BACKGROUND: Previous studies have indicated that progression independent of relapse activity (PIRA) is uncommon in patients with aquaporin- 4 antibody-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD). However, the patterns of disability accumulation in seronegative NMOSD are unknown. This study aimed to evaluate the prevalence of PIRA and relapse-associated worsening (RAW) in seronegative NMOSD. METHODS: We conducted a retrospective, multicentre cohort study of seronegative NMOSD patients from the MSBase registry. Inclusion criteria required at least three recorded expanded disability status scale (EDSS) scores: baseline, progression, and 6 months confirmed disability progression (CDP). For those with 6-month CDP, the presence or absence of relapse between baseline and progression determined the classification as RAW or PIRA, respectively. Descriptive statistics were employed to present the data. RESULTS: This study included 93 patients, with a median follow-up duration of 5.0 years (Q1 2.8, Q3 8.4). The cohort predominantly consisted of female patients (77.4%), with a median age of onset of 33.9 years (Q1 26.1, Q3 41.2). PIRA was observed in 1 case (1.1%), whilst RAW was documented in 7 cases (7.5%). CONCLUSION: This international cohort study confirms that CDP is uncommon in seronegative NMOSD. Given more than three quarters of CDP occur due to RAW, therapeutic strategies should focus primarily on preventing relapses.

• MeSH
• Aquaporin 4 immunology   MeSH
• Autoantibodies blood   MeSH
• Adult MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Follow-Up Studies MeSH
• Neuromyelitis Optica * physiopathology   epidemiology   blood   immunology   MeSH
• Disability Evaluation MeSH
• Disease Progression * MeSH
• Recurrence MeSH
• Registries MeSH
• Retrospective Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) can be categorised into aquaporin-4 antibody (AQP4-IgG) NMOSD or seronegative NMOSD. While our knowledge of AQP4-IgG NMOSD has evolved significantly in the past decade, seronegative NMOSD remains less understood. This study aimed to evaluate the predictors of relapses and treatment responses in AQP4-IgG NMOSD and seronegative NMOSD. METHODS: This was a multicentre, international, retrospective cohort study using the MSBase registry. Recurrent relapse risk was assessed using an Andersen-Gill model and risk of first relapse was evaluated using a Cox proportional hazards model. Covariates that putatively influence relapse risk included demographic factors, clinical characteristics and immunosuppressive therapies; the latter was assessed as a time-varying covariate. RESULTS: A total of 398 patients (246 AQP4-IgG NMOSD and 152 seronegative NMOSD) were included. The AQP4-IgG NMOSD and seronegative NMOSD patients did not significantly differ by age at disease onset, ethnicity or annualised relapse rate. Both low-efficacy and high-efficacy immunosuppressive therapies were associated with significant reductions in recurrent relapse risk, with notably greater protection conferred by high-efficacy therapies in both AQP4-IgG NMOSD (HR 0.27, 95% CI 0.15 to 0.49, p<0.001) and seronegative NMOSD (HR 0.21, 95% CI 0.08 to 0.51, p<0.001). Longer disease duration (HR 0.97, 95% CI 0.95 to 0.99, p<0.001) and male sex (HR 0.52, 95% CI 0.34 to 0.84, p=0.007) were additional protective variables in reducing the recurrent relapse risk for the AQP4-IgG NMOSD group. CONCLUSION: Although further studies are needed to improve our understanding of seronegative NMOSD, our findings underscore the importance of aggressive treatment with high-efficacy immunotherapies in both NMOSD subtypes, regardless of serostatus.

• MeSH
• Aquaporin 4 * immunology   MeSH
• Autoantibodies blood   MeSH
• Adult MeSH
• Immunoglobulin G * blood   MeSH
• Immunosuppressive Agents therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neuromyelitis Optica * immunology   drug therapy   MeSH
• Recurrence * MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Ravulizumab is a humanized monoclonal antibody targeting the complement C5 protein. This drug has been approved by different regulatory agencies worldwide for the treatment of AQP-4 seropositive NMOSD based on the results of the CHAMPION-NMOSD trial. Similar to eculizumab, ravulizumab offers highly effective prevention of NMOSD relapses. Both molecules demonstrated more than 90% reduction in relapse risk compared to the placebo group. Ravulizumab has a longer half-life allowing extending interval dosing from two to eight weeks compared to eculizumab. Patients taking C5 complement inhibitors have an increased risk of serious meningococcal infections, therefore vaccination is mandatory before treatment initiation.

• Keywords
• studie CHAMPION-NMOSD, Ravulizumab, AQP4-IgG pozitivní NMOSD,
• MeSH
• Aquaporin 4 antagonists & inhibitors   immunology   MeSH
• Antibodies, Monoclonal, Humanized * pharmacology   classification   therapeutic use   MeSH
• Clinical Studies as Topic MeSH
• Complement C5 antagonists & inhibitors   MeSH
• Humans MeSH
• Meningococcal Infections immunology   prevention & control   MeSH
• Neuromyelitis Optica * diagnosis   drug therapy   immunology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Publikace, která se zaměřuje na různé aspekty optické neuromyelitidy, zejména na možnosti diagnostiky a terapie. Určeno odborné veřejnosti.; Neuromyelitis optica a poruchy jejího širšího spektra (NMOSD) patří mezi autoimunitní onemocnění centrálního nervového systému. Typicky se projevují zánětem zrakových nervů a míchy, méně často mozkového kmene. U většiny pacientů nacházíme v séru protilátky proti akvaporinu-4 (AQP4-IgG), které jsou pro toto onemocnění specifické a hrají zásadní roli v patogenezi choroby u více než asi 75 % pacientů. Mezi časté klíčové klinické charakteristiky patří optická neuritida, myelitida a syndrom area postrema. I přes výrazné zlepšení diagnostického procesu díky dostupnosti vyšetření protilátek proti AQP4 stále dochází k prodlení u stanovení diagnózy u AQP4-IgG séronegativních pacientů, pacientů s parciálními míšními syndromy, u pacientů vyššího věku apod. Mezi nejčastěji stanovené chybné diagnózy patří roztroušená skleróza, míšní tumory, ischemické léze zrakových nervů, neuroinfekce a další. Důležité je také odlišení AQP4-IgG pozitivních pacientů od pacientů s pozitivitou protilátek proti myelinovému oligodendrocytárnímu glykoproteinu. Tyto protilátky také definují novou skupinu demyelinizací CNS, tzv. „myelin oligodendrocyte glycoprotein antibody–associated disease“ – MOGAD. Tato kniha přináší přehled základních patogenetických mechanismů u NMOSD a MOGAD, osvětluje diferenciálnědiagnostické postupy, předkládá typické nálezy při zobrazení magnetickou rezonancí a optickou koherenční tomografií u optických neuritid. Dále pak shrnuje možnosti terapie relapsů a dlouhodobou chronickou léčbu nemocných s těmito autoimunitními onemocněními CNS. Kniha je zajímavá pro neurology, oftalmology a radiology.

• MeSH
• Neuromyelitis Optica MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• neurologie
• oftalmologie
• alergologie a imunologie
• NML Publication type
• kolektivní monografie

OBJECTIVES: In aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), disability accrual is mostly attributed to relapses. This study aimed to assess the prevalence of progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in AQP4-IgG NMOSD. METHODS: This was a retrospective cohort study of patients with AQP4-IgG NMOSD enrolled in the MSBase international data registry. Patients required a minimum of 3 recorded Expanded Disability Status Scale (EDSS) scores: baseline, event, and a 6-month confirmation score. Presence and absence of relapses between the baseline and event EDSS scores determined RAW and PIRA, respectively. Descriptive statistics were used to present the results. RESULTS: A total of 181 patients followed for a median of 4.5 years (Q1 1.7, Q3 7.8) were included. Most patients were female (88.4%), and the median age at disease onset was 38.1 years. Overall, 4 patients (2.2%) developed 5 incidences of PIRA and 13 patients developed RAW (7.2%). DISCUSSION: This multicenter study highlights that PIRA is very rare in AQP4-IgG NMOSD. Limitations of this study include the sole focus of overall EDSS to measure disability, lack of requirement for a second EDSS score to confirm baseline EDSS, and the absence of magnetic resonance imaging information for all patients.

• MeSH
• Aquaporin 4 * immunology   MeSH
• Autoantibodies * blood   MeSH
• Adult MeSH
• Immunoglobulin G * blood   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Neuromyelitis Optica * immunology   epidemiology   MeSH
• Disability Evaluation MeSH
• Prevalence MeSH
• Disease Progression * MeSH
• Recurrence * MeSH
• Retrospective Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

BACKGROUND: We recently described magnetic resonance imaging (MRI) features of children with transverse myelitis (TM) at first event with important and unique differences depending on the underlying disease entity. OBJECTIVE: To study the resolution of lesions over time in children with TM due to MOG-antibody associated disorders (MOGAD), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) or double seronegative TM. PATIENTS AND METHODS: In this prospective study, 78 children from 29 different medical centres with TM as part of MOGAD (n = 34), MS (n = 20), NMOSD (n = 5) and in double seronegative children (n = 19) were included. A grading system consisting of 4 grades (grade 0 = complete resolution; grade 3 = no resolution at all) was used to compare the degree of lesion resolution over time in the different disease entities. Time to lesion resolution was evaluated by Kaplan-Meier statistics and log-rank test. RESULTS: Significant differences of the interval between first MRI until resolution of lesions were observed between the four disease entities. The most rapid and complete resolution was seen in MOGAD, followed by double seronegative, MS and NMOSD. Median periods until total resolution (grade 0) were 191 days (MOGAD), 750 days (double seronegative), 1117 days (MS), while none of the patients with NMOSD reached a complete resolution during the observation period. The better prognosis of MOGAD compared to MS was independent of sex, age, oligoclonal bands and cell count in the multivariate Cox analysis (P < 0.001). CONCLUSION: Children with TM and antibodies to MOG show a faster resolution of radiological lesions compared to children with MS and NMOSD.

• MeSH
• Autoantibodies blood   MeSH
• Child MeSH
• Myelin-Oligodendrocyte Glycoprotein immunology   MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Spinal Cord diagnostic imaging   pathology   MeSH
• Adolescent MeSH
• Follow-Up Studies MeSH
• Neuromyelitis Optica * diagnostic imaging   MeSH
• Child, Preschool MeSH
• Prospective Studies MeSH
• Multiple Sclerosis * diagnostic imaging   pathology   MeSH
• Myelitis, Transverse * diagnostic imaging   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Primary Sjögren's syndrome is an autoimmune disorder that is characterized by lymphocytic infiltration of salivary and lacrimal glands. The extra-glandular manifestations might be arthritis, myalgia, glomerulonephritis, skin rashes, and neurologic involvement. One of the uncommon neurologic manifestations is neuromyelitis optica spectrum disorder (NMOSD). In the present case, an older woman is reported that was diagnosed with NMOSD secondary to keratoconjunctivitis sicca, which is rare in geriatric practice.

• MeSH
• Humans MeSH
• Neuromyelitis Optica * diagnosis   complications   etiology   MeSH
• Aged MeSH
• Sjogren's Syndrome * complications   diagnosis   MeSH
• Keratoconjunctivitis Sicca etiology   diagnosis   MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

V článku sa uvádza prehľad súčasného stavu poznatkov o imunoterapii spektra ochorení neuromyelitis optica (NMOSD, neuromyelitis optica spectrum disorders). Zneschopnenie pri NMOSD je následkom atakov a relapsov choroby, na ktoré sa sústreďuje liečba. Diagnostickým biomarkerom ochorenia sú autoprotilátky proti aquaporínu 4 (AQP4-IgG), ktoré zohrávajú dôležitú úlohu v patogenéze poškodenia astrocytov. Nedávny pokrok v chápaní NMOSD viedol k vývoju nových terapií a overeniu ich účinnosti v randomizovaných kontrolovaných štúdiách. Pre pacientov s pozitívnymi protilátkami proti AQP4 boli schválené nové imunoterapie, ktoré majú potenciál znížiť aktivitu ochorenia redukciou relapsov, sú to ekulizumab, ravulizumab, inebilizumab a satralizumab.

The article provides an overview of the current state of knowledge about neuromyelitis optica spectrum disorder (NMOSD) immunotherapy. Therapy focuses on the relapses that determine disability in NMOSD. Autoantibodies against aquaporin 4 (AQP4-IgG) are a diagnostic biomarker of the disease and have an important role in the pathogenesis of damage to astrocytes. Recent advances in the understanding of NMOSD have led to the development of new therapies and validation of their effectiveness in randomized controlled trials. New immunotherapies have been approved for patients with positive AQP4-igG antibodies, with the potential to reduce the number of relapses, namely eculizumab, ravulizumab, inebilizumab and satralizumab.

• MeSH
• Aquaporin 4 immunology   MeSH
• B-Lymphocytes drug effects   MeSH
• Immunosuppressive Agents pharmacology   classification   adverse effects   therapeutic use   MeSH
• Immunotherapy classification   methods   MeSH
• Interleukin-6 Inhibitors pharmacology   classification   therapeutic use   MeSH
• Complement Inactivating Agents pharmacology   classification   therapeutic use   MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Lymphocyte Depletion methods   MeSH
• Antibodies, Monoclonal pharmacology   classification   therapeutic use   MeSH
• Neuromyelitis Optica * drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

BACKGROUND: AntiCD20 therapy, such as rituximab, ocrelizumab, or ofatumumab, effectively treats patients with multiple sclerosis (pwMS) or neuromyelitis optica spectrum disorder (pwNMOSD) but negatively affects the humoral immune response to COVID-19 vaccination. One strategy to protect these patients is using tixagevimab/cilgavimab (T/C) as pre-exposure prophylaxis. This study aimed to evaluate the effect of T/C on the incidence of COVID-19 in pwMS and pwNMOSD. METHODS: Data in this observational cohort study were collected in two Czech MS centres through ReMuS registry between March 1, 2020 and December 31, 2022. Adult pwMS and pwNMOSD who were (1) treated with antiCD20 therapy at least six months before T/C administration, or at least from February 1, 2022 in the control group; (2) were already on antiCD20 therapy at the time of vaccination or COVID-19 infection; and (3) were on antiCD20 therapy at least 100 days after T/C, or at least 90 days after August 1, 2022 in the control group, were included. Analysis was performed using frequency-based (propensity score matching) and Bayesian statistical methods (informative and non-informative priors). RESULTS: Using propensity score matching 1:1, 47 patients who received T/C (mean age 45.7 years, median disease duration 12.5 years) were matched with those who did not receive T/C (n = 341; mean age 46.6 years, median disease duration 11.4 years) based on age, MS/NMOSD duration, and number of vaccine doses. None of the T/C patients and three in the control matched group, developed COVID-19 between 10 and 100 days after receiving T/C, August 1, 2022, respectively. The frequency of COVID-19 was not significantly different between groups (p = 0.242). Due to the low number of patients, a Bayesian analysis was also added. Using a non-informative Bayesian prior, the median relative risk of COVID-19 after T/C was 7.6 % (95 % CrI 0.02-115.9 %). The posterior probability of risk difference lower than zero was 96.4 %. Using an informative prior (based on the registration study of Evusheld), the median relative risk of COVID-19 after T/C was 20.2 % (95 % CI 8.4-43.8 %). The posterior probability of the risk difference lower than zero was 100 %. CONCLUSION: This work highlights the possible good efficacy of T/C in antiCD20-treated pwMS and pwNMSOD. Based on Bayesian analysis with an informative prior, the T/C group's risk of COVID-19 infection was approximately 20.2 % of the control group's risk. However, given the low frequency of COVID-19, the results of this pilot analysis must be interpreted with caution.

• MeSH
• COVID-19 * prevention & control   complications   MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized therapeutic use   MeSH
• Immunologic Factors MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Neuromyelitis Optica * drug therapy   MeSH
• Pre-Exposure Prophylaxis methods   MeSH
• Multiple Sclerosis * drug therapy   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Geographicals
• Czech Republic MeSH

Inebilizumab, a humanized, glycoengineered, IgG1 monoclonal antibody that depletes CD19+ B-cells, is approved to treat aquaporin 4 (AQP4) IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is afucosylated and engineered for enhanced affinity to Fc receptor III-A (FCGR3A) receptors on natural killer cells to maximize antibody-dependent cellular cytotoxicity. Previously, the F allele polymorphism at amino acid 158 of the FCGR3A gene (F158) was shown to decrease IgG-binding affinity and reduce rituximab (anti-CD20) efficacy for NMOSD attack prevention. In contrast, our current findings from inebilizumab-treated NMOSD patients indicate similar clinical outcomes between those with F158 and V158 allele genotypes.

• MeSH
• Aquaporin 4 genetics   MeSH
• Antibodies, Monoclonal, Humanized therapeutic use   MeSH
• Immunoglobulin G MeSH
• Humans MeSH
• Neuromyelitis Optica * drug therapy   genetics   MeSH
• Receptors, IgG genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH