Tests
1st tests to order
MRI - brain
Test
Should be performed on high-field magnet (3 T is preferred, but 1.5 T is acceptable), with intravenous gadolinium-based contrast. Image field should cover optic nerves and chiasm.[3] Findings support the diagnosis of optic neuritis and rule out other causes of optic nerve damage such as compressive neuropathy. Also helpful for predicting conversion to clinically definite multiple sclerosis.
Result
swelling of optic nerve; enhancement in optic nerve; white matter lesions in patients with multiple sclerosis (MS) or at risk of MS
CBC
Test
Nonspecific marker for infection.
Result
high WBC (infection)
ESR
Test
Nonspecific marker for infection/inflammation; very high in arteritic ischemic optic neuropathy as part of giant cell arteritis, which can mimic ON.
Result
high in giant cell arteritis
C-reactive protein
Test
Nonspecific marker for infection/inflammation.
Result
high in infection/inflammation
venereal disease research laboratory (VDRL)
Test
Positive in syphilis.
Result
positive in syphilis infection
aquaporin-4 (AQP4) antibody, myelin oligodendrocyte glycoprotein (MOG) antibody, and collapsin response mediator protein 5 (CRMP5) antibody
Test
Indicated in suspected neuromyelitis optica (NMO; Devic disease); currently incorporated in NMO spectrum disorder (NMOSD) for example, with bilateral ON or coexistence with longitudinally extensive transverse myelitis.
Highly specific (about 99%) for this condition.[30][31] Of the patients with NMOSD who are negative for AQP4 antibodies (approximately 30%), a proportion are positive for MOG antibodies, have more frequent optic neuritis, and have a better overall prognosis.[32] CRMP5 seropositivity is associated with paraneoplastic neurologic syndrome.[33]
Result
negative to rule out/positive to confirm ON in the context of NMOSD (AQP4 antibodies), MOG antibody-associated neurologic disease (MOG antibodies), or paraneoplastic neurologic syndrome (CRMP5 antibodies)
uric acid
Test
Nonspecific indicator of reduced antioxidant reserve; has been shown to be low in MS and in primary demyelinating ON.[34]
Result
low
serum ACE
Test
Elevated in patients with sarcoidosis, and responds to treatment. May be nonspecifically elevated in other inflammatory diseases, including a proportion of patients with MS, although not at the high levels seen in sarcoidosis.[35]
Result
normal or elevated
ANA
Test
Positive in patients with systemic lupus erythematosus (SLE). Consider for anyone suspected of having SLE. Currently the most sensitive test for confirming the diagnosis of SLE when accompanied by typical clinical findings. A positive ANA in itself is not diagnostic as it may be nonspecifically elevated in other inflammatory diseases including a proportion of patients with multiple sclerosis, although not at the high titers seen in SLE.[36]
Result
negative or positive
B12 and folate
Test
Low B12 and folate levels may mimic primary demyelinating disease, including occasionally inflammatory optic neuropathies.
Result
normal to rule out B12 deficiency
Tests to consider
Lyme titer
Test
A Lyme titer testing for Borrelia burgdorferi should be ordered in endemic areas or otherwise in special circumstances (e.g., history of tick bite, erythema chronicum migrans).
Result
negative or positive
cerebrospinal fluid analysis
Test
Denote intrathecal production of immunoglobulins; a sensitive but not highly specific test for primary demyelinating disease. When ON is a clinically isolated syndrome (CIS), positive oligoclonal bands or high IgG index signify risk of conversion to clinically definite multiple sclerosis (CDMS). Due to the invasive nature of lumbar puncture, all other noninvasive tests should be pursued first.[27] Note that the CSF is normal in 10% to 20% of MS cases.
The current (McDonald) MS diagnostic criteria incorporate CSF oligoclonal bands as indicator of dissemination in time.[27]
Result
positive oligoclonal bands; high IgG index
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