Autoimmune Encephalitis and Autism Spectrum Disorder

Abstract

The concept of “acquired autism” refers to the hypothesis that amongst the massive heterogeneity that encompasses autism spectrum disorder (ASD) there may be several phenotypes that are neither syndromic nor innate. Strong and consistent evidence has linked exposure to various pharmacological and infective agents with an elevated risk of a diagnosis of ASD including maternal valproate use, rubella and herpes encephalitis. Autoimmune encephalitis (AE) describes a group of conditions characterised by the body's immune system mounting an attack on healthy brain cells causing brain inflammation. The resultant cognitive, psychiatric and neurological symptoms that follow AE have also included ASD or autism-like traits and states. We review the current literature on AE and ASD. Drawing also on associated literature on autoimmune psychosis (AP) and preliminary evidence of a psychosis-linked subtype of ASD, we conclude that AE may either act as a potentially causative agent for ASD, and/or produce symptoms that could easily be mistaken for or misdiagnosed as autism. Further studies are required to discern the connection between AE and autism. Where autism is accompanied by regression and atypical onset patterns, it may be prudent to investigate whether a differential diagnosis of AE would be more appropriate.

Disease Course and Response to Immunotherapy in Children With Childhood Disintegrative Disorder: A Retrospective Case Series

“…6 Autistic regression and psychosis as seen in this cohort have been identified as potential presentations of autoimmune encephalitis. [12][13][14]22 Thus, etiologic evaluation for autoimmune encephalitis should be considered in addition to possible genetic, metabolic, infectious, and trauma-reactivity causes of rapid-onset neurobehavioral regression. Of note, EEG background changes are not paraclinical markers of inflammation and are common in both autism spectrum disorder and childhood disintegrative disorder.…”

“…As childhood disintegrative disorder is a clinical diagnosis that shares features with autoimmune encephalitis, consideration of childhood disintegrative disorder may be appropriate for some children with possible autoimmune encephalitis and vice versa. 14,15 Accurate differentiation between these populations is crucial given the notable lack of specific treatments in childhood disintegrative disorder whereas immunomodulatory treatments may significantly impact the course of autoimmune encephalitis; however, misdiagnosis and treatment of patients without autoimmune encephalitis carry risk of immunomodulatory agent side effects and potential delay of optimal engagement in symptomatic management of childhood disintegrative disorder. 16 Often, when diagnostic testing is underway, a trial of immunomodulation is considered in patients with possible autoimmune encephalitis; however, current recommendations support that if no paraclinical marker of inflammation results, further treatment is not supported.…”

Neuroinflammatory syndromes in children

“…Beyond infectious or post-infectious inflammatory disorders, ongoing developments in the literature emphasize the role of inflammation in normal and abnormal brain development. Although the question of neuroinflammatory factors in autism spectrum disorder has long been considered, including recent discussion of the relationships between autism and autoimmune encephalitis, considerations across different neurodevelopmental disorders have been expanding, potentially mediated by DNA methylation and miRNA expression due to inflammatorily driven epigenetic factors [52,53].…”

The importance of genetics in an advanced integrative model of autism spectrum disorder

“…The authors proposed a "multidisciplinary approach and interdisciplinary sharing of knowledge". Special issues of the Journal of Personalized Medicine about ASD in 2021 [47] and 2022 [48] include a plethora of information about these topics from different research groups around the world. Recent manuscripts have correlated ASD and autoimmune issues as autoimmune encephalitis [49] and presented sociological aspects and clinical challenges for treating CMP in people diagnosed with ASD [50] .…”

“…Figure 3 shows the approach of the AIM and how the GM is included. The brain and body interact through different pathways and mechanisms, and CMP outside the brain may influence neurological and psychiatric CMP in people with ASD [47,48] . The findings of genetic testing should not be considered as confirmation that a patient's overall presentation is solely related to genetics, especially given the exhaustive clinical studies on CMP that are needed.…”