scholarly journals Anti-B-cell therapy in patients with neuromyelitis optica spectrum disorders

2021 ◽  
Vol 13 (4) ◽  
pp. 18-24
Author(s):  
S. V. Kotov ◽  
E. S. Novikova ◽  
A. S. Kotov
Keyword(s):  
Optic Neuritis ◽  
Relapse Rate ◽  
Neuromyelitis Optica ◽  
Clinical Manifestations ◽  
Treatment Protocol ◽  
Transverse Myelitis ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Intravenous Infusions ◽  
Annualized Relapse Rate ◽  
Spectrum Disorders

Neuromyelitis optica spectrum disorders (NMOSDs) are a group of central nervous system autoimmune diseases characterized by similar clinical manifestations, optic neuritis, and transverse myelitis being the most frequent among them. In most cases, the pathogenesis of NMOSDs is associated with autoantibodies to aquaporin-4 (AQP4-IgG). However, AQP4-IgG is not detected in at least 10-20% of patients with NMOSDs. In this subgroup and in patients with isolated transverse myelitis or optic neuritis, IgG antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) were detected. Patients seronegative for both AQP4-IgG and MOG-IgG have also been described.Objective: to evaluate rituximab (RTX) effectiveness in preventing relapses and disability in patients with NMOSDs.Patients and methods. The study included 27 patients with NMOSDs (9 men and 18 women) aged 20-51 years who received RTX in 2019-2021. The treatment protocol included intravenous infusions of 1000 mg of RTX on the 1st and 15th days, the second and subsequent courses (maintenance therapy) - intravenous infusions of 1000 mg of RTX once every six months. Treatment effectiveness was assessed by the average annualized relapse rate, the median changes of the Expanded Disability Status Scale (EDSS), and based on the magnetic resonance imaging (MRI) changes.Results and discussion. The annualized relapse rate at baseline and 18 months after the start of treatment was: all patients (n=27) — 0.6±0.3 and 0.07±0.27(p<0.0001); AQP4-IgG+ patients (n=6) — 1.1±0.9 and 0.17±0.41 (p=0.028); MOG-IgG+ patients (n=14) — 0.4±0.3 and 0.07±0.28(p=0.001); AQP4-IgG-, MOG-IgG-patients (n=7) — 0.8±0.4 and 0.0±0.0 (p=0.018). The EDSSscore at baseline and 18months after the start of treatment was: all patients — 4.5 [3.25; 6.0] and 4.0 [3.0; 5.75] (p=0.679); AQP4-IgG+ — 3.5 [2.625; 4.75] and 3.5 [2.5; 4.5] (p=0.869); MOG-IgG+ - 5.5[3.75; 6.5] and 5.5[2.75; 6.25] (p=0.465); AQP4-IgG-, MOG-IgG- - 4.0[3.75; 5.25] and 3.5[3.0; 3.5] (p=0.043). We observed two clinical relapses during the study period: one in an AQP4-IgG+ male and another one in a MOG-IgG+ woman. There was a significant decrease in the annualized relapse rate in all groups. The disability indicator did not increase during the study period, and in AQP4-IgG and MOG-IgG seronegative patients, it slightly but significantly decreased. Brain and spinal cord MRI monitoring during the treatment period revealed new active foci only in two patients with clinical relapses.Conclusion. RTX treatment in NMOSDs is reasonably efficient and safe, but with the obligatory prior patient evaluation and monitoring of treatment results.

Atypical myelitis in patients with multiple sclerosis: Characterization and comparison with typical multiple sclerosis and neuromyelitis optica spectrum disorders

2020 ◽  
pp. 135245852090699
Author(s):  
K Bigaut ◽  
C Lambert ◽  
L Kremer ◽  
C Lebrun ◽  
M Cohen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Transverse Myelitis ◽  
First Episode ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Disability Status ◽  
Plane Transverse ◽  
Spectrum Disorders ◽  
Extensive Transverse Myelitis

Background: Atypical myelitis in multiple sclerosis (MS) is characterized by extensive myelitis in the longitudinal (longitudinally extensive transverse myelitis) or axial plane (transverse myelitis). Objective: To characterize a cohort of MS patients with atypical myelitis. Methods: Atypical myelitis was extracted from the French and Luxembourg MS databases and compared to two cohorts of MS patients with typical myelitis and neuromyelitis optica spectrum disorders (NMOSDs) patients with myelitis. Results: We enrolled 28 MS patients with atypical myelitis, 68 MS patients with typical myelitis and 119 NMOSD patients with a first episode of myelitis. MS patients with atypical myelitis were characterized by a mean age of 34.0 (±10.7) years and 64.3% were women. In 82.1% of the patients, atypical myelitis was the first episode of MS. Mean Expanded Disability Status Scale (EDSS) scores at nadir and 3–6 months after onset were 4.1 ± 2.1 and 3.3 ± 2, respectively. Differences between groups revealed a predominance of cervicothoracic myelitis and a higher level of disability in NMOSD patients. Disability in MS patients with atypical myelitis was more severe than in the MS patients with typical myelitis; 28% had already converted to progressive MS within our mean follow-up of 39.6 (±30.4) months. Conclusion: Atypical myelitis may be the first presentation of MS and is associated with poorer prognosis.

scholarly journals Neuromyelitis Optica Spectrum Disorder and Anti-MOG Syndromes

Biomedicines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 42 ◽  
Author(s):  
Marco A. Lana-Peixoto ◽  
Natália Talim
Keyword(s):  
Optic Neuritis ◽  
Neuromyelitis Optica ◽  
Area Postrema ◽  
Water Channel ◽  
Clinical Manifestations ◽  
Transverse Myelitis ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Immunosuppressive Drugs ◽  
Spectrum Disorder ◽  
Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein (anti-MOG) syndromes are immune-mediated inflammatory conditions of the central nervous system that frequently involve the optic nerves and the spinal cord. Because of their similar clinical manifestations and habitual relapsing course they are frequently confounded with multiple sclerosis (MS). Early and accurate diagnosis of these distinct conditions is relevant as they have different treatments. Some agents used for MS treatment may be deleterious to NMOSD. NMOSD is frequently associated with antibodies which target aquaporin-4 (AQP4), the most abundant water channel in the CNS, located in the astrocytic processes at the blood-brain barrier (BBB). On the other hand, anti-MOG syndromes result from damage to myelin oligodendrocyte glycoprotein (MOG), expressed on surfaces of oligodendrocytes and myelin sheaths. Acute transverse myelitis with longitudinally extensive lesion on spinal MRI is the most frequent inaugural manifestation of NMOSD, usually followed by optic neuritis. Other core clinical characteristics include area postrema syndrome, brainstem, diencephalic and cerebral symptoms that may be associated with typical MRI abnormalities. Acute disseminated encephalomyelitis and bilateral or recurrent optic neuritis are the most frequent anti-MOG syndromes in children and adults, respectively. Attacks are usually treated with steroids, and relapses prevention with immunosuppressive drugs. Promising emerging therapies for NMOSD include monoclonal antibodies and tolerization.

The clinical spectrum associated with myelin oligodendrocyte glycoprotein antibodies (anti-MOG-Ab) in Thai patients

2015 ◽  
Vol 22 (7) ◽  
pp. 964-968 ◽  
Author(s):  
Sasitorn Siritho ◽  
Douglas K Sato ◽  
Kimihiko Kaneko ◽  
Kazuo Fujihara ◽  
Naraporn Prayoonwiwat
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Optic Neuritis ◽  
Neuromyelitis Optica ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Visual Recovery ◽  
Central Nervous System Disorders ◽  
Spectrum Disorders

Background: Myelin oligodendrocyte glycoprotein (anti-MOG) antibody was reported in anti-aquaporin-4 (anti-AQP4) seronegative neuromyelitis optica spectrum disorders (NMOSD) patients. Objectives: To describe clinical phenotypes associated with anti-MOG. Methods: Seventy consecutive Thai patients with inflammatory idiopathic demyelinating central nervous system disorders (IIDCD) who were previously anti-AQP4 seronegative were tested for anti-MOG. Results: Anti-MOG was positive in six patients, representing 20.7% of the IIDCD anti-AQP4 seronegative patients with a non-multiple sclerosis phenotype, and most had relapses. All first presented with optic neuritis with good visual recovery after treatment. Conclusions: Anti-MOG positive patients may have manifestations that mimic NMOSD but differ in their course and prognosis from anti-AQP4 positive NMOSD.

scholarly journals Memantine ameliorates motor impairments and pathologies in a mouse model of neuromyelitis optica spectrum disorders.

2020 ◽  
Author(s):  
Leung-Wah Yick ◽  
Chi-Ho Tang ◽  
Oscar Ka-Fai Ma ◽  
Jason Shing-Cheong Kwan ◽  
Koon Ho CHAN
Keyword(s):  
Spinal Cord ◽  
Neuromyelitis Optica ◽  
Neurotrophic Factor ◽  
Water Channel ◽  
Transverse Myelitis ◽  
Aquaporin 4 ◽  
Glutamate Excitotoxicity ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Motor Impairments ◽  
Spectrum Disorders

Abstract Background: Neuromyelitis optica spectrum disorders (NMOSD) are central nervous system (CNS) autoimmune inflammatory demyelinating diseases characterized by recurrent episodes of acute optic neuritis and transverse myelitis. Aquaporin-4 immunoglobulin G (AQP4-IgG) autoantibodies, which target the water channel aquaporin-4 (AQP4) on astrocytic membrane, are pathogenic in NMOSD. Glutamate excitotoxicity, which is triggered by internalization of AQP4-glutamate transporter complex after AQP4-IgG binding to astrocytes, is involved in early NMOSD pathophysiologies. We studied the effects of memantine, a N-methyl-D-aspartate (NMDA) receptor antagonist, on motor impairments and spinal cord pathologies in mice which received human AQP4-IgG. Methods: Purified IgG from AQP4-IgG-seropositive NMOSD patients were passively transferred to adult C57BL/6 mice with disrupted blood-brain barrier. Memantine was administered by oral gavage. Motor impairments of the mice were assessed by beam walking test. Spinal cords of the mice were assessed by immunofluorescence and ELISA. Results: Oral administration of memantine ameliorated the motor impairments induced by AQP4-IgG, no matter the treatment was initiated before (preventive) or after (therapeutic) disease flare. Memantine profoundly reduced AQP4 and astrocyte loss, and attenuated demyelination and axonal loss in the spinal cord of mice which had received AQP4-IgG. The protective effects of memantine were associated with inhibition of apoptosis and suppression of neuroinflammation, with decrease in microglia activation and neutrophil infiltration and reduction of increase in levels of proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α). In addition, memantine elevated growth factors including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) in the spinal cord. Conclusions: Our findings support that glutamate excitotoxicity and neuroinflammation plays important roles in complement-independent pathophysiology during early development of NMOSD lesions, and highlight the potential of oral memantine as a therapeutic agent in NMOSD acute attacks.

scholarly journals Efficacy and Safety of Mycophenolate Mofetil Therapy in Neuromyelitis Optica Spectrum Disorders: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Sakdipat Songwisit ◽  
Punchika Kosiyakul ◽  
Jiraporn Jitprapaikulsan ◽  
Naraporn Prayoonwiwat ◽  
Patompong Ungprasert ◽  
...  
Keyword(s):  
Systematic Review ◽  
Mycophenolate Mofetil ◽  
Disease Severity ◽  
Relapse Rate ◽  
Neuromyelitis Optica ◽  
Meta Analysis ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Efficacy And Safety ◽  
Number Of Patients ◽  
Spectrum Disorders

Abstract Background: Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune demyelinating disease of the central nervous system characterized by severe attacks of optic nerve and spinal cord. Mycophenolate mofetil (MMF) is an immunosuppressive agent (IS) which is widely prescribed for NMOSD patients. This systematic review and meta-analysis aims to assess the efficacy and safety of MMF in controlling relapse and disease severity.Methods: Studies were obtained from the EMBASE and Ovid MEDLINE databases. Eligible studies were the studies of NMOSD patients treated with MMF which reported treatment outcomes as Annualized Relapse Rate (ARR) or Expanded Disability Status Scale (EDSS) before and after treatment. Case reports, case series less than 3 patients, and reviews were excluded.Results: Fifteen studies included 1047 patients, of whom 915 (87.4%) were aquaporin-4 immunoglobulin seropositive. The total number of patients that received MMF was 799. Meta-analysis on ARR and EDSS were conducted in 4 studies with a total of 200 patients and 3 studies with a total of 158 patients, respectively. The result showed a significant improvement with a mean reduction of 1.13 (95% confidence interval (CI), 0.60 to 1.65) in ARR and a mean reduction of 0.85 (95% CI, 0.36 to 1.34) in EDSS after MMF therapy. Adverse drug reactions occurred in 106 (17.8%) of 594 patients that were documented having side effects during MMF therapy.Conclusion: This systematic review and meta-analysis showed that using MMF as a preventive therapy in NMOSD patients can significantly reduce relapse rate and improve disease severity with an acceptable tolerability.

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