(See also Overview of Demyelinating Disorders Overview of Demyelinating Disorders Myelin sheaths cover many nerve fibers in the central and peripheral nervous system; they accelerate axonal transmission of neural impulses. Disorders that affect myelin interrupt nerve transmission... read more .)
Neuromyelitis optica spectrum disorder causes acute optic neuritis Optic Neuritis Optic neuritis is inflammation of the optic nerve. Symptoms are usually unilateral, with eye pain and partial or complete vision loss. Diagnosis is primarily clinical. Treatment is directed... read more , sometimes bilateral, plus demyelination of the cervical or thoracic spinal cord. It was previously considered to be a variant of multiple sclerosis Multiple Sclerosis (MS) Multiple sclerosis (MS) is characterized by disseminated patches of demyelination in the brain and spinal cord. Common symptoms include visual and oculomotor abnormalities, paresthesias, weakness... read more 
(MS) but is now recognized as a different disorder.
In neuromyelitis optica spectrum disorder, the immune system targets aquaporin 4, a protein that is present on astrocytes in the brain and particularly the spinal cord and optic nerves, or myelin oligodendrocyte glycoprotein (MOG), which is present on the myelin of oligodendrocytes in the same areas of the CNS and possibly other targets. Astrocytes and oligodendrocytes are damaged by autoimmune-mediated inflammation as well as demyelination.
There are three types of neuromyelitis optica spectrum disorder:
Aquaporin-4 antibody positive (formerly known as NMO antibody positive)
Myelin oligodendrocyte glycoprotein (MOG) positive
Double-antibody negative (patients with this type have clinical neuromyelitis optica spectrum disorder but have neither antibody)
Symptoms and Signs of NMOSD
Symptoms of neuromyelitis optica spectrum disorder include visual loss, muscle spasms, paraparesis or quadriparesis, and incontinence.
Specific characteristic presentations include
Severe bilateral optic neuritis that involves the optic chiasm, causing loss of vision in the horizontal half (upper or lower) of the visual field (altitudinal visual field defect) or loss of acuity (20/200 or worse)
A complete spinal cord syndrome, particularly with paroxysmal tonic spasms
An area postrema syndrome, causing intractable hiccups or nausea and vomiting (the area postrema is a structure that controls vomiting and is located on the floor of the 4th ventricle)
Acute transverse myelitis Acute Transverse Myelitis Acute transverse myelitis is acute inflammation of gray and white matter in one or more adjacent spinal cord segments, usually thoracic. Causes include multiple sclerosis, neuromyelitis optica... read more extending over ≥ 3 contiguous spinal cord segments
Diagnosis of NMOSD
Brain and spinal cord MRI
Visual evoked potentials
Diagnosis of neuromyelitis optica spectrum disorder usually includes brain and spinal cord MRI and visual evoked potentials (1 Diagnosis reference Neuromyelitis optica spectrum disorder is a demyelinating disorder that predominantly affects the eyes and spinal cord but can affect other structures in the central nervous system (CNS) that... read more ).
The following features help distinguish neuromyelitis optica from multiple sclerosis (MS):
Neuromyelitis optica affects several (typically ≥ 3) contiguous spinal segments of the spinal cord, whereas MS typically affects a single segment.
On MRI, cerebral white matter lesions are uncommon in neuromyelitis optica, unlike in MS.
On MRI, morphology and distribution of the lesions differ from those in MS.
Visual evoked potentials Measurement of Evoked Responses Visual, auditory, or tactile stimuli are used to activate corresponding areas of the cerebral cortex, resulting in focal cortical electrical activity. Ordinarily, these small potentials are... read more can help differentiate neuromyelitis optica from other optic neuropathies. Findings in neuromyelitis optica spectrum disorder include reduced amplitudes or prolonged latencies. This test is also useful for detecting clinically inapparent damage before symptoms develop.
Blood tests to measure an IgG antibody specific for neuromyelitis optica spectrum disorder (aquaporin-4 antibody [also known as NMO-IgG]) may be done to differentiate it from MS. Anti-MOG (myelin oligodendrocyte glycoprotein) antibodies identify a subset of patients who have neuromyelitis optica spectrum disorder and who appear to have different clinical features, fewer exacerbations, and better recovery than patients with aquaporin-4 antibodies or with neither antibody. Some patients with clinical evidence of neuromyelitis optical spectrum disorder do not have either antibody and are classified as having double antibody negative neuromyelitis optica spectrum disorder.
Diagnosis reference
1. Wingerchuk DM, Banwell B, Bennett JL, et al: International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85 (2):177–189, 2015. doi: 10.1212/WNL.0000000000001729 Epub 2015 Jun 19
Treatment of NMOSD
Corticosteroids and immunomodulatory or immunosuppressive treatments
There is no cure for neuromyelitis optica. However, treatment can prevent, slow, or decrease the severity of exacerbations and may reduce the risk of disability in the short term (1 Treatment references Neuromyelitis optica spectrum disorder is a demyelinating disorder that predominantly affects the eyes and spinal cord but can affect other structures in the central nervous system (CNS) that... read more , 2 Treatment references Neuromyelitis optica spectrum disorder is a demyelinating disorder that predominantly affects the eyes and spinal cord but can affect other structures in the central nervous system (CNS) that... read more ).
Eculizumab, a C5 complement inhibitor, is available for the treatment of aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. Adverse effects include respiratory infections, headache, and pneumonia and may be significant; thus, patients should be closely monitored (3 Treatment references Neuromyelitis optica spectrum disorder is a demyelinating disorder that predominantly affects the eyes and spinal cord but can affect other structures in the central nervous system (CNS) that... read more ) Because one patient developed meningococcal sepsis, vaccination for meningococcus is required before initiating therapy.
Satralizumab (a monoclonal antibody that targets the interleukin-6 receptor) and inebilizumab (a monoclonal antibody that targets CD19 on B-cells) are also available for the treatment of aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. Patients should be closely monitored for infections such as urinary tract and respiratory infections.
Methylprednisolone and azathioprine are often used together. Plasma exchange Plasma exchange Apheresis refers to the process of separating the cellular and soluble components of blood using a machine. Apheresis is often done on donors where whole blood is centrifuged to obtain individual... read more may help people who do not respond to corticosteroids.
Rituximab, an anti–B-cell antibody, has been shown to reduce relapses in a double-blind, placebo-controlled trial (4 Treatment references Neuromyelitis optica spectrum disorder is a demyelinating disorder that predominantly affects the eyes and spinal cord but can affect other structures in the central nervous system (CNS) that... read more ). Other immunomodulatory and immunosuppressive therapies are sometimes used.
Natalizumab and fingolimod appear ineffective and may be harmful.
Treatment of symptoms Symptom control is similar to that for MS. Baclofen or tizanidine may relieve muscle spasms.
Treatment references
1. Kong F, Wang J, Zheng H, et al: Monoclonal antibody therapy in neuromyelitis optica spectrum disorders: A meta-analysis of randomized control trials. Front Pharmacol 20;12:652759, 2021. doi: 10.3389/fphar.2021.652759
2. Xue T, Yang Y, Lu Q, et al: Efficacy and safety of monoclonal antibody therapy in neuromyelitis optica spectrum disorders: Evidence from randomized controlled trials. Mult Scler Relat Disord 43:102166, 2020. doi: 10.1016/j.msard.2020.102166 Epub 2020 May 11.
3. Pittock SJ, Berthele A, Fujihara K, et al: Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med 381 (7):614–625, 2019. doi: 10.1056/NEJMoa1900866 Epub 2019 May 3
4. Tahara M, Oeda T, Okada K, et al: Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): A multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol 19 (4):298–306, 2020. doi: 10.1016/S1474-4422(20)30066-1
Key Points
Neuromyelitis optica spectrum disorder causes demyelination, typically with antibodies to aquaporin-4 or myelin oligodendrocyte glycoprotein.
Typical symptoms include visual loss, muscle spasms, paraparesis or quadriparesis, and incontinence.
Diagnose neuromyelitis optica spectrum disorder using brain and spinal cord MRI and visual evoked potentials.
Treatments include corticosteroids and immunomodulatory or immunosuppressive treatments (eg, eculizumab, rituximab).
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
eculizumab |
Soliris |
satralizumab |
ENSPRYNG |
inebilizumab |
UPLIZNA |
methylprednisolone |
A-Methapred, Depmedalone-40, Depmedalone-80 , Depo-Medrol, Medrol, Medrol Dosepak, Solu-Medrol |
azathioprine |
Azasan, Imuran |
rituximab |
RIABNI, Rituxan, RUXIENCE, truxima |
natalizumab |
Tysabri |
fingolimod |
Gilenya, TASCENSO |
baclofen |
ED Baclofen, FLEQSUVY, Gablofen, Lioresal, Lioresal Intrathecal, LYVISPAH, OZOBAX |
tizanidine |
Zanaflex |
