Neural Antibody Testing in AIE
Paired CSF & Serum Neural Antibody Testing
- It is recommended to order a paired CSF and serum comprehensive panel-based neural antibody testing.
- Sensitivity of serum is higher than CSF for some neural antibodies (e.g.LGI1 and CASPR2), while sensitivity of CSF is higher than serum for others (e.g.NMDAR and GFAP).
Isolated Positive Serum Anti-NMDA
- Anti-NMDA Ab positivity in serum is less sensitive compared to CSF. It is highly specific in CSF.
- Isolated serum Anti-NMDA Ab has been reported in healthy individuals and in patients with schizophrenia and other psychotic disorders.
- Caution must be exercised in cases of isolated psychiatric manifestations.
- Patients with Anti-NMDA encephalitis present with a subacute onset of psychiatric presentation with concurrent neurological symptoms, rapid progression and abnormal para-clinical investigations including for example EEG and MRI brain.
Interpretation
- Caution must be exercised in the context of atypical presentation and positive serum Anti-NMDA Ab done only by Cell Based Assay (CBA) without confirmatory TIIF/IHC* testing. Therefore, it is recommended to inquire about the methods used by the testing laboratory.
- Isolated positive blot testing for intracellular antibodies should be interpreted with caution in a patient with an atypical clinical presentation. Some laboratories only perform blot testing for intracellular antibodies without confirmatory TIIF/IHC* testing.
* TIIF/IHC:Tissue Indirect Immunofluorescence/Immunohistochemistry
Elevated Anti-GAD-65 Antibodies
- Anti-GAD-65 neurological autoimmunity is typically associated with very high levels of Anti-GAD-65 Ab (ELISA: Serum > 10000 IU/ml or CSF > 100 IU/ml )
-Very Low serum or CSF Anti-GAD-65 Ab titer (ELISA Testing) is not specific for neurological autoimmunity including Serum < 2000 IU/ml, CSF: < 100 IU/ml
- Low levels of Anti-GAD-65 Ab are not specific for neurological autoimmunity and can be seen in patients with type I diabetes and up to 8% of healthy individuals.