ANNALS of Neurology MS lesions are in the cortex67,68 and can be detected using double inversion recovery imaging.69–74 The pres- ence of at least 1 intracortical lesion in subjects with CIS may help identify subjects at high risk for developing CDMS.75 Magnet strengths >1.5T with tailored acquisi- tion protocols76–79 may also enhance diagnosis, with improvements in image resolution, signal-to-noise ratio, and chemical shift. Scans at 7.0T showed lesions in the white and gray matter with enhanced in vivo detection of pathological hallmarks of MS lesions.80–83 Finally, MRI techniques such as magnetic transfer imaging allow the detection of damage outside focal lesions (for instance, in normal-appearing brain tissues) not present in conditions such as ADEM and NMO.15,84,85 The utility of these scanning technologies for MS diagnosis in patients with CIS remains a matter for future research and validation. Many individuals with high lesion loads may have had a protracted subclinical disease course prior to their first clinical event. As a consequence, occasional individu- als investigated by MRI for indications unrelated to MS have incidental findings of brain lesions with appearance and topography consistent with MS. Detection of this presymptomatic phase, or radiologically isolated syn- drome, is increasingly common. Some of these individu- als followed clinically and by serial imaging will develop DIT by MRI, and some have clinical disease-defining events after several years.86–89 However, in the absence of supportive research findings, the Panel concluded that a firm diagnosis of MS based on incidental findings on MRI alone, even with additional supportive findings on evoked potentials or typical CSF findings in the absence of MS-relevant clinical symptoms, is problematic. A future definite diagnosis of MS, however, cannot be excluded and may be likely, depending on the evolution of neurologic symptoms and signs. Conclusions The 2010 revisions to the McDonald Criteria will in some instances allow a more rapid diagnosis of MS, with equivalent or improved specificity and/or sensitivity com- pared with past Criteria and will in many instances clar- ify and simplify the diagnostic process with fewer required MRI examinations. A proportion of patients with nonspecific symptoms (eg, fatigue, weakness, or dizziness) and nonspecific MRI findings are referred to secondary and tertiary MS centers in the developed world for a sec- ond opinion and do not in fact have MS.90 These revised McDonald Criteria for MS diagnosis should therefore be applied only when patients have experienced a typical CIS (or progressive paraparesis/cerebellar/cognitive syndrome in the case of suspected PPMS). 298 The Panel acknowledges that using these refined diagnostic criteria may change some of the outcomes of patients in natural history studies and clinical trials, when original expectations for outcomes may be based on subjects whose diagnosis was made using past, some- what different criteria.91 Most of the currently recom- mended revisions are based upon new data generated since the 2005 revisions. However, there remains a need for further testing in prospective and retrospective data- sets of many of these criteria, especially in populations of patients typical of those seen in general neurology prac- tices, both to further assess their value and utility and to provide suggestions for further refinements in the future. Acknowledgment The work of the Panel was supported by the US National Multiple Sclerosis Society (NMSS), the Euro- pean Committee for Treatment and Research in Multiple Sclerosis, the Multiple Sclerosis International Federation, and MS Ireland. The Panel thanks Drs T. Saida, M. Lana-Peixoto, D. Callegaro, and C. Oehninger for help in gaining per- spective on the use of the McDonald Criteria in Asia and Latin America. This work is dedicated to the memory of Dr W. Ian McDonald, who chaired the original Panel and whose continuing inspiration has driven the work for the second and third revisions to the Criteria that now bear his name. Potential Conflicts of Interest C.H.P.: consultancy, Actelion, Biogen Idec, Bayer Scher- ing, Teva, Merck-Serono, Novartis, Glaxo SK, UCB, Roche, Antisense Ther; expert testimony, Biogen Idec; grants/grants pending, Biogen Idec, Bayer Schering, Teva, Merck-Serono, Novartis, Glaxo SK, UCB. S.C.R.: travel support, US NMSS, ECTRIMS, Multiple Sclerosis International Federation, MS Ireland; payment for writing or reviewing manuscript, US NMSS, ECTRIMS; con- sultancy, US NMSS, ECTRIMS, Sanofi-Aventis, Bayer Schering Pharma, BioMarin, EMD Merck Serono, Mt Sinai College of Medicine (New York, NY), European Committee for Treatment and Research in MS, Eisai, INC Research, Eli Lilly Inc, Isis Pharmaceuticals Inc, Medici- Nova, Cleveland Clinic Foundation, Free University Amsterdam, Genentech/F. Hoffmann-LaRoche, Synthon BV, Antisense Therapeutics Ltd, BaroFold, Protein Design Laboratories; royalties, Demos Medical Publishers (New York, NY). B.B.: travel support, US NMSS, ECTRIMS, MSIF, MS Ireland; consultancy, Biogen Idec, Genzyme; grants/grants pending, Multiple Sclerosis Society of Volume 69, No. 2