Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategies

Neuromyelitis optica (NMO) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by acute optic neuritis (ON) and transverse myelitis (TM). NMO is caused by a pathogenic serum IgG antibody against the water channel aquoporin 4 (AQP4) in the majority of patients. AQP4-antibody (AQP4-ab) presence is highly specific, and differentiates NMO from multiple sclerosis. It binds to AQP4 channels on astrocytes, triggering activation of the classical complement cascade, causing granulocyte, eosinophil, and lymphocyte infiltration, culminating in injury first to astrocyte, then oligodendrocytes followed by demyelination and neuronal loss. NMO spectrum disorder (NMOSD) has recently been defined and stratified based on AQP4-ab serology status. Most NMOSD patients experience severe relapses leading to permanent neurologic disability, making suppression of relapse frequency and severity, the primary objective in disease management. The most common treatments used for relapses are steroids and plasma exchange.Currently, long-term NMOSD relapse prevention includes off-label use of immunosuppressants, particularly rituximab. In the last 2 years however, three pivotal clinical trials have expanded the spectrum of drugs available for NMOSD patients. Phase III studies have shown significant relapse reduction compared to placebo in AQP4-ab-positive patients treated with satralizumab, an interleukin-6 receptor (IL-6R) inhibitor, inebilizumab, an antibody against CD19+ B cells; and eculizumab, an antibody blocking the C5 component of complement. In light of the new evidence on NMOSD pathophysiology and of preliminary results from ongoing trials with new drugs, we present this descriptive review, highlighting promising treatment modalities as well as auspicious preclinical and clinical studies.

Optical Coherence Tomography Reveals Longitudinal Changes in Retinal Damage Under Different Treatments for Neuromyelitis Optica Spectrum Disorder

Background: Progressive retinal neuroaxonal damage after acute optic neuritis may occur in neuromyelitis optica spectrum disorder (NMOSD). However, it is unclear if treatments used to prevent attacks influence neurodegeneration.Objectives: We aimed to investigate retinal damage in patients treated with disease-modifying drugs in a longitudinal study.Methods: We retrospectively included 50 patients with aquaporin 4-antibody-seropositive NMOSD. Peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell complex (mGCC) thickness, total macular volume (TMV), and optic disc measures were acquired by spectral domain optical coherence tomography in patients treated with tocilizumab, rituximab, and azathioprine.Results: Longitudinally, in eyes with a history of ON (NMOSDON+), we observed annual thinning of mGCC [tocilizumab: −1.77 (−3.44, −0.09) μm, p = 0.041; rituximab: −2.03 (−3.58, −0.48) μm, p = 0.017; azathioprine: −1.79 (−2.22, −1.37) μm, p < 0.001], and pRNFL [tocilizumab: −2.07 (−0.75, −3.39) μm, p = 0.005; rituximab: −2.18 (−0.36, −4.00) μm, p = 0.023; azathioprine: −2.37 (−0.98, −3.75) μm, p = 0.003], reduced TMV [tocilizumab: −0.12 (−0.22, −0.01) mm3, p = 0.028; rituximab: −0.15 (−0.21, −0.08) mm3, p = 0.001; azathioprine: −0.12 (−0.20, −0.04) mm3, p = 0.006], and increased cup area [tocilizumab: 0.08 (−0.01, 0.16) mm2, p = 0.010; rituximab: 0.07 (0.01, 0.12) mm2, p = 0.019; azathioprine: 0.14 (0.02, 0.26) mm2, p = 0.023]. However, we detected no significant differences in annual changes in mGCC, pRNFL, TMV, and cup area between patients with tocilizumab, rituximab, and azathioprine in NMOSDON+ eyes. NMOSDON− eyes did not display mGCC or pRNFL thinning in patients treated with tocilizumab and rituximab. Intriguingly, we observed significant thinning of mGCC in patients treated with azathioprine compared with tocilizumab [−0.84 (−1.50, −0.18) μm vs. −0.19 (−0.87, 0.48) μm, p = 0.012] and rituximab [−0.84 (−1.50, −0.18) μm vs. −0.07 (−1.25, −2.51) μm, p = 0.015] in NMOSDON− eyes.Conclusions: This study demonstrated that retinal ganglion cell loss is independent of ON attacks in NMOSD. Tocilizumab and rituximab may delay mGCC thinning in NMOSDON− eyes compared with azathioprine.

Immunotherapy in complex treatment of acute optic neuritis associated with herpesvirus infection

Purpose. Evaluation clinical efficacy of complex treatment of optic neuritis (ON) associated with herpesvirus infection (HVI), including methods of immunotherapy. Material and methods. The clinical study involved 26 people (26 eyes) with acute ON associated with HVI. The treatment regimen for all patients within 10 days included delivery through irrigation system implanted into the retrobulbar space to optic nerve: solutions Dexamethasone on decreasing scheme, Emoxypine 1% 0.5 ml and Dicynone 12.5% 0.5 ml. All patients were divided into 2 groups depending on characteristics of therapy. The 1st group consisted of 12 patients, who were treated according to the standard method. 2nd group consisted of 14 patients who received additional intramuscular Imunofan. The duration of immunotherapy was 10–12 days. Results. Analysis of obtained datas showed that more significant positive dynamics was noted in the clinical course of ON in patients of the 2nd group of observation in comparison with the 1st group. Conclusion. The developed strategy of etiotropic and pathogenetic immunotherapy at ON associated with HVI infection, allows shortening recovery time and improving functional results of treatment in absence of relapses of disease within 1 year of follow-up. Key words: optic neuritis, herpesvirus infection, corticosteroid therapy, immunotherapy.

Evaluation clinical efficacy of immunotherapy in complex treatment of acute optic neuritis associated with herpesvirus infection

Purpose. To study the clinical efficacy of complex treatment of optic neuritis (ON) associated with herpesvirus infection (HVI), including methods of immunotherapy. Material and methods. The clinical study involved 37 people (37 eyes) with acute ON associated with HVI. The treatment regimen for all patients within 10 days included delivery through irrigation system implanted into the retrobulbar space to optic nerve: solutions Dexamethasone on decreasing scheme, Emoxypine 1% 0.5 ml and Dicynone 12.5% 0.5 ml, in combination with administration of drugs neuroprotection. All patients were divided into 2 groups depending on characteristics of therapy. The 1st group consisted of 17 patients, who were treated according to the standard method. 2nd group consisted of 20 patients who received additional intramuscular Imunofan in the regimen and doses according to the manufacturer's instructions. Results. Analysis of obtained datas showed that more significant positive dynamics was noted in the clinical course of ON in patients of the 2nd group of observation in comparison with the 1st group. Conclusion. The strategy of etiotropic and pathogenetic immunotherapy at ON, associated with HVI infection, developed by us, allows to shorten recovery time and improve functional results of treatment in absence of relapses of disease within 1 year of follow-up. Key words: optic neuritis, herpesvirus infection, corticosteroid therapy, immunotherapy.