Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient

Commentary

Hiroya Nishida
Assistant researcher
Tokyo Metropolitan Institute of Medical Science

The diagnostic criteria for autoimmune encephalitis (AE) and some of its specific syndromes were proposed in 2016 and were aimed at facilitating the early administration of immunotherapy to patients with suspected AE, regardless of the antibody status. They were based on evidence primarily from adult patients, focusing on the identification of specific, well-defined syndromes (e.g. NMDAR encephalitis, limbic encephalitis, etc.)

In the present study, the criteria for adult AE were modified for application in pediatric AE. Provisional classification criteria for the following three statuses were proposed: (1) possible pediatric AE, (2) probable antibody-negative pediatric AE, and (3) definite antibody-positive pediatric AE. (Details are described in table 4 of the article). As many pediatric patients do not present with well-defined syndromes, the present criteria are aimed at guiding physicians in the clinical assessment of pediatric patients with suspected AE and they make an appropriate diagnosis of AE. In contrast to the criteria for adults, they include both acute and subacute time frames for the symptom onset, and distinguish the clinical evidence of neurologic dysfunction and paraclinical evidence of neuroinflammation.

In addition to proposing a provisional classification criteria and diagnostic algorithm for pediatric AE, the authors provide a brief, review of AE and recognizable syndromes, such as anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, focusing on the differences between adult and pediatric patients. They also review methods for assessment of pediatric patients with suspected AE, and outline of some recognizable AE syndromes in pediatric patients. The tables and algorithm are succinct and well summarized to aid the readers' understanding.

Some issues regarding the proposed criteria for pediatric AE remain unsolved. First, there may be neuronal antibodies that have not been identified, particularly in patients with probable antibody-negative pediatric AE, which is clinically challenging for physicians. Second, the treatment protocol for pediatric patients with AE is yet to be established. The proposed criteria and algorithm need to be validated in future studies. The authors concluded that a prospective pediatric cohort study is required to solve the issues.

Abstract:

Objective: Autoimmune encephalitis (AE) is an important and treatable cause of acute encephalitis. Diagnosis of AE in a developing child is challenging because of overlap in clinical presentations with other diseases and complexity of normal behavior changes. Existing diagnostic criteria for adult AE require modification to be applied to children, who differ from adults in their clinical presentations, paraclinical findings, autoantibody profiles, treatment response, and long-term outcomes.

Methods: A subcommittee of the Autoimmune Encephalitis International Working Group collaborated through conference calls and email correspondence to consider the pediatric-specific approach to AE. The subcommittee reviewed the literature of relevant AE studies and sought additional input from other expert clinicians and researchers.

Results : Existing consensus criteria for adult AE were refined for use in children. Provisional pediatric AE classification criteria and an algorithm to facilitate early diagnosis are proposed. There is also discussion about how to distinguish pediatric AE from conditions within the differential diagnosis.

Conclusions : Diagnosing AE is based on the combination of a clinical history consistent with pediatric AE and supportive diagnostic testing, which includes but is not dependent on antibody testing. The proposed criteria and algorithm require validation in prospective pediatric cohorts.