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Page 4 of 16 Zhang et al. Neuroimmunol Neuroinflammation 2019;6:8 I http://dx.doi.org/10.20517/2347-8659.2019.06

shown the safety of stopping a short course of high-dose corticosteroids without a tapering regimen [53,54] .
In addition, one study showed that in MS, IVMP combined with low-dose oral hormones did not improve
[55]
disability progression compared with IVMP alone . However, low-dose oral corticosteroids may help
[56]
prevent relapses in NMOSD . In some patients with NMOSD, a rebound effect may occur if corticosteroids
are stopped quickly. A study of 59 patients with relapsing MOG antibody-associated demyelination showed
that most cases of relapse occurred within 2 months of prednisolone cessation and in patients who had been
[57]
administered daily doses of < 10 mg . Therefore, an oral weaning course of prednisolone over 2-6 months
and long-term maintenance with low-dose oral prednisolone is recommended [58,59] . Compared with MS,
NMOSD relapse is often more severe and less responsive to IVMP [60,61] . A retrospective study showed that
IVMP has a significant effect on acute relapses in both MS and NMOSD patients, but the effects in MS were
slightly better than those in NMOSD based on the changes in the Expanded Disability Status Scale score
[62]
before and after IVMP .
PE can remove circulating autoantibodies, macromolecular immune complexes, inflammatory cytokines,
[63]
and other mediators. It can also affect lymphocyte proliferation and activation . Common side effects of PE
include hypocalcemia, bleeding, and infections. When remission is absent or insufficient, PE every other day
is recommended, with removal of 1-1.5 plasma volumes each time (30-40 mL/kg). A total of 5-7 treatments
are recommended. Studies have found that the exchanged molecules will drop to less than 20% of their
initial level after 5 exchanges [64,65] . In addition, IA is a more selective method that eliminates certain proteins,
such as antibodies, while retaining other plasma proteins. The effects of IA and PE are comparable in the
[66]
treatment of MS- or NMOSD-relapses . Patients with a suboptimal response to methylprednisolone and
those who present with severe symptoms should be treated with PE/IA. Some results support the use of PE
[67]
in severe relapses of MS unresponsive to corticosteroids . PE and IA can clear AQP4-IgG and are effective
therapies for NMOSD. The results of a retrospective cohort study suggest early use of PE/IA in NMOSD
[68]
[68]
attacks . And no superiority was shown for one of the 2 apheresis techniques . PE/IA combined with
IVMP is more effective than IVMP alone in NMOSD [69,70] . In addition to steroids, it is recommended that
PE/IA be started as soon as possible [71,72] . A study showed that the early initiation of PE (≤ 5 days) is more
[71]
beneficial than delayed PE for cases that are refractory to IVMP .

IVIG is another important therapy that can affect a variety of immunomodulatory and antigenic-recognition
pathways, including humoral and cellular immunity. It interacts with various subsets of B- and T-cells,
[73]
modulates cytokines, scavenges complement, and blocks idiotypic antibodies . Patients should be given
[74]
IVIG at a dose of 0.4 g/kg/day for 5 days . In MS, studies have shown that IVIG combined with IVMP
is not superior to IVMP alone [75,76] . Few studies have assessed the efficacy of IVIG monotherapy for MS
relapses. IVIG has a good effect in other humoral immune-mediated neuroimmunological diseases. IVIG
may affect certain steps of pathological processes in NMOSD. Clinical experience suggests that this therapy
[44]
may be of benefit in NMOSD patients . A retrospective study with a small sample size has shown the
[43]
efficacy of IVIG treatment for NMOSD relapses . Furthermore, it has been shown that regular IVIG could
prevent relapses in both MS and NMOSD [77-80] .

TREATMENTS IN THE REMISSION PERIOD
In most instances, the initial course of MS consists of relapses and remissions, known as relapsing-remitting
MS (RRMS), with disability progression over the course of the disease. Most patients eventually enter a
secondary phase of progressive disease, i.e., secondary progressive MS (SPMS). In a few patients, the initial
[81]
course is progressive with no relapsing-remitting phase; that is known as primary progressive MS (PPMS) .
The relationship between disability progression and relapses in MS is not yet clear. Unlike MS, in NMOSD,
[58]
disability is the result of cumulative inflammatory damage caused by acute attacks . The purpose of
treatment during the remission period is reducing the risk of relapse and disability progression. In both MS
and NMOSD, treatment during remission should be started as soon as possible [58,59,82,83] . Therapeutic drugs