Expert Panel Publishes Revised Consensus Recommendations for Diagnosis and Management of NMOSD

A multidisciplinary panel of experts published a new revision of evidence-based recommendations for the diagnosis and management of neuromyelitis optica spectrum disorder (NMOSD) in Saudi Arabia, incorporating recent therapeutic developments and evolving biomarker insights since the 2022 consensus publication.^1,2 The updated guidance emphasized individualized care, antibody testing, long-term immunosuppressive strategies, and underscored the need for further research on treatment duration as well as failure criteria.

A group of neurologists, neuroimmunologists, epidemiologists, and pharmacists convened under the Saudi Neurology Society - Multiple Sclerosis Chapter reviewed 56 studies through a GRADE assessment. From the initial 128 statements and 25 recommendations developed under various themes for voting, the process resulted in a final set of 27 recommendations and 90 statements. The finalized recommendations addressed key areas, including diagnostic strategies, diagnostic criteria, and acute and chronic treatments in NMOSD, as well as recommendations regarding the diagnosis and treatment of MOGAD.

“The expert review underscores key considerations in the diagnosis and management of NMOSD, highlighting areas of uncertainty and the need for region-specific guidelines,” lead author Salman Aljarallah, MBBS, assistant professor at King Saud University in Saudi Arabia, and colleagues wrote.¹ “In addition, challenges persist in the diagnosis of seronegative NMOSD and MOGAD, particularly due to overlapping clinical features, such as optic neuritis, transverse myelitis, and brainstem lesions. While MOG-IgG positivity is more closely correlated with disease presence, the diagnostic process remains controversial, especially in low-positive antibody titers, where repeat testing may be necessary.”

Published in Multiple Sclerosis and Related Disorders, the guidance covered acute attack management, initial immunosuppressive therapies, treatment duration, and prognostic factors at diagnosis for potential failure of first-line treatments. The recommendations also discussed the use of rituximab, azathioprine (Imuran), mycophenolate mofetil (CellCept), and newer therapies such as ravulizumab (Ultomiris; Alexion), tocilizumab, inebilizumab (Uplizna; Amgen), satralizumab (Enspryng; Genentech), and eculizumab (Soliris; Alexion). Although newer therapies demonstrate promising efficacy, differences in safety, accessibility, and patient response highlight the need for further research to clarify their optimal role in treatment regimens.

Recommendations for Diagnosing and Managing NMOSD

Serology

• Serum AQP4-IgG testing using live cell-based assays (CBAs) is recommended as the first-line diagnostic test for patients with one or more core NMOSD clinical features.
• Testing is ideally performed during an active relapse and before starting immunosuppressive therapy to optimize detection.
• Repeat testing may be indicated in seronegative patients with strong clinical suspicion to improve diagnostic sensitivity.

MRI

• MRI findings should be interpreted cautiously in regions with high multiple sclerosis prevalence to reduce the risk of misclassification.
• MRI with gadolinium contrast may be used for additional evaluation in patients who are AQP4-IgG negative or when antibody testing is inconclusive or unavailable.

Diagnostic Criteria

• The 2015 International Panel for NMO Diagnosis (IPND) criteria provide a framework integrating clinical, serological, and radiological data and are recommended for distinguishing NMOSD from other neurological disorders.

Treatment of NMOSD: Acute Attacks

Corticosteroids

• Intravenous methylprednisolone (1 g/day for 3–5 days) is recommended as first-line therapy for acute NMOSD relapses.

Plasmapheresis / Plasma Exchange (PLEX/TPE)

• PLEX may be considered for patients who do not respond to high-dose corticosteroids within 48–72 hours or for those with severe relapses.
• Therapeutic plasma exchange can be used for severe or refractory relapses.

Intravenous Immunoglobulin (IVIg)

• IVIg may be considered as an alternative when corticosteroids or PLEX are contraindicated, unavailable, or not feasible.

Relapse Prevention / Initial Immunotherapy

• Steroid-sparing immunosuppressive therapy is recommended for all patients.
• Rituximab is commonly used as a first-line therapy due to established efficacy and reduced steroid requirements.
• Mycophenolate mofetil (MMF) and azathioprine (Imuran) may be considered for patients unable to tolerate rituximab.
• Azathioprine may also be used in seropositive patients with low disability or in seronegative patients without access to monoclonal antibodies.
• Complement inhibitors may be considered for patients with severe disease or a high risk of disability.
• Monoclonal antibodies, including eculizumab, ravulizumab, tocilizumab, and inebilizumab, may be considered for patients who cannot tolerate or do not respond to conventional immunosuppressive therapies.

IL-6 Pathway Inhibitors

• IL-6 receptor antibodies, such as tocilizumab and satralizumab, may be used for relapse prevention.
• Satralizumab is administered subcutaneously at weeks 0, 2, and 4, followed by every 4 weeks for AQP4-positive patients.

Switching Treatment

• For AQP4-positive patients not responding to rituximab, alternative therapies may include complement inhibitors, IL-6 inhibitors, or anti-CD19 agents.

Treatment Duration

• Lifelong therapy is recommended for seropositive patients with relapsing disease.
• Gradual tapering may be considered for seronegative patients with stable disease; optimal timing requires further study.
• Decisions to discontinue therapy should consider relapse history, treatment-related toxicity, duration of therapy, and patient-specific factors.

MOGAD: Diagnosis

• Serum testing using live CBAs for full-length MOG-IgG is recommended, ideally at the time of the incident event; repeat testing at least 3 months later is suggested if the initial test is negative.
• Alternative diagnoses should be excluded to prevent misdiagnosis and avoid unnecessary testing.
• The International MOGAD criteria are recommended to guide diagnosis and management.
• MOG antibody testing is suggested in seronegative patients, particularly those with optic neuritis, myelitis, or atypical MRI features.

MOGAD: Management

• High-dose corticosteroids are recommended for acute relapses; long-term use should be minimized to reduce risk of complications.
• IVIg and plasma exchange may be used for management of acute attacks.
• There is no general consensus on treatment for newly diagnosed cases, but some evidence supports intervention in acute cases.
• Corticosteroids, cyclic IVIg, azathioprine, mycophenolate, or tocilizumab may be considered for patients at high risk of relapse.

“Despite significant advances in the diagnosis and management of NMOSD, several gaps remain in the literature that warrant further investigation,” Aljarallah et al noted.¹ “Identifying predictors of treatment failure, optimal dosing strategies, and the need for bridging therapies during treatment transitions will be crucial areas of research. Addressing these knowledge gaps through well-designed prospective trials, real-world evidence studies, and international collaborations will be essential for refining NMOSD management strategies and improving patient care outcomes.”

REFERENCES
1. Aljarallah S, AlThobaiti A, Abulaban A, et al. Consensus recommendations for the diagnosis and management of neuromyelitis optica spectrum disorder: A Saudi expert panel review. Mult Scler Relat Disord. Published online November 8, 2025. doi:10.1016/j.msard.2025.106847
2. Shosha E, Aljarallah SA, Al Fugham N, et al. Saudi consensus recommendations on the management of Neuromyelitis Optica Spectrum Disorders (NMOSD). Mult Scler Relat Disord. 2022;66:104062. doi:10.1016/j.msard.2022.104062