BASICS
DESCRIPTION
Neuromyelitis Optica (NMO) or Devic’s disease is an autoimmune relapsing demyelinating disease of the CNS that has been thought to be a variant of multiple sclerosis (MS). It manifests with severe optic neuritis, often bilateral, and transverse myelitis, usually sparing the brain and the brainstem. Recovery of vision can occur in a few weeks, though myelitis takes months to recover. NMO was found to be a distinct entity from MS when an autoantibody, NMO-IgG, to the aquaporin-4 channel protein (AQP4), a water channel protein important in the regulation of cell fluid balance in the CNS, was discovered in 2004 (1)[A].
EPIDEMIOLOGY
Incidence
The incidence is unknown but rare.
Prevalence
Prevalence in the Caribbean is about 1:100,000. It is very uncommon in White patients in Europe and North America, and makes up <1% of demyelinating diseases in that group. It is most common in Japan, where it may represent one-third of all demyelinating diseases.
RISK FACTORS
Women have 4–9 times the risk than men, and median onset is in the thirties, a decade later than MS.
Genetics
No genetic influence has been discovered.
GENERAL PREVENTION
No primary preventive measures are known, but immunomodulatory therapies discussed below are used for secondary prevention.
PATHOPHYSIOLOGY
Autoantibodies targeting the aquaporin-4 channel activate complement and cause inflammation, resulting in demyelination and extensive tissue necrosis.
ETIOLOGY
The etiology of NMO is idiopathic, but post-infectious cases linked to syphilis, HIV, Chlamydia, varicella, CMV, and EBV have been reported.
COMMONLY ASSOCIATED CONDITIONS
No other conditions are known to be associated with NMO.
DIAGNOSIS
HISTORY
Following a viral-type prodrome, sudden, painful, complete loss of vision in one eye occurs, often followed by similar symptoms in the other eye. Paraplegia due to multilevel spinal cord involvement is a less common presentation. Patients often have concurrent fever, headache, severe muscle spasms, and anorexia.
PHYSICAL EXAM
• Visual loss presents as central and peripheral visual loss and achromatopsia.
• The usual pattern of spinal cord involvement is transverse myelitis, or complete spinal dysfunction with paraparesis or quadriparesis (depending on location of lesion), and bowel and bladder dysfunction.
• Hemisection (Brown-Sequard) or central cord syndromes (loss of function in upper extremities, with preservation of lower extremities) have been reported.
• Severe, painful flexor spasms of the trunk and extremities are common.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
Initial lab tests
IgG test for aquaporin-4 antibody is positive in 80% of cases.
Follow-up & special considerations
Optical coherence tomography (OCT) findings in NMO parallel central and peripheral vision defects.
Imaging
Initial approach
• MRI of the brain, optic nerves, and appropriate portions of the spinal cord are mandatory for the correct diagnosis.
• The earlier diagnostic requirement that the initial brain MRI be normal has been dropped in the revised criteria (2)[A]. Brain MRI is atypical and does not meet diagnostic criteria for MS.
• Brain lesions are ovoid and concentrated in the cerebellum, brainstem, and in periventricular regions.
• MRI lesions in the spinal cord typically cause expansion of the cord, and extend over more than 3 spinal segments.
Follow-up & special considerations
Follow-up imaging is dependent on the development of new symptoms.
Diagnostic Procedures/Other
Lumbar puncture is useful in differentiating NMO from MS; 50 or more WBC/mm3 or 5 or more neutrophils/mm3 is considered diagnostic. Oligoclonal bands are generally absent.
Pathological Findings
The hallmark of NMO distinction from MS is the severe inflammatory demyelination seen in spinal cord lesions, with neutrophil, eosinophil and macrophage predominance, severe edema, and patchy necrosis involving both the white and gray matter. Perivascular complement activation and immunoglobulin deposition suggest an antibody-mediated response. It is postulated that NMO antibody to aquaporin-4 channels is a component of this antibody-mediated inflammation.
DIFFERENTIAL DIAGNOSIS
• Demyelinating optic neuritis
• Recurrent/relapsing optic neuritis
• Relapsing inflammatory optic neuropathy
• Multiple sclerosis and variant forms
• Acute transverse myelitis
• Tropical spastic paraparesis
• Neurosarcoidosis
• Systemic lupus erythematosus
• Neuro-Behçet’s disease
• Neurosyphilis
• HIV-related myelopathy
TREATMENT
MEDICATION
First Line
• High-dose intravenous corticosteroids (e.g., methylprednisolone 1 g/d for 5 days). Patients who do not respond can be treated with plasmapheresis (7 exchanges of 55 mL/kg every other day).
• Early treatment has been found to be more effective.
Second Line
• Prevention of relapsing disease (more than 1 attack), especially in patients with positive NMO serology, requires immunosuppressive therapy.
• The most standard approach is a combination of oral prednisone (1 mg/kg/d) and azathioprine (2–3 mg/kg/d), with the prednisone being tapered as azathioprine exerts its effect (reduction in WBC and MCV, mean corpuscular volume).
• Rituximab, a murine monoclonal CD-20 positive B-cell depleting agent, has been used, based on the theory that NMO is a humorally-mediated disease, and small studies have shown success.
• Other agents, such as mycophenolate mofetil, mitoxantrone, methotrexate, and cyclophosphamide, have been used, although no studies have been conducted.
ADDITIONAL TREATMENT
General Measures
No specific measures other than medication treatment are available.
Issues for Referral
Since NMO is potentially a relapsing disease, even patients with full recovery need to be followed on a regular basis.
Additional Therapies
Rehabilitation, such as physical or occupational therapy, is indicated for patients with spinal cord involvement.
COMPLEMENTARY & ALTERNATIVE THERAPIES
No specific therapies have been used.
SURGERY/OTHER PROCEDURES
No surgical procedures available.
IN-PATIENT CONSIDERATIONS
Initial Stabilization
Patients with severe myelopathy need to be admitted to hospital, and if they have a high cervical lesion that interferes with respiration, may need to be intubated and artificially ventilated.
Admission Criteria
Severe visual loss, paraparesis or quadriparesis
IV Fluids
As needed for hydration.
Nursing
Ventilator care, management of paralysis, and bladder and bowel care are the mainstay of nursing care.
Discharge Criteria
Patients can be discharged as they finish their treatments; often, transfer to a rehabilitation facility will be necessary.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patients with spinal cord involvement will need rehabilitation by physical and occupational therapy.
Patient Monitoring
Follow-up visits with an ophthalmologist or neurologist usually will occur on a quarterly basis.
DIET
No specific diet needed
PATIENT EDUCATION
Patients need to be educated on all the possible visual, motor, and sensory manifestations of a relapse and advised to seek immediate medical attention if any occur.
PROGNOSIS
The mortality rate can be as high as 20–25%, and median survival has been found to be 8 years from date of diagnosis. The mortality rates are highest in patients of African origin.
COMPLICATIONS
Permanent neurologic defects are common, with only partial remission of symptoms, after each attack.
REFERENCES
1. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: Distinction from multiple sclerosis. Lancet 2004;354(9451):2106–2112.
2. Wingerchuk DM, Lennon VA, Pittock SJ, et al. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006;66:1485–1489.
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