BACKGROUND: Complement mediated autoimmunity against aquaporin-4 results in astrocytic damage in neuromyelitis optica (NMO). There is evidence for increased CSF glial fibrillary acidic protein (GFAP) and S100B levels in acute NMO. Here we tested whether the CSF finding also holds true for the diagnostic value of serum GFAP and S100B levels in NMO. METHODS: A multicentre study included 322 patients from London (n=160), Nijmegen (n=95), Pecs (n=44), and Lyon (n=24). Patients were classified into the following diagnostic categories: neurological control patients (n=45), MS optic neuritis (MSON, n=38), isolated optic neuritis (ION, n=11), relapsing isolated optic neuritis (RION, n=48), chronic relapsing isolated optic neuropathy (CRION, n=18), unclassified optic neuritis (UCON, n=39), NMO (n=77) and relapsing remitting multiple sclerosis (RRMS, n=47). Serum GFAP and S100B levels were quantified using ELISA. RESULTS: Median serum GFAP but not S100B levels were significantly higher (p