Treatment Options in Refractory Autoimmune Encephalitis

Abstract

Autoimmune encephalitis represents a potentially treatable immune-mediated condition that is being more frequently recognized. Prompt immunotherapy is a key factor for the management of autoimmune encephalitis. First-line treatments include intravenous steroids, plasma exchange, and intravenous immunoglobulins, which can be combined in most severe cases. Rituximab and cyclophosphamide are administered as second-line agents in unresponsive cases. A minority of patients may still remain refractory, thus representing a major clinical challenge. In these cases, treatment strategies are controversial, and no guidelines exist. Treatments proposed for refractory autoimmune encephalitis include (1) cytokine-based drugs (such as tocilizumab, interleukin-2/basiliximab, anakinra, and tofacitinib); (2) plasma cell-depleting agents (such as bortezomib and daratumumab); and (3) treatments targeting intrathecal immune cells or their trafficking through the blood-brain barrier (such as intrathecal methotrexate and natalizumab). The efficacy evidence of these drugs is mostly based on case reports or small case series, with few reported controlled studies or systematic reviews. The aim of the present review is to summarize the current evidence and related methodological issues in the use of these drugs for the treatment of refractory autoimmune encephalitis.

Fig. 1

Mechanisms of action of therapeutic options applied to refractory autoimmune encephalitis. These drugs may be classified as plasma cell-depleting agents (in red), cytokine-based drugs (in black), and treatments targeting intrathecal immune cells or their trafficking through the blood–brain barrier (in orange). The lines depicted in the figure, as well as the description in italics, indicate the molecular and cellular target of each treatment. Dashed lines indicate that the drug affects peripheral immune cells, whilst solid lines indicate that treatment affects intrathecal immune cells or their trafficking across the blood–brain barrier. CD cluster of differentiation, IL interleukin, JAK Janus kinase