What is Devic disease (Neuromyelitis Optica), a rare autoimmune disorder affecting the optic nerve and spinal cord, typically diagnosed in adult women with a history of other autoimmune diseases?

What is Devic Disease (Neuromyelitis Optica)?

Devic disease, now termed neuromyelitis optica spectrum disorder (NMOSD), is a rare autoimmune inflammatory demyelinating disease of the central nervous system that predominantly attacks the optic nerves and spinal cord, distinct from multiple sclerosis, and is characterized by the presence of aquaporin-4 (AQP4) antibodies in approximately 75% of cases. 1, 2

Core Pathophysiology

• NMOSD results from autoimmune attack against aquaporin-4, the dominant water channel protein located in astrocyte foot processes throughout the CNS 2, 3
• The disease causes severe immune-mediated demyelination and axonal damage with distinctive pathological features including perivascular IgG and complement deposition, granulocyte and eosinophil infiltrates, and vascular wall hyalinization 3
• These pathological characteristics clearly distinguish NMOSD from multiple sclerosis and other demyelinating diseases 3

Clinical Presentation

Hallmark Features

• Severe optic neuritis (often bilateral and simultaneous) leading to visual loss, frequently with posterior optic nerve involvement extending to the chiasm 4, 2
• Longitudinally extensive transverse myelitis (LETM) spanning ≥3 contiguous vertebral segments, causing limb weakness and bladder dysfunction 4, 2
• The disease typically follows a relapsing course rather than being monophasic 2, 3

Additional Clinical Syndromes

• Area postrema syndrome with intractable nausea, vomiting, and hiccups 5
• Brainstem syndromes with peri-ependymal brainstem lesions 5
• Diencephalic and cerebral syndromes affecting regions around the third and fourth ventricles 5

Diagnostic Criteria

For AQP4-IgG Positive Patients

At least one core clinical characteristic is required including optic neuritis, acute myelitis, area postrema syndrome, brainstem syndrome, diencephalic syndrome, or cerebral syndrome 4

For AQP4-IgG Negative or Unknown Status

More stringent criteria apply: definite NMOSD requires optic neuritis AND acute myelitis AND at least 2 of 3 supportive criteria:

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

Key Imaging Characteristics

Spinal Cord Features

• Longitudinally extensive lesions affecting ≥3 vertebral segments (LETM), often with central cord involvement and associated swelling 5, 4
• Lesions are typically T1 hypointense and show prominent cord swelling 5
• "Cloud-like" enhancement pattern that is poorly marginated, distinct from MS 5

Optic Nerve Features

• Long optic nerve lesions with T2 hyperintensity and gadolinium enhancement extending over half the optic nerve length or involving the optic chiasm 5, 4
• Posterior optic nerve involvement including the chiasm is highly suggestive 5, 6

Brain Features

• Brain lesions are atypical for MS, often involving regions around the third and fourth ventricles 5, 3
• "Cloud-like," poorly margined corpus callosum lesions with marbled pattern 5
• Periaqueductal and area postrema lesions are characteristic 5

Critical Distinctions from Multiple Sclerosis

• NMOSD is a distinct disease entity, not a variant of MS, with important immunopathological, clinical, prognostic, and therapeutic differences 7
• MS lesions are typically small (<2 vertebral segments), peripheral, and wedge-shaped, whereas NMOSD shows LETM 5
• MS brain lesions show periventricular ovoid lesions and Dawson's fingers, which are absent in typical NMOSD 5
• CSF oligoclonal bands are typically absent in NMOSD but present in 85-95% of MS cases 5

Seronegative NMOSD

• Approximately 25% of NMOSD patients are AQP4-IgG seronegative 4
• Some seronegative patients may have anti-MOG antibodies, representing a distinct entity (MOG-antibody disease) requiring different management 5, 4
• Cell-based assays using full-length human MOG are the gold standard for antibody testing 8

Epidemiology and Risk Factors

• NMOSD is a rare disorder that predominantly affects adult women 1
• Association with other autoimmune diseases is common, including autoimmune thyroiditis 9
• Certain environmental and genetic factors have been identified as risk factors 1

Treatment Implications

Acute Attack Management

• High-dose intravenous methylprednisolone (1 gram daily for 3-5 consecutive days) should be initiated immediately 2
• Plasma exchange therapy should be used in severe cases or steroid-refractory attacks 2, 3

Relapse Prevention

• Every patient with NMOSD should be started on immunosuppressive therapy soon after the acute attack 2
• Options include azathioprine, methotrexate, mycophenolate, or rituximab, typically continued for approximately 5 years 2
• Treatment differs fundamentally from MS, as MS disease-modifying therapies may worsen NMOSD 2

Critical Pitfalls to Avoid

• Delaying diagnosis while waiting for dissemination in space can be harmful, as many NMOSD patients present with isolated syndromes warranting immediate antibody testing 4
• Assuming all NMOSD is AQP4-positive is incorrect; approximately 25% are seronegative and may have anti-MOG antibodies requiring different management 4
• Treating NMOSD as MS can be catastrophic, as certain MS therapies may exacerbate NMOSD 2
• Failure to obtain urgent MRI with contrast delays treatment, and treatment delay beyond 2 weeks is an unfavorable prognostic factor 8