Frequency of anti-MOG antibodies in serum and CSF of patients with possible autoimmune encephalitis: Results from a Brazilian multicentric study.

MOGAD encephalitis and ADEM share several clinical features with autoimmune encephalitis (AE) associated with antineuronal antibodies (ANeA); nonetheless, treatment and prognosis differ. Anti-MOG antibodies (abs) are not routinely tested in possible AE, and epidemiological studies on MOGAD encephalitis are scarce. To determine the frequency of anti-MOG abs in the serum and CSF in a cohort of possible AE and to compare the clinical characteristics of MOGAD patients and those with seropositive AE. 481 patients with possible AE from the Brazilian Autoimmune Encephalitis Network underwent tissue-based assay and cell-based assay (CBA) for ANeA. Anti-MOG abs were assessed in serum and CSF with in-house CBA. Clinical and laboratory characteristics of MOGAD and seropositive AE patients were compared. Of the 481 patients, 87 (18 %) had ANeA, and 17 (3.5 %) had anti-MOG abs. Three AE patients with anti-MOG abs and ANeA were excluded from further analysis. Anti-MOG abs were detected in 4 (1.2 %) of the 328 adults and 10 (6.5 %) of the 153 children. Of the 14 patients with MOGAD, nine had ADEM (mostly children), and five had encephalitis (including three adults). Only one patient with ADEM had anti-MOG abs exclusively in CSF. All patients with MOGAD encephalitis were seropositive for anti-MOG abs, and three had normal brain MRI. Patients with MOGAD had fewer behavioral changes (MOGAD 21 % x AE 96 %, p ≤ 0.0001) and movement disorders (MOGAD 42 % x AE 81 %, p = 0.0017) and more demyelinating symptoms, such as myelitis and optic neuritis (MOGAD 14 % x AE 0 %, p = 0.013). Approximately 3.5 % of patients with possible AE harbor anti-MOG abs, and 0.9 % of the adults had MOGAD encephalitis. Anti-MOG abs were more frequent than other ANeAs regularly tested in AE. We provide evidence that MOGAD is a differential diagnosis in possible AE, even in adult patients with normal brain MRI, and that serum anti-MOG should be considered as an add-on diagnostic tool in AE among adults and pediatric patients.

de Freitas Dias B ，Toso FF ，Barreto MESF ，Dellavance A ，Thomaz RB ，Kowacs PA ，Teive H ，Spitz M ，Juliano AFB ，Rocha LJA ，Granja VNT ，Braga-Neto P ，Nóbrega PR ，Oliveira-Filho J ，Dias RM ，Amoras JAP ，Pereira RBR ，Júnior COG ，Maia FM ，Santos ML ，de Melo ES ，Júnior AWDN ，Lin K ，Paolilo RB ，Krueger MB ，Barsottini OGP ，Endmayr V ，Andrade LEC ，Hoftberger R ，Dutra LA ... -  《-》

Significance of Myelin Oligodendrocyte Glycoprotein Antibodies in CSF: A Retrospective Multicenter Study.

Although the diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is based on serum MOG antibodies (MOG-Abs) positivity, patients with coexisting or restricted MOG-Abs in the CSF have been reported. The aim of this study is to characterize the relevance of CSF MOG-Abs positivity in clinical practice. Eleven medical centers retrospectively collected clinical and laboratory data of adult and pediatric patients with suspected inflammatory CNS disease and MOG-Abs positivity in serum and/or CSF using live cell-based assays. Comparisons were performed using parametric or nonparametric tests, as appropriate. Potential factors of unfavorable outcomes were explored by Cox proportional hazard models and logistic regression. The cohort included 255 patients: 139 (55%) women and 132 (52%) children (i.e., <18-year-old). Among them, 145 patients (56.8%) had MOG-Abs in both serum and CSF (MOG-Abs seropositive and CSF positive), 79 (31%) only in serum (MOG-Abs seropositive and CSF negative), and 31 (12%) only in CSF (MOG-Abs seronegative and CSF positive). MOG-Abs seronegative and CSF positive predominated in adults (22% vs 3% of children), presented more commonly with motor (n = 14, 45%) and sensory symptoms (n = 13, 42%), and all but 4 (2 multiple sclerosis, 1 polyradiculoneuritis, and 1 Susac syndrome) had a final diagnosis compatible with MOGAD. When comparing seropositive patients according to MOG-Abs CSF status, MOG-Abs seropositive and CSF positive patients had a higher Expanded Disability Status Scale (EDSS) at nadir during the index event (median 4.5, interquartile range [IQR] 3.0-7.5 vs 3.0, IQR 2.0-6.8, p = 0.007) and presented more commonly with sensory (45.5% vs 24%, p = 0.002), motor (33.6% vs 19%, p = 0.021), and sphincter symptoms (26.9% vs 7.8%, p = 0.001) than MOG-Abs seropositive and CSF negative. At the last follow-up, MOG-Abs seropositive and CSF positive cases had more often persistent sphincter dysfunction (17.3% vs 4.3%, p = 0.008). Compared with seropositive patients, those MOG-Abs seronegative and CSF positive had higher disability at the last follow-up (p ≤ 0.001), and MOG-Abs seronegative and CSF positive status were independently associated with an EDSS ≥3.0. Paired serum and CSF MOG-Abs positivity are common in MOGAD and are associated with a more severe clinical presentation. CSF-only MOG-Abs positivity can occur in patients with a phenotype suggestive of MOGAD and is associated with a worse outcome. Taken together, these data suggest a clinical interest in assessing CSF MOG-Abs in patients with a phenotype suggestive of MOGAD, regardless of the MOG-Abs serostatus.

Carta S ，Cobo Calvo Á ，Armangué T ，Saiz A ，Lechner C ，Rostásy K ，Breu M ，Baumann M ，Höftberger R ，Ayzenberg I ，Schwake C ，Sepulveda M ，Martínez-Hernández E ，Olivé-Cirera G ，Arrambide G ，Tintoré M ，Bernard-Valnet R ，Du Pasquier R ，Brilot F ，Ramanathan S ，Schanda K ，Gajofatto A ，Ferrari S ，Sechi E ，Flanagan EP ，Pittock SJ ，Redenbaugh V ，Reindl M ，Marignier R ，Mariotto S ... -  《-》

Differential diagnosis and comparison of diagnostic algorithms in children and adolescents with autoimmune encephalitis in Spain: a prospective cohort study and retrospective analysis.

The usefulness of current diagnostic approaches in children with suspected autoimmune encephalitis is unknown. We aimed to assess the diagnosis of autoimmune encephalitis in clinical practice and to compare the performance of two international diagnostic algorithms (one intended for patients of any age [general], the other intended for paediatric patients), with particular emphasis on the evaluation of patients with probable antibody-negative autoimmune encephalitis because this diagnosis suggests that immunotherapy should be continued or escalated but is difficult to establish. We did a prospective cohort study that included all patients (<18 years of age) with suspected autoimmune encephalitis recruited at 40 hospitals in Spain whose physicians provided clinical information every 6 months for 2 years or more. Neural antibody testing to confirm diagnosis of antibody-positive autoimmune encephalitis was done at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic, Barcelona. Patients were classified according to the most probable diagnosis at last follow-up into four prespecified categories. We used multivariable logistic analysis to assess a potential association between immunotherapy and outcome in individuals with probable antibody-negative autoimmune encephalitis. We also did a retrospective analysis of agreement, assessed with the kappa index, between diagnoses made according to the general and paediatric diagnostic algorithms. Between June 1, 2013, and May 31, 2021, 729 children (mean age 7·1 years [SD 4·9]; 383 boys [53%], 346 girls [47%]) with suspected autoimmune encephalitis were recruited. After a median follow-up of 36 months (IQR 26-60), patients were classified according to their most probable diagnosis: definite autoimmune encephalitis or well defined inflammatory or autoimmune disorders (n=230 [32%]); CNS infections (n=112 [15%]); inflammatory CNS disorders of unknown cause (n=81 [11%], including three (4%) with a novel Klüver-Bucy-like syndrome; and non-inflammatory disorders (n=306 [42%]), which were predominantly epileptic or psychiatric disorders (177 [58%] of 306). Neural antibodies were detected in 150 (65%) of 230 patients who had definite autoimmune encephalitis; 127 (85%) of these 150 individuals had antibodies to the NMDA receptor or myelin oligodendrocyte glycoprotein (MOG). Agreement between algorithms was excellent (kappa index 0·99, 95% CI 0·97-1·00) for the diagnosis of children with antibody-positive autoimmune encephalitis, good (0·59, 0·54-0·65) for recommendations of empiric immunotherapy, and poor (0·29, 0·21-0·37) for the diagnosis of probable antibody-negative autoimmune encephalitis. Compared with the general algorithm, the paediatric algorithm included more patients in the probable antibody-negative autoimmune encephalitis category (173 vs 41). These patients included some of those who had a diagnosis of CNS inflammatory disorder of unknown cause at the last follow-up (80 of 81 with the paediatric algorithm vs 31 of 81 with the general algorithm), who might have benefitted from immunotherapy, and some of those diagnosed with a non-inflammatory disorder at the last follow-up (47 of 306 with the paediatric algorithm vs six of 306 with the general algorithm), who did not need immunotherapy. About a third of children with suspected autoimmune encephalitis eventually had confirmation of this diagnosis, or diagnosis of another well defined inflammatory disorder. Frequent mimics of autoimmune encephalitis were infectious, epileptic, and psychiatric disorders. Both algorithms performed well in the diagnosis of antibody-positive autoimmune encephalitis, but the paediatric algorithm under-recognised definite autoimmune encephalitis that can occur without autoantibodies and might have overdiagnosed patients with probable antibody-negative autoimmune encephalitis. By contrast, the general algorithm might have underdiagnosed patients with probable antibody-negative autoimmune encephalitis. Given that the diagnosis of probable antibody-negative autoimmune encephalitis has treatment implications, inaccuracies on this diagnostic category leads to overuse or underuse of immunotherapy. Instituto de Salud Carlos III, Fundació Clínic per la Recerca Biomèdica, The Edmond J Safra Foundation, and la Caixa Foundation. For the Spanish translation of the abstract see Supplementary Materials section.

Olivé-Cirera G ，Fonseca E ，Chen LW ，Fetta A ，Martínez-Hernández E ，Guasp M ，González-Álvarez V ，Delgadillo V ，Cantarín-Extremera V ，Jiménez-Legido M ，Monge-Galindo L ，Felipe A ，Beseler B ，Turón-Viñas E ，Fernández-Ramos J ，Martínez-González MJ ，Vázquez-López M ，Arrabal Fernandez L ，Alvarez-Molinero M ，Muñoz-Cabello B ，Camacho A ，Nuñez-Enamorado N ，Spatola M ，Sabater L ，Blanco Y ，Saiz A ，Graus F ，Dalmau J ，Armangué T ，Spanish Pediatric Autoimmune Encephalitis study group ... -  《-》

Clinical characteristics of pediatric and adult myelin oligodendrocyte antibody-associated disease (MOGAD): A single-center study in the Northeast.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an immune-mediated, inflammatory, demyelinating disorder with a range of clinical presentations including acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), myelitis, and cerebral cortical encephalitis. Phenotypic expression of MOGAD varies with age. MOG antibody (MOG-Ab) titers at disease onset, as well as longitudinally, may predict clinical disease course. The objectives of this study were to (1) describe a cohort of pediatric and adult patients with MOGAD at a single center and (2) investigate if clinical outcomes correlate with ethnicity and MOG-Ab. The clinical data of 36 pediatric and adult patients with MOGAD who were evaluated at onset and longitudinally were collected between January 2018 and June 2023 at our center. Inclusion criteria were positive MOG-Ab titers, a presentation consistent with proposed consensus criteria for MOGAD, and at least one initial or follow-up visit at our center. Patients were divided into monophasic and relapsing courses. Demographic data and clinical phenotypes were assessed as possible predictors of relapsing disease. We describe demographic and clinical characteristics of 36 patients with MOGAD. Hispanic adults and children had increased rates of disease relapse compared to other ethnicities. Male sex and pediatric onset disease were also associated with increased risk of relapse. MOG-Ab titers at disease onset were not associated with a particular disease course. In adults, an initial phenotype of unilateral optic neuritis was associated with monophasic disease. Our findings within a diverse population suggest that specific characteristics, both of patients and of disease presentation, may be associated with a monophasic or relapsing course. Additional studies with larger cohorts are needed.

Brown AM ，Sridhar A ，Gliksman F ，Thomas FP ，Pandey KS ... -  《-》

New insights into the use of high dose corticosteroids and plasmapheresis in persons with MOGAD and NMOSD.

Anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD) and neuromyelitis optica spectrum disease (NMOSD) are antibody mediated diseases characterized by neurological symptoms including recurrent relapses of optic neuritis and/or myelitis, as well as other less frequent syndromes. The current treatment for acute attacks of NMOSD/MOGAD are based on clinical studies for other demyelinating diseases(i.e. Multiple Sclerosis). In NMOSD, high dose corticosteroids (HDS) are considered the standard first line therapy, with emerging evidence supporting the use of plasmapheresis (PLEX) as an acute therapy. In MOGAD, being a relatively new clinical syndrome, the consensus on acute treatments is yet to be reached. The objective of our study was to assess the efficacy of treatment regimens (no treatment vs. HDS vs. HDS and PLEX) on disability outcomes in persons with NMOSD and MOGAD-optic neuritis and myelitis. We retrospectively extracted data from the MuSicaL-NeMo database using a mixed Natural Language Processing followed by investigators verification. We assessed the change in Expanded Disability Status Scale (EDSS) and Visual Acuity (VA) following HDS and PLEX, in persons with MOGAD and NMOSD following myelitis and optic neuritis. We used the novel statistical measure Wilcoxon-Mann-Whitney Odd (WMW-Odd) to calculate the change through all the spectrum of each ordinal scale (VA and EDSS). Eleven myelitis and 12 optic neuritis in 22 persons with MOGAD and 30 myelitis and 12 optic neuritis in 20 persons with NMOSD were included(15 Aquaporin-4 seropositive). In persons with MOGAD-optic neuritis the group receiving HDS had a WMW-Odd of 15.33(p ≤ 0.001), however those not receiving treatment also tended to improve (WMW-Odd=3.17, p = 0.06). NMOSD-optic neuritis treated with HDS only improve 33.3 % of the times (p=NS). Persons with MOGAD-myelitis receiving HDS significantly improved (WMW-Odd=7.33, p = 0.002). Persons with NMOSD-myelitis treated with HDS had an WMW-Odd of 2.56 (p = 0.002) and those treated with PLEX plus HDS (PLEX+), had similar WMW-Odd of 2.51 (p = 0.03). When correcting for disease severity by restricting inclusion to persons with NMOSD with EDSS≥4, both treatments showed a higher WMW-Odd, however the group receiving HDS continued to show higher WMW-Odd than the PLEX+ group(WMW-Odd= 3.75, p = 0.002 vs. WMW-Odd =3.05, p = 0.02, respectvely) CONCLUSION: Our study suggests that persons with MOGAD-optic neuritis improve without acute treatments, however they have very marked improvement when using HDS, as previously suggested. Patient with MOGAD-myelitis are also very responsive to HDS, however, as compared to MOGAD-optic neuritis, they displayed less improvement, if not treated. In the NMOSD group the use of PLEX in addition to HDS did not demonstrate any significant difference in EDSS outcomes. Contrary to previous suggestions, when adjusting for group differences (by only including EDSS ≥4), the use of HDS and PLEX+ did not show better results than the group using HDS.

Kosior N ，Perrier RL ，Casserly C ，Morrow SA ，Racosta JM ... -  《-》