Abstract
Background Despite clinical symptoms and signs of central nervous system dysfunction, conventional magnetic resonance imaging (MRI) of the brain and spinal cord may appear normal in multiple sclerosis (MS) at clinical onset. Objective To demonstrate cortical pathology, namely the presence of cortical lesions (CLs) in patients with symptoms/signs suggestive of MS but having normal appearing white matter (WM) on MRI. Methods CLs were disclosed by double inversion recovery (DIR) MRI sequence. The final diagnosis of MS was achieved by the demonstration of the dissemination in space and time of WM lesions, and the absence of a better explanation of symptoms/signs, according to the established international diagnostic criteria. Results We describe four patients with MS, in which CLs were observed by DIR months/years before the MRI evidence of inflammatory lesions in the WM. Interpretation We suggest that, at least in some patients with MS, the pathological process underlying MS starts in the cortex. DIR sequence should be included in the MRI examination of suspected patients with MS with normal conventional MRI sequences at clinical onset. CLs should be evaluated for their inclusion in the MRI diagnostic criteria for MS.

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