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Clinically isolated syndromes (CIS) classically refer to optic neuritis (ON), brainstem or spinal cord syndromes. Less common first episodes suggestive of central nervous system (CNS) demyelination, such as hemispheric or clinically polyregional syndromes, have been only slightly studied. The aim of this study was to describe these CIS topographies in our cohort of patient with a CIS. We evaluated 320 patients with a CIS, and classified the topographies of the attacks according to clinical symptoms only into CIS of the optic nerve (123), brainstem (78), spinal cord (89), hemispheric (6), polyregional (12) or undetermined (12) topographies. Patients underwent brain MRI within three months of their first attack, and again 12 months later. Conversion to multiple sclerosis (MS), determined either clinically or by magnetic resonance imaging (MRI), was evaluated according to topography. Hemispheric and polyregional syndromes were closer to brainstem or spinal cord syndromes than ON in clinical and MRI conversion terms, although a statistical analysis was not performed because of the small number of patients. There are differences between several studies in the definition, and, therefore, the prevalence of these so-called atypical CIS. Consensus on the denomination and definition of these syndromes must be reached. Multiple Sclerosis 2007; 13: 731-736. http://msj.sagepub.com