ANNALS of Neurology periventricular lesions, and the absence of a diffuse lesion pattern,54 these features are not absolutely discriminatory. Furthermore, MRI scans of children with monophasic ADEM typically demonstrate multiple variably enhancing lesions (often >2) typically located in the juxtacortical white matter, infratentorial space, and spinal cord. Thus, application of the revised MAGNIMS-based criteria for DIS and DIT on initial MRI would be inappropriate for such patients, and serial clinical and MRI observations are required to confirm a diagnosis of MS. In this young age group, there can be marked lesion resolution following an initial attack49 prior to emergence over time of new lesions and attacks leading to a diagnosis of MS. MS in Asian and Latin American Populations Among Asian patients with CNS inflammatory demyeli- nating disease, a phenotype characterized by NMO, lon- gitudinally extensive spinal cord lesions, and positive AQP4 autoantibody seropositivity19 has been relatively more common than in Western populations.55–57 The Panel solicited input on use of the McDonald Criteria in Asia and Latin America, where there is evidence of a sim- ilar phenotype distinction.41 Although the McDonald Criteria are widely used in these parts of the world, there is some uncertainty, especially in Asia, about whether MS and NMO are distinct and if so, how they should be dis- tinguished.39 As currently applied, the term opticospinal MS appears to be an admixture of conventional MS and NMO. Confusion has arisen (1) because of the recognition that most cases of NMO are relapsing; (2) because AQP4 autoantibody testing has facilitated the diagnosis of NMO and permitted inclusion of individuals with symptomatic brain lesions who would previously have been excluded; and (3) because of the recognition that selective involve- ment of optic nerve and spinal cord alone does not differ- entiate NMO from MS.58 It is insufficient to make a diag- nosis of NMO in the absence of the required specificity criteria of the revised Wingerchuk Criteria for ‘‘definite’’ NMO, which recommend presence of optic neuritis, acute myelitis, and at least 2 of 3 supportive paraclinical assess- ments (a contiguous spinal cord lesion at least 3 segments in length, brain MRI at onset that is nondiagnostic for MS, or NMO-IgG seropositivity).59 These criteria are suc- cessful in most instances to distinguish NMO from MS in patients with optic neuritis and myelitis, but the spectrum of NMO includes recurrent myelitis and optic neuritis, NMO syndromes with symptomatic brain lesions at pre- sentation, and NMO associated with systemic autoimmune diseases.60 Failure to make the correct diagnosis in patients with NMO may impact treatment.20 The Panel recommends testing for AQP4 autoanti- bodies with validated assays in patients who are suspected 296 of having NMO or NMO spectrum disorders, especially in patients with Asian or Latin American genetic background because of the higher prevalence of the disease in these populations. Such testing may be less important in those subjects presenting with conventional Western type MS. Although not all patients with an NMO-like presentation will be AQP4 antibody positive, the majority are, whereas those with MS are more likely to be AQP4 antibody nega- tive.16,56,61 Current evidence suggests that once NMO and NMO spectrum disorders have been excluded, Western type MS in Asia or Latin America is not fundamentally dif- ferent from typical MS in the Caucasian population, and that the MAGNIMS MRI criteria would apply for such patients, although confirmatory studies should be done. The McDonald Criteria: 2010 Revisions APPLICATION OF THE CRITERIA. The Panel recom- mends revisions to the McDonald Criteria for diagnosis of MS (Table 4) focusing specifically on requirements to dem- onstrate DIS, DIT, and on diagnosis of PPMS. These 2010 revisions to the McDonald Criteria are likely to be applica- ble in pediatric, Asian, and Latin American populations once careful evaluation for other potential explanations for the clinical presentation is made. The predictive validity of DIS and DIT based on a single first scan in children with CIS needs to be confirmed in prospective studies. The McDonald Criteria have not yet been validated in Asian and Latin American populations, and studies need to be done to confirm the sensitivity and specificity of the Criteria in such patients. Care must be taken to exclude NMO as a differential diagnosis, which can be confounded by the imperfect sensitivity of AQP-4 autoantibody assays, the pres- ence of brain lesions in NMO, and the difficulty of detect- ing long spinal cord lesions in immunosuppressed patients. Future Directions POTENTIAL ADDED VALUE OF BIOMARKERS. Al- though increased IgG index or the presence of oligoclonal bands in the CSF support an MS diagnosis, and AQP4 antibody assays can help in the differential diagnosis pro- cess, there are still no specific biomarkers to confirm the di- agnosis. Several blood and CSF biomarkers may be promis- ing,62–65 and high-resolution spectral domain optical coherence tomography might be as good as VEP in assess- ing visual involvement.66 The diagnostic utility of such markers needs to be validated and tested prospectively. REFINEMENTS IN IMAGING CRITERIA. The McDo- nald Criteria were based on detection of lesions generally using 1.5T magnet strength in noncortical regions of the brain and spinal cord. However, a large proportion of Volume 69, No. 2