Neuromyelitis Optica

Pathophysiology

Neuromyelitis Optica (NMO, Devic’s Disease) is an autoimmune inflammatory disorder of the CNS. It is characterised by antibody-mediated inflammatory demyelination and necrosis of the grey and white matter. Lesions have a particular predilection for the optic nerves and the spinal cord, although the brainstem, midbrain and cortex can also be affected. The most common antibody associated with NMO is the anti-Aquaporin 4 IgG. Aquaporin 4 is a water channel expressed highly in astrocytes at the blood-brain barrier and in periventricular regions.

Epidemiology

Prevalence: 1 / 20 000

Risk factors:

  • Female (10:1)

Age of onset: 30s – 40s (slightly older than people with MS)

Symptoms

NMO classically presents with one of:

  • Optic neuritis
  • Longitudinally-extensive transverse myelitis

NMO has a relapsing course – people typically experience multiple episodes of acute demyelination. Although recovery from acute attacks may be very good, over time most people develop visual impairment due to repeated episodes of optic neuritis and impaired motor, bladder, and bowel function due to repeated episodes of transverse myelitis.

Optic neuritis

Inflammatory demyelination of the optic nerve presents with a history of decreased visual acuity, pain on movement of the eye, impaired colour vision, with or without systemic upset. These symptoms develop over a short period (~24 hours) and reach their worst after ~ 2 weeks. In NMO, people may present with bilateral optic neuritis. This is rare in other disorders.

Transverse myelitis

Transverse myelitis refers to a spinal cord syndrome which is caused by an inflammatory lesion of the spinal cord. In NMO, transverse myelitis typically is complete (i.e. mimics a complete spinal cord transection) and extends longitudinally (i.e. affects multiple adjacent spinal cord segments). Presenting features therefore include symmetrical, bilateral, upper motor neuron weakness, a sensory level with loss of all modalities below the affected cord level, autonomic dysfunction (e.g. urinary incontinence), and variable weakness and sensory loss at the level of the affected spinal cord segments.

Other features

NMO may cause inflammatory demyelination in any part of the CNS including the hypothalamus and cortex. Symptoms suggestive of wider involvement include excessive daytime sleepiness (hypothalamus) and intractable vomiting (area postrema in the medulla).

On examination

  • On inspection
    • Visual aids
    • Walking aids
    • Long-term catheter
  • Eyes
    • Look for evidence of current or previous bilateral optic neuritis
      • Relative afferent pupillary defects (may be difficult to elicit if both eyes affected)
      • Achromatopsia
      • Visual field defects: classically ON produces a central scotoma but lots of other patterns of visual loss are possible
      • Fundoscopy: a pale disc implies optic atrophy secondary to previous optic neuritis
  • Arms & legs
    • Look for evidence of longitudinally extensive transverse myelitis
      • Symmetrical UMN weakness
      • Sensory level

Diagnosis

The diagnosis of NMO is based on a combination of clinical findings, serology, imaging, and CSF analysis.

  • Serology:
    • Anti-AQP4 is positive in most cases of what is clinically NMO (~90%). A subset of patients are positive for anti-Myelin Oligodendrocyte Glycoprotein (anti-MOG).
  • MRI brain and spinal cord:
    • T2W: demonstrates demyelinating lesions
    • T1-Gd: demonstrates Gadolinium-enhancement (BBB breakdown)

      Case courtesy of A.Prof Frank Gaillard, Radiopaedia.org. From the case rID: 26591

  • CSF: not always required but may help to distinguish from MS.
    • Oligoclonal bands are present in ~ 20% vs 90% of people with MS.
    • Raised CSF WCC and protein are more common in NMO than MS.

Treatments

Management involves two aspects:

  • Treating acute attacks
  • Preventing further attacks

Treating acute relapses

Acute relapses are generally treated with pulsed IV steroids and/or plasma exchange.

Long-term preventative therapy

Widely-used long-term preventative therapy for NMO includes azathioprine, rituximab, and MMF.

Prognosis

The prognosis of NMO is worse than MS. People generally accrue disability with each acute relapse. Mortality rates are high.