Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare relapsing autoimmune disorder that preferentially causes inflammation in the optic nerve and spinal cord. It is typically characterized by longitudinally extensive transverse myelitis (LETM, myelitis which is 3 vertebral segments in length or greater), which can leave one quite debilitated at presentation, and unilateral or bilateral optic neuritis. Individuals can present with short lesions as well. It was once thought of as a variant of Multiple Sclerosis (MS), and is still often times misdiagnosed as MS. However, several factors can differentiate it from MS: 1) it typically involves different parts of the brain than in MS, 2) the severity of attacks can be more robust as compared to MS, and 3) the pathophysiology differs from MS – whereas MS is thought to largely be a T-cell mediated disease, NMOSD is mediated by anti-aquaporin 4 antibodies. Blood testing includes an anti-aquaporin-4 antibody (NMO-IgG) test, which is highly specific (>99%) and its sensitivity ranges from 48-72%, depending on the assay used. Antibodies to Myelin Oligodendrocyte Glycoprotein or anti-MOG have been found in individuals diagnosed with NMOSD. Those with anti-MOG NMOSD tend to have attacks most often in the optic nerve, or optic neuritis (ON). Treatment for this disorder involves acute management with therapies, including IV methylprednisolone and plasma exchange (PLEX), and prevention of future attacks with immunosuppressants, including mycophenolate mofetil or rituximab, and aggressive rehabilitation.
Previously the disorder was split into two categories: Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorder, but The International Panel for NMO Diagnosis (IPND) released an updated set of guidelines in 2015 for diagnosing Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD), and these disorders are now simply called Neuromyelitis Optica Spectrum Disorder. This is because those with NMO and NMOSD generally do not have differing clinical behavior and should receive the same treatment.
NMOSD
Acute Treatments
While not all individuals present alike, the following are possible treatments in the management of an acute event.
Intravenous Steroids
Although there are no clinical trials that support a unique approach to treat patients experiencing Transverse Myelitis (TM) or Optic Neuritis (ON), it is well recognized as a standard of care to give high-dose intravenous methylprednisolone for suspected acute myelitis, generally for 5 days, unless there are compelling reasons not to. The decision to offer continued steroids or add a new treatment is often based on the clinical course and MRI appearance at the end of 5 days of steroids.
Plasma Exchange (PLEX)
PLEX is often recommended for moderate to aggressive forms of TM and ON, as is very often the case with NMOSD, if there is not much improvement after being treated with intravenous steroids. If presenting symptoms are severe, PLEX may be initiated concurrently with steroids. There have been no prospective clinical trials that prove PLEX’s effectiveness in NMOSD but retrospective studies of TM treated with IV steroids followed by PLEX have shown a beneficial outcome. PLEX also has been shown to be effective in other autoimmune or inflammatory central nervous system disorders. Early treatment is beneficial – PLEX is typically started within days of administering steroids, very often before the course of steroids has finished. Particular benefit has been shown if started within the acute or sub-acute stage of the myelitis or if there is continued active inflammation on MRI.
Other Acute Treatments
In cases of no response to either steroids or PLEX therapy and continued presence of active inflammation in the spinal cord, other forms of immune-based interventions may be required. The use of immunosuppressants or immunomodulatory agents may be considered in some cases. One of those approaches is the use of intravenous cyclophosphamide (a chemotherapy drug often used for lymphomas or leukemia). Initial presentation with aggressive forms of myelitis, or if particularly refractory to treatment with steroids and/or PLEX, aggressive immunosuppression with cyclophosphamide is considered. Individuals should be monitored carefully as potential complications may arise from immunosuppression. As with all medications, risks versus benefits of aggressive immunosuppression need to be considered and discussed with the clinical care team.
The use of IV immunoglobulin (IVIG) has not been tested and its use in the management of acute or sub-acute NMOSD is not supported.
