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which injured astrocytes, followed by marked NK cell, promising improvement after PE, it can be considered
granulocyte and monocyte infiltration along with BBB as the first-line therapy for the next acute attack. The
breakdown, oligodendrocyte death and demyelination, treatment with intravenous immunoglobulin (IVIg),
microglia activation and even neuronal apoptosis. which is an ideal alternative for PE in other neurological
[12]
Unfortunately, the mechanism of AQP4-IgG generation disorders such as myasthenia gravis, multiple sclerosis
remains unclear; predictions include AQP4 molecular and Guillain-Barré syndrome, in acute NMO has also
mimicry and infection. [13,14] Although T cells are rare been reported; [19,20] however, the improvement of the
in the CNS lesions, recent studies indicate that some prognosis of steroid refractory individuals has not been
T cell subsets may also involve in the pathological clearly demonstrated, indicating IVIg therapy may need
[13]
process. Th17 cells and follicular helper T cells further investigation in acute NMO.
(Tfh) significantly increase during the relapse period,
[15]
which are critical for breaking down BBB and antibody Prevention of acute attacks
production. Further investigation into the pathogenesis Given its high recurrence rate and severe
mechanism of NMO may facilitate the development of morbidity associated with one relapse, long-term
more therapeutic targets. immunosuppressive treatment should be instituted
right after the recovery of the first attack. Due to
CURRENT THERAPIES OF NMO its low incidence, data of prospective randomized
controlled trials of preventive agents are still limited.
Since NMO has a relapsing-remitting clinical course, For developing a treatment protocol, the effects of prior
the treatment of NMO is divided into two stages: treatment, the short-term and long-term side effects,
management of acute attacks and prevention of other system complications and even economic status
future relapses. The main aims of acute therapies are of patients should be considered intensively.
to suppress the inflammatory response, minimize
the irreversible neurological damages and accelerate Azathioprine
recovery, whereas preventive therapies are designed to Azathioprine is shown to be the most popular oral
reduce relapse frequency. Treatment strategies for these immunosuppressive agent currently used in NMO
two stages are discussed as follows. treatment, which can effectively disrupt purine
synthesis and inhibit the proliferation of T and
Therapies of acute attacks B cells. A large retrospective study including 99
The most typical treatment for an acute attack patients with NMO or NMOSD demonstrated that
of NMO is the administration of intravenous the annualized relapse rate (ARR) decreased from
methylprednisolone (IVMP). Glucocorticoids exert 2.20 to 0.52 during a median treatment interval of 22
[21]
profound anti-inflammatory and immunosuppressive months. The usual initial dose is 50 mg/day, and
effects, including down regulation of pro-inflammatory subsequently increased to 2-3 mg/kg per day, which
cytokines, reduction of adhesion molecules and provides better improvement. As azathioprine may
matrix metalloproteinases, prevention of apoptosis take full effect only after 3-6 months, oral steroids
of mononuclear cells and restoration of the BBB should be used simultaneously (1 mg/kg per day). A
integrity. Up to now, there have been no prospective recent prospective trial has showed azathioprine plus
[16]
clinical trials for acute treatment of NMO, meaning low dose corticosteroid distinctly reduced the ARR
that the reliable dosages and duration have not (from 0.923 to 0) of the NMO patients in Southern
been reviewed. Methylprednisolone is commonly China and 57.1% of patients were relapse-free during
[22]
prescribed for 1,000 mg per day for 3-5 days, followed a median follow-up of 20 months.
by prednisone starting from 60-100 mg per day. If Mycophenolate mofetil
patients demonstrated no improvement after IVMP, Mycophenolate mofetil is a potent immunosuppressive
plasma exchange (PE) should be considered. PE is drug that inhibits the inosine monophosphate
recommended as a second-line therapy for refractory dehydrogenase and suppresses the proliferation of T
patients, accelerating the removal of antibodies, and B cells. It has been demonstrated in a retrospective
complements, pro-inflammatory cytokines and case series of 24 patients (median dose 2 g daily) that
chemokines. Generally PE is performed daily or mycophenolate mofetil decreased the ARR from 1.28
every other day for five cycles each of which remove to 0.09 over a median follow-up of 28 months, but the
1.0-1.5x volumes of plasma. Retrospective studies expanded disability scale score (EDSS) remained almost
[17]
and case series have reported that the total remission unchanged (6.0 pretreatment vs. 5.5. post-treatment). [23]
rate of PE therapy was between 44-75%. Male
[18]
patients and early initiation therapy were associated Mitoxantrone
with better improvement. If patients demonstrated Mitoxantrone, an inhibitor of topoisomerase II, is
[18]

128 Neuroimmunol Neuroinflammation | Volume 3 | June 20, 2016