Test codes:

Pediatric Autoimmune Encephalitis Evaluation With Reflexes, Serum 18410
Pediatric Autoimmune Encephalitis Evaluation With Reflexes, CSF 18420

Clinical use

• Diagnose autoimmune encephalitis in children

Clinical background

Autoimmune encephalitis (AIE) is inflammation of the brain caused by an autoimmune response. The clinical presentation is different in children compared to adults. Children with AIE are more likely to present with multifocal neuropsychiatric symptoms (ie, a mix of psychiatric and neurological issues), rather than isolated clinical syndromes where symptoms are more homogeneous (eg, vision or mood only).¹ Pediatric AIE is also less associated with tumors when compared with AIE in adults.¹

Diagnosis of AIE in children relies on the detection of specific antibodies in addition to a combination of clinical criteria.¹ Because clinical symptoms often overlap significantly between different AIE subtypes (eg, anti-N-methyl-D-aspartate receptor [NMDAR] encephalitis, anti-myelin oligodendrocyte glycoprotein [MOG]–associated encephalitis), guideline recommendations include using a panel of neural autoantibodies rather than testing for single antigens.¹ However, diagnostic testing for AIE can be challenging due to potentially long turnaround times when using broad antibody panels. Furthermore, broad panels, though exhaustive, may include adult-onset paraneoplastic markers (eg, anti-Hu) that are very rare in children.² 

Smaller panels targeting commonly detected pediatric AIE antibodies require less volume than the large panels used for adults and have a faster turnaround time. For children, these include antibodies that target the NMDAR1 subunit of NMDAR, MOG, and glutamic acid decarboxylase 65 (GAD65) (Table 1 and Figure).^1,3–11 

Table 1. Characteristics of Commonly Detected Autoantibodies in Pediatric AIE

Figure. Suggested Use of Pediatric Autoimmune Encephalitis Panels in the Diagnosis of Autoimmune Encephalitis.

Testing for other serum and/or CSF antibodies may be considered when results for commonly detected antibodies are negative.¹  Serum aquaporin-4 (AQP4) antibodies, though rare in children (≤5% of patients with AQP4 antibodies), are highly specific for AIE when titers are high and are diagnostic of neuromyelitis optica spectrum disorder (NMOSD).^12,13  Collapsin response mediator protein 5 (CRMP5) antibodies detected in the serum and CSF indicate pediatric AIE and are associated with paraneoplastic syndrome—although CRMP5 antibodies are rare in children, they can be linked to thymomas.¹⁴  

Quest Diagnostics offers Pediatric Autoimmune Encephalitis Evaluation With Reflexes, Serum (test code: 18410) and CSF (test code: 18420) panels (Table 2). Guideline recommendations indicate that diagnostic testing for children with suspected AIE should prioritize comprehensive antibody testing of serum and/or CSF as the sensitivity for certain antibodies may be higher or lower depending on specimen type (Table 1).^1,3–8

Table 2. Pediatric Autoimmune Encephalitis Evaluation Panels With Reflexes

Interpretive information

While positive antibodies can confirm a definitive diagnosis (Table 1 and Figure), they are not mandatory; a diagnosis can still be made based on clinical history and other paraclinical findings.¹ 

Negative results do not rule out AIE; a diagnosis can be made with evidence of acute or subacute symptom onset, clinical evidence that includes 2 or more features of neurologic dysfunction, 1 or more paraclinical features that indicate neuroinflammation, and the exclusion of other etiologies.¹