Neuromyelitis Optica (NMO)

Neuromyelitis optica is an uncommon, idiopathic, demyelinating syndrome of the central nervous system that
preferentially affects the optic nerves and spinal cord. It frequently is misdiagnosed as severe multiple sclerosis,
but usually is readily distinguished from multiple sclerosis in fully developed cases because of its severity,
typical magnetic resonance imaging (MRI) findings (normal brain MRI longitudinally extensive lesions on
spinal cord MRI), and cerebrospinal fluid analysis (polymorphonuclear pleocytosis and absence of oligoclonal
banding). A serum auto-antibody marker, NMO-IgG, is highly specific for the disorder.
Most patients have relapsing disease, and natural history studies confirm early and severe disability. We treat
acute myelitis and optic neuritis exacerbations with parenteral corticosteroids and use rescue plasmapheresis for
severe, refractory attacks. Immunomodulatory drugs used for typical multiple sclerosis seem ineffective for
relapse prevention. We recommend systemic immunosuppression, usually with azathioprine and oral cortico-
steroids, for most patients. Fulminant disease and breakthrough disease may respond to other forms of humoral
immunotherapy such as rituximab.
NMO is a disorder of the central nervous system which has many features in common with multiple sclerosis. It
is also known as Devic's disease. Traditionally, it has been defined as a syndrome where patients had a
combination of transverse myelitis and optic neuritis, often with relatively severe symptoms in both the optic
nerves and the spinal cord.
Causes & Risk Factors
NMO tends to affect young adults, a similar age group to those affected by MS. It affects women more than
men. It's unclear how common this is, but in the past it has been thought of as a rare disease. It is likely that
some cases considered to be multiple sclerosis in the past had NMO.
NMO does appear to be more common in African-Americans, as well as people of Asian and Pacific rim origin.
It can be associated with other disorders of the immune system such as rheumatoid arthritis, Hashimoto's
thyroiditis, systemic lupus erythematosis, and Sjögren's syndrome. People with NMO who don't have symptoms
of these other disorders may still have bloodwork seen commonly in these other disorders.
Recent studies have shown that in NMO there are deposits of antibodies around blood vessel walls in the spinal
cord and optic nerves of affected patients. These findings suggest an immune attack upon these tissues. There
are areas of demyelination, inflammation, and occasionally more destructive changes in these affected areas.
The role of genetic factors is still unknown in NMO.
Symptoms
In NMO, symptoms of optic neuritis and transverse myelitis may occur once (monophasic illness) or recur
multiple times (relapsing). When they are monophasic, symptoms of optic neuritis and myelitis tend to occur
close to each other or even at the same time. When relapsing they can occur at intervals over years.
Other less common symptoms of NMO include vertigo (a spinning sensation), facial numbness, headache, and
tremors.
Diagnostic & Testing
The diagnosis if NMO should be considered when there is optic neuritis of one or both eyes closely related in
time to the development of spinal cord symptoms and signs. Often the symptoms are more severe than is usual
for MS, but the symptoms can overlap.
MRI scanning: MRI scanning is an important part of the diagnosis of NMO. In NMO the brain MRI is usually
relatively unaffected. This is different from most patients with MS where the brain is commonly affected with
multiple white matter lesions. In NMO the optic nerves may show changes consistent with demyelination. The
spinal cord often has a distinct finding of long areas of abnormality extending multiple segments of the spinal
cord. During an attack of myelitis the spinal cord may be swollen. These findings are different from multiple
sclerosis in which the demyelination is usually over a single segment.
Spinal fluid testing: A lumbar puncture is typically needed in patients with NMO. This is partially to rule out
direct infections or other processes that can look like NMO. The lumbar puncture allows the neurological team
to test the cerebrospinal fluid for many different things that assist in the diagnostic process.
In NMO, the spinal fluid frequently shows an increase in white blood cells. This may be more of an increase
than is usually seen in multiple sclerosis, and there may be cells called neutrophils which are unusual in MS. In
addition, patients with NMO usually do not have oligoclonal banding, which is relatively common in MS.
Patients with NMO may show an abnormal blood test, the NMO-IGG test. This seems to be specific for NMO
and is an antibody test. It is an antibody that seems to be targeted at the same blood vessel areas that are affected
in NMO, and the finding of a positive NMO-IGG blood test strongly supports the diagnosis of NMO. Patients
with MS do not seem to show NMO-IGG positivity. Not all patients with NMO have a positive NMO-IGG
however.
Like all of the disorders of the immune system which affect the brain, the diagnosis of NMO is a combination of
clinical history, examination, MRI scanning, CSF results, and laboratory work.
Treatment
NMO is a relatively rare disease, and so there are no well defined randomized trials of treatment in this disease.
Most of what we know about treatment for NMO comes from case studies or groups of treated patients.
At this time, intravenous methylprednisolone is the front line treatment for an attack of NMO. Usually this is
given over a 5-7 day course. In NMO it appears that patients require a very slow taper of oral steroids (usually
prednisone) after this course, to avoid relapses. This is different from the typical treatment for MS where
steroids are usually tapered over a few days. The aim is to reduce inflammation and speed recovery from the
disease. Patients on steroids need to be monitored for increased blood glucose, low potassium, and sleep
disturbance. There may be mood changes (irritability, crying, anxiety) when people are on steroid therapy. Other
short term complications of steroid therapy include weight gain, flushed cheeks, facial swelling, a metallic taste
(when using IV solumedrol), and disturbed sleep. Long term complications of steroids include susceptibility to
infection, osteoporosis, development of cataracts, personality change, obesity, skin changes, and rarely injury to
the shoulder or hip joint (aseptic necrosis). If the attack of NMO is severe enough hospitalization and therapy
may be necessary.
If a patient does not respond to IV methylprednisolone another approach to treatment may be Intravenous
Immune Globulin. This is an intravenous treatment using a blood product which has been shown to reduce the
activity in certain immune diseases including NMO. Treatment is usually given for a few hours daily over 5
days for NMO. IVIG has the risks of any blood product (allergic reaction, infection) as well as sometimes
causing shortness of breath due to fluid overload. Rarely patients lack an antibody important to the system and
may react more strongly to IVIG.
Another approach to treatment is a process called plasmapheresis. This may be particularly beneficial in NMO
since it seems that it effectively removes antibodies from the circulation. This is a treatment in which the blood
is circulated through a machine that withdraws components of the immune system from the circulation, reducing
immune activity. It is usually a process which takes a few hours and is done every other day for 10-14 days,
often as part of a hospital stay. In NMO a seven treatment course of plasmapheresis is usually needed.
Plasmapheresis may required the placement of a central venous catheter to allow for blood to be removed from
the system rapidly. Risks of plasmapheresis include discomfort from taking blood, sometimes a tendency to
bleed due to a reduction in platelets, and infections.
In the monophasic form of NMO further treatment may not be needed. However in the relapsing forms, further
therapy may be necessary to try to head off new attacks. Anecdotally, the standard treatment for multiple
sclerosis (glatiramer acetate or interferons) do not seem to be effective in NMO.
Published treatments for relapsing NMO have included a combination of prednisone orally as well as
azathioprine orally. Azathioprine partially suppresses the immune system and can have side effects of nausea,
fever, inflammation of the pancreas, susceptibility to infections, inflammation of the liver, and fatigue. Both
require close monitoring of blood studies.
Other medicines which have been used for the relapsing form, particularly when it does not respond to the
prednisone/azathioprine combination, include rituximab or mitoxantrone. These are both powerful medications
which need to be administered by physicians who are experienced in their use and monitoring. At the Mellen
Center all of these medication have been used and are part of our standard treatments for various diseases.

http://my.clevelandclinic.org/disorders/neuromyelitis_optica_nmo/ns_overview.aspx