Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management

Abstract

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. The most popular bridging therapy was oral prednisone taper chosen by 38% of responders while rituximab was the most popular maintenance therapy chosen by 46%. Most responders considered maintenance immunosuppression after a second relapse in patients with neuronal surface antibodies (70%) or seronegative autoimmune encephalitis (61%) as opposed to those with onconeuronal antibodies (29%). Most responders opted to cancer screening for 4 years in patients with neuronal surface antibodies (49%) or limbic encephalitis (46%) as opposed to non-limbic seronegative autoimmune encephalitis (36%). Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.

Rituximab Treatment and Long-term Outcome of Patients With Autoimmune Encephalitis

“…As patients treated with induction or maintenance therapy did not significantly differ in the outcome, our data support the notion that in many patients with NMDAR-AE, short-term rituximab treatment might be sufficient to control the disease. In a recent position paper by the Autoimmune Encephalitis Alliance Clinicians Network, 22 this is reflected by the recommendation to consider long-term rituximab treatment mainly in relapsing disease.…”

Efficacy of tacrolimus as long-term immunotherapy for neuronal surface antibody-mediated autoimmune encephalitis

“…The clinical effectiveness of immunotherapy in the acute phase has been confirmed by previous studies; however, the clinical experience of long-term management of AE is currently insufficient. 1 , 4 , 7 The conventional long-term immunotherapeutic agents include azathioprine and MMF. A few reported studies include the use of immunosuppressants such as tacrolimus, cyclosporine, and methotrexate.…”

“… 5 , 18 In addition, rituximab is recognized as both a second-line treatment for acute immunotherapy and a long-term agent for relapse cases. 1 In this study, we focused on tacrolimus, which is used to treat several autoimmune disorders involving humoral immunity such as rheumatoid arthritis, systemic lupus erythematosus, myasthenia gravis, polymyositis, and neuromyelitis optica spectrum disorder. 9 – 11 , 19 , 20 Tacrolimus, an orally available macrolide calcineurin inhibitor, inhibits the production and release of cytokine [e.g.…”

“…Autoimmune encephalitis (AE) is acute or subacute onset encephalitis that occurs via autoimmune processes. 1 Since anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis was first reported in 2007, 2 an increasing number of antibodies against neuronal cell-surface antigens have been identified. 3 AE presents with a wide spectrum of symptoms with limbic and extra-limbic dysfunctions.…”

“…The neurological symptoms may be reversible and respond relatively well to immunosuppressive therapy. 1 Treatment approaches for AE broadly include immunosuppressive drugs and those targeting antibody-mediated immune processes. 4 Corticosteroids, intravenous immunoglobulin (IVIG), and plasma exchange are the commonly used first-line treatments in the acute phase of AE.…”