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Diagnosis of a neuromyelitis optica spectrum disorder (NMOSD)
Distinguishing NMOSD from multiple sclerosis early in the course of disease
Neuromyelitis optica (NMO), sometimes called Devic disease, is a severe, relapsing, autoimmune inflammatory, and demyelinating central nervous system disease that predominantly affects optic nerves and the spinal cord. The disorder is now recognized as a spectrum of autoimmunity targeting the astrocytic water channel aquaporin-4 (AQP4). NMO spectrum disorders (NMOSD) may involve the brain and brainstem with symptoms of encephalopathy (particularly in children). The initial symptoms may be bouts of intractable nausea and vomiting. 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.
Prior to introducing a serological biomarker for NMO, the disorder was thought to be confined exclusively to the optic nerves and spinal cord, that the clinical course was monophasic, and that NMO was a subset of multiple sclerosis (MS). The discovery of a highly specific disease marker for NMO, NMO-IgG/AQP4-IgG helped to define the full clinical spectrum of NMOSD and distinguish these disorders from MS.
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). Within 5 years, 50% of patients lose functional vision in at least 1 eye or are unable to walk independently. 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.
Detection of NMO IgG by cell-binding assay allows distinction of NMOSD (73% are positive) from MS (0% positive), and is indicative of a relapsing disease, mandating initiation of immunosuppression, even after the first attack, thereby reducing attack frequency and disability in the future.
A positive value is consistent with a neuromyelitis optica spectrum disorder (NMOSD) and justifies initiation of appropriate immunosuppressive therapy at the earliest possible time. This allows early initiation and maintenance of optimal therapy. Recommend follow-up in 6 months if NMOSD is suspected. This autoantibody is not found in healthy subjects.
A negative result does not exclude a diagnosis of neuromyelitis optica spectrum disorder (NMOSD).
1. Waters P, McKeon A, Leite MI, et al: Multicenter comparison of aquaporin-4 IgG assays in NMO spectrum disorders. Neurology 2012;78:665-671
2. Lennon VA, Wingerchuk DM, Kryzer TJ, et al: A serum autoantibody marker of neuromyelitis optica; distinction from multiple sclerosis. Lancet 2004;364:2106-2112