Question

A 16-year-old girl presents with subacute onset behavioral changes, confusion, and visual blurring in one eye. On examination, she has optic neuritis and altered sensorium. MRI shows hyperintensities in the temporal lobes and optic nerve involvement. Autoimmune encephalitis is suspected. CSF is normal. What is the next best investigation?

• A. Repeat CSF analysis
• B. Serum anti-MOG and anti-AQP4 antibodies
• C. Anti-NMDAR antibody in CSF
• D. Visual evoked potentials

Hint:

Autoantibody Testing Location Pearls:
- Anti-MOG & Anti-AQP4: Serum is MORE sensitive than CSF (Cell-based assay).
- Anti-NMDAR: CSF is MORE sensitive than Serum.
- Encephalitis + Optic Neuritis $\rightarrow$ Think MOGAD NMOSD $\rightarrow$ Send Serum anti-MOG & anti-AQP4.

Answer 1

The Correct Option is B

Concept:
The combination of acute/subacute encephalopathy (altered behavior, confusion) accompanied by central demyelination manifesting as optic neuritis represents an inflammatory demyelinating central nervous system spectrum disorder, notably MOG-antibody-associated disease (MOGAD) or Neuromyelitis Optica Spectrum Disorder (NMOSD).
Explanation:
• Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (MOGAD) frequently manifests in children and adolescents as acute disseminated encephalomyelitis (ADEM), cortical encephalitis, or severe unilateral/bilateral optic neuritis.

• Similarly, Aquaporin-4 (AQP4) IgG-positive Neuromyelitis Optica Spectrum Disorder (NMOSD) presents with optic neuritis and brainstem/diencephalic/cerebral lesions.

• Testing for serum anti-MOG IgG and anti-AQP4 antibodies using cell-based assays (CBA) is the most specific and sensitive next diagnostic step.

• Serum is significantly more sensitive than CSF for detecting both MOG and AQP4 antibodies because these autoantibodies are primarily produced in peripheral lymphoid tissues and enter the central nervous system across a disrupted blood-brain barrier.

• While anti-NMDAR encephalitis causes psychiatric symptoms, cognitive decline, and seizures, it does not typically present with classic optic neuritis and optic nerve demyelinating hyperintensities on MRI.

• Repeating CSF analysis when basic CSF parameters are non-diagnostic does not provide disease-defining specificity compared to serum autoantibody testing.
Final Answer:
The next best investigation to confirm the underlying neuroinflammatory demyelinating etiology in a patient presenting with encephalopathy and optic neuritis is serum anti-MOG and anti-AQP4 antibodies.