Autoimmune encephalitis: new hammers in the toolbox

Abstract

Recently, the field of autoimmune neurology has been expanding and evolving at a brisk pace. There has been renewed interest in the field, especially with the discovery that many rapidly progressive dementias, cryptogenic refractory seizures and movement disorders are autoimmune in aetiology. Excitement has grown with the recognition that numerous novel neural autoantibodies identified over the past decade and a half are associated with highly treatable autoimmune encephalitides, where patients have demonstrated good outcomes, particularly if diagnosed and treated early. This provides great hope for patients, families and practitioners alike and is in stark contrast with many of the now ‘classic’ paraneoplastic neurological disorders associated with intracellularly targeted antibodies, such as antiHu/antineuronal nuclear antibody type 1 (ANNA-1) or antiYo/Purkinje cell cytoplasmic antibody type 1 (PCA-1), which are well known to be poorly responsive to treatment, often leaving patients with devastating neurological sequelae. Knowing that full autoantibody testing results can take a few weeks to return, the realisations that (1) the best patient outcomes are associated with prompt diagnosis and treatment and (2) not all cases are associated with readily identifiable neural autoantibodies, have led to efforts to publish guidelines for the diagnosis and treatment of autoimmune encephalitides. The latest guidelines are laid out by Abboud and coauthors in the paper entitled ‘Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management’. To date, the best known and most widely accepted criteria for the diagnosis of autoimmune encephalitis are the Graus et al clinical guidelines published in 2016. These criteria aim to give clinicians the tools to diagnose autoimmune encephalitis without needing to wait for antibody testing results, enabling patients to be treated earlier, particularly in situations where antibody testing might be delayed or unobtainable, due to lack of funds or access to testing, for example. These guidelines organise patient symptomatology; paraclinical markers including cerebrospinal fluid analysis, electroencephalography, brain MRI; and wellcharacterised syndromes into a schema enabling patients to be diagnosed with ‘possible’, ‘probable’ or ‘definite’ autoimmune encephalitis. Similar guidelines were recently published for paediatric patients, who develop these disorders more rarely, but also benefit from timely diagnosis and treatment. Abboud and coauthors deemphasise named autoimmune syndromes, such as antiNmethylDaspartate (NMDA) receptor encephalitis or Hashimoto’s encephalopathy, in favour of diagnoses based on anatomical classifications. In comparison to earlier guidelines, Abboud and coauthors provide expanded differential diagnoses, with associated recommendations for additional testing, more details on what to look for from paraclinical tests, advice on how to screen for potential associated malignancies, and perhaps most importantly, recommendations for treatment in the acute phase of illness. One potential drawback of this manuscript is that it is written on behalf of the Autoimmune Encephalitis Alliance Clinicians Network, a group of practitioners from heterogeneous clinical disciplines, that ‘selfidentified’ as having ‘clinical expertise in autoimmune encephalitis management’. Treatment recommendations are made based on the results of a survey of these healthcare professionals. However, many of the authors, including the senior authors, are well established authorities within the field of autoimmune neurology, lending credibility to the work. Any mechanism which advances the capabilities of practitioners with less experience with autoimmune encephalitis to improve their patients’ recoveries from this potentially devastating illness is welcome. As a discipline, autoimmune neurology is a relatively nascent field. The first and thus far only randomised control trial in the field, which closed prior to gathering the originally intended number of subjects due to difficulties with recruitment, was published in early 2020. As a disease, autoimmune encephalitis is steadily marching towards the future, following in the footsteps of its ‘big sibling’ disorder neuromyelitis optica (NMO), which is a few years ahead. With the publication of three promising new treatment trials, 2019 was declared ‘the year of NMO’ by the American Academy of Neurology. As more clinical trials get underway, the ‘year of autoimmune encephalitis’ is on the horizon. In the meantime, clinicians can make use of an expanding toolbox, including the guidelines outlined in this manuscript and scales for predicting antibody prevalence and response to immunotherapy, functional status a year out from a diagnosis of NMDA receptor encephalitis, and clinical assessment in autoimmune encephalitis.