Volume 8, Issue 1, January 2013
Bob Wilson MSc, FFS(RCPA), Kerri Prain, BSc, David Gillis, FRCPA FRACP FFS(RCPA) and Richard Wong GDM FRCPA FRACP FRCP.
Division of Immunology, Central Laboratory, HSSA-Pathology Queensland, Royal Brisbane and Women’s Hospitals, Herston, Brisbane, 4061, Australia.
Introduction
The spectrum of antibodies against intracellular, cell surface and synaptic neuronal antigens has expanded rapidly in recent years. The antigenic targets include ion channels, receptors involved in neurotransmission across synapses and proteins associated with them. There are now more than twenty anti-neuronal antibodies detected in association with neurological diseases. These antibodies may be associated with underlying malignancies and are commonly referred to as paraneoplastic antibodies (PNAs). Many PNAs have been correlated with neurological manifestations and fall into two groups: those that are cytotoxic for example anti-purkinje cell antibody-1 (PCA-1/Yo) and anti-neuronal nuclear antibody-1 (ANNA-1/Hu); and others that have functional activity, such as anti-N-Methyl-D-Aspartate receptor (NMDAR) and anti-Voltage-gated potassium channel (VGKC). Recently there has been a marked interest in both anti-NMDAR and anti-VGKC antibodies as the presence of these antibodies identify patients with treatable neurological disease.
Anti-NMDAR was initially described as a paraneoplastic antibody associated with ovarian teratoma, with a characteristic clinical picture of encephalitis with psychiatric features, cognitive dysfunction and seizures. 1 2 Although subsequent case series have confirmed that ovarian teratoma is a frequent association, it has become apparent that many patients who are positive for anti-NMDAR do not have evidence of an associated malignancy.
There is also some evidence supporting the need for rapid identification of anti-NMDAR. Patients who are diagnosed and treated with immuno-suppressive/immunomodulatory therapy within 40 days of disease onset, have been reported to have a better clinical outcome than those treated after 40 days.