- •Experts in Saudi Arabia have developed comprehensive guidelines on the diagnosis and management of Neuromyelitis Optica spectrum disorder.
- •Treatment with Immunosuppressants such as rituximab requires monitoring of CD19 levels, organ functions, and latent infections.
- •Replacement with intravenous immunoglobulins is recommended for patients with a serum total IgG level below 150.
- •Methotrexate, Mycophenolate mofetil, and azathioprine are all acceptable treatment medications with rituximab being administered as a second-line agent.
- •All patients positive for aquaporin-4 antibodies should receive long-term immunosuppression with a steroid-sparing medication.
|Box 1. Key diagnostic criteria for NMOSD9.|
|• Presence of any neurological manifestation, or a CNS lesion with a corresponding non-neurological manifestation, along with positive AQP4-IgG or|
|• NMOSD symptoms alongside radiologic changes fulfilling the MRI criteria according to IPND, in addition to:|
|– Absence of AQP4-IgG and anti-MOG antibodies in the serum and in CSF using cell-based assay (CBA)|
|– Supportive criteria from CSF (neutrophilic or eosinophilic pleocytosis and absence of oligoclonal bands)|
|– Testing for antibodies is performed during the attack and off immunotherapies|
|– Exclusion of other demyelinating diseases|
|• Asymptomatic positivity for AQP4-IgG does not qualify for diagnosis|
|• Double seropositive (for AQP-4 IgG4 and anti-MOG antibodies) patients is uncommon (0.7%)|
|• The presentation of NMOSD may overlap with a number of other conditions, including systemic lupus erythematosus (SLE), Sjögren's syndrome, Behçet's disease, neurosarcoidosis, vascular pathologies, chronic infections, lymphoma, genetic conditions, autoimmune diseases/autoantibodies, compressive disorders, CNS or other malignancy, and neurodegenerative conditions.|
|IPND: International Panel for NMO Diagnosis.|
3. Managing acute NMOSD relapses
- 1Initiating early treatment with a short (3–5 day) course of pulse IV methylprednisolone (1000 mg), followed by tapering the course of steroids and maintenance dose (10–20 mg), until effective steroid-sparing immunosuppression is achieved.
- 2PLEX to be given as 5 to 7 exchanges of 1–1.5 plasma volume per session as an effective management option for NMOSD relapses. PLEX should be considered for NMOSD in the following scenarios:
- lowerRoman%1Patients with prior history of poor response to steroids.
- lowerRoman%1Patients with severe relapses. Early use of plasma exchange is highly recommended for any patient with disabling relapse.
- lowerRoman%1The panel agreed on the following definitions of severe relapses:
- aSevere overall disability (EDSS ≥4) or,
- bAmbulatory functional systems scale (FS) ≥5 or,
- cA relapse causing pyramidal FS ≥4 or
- dSevere optic neuritis (visual FS ≥4) or bilateral involvement
- 1IVIG can be considered as an alternative to steroids or plasma exchange if they are contraindicated or not available and the patient cannot be transferred to a center with PLEX.
- 2In the availability of a single modality, a repeated course can be considered, in refractory cases.
3.1 Preventing NMOSD relapses
|Serum total IgG level (mg/dL)||Recommendation|
|>500||unlikely to need replacement|
|300–500||heavily dependent on infection history; may use responses to vaccines to judge|
|150–300||consider replacing with IVIG, especially if a clearly documented history of recurrent infections|
|<150||recommend replacing with IVIG regardless of infections|
- iGiving two doses of Rituximab, 1000 mg each, 2 weeks apart, the following regimen, is a single dose of 1000 mg IV iii. To avoid relapses following rituximab infusion, maintain oral prednisone in the first month (30–40 mg).
- iiThe subsequent doses can be administrated either according to CD19 level, or every 6 months.
- iiiReplacement with IVIG is indicated for patients with very low IgG levels and severe or recurrent infections. In this meeting, we discussed the following IgG cut-offs and threshold for immunoglobulin replacement (see Table 1).
3.6 Conventional Immunosuppressants
3.7 Our recommendations for the prevention of NMOSD relapses
3.7.1 AQP4+ NMOSD
|Dosing||Pre-treatment||Monitoring||Options for switching||Side effects|
|Azathioprine (AZA)||2.5–3 mg/kg/day given once or twice daily.|
Start 25 mg/d if TPMT is not available
Prednisone bridge starting 1 mg/kg/day, then taper to not less than 30 mg/day until AZA is effective (typically within 6 months) then taper slowly to discontinue.
|Check CBC, LFT, creatinine.|
Exclude TB and hepatitis B and C
Check thiopurine S-methyltransferase enzyme (TPMT) status
|CBC, LFT, creatinine; weekly for 1 month then every 2 weeks for 2 months, then monthly for 1 year. Frequency can be reduced thereafter. Increasing MCV can be used as a target||Rituximab|
|Transaminitis, hypersensitivity, neoplasms (skin, lymphoma),|
|Mycophenolate mofetil (MMF)||1000 mg bid (up to 3000 mg/d)|
(start low and increase to target dose over 2 weeks)
Prednisone bridge starting 1 mg/kg/day, then taper to not less than 30 mg/day until AZA is effective (typically within 3–6 months) then taper slowly to discontinue.
|Check CBC, LFT, creatinine.|
Exclude TB and hepatitis B and C
|Initially, monthly CBC, LFT, creatinine (weekly if no TPMT) until a stable dose|
Best benefit when absolute lymphocyte count is less than 1.5 k/ml
|Rituximab||Abdominal pain, diarrhea, teratogenicity, infections, malignancy, bone marrow suppression, renal impairment|
|Methotrexate (MTX)||Orally, 15–25 mg/week|
Supplement folic acid 1 mg/day
|Check CBC, LFT, creatinine.|
Exclude TB and hepatitis B and C
|Monitor liver function regularly|
3.8 Seronegative NMOSD
3.9 Managing NMOSD in pregnant women
3.9.1 Relapses in pregnancy
3.9.2 Relapse prevention in pregnancy
3.10 Anti-MOG associated diseases (MOGAD)
3.10.1 Medications to avoid in NMOSD
3.10.2 Relapses and symptom treatment
Declaration of Competing Interest
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