Clinical Information

Neuromyelitis optica (NMO), sometimes called Devic disease or opticospinal multiple sclerosis (MS) is a severe, relapsing, autoimmune, inflammatory and demyelinating central nervous system disease that predominantly affects optic nerves and spinal cord.(1) The disorder is now recognized as a spectrum of autoimmunity (termed NMO spectrum disorders: NMOSD) targeting the astrocytic water channel aquaporin-4 (AQP4).(1,2) Brain lesions are observed in >60% of patients with NMOSD and approximately 10% will be MS-like.(3) Children tend to have greater brain involvement than adults and brain lesions are more symptomatic than is typical for adult patients.(4) Extensive cerebral white matter signal abnormalities are sometimes encountered, most commonly in children, and are sometimes associated with encephalopathy. Circumventricular organs (CVO; eg, area postrema) are preferentially involved.

Symptoms and signs attributable to area postrema involvement include intractable hiccups, nausea and vomiting, and these may occur in isolation, herald the onset of NMO, or occur in association with the more classical optic neuritis or Longitudinally Extensive Transverse Myelitis (LETM).(5) Magnetic resonance imaging typically reveals large inflammatory spinal cord lesions involving 3 or more vertebral segments.

During acute attacks, the cerebrospinal fluid contains inflammatory cells, but usually lacks evidence of intrathecal IgG synthesis. The clinical course is characterized by relapses of optic neuritis or transverse myelitis, or both. Many patients with NMOSD are misdiagnosed as having MS. Importantly, the prognosis and optimal treatments for the 2 diseases differ. NMOSD typically has a worse natural history than MS, with frequent and early relapses. NMOSD attacks are often severe resulting in a rapid accumulation of disability (blindness and paraplegia). More effective treatments combined with earlier and more accurate diagnosis has led to improved outcomes. Currently, in the AQP4-IgG era, 5 years after onset, approximately 30% of NMO patients will require a cane to walk and 10% will be wheelchair bound.

Treatments for NMOSD include corticosteroids and plasmapheresis for acute attacks and mycophenolate mofetil, azathioprine, and rituximab for relapse prevention. Beta-interferon, a treatment promoted for MS, exacerbates NMOSD. Therefore, early diagnosis and initiation of NMO-appropriate immunosuppressant treatment is important to optimize the clinical outcome by preventing further attacks. Skeletal muscle abnormalities with hyerCKemia have been reported in a few NMOSD patients. Recent reports indicate focal retinal vascular attenuation, inner nuclear layer thickening and microcystic edema in some NMO patients.

Detection of AQP4-IgG by NMO/AQP4 FACS in cerebrospinal fluid (CSF) allows distinction from MS and is indicative of an NMOSD.

Though serum is optimal for AQP4-IgG testing, occasionally physicians submit only CSF for testing. A previous study, based on our first-generation indirect immunofluorescence assay compared the frequencies of AQP4-IgG in serum and CSF. The positivity rate was greater for serum alone than for CSF alone.(6) However, testing of CSF was helpful when the serum was negative. Detection of AQP4-IgG in CSF allowed unambiguous distinction of NMO from MS. CSF testing offered the additional advantage of generally lacking the nonorgan-specific IgG autoantibodies (eg, antinuclear, antimitochondrial, and smooth muscle) that are common in serum of patients with NMO and also with classic paraneoplastic autoimmune disorders. Recent AQP4 FACS analysis of paired CSF and serum samples from 66 patients submitted for AQP4-IgG testing reveals a slightly better detection rate in serum (n=59) compared with CSF (n=55). All 7 patients who tested negative in serum also tested negative in CSF.