What is the difference between multiple sclerosis and neuromyelitis optica?

Distinguishing Multiple Sclerosis from Neuromyelitis Optica

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are distinct demyelinating diseases that require different treatment approaches, with NMOSD demanding long-term immunosuppression while MS typically responds to disease-modifying therapies—accurate differentiation is critical because misdiagnosis leads to inappropriate treatment and worse outcomes. 1, 2

Key Clinical Differences

Disease Distribution Pattern

MS demonstrates widespread CNS involvement with multiple small lesions throughout the brain and spinal cord, while NMOSD predominantly targets the optic nerves and spinal cord with limited brain involvement. 1, 2

• MS lesions: Multiple discrete focal lesions, typically small (<2 vertebral segments in cord), distributed throughout periventricular white matter (41%), deep white matter (42%), and juxtacortical regions 3, 4
• NMOSD lesions: Preferentially affect deep white matter (68%) over periventricular regions (17%), with characteristic longitudinally extensive transverse myelitis (LETM) spanning ≥3 vertebral segments 4, 2

Spinal Cord Involvement

The spinal cord lesion pattern is the most reliable imaging discriminator between these diseases. 4, 2

• NMOSD: Thoracic lesions predominate (71% vs 29% cervical), with significantly longer thoracic lesions than cervical lesions; contiguous lesions extending ≥3 vertebral segments are characteristic 4, 2
• MS: Equal distribution between cervical and thoracic regions (46% vs 54%), with no significant length difference between locations; lesions are typically short (<2 segments), peripheral, wedge-shaped on axial imaging 3, 4

Optic Nerve Characteristics

Optic nerve involvement patterns reliably distinguish these conditions. 3, 5

• NMOSD red flags: Bilateral simultaneous involvement, posterior optic nerve extending to chiasm, long optic nerve lesions 3, 5
• MS: Typically unilateral, short anterior optic nerve lesions not involving chiasm 3

Diagnostic Biomarkers

Serum Antibody Testing

NMO-IgG (aquaporin-4 antibody) is 76% sensitive and 94% specific for NMOSD and should be tested in all suspected cases. 1, 2

• Positive aquaporin-4 antibody virtually confirms NMOSD diagnosis 1, 2
• Anti-MOG antibodies may be present in seronegative NMOSD cases 3

Brain MRI Patterns

Brain MRI at disease onset is often normal or nondiagnostic for MS in NMOSD, whereas MS typically shows multiple periventricular lesions meeting dissemination in space criteria. 1, 2

• NMOSD brain lesions (when present): "Cloud-like" poorly marginated corpus callosum lesions, diencephalic involvement, area postrema lesions 3
• MS brain lesions: Ovoid periventricular lesions perpendicular to corpus callosum ("Dawson's fingers"), juxtacortical U-fiber involvement, multiple small discrete lesions 3

Revised Diagnostic Criteria for NMOSD

Definite NMOSD requires optic neuritis AND acute myelitis AND at least 2 of the following 3 supportive criteria: 1, 2

1. Contiguous spinal cord MRI lesion extending ≥3 vertebral segments 2
2. Brain MRI at onset nondiagnostic for MS 2
3. NMO-IgG (aquaporin-4 antibody) seropositivity 2

Critical Pitfalls to Avoid

Common Misdiagnosis Scenarios

Up to 7.2% of clinically isolated syndromes may transiently meet some NMO criteria, but only 0.3% meet full diagnostic criteria—premature diagnosis should be avoided. 6

• Some NMOSD patients have extra-optic-spinal CNS symptoms (14.6%), which does not exclude the diagnosis 2
• Presence of brain MRI lesions does not exclude NMOSD, though they differ in pattern from MS 2
• Historical classification systems considered NMOSD a variant of MS, but current evidence establishes them as separate diseases requiring different treatments 3, 1

Structural Brain Differences

Advanced MRI reveals larger thalamic volume reductions and more diffuse white matter changes in MS compared to NMOSD, with the thalamus being the most discriminating region. 7

• Both diseases show global gray matter volume reductions compared to healthy controls 7
• MS demonstrates significantly greater bilateral thalamic involvement than NMOSD 7
• Fractional anisotropy reductions are more extensive in MS 7

Treatment Implications

The distinction is clinically critical because NMOSD requires long-term immunosuppressive therapy (not standard MS disease-modifying therapies), and some MS treatments may worsen NMOSD. 1