Question:

Why does it take so long to diagnose a child with autoimmune encephalitis?

Answer:

Diagnosing AE is challenging because of overlap in clinical presentations between the types of AE, other inflammatory brain diseases, infections, metabolic diseases, and psychiatric disorders. It is especially difficult in children because of the complexity of normal behavioral changes during childhood and the limited capacity of younger children to describe their symptoms. Compared to adults with AE, children may manifest important differences in symptoms, paraclinical findings, comorbidities, treatment response, and prognosis. There is an urgent need to recognize pediatric AE because treatment delays worsen prognosis and increase the risk of permanent neurocognitive deficits.

Children with AE present with acute or subacute onset of neuropsychiatric symptoms due to an underlying abnormal immune response to the CNS. A number of different antibodies have been described in children with AE. Currently, the most common autoantibodies in children target the N-methyl-D-aspartate receptor (NMDAR), Acute Disseminated Encephalomyelitis, (ADEM), myelin oligodendrocyte glycoprotein (MOG), and glutamic acid decarboxylase 65 (GAD65). It is also recognized that not all children with a clinical phenotype of AE have a known autoantibody.

Deficits in working memory are challenging to identify in younger children. Also, children are less likely to present with a well-defined neurologic syndrome and, even in anti-NMDAR encephalitis, the sequence of symptom development may differ from adults. Furthermore, the differential diagnosis for a child presenting with temporal lobe seizures and cognitive slowing is broad, whereas this presentation in adults suggests limbic encephalitis or acquired temporal pathology.

Diagnosing AE is based on the combination of a clinical history consistent with the disease and supportive diagnostic testing, which includes but is not dependent on antibody testing.

References:

Proposed classification criteria and algorithm for diagnosis of pediatric AE. (Possible pediatric AE, probable antibody-negative pediatric AE, and definite antibody-positive pediatric AE).