No abstract

Autoimmune encephalitis is one of the most rapidly growing research topics in neurology. Along with discoveries of novel antibodies associated with the disease, clinical experience and outcomes with diverse immunotherapeutic agents in the treatment of autoimmune encephalitis are accumulating. Retrospective observations indicate that early aggressive treatment is associated with better functional outcomes and fewer relapses. Immune response to first-line immunotherapeutic agents (corticosteroids, intravenous immunoglobulin, plasma exchange, and immunoadsorption) is fair, but approximately half or more of patients are administered second-line immunotherapy (rituximab and cyclophosphamide). A small but significant proportion of patients are refractory to all first- and second-line therapies and require further treatment. Although several investigations have shown promising alternatives, the low absolute number of patients involved necessitates more evidence to establish further treatment strategies. In this review, the agents used for first- and second-line immunotherapy are discussed and recent attempts at finding new treatment options are introduced.

We read with great interest the study by Lim et al, 1 which aimed to develop an easily applicable scale to grade the severity of autoimmune encephalitis (AE). Nine key clinical features were identified and included in the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CASE showed good interobserver and intraobserver reliability, and internal consistency, as well as a high correlation with the modified Rankin Scale (mRS).We applied CASE retrospectively to a cohort of 60 patients with AE, admitted to our institution between 2012 and 2018, and prospectively in 3 additional patients. Median age at onset was 55 years (range = 3 months-88 years), in 13 of 63 (21%) onset was before 18 years of age, and 34 of 63 (54%) were female. All patients fulfilled the clinical diagnostic criteria for AE 2 : definite AE was diagnosed in 16 of 63 patients (25%), definite anti-NMDA receptor encephalitis in 11 of 63 (17%), definite autoimmune limbic encephalitis in 6 of 63 (10%), antibody-negative probable AE in 4 of 63 (6 %), possible AE in 25 of 63 (40%), and Hashimoto encephalopathy in 1 of 63 (2%). At the disease nadir, median mRS score was 4 (range = 3-5). We applied CASE at maximum clinical severity (median CASE score = 9, range = 3-24). In our cohort, CASE significantly correlated with mRS (p < 0.0001, r 2 = 0.5025; Fig), although the correlation strength was weaker than that reported by Lim et al. However, we encountered several issues when CASE was applied to our patients that need to be clarified. Severe clinical conditions, such as coma and status epilepticus, make other items hardly assessable (eg, gait instability, language). In such cases, it is not specified what score should be given to items that are not directly assessable (we gave the maximum score). Postictal state after seizures also interferes with the evaluation of most items. The authors should clarify how to apply the scale in these situations and whether this score is meant to be used only in clinically stable patients. Furthermore, when applying CASE to a pediatric population, some items, such as memory and language, were not easily assessable. We think that the scale is more suitable for adult patients. Moreover, it would be appropriate to develop a different scale for patients with altered consciousness.CASE is potentially a useful tool and addresses the unmet need of clinical scales to grade AE severity, as mRS is quite coarse in evaluating this condition. However, CASE needs further improvement and validation to be employed in clinical trials.

This finding suggests that most anti-LGI1 encephalitis develops in a population with specific HLA subtypes, providing insight into a novel disease mechanism. Ann Neurol 2017;81:183-192.

In anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, we analysed the efficacy of a combined immunotherapy protocol consisting of teratoma removal, steroid, intravenous immunoglobulin (IVIG), rituximab and tocilizumab (T-SIRT). This cohort study included seventy-eight consecutive patients treated for anti-NMDAR encephalitis between Jan 2014 and Oct 2019 in a national referral hospital. Detailed 2-year disease time course was analysed using Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores at every 2 weeks for 12 weeks from baseline, every month for the next 3 months and then every 3 months. Treatment regimens at each time point were categorized as SI, SIR, or SIRT with/without teratoma removal (T). Adverse events were classified according to the Common Terminology Criteria for Adverse-Events (CTCAE v5.0), where a severe adverse event was defined as an adverse event with CATAE grade 4. In a linear mixed model analysis, using the SIRT regimen was more effective than SIR or SI regimens in lowering CASE scores (P < 0.001 and P = 0.001, respectively). The presence of teratoma (P = 0.001), refractory status epilepticus (P < 0.001) and a higher CASE score at baseline (P < 0.001) predicted a higher CASE score at each time point. Completion of the (T)-SIRT regimen within 1 month of onset resulted in better 1-year improvements in CASE score (P < 0.001) and modified Rankin scale scores (P = 0.001), compared to those of using other regimens within 1 month or delaying teratoma removal for more than 1 month. Pneumonia was a frequent adverse event (52/78, 66.7%) in the whole study population and neutropenia was frequent during SIRT (11/52, 21.2%), but the regimen was well tolerated in most patients. We concluded that the early application of combined immunotherapy consisting of T-SIRT had better efficacy than was found for delayed or partial application of this combination in anti-NMDAR encephalitis.