Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition

Abstract

The concept of antibody mediated CNS disorders is relatively recent. The classical CNS paraneoplastic neurological syndromes are thought to be T cell mediated, and the onconeural antibodies merely biomarkers for the presence of the tumour. Thus it was thought that antibodies rarely, if ever, cause CNS disease. Over the past 10 years, identification of autoimmune forms of encephalitis with antibodies against neuronal surface antigens, particularly the voltage gated potassium channel complex proteins or the glutamate N-methyl-D-aspartate receptor, have shown that CNS disorders, often without associated tumours, can be antibody mediated and benefit from immunomodulatory therapies. The clinical spectrum of these diseases is not yet fully explored, there may be others yet to be discovered and some types of more common disorders (eg, epilepsy or psychosis) may prove to have an autoimmune basis. Here, the known conditions associated with neuronal surface antibodies are briefly reviewed, some general aspects of these syndromes are considered and guidelines that could help in the recognition of further disorders are suggested.

Figure 1

Flowchart indicating our suggestions for approaches to the recognition and diagnostic criteria for the neuronal surface antibody syndromes (NSAS). The field is developing and the scheme is intended to help identify further NSAS. *For details, see Graus et al. **History of other antibody mediated disorders or organ specific autoimmunity, or previous infectious/febrile illness. GAD, glutamic acid decarboxylase; IVIG, intravenous immunoglobulins; NSAbs, neuronal surface antibodies; OMS, opsoclonus–myoclonus syndrome; PE, plasma exchange; SPS, stiff person syndrome.