Treatment of Neuromyelitis Optica Spectrum Disorders

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune central nervous system (CNS) inflammatory disorder that can lead to serious disability and mortality. Females are predominantly affected, including those within the reproductive age. Most patients develop relapsing attacks of optic neuritis; longitudinally extensive transverse myelitis; and encephalitis, especially brainstem encephalitis. The majority of NMOSD patients are seropositive for IgG autoantibodies against the water channel protein aquaporin-4 (AQP4-IgG), reflecting underlying aquaporin-4 autoimmunity. Histological findings of the affected CNS tissues of patients from in-vitro and in-vivo studies support that AQP4-IgG is directly pathogenic in NMOSD. It is believed that the binding of AQP4-IgG to CNS aquaporin-4 (abundantly expressed at the endfoot processes of astrocytes) triggers astrocytopathy and neuroinflammation, resulting in acute attacks. These attacks of neuroinflammation can lead to pathologies, including aquaporin-4 loss, astrocytic activation, injury and loss, glutamate excitotoxicity, microglial activation, neuroinflammation, demyelination, and neuronal injury, via both complement-dependent and complement-independent pathophysiological mechanisms. With the increased understanding of these mechanisms underlying this serious autoimmune astrocytopathy, effective treatments for both active attacks and long-term immunosuppression to prevent relapses in NMOSD are increasingly available based on the evidence from retrospective observational data and prospective clinical trials. Knowledge on the indications and potential side effects of these medications are essential for a clear evaluation of the potential benefits and risks to NMOSD patients in a personalized manner. Special issues such as pregnancy and the coexistence of other autoimmune diseases require additional concern and meticulous care. Future directions include the identification of clinically useful biomarkers for the prediction of relapse and monitoring of the therapeutic response, as well as the development of effective medications with minimal side effects, especially opportunistic infections complicated by long-term immunosuppression.

Sociodemographic and Illness-Related Indicators to Predict the Status of Neuromyelitis Optica Spectrum Disorder (NMOSD) Five Years after Disease Onset

“…Fifth, it is conceivable that latent and unassessed factors might have biased two or more dimensions in the same or opposite directions. Sixth, two major issues must be considered: First, the lack of CSF findings might bear the risk of the blurred exclusion of alternative diagnosis as a key element of the NMOSD diagnostic criteria [1][2][3][4][5][6][7]. Relatedly, seventh, at the second time point, visual acuity was not assessed.…”

“…Neuromyelitis optica (NMO) or Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune inflammatory disorder, which prevalently affects the optic nerve and the spinal cord [1][2][3][4][5][6][7]. Accordingly, simultaneous or consecutive attacks of acute optic neuritis and transverse myelitis characterize NMOSD [7].…”

“…To summarize, while meanwhile the etiopathology and pathophysiology of NMOSD appeared to be well understood [7], in contrast, the current literature showed that the identification of clinically useful biomarkers and further disease-related indices for the prediction of relapses and the therapeutic response appeared modest and unsatisfactory [6,7]. Further, the clinical course of the NMOSD causes a substantial burden for the patient, and such burdens are associated with substantial healthcare utilizations in addition to expenditure for the public sector [21].…”

Treatment and Relapse Prevention of Typical and Atypical Optic Neuritis

“…MMF is a noncompetitive inhibitor of inosine monophosphate dehydrogenase, an enzyme essential for de novo synthesis of the purine nucleotide guanosine-5′-monophosphate, which inhibits the proliferation of lymphocytes [ 105 , 106 , 107 ]. MMF is a semi-synthetic derivative of mycophenolic acid (MPA), which is the active metabolite of MMF.…”

“…Among the benefits of AZA treatment are the convenient oral administration and the affordability of the agent compared to rituximab [ 106 ]. Recently, data from 150 NMOSD patients treated with AZA showed that 69% had no accumulation of disability after a 5-year follow-up [ 111 ].…”