What are the differences between Neuromyelitis Optica (NMO) and Multiple Sclerosis (MS)?

Contrasting NMO and MS

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are distinct autoimmune demyelinating diseases that differ fundamentally in their pathophysiology, clinical presentation, imaging features, and treatment responses, with NMO being more severe and requiring different therapeutic approaches than MS. 1

Serologic Differentiation

• AQP4-IgG antibodies are highly specific for NMO/NMOSD and are absent in MS, making this the most definitive distinguishing feature 1, 2
• AQP4-IgG testing should be performed using cell-based assays for optimal sensitivity and specificity 3
• The presence of AQP4 antibodies unequivocally differentiates NMO from MS 4

Clinical Presentation Differences

Attack Characteristics

• NMO causes more severe attacks with poorer recovery compared to MS, particularly affecting vision and motor function 5, 4, 6
• NMO patients frequently experience bilateral optic neuritis, whereas MS typically presents with unilateral involvement 4
• Intractable nausea, vomiting, and hiccups (area postrema syndrome) are characteristic of NMO but not MS 3, 4
• Respiratory failure from cervical myelitis occurs in NMO but is rare in MS 6

Disease Course

• NMO typically follows a relapsing course with severe stepwise disability accumulation, with one-third of patients dying from respiratory failure 6
• MS more commonly shows a relapsing-remitting pattern with variable recovery and less severe individual attacks 2, 4
• Progressive disability in NMO is attack-related, while MS can develop primary or secondary progressive forms 4, 6

MRI Imaging Distinctions

Spinal Cord Lesions

• NMO characteristically shows longitudinally extensive transverse myelitis (LETM) extending over ≥3 contiguous vertebral segments, which rarely occurs in MS 1, 3, 5
• LETM with T1 hypointensity is particularly suggestive of NMO over MS 4
• MS spinal cord lesions are typically short (<2 segments) and peripherally located 1

Brain MRI Features

• MS shows characteristic perivenular lesions, Dawson's fingers, ovoid periventricular lesions, and juxtacortical U-fiber lesions that are absent or rare in NMO 1, 4
• NMO brain lesions, when present, tend to be periependymal (especially around the brainstem and area postrema) rather than periventricular 1, 4
• Initial brain MRI is often normal or shows only nonspecific white matter lesions in NMO, whereas MS typically shows multiple characteristic lesions 1, 5
• Thalamic involvement is more prominent in MS than NMO 7

Optic Nerve Involvement

• NMO optic nerve lesions extend over >50% of the optic nerve length or involve the optic chiasm, whereas MS optic neuritis typically involves only 1-2 segments 1
• Perioptic enhancement (optic nerve sheath involvement) occurs in NMO but not typically in MS 1

Laboratory Findings

CSF Analysis

• NMO frequently shows CSF pleocytosis >50 cells/mm³, often with neutrophils and/or eosinophils, which is uncommon in MS 4, 6
• Oligoclonal bands are present in >90% of MS patients but are often absent in NMO 1, 4
• Elevated CSF glial fibrillary acidic protein is more characteristic of NMO than MS 4

Demographic Patterns

• NMO shows predilection for non-white populations, whereas MS is more common in white populations 4
• Very late onset (>50 years) is more suggestive of NMO than MS 4
• Both conditions affect women more than men, but the female predominance may be more pronounced in NMO 2, 4

Critical Treatment Implications

• Some MS disease-modifying therapies (particularly interferon-beta and natalizumab) may exacerbate NMO, making early accurate diagnosis crucial 2, 5
• NMO requires long-term immunosuppressive therapy with agents like rituximab, while MS is typically treated with immunomodulatory therapies 3, 2, 5
• B-cell depleting therapies, anti-IL-6 receptor antibodies, and complement inhibitors are effective for AQP4-positive NMO but are not standard MS treatments 3

Common Diagnostic Pitfalls

• Up to 70% of NMOSD patients have brain MRI lesions at onset, which can lead to misdiagnosis as MS 1
• AQP4-antibody negative patients with overlapping features require careful evaluation of all clinical, imaging, and laboratory discriminators 4
• The presence of brain lesions does not exclude NMO diagnosis, contrary to older diagnostic criteria 2, 5
• When AQP4-IgG and MOG-IgG are both negative, distinguishing NMO from MS becomes more challenging and requires integration of multiple clinical and imaging features 1, 4