BackgroundNeuromyelitis optica (NMO) is a severely disabling inflammatory disorder of the central nervous system and is often misdiagnosed as multiple sclerosis (MS). There is increasing evidence that treatment options shown to be beneficial in MS, including interferon-ß (IFN-ß), are detrimental in NMO.Case presentationWe here report the first Caucasian patient with aquaporin 4 (AQP4)-seropositive NMO presenting with a tumefactive brain lesion on treatment with IFN-ß. Disease started with relapsing optic neuritis and an episode of longitudinally extensive transverse myelitis (LETM) in the absence of any brain MRI lesions or cerebrospinal fluid-restricted oligoclonal bands. After initial misdiagnosis of multiple sclerosis (MS) the patient received subcutaneous IFN-ß1b and, subsequently, subcutaneous IFN-ß1a therapy for several years. Under this treatment, the patient showed persisting relapse activity and finally presented with a severe episode of subacute aphasia and right-sided hemiparesis due to a large T2 hyperintensive tumefactive lesion of the left brain hemisphere and a smaller T2 lesion on the right side. Despite rituximab therapy two further LETM episodes occurred, resulting in severe neurological deficits. Therapeutic blockade of the interleukin (IL)-6 signalling pathway by tocilizumab was initiated, leading to clinical and radiological stabilization.ConclusionOur case (i) illustrates the relevance of correctly distinguishing NMO and MS since these disorders differ markedly in their responsiveness to immunomodulatory and -suppressive therapies; (ii) confirms and extends a previous report describing the development of tumefactive brain lesions under IFN-ß therapy of two Asian NMO patients; and (iii) suggests tocilizumab as a promising therapeutic alternative in highly active NMO disease courses.Interferon-ß (IFN-ß) is one of the established first-line therapies for patients with relapsing-remitting multiple sclerosis (MS). While the efficacy of IFN-ß in MS is widely accepted, the possible benefit in non-classical MS variants has been disputed. This is the case for neuromyelitis optica (NMO/Devic¿s syndrome), considered an MS subtype until the discovery of the anti-aquaporin 4 (AQP4) antibodies (AQP4-Ab) [1,2]. In both Asian and European NMO patients, IFN-ß failed to show therapeutic efficacy [3-5]. Of note, Shimizu and colleagues recently reported two Asian patients with NMO spectrum disease (NMOSD) who developed extensive brain lesions following IFN-ß therapy [6]. Here we report the case of an AQP4-seropositive NMO patient of Caucasian descent presenting with a tumefactive lesion on IFN-ß treatment. Of note, our patient did not respond to B cell depletion by the monoclonal anti-CD20 antibody rituximab but improved upon blockade of the IL-6 pathway using tocilizumab.