Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute 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. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.

Keywords: autoimmune encephalitis; neuroimmunology; paraneoplastic syndrome.

Figure 1

AEACN survey results for acute and bridging therapy. AE, autoimmune encephalitis; AEACN, Autoimmune Encephalitis Alliance Clinicians Network; IVMP, intravenous methylprednisolone; IVIg, intravenous Ig; PLEX, plasma exchange.

Figure 2

Diagnostic algorithm for autoimmune encephalitis. *EEG can confirm focal or multifocal brain abnormality and rule out subclinical seizures. **In addition to neuronal autoantibodies, cerebrospinal fluid should be tested for infections, inflammatory markers (IgG index and oligoclonal bands), and in some cases cytology. ***In addition to neuronal autoantibodies, the differential diagnosis generated based on MRI results will guide what blood tests to send. ****In most cases, general neoplasm screening starts with CT then other screening modalities are added until a neoplasm is found or eventually ruled out. If the clinical picture is highly suggestive of a specific neoplasm, a targeted screening approach could be implemented (eg, starting with pelvic ultrasound if the clinical picture is suggestive of anti-NMDAR encephalitis). AE, autoimmune encephalitis; EEG, electroencephalogram; MRI WWO, MRI with or without contrast; PET, positron emission tomography.

Figure 3

Anatomical subtypes of autoimmune encephalitis. (A) Limbic encephalitis, (B) cortical/subcortical encephalitis, (C) striatal encephalitis, (D) diencephalic encephalitis, (E) brainstem encephalitis (arrow), (F) meningoencephalitis (arrow).

Figure 4

Therapeutic algorithm for autoimmune encephalitis. *Relative contraindications to steroids include uncontrolled hypertension, uncontrolled diabetes, acute peptic ulcer and severe behavioural symptoms that worsen with corticosteroid therapy. **Steroid-responsive conditions include faciobrachial dystonic seizures suggestive of LGI1-antibody encephalitis, autoimmune encephalitis in the setting of immune checkpoint inhibitors, central demyelination, autoimmune GFAP astrocytopathy, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, and steroid-responsive encephalopathy associated with autoimmune thyroiditis. ***High thromboembolic risk includes patients with known or suspected cancer, smoking history, hypertension, diabetes, hyperlipidaemia and hypercoagulable states. Ab, antibody; AE, autoimmune encephalitis; Ag, antigen; IVMP, intravenous methylprednisolone; IVIg, intravenous Ig; IL-6: interleukin 6; NORSE, new-onset refractory status epilepticus; PLEX, plasma exchange.