Description
Neuromyelitis Optica Spectrum Disorder (NMOSD) is an immune-mediated inflammatory disorder of the central nervous system. It is characterised by the presence of specific antibodies against aquaporin-4 (AQP4-IgG), a water channel protein on astrocytes, which leads to recurrent attacks of optic neuritis and transverse myelitis.
Pathogenesis
The pathogenesis of NMOSD involves the production of autoantibodies (AQP4-IgG) that target the AQP4 water channels. These channels are found predominantly on astrocytes, which are support cells in the central nervous system. The binding of the autoantibodies initiates an inflammatory response leading to damage of the optic nerve and spinal cord. This mechanism contrasts with Multiple Sclerosis (MS), where the main target is the myelin sheath of neurons.
Subtypes
NMOSD can be divided into two subtypes based on the presence of AQP4-IgG:
- AQP4-IgG seropositive NMOSD: This is the most common type and is associated with severe attacks of optic neuritis and transverse myelitis.
- AQP4-IgG seronegative NMOSD: This type is less common and the clinical features can be similar or less severe than the seropositive type. However, it is associated with a different antibody (MOG-IgG) in some cases.
Epidemiology, Risk Factors & Associations
- The prevalence of NMOSD varies geographically but it is less common than MS. In Europe, it is estimated to affect about 0.5-10 individuals per 100,000 population.
- Females are more affected than males (ratio 9:1), and the average age of onset is between 30 and 40 years.
- NMOSD is typically seen with optic neuritis and longitudinally extensive transverse myelitis (LETM).
- Risk factors for developing NMOSD include having other autoimmune diseases, such as systemic lupus erythematosus and Sjögren’s syndrome. There is an increased risk of relapse during pregnancy.
Clinical Features
Typical features of NMOSD include:
- Optic neuritis: This is characterised by painful eye movement and visual loss. It often affects both eyes but can be unilateral.
- Transverse myelitis: This presents as weakness or paralysis of limbs, sensory disturbances, and often loss of bladder and bowel control.
- Other less common symptoms can include intractable nausea and vomiting or hiccups due to involvement of the area postrema in the brainstem.
Complications
Common complications of NMOSD include permanent visual loss, motor disability due to spinal cord damage, and psychological distress related to living with a chronic, debilitating condition.
Pathological Features
Histopathology
On histopathology, NMOSD lesions show loss of AQP4 staining and glial fibrillary acidic protein (GFAP) with preservation of myelin initially. There is also infiltration by granulocytes, macrophages, and eosinophils, along with perivascular deposition of activated complement components.
AQP4 protein is highly expressed in the periependymal regions, such as the area postrema.
Serology
The presence of AQP4-IgG is confirmatory for the diagnosis of NMOSD.
Systemic autoimmune disorders & autoantibodies may coexist in NMO (e.g., thyroid disease, myasthenia gravis, coeliac disease, systemic lupus erythematosus, & Sjögren syndrome).
Biochemistry
No specific biochemical markers are associated with NMOSD, although general markers of inflammation may be elevated during active disease.
Genetics
There is currently no known genetic link or hereditary factor for NMOSD.
Radiological Features
General Features
- Typically involve the optic nerves and spinal cord (both halves).
- Optic nerve enhancement and enlargement can be seen on MRI, and the spinal cord lesions are often longitudinally extensive, spanning three or more vertebral segments.
MRI
- Brain: Non-specific white matter lesions or involvement of specific areas like the area postrema, causing intractable nausea and vomiting or hiccups.
- T2WI:
- Longitudinally extensive lesion causing fusiform enlargement of the spinal cord – most specific non-serological feature
- T2 abnormality tends to involve entire cross-section of cord (MS tends to be more focal).
- Hyperintense lesions also seen in the optic nerve
- T1WI C+: Enhancement of the optic nerve or spinal cord lesions may be observed (85%).
Diagnosis
The diagnosis of NMOSD requires the presence of at least one core clinical characteristic (optic neuritis, acute myelitis, etc.), positive AQP4-IgG serology, and exclusion of alternative diagnoses.
Differential Diagnosis
- Multiple Sclerosis (MS): NMOSD can be differentiated from MS by the presence of AQP4-IgG, longitudinally extensive transverse myelitis, and bilateral optic neuritis. MS demonstrates focal (not involving both sides of cord), short-segment (< 2 vertebral segments) neural enhancement, rather than long-segment (> 3 vertebral segments) as seen in NMOSD. NMOSD patients tends to be older at onset and more severe in course.
- Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD): Like NMOSD, MOGAD can present with optic neuritis and transverse myelitis. However, patients with MOGAD test positive for MOG-IgG and negative for AQP4-IgG.
- Transverse Myelitis: Not a specific diagnosis – reaction to various autoimmune or infectious stimuli. Both halves of cord involved, as with NMOSD.
- Acute Ischaemia: May be seen as a complication of aortic aneurysm repair or catherisation, result of venous hypertension or arterial steal as seen in vascular malformations. Abnormality is located in the anterior cord.
Management
- Management of NMOSD typically involves neurologists and often includes immunosuppressive therapy to reduce the frequency and severity of attacks.
- Acute attacks are typically treated with high-dose corticosteroids, and plasma exchange may be considered in severe cases or when response to steroids is inadequate.
- Long-term management may include medications such as azathioprine, mycophenolate mofetil, or rituximab to reduce the frequency and severity of relapses.