RESUMEN
BACKGROUND AND OBJECTIVES: The 2022 International Consortium for Optic Neuritis diagnostic criteria for optic neuritis (ON) include optical coherence tomography (OCT). The diagnostic value of intereye difference (IED) metrics is high for ON in patients with multiple sclerosis and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders, but unknown in myelin oligodendrocyte glycoprotein antibody-associated ON (MOG-ON). METHODS: A multicenter validation study was conducted on the published IED cutoff values (>4% or >4 µm in the macular ganglion cell and inner plexiform layer [mGCIP] or >5% or >5 µm in the peripapillary retinal nerve fiber layer [pRNFL]) in individuals with MOG-ON and age-matched and sex-matched healthy controls (HCs). Structural data were acquired with Spectralis spectral-domain OCT >6 months after ON. We calculated sensitivity, specificity, and receiver operating characteristics for both intereye percentage (IEPD) and absolute difference (IEAD). RESULTS: A total of 66 individuals were included (MOG-ON N = 33; HCs N = 33). ON was unilateral in 20 and bilateral in 13 subjects. In the pooled analysis, the mGCIP IEPD was most sensitive (92%), followed by the mGCIP IEAD (88%) and pRNFL (84%). The same pattern was found for the specificity (mGCIP IEPD 82%, IEAD 82%; pRNFL IEPD 82%, IEAD 79%).In subgroup analyses, the diagnostic sensitivity was higher in subjects with unilateral ON (>99% for all metrics) compared with bilateral ON (61%-78%). DISCUSSION: In individuals with MOG-ON, the diagnostic accuracy of OCT-based IED metrics for ON was high, especially of mGCIP IEPD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the intereye difference on OCT can distinguish between those with MOG and normal controls.
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Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Neuritis Óptica , Tomografía de Coherencia Óptica , Humanos , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuritis Óptica/inmunología , Neuritis Óptica/diagnóstico , Neuritis Óptica/diagnóstico por imagen , Femenino , Masculino , Adulto , Persona de Mediana Edad , Autoanticuerpos/sangre , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has highly heterogeneous clinical presentations, in which encephalitis is an important phenotype. Moreover, MOGAD has been reported to exhibit diverse imaging findings. However, there have been no previous reports of cases with perivascular radial gadolinium enhancement in periventricular regions, commonly reported in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. In this paper, we present two cases of MOGAD with this MRI feature, both of which underwent brain biopsy for the lesions. Brain biopsies revealed perivenous demyelination and inflammation consistent with acute disseminated encephalomyelitis (ADEM), with pronounced axonal damage in Case 1 and minimal axonal involvement in Case 2. Case 1 exhibited more severe cerebral atrophy than Case 2, correlating with the extent of axonal damage. Through these cases, we highlight the heterogeneity of radiological manifestations of MOGAD, expanding the spectrum beyond previously defined MRI patterns. Furthermore, histopathological analysis revealed distinct axonal involvement as a potential prognostic marker of brain atrophy. These observations emphasize the importance of considering MOGAD in the differential diagnosis, even in cases with atypical imaging findings, and highlight the significance of brain biopsy in guiding both diagnosis and prognosis.
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Autoanticuerpos , Gadolinio , Imagen por Resonancia Magnética , Glicoproteína Mielina-Oligodendrócito , Humanos , Glicoproteína Mielina-Oligodendrócito/inmunología , Masculino , Femenino , Autoanticuerpos/inmunología , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Adulto , Persona de Mediana Edad , Biopsia , Encefalomielitis Aguda Diseminada/diagnóstico por imagen , Encefalomielitis Aguda Diseminada/inmunología , Encefalomielitis Aguda Diseminada/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: To identify predictors for relapse in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to develop and validate a simple risk score for predicting relapse. METHODS: In China National Registry of Neuro-Inflammatory Diseases (CNRID), we identified patients with MOGAD from March 2023 and followed up prospectively to September 2023. The primary endpoint was MOGAD relapse, confirmed by an independent panel. Patients were randomly divided into model development (75%) and internal validation (25%) cohorts. Prediction models were constructed and internally validated using Andersen-Gill models. Nomogram and relapse risk score were generated based on the final prediction models. RESULTS: A total of 188 patients (comprising 612 treatment episodes) were included in cohorts. Female (HR: 0.687, 95% CI 0.524-0.899, p = 0.006), onset age 45 years or older (HR: 1.621, 95% CI 1.242-2.116, p < 0.001), immunosuppressive therapy (HR: 0.338, 95% CI 0.239-0.479, p < 0.001), oral corticosteroids >3 months (HR 0.449, 95% CI 0.326-0.620, p < 0.001), and onset phenotype (p < 0.001) were identified as factors associated with MOGAD relapse. A predictive score, termed MOG-AR (Immunosuppressive therapy, oral Corticosteroids, Onset Age, Sex, Attack phenotype), derived in prediction model, demonstrated strong predictive ability for MOGAD relapse. MOG-AR score of 13-16 indicates a higher risk of relapse (HR: 3.285, 95% CI 1.473-7.327, p = 0.004). DISCUSSION: The risk of MOGAD relapse seems to be predictable. Further validation of MOG-AR score developed from this cohort to determine appropriate treatment and monitoring frequency is warranted. TRIAL REGISTRATION INFORMATION: CNRID, NCT05154370, registered December 13, 2021, first enrolled December 15, 2021.
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Glicoproteína Mielina-Oligodendrócito , Recurrencia , Sistema de Registros , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Glicoproteína Mielina-Oligodendrócito/inmunología , Adulto Joven , China , Medición de Riesgo , Autoanticuerpos/sangre , Adolescente , Factores de Riesgo , Estudios de Seguimiento , Enfermedades Autoinmunes Desmielinizantes SNC/inmunología , Enfermedades Autoinmunes Desmielinizantes SNC/diagnósticoRESUMEN
OBJECTIVES: In MOG antibody-associated disease (MOGAD), relapse prevention and the treatment approach to refractory symptoms are unknown. We report a patient with refractory MOGAD treated with CD19-directed CAR T-cells. METHODS: CD19-directed CAR T-cells (ARI-0001) were produced in-house by lentiviral transduction of autologous fresh leukapheresis and infused after a conventional lymphodepleting regimen. RESULTS: A 18-year-old man developed 2 episodes of myelitis associated with serum MOG-IgG, which were followed by 6 episodes of left optic neuritis (ON) and sustained the presence of MOG-IgG over 6 years despite multiple immunotherapies. After the sixth episode of ON, accompanied by severe residual visual deficits, CAR T-cell treatment was provided without complications. Follow-up of cell counts showed complete depletion of CD19+ B cells at day +7; reconstituted B cells at day +141 showing a naïve B-cell phenotype, and low or absent memory B cells and plasmablasts for 1 year. MOG-IgG titers have remained undetectable since CAR T-cell infusion. The patient had an early episode of left ON at day +29, when MOG-IgG was already negative, and since then he has remained free of relapses without immunotherapy for 1 year. DISCUSSION: This clinical case shows that CD19-directed CAR T-cell therapy is well-tolerated and is a potential treatment for patients with refractory MOGAD. CLASSIFICATION OF EVIDENCE: This provides Class IV evidence. It is a single observational study without controls.
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Antígenos CD19 , Inmunoterapia Adoptiva , Glicoproteína Mielina-Oligodendrócito , Humanos , Masculino , Antígenos CD19/inmunología , Adolescente , Glicoproteína Mielina-Oligodendrócito/inmunología , Estudios de Seguimiento , Neuritis Óptica/inmunología , Neuritis Óptica/terapia , Receptores Quiméricos de Antígenos/inmunología , Linfocitos T/inmunologíaRESUMEN
OBJECTIVES: In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD. METHODS: CSF-C3a, CSF-C4a, CSF-C5a, and CSF-C5b-9 levels during the acute phase before treatment in patients with MOGAD (n = 12), AQP4+NMOSD (n = 11), multiple sclerosis (MS) (n = 5), and noninflammatory neurologic disease (n = 2) were measured. RESULTS: CSF-C3a and CSF-C5a levels were significantly higher in MOGAD (mean ± SD, 5,629 ± 1,079 pg/mL and 2,930 ± 435.8 pg/mL) and AQP4+NMOSD (6,017 ± 3,937 pg/mL and 2,544 ± 1,231 pg/mL) than in MS (1,507 ± 1,286 pg/mL and 193.8 ± 0.53 pg/mL). CSF-C3a, CSF-C4a, and CSF-C5a did not differ between MOGAD and AQP4+NMOSD while CSF-C5b-9 (membrane attack complex, MAC) levels were significantly lower in MOGAD (17.4 ± 27.9 ng/mL) than in AQP4+NMOSD (62.5 ± 45.1 ng/mL, p = 0.0019). Patients with MOGAD with severer attacks (Expanded Disability Status Scale [EDSS] ≥ 3.5) had higher C5b-9 levels (34.0 ± 38.4 ng/m) than those with milder attacks (EDSS ≤3.0, 0.9 ± 0.7 ng/mL, p = 0.044). DISCUSSION: The complement pathway is activated in both MOGAD and AQP4+NMOSD, but MAC formation is lower in MOGAD, particularly in those with mild attacks, than in AQP4+NMOSD. These findings may have pathogenetic and therapeutic implications in MOGAD.
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Acuaporina 4 , Activación de Complemento , Inmunoglobulina G , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/líquido cefalorraquídeo , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/sangre , Acuaporina 4/inmunología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Glicoproteína Mielina-Oligodendrócito/inmunología , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/sangre , Anciano , Complemento C5a/líquido cefalorraquídeo , Complemento C5a/metabolismo , Complemento C5a/inmunología , Adulto Joven , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/inmunología , Complemento C3a/metabolismo , Complemento C3a/líquido cefalorraquídeo , Complemento C3a/inmunología , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/líquido cefalorraquídeo , Complejo de Ataque a Membrana del Sistema Complemento/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVES: The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children. METHODS: This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MOG-immunoglobulin G (IgG) positive at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic of Barcelona (Spain). Exclusion criteria were lack of clinical information and follow-up <1 year, and serum unavailable for antibody testing. The primary outcome was to assess the accuracy of the 2023 MOGAD criteria, using as gold standard the most plausible diagnosis after a follow-up >1 year. MOGAD criteria were retrospectively applied assessing core syndromes, supportive clinical-radiological features, and MOG-IgG titers. Patients tested ≤3 months of a disease attack (acute phase) or afterward (remission) were considered separately. The positive predictive value (PPV) of the criteria (true-positive [patients classified as MOGAD and MOGAD diagnosis last follow-up] divided by total positive [all patients classified as MOGAD]), and its 95% CI, was calculated with the Wilson procedure. RESULTS: A total of 257 patients (133 children) were included in the study (median age 15 years [interquartile range 6-38], 54% female). Among 202 patients assessed during a disease attack, 158 (78%) had high MOG-IgG serum titers, 36 (18%) low titers, and 8 (4%) antibodies only in CSF. No differences were identified between patients with high and low titers, but those with low titers were more likely to have an alternative diagnosis at last follow-up (2/36 [6%] vs 0/158, p = 0.012). Supportive features were present in 230 of 257 (89%) patients, regardless of age, MOG-IgG titers, and core syndromes except for optic neuritis in adults whose assessment with orbital MRI was not systematic. Overall, 240 of 257 (94%) patients were well classified by the MOGAD criteria (e.g., 236 eventually having MOGAD and 4 alternative diagnoses), and 17 were wrongly classified (e.g., 11 eventually having MOGAD and 6 alternative diagnoses). Although the criteria classified better during disease attacks than during remissions (187 [96%] vs 49 [89%] serum MOG-IgG-positive patients were well-classified, p = 0.038), the PPV was high in both settings (99% [95% CI 97-100] vs 98% [95% CI 89-100]). DISCUSSION: The 2023 MOGAD criteria correctly identified most children and adults with MOGAD. The highest accuracy occurred when they were applied during disease attacks. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the 2023 MOGAD criteria accurately identify adults and children with MOGAD.
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Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Humanos , Glicoproteína Mielina-Oligodendrócito/inmunología , Niño , Masculino , Femenino , Adulto , Adolescente , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Adulto Joven , Estudios Prospectivos , Inmunoglobulina G/sangre , Inmunoglobulina G/líquido cefalorraquídeo , Preescolar , España , Persona de Mediana Edad , Encefalitis/inmunología , Encefalitis/diagnóstico , Encefalitis/sangre , Estudios RetrospectivosRESUMEN
Purpose: Experimental autoimmune encephalomyelitis (EAE) scoring, the most commonly used primary outcome metric for an in vivo model of multiple sclerosis (MS), is highly variable and subjective. Here we explored the use of visual biomarkers in EAE as more objective and clinically relevant primary outcomes. Methods: Motor impairment in myelin oligodendrocyte glycoprotein-immunized C57BL/6J mice was quantified using a five-point EAE grading scale. Pattern electroretinography (pERG) and retinal ganglion cell/inner plexiform layer (RGC/IPL) complex thickness were measured 60 days after induction. Optic nerve histopathology was analyzed at endpoint. Results: EAE mice displayed motor impairments ranging from mild to severe. Significant correlations were seen between pERG amplitude and last EAE score, mean EAE score, and cumulative EAE score. Optical coherence tomography (OCT) analysis demonstrated a significant correlation between thinning of the RGC/IPL complex and both EAE score and pERG amplitude. Optic nerve histopathology showed significant correlations between demyelination and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness, as well as between immune cell infiltration and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness in EAE mice. Conclusions: Unlike EAE scoring, pERG and OCT show direct measurement of retinal structure and function. Therefore we conclude that visual outcomes are well suited as a direct assessment of optic nerve involvement in this EAE model of MS while also being indicative of motor impairment. Translational Relevance: Standardizing directly translatable measurements as primary outcome parameters in the murine EAE model could lead to more rapid and relevant testing of new therapeutic approaches for mitigating MS.
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Biomarcadores , Electrorretinografía , Encefalomielitis Autoinmune Experimental , Ratones Endogámicos C57BL , Neuritis Óptica , Células Ganglionares de la Retina , Tomografía de Coherencia Óptica , Animales , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/fisiopatología , Neuritis Óptica/patología , Neuritis Óptica/fisiopatología , Neuritis Óptica/inmunología , Ratones , Femenino , Electrorretinografía/métodos , Células Ganglionares de la Retina/patología , Nervio Óptico/patología , Glicoproteína Mielina-Oligodendrócito/inmunología , Modelos Animales de EnfermedadRESUMEN
We report a rare diagnosis of ring-enhanced brain lesions. We describe a case of a 4-year-old immunocompetent girl presenting with a subacute alteration of her general condition and a walking disorder a few weeks after her return from a trip to Bangladesh. The etiological work-up revealed ring-enhanced brain lesions on magnetic resonance imaging (MRI). A wide range of etiologies, including infectious, tumoral and inflammatory causes, were considered. Given the clinical and radiological suspicion of neurocysticerosis, the patient was initially treated with corticosteroids and various infectious serologies were carried out, with negative results. Following a rapidly favourable clinical course on corticosteroids alone, further biological investigations revealed the presence of anti-MOG antibodies in both serum and cerebrospinal fluid, suggesting MOGAD (myelin oligodendrocyte glycoprotein antibody-associated disease). This case report highlights the complexity of diagnosing ring-enhanced brain lesions. It also draws attention to MOGAD in immunocompetent patients as a rare but possible etiology, to be systematically investigated in the presence of this type of lesion. Indeed, consideration of inflammatory and autoimmune causes is crucial for accurate diagnosis, enabling earlier targeted treatment.
Nous rapportons un diagnostic rare de lésions cérébrales à rehaussement annulaire. Il s'agit d'une jeune patiente immunocompétente de 4 ans présentant une altération subaiguë de son état général et un trouble de la marche survenus quelques semaines après son retour d'un voyage au Bengladesh. La mise au point étiologique a mis en évidence la présence de lésions cérébrales à rehaussement annulaire à l'imagerie par résonnance magnétique (IRM). Un large éventail d'étiologies a été envisagé. Devant la suspicion clinique et radiologique de neurocysticerose, la patiente a initialement été traitée avec des corticoïdes. Les différentes sérologies infectieuses sont revenues négatives. Face à une évolution clinique rapidement favorable sous corticothérapie seule, des investigations biologiques supplémentaires ont été réalisées révélant la présence d'anticorps anti-myéline oligodendrocyte (MOG) au niveau du sérum et du liquide céphalo-rachidien, suggérant une MOGAD (maladie auto-immune avec anticorps anti-myéline oligodendrocyte). Ce cas clinique met en lumière la complexité du diagnostic de ces lésions cérébrales. Il attire également l'attention sur la MOGAD chez des patients immunocompétents comme une étiologie possible à rechercher de manière systématique devant ce type de lésion. En effet, la prise en compte des causes inflammatoires et auto-immunes est cruciale pour un diagnostic précis permettant un traitement ciblé plus précoce.
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Glicoproteína Mielina-Oligodendrócito , Humanos , Femenino , Glicoproteína Mielina-Oligodendrócito/inmunología , Preescolar , Autoanticuerpos/sangre , Imagen por Resonancia Magnética , Inmunocompetencia , Encéfalo/diagnóstico por imagen , Encéfalo/patologíaRESUMEN
RATIONALE: Myelin oligodendrocyte glycoprotein (MOG) antibody-related disease is a relatively recent entity in inflammatory demyelinating disease. Its clinical presentation varies in severity and the lack of specific imaging features makes it easy to misdiagnose. We now report the case of a MOG antibody-positive patient who presented with diplopia and dizziness, and whose brain magnetic resonance imaging (MRI) showed abnormal signals in the bilateral pontine brachium. PATIENT CONCERNS: A previously healthy 52-year-old woman presented with diplopia and dizziness, and was hospitalized 4 days after onset. DIAGNOSES: Brain MRI demonstrated abnormal hyperintense signals in the bilateral pontine brachium on T2-weighted fluid attenuated inversion recovery imaging. MRI enhancement showed abnormal enhancement foci in bilateral pontine brachium and pons. Cerebrospinal fluid examination showed Oligoclonal IgG bands were negative. The IgG index was normal, and serum aquaporin-4 antibody was negative, while serum MOG-Ab was positive (1:100). In conjunction with a positive serum MOG antibody and exclusion of other diseases, diagnosis of MOG antibody-related disease was made. INTERVENTIONS: Intravenous methylprednisolone followed by oral corticosteroids. OUTCOMES: Symptoms resolved completely. At 4-month follow-up. Follow-up after 4 months showed disappearance of the abnormal signal in the left pontine brachium and diminution of abnormal high signal in the right compared to the previous one, and there was no recurrence 1 year after the onset of the disease. LESSONS: If brain MRI indicating bilateral, multiple, and diffuse abnormal signals in the pontine brachium, and a discrepancy between the clinical symptoms and the imaging severity, a diagnosis of demyelinating disease should be considered highly probable. In such cases, anti-MOG antibody testing is essential for further defining the etiology. The clinical phenotype and imaging manifestations of MOG antibody-positive brainstem encephalitis may lack sufficient specificity to be readily identifiable. Timely diagnosis and early glucocorticoid therapy are beneficial in improving prognosis and preventing recurrence.
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Autoanticuerpos , Imagen por Resonancia Magnética , Glicoproteína Mielina-Oligodendrócito , Puente , Humanos , Femenino , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/inmunología , Autoanticuerpos/sangre , Puente/diagnóstico por imagen , Puente/patología , Metilprednisolona/uso terapéuticoRESUMEN
Autoantibodies are the cause of the chronic inflammatory diseases known as neuromyelitis optica spectrum disorders (NMOSD). Serum antibodies (Abs) that specifically target the aquaporin-4 (AQP-4) water channel are the cause of recurrent episodes of optic neuritis, myelitis, and/or brain stem disorders. In contrast to AQP-4 Abs, myelin oligodendrocyte glycoprotein (MOG) Abs are detected in some patients exhibiting nonmotor cognitive impairment. These days, the term "MOG-encephalomyelitis" (MOG-EM) is frequently used to describe these clinical syndromes. The diagnosis of these cases involves the use of magnetic resonance imaging, optical coherence tomography, antibody detection, and additional laboratory testing. By detecting the patient's Abs in their serum or cerebrospinal fluid (CSF), indirect immunofluorescence (IIF) aids in the proper diagnosis. We highlight five NMOSD cases where serum anti-MOG antibody positivity was found using IIF, but CSF was not. In none of the cases, anti-AQP Abs were found. Effective patient management strategies include the treatment of acute attacks and long-term immunosuppressive drugs such as rituximab, azathioprine, and immunoglobulins. IIF is a quick and easy tool to detect anti-MOG Abs in patients with NMOSD/myelin oligodendrocyte glycoprotein antibody-associated disorder. CSF testing for MOG or AQP-4 Abs is not usually advised. It does not offer additional benefits to help with MOG-EM or NMOSD diagnosis.
RésuméLes autoanticorps sont à l'origine de maladies inflammatoires chroniques connues sous le nom de troubles du spectre de la neuromyélite optique (NMOSD). Sérum les anticorps (Abs) qui ciblent spécifiquement le canal hydrique de l'aquaporine-4 (AQP-4) sont à l'origine d'épisodes récurrents de névrite optique, de myélite, et/ou des troubles du tronc cérébral. Contrairement aux Abs AQP-4, les Abs glycoprotéines oligodendrocytes de myéline (MOG) sont détectés chez certains patients présentant déficience cognitive non motrice. De nos jours, le terme « MOG encéphalomyélite ¼ (MOG-EM) est fréquemment utilisé pour décrire ces troubles cliniques syndrome. Le diagnostic de ces cas fait appel à l'imagerie par résonance magnétique, à la tomographie par cohérence optique, à la détection d'anticorps, et des tests de laboratoire supplémentaires. En détectant les Abs du patient dans son sérum ou liquide céphalo-rachidien (LCR), immunofluorescence indirecte (IIF) aide au bon diagnostic. Nous mettons en évidence cinq cas de NMOSD où la positivité des anticorps anti-MOG sériques a été trouvée en utilisant l'IIF, mais le LCRn'était pas. Dans aucun des cas, des Ac anti-AQP n'ont été trouvés. Les stratégies efficaces de prise en charge des patients comprennent le traitement des crises aiguës et médicaments immunosuppresseurs à long terme tels que le rituximab, l'azathioprine et les immunoglobulines. IIF est un outil simple et rapide pour détecter les anti-MOG Abs chez les patients atteints d'un trouble associé aux anticorps anti-glycoprotéine oligodendrocytaire de NMOSD/myéline. Les tests CSF pour MOG ou AQP-4 Abs ne sont pas habituellement conseillé. Il n'offre pas d'avantages supplémentaires pour faciliter le diagnostic MOG-EM ou NMOSD.
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Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/diagnóstico por imagen , Glicoproteína Mielina-Oligodendrócito/inmunología , Autoanticuerpos/sangre , Femenino , Adulto , Masculino , Técnica del Anticuerpo Fluorescente Indirecta/métodos , Acuaporina 4/inmunología , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Inmunosupresores/uso terapéuticoRESUMEN
BACKGROUND: The previous Japanese clinical practice guidelines for multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) were published in 2017. Recently, for the first time in 6 years, the MS and NMOSD guideline development committee revised the Japanese guidelines for MS, NMOSD, and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). METHODS: The committee utilized the Grading of Recommendations Assessment, Development, and Evaluation system based on the "Minds Handbook for Clinical Practice Guideline Development 2020 Ver. 3.0â³ with a focus on clinical questions (CQs). The committee also discussed clinical issues other than CQs, categorizing them as a question-and-answer (Q&A) section, including "issues on which experts' opinions agree to a certain extent" and "issues that are important but not included in the CQ". RESULTS: The committee identified 3, 1, and 1 key CQs related to MS, NMOSD, and MOGAD, respectively, and presented recommendations. A Q&A session regarding disease-modifying therapies and relapse prevention therapies for MS, NMOSD, and MOGAD was conducted. The revised guidelines were published in September 2023. CONCLUSIONS: The Japanese guidelines for clinical practice on MS, NMOSD, and MOGAD were updated. Treatment strategies for MS, NMOSD, and MOGAD are changing, and these updated guidelines may assist with treatment decisions for these diseases in clinical practice.
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Esclerosis Múltiple , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/terapia , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/tratamiento farmacológico , Glicoproteína Mielina-Oligodendrócito/inmunología , Esclerosis Múltiple/terapia , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/diagnóstico , Japón , Guías de Práctica Clínica como Asunto/normas , Autoanticuerpos/sangreRESUMEN
RATIONALE: Anti-Myelin oligodendrocyte glycoprotein (MOG) and anti-metabotropic glutamate receptor 5 (mGluR5) double antibody positive encephalitis characterized by optic neuritis is extremely rare. We present a case of overlapping syndrome of MOG-IgG-associated disease and anti-mGluR5 encephalitis manifested as optic neuritis. PATIENT CONCERNS: A 60-year-old Chinses woman presented to the hospital with progressive vision loss and headache for 1 week. The cerebrospinal fluid examination was within the normal range. Visual evoked potentials study disclosed prolonged latency of P100 bilaterally. Fundus examination revealed indistinct boundaries of both optic discs. Her brain magnetic resonance imaging showed patchy hyperintensity in the posterior horn of the left ventricle and the left optic nerve. Her serum was positive for anti-MOG and anti-mGluR5 antibodies. DIAGNOSIS: The patient was diagnosed with overlapping syndrome of anti-MOG antibody-associated disease and anti-mGluR5 encephalitis mainly based on the clinical symptoms and further test of the antibody in serum. INTERVENTIONS AND OUTCOMES: She was subsequently subjected to empirical treatment with intravenous methylprednisolone. After discharge, she was given a tapering dose of oral prednisone, alongside mycophenolate mofetil. On outpatient follow-up, her symptoms showed no relapse after 1 month, and her condition remained stable. LESSONS: Early recognition of autoimmune encephalitis is crucial. The detection of cerebrospinal fluid and serum of autoimmune encephalitis and demyelinating diseases of the CNS, including MOG-IgG and mGluR5-IgG, should be strengthened in order to make a precise diagnosis and develop a comprehensive treatment plan in a timely manner.
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Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Neuritis Óptica , Receptor del Glutamato Metabotropico 5 , Humanos , Femenino , Neuritis Óptica/diagnóstico , Neuritis Óptica/inmunología , Neuritis Óptica/tratamiento farmacológico , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/inmunología , Autoanticuerpos/sangre , Encefalitis/diagnóstico , Encefalitis/inmunología , Encefalitis/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Imagen por Resonancia Magnética , SíndromeRESUMEN
BACKGROUND: Seasonal variation in attacks of acute disseminated encephalomyelitis (ADEM1) is reported in some studies. Myelin oligodendrocyte glycoprotein (MOG) antibodies are found in up to 50 % of ADEM cases. Despite this, there has been no adequately powered study of seasonality in MOG antibody-associated disease (MOGAD). We sought to determine whether there was an effect of season on incidence of total attacks and onset attacks of MOGAD. METHODS: We searched the large national Oxford-based NMO Service database to identify attacks of MOGAD occurring between 2010 and 2021. Month of each attack was extracted and Edwards' test of seasonal variation was applied to determine whether there was a seasonal effect on total attacks and onset attacks. RESULTS: Neither incidence of total attacks nor incidence of onset attacks varied significantly by month. CONCLUSION: There is no evidence of seasonal fluctuations in the incidence of MOGAD attacks in the UK.
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Glicoproteína Mielina-Oligodendrócito , Estaciones del Año , Humanos , Glicoproteína Mielina-Oligodendrócito/inmunología , Incidencia , Autoanticuerpos/sangre , Reino Unido/epidemiología , Encefalomielitis Aguda Diseminada/epidemiología , Encefalomielitis Aguda Diseminada/inmunología , Masculino , Femenino , Adulto , Bases de Datos FactualesRESUMEN
INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) and MOG-associated disease (MOGAD) are an increasingly recognized group of demyelinating disorders of the central nervous system. Previous studies suggest that prognosis is predicted by older age at onset, number of relapses, the severity of the first attack and autoantibody status. OBJECTIVE: To study prognostic factors associated with disability progression and additional relapses in the 3-year follow-up of a national NMOSD/MOGAD cohort. RESULTS: Out of 180 of the initial Portuguese cohort, data on 82 patients was available at the end of the follow-up period (2019-2022). Two patients died. Twenty (24.4%) patients had one or more attack in this period (25 attacks in total), mostly transverse myelitis (TM) (56.0%) or optic neuritis (32.0%). MOGAD was significantly associated with a monophasic disease course (p = 0.03), with milder attacks (p = 0.01), while AQP4 + NMOSD was associated with relapses (p = 0.03). The most common treatment modalities were azathioprine (38.8%) and rituximab (18.8%). AQP4 + NMOSD more frequently required chronic immunosuppressive treatment, particularly rituximab (p = 0.01). Eighteen (22.5%) had an EDSS ≥6 at the end of the follow-up. AQP4 + NMOSD (p < 0.01) and the occurrence of transverse myelitis (TM) during disease (p = 0.04) correlated with an EDSS≥6 at the end of the follow-up period. MOGAD was significantly associated with an EDSS<6 (p < 0.01), and MOG+ cases that reached an EDSS>6 were significantly older (64.0 ± 2.8 versus 31.0 ± 17.1, p = 0.017). A bivariate logistic regression model including the serostatus and TM attacks during disease history successfully predicted 72.2% of patients that progressed to an EDSS≥6. CONCLUSION: This study highlights that myelitis predict increased disability (EDSS≥6) in NMOSD/MOGAG and AQP4 positivity is associated with increased disability.
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Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica , Sistema de Registros , Humanos , Neuromielitis Óptica/epidemiología , Femenino , Masculino , Portugal/epidemiología , Adulto , Pronóstico , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/inmunología , Estudios de Cohortes , Progresión de la Enfermedad , Autoanticuerpos/sangre , Personas con Discapacidad , Evaluación de la Discapacidad , Acuaporina 4/inmunología , Adulto Joven , Estudios de Seguimiento , Anciano , RecurrenciaRESUMEN
Rare demyelinating diseases are a group of diseases whose pathogenesis is based on the process of demyelination. This group of diseases includes acute multiple encephalomyelitis (ADEM), opticoneuromyelitis spectrum diseases (NMOSD) and anti-myelin-oligodendrocyte glycoprotein-associated diseases (MOG-antibodies-associated diseases - MOGAD). Recently, new biological drugs for pathogenetic therapy have been developed, which have shown their effectiveness and good tolerability in comparison with therapy with first- and second-line drugs. Aim of the study - analysis of modern possibilities of pathogenetic treatment of patients with ADEM, seronegative and seropositive patients with NMOSD. The analysis was carried out on the basis of English-language publications in PubMed published over the past five years. This review summarizes current ideas about the possibilities of pathogenetic treatment of rare diseases. The advantages of using ravulizumab over other representatives of a new biological therapy associated with the use of monoclonal antibodies are shown. The analyzed data allow us to conclude that there is a significant development of pathogenetic treatment options for ZSONM. However, the effectiveness of new therapeutic biological drugs is still limited due to the lack of a large amount of clinical data to confirm, which creates the need to continue analyzing the experience of their use.
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Enfermedades Raras , Humanos , Enfermedades Raras/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neuromielitis Óptica/tratamiento farmacológico , Neuromielitis Óptica/inmunología , Glicoproteína Mielina-Oligodendrócito/inmunología , Enfermedades Desmielinizantes/tratamiento farmacológicoRESUMEN
OBJECTIVE: This article reviews the clinical features, MRI characteristics, diagnosis, and treatment of aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). The main differences between these disorders and multiple sclerosis (MS), the most common demyelinating disease of the central nervous system (CNS), are also highlighted. LATEST DEVELOPMENTS: The past 20 years have seen important advances in understanding rare demyelinating CNS disorders associated with AQP4 IgG and myelin oligodendrocyte glycoprotein (MOG) IgG. The rapidly expanding repertoire of immunosuppressive agents approved for the treatment of AQP4-NMOSD and emerging as potentially beneficial in MOGAD mandates prompt recognition of these diseases. Most of the recent literature has focused on the identification of clinical and MRI features that help distinguish these diseases from each other and MS, simultaneously highlighting major diagnostic pitfalls that may lead to misdiagnosis. An awareness of the limitations of currently available assays for AQP4 IgG and MOG IgG detection is fundamental for identifying rare false antibody positivity and avoiding inappropriate treatments. For this purpose, diagnostic criteria have been created to help the clinician interpret antibody testing results and recognize the clinical and MRI phenotypes associated with AQP4-NMOSD and MOGAD. ESSENTIAL POINTS: An awareness of the specific clinical and MRI features associated with AQP4-NMOSD and MOGAD and the limitations of currently available antibody testing assays is crucial for a correct diagnosis and differentiation from MS. The growing availability of effective treatment options will lead to personalized therapies and improved outcomes.