.1 MS diagnostic criteria fail in this situation, but are often applied in clinical practice. In 60% of cases, declaring MRI criteria for dissemination in space satisfied in a patient with nonspecific symptoms contributed to misdiagnosis.1 Ultimately, these 2 errors perpetuate one another. Nonspecific symptoms acquire additional and unwarranted attention when nonspecific MRI lesions are present, and nonspecific MRI lesions are accorded undue attention in the presence of symptoms of common conditions such as migraine. Further studies should establish the frequency of misdiagnosis, but the combination of nonspecific symptoms and nonspecific MRI abnormalities is likely a common contemporary source of MS misdiagnosis.

Update on clinically isolated syndrome

Optic neuritis, myelitis and brainstem syndrome accompanied by a symptomatic MRI T2 or FLAIR hyperintensity and T1 hypointensity are highly suggestive of multiple sclerosis (MS) in young adults. They are called "clinically isolated syndrome" (CIS) and correspond to the typical first multiple sclerosis (MS) episode, especially when associated with other asymptomatic demyelinating lesions, without clinical, radiological and immunological sign of differential diagnosis. After a CIS, the delay of apparition of a relapse, which corresponds to the conversion to clinically definite MS (CDMS), varies from several months to more than 10 years (10-15% of cases, generally called benign RRMS). This delay is generally associated with the number and location of demyelinating lesions of the brain and spinal cord and the results of CSF analysis. Several studies comparing different MRI criteria for dissemination in space and dissemination in time of demyelinating lesions, two hallmarks of MS, provided enough substantial data to update diagnostic criteria for MS after a CIS. In the last revision of the McDonald's criteria in 2010, diagnostic criteria were simplified and now the diagnosis can be made by a single initial scan that proves the presence of active asymptomatic lesions (with gadolinium enhancement) and of unenhanced lesions. However, time to conversion remains highly unpredictable for a given patient and CIS can remain isolated, especially for idiopathic unilateral optic neuritis or myelitis. Univariate analyses of clinical, radiological, biological or electrophysiological characteristics of CIS patients in small series identified numerous risk factors of rapid conversion to MS. However, large series of CIS patients analyzing several characteristics of CIS patients and the influence of disease modifying therapies brought important information about the risk of CDMS or RRMS over up to 20 years of follow-up. They confirmed the importance of the initial MRI pattern of demyelinating lesions and of CSF oligoclonal bands. Available treatments of MS (immunomodulators or immunosuppressants) have also shown unequivocal efficacy to slow the conversion to RRMS after a CIS, but they could be unnecessary for patients with benign RRMS. Beyond diagnostic criteria, knowledge of established and potential risk factors of conversion to MS and of disability progression is essential for CIS patients' follow-up and initiation of disease modifying therapies.

A search for new MRI criteria for dissemination in space in subjects with a clinically isolated syndrome

The International Panel on the Diagnosis of Multiple Sclerosis (MS) incorporated the Barkhof/Tintoré (B/T) magnetic resonance criteria into their diagnostic scheme to provide evidence of dissemination in space of central nervous system lesions, a prerequisite for diagnosing MS in patients who present with clinically isolated syndromes (CIS). Although specific for MS, the B/T criteria were criticised for their low sensitivity and relative complexity in clinical use. We used lesion characteristics at onset from 349 CIS patients in logistic regression and recursive partitioning modelling in a search for simpler and more sensitive criteria, while maintaining current specificity. The resulting models, all based on the presence of periventricular and deep white matter lesions, performed roughly in agreement with the B/T criteria, but were unable to provide higher diagnostic accuracy based on information from a single scan. Apparently, findings from contrast-enhanced and follow-up magnetic resonance scans are needed to improve the diagnostic algorithm.

Accuracy of CSF and MRI criteria for dissemination in space in the diagnosis of multiple sclerosis

Demonstration of lesion dissemination in space (DIS) and time (DIT) is necessary for the diagnosis of multiple sclerosis (MS) in clinically isolated syndromes (CIS). The McDonald criteria accepted two methods to demonstrate DIS. The fulfillment of at least three of four MRI Barkhof criteria (MRI-BC) or, alternatively, the finding of at least two MRI lesions on T2-weighted images (T2 lesions) plus the presence of oligoclonal IgG bands (OCGB) in cerebrospinal fluid (CSF). We aimed to evaluate the accuracy of both methods for DIS demonstration to predict conversion of CIS to MS using a new OCGB test. We studied fifty-eight CIS patients with OCGB detection and brain MRI, and followed them up during 6 years. Twenty-eight patients fulfilled MRI-BC. Twenty-five of them converted to MS during follow-up (sensitivity 73.53%, specificity 87.50%, accuracy 79.31%). Thirty-four patients had at least two T2 lesions plus oligoclonal bands. Thirty-three converted to MS during follow-up (sensitivity 94.29%, specificity 95.65%, accuracy 94.82%). The presence of oligoclonal IgG bands plus two T2 lesions accurately predicts CIS conversion to MS. MRI-BC criteria have a high specificity but less sensitivity and accuracy. These results reinforce the role of CSF study in MS diagnosis.

MRI criteria for dissemination in space in patients with clinically isolated syndromes: a multicentre follow-up study

The McDonald International Panel accepted the Barkhof/Tintoré criteria for providing MRI evidence of dissemination in space to allow a diagnosis of multiple sclerosis in patients with clinically isolated syndromes (CIS). We applied these criteria in a large cohort of patients with CIS, representative of those seen in a general diagnostic setting, to assess their accuracy in predicting conversion to definite multiple sclerosis and to identify factors that affect this risk. In a collaborative study of seven centres, baseline MRI and clinical follow-up data for 532 patients with CIS were studied, with the development of a second clinical event used as the main outcome. All scans were scored for lesion counts and spatial lesion distribution to assess the fulfilment--ie, at least three out of four--of the Barkhof/Tintoré criteria. We used survival analysis and 2x2 tables to assess the test characteristics of the criteria at baseline. Overall conversion rate was 32.5% with a median survival time of 85.3 months. Fulfilment of the criteria at baseline showed, after a survival time of 2 years, a conversion rate of about 45% (95% CI 37-53) versus about 10% (6-16) in those with no asymptomatic lesions at baseline (p<0.0001). For patients with a follow-up of at least 2 years, the fulfilment of the MRI criteria showed an accuracy of 68% (sensitivity 49%, specificity 79%) for predicting conversion and an increase in risk of nearly four times for conversion compared with those not fulfilling the criteria (odds ratio 3.7, 95% CI 2.3-5.9; p<0.0001). Cox proportional hazards regression analysis accorded with this increased risk. No effects were recorded on the performance of the criteria by sex, presenting symptoms, or centre. Age at baseline did have a small but significant effect as predictor (hazard ratio 0.97, 0.95-0.99; p=0.002), but did not affect the prognostic value of the MRI criteria. MRI abnormalities have important prognostic value. The cut-off, based on the Barkhof/Tintoré criteria, as incorporated in the McDonald diagnostic scheme yields acceptable specificity, but could have lower sensitivity than previously reported.