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
Sjgren'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