Neuromyelitis optica spectrum disorder
NMOSD
Neuromylitis optics spectrum disorder (NMOSD) mainly includes neuromyelitis optica (NMO), an autoimmune disease, in which attacks of optic neuritis and myelitis can be simultaneous or continuous. Recurrent episodes are common in untreated patients. In more than 80% of cases, NMO is caused by immunoglobulin (IgG) G autoantibodies against aquaporin 4 (anti-AQP4), the most abundant water channel in the central nervous system. In some cases, the cause remains unknown.
NMO has been mistakenly thought to be a clinical variant of multiple sclerosis (MS) in the past. However, in the vast majority of cases, NMO is not associated with MS and differs significantly from it in pathogenesis, clinical presentation, magnetic resonance imaging, cerebrospinal fluid manifestations, course, and prognosis.
Traditionally, NMO includes only symptoms of optic neuritis and myelitis. Currently, the broader disease manifestations have been classified in the diagnosis of NMOSD along with NMO. NMOSD is less common than NOM and can affect the brainstem, leading to respiratory insufficiency. Post medullary lesions can cause vomiting or hiccups, as well as pain and tonic cramps. Lesions may also affect the diencephalon.
Epidemiology
Prevalence varies by region, ranging from 0.5 to 10 cases per 100,000 population. NMO is more common in women than men, accounting for more than two-thirds of patients and more than 80% of patients with relapsed disease, and is more common in Asians than in Caucasians. Most patients with NMO have no affected relatives and are generally considered non-familial disease.
Signs and symptoms
The signs and symptoms of NMOSD depend on the structure of the nervous system affected by the disease, and to some extent the antibodies involved. Signs and symptoms usually follow the course of relapse and remission, but occasionally can be progressive (unipolar). The damage can be temporary or permanent without treatment.
The initial manifestations of the disease are often inflammation of the spinal cord, causing spinal cord dysfunction, resulting in muscle weakness, quadriplegia, loss or decrease in sensation, spasticity, loss of bladder and bowel control, or erectile dysfunction. Myelitis can be transverse, affecting the entire cross-section of the spinal cord, and exhibit bilateral symptoms.
Initial presentation is followed by optic nerve inflammation, which can lead to varying degrees of visual impairment. Compared with idiopathic optic neuritis caused by MS, optic neuritis caused by NMOSD is more common to cause severe vision loss, bilateral involvement, and permanent visual defect at the time of onset.
Treat
- NMO cannot be cured — some patients recover, but many are left with impaired vision and limbs, and long-term neurological deficits are cumulative effects of acute attacks and can be severe. Steroid therapy may improve vision-related outcomes after an acute attack.
- When seizures progress after corticosteroid administration, plasmapheresis may be an effective treatment.
- FDA-approved eculizumab (Soliris) was first marketed in 2019. As of 2020, they are one of the most expensive drugs worldwide. This was followed by ebilizumab against CD19+ B cells and monoclonal antibodies against IL-6.
- Off-label drugs can be selected, of which rituximab is the most widely used. Despite the lack of phase III clinical trials testing their efficacy, these drugs are currently the standard of care given their relative inexpensive and easy to use.
Off-label drugs to choose from
Drugs (brands) | Mechanism of action |
Rituximab (rituximab). | Anti-CD20 antibody – B cell depletion [61]. |
Azathioprine (Imoulan, Azazsan). | Inhibits purine metabolism |
Mycophenolate mofetil (CellCept). | Inhibits purine metabolism |
Mitoxantrone | DNA synthesis/repair inhibitors |
methotrexate | Inhibits folate metabolism |
Cyclophosphamide | DNA crosslinker |
- Hematopoietic stem cell transplantation: may be used in severe cases of NMO. Available data suggest that this procedure reduces inflammatory activity in the short term, but the vast majority of patients will relapse within 5 years.
Special note: Certain immunosuppressants for the treatment of MS can worsen NMO disease progression and should not be used in the treatment of NMO, such as interferon-β, fingolimod, natalizumab, and altuzumab.
Prognosis
Normally, some improvement occurs within a few weeks, but severe residual symptoms and disability may persist. The disease can be unipolar, i.e., a single episode followed by permanent remission. However, at least 85% of patients have recurrent forms of the disease with recurrent episodes of transverse myelitis and/or optic neuritis.
Approximately 20% of patients with unipolar NMO have permanent vision loss, and 30% have permanent paralysis of one or both legs. In patients with recurrent NMO, 50% are blind or paralyzed within five years. In some patients (33% in one study), cervical transverse myelitis leads to respiratory failure and subsequent death.