We explored the neuronal component of grey matter damage in the earliest phase of multiple sclerosis (MS) with [11C]Flumazenil positron emission tomography (PET). Using a novel post-processing approach based on the generation of individual maps of neuronal pathology, we found a significant neuronal damage in the cortical lesions of patients with MS which preceded the occurrence of cortical atrophy, and correlated with white matter lesion load. These results suggest that cortical demyelination, together with retrograde degeneration of transected axons within white matter lesions, are among the key pathogenic contributors to neuronal cortical damage at the earliest stage of the disease.
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