BACKGROUND: In 2016, the Magnetic Resonance Imaging in Multiple Sclerosis 
(MAGNIMS) network proposed modifications to the MRI criteria to define 
dissemination in space (DIS) and time (DIT) for the diagnosis of multiple 
sclerosis in patients with clinically isolated syndrome (CIS). Changes to the 
DIS definition included removal of the distinction between symptomatic and 
asymptomatic lesions, increasing the number of lesions needed to define 
periventricular involvement to three, combining cortical and juxtacortical 
lesions, and inclusion of optic nerve evaluation. For DIT, removal of the 
distinction between symptomatic and asymptomatic lesions was suggested. We 
compared the performance of the 2010 McDonald and 2016 MAGNIMS criteria for 
multiple sclerosis diagnosis in a large multicentre cohort of patients with CIS 
to provide evidence to guide revisions of multiple sclerosis diagnostic 
criteria.
METHODS: Brain and spinal cord MRI and optic nerve assessments from patients 
with typical CIS suggestive of multiple sclerosis done less than 3 months from 
clinical onset in eight European multiple sclerosis centres were included in 
this retrospective study. Eligible patients were 16-60 years, and had a first 
CIS suggestive of CNS demyelination and typical of relapsing-remitting multiple 
sclerosis, a complete neurological examination, a baseline brain and spinal cord 
MRI scan obtained less than 3 months from clinical onset, and a follow-up brain 
scan obtained less than 12 months from CIS onset. We recorded occurrence of a 
second clinical attack (clinically definite multiple sclerosis) at months 36 and 
60. We evaluated MRI criteria performance for DIS, DIT, and DIS plus DIT with a 
time-dependent receiver operating characteristic curve analysis.
FINDINGS: Between June 16, 1995, and Jan 27, 2017, 571 patients with CIS were 
screened, of whom 368 met all study inclusion criteria. At the last evaluation 
(median 50·0 months [IQR 27·0-78·4]), 189 (51%) of 368 patients developed 
clinically definite multiple sclerosis. At 36 months, the two DIS criteria 
showed high sensitivity (2010 McDonald 0·91 [95% CI 0·85-0·94] and 2016 MAGNIMS 
0·93 [0·88-0·96]), similar specificity (0·33 [0·25-0·42] and 0·32 [0·24-0·41]), 
and similar area under the curve values (AUC; 0·62 [0·57-0·67] and 0·63 
[0·58-0·67]). Performance was not affected by inclusion of symptomatic lesions 
(sensitivity 0·92 [0·87-0·96], specificity 0·31 [0·23-0·40], AUC 0·62 
[0·57-0·66]) or cortical lesions (sensitivity 0·92 [0·87-0·95], specificity 0·32 
[0·24-0·41], AUC 0·62 [0·57-0·67]). Requirement of three periventricular lesions 
resulted in slightly lower sensitivity (0·85 [0·78-0·90], slightly higher 
specificity (0·40 [0·32-0·50], and similar AUC (0·63 [0·57-0·68]). Inclusion of 
optic nerve evaluation resulted in similar sensitivity (0·92 [0·87-0·96]), and 
slightly lower specificity (0·26 [0·18-0·34]) and AUC (0·59 [0·55-0·64]). AUC 
values were also similar for DIT (2010 McDonald 0·61 [0·55-0·67] and 2016 
MAGNIMS 0·61 [0·55-0·66]) and DIS plus DIT (0·62 [0·56-0·67] and 0·64 
[0·58-0·69]).
INTERPRETATION: The 2016 MAGNIMS criteria showed similar accuracy to the 2010 
McDonald criteria in predicting the development of clinically definite multiple 
sclerosis. Inclusion of symptomatic lesions is expected to simplify the clinical 
use of MRI criteria without reducing accuracy, and our findings suggest that 
needing three lesions to define periventricular involvement might slightly 
increase specificity, suggesting that these two factors could be considered 
during further revisions of multiple sclerosis diagnostic criteria.
FUNDING: UK MS Society, National Institute for Health Research University 
College London Hospitals Biomedical Research Centre, Dutch MS Research 
Foundation.