Neuromyelitis Optica

Neuromyelitis Optica spectrum disorders (NMOSD) and MOG-IgG-associated disorders (MOGAD)

Neuromyelitis Optica Spectrum Disorders (NMOSD), also known as Neuromyelitis Optica (NMO) or Devic’s Disease, are autoimmune conditions that affect the central nervous system (CNS), primarily targeting the optic nerves and spinal cord, and occasionally involving the brain and brainstem. NMOSD was once considered a variant of multiple sclerosis (MS), but it is now classified as a distinct disorder with different pathological mechanisms and treatment responses. Unlike MS, where disability may accumulate slowly or independently of relapses, NMOSD-related disability is relapse-driven. Each attack can result in permanent neurological damage. Common clinical symptoms include vision loss in one or both eyes, weakness or paralysis of the limbs, and bladder or bowel dysfunction.

At the core of NMOSD pathology is the immune-mediated attack against aquaporin-4 (AQP4), a water channel protein found on astrocytes in the CNS. In AQP4-positive NMOSD, the immune system generates AQP4-IgG antibodies that are approximately 500 times more concentrated in plasma than in cerebrospinal fluid (CSF), suggesting that these antibodies originate peripherally and cross into the CNS. Once inside, they initiate a cascade of inflammatory events, damaging the blood-brain barrier, destroying astrocytes, and ultimately resulting in demyelination and neuronal death. Lesions typically occur in the cervical spinal cord and can extend into the brainstem.

The discovery of AQP4-IgG has revolutionized the diagnosis and classification of NMOSD. In 2015, the Wingerchuk diagnostic criteria were revised to include AQP4-IgG serostatus as a key differentiator. While approximately 65–75% of NMOSD patients are seropositive for AQP4-IgG, around 25% are seronegative. Among these seronegative patients, 15–40% test positive for myelin oligodendrocyte glycoprotein (MOG) antibodies. MOG-IgG is associated with a related condition known as MOG-IgG-associated disease (MOGAD), which clinically overlaps with NMOSD and MS. MOG is a myelin surface protein that contributes to the structural integrity of the myelin sheath. Antibodies against MOG can cause inflammation and demyelination, often resulting in optic neuritis or transverse myelitis. Unlike AQP4 lesions, MOG-related inflammation often involves one eye and may extend further down the spinal cord into lumbar regions. Despite its lower prevalence in NMOSD, MOG-IgG is found in a significant subset (~20%) of patients who are AQP4-IgG seronegative.

The development of advanced diagnostic assays has significantly improved the ability to distinguish NMOSD and MOGAD from other demyelinating diseases. Live cell-based assays (CBAs) are considered the gold standard for detecting both AQP4-IgG and MOG-IgG antibodies due to their superior sensitivity (~77–94%) and specificity (~99–100%) compared to ELISA or fixed CBAs.

The BC Neuroimmunology Lab (BCNI) is the only accredited laboratory in Canada currently offering live CBAs for these antibodies, under license from Oxford University. Their tests have demonstrated 100% concordance with the NHS Neuroimmunology Laboratory at the John Radcliffe Hospital in Oxford, UK. Additional testing options, including STAT AQP4-IgG analysis by rat brain immunohistochemistry, are also available. BCNI was recently recognized in The Lancet as one of North America’s reference laboratories for MOG antibody testing, alongside Harvard and the Mayo Clinic.