language publications containing the terms multiple sclerosis and diagnosis, and from specific recommendations of rele- vant papers by Panel members. The Panel concluded that most recent research supports the utility of the McDonald Criteria in a typical adult Caucasian population seen in MS centers, despite only limited research and practical experi- ence in general neurology practice populations. In its discussions, the Panel stressed that the McDo- nald Criteria should only be applied in those patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a CNS inflammatory demyelinating disease, because the development and validation of the Criteria have been limited to patients with such presentations. CIS presenta- tions can be monofocal or multifocal, and typically involve the optic nerve, brainstem/cerebellum, spinal cord, or cerebral hemispheres. In applying the McDonald Criteria, it remains im- perative that alternative diagnoses are considered and excluded. Differential diagnosis in MS has been the sub- ject of previous data- and consensus-driven recommenda- tions that point to common and less common alternative diagnoses for MS and identify clinical and paraclinical red flags that should signal particular diagnostic cau- tion.14,15 In its current review, the Panel focused specifi- cally on the often-problematic differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders. There is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aqua- porin-4 (AQP4) autoantibodies.16,17 There was agree- ment that this phenotype should be separated from typi- cal MS because of different clinical course, prognosis, and underlying pathophysiology and poor response to some available MS disease-modifying therapies.18 The Panel recommends that this disorder should be carefully considered in the differential diagnosis of all patients pre- senting clinical and MRI features that are strongly sug- gestive of NMO or NMO spectrum disorder, especially if (1) myelopathy is associated with MRI-detected spinal cord lesions longer than 3 spinal segments and primarily involving the central part of the spinal cord on axial sec- tions; (2) optic neuritis is bilateral and severe or associ- ated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and (3) intractable hiccough or nau- sea/vomiting is present for >2 days with evidence of a periaqueductal medullary lesion on MRI.19,20 In patients with such features, AQP4 serum testing should be used February 2011 Polman et al: 2010 Revisions to MS Diagnosis to help make a differential diagnosis between NMO and MS to help avoid misdiagnosis and to guide treatment. Correct interpretation of symptoms and signs is a fundamental prerequisite for diagnosis.21 The Panel con- sidered again what constitutes an attack (relapse, exacer- bation) and defined this as patient-reported symptoms or objectively observed signs typical of an acute inflamma- tory demyelinating event in the CNS, current or histori- cal, with duration of at least 24 hours, in the absence of fever or infection. Although a new attack should be documented by contemporaneous neurological examina- tion, in the appropriate context, some historical events with symptoms and evolution characteristic for MS, but for which no objective neurological findings are docu- mented, can provide reasonable evidence of a prior demyelinating event. Reports of paroxysmal symptoms (historical or current) should, however, consist of multi- ple episodes occurring over not less than 24 hours. There was consensus among the Panel members that before a definite diagnosis of MS can be made, at least 1 attack must be corroborated by findings on neurological exami- nation, visual evoked potential (VEP) response in patients reporting prior visual disturbance, or MRI con- sistent with demyelination in the area of the CNS impli- cated in the historical report of neurological symptoms. The Panel concluded that the underlying concepts of the original (2001) and revised (2005) McDonald Cri- teria8,9 are still valid, including the possibility of estab- lishing a diagnosis of MS based on objective demonstra- tion of dissemination of lesions in both space and time on clinical grounds alone or by careful and standardized integration of clinical and MRI findings. However, the Panel now recommends key changes in the McDonald Criteria related to the use and interpretation of imaging criteria for DIS and DIT as articulated by the recently published work from the MAGNIMS research group.22–24 Such changes are likely to further increase diagnostic sensi- tivity without compromising specificity, while simplifying the requirements for demonstration of both DIS and DIT, with fewer required MRI examinations. The Panel also makes specific recommendations for application of the McDonald Criteria in pediatric and in Asian and Latin American populations. Recommended Modifications to the McDonald Criteria: The 2010 Revisions MAGNETIC RESONANCE IMAGING CRITERIA FOR DIS. In past versions of the McDonald Criteria, DIS demonstrated by MRI was based on the Barkhof/Tintore´ criteria.4,6 Despite having good sensitivity and specificity, these criteria have been difficult to apply consistently by 293