Antibody mediated encephalitis

Abstract

One of the most fascinating aspects of clinical neurology is the unravelling of conditions which have previously been poorly defined and commonly under-recognised. Although selected antibody-mediated neurological diseases, such as myasthenia gravis and some paraneoplastic neurological syndromes, are well-described and familiar to the general neurologist, a number of relatively novel antibodies have more recently been associated with specific neurological syndromes. Furthermore, whereas the onconeural antibodies directed against intracellular antigens are not considered pathogenic, and; therefore, not usually amenable to immunotherapies, the description of antibodies that bind to proteins on the cell-surface of neural cells, commonly associated with sub-acute, mainly monophasic neurological disease, raise the possibility of more effective therapeutic intervention. It also seems likely that these newer antibodies may be truly pathogenic rather than epiphenomenon since there have been plausible attempts to attribute syndrome-specific symptoms to antibody binding sites and correlate antibody titres with clinical state and treatment response. For the clinician, a key factor is undoubtedly the ability to recognise phenotypic characteristics which define these antibody-specific neurological disorders. This in turn allows appropriate and focussed antibody testing, rapid diagnosis, early effective treatment and appropriate investigations for underlying causes such as tumours. Although early open label studies hint at a good response to immunotherapy for defined neurological syndromes mediated by auto-antibodies that bind to the cell-surface or synaptic proteins, no data are yet available from robust clinical trials to inform on treatment type, dose, regime and length. Until recently it was generally considered that the low incidence of these conditions precluded appropriately powered randomised control trials, but the large numbers of patients currently being reported suggests that this view should now be reconsidered. In this month’s journal club, we review three recent papers examining antibody-mediated neurological syndromes. The first two papers examine the clinical features and outcome of neurological disease associated with two specific auto-antibodies whose assays are widely available in routine clinical practice, albeit usually at specialist centres. The third explores a rarer form of paediatric encephalitis and describes a new, possibly pathogenic, disease associated antibody.