Epidemiology and Clinical Presentation
The disease is extremely rare (accounting for less than 1.5% of all demyelinating pathologies). It manifests sporadically, predominantly in women, with a mean age of onset in the late fourth decade (approximately 10 years later than typical multiple sclerosis).
The course is most often relapsing (about 85% of cases). Each relapse is severe and responds poorly to recovery, leading to a stepwise accumulation of disability. Symptoms directly depend on the localization of inflammatory lesions:
- Optic nerves: pronounced mono- or bilateral neuritis, often with severe vision loss.
- Spinal cord: acute spinal syndrome. Cervical myelitis is especially dangerous due to the development of respiratory failure.
- Area postrema (the most caudal part of the medulla oblongata): episodes of intractable hiccups, nausea, and vomiting.
- Diencephalic region: hypersomnia, symptomatic narcolepsy, hypothermia, and inappropriate diuresis.
- Brainstem: oculomotor disturbances and ataxia.
Serological phenotypes
Blood testing for specific antibodies determines the severity and nature of the disease course:
- Patients with AQP4-IgG: have a worse prognosis and an extremely high relapse rate (up to 91%). Attacks are aggressive. The vast majority in this group are women, and they frequently have comorbid autoimmune diseases.
- Patients without AQP4-IgG (often MOG-IgG positive): these are antibodies to myelin oligodendrocyte glycoprotein. Such patients are usually younger, and the gender distribution is more balanced. Their disease tends to have a monophasic course (without repeated attacks) and leaves fewer residual neurological deficits.
MRI diagnostics: specific patterns
The neuroimaging picture in NMOSD has striking distinctive features, especially in the spinal cord and optic pathways.
Spinal cord involvement: Characterized by longitudinally extensive transverse myelitis (LETM). The lesion continuously spans 3 or more contiguous vertebral segments. Inflammation is centrally localized (in the gray matter) and occupies the majority of the cross-sectional area of the cord. Specific MRI phenomena:
- Bright spotty sign: highly destructive punctate foci on T2-weighted images within the area of myelitis.
- Pseudosyringomyelia: lesions appear hypointense on T1-weighted images, resembling syringomyelic cavities.
- Short transverse myelitis (STM): a lesion shorter than 3 segments. It may occur during the first attack of the disease, but in AQP4-positive patients, it almost always transforms into LETM during relapses.
Brain and optic nerve involvement: Contrary to old concepts, the brain is frequently involved. Inflammation targets areas with a high concentration of aquaporin-4: circumventricular organs, the hypothalamus, and the cerebral aqueduct. When the corpus callosum is affected, its ependymal lining suffers, which produces the "marble-like" or "arch-bridge" sign on MRI. The optic nerves are affected bilaterally over more than half of their length, with typical involvement of the posterior pathways (intracranial portion, chiasm).
Critical importance of differential diagnosis with MS
It is critically important to distinguish neuromyelitis optica from multiple sclerosis (MS). The prescription of standard disease-modifying therapies for MS (DMTs — interferons, natalizumab) is strictly contraindicated, as they provoke severe exacerbations of NMOSD. Treatment of NMO requires classical immunosuppressants (rituximab, azathioprine).
| Sign | NMOSD | Multiple sclerosis (MS) |
|---|---|---|
| Spinal cord | Long lesions (>3 segments), central, occupy the entire cross-section | Short lesions (<2 segments), peripheral (posterolateral) |
| Optic nerve | Bilateral involvement, long lesions involving the chiasm | Unilateral involvement, short lesions |
| Corpus callosum | Diffuse involvement across the entire width along the ependyma | Focal involvement, affecting the lower margin |
| Brain | Large (tumefactive) lesions, no dissemination in space | Small ovoid lesions (perivenular), dissemination in space is present |
Briefly: answers to topical questions
What diagnostic criteria are used to confirm the diagnosis of neuromyelitis optica according to international standards?
To confirm the diagnosis, the 2015 international consensus criteria are used, which divide patients based on aquaporin-4 antibody status (AQP4-IgG).
Criteria in the presence of AQP4-IgG:
- Clinical presentation — at least 1 core clinical characteristic.
- Serology — positive test for AQP4-IgG.
- Differential diagnosis — exclusion of alternative diagnoses.
Criteria without AQP4-IgG or with unknown status:
- Clinical presentation — at least 2 core clinical characteristics occurring as a result of one or more clinical attacks; one of these must necessarily be: optic neuritis, acute myelitis with longitudinally extensive spinal cord lesions (LETM), or area postrema syndrome.
- Dissemination — dissemination in space, meaning the presence of two or more different core clinical characteristics.
- MRI findings — fulfillment of additional MRI requirements.
- Serology — negative test for AQP4-IgG using the best available method or testing not available.
- Differential diagnosis — exclusion of alternative diagnoses.
Classic triad of NMOSD manifestations: Eyes (bilateral long neuritis), Spine (myelitis >3 segments), and Brainstem (intractable hiccups and vomiting due to area postrema involvement).
Class and exam questions
Why was optico-neuromyelitis renamed to spectrum disorders (NMOSD)?
The discovery of aquaporin-4 antibodies showed that inflammation extends far beyond the optic nerves and spinal cord. The pathological process frequently involves the brainstem, diencephalic region, and cerebral white matter.
What spinal cord MRI finding is the most specific in adults?
Longitudinally extensive transverse myelitis (LETM). This is a continuous intramedullary lesion that extends over three or more contiguous vertebral segments.
Can a patient with NMOSD be treated with multiple sclerosis medications?
No, this is strictly contraindicated. Drugs like interferon-beta or natalizumab exacerbate neuromyelitis optica. Patients with NMOSD require targeted immunosuppression.
What else to study on this topic
- Wingerchuk criteria (2015) for diagnosing patients with unknown status or negative test for AQP4-IgG.
- Features of the clinical course and MRI patterns in MOG-IgG-positive patients (especially in children).
- Acute disseminated encephalomyelitis (ADEM): infectious triggers and clinical-radiological picture.
- Differences between ADEM lesions and lesions in multiple sclerosis and NMOSD.
- MR spectroscopy (1H-MRS) in NMOSD: why metabolites in normal-appearing white matter remain unchanged.
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