However, clinicians should pay particular attention in anti-AQP4 unfavorable patients, in patients with a known malignancy or cancer risk factors (e.g. suggest that there is no need to routinely screen anti-AQP4 antibody positive NMOSD patients with a typical ELF2 presentation for onconeural antibodies. Furthermore, absence of these antibodies B-Raf inhibitor 1 dihydrochloride in NMOSD, which is typically non-paraneoplastic, confirms their high specificity for PNS. neuromyelitis optica spectrum disorders, aquaporin-4, optic neuritis, longitudinal extensive transverse myelitis, acute myeloid leukemia aAnaplastic astrocytoma that progressed to secondary glioblastoma Discussion Inspired by previous reports suggesting a paraneoplastic etiology in rare cases of cancer-associated NMOSD [11C22], this is the first study systematically investigating the seroprevalence of onconeural antibodies (anti-Hu, Yo, Ri, CV2/CRMP5, Ma1, Ma2, Zic4, SOX1, Tr, and amphiphysin) in NMOSD patients. The principal obtaining was that all 23 patients B-Raf inhibitor 1 dihydrochloride samples were antibody-negative. However, we acknowledge that this absence of onconeural antibodies does not exclude PNS . In addition, only two patients in our study had a malignancy; yet neoplastic entities (astrocytic brain tumor and AML) are not typically associated with PNS . By contrast, previous reports on putative paraneoplastic NMOSD described associated malignancies that typically occur in PNS patients, predominantly lung and breast malignancy [11C22]. Unfortunately, these reports did not systematically investigate onconeural antibodies for comparison with our data. In this regard, there is currently only one case report describing anti-Hu antibodies in a patient with anti-AQP4 positive NMOSD and recurrent thymoma . Limitations of our study were the retrospective design and therefore patients were not systematically screened for occult malignomas. Furthermore, the case number was limited, since serum was available for only 25 of 35 patients (71.4%) previously identified by an electronic database search for those with an NMOSD diagnosis. Conclusions According to our data, the routine screening for onconeural antibodies in NMOSD patients is not mandatory. However, clinicians should pay particular attention in anti-AQP4 unfavorable patients, in patients with a known malignancy or cancer risk factors (e.g. smoking), and/or if clinical presentation is usually atypical, since paraneoplastic myelitis and/or ON in association with anti-CV2/CRMP5, B-Raf inhibitor 1 dihydrochloride CHu or Camphiphysin antibodies might clinically mimic NMOSD [7C10]. Finally, the absence of onconeural antibodies in a typically non-paraneoplastic disorder corresponds to their high specificity for PNS . Finally, larger retrospective trials are necessary to verify these results and to determine the proportion of anti-AQP4 unfavorable NMOSD patients with onconeural antibodies. Acknowledgements Not applicable. Funding Not applicable. Availability of data and material All data generated or analyzed during this study are included in this published article. Authors contributions BB conceived the study, drafted the manuscript, performed antibody testing, and collected patients data. TH collected patients data. SR and OS helped to draft the manuscript. All authors read and approved the final manuscript. Competing interests BB received travel grants from Bayer Vital GmbH, Ipsen Pharma GmbH, and Genzyme. TH received travel grants from Bayer Vital GmbH and Novartis. SR and OS report receiving consulting and lecture charges, and study and give support from Baxter, Bayer Essential GmbH, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva. Furthermore, SR can be a founding professional board person in ravo Diagnostika GmbH, which offers in-vitro diagnostic medical products for the recognition of infectious illnesses and paraneoplastic autoantibodies. non-e from the authors possess any monetary or personal interactions with people or agencies that could inappropriately impact this publication. Consent for publication All individuals gave written informed consent towards the scholarly research process also to publication of their data. Ethics authorization and consent to take part The neighborhood ethics committee from the Albert-Ludwigs-University (Freiburg, Germany) authorized the analysis (EK-Freiburg 47/16). All individuals gave written informed consent to take part in the scholarly research. Abbreviations AMLAcute myeloid leukemiaAQP4Aquaporin-4CNSCentral anxious systemLETMLongitudinally intensive transverse myelitisNMONeuromyelitis opticaNMOSDNeuromyelitis B-Raf inhibitor 1 dihydrochloride optica range disordersONOptic neuritisPNSParaneoplastic neurological syndromesSDStandard deviation Contributor Info Benjamin Berger, Telephone: +49 761 270 50010, Email: firstname.lastname@example.org. Tilman Hottenrott, Email: email@example.com. Sebastian Rauer, Email: firstname.lastname@example.org. Oliver Stich, Email: email@example.com..