Finally, predominantly central, longitudinally extensive spinal cord lesions extending over more than three vertebral segments are extremely rare in MS while their presence is highly suggestive of NMOSD [30]. Our case supports the conclusion that the development of tumefactive brain lesions under IFN- therapy for suspected MS should prompt considering NMOSD as the underlying disease, obviously not only in Asian but Cyantraniliprole D3 Cyantraniliprole D3 also in Caucasian patients. 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, followed by clinical and radiological stabilization. Conclusion Our 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 Cyantraniliprole D3 of tumefactive brain lesions under IFN- therapy in two Asian NMO patients; and (iii) suggests tocilizumab as a promising therapeutic alternative in highly active NMO disease courses. experimental model of NMO spinal cord slice cultures exposed to NMO-IgG and complement showed a marked loss of AQP4 and myelin which was enhanced by adding IL-6 [19]. Moreover, Chihara and colleagues described PRKAR2 a specific IL-6-dependent B lymphocyte subpopulation in the peripheral blood and CSF of NMO patients: these CD19+ CD27+ CD38+ CD180+ B cells were found to produce AQP4 antibodies and showed enhanced survival as well as AQP4 antibody secretion in the presence of IL-6, whereas blockage of the IL-6 receptor signalling by an anti-IL-6R antibody shortened their survival [20]. Our report illustrates the importance of correctly diagnosing NMO and MS to avoid mistreatment with potentially severe or even fatal consequences. Two recent studies have revealed that up to 30% of patients with NMO were falsely diagnosed with MS [21,22] and, in consequence, often treated with drugs not effective in NMO. While AQP4-IgG serum testing is certainly the most important differential diagnostic measure, other investigations such as lumbar puncture or brain and spinal cord MRI are important as well. In the present case, the diagnosis of MS was made in the absence of CSF-restricted OCBs. OCB negativity is extremely rare in MS (~2-5%) and should prompt physicians to question that diagnosis; by contrast, around 70% of patients with AQP4-IgG-positive NMOSD lack OCBs [22-24]. Normal CSF/serum concentration quotient values of IgG (QIgG) in NMOSD are especially common during periods of clinical remission [23]. Similarly, a persistently normal brain MRI as observed in our patient should warn against the diagnosis of MS [25]. Brain lesions are absent in most patients with NMO at disease onset, but may occur later in the disease and may even meet MRI criteria for MS [23,26]. Of note, for Asian NMO patients, independent case reports described the occurrence of hemispheric brain lesions even without association to IFN- therapy [27-29], while we are not aware of such observations for NMO patients of other ethnic background. Finally, predominantly central, longitudinally extensive spinal cord lesions extending over more than three vertebral segments are extremely rare in MS while their presence is highly suggestive of NMOSD [30]. Our case Cyantraniliprole D3 supports the conclusion that the development of tumefactive brain lesions under IFN- therapy for suspected MS should prompt considering NMOSD as the underlying disease, obviously not only in Asian but also in Cyantraniliprole D3 Caucasian patients. Moreover, our report underlines C in accordance with previous reports and recommendations [31] C the need to treat MS and NMO, two conditions with substantial differences in pathogenesis [32,33] differentially and, in particular, to avoid treatment with IFN- in patients with NMO. Our report adds to previous evidence indicating a potential treatment effect of tocilizumab, an IL-6 signalling pathway blocker in NMO therapy. Consent Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. Acknowledgements We thank the patient for giving her consent to publishing this case report. We thank the Walter-und-Ilse-Rose-Stiftung for supporting the Multiple Sclerosis Center at the Department of Neurology, Heinrich-Heine University, Dsseldorf, Germany. S.J. thanks the Dietmar Hopp Foundation and Merck Serono for supporting research at the Department of Neurology, University of Heidelberg, Heidelberg, Germany. This work was supported by the Eugne Devic European Network (EDEN, BMBF 01GM1203A; EU-FP7). Footnotes Competing interests J.H. received speaker honoraria from Novartis and travel expenses from Merck Serono M.R. received speaker honoraria from Novartis and travel reimbursement from Bayer Schering and Biogen Idec. J.I. reports no conflicts of interest. C.M. reports no conflicts of interest. N.G. reports no conflicts of.