Autoimmune Encephalitis, Including Anti-MOG Antibody Related Encephalitis, is Rare in Children with Suspected Meningitis or Encephalitis

Encephalitis is characterized by brain inflammation that can result in severe sequelae in children. The etiologies for encephalitis are numerous, but the two more common etiologies considered in children are infectious and autoimmune.[1] Other causes for clinically suspected encephalitis can include systemic conditions and genetic and metabolic disorders.[2] [3] Autoimmune encephalitis is attributed to anti-neuronal antibodies targeting the brain which results in neuropsychiatric symptoms.[2] [3] One such antibody that is associated with autoimmune encephalitis is the anti-myelin oligodendrocyte glycoprotein (MOG) antibody, which is associated with anti-MOG antibody-associated disorder (MOGAD).[4] While MOGAD is often presented as a demyelinating disorder, MOGAD can also mimic infectious or autoimmune encephalitis.[5] [6] [7] [8]

This study by Fellmeth et al. evaluates the frequency of autoimmune encephalitis in a large prospective cohort of 1,341 children with suspected encephalitis. This study includes the frequency of seronegative and anti-MOG antibody-associated autoimmune encephalitis in this cohort. Autoimmune encephalitis was diagnosed in 39 of these children, with 3/39 with anti-MOG antibodies and 5/39 with probable seronegative autoimmune encephalitis. Thus, while autoimmune encephalitis, including seronegative, can occur in children, these diagnoses are rare in children with suspected encephalitis. Another study of pediatric autoimmune encephalitis found that in a cohort of 2,750 children, 20% (542/2750) had brain immunoreactivity against neural antigens.[8] The most common antibody in that study was anti-NMDA receptor antibodies, followed by anti-MOG antibodies.[8]

Autoimmune encephalitis is also rare in people with new-onset psychosis. In a cohort of 105 participants (median age: 30, range: 14–75 years), only 4 (4%) had a nonpsychiatric cause of symptoms.[9] In a pediatric-specific cohort of acute psychosis (n = 24), only five had autoimmune encephalitis (all anti-NMDAR encephalitis). The others had additional diagnoses including primary psychiatric and genetic causes, including a child with cobalamin C deficiency.[10]

The diagnosis of probable seronegative autoimmune encephalitis is challenging in both children[2] and adults.[3] Probable seronegative autoimmune encephalitis in children is defined as (1) acute or subacute onset of neuropsychiatric symptoms often within the past 3 months; (2) abnormal neuropsychiatric findings on examination; (3) abnormal ancillary test results (cerebrospinal fluid-CSF elevated white cell count, an elevated immunoglobulin G index, and/or positive CSF-specific oligoclonal bands); and (4) exclusion of alternative causes. These alternative causes can include infectious, drug toxicity, metabolic/genetic conditions, systemic autoimmune conditions, epilepsies, amongst others.[2] However, these consensus criteria for the diagnosis of seronegative autoimmune encephalitis may both overdiagnose and underdiagnose autoimmune encephalitis, and thus these patients require evaluation by an expert in autoimmune encephalitis.[11] Moreover, access to an autoimmune encephalitis expert may not be readily available to many, and thus additional research in accurate diagnosis of seronegative autoimmune encephalitis is needed. Nevertheless, anti-MOG antibodies should be considered in children with suspected encephalitis.

Publication History

Article published online:
08 July 2025

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