Neuromyelitis Optica Spectrum Disorders

Abstract

PURPOSE OF REVIEW: This article reviews the cardinal clinical features, distinct immunopathology, current diagnostic criteria, relapse-related risk factors, emerging biomarkers, and evolving treatment strategies pertaining to neuromyelitis optica spectrum disorders (NMOSD).RECENT FINDINGS: The discovery of the pathogenic aquaporin-4 (AQP4)-IgG autoantibody and characterization of NMOSD as an autoimmune astrocytopathy have spearheaded the identification of key immunologic therapeutic targets in this disease, including but not limited to the complement system, the interleukin 6 (IL-6) receptor, and B cells. Accordingly, four recent randomized controlled trials have demonstrated the efficacy of three new NMOSD therapies, namely eculizumab, satralizumab, and inebilizumab.SUMMARY: Currently, NMOSD poses both diagnostic and treatment challenges. It is debated whether individuals who are seropositive for myelin oligodendrocyte glycoprotein (MOG)-IgG belong within the neuromyelitis optica spectrum. This discussion is fueled by disparities in treatment responses between patients who are AQP4-IgG seropositive and seronegative, suggesting different immunopathologic mechanisms may govern these conditions. As our understanding regarding the immune pathophysiology of NMOSD expands, emerging biomarkers, including serum neurofilament light chain and glial fibrillary acidic protein (GFAP), may facilitate earlier relapse detection and inform long-term treatment decisions. Future research focal points should include strategies to optimize relapse management, restorative treatments that augment neurologic recovery, and practical solutions that promote equitable access to approved therapies for all patients with NMOSD.

Optic neuritis: current challenges in diagnosis and management

“…In the setting of suspected NMOSD-ON, cell-based assays for AQP4-IgG yield a sensitivity of between 80% and 100%, with specificity scores of 86% and 100%. Notably, serum AQP4-IgG titers are germane to NMOSD diagnosis but may not predict long-term disease course or response to therapy [18,19]. There are also challenges to interpreting serum MOG IgG titers: Waters et al compared three different MOG-IgG cell-based assays from three international centers and reported consistently high measures of clinical specificity: 98.1% [positive predictive value (PPV) 82.1%; negative predictive value (NPV) 79.0%] for Euroimmun, 99.6% (PPV 95.5%; NPV 78.8%) for the Mayo Clinic, and 100% (PPV 100%; NPV79.8%) for Oxford [20].…”

“…Treatment benefits with traditional MS diseasemodifying drugs (median ARR 1.5; range 0.2-4.5) are negligible and these agents should be avoided in MOGAD [38]. Importantly, MS disease modifying therapies have been shown to exacerbate disease course in NMOSD [19,41].…”

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): current understanding and challenges

“…Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a relatively new addition to the category of central nervous system (CNS) inflammatory demyelinating diseases [ 1 , 2 ]. CNS inflammatory demyelinating conditions, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), are differentiated based on severity, clinical phenotype, imaging, laboratory, and pathological findings [ 2 ] (Table 1 ).…”

“…Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a relatively new addition to the category of central nervous system (CNS) inflammatory demyelinating diseases [ 1 , 2 ]. CNS inflammatory demyelinating conditions, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), are differentiated based on severity, clinical phenotype, imaging, laboratory, and pathological findings [ 2 ] (Table 1 ). While patients with MS, MOGAD and NMOSD may present with similar clinical manifestations, such as optic neuritis and myelitis, those with MOGAD lack a clear sex predilection, and more commonly experience a monophasic course [ 2 – 5 ].…”

“…CNS inflammatory demyelinating conditions, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), are differentiated based on severity, clinical phenotype, imaging, laboratory, and pathological findings [ 2 ] (Table 1 ). While patients with MS, MOGAD and NMOSD may present with similar clinical manifestations, such as optic neuritis and myelitis, those with MOGAD lack a clear sex predilection, and more commonly experience a monophasic course [ 2 – 5 ]. MOGAD also has the greatest predilection in children, representing 20–30% of inflammatory CNS syndromes in this population as compared to approximately 5% in adults.…”