Neuromyelitis optica spectrum disorder

Neuromyelitis optica (NMO) also known Devic disease is a severe demyelinating disease ². Exactly how NMO relates to multiple sclerosis (MS) continues to be uncertain. It is clear that it is a distinct entity, however, there are many overlapping features ⁴. 

Epidemiology

NMO is typically found in patients that are somewhat older than those with MS and there is an even stronger female predilection ⁶. 

Clinical presentation

Neuromyelitis optica is characterized by bilateral optic neuritis and myelitis, with blindness and paraplegia. Although the two usually present concurrently, it is not uncommon for one to precede the other by up to a number of weeks ³. Additionally it is now recognized that some patients have unilateral optic nerve involvement, and may suffer from a relapsing course. 

Although NMO was initially thought of as a monophasic illness it is now evident that, like many patients with multiple sclerosis, it is usually a relapsing disease with symptomatic events separated by many years ⁵. 

Pathology

Histopathology and immunohistochemistry are helpful. Early in the disease demyelinating regions will demonstrate similar findings to multiple sclerosis such as macrophage/microglia activation and axonal damage. Additionally however, and relatively specific for NMO, these regions will also demonstrate extensive eosinophilic infiltration, perivascular deposition of immunoglobulins (especially IgM), and local activation of the complement cascade ³. Additionally, axonal damage precedes demyelination in NMO ⁵. 

In approximately 70% of patients with NMO, a specific immunoglobulin can be isolated (NMO-Immunoglobulin G) which targets a transmembrane water channel (aquaporin 4) present on astrocyte foot processes abutting the limiting membrane ⁵. This accounts for some of the predilection for certain parts of the brain (e.g. periaqueductal grey matter) which is particularly rich in aquaporin 4. 

Radiographic features

MRI

MRI is the modality of choice, with imaging of the orbits, brain and spinal cord required. 

Brain

Although traditionally NMO was thought to have normal intracranial appearance it is increasingly evident that in the majority of patients asymptomatic abnormalities are present. These can be divided into 4 categories ⁵:

1. lesions which mirror distribution of aquaporin 4 in the brain, which is particularly found in the periependymal brain adjacent to the ventricles
   • periventricular (hemispheric) confluent white matter involvment (unlike MS there are usually no Dawson's fingers)
   • periaqueductal grey matter
   • hypothalamus / medial/medial thalamus
   • dorsal pons / medulla/medulla 
   • corpus callosum
     • multiple corpus colossal lesions with heterogeneous signal leading to a marbled pattern ⁷ 
     • splenium may be diffusely involved and expanded
2. deep (or less frequently subcortical) punctate white matter lesions (which may appear similar to those seen in multiple sclerosis) 
3. corticospinal tract involvement by extensive longitudinal lesions; has been reported more frequently in Korean patients ⁵
4. larger "spilled ink pattern" of hemispheric white matter lesions which often vanish with steroid administration; may be more common in children and in patients from the Far East and Africa

Unlike MS, NMO does not appear to involve the cortex ⁵. 

Orbits

Targeted imaging of the orbits (including fat saturated T1 C+ and T2 weighted sequences) may demonstrate typical features of optic neuritis, with the optic nerves appearing hyperintense on T2 weighted sequences, swollen and enhancement. Bilateral involvement and extension of the signal back into the chiasm is particularly suggestive of NMO ⁵. 

Spinal cord

Spinal cord involvement is extensive, with high T2 signal extend over long distances (over three or more vertebral segments, often much more). This is known as a longitudinaly extensive spinal cord lesion (LESCL) ^4,5. Also helpful in distinguishing it from multiple sclerosis demyelination is the involvement of the central part of the cord (MS lesions tend to involve individual peripheral white matter tracts). 

Imaging features acutely include ⁵: 

• >3 vertebral body length of involvement 
• T1: hypointense
• T2: hyperintense with involvement of the central grey matter
• T1 C+
  • ​patchy "cloud like" enhancement of T2 brighbright lesions may be present
  • thin ependymal enhancement similar to ependymitis
  • NB open ring enhancement is not a feature of NMO

Follow-up scans may demonstrate cord atrophy and low T1 signal ⁵. 

Treatment and prognosis

Treatment of NMO is evolving, with immunosuppression (e.g. anti-CD20 monoclonal antibody rituximab) appearing effective ⁵.

It is important to distinguish NMO from MS as treatment not only is different but treating a patient with NMO with MS-specific therapies (e.g. beta-interferon or natalizumab) can actually lead to exacerbation of NMO ⁵. 

Patients with relapsing course have a poorer prognosis ⁴:

• blind in one or both eyes: monophasic  22%, relapsing 60%
• monoplegia or paraplegia: monophasic 31%, relapsing  52%

Differnetial diagnosis

The differential diagnosis depends on the presentation, and when classical then the diagnosis can be made with a fair degree of certainty. 

For patients with spinal cord involvement the differential is that of a longitudinally extensive spinal cord lesion. 

Cerebral white matter and corpus callosal involvement has a broad differential depending on the pattern, but the most important differential is multiple sclerosis (MS). Features helpful favouring NMO over MS include ^5,7: 

• periventricular/aqueductal distribution (see above)
• absent perivenular orientation of periventricular lesions (no Dawson's fingers)
• more extensive involvement of the corpus callosum
• larger more confluent lesions
• lack of open ring enhancement
• lack of cortical grey matter involvement