Neuromyelitis Optica Spectrum Disorder (NMOSD) in Israel – Diagnosis and Treatment

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system, characterized by inflammation of the optic nerves and spinal cord. Accurate laboratory diagnostics and correct treatment selection are crucial, as NMOSD management differs significantly from multiple sclerosis (MS).

Dr. Lidiia Prakhova is a neurologist with over 35 years of clinical experience, specializing in demyelinating and autoimmune CNS diseases: NMOSD, MOG-antibody–associated disorders, multiple sclerosis, and chronic inflammatory polyradiculoneuropathies.

Diagnosis is based on AQP4 and MOG antibodies, clinical presentation, MRI, and cerebrospinal fluid (CSF) analysis. Patients receive modern pathogenetic therapy with continuous clinical follow-up.

Consultations are provided at Shamir Medical Center (Assaf HaRofeh), Israel, by prior appointment.

What is NMOSD?

Neuromyelitis optica spectrum disorder is a rare but severe autoimmune disease of the central nervous system, primarily affecting the optic nerves and spinal cord. It was previously considered a variant of multiple sclerosis, but today it is recognized as an independent disease entity with its own pathogenesis and treatment principles.

Key features:

• Antibody-mediated autoimmune mechanism (antibodies to aquaporin-4, AQP4-IgG, in most patients)
• Strong female predominance (approximately 9:1)
• Severe attacks and a high risk of disability without timely treatment

Clinical manifestations

Typical symptoms of NMOSD include:

Optic neuritis

• Sudden decrease or loss of vision (in one or both eyes)
• Pain with eye movements
• Impaired color vision

Longitudinally extensive transverse myelitis (LETM)

• Weakness in the legs and/or arms
• Sensory disturbances (numbness, tingling, altered sensation)
• Bladder and bowel dysfunction
• Gait impairment and balance problems

Brainstem and area postrema syndromes

• Intractable vomiting or persistent hiccups of central origin
• Lesions of the brainstem and floor of the fourth ventricle
• Often prolonged and severe course of symptoms

Combined involvement of the optic nerves and spinal cord and a relapsing disease course are also possible. These manifestations require careful differentiation from other CNS diseases, particularly multiple sclerosis and MOG-antibody–associated disease (MOGAD).

Diagnosis of NMOSD in Israel

Accurate diagnosis of NMOSD requires a comprehensive assessment combining clinical data, laboratory tests, neuroimaging, and ophthalmologic/neurophysiological evaluation.

Laboratory tests

• AQP4-IgG (aquaporin-4 antibodies) – the main serological marker of NMOSD
• MOG-IgG (myelin oligodendrocyte glycoprotein antibodies) – especially important in AQP4-negative cases and when MOGAD is suspected
• CSF analysis: oligoclonal bands are often absent, which helps distinguish NMOSD from multiple sclerosis

MRI (magnetic resonance imaging)

• Spinal cord MRI: longitudinally extensive lesions (LETM) involving three or more vertebral segments
• Optic nerve MRI: bilateral involvement, possible chiasmal and posterior optic pathway lesions
• Brain and brainstem MRI: lesions typical for NMOSD, for example around the fourth ventricle or area postrema

Ophthalmologic and neurophysiological assessment

• OCT (optical coherence tomography): evaluation of retinal nerve fiber layer thickness
• Visual evoked potentials (VEP): assessment of conduction along the visual pathway

Differential diagnosis

It is especially important to distinguish NMOSD from multiple sclerosis and MOGAD, as their prognosis and treatment strategies differ:

• In NMOSD, attacks tend to be more severe, with slower or incomplete recovery.
• Some disease-modifying therapies used in MS (for example, interferons and fingolimod) are contraindicated in NMOSD and may worsen the disease.

Treatment of NMOSD: Israeli practice

The main goals of treatment are rapid control of acute attacks and effective prevention of future relapses to minimize the risk of disability.

Acute relapse treatment

• High-dose intravenous methylprednisolone (1 g/day for 3–5 days), followed by tapering oral steroids
• Plasma exchange (PLEX) or immunoadsorption in severe attacks or when response to steroids is insufficient

Maintenance and preventive therapy

Long-term maintenance treatment aims to suppress autoimmune activity and prevent new relapses.

Targeted biologic therapies

Rituximab (MabThera, Truxima, Rixathon, Riximyo)

A chimeric monoclonal antibody against CD20, leading to depletion of pre-plasma B cells and suppression of antibody production, including anti-AQP4 antibodies. Although rituximab is not formally FDA/EMA-approved for NMOSD, it is widely used in Israel as a first-line therapy.

• AQP4-IgG–positive NMOSD: high efficacy with a marked reduction in relapse rate
• Seronegative NMOSD: moderate but clinically meaningful effectiveness

Eculizumab (Soliris)

A monoclonal antibody targeting complement component C5, blocking the terminal complement cascade and preventing astrocyte damage mediated by anti-AQP4 antibodies. Eculizumab is approved by the FDA and EMA for AQP4-IgG–positive NMOSD.

• AQP4-positive NMOSD: clinical trials (including PREVENT) demonstrated up to ~94% reduction in relapse risk
• Seronegative NMOSD: data are limited; use is generally not recommended

Ravulizumab (Ultomiris)

A second-generation, long-acting C5 inhibitor that fully suppresses the terminal complement cascade, similar to eculizumab, but with a much longer half-life and more stable complement blockade.

• AQP4-IgG–positive NMOSD: clinical data (e.g., CHAMPION-NMOSD) show near-complete prevention of relapses in many patients
• Seronegative NMOSD: efficacy has not been demonstrated
• Dosing advantage: infusion once every 8 weeks (vs every 2 weeks with eculizumab), which improves convenience and adherence

Inebilizumab (Uplizna)

A monoclonal antibody targeting CD19, resulting in deep depletion of the entire B-cell spectrum, including plasmablasts, memory B cells, and pre-plasma cells. This provides more profound suppression of pathogenic AQP4 antibody production than CD20-directed therapies. Approved for AQP4-IgG–positive NMOSD.

• AQP4-positive NMOSD: the N-MOmentum trial demonstrated a relapse reduction of about 77%
• AQP4-seronegative NMOSD: no significant benefit; not recommended in this group

Satralizumab (Enspryng)

A monoclonal antibody against the interleukin-6 receptor (IL-6R), blocking IL-6–dependent activation of B cells and plasma cells, reducing autoantibody production and inflammatory activity. Approved by the FDA/EMA for AQP4-IgG–positive NMOSD.

• AQP4-positive NMOSD: clinical trials (SAkuraSky, SAkuraStar) showed a significant reduction in relapse rate
• AQP4-seronegative NMOSD: effect is moderate and less consistent; treatment decisions are individualized

Classical immunosuppressants

In some cases, or when targeted biologic therapies are not available, conventional immunosuppressants may be used:

• Azathioprine
• Mycophenolate mofetil
• Cyclosporine or methotrexate in selected situations

Specifics of Israeli clinical practice

In Israel, patients with NMOSD can receive highly specialized diagnostics and treatment in leading neurological centers. Clinical practice is based on international guidelines and adapted to the Israeli healthcare system.

• Early and comprehensive diagnostics (AQP4/MOG antibody testing, MRI, CSF analysis)
• Multidisciplinary care (neurology, ophthalmology, immunology, rehabilitation)
• Individualized therapy selection based on serostatus (AQP4-positive vs AQP4-negative) and comorbidities
• Continuous dynamic follow-up to detect relapses as early as possible

When to consult a neurologist

Consultation with a neurologist experienced in demyelinating diseases, including NMOSD, is recommended in the following situations:

• Recurrent optic neuritis, especially with incomplete recovery
• Myelitis with lesions involving three or more vertebral segments or with pronounced weakness and sensory loss
• Diagnostic uncertainty between multiple sclerosis and NMOSD
• Unexplained deterioration of vision or sensory symptoms

Early diagnosis and correct therapy are crucial for long-term prognosis and quality of life.

NMOSD, MOGAD and MS: key differences

Key points:

• NMOSD often has an acute and severe onset, while MS usually progresses more gradually.
• Several MS therapies (for example interferons, fingolimod) can worsen NMOSD and must be avoided.
• Antibody status (AQP4 and MOG) is critical for correct diagnosis and treatment planning.

Prognosis and important points for patients

• Without adequate treatment, the risk of severe disability in NMOSD is high.
• With modern targeted therapies, long-term remission and good quality of life are achievable.
• Lifelong monitoring and, in many patients, maintenance therapy are required, especially in AQP4-positive NMOSD.
• Vaccinations and infection prevention measures are essential in patients receiving immunosuppressants or monoclonal antibodies.

Why choose a consultation with me

• Over 35 years of experience in neurology
• Specialization in autoimmune and demyelinating diseases of the central nervous system
• Work in a large Israeli multidisciplinary hospital with access to modern diagnostics and treatments
• Individualized treatment selection and regular monitoring
• Consultations in Russian and English, with therapy adapted to everyday life in Israel

Consultation with Dr. Lidiia Prakhova

Shamir Medical Center (Assaf HaRofeh)

Phone: 08-977-97-75
Phone: 08-977-91-45
E-mail: neuro@shamir.gov.il
Personal e-mail: l.n.prakhova@hotmail.com