Screening for onconeural antibodies in neuromyelitis optica spectrum disorders

Benjamin Berger,Sebastian Rauer,Tilman Hottenrott,Oliver Stich

doi:10.1186/s12883-016-0779-9

Abstract

BackgroundSome so-called “non-classical” paraneoplastic neurological syndromes (PNS), namely optic neuritis and myelitis, clinically overlap with neuromyelitis optica spectrum disorders (NMOSD), and conversely, in cancer-associated NMOSD, a paraneoplastic etiology has been suggested in rare cases. Therefore, we retrospectively investigated the prevalence of onconeural antibodies, which are highly predictive for a paraneoplastic etiology, and the prevalence of malignancies in NMOSD patients.MethodsWe retrospectively screened 23 consecutive patients from our clinic with NMOSD (13 were anti-aquaporin-4 [AQP4] antibody positive, 10 were AQP4 negative) for onconeural antibodies using an immunoblot.ResultsAll patients were negative for a broad spectrum of antibodies targeting intracellular onconeural antigens (Hu, Yo, Ri, CV2/CRMP5, Ma1, Ma2, Zic4, SOX1, Tr, and amphiphysin). Notably, only two patients had a malignancy. However, neoplastic entities (astrocytic brain tumor and acute myeloid leukemia) were not typical for PNS.ConclusionsOur data suggest that there is no need to routinely screen anti-AQP4 antibody positive NMOSD patients with a typical presentation for onconeural antibodies. Furthermore, absence of these antibodies in NMOSD, which is typically non-paraneoplastic, confirms their high specificity for PNS.

Highlights

Some so-called “non-classical” paraneoplastic neurological syndromes (PNS), namely optic neuritis and myelitis, clinically overlap with neuromyelitis optica spectrum disorders (NMOSD), and in cancer-associated NMOSD, a paraneoplastic etiology has been suggested in rare cases
Diagnostic criteria have recently been revised, introducing the term “neuromyelitis optica spectrum disorders (NMOSD)” [5]. According to these revised criteria, an NMOSD diagnosis can be established in absence of anti-AQP4 antibodies
Regarding a previously suggested paraneoplastic etiology in rare cases, we retrospectively investigated the prevalence of onconeural antibodies and malignancies in NMOSD patients

Summary

Introduction

Some so-called “non-classical” paraneoplastic neurological syndromes (PNS), namely optic neuritis and myelitis, clinically overlap with neuromyelitis optica spectrum disorders (NMOSD), and in cancer-associated NMOSD, a paraneoplastic etiology has been suggested in rare cases. Pathogenetic antibodies targeting the water channel protein aquaporin-4 (AQP4) are found in the majority of patients with NMO [3]. Since their discovery, the spectrum of clinical manifestations within the CNS associated with AQP4 antibodies has expanded [4]. Diagnostic criteria have recently been revised, introducing the term “neuromyelitis optica spectrum disorders (NMOSD)” [5]. According to these revised criteria, an NMOSD diagnosis can be established in absence of anti-AQP4 antibodies. In the following, the term “NMOSD” is consistently used for both NMO and NMOSD

Methods

Results

Conclusion