Articles Introduction In 2001, the McDonald International Panel proposed a new diagnostic scheme for the diagnosis of multiple sclerosis, 1 which replaced previous criteria by Poser and colleagues. 2 A novel feature of this scheme is that in patients with clinically isolated syndromes(CIS) suggestive of demyelination, evidence for dissemination in time and space, essential for a diagnosis of multiple sclerosis, can be provided with MRI alone. Dissemination in space can be identified by meeting three of four Barkhof/Tintoré criteria 3,4 or, alternatively, by showing at least two lesions plus the presence of oligoclonal bands in CSF. The MRI criteria were originally developed by Barkhof and colleagues 3 as a dichotomised cumulative chance model to predict, at baseline scan, the development of clinically definite multiple sclerosis in patients with CIS. This model was modified by Tintoré and colleagues, 4 who showed that fulfilling three of four Barkhof criteria had higher accuracy and specificity in predicting conversion to clinically definite multiple sclerosis than did other available MRI criteria. Because of their specificity for multiple sclerosis, the McDonald International Panel incorporated these dichotomised Barkhof/Tintoré criteria into their schemeto show dissemination in space on MRI. Additionally, these new criteria can also convey prognostic information because fulfilling these criteria implied a certain risk for conversion to clinically definite multiple sclerosis in patients with CIS in the original model. Barkhof, Tintoré, and their colleagues developed the MRI criteria in small studies; 74 and 70 patients, respectively. They showed good accuracy when applied in other cohorts. 5,6 Again, those studies used only a few patients, often derived from a single or a few centres, which may have caused selection bias. Furthermore, the follow-up period was typically short (2–3 years) relative to the protracted course of the disease. Two larger studies were undertaken in patients with CIS, which assessed the ability of baseline MRI characteristics to predict the early development of clinically definite multiple sclerosis in CIS: the Early Treatment of Multiple Sclerosis (ETOMS) study and the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS). 7–9 Both Lancet Neurol 2006; 5: 221–27 Published Online January 30, 2006 DOI:10.1016/S1474-4422(06) 70353-2 Department of Neuroradiology (T Korteweg MD, F Barkhof MD, B Uitdehaag MD), Department of Clinical Epidemiology and Biostatistics (B Uitdehaag), and Department of Neurology (C Polman MD, B Uitdehaag), VU University Medical Centre, Amsterdam, Netherlands; Department of Neuroimmunology (M Tintoré MD, X Montalban MD) and Department of Radiology, Magnetic Resonance Unit (A Rovira MD), Hospital Vall d’Hebron, Barcelona, Spain; The MS Clinic, Department of Neurology, University of Copenhagen, Glostrup Hospital, Denmark (J Frederiksen MD); MS NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, University College London, London, UK (D Miller FRCP, K Fernando MRCP); Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy (M Filippi MD, F Agosta MD, M Rocca MD); Department of Neurology, Medical University Graz, Graz, Austria (F Fazekas MD, C Enzinger MD); Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford, UK (P Matthews FRCP, A Parry MRCP) Correspondence to: Tijmen Korteweg, VU University Medical Centre, Department of Radiology, De Boelelaan 1118, 1081 HV Amsterdam, Netherlands T.Korteweg@vumc.nl http://neurology.thelancet.com Vol 5 March 2006 221 Tijmen Korteweg, Mar Tintoré, Bernard Uitdehaag, Alex Rovira, Jette Frederiksen, David Miller, Kryshani Fernando, Massimo Filipp Federica Agosta, Maria Rocca, Franz Fazekas, Christian Enzinger, Paul Matthews, Allyson Parry, Chris Polman, Xavier Montalban, Frederik Barkhof Summary Background The McDonald International Panel accepted the Barkhof/Tintoré criteria for providing MRI evidenc dissemination in space to allow a diagnosis of multiple sclerosis in patients with clinically isolated syndrome We applied these criteria in a large cohort of patients with CIS, representative of those seen in a general dia setting, to assess their accuracy in predicting conversion to definite multiple sclerosis and to identify factors affect this risk. Methods In a collaborative study of seven centres, baseline MRI and clinical follow-up data for 532 patients w were studied, with the development of a second clinical event used as the main outcome. All scans were scor lesion counts and spatial lesion distribution to assess the fulfilment—ie, at least three out of four— Barkhof/Tintoré criteria. We used survival analysis and 2⫻2 tables to assess the test characteristics of the cr baseline. Findings Overall conversion rate was 32·5% with a median survival time of 85·3 months. Fulfilment of the crite baseline showed, after a survival time of 2 years, a conversion rate of about 45% (95% CI 37–53) versus abou (6–16) in those with no asymptomatic lesions at baseline (p⬍0·0001). For patients with a follow-up of at leas the fulfilment of the MRI criteria showed an accuracy of 68% (sensitivity 49%, specificity 79%) for p conversion and an increase in risk of nearly four times for conversion compared with those not fulfilling the c (odds ratio 3·7, 95% CI 2·3–5·9; p⬍0·0001). Cox proportional hazards regression analysis accorded wi increased risk. No effects were recorded on the performance of the criteria by sex, presenting symptoms, or Age at baseline did have a small but significant effect as predictor (hazard ratio 0·97, 0·95–0·99; p=0·002), b not affect the prognostic value of the MRI criteria. Interpretation MRI abnormalities have important prognostic value. The cut-off, based on the Barkhof/Tin criteria, as incorporated in the McDonald diagnostic scheme yields acceptable specificity, but could h sensitivity than previously reported. MRI criteria for dissemination in space in patients with clinically isolated syndromes: a multicentre follow-up study