RESUMO
BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disorder of central nervous system (CNS). Tryptophan indole catabolites have been reported to associate with the inflammatory diseases of the CNS. However, the roles of tryptophan indole catabolites have been rarely elucidated in MOGAD. METHODS: This cross-sectional study enrolled forty MOGAD patients, twenty patients with other non-inflammatory neurological diseases (OND) and thirty-five healthy participants. Serum and cerebrospinal fluid (CSF) samples of MOGAD and OND subjects during clinical attacks, serum samples of healthy participants were obtained. The concentrations of tryptophan, indoleacetic acid (IAA), indoleacrylic acid (IA) and indole-3-carboxylic acid (I-3-CA) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The correlations between tryptophan indole catabolites and maintenance immunotherapy, disease duration, overall numbers of attacks, short-term outcome in MOGAD patients were investigated. RESULTS: Levels of serum tryptophan, IAA, IA and CSF tryptophan in MOGAD patients were significantly decreased, while levels of serum I-3-CA and CSF IA were markedly increased compared with OND patients and healthy controls. Levels of serum tryptophan, CSF tryptophan and IA were significantly decreased in MOGAD patients who had received maintenance immunotherapy within 6 months before the attack. In MOGAD patients, serum and CSF tryptophan conversely correlated with disease duration and overall numbers of attacks, and serum IA negatively correlated with disease duration. Furthermore, serum tryptophan in MOGAD patients negatively correlated with the modified Rankin Scale (mRS) scores at 3 months. CONCLUSION: This study manifested decreased serum tryptophan levels and serum tryptophan may be the potential marker to predict the short-term outcome in MOGAD patients.
Assuntos
Triptofano , Humanos , Triptofano/sangue , Estudos Transversais , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/sangue , Espectrometria de Massas em Tandem , Adulto Jovem , Cromatografia Líquida de Alta Pressão , IdosoRESUMO
The spectrum of MOG-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE) and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgGSERUM), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgGCSF), and its diagnostic implications remains unclear. In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgGSERUM and MOG-IgGCSF titres were assessed with serial 2-fold dilutions to determine end point titres [≥1:128 in serum and ≥1:1 (no dilution) in CSF were considered positive]. We analysed the relationship between MOG-IgGSERUM, MOG-IgGCSF and the phenotypes with multivariable regression. A total of 671 patients were tested [405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD and 119 with other neurological diseases (OND)] before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15 and Others 11); 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5 and Others 4); and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0 and Others 7). None of AQP4-IgG-positive NMOSD, multiple sclerosis or OND cases tested positive for MOG-IgGSERUM, but two with multiple sclerosis cases were MOG-IgGCSF-positive; the specificities of MOG-IgGSERUM and MOG-IgGCSF in suspected MOGAD were 100% [95% confidence interval (CI) 99-100%] and 99% (95% CI 97-100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgGSERUM and MOG-IgGCSF titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgGSERUM was associated with ON and ADEM, whereas MOG-IgGCSF was associated with ADEM and CE. The number needed to test for MOG-IgGCSF to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY and 6.1 for Others). In terms of MOG-IgGSERUM/CSF status, most cases were double-positive while including either serum-restricted (13%) or CSF-restricted (17%) cases. These statuses were independently associated with clinical phenotypes, especially in those with ON in serum and CE in CSF, suggesting pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted to deduce the clinical and pathological significance of compartmentalized MOG-IgG.
Assuntos
Encefalite , Imunoglobulina G , Esclerose Múltipla , Glicoproteína Mielina-Oligodendrócito , Mielite , Neuromielite Óptica , Neurite Óptica , Humanos , Aquaporina 4 , Autoanticorpos , Estudos Transversais , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico , Glicoproteína Mielina-Oligodendrócito/sangue , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquidianoRESUMO
Importance: In multiple sclerosis, magnetic resonance imaging (MRI) new silent lesions contribute to the diagnostic criteria, have prognostic value, and are used in treatment monitoring; but in aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD), they are rare between attacks. Their frequency and their association with relapses in adults with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are still unclear. Objective: To examine the frequency and characteristics of MRI new silent lesions in MOGAD and AQP4-NMOSD. Design, Setting, and Participants: This retrospective cohort study analyzed clinical and MRI data of 404 patients with MOGAD or AQP4-NMOSD between February 1, 1994, and April 1, 2021; data were prospectively recorded on the Oxford NMOSD clinical database under follow-up. The study was conducted at the Oxford National Referral Center for NMOSD. Participants included patients with MOGAD and AQP4-NMOSD who were treated within the Oxford National NMO Specialist Service. Exposures: Seropositive MOGAD and AQP4-NMOSD patients who had MRIs during attacks and the remission phase of their disease. Main Outcomes and Measures: Frequency of new silent lesions detected by either attack MRIs (during the acute clinical event) or remission MRIs (performed outside of a relapse and at least 3 months from last attack). Median time to next relapse in the presence of definite (reference MRI performed at least 4 weeks from last attack onset), probable (reference MRI performed during last attack), and no new silent lesions on remission MRIs was also evaluated. Results: One hundred eighty-two MOGAD patients and 222 AQP4-NMOSD patients were included. Of the MOGAD patients, 113 (62%) were female, median age at onset was 28 years (range, 2-72), and median follow-up was 52 months (range, 11-253). Of the AQP4-NMOSD patients, 189 (85%) were female, median age at onset was 43 years (range, 2-82), and median follow-up was 87.5 months (range, 11-260). MOGAD patients had 296 attack MRI sessions and 167 remission MRI sessions. New attack silent lesions were found in 97 of 296 (33%) attack MRI sessions, whereas new remission silent lesions were found in 5 of 167 (3.0%) remission MRI sessions. Median time from remission scan to the next relapse in the presence of definite or probable new remission lesions was 2 months (IQR, 1-6), whereas in the absence of any new remission lesions it was 73 months (IQR, 20-104; hazard ratio, 23.86; 95% CI, 7.51-75.79; P < .001). AQP4-NMOSD patients had 470 attack MRI sessions and 269 remission MRI sessions. New attack silent lesions were detected in 88 of 470 (18.7%) attack MRI sessions, whereas new remission silent lesions were found in 7 of 269 (2.6%) remission MRI sessions. Median time from remission scan to the next relapse in the presence of definite or probable new remission lesions was 5 months (IQR, 2-6), whereas in the absence of any new remission lesions it was 85 months (IQR, 29-167; hazard ratio, 21.23; 95% CI, 8.05-53.65; P < .001). Conclusions and Relevance: In contrast to that reported in multiple sclerosis, results of this cohort study suggest that new remission silent lesions are rare on follow-up scans in MOGAD and AQP4-NMOSD and appear to indicate a high risk of imminent relapse.
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Aquaporina 4/imunologia , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aquaporina 4/sangue , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Glicoproteína Mielina-Oligodendrócito/sangue , Neuromielite Óptica/fisiopatologia , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: Myelin oligodendrocyte glycoprotein antibodies (MOG-abs) are associated with demyelinating diseases. Leptomeningeal enhancement occurs in 6% of adult MOG-abs patients but rates in pediatric MOG-abs patients are unknown. METHODS: Retrospective review of pediatric MOG-abs patients was performed. RESULTS: Twenty-one patients (7 boys, 14 girls) were included with an average age of 8.6 years (range 2-15 years). Seven of 21 (33%) pediatric MOG-abs patients had leptomeningeal enhancement. Two patients' relapses were manifested by leptomeningeal enhancement alone and another patient presented with seizures, encephalopathy, and aseptic meningitis without demyelinating lesions. Cerebrospinal fluid pleocytosis was seen in both leptomeningeal (4/7 patients) and nonleptomeningeal enhancement (10/14 patients). Interestingly, 3 patients with leptomeningeal enhancement had normal cerebrospinal fluid white blood cell count. Cortical edema was more likely in patients with leptomeningeal enhancement (P = .0263). CONCLUSION: We expand the clinical spectrum of anti-MOG antibody-associated disorder. Patients with recurrent leptomeningeal enhancement without demyelinating lesions should be tested for MOG antibodies.
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Autoanticorpos/sangue , Encefalomielite/sangue , Encefalomielite/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Meninges/diagnóstico por imagem , Glicoproteína Mielina-Oligodendrócito/sangue , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos RetrospectivosAssuntos
Autoanticorpos/sangue , COVID-19/sangue , COVID-19/terapia , Encefalomielite Aguda Disseminada/sangue , Encefalomielite Aguda Disseminada/terapia , Glicoproteína Mielina-Oligodendrócito/sangue , Autoanticorpos/imunologia , COVID-19/complicações , Criança , Encefalomielite Aguda Disseminada/etiologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Metilprednisolona/uso terapêutico , Glicoproteína Mielina-Oligodendrócito/imunologia , Plasmaferese/métodosAssuntos
COVID-19/complicações , Doenças Desmielinizantes/complicações , Glicoproteína Mielina-Oligodendrócito/sangue , Doença Aguda , Encéfalo/diagnóstico por imagem , COVID-19/diagnóstico , Criança , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/tratamento farmacológico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Metilprednisolona/uso terapêutico , Nervo Óptico/diagnóstico por imagem , Prednisolona/uso terapêutico , SARS-CoV-2 , Medula Espinal/diagnóstico por imagem , Síndrome , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: Aseptic meningitis can be caused by autoimmune diseases, such as lupus and sarcoidosis. Aseptic meningitis with leptomeningeal enhancement can be the initial presentation of a neuroinflammatory syndrome associated with antibodies to myelin oligodendrocyte glycoprotein (MOG-abs). MOG-abs is a serum biomarker for MOG-associated disorder (MOG-AD), an acquired demyelinating syndrome that includes features of neuromyelitis optica, multiple sclerosis, optic neuritis, and acute disseminated encephalomyelitis. The purpose of this study is to review cases of aseptic meningitis and leptomeningeal enhancement associated with MOG-abs. METHODS: Systematic review using PubMed, Embase, Ovid MEDLINE, Web of Science Core Collection, and Google Scholar up to December 2020 was performed. Cases of MOG-AD were included if they met the following criteria: 1) Initial clinical presentation of aseptic meningitis; 2) positive leptomeningeal enhancement and 3) MOG-Ab seropositivity. Descriptive statistics were used. This analysis was limited to the cases available in the literature. RESULTS: 11 total cases of aseptic meningitis and leptomeningeal enhancement in setting of MOG-ab were identified. Demyelinating type T2 lesions were also present at time of presentation in 6/11; however, 5/11 of patients had leptomeningeal enhancement alone without demyelinating lesions. All 5 patients required immunotherapy for improvement, including one patient with symptoms for 28 days, with 4/5 receiving steroids and 1/5 receiving intravenous immunoglobulin (IVIG). CONCLUSIONS: Aseptic meningitis with leptomeningeal enhancement can be the initial presenting symptom of MOG-AD. MOG-ab testing should be considered in a patient presenting with aseptic meningitis and leptomeningeal enhancement of unknown etiology.
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Autoanticorpos/sangue , Meningite Asséptica/sangue , Meningite Asséptica/diagnóstico por imagem , Glicoproteína Mielina-Oligodendrócito/sangue , Autoanticorpos/imunologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/sangue , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/diagnóstico por imagem , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Humanos , Meningite Asséptica/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/sangue , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/imunologiaRESUMO
Improvements in assays for detecting serum antibodies against myelin oligodendrocyte glycoprotein (MOG) have led to the appreciation of MOG-antibody-associated disease (MOGAD) as a novel disorder. However, much remains unknown about its etiology. We performed human leukocyte antigen (HLA) analysis in 82 MOGAD patients of European ancestry in the UK population. No HLA class II associations were observed, thus questioning the mechanism of anti-MOG antibody generation. A weak protective association of HLA-C*03:04 was observed (OR = 0.26, 95% CI = 0.10-0.71, pc = 0.013), suggesting a need for continued efforts to better understand MOGAD genetics and pathophysiology.
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Autoanticorpos/sangue , Estudos de Associação Genética/métodos , Antígenos HLA/sangue , Glicoproteína Mielina-Oligodendrócito/sangue , Neuromielite Óptica/sangue , Neuromielite Óptica/epidemiologia , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Antígenos HLA/genética , Humanos , Masculino , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/genética , Neuromielite Óptica/genética , Reino Unido/epidemiologia , Adulto JovemRESUMO
Importance: Myelin oligodendrocyte glycoprotein-IgG1-associated disorder (MOGAD) is a distinct central nervous system-demyelinating disease. Positive results on MOG-IgG1 testing by live cell-based assays can confirm a MOGAD diagnosis, but false-positive results may occur. Objective: To determine the positive predictive value (PPV) of MOG-IgG1 testing in a tertiary referral center. Design, Setting, and Participants: This diagnostic study was conducted over 2 years, from January 1, 2018, through December 31, 2019. Patients in the Mayo Clinic who were consecutively tested for MOG-IgG1 by live cell-based flow cytometry during their diagnostic workup were included. Patients without research authorization were excluded. Main Outcomes and Measures: Medical records of patients who were tested were initially reviewed by 2 investigators blinded to MOG-IgG1 serostatus, and pretest probability was classified as high or low (suggestive of MOGAD or not). Testing of MOG-IgG1 used a live-cell fluorescence-activated cell-sorting assay; an IgG binding index value of 2.5 or more with an end titer of 1:20 or more was considered positive. Cases positive for MOG-IgG1 were independently designated by 2 neurologists as true-positive or false-positive results at last follow-up, based on current international recommendations on diagnosis or identification of alternative diagnoses; consensus was reached for cases in which disagreement existed. Results: A total of 1617 patients were tested, and 357 were excluded. Among 1260 included patients tested over 2 years, the median (range) age at testing was 46 (0-98) years, and 792 patients were female (62.9%). A total of 92 of 1260 (7.3%) were positive for MOG-IgG1. Twenty-six results (28%) were designated as false positive by the 2 raters, with an overall agreement on 91 of 92 cases (99%) for true and false positivity. Alternative diagnoses included multiple sclerosis (n = 11), infarction (n = 3), B12 deficiency (n = 2), neoplasia (n = 2), genetically confirmed adrenomyeloneuropathy (n = 1), and other conditions (n = 7). The overall PPV (number of true-positive results/total positive results) was 72% (95% CI, 62%-80%) and titer dependent (PPVs: 1:1000, 100%; 1:100, 82%; 1:20-40, 51%). The median titer was higher with true-positive results (1:100 [range, 1:20-1:10000]) than false-positive results (1:40 [range, 1:20-1:100]; P < .001). The PPV was higher for children (94% [95% CI, 72%-99%]) vs adults (67% [95% CI, 56%-77%]) and patients with high pretest probability (85% [95% CI, 76%-92%]) vs low pretest probability (12% [95% CI, 3%-34%]). The specificity of MOG-IgG1 testing was 97.8%. Conclusions and Relevance: This study confirms MOG-IgG1 as a highly specific biomarker for MOGAD, but when using a cutoff of 1:20, it has a low PPV of 72%. Caution is advised in the interpretation of low titers among patients with atypical phenotypes, because ordering MOG-IgG1 in low pretest probability situations will increase the proportion of false-positive results.
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Autoanticorpos/sangue , Doenças Desmielinizantes/sangue , Doenças Desmielinizantes/diagnóstico , Imunoglobulina G/sangue , Glicoproteína Mielina-Oligodendrócito/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Criança , Pré-Escolar , Técnicas e Procedimentos Diagnósticos/normas , Feminino , Citometria de Fluxo/métodos , Citometria de Fluxo/normas , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: The diagnosis of spontaneous spinal cord infarction (SCI) is limited by the lack of diagnostic biomarkers and MRI features that often overlap with those of other myelopathies, especially acute myelitis. We investigated whether the ratio between serum neurofilament light chain levels and MRI T2-lesion area (neurofilament light chain/area ratio-NAR) differentiates SCI from acute myelitis of similar severity. METHODS: We retrospectively identified Mayo Clinic patients (January 1, 2000-December 31, 2019) with (1) SCI, (2) AQP4 (aquaporin 4)-IgG or MOG (myelin oligodendrocyte glycoprotein)-IgG-associated myelitis at disease clinical presentation, or (3) idiopathic transverse myelitis from a previously identified population-based cohort of patients seronegative for AQP4-IgG and MOG-IgG. Serum neurofilament light chain levels (pg/mL) were assessed at the Verona University (SIMOA, Quanterix) in a blinded fashion on available stored samples obtained ≤3 months from myelopathy presentation. For each patient, the largest spinal cord lesion area (mm2) was manually outlined by 2 independent raters on sagittal T2-weighted MRI images, and the mean value was used to determine NAR (pg/[mL·mm2]). RESULTS: Forty-eight patients were included SCI, 20 (definite, 11; probable, 6; possible, 3); acute myelitis, 28 (AQP4-IgG-associated, 17; MOG-IgG-associated, 5; idiopathic transverse myelitis, 6). The median expanded disability status scale score (range) at myelopathy nadir were 7.75 (2-8.5) and 5.5 (2-8), respectively. Serum neurofilament light chain levels (median [range] pg/mL) in patients with SCI (188 [14.3-2793.4]) were significantly higher compared with patients with AQP4-IgG-associated myelitis (37 [0.8-6942.9]), MOG-IgG-associated myelitis (45.8 [4-283.8]), and idiopathic transverse myelitis (15.6 [0.9-217.8]); P=0.01. NAR showed the highest accuracy for identification of SCI versus acute myelitis with values ≥0.35 pg/(mL·mm2) yielding 86% specificity and 95% sensitivity (area under the curve=0.93). The positive and negative likelihood ratios were 6.67 and 0.06, respectively. NAR remained independently associated with SCI after adjusting for age, gender, immunotherapy before sampling, and days from myelopathy symptoms onset to sampling (P=0.0007). CONCLUSIONS: NAR is a novel and promising clinical biomarker for differentiation of SCI from acute myelitis.
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Infarto/sangue , Infarto/diagnóstico por imagem , Mielite Transversa/sangue , Mielite Transversa/diagnóstico por imagem , Proteínas de Neurofilamentos/sangue , Isquemia do Cordão Espinal/diagnóstico por imagem , Isquemia do Cordão Espinal/diagnóstico , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Aquaporina 4/sangue , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Imunoterapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/sangue , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
AIMS: Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been proposed to define "MOG encephalomyelitis" (MOG-EM), with published diagnostic and "red flag" criteria. We aimed to evaluate these criteria in a routine clinical setting. METHODS: We retrospectively analyzed patients with borderline/positive MOG-IgG and applied the diagnostic and red flag criteria to determine likelihood of MOG-EM diagnosis. Para-/clinical parameters were described and analyzed with chi-square test. RESULTS: In total, 37 patients fulfilled MOG-EM diagnostic criteria (female-to-male ratio: 1.6:1, median onset age: 28.0 years [IQR 18.5-40.5], n = 8 with pediatric onset). In 24/37, red flags were present, predominantly MOG-IgG at assay cutoff and/or MRI lesions suggestive of multiple sclerosis (MS). As proposed in the consensus criteria, these patients should rather be described as "possible" MOG-EM. Of these, we classified 13 patients as "unlikely" MOG-EM in the presence of the red flag "borderline MOG-IgG" with negative MOG-IgG retest or coincidence of ≥1 additional red flag. This group mainly consisted of patients diagnosed with MS (n = 11). Frequency of cerebrospinal fluid (CSF-)-specific oligoclonal bands (OCB) is significantly lower in definite vs possible and unlikely MOG-EM (P = .0005). CONCLUSION: Evaluation of diagnostic and red flag criteria, MOG-IgG retesting (incl. change of assay), and CSF-specific OCB are relevant in clinical routine cohorts to differentiate MOG-EM from MS.
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Autoanticorpos/sangue , Encefalomielite/sangue , Encefalomielite/diagnóstico por imagem , Imunoglobulina G/sangue , Glicoproteína Mielina-Oligodendrócito/sangue , Adolescente , Adulto , Estudos de Coortes , Feminino , Células HEK293 , Humanos , Imageamento por Ressonância Magnética/tendências , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
To compare the clinical, imaging, and prognostic characteristics of AQP4 antibody-related diseases and MOG antibody-related diseases. The clinical data of 56 AQP4 antibody-positive patients and 14 MOG antibody-positive patients in the Second Xiangya Hospital of Central South University from June 2016 to June 2019 were collected. 92.9% of the patients with positive AQP4 antibody were females and 64.3% of patients with positive MOG antibody were females (P = 0.004). Patients with positive AQP4 antibody were more likely to have limb movement (P < 0.001) or limb sensory dysfunction (P < 0.001), and were more likely to have limb twitching (P = 0.036). In addition, AQP4 antibody-positive patients were more likely to have positive ANA (P = 0.013) and SSA antibody (P = 0.029), Ro-52 antibody (P = 0.047), immunoglobulin (P = 0.007), thyroid antibody (P = 0.007), abnormal C3 (P = 0.011), abnormal C4 (P = 0.014) than MOG antibody-positive patients. The involvement rate of head in MOG antibody-positive patients was higher than AQP4 antibody-positive patients (P = 0.029). The severity of clinical symptoms in AQP4-positive patients was usually more serious than that in MOG-positive patients (P < 0.001). The residual neurological deficit after treatment in AQP4-positive group was usually more serious than that in MOG-positive group (P < 0.001). AQP4 antibody-positive patients had a higher prevalence in women than MOG antibody-positive patients, and AQP4 antibody-positive patients were more likely to have spinal cord involvement symptoms and connective tissue antibody abnormalities. The EDSS score of them were higher than that of MOG antibody-positive patients after treatment, and the prognosis was worse.
Assuntos
Aquaporina 4/sangue , Autoanticorpos/sangue , Glicoproteína Mielina-Oligodendrócito/sangue , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/diagnóstico por imagem , Vigilância da População , Adulto , China/epidemiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Estudos Retrospectivos , Fatores SexuaisRESUMO
Myelin oligodendrocyte glycoprotein antibody (MOG-Ab) is involved in the pathogenesis of central nervous system (CNS) demyelination disorders. We aimed to explore the spectrum of MOG-Ab-associated diseases in eastern India. A single-center, prospective observational study was done over a period of 2 years in a tertiary care hospital of eastern India. Patients with CNS demyelination disorders who tested positive for MOG-Ab using live cell-based assay were included in the study; while, those with age less than 1 year, documented preexisting CNS structural lesions, developmental delays or diagnosed multiple sclerosis were excluded. Demographic profile, clinical spectrum, disease course, radiological features as well as response to treatment were analyzed among included patients. Twenty MOG-Ab-positive patients were included (M:F 1:1.85). The median age of symptom onset was 10.5 years. The median follow-up of patients was 13 months. Acute disseminated encephalomyelitis (ADEM) was the commonest presentation at first attack (55%), followed by optic neuritis (ON) (45%). Patients with ADEM had a significantly lower age at first attack (p = 0.025). Monophasic and relapsing disease courses were seen in 45% and 55% patients, respectively. While all patients with only ADEM had a monophasic course, 77.8% with ON had a relapsing course. Among patients who presented with isolated transverse myelitis, 75% had a monophasic course and all had disease confined to the spinal cord. Good response to corticosteroids was seen in majority of participants. Second-line drugs were needed in 55% patients, rituximab being the commonest second-line agent used. 35% patients had significant disability (EDSS > 4) at last follow-up. MOG-Ab-associated diseases have diverse clinical phenotypes characterized by age-dependent pattern-specific courses.
Assuntos
Autoanticorpos/sangue , Encefalomielite Aguda Disseminada/sangue , Glicoproteína Mielina-Oligodendrócito/sangue , Mielite Transversa/sangue , Neurite Óptica/sangue , Adolescente , Adulto , Criança , Encefalomielite Aguda Disseminada/diagnóstico por imagem , Encefalomielite Aguda Disseminada/epidemiologia , Feminino , Seguimentos , Humanos , Índia/epidemiologia , Masculino , Mielite Transversa/diagnóstico por imagem , Mielite Transversa/epidemiologia , Neurite Óptica/diagnóstico por imagem , Neurite Óptica/epidemiologia , Estudos Prospectivos , Adulto JovemRESUMO
Anti-myelin oligodendrocyte glycoprotein antibodies have been associated with a wide range of clinical presentations including monophasic and relapsing disease courses. Lack of a definitive marker for predicting further relapses and the final diagnoses complicates the clinical follow-up and treatment decisions for patients with the first episode. This study retrospectively analyzed the clinical spectrum, treatment protocols and outcome of nine children with MOG antibody-associated demyelinating disease. Diagnoses at first presentation were acute disseminated encephalomyelitis (ADEM) in six cases (67%), optic neuritis in two cases (22%), and clinically isolated syndrome in one case (11%). The disease remained monophasic in five (56%) cases. All cases with a monophasic disease course were negative for anti-MOG antibody titers in the third month. The initial diagnosis of all relapsing cases was ADEM. Three of the four cases with a relapsing disease course were available for anti-MOG antibody testing at the third month and all were positive, however, antibody titers at the sixth month were inconsistent. Cases with a relapsing disease course had no further attacks after monthly intravenous immunoglobulin treatment. Relapsing disease course is not rare in childhood MOG-antibody associated demyelinating disease. Monthly IVIG treatment may be a good alternative for the long-term treatment of relapsing cases with a low side effect profile. Anti-MOG antibody serostatus at remission periods should be interpreted cautiously. Further studies are needed to better understand and predict the clinical course of pediatric patients with MOG-antibody associated diseases.
Assuntos
Autoanticorpos/sangue , Doenças Desmielinizantes/sangue , Doenças Desmielinizantes/diagnóstico por imagem , Glucocorticoides/uso terapêutico , Glicoproteína Mielina-Oligodendrócito/sangue , Centros de Atenção Terciária , Criança , Pré-Escolar , Doenças Desmielinizantes/tratamento farmacológico , Feminino , Seguimentos , Glucocorticoides/farmacologia , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This study aimed to determine the seasonal impact on the clinical onset of inflammatory neurological diseases of the central nervous system by analyzing the onset month with information on clinical manifestations in Japanese patients. As a result, patients with anti-aquaporin-4 antibodies (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSD) showed spring-summer predominance of the clinical onset. Conversely, patients with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease showed autumn-winter predominance of the clinical onset. Both seasonal variations were irrespective of the clinical manifestation. Environmental factors with seasonal variation influence the development of neurological conditions related to AQP4-IgG and MOG-IgG.
Assuntos
Aquaporina 4/sangue , Autoanticorpos/sangue , Glicoproteína Mielina-Oligodendrócito/sangue , Neuromielite Óptica/sangue , Estações do Ano , Adulto , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/epidemiologia , Adulto JovemRESUMO
A 44-year-old male patient with no past medical history presented 2 weeks after seropositive coronavirus disease 2019 (COVID-19) infection with vision problems suggestive of optic neuritis. Radiological testing showed findings suspicious for acute bilateral optic neuritis. The patient had also anti-MOG antibodies. Whether this was an optic neuritis due to COVID-19, MOG antibody disease, or an activation of MOG antibody disease by COVID-19 is discussed in this case.
Assuntos
COVID-19/complicações , Glicoproteína Mielina-Oligodendrócito/sangue , Neurite Óptica/diagnóstico por imagem , COVID-19/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Disco Óptico/patologia , Neurite Óptica/sangue , Neurite Óptica/etiologia , SARS-CoV-2RESUMO
Anti-N-methyl-D-aspartate receptor encephalitis (NMDARe) can coexist with myelin oligodendrocyte glycoprotein antibody (MOG-ab) disease.To characterize MOG-ab disease during NMDARe, we analyzed all the patients with MOG-ab disease and NMDARe from our hospital from December 2018 to December 2019 and data from a systematical review of previously published reports. Details of the patients identified were summarized and literature was reviewed.Four of thirty (14.2%) patients with anti-NMDARe had overlapping MOG-ab disease in our department. Analyze together with previously reported cases. Thirty-two NMDARe patients had overlapping MOG-ab disease. The onset age ranged from 3 to 48 years. Twenty-four patients (74%) developed abnormal behavior or cognitive dysfunction during the episodes of anti-NMDARe. None of these patients had tumors. 84% (27/32) patients received high doses of steroids as first-line immunotherapy and 28% (9/32) received mycophenolate mofetil (MMF) to prevent relapse. Twenty-six of twenty-seven (96%) had a good outcome.Steroids are the most common first-line immunotherapies in NMDARe overlapping MOG-ab disease. Most of the NMDARe patients overlapping MOG-ab disease have a good prognosis.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Esclerose Múltipla/diagnóstico , Glicoproteína Mielina-Oligodendrócito/sangue , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/sangue , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/complicações , Estudos Retrospectivos , Convulsões/etiologia , Adulto JovemRESUMO
BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG)-IgG associated disorders are increasingly recognized as a distinct disease entity. However, diagnostic sensitivity and specificity of serum MOG-IgG as well as recommendations for testing are still debated. MATERIALS AND METHODS: Between October 2015 and July 2017 we tested serum MOG-IgG in 91 adult patients (49 females) with a demyelinating event (DE) not fulfilling 2010 McDonald criteria for MS at sampling, negative for neuromyelitis optica (NMO)-IgG and followed-up for at least 12 months. We assessed the sensitivity and specificity of a live-cell MOG-IgG assay for each final diagnosis at last follow-up, for the 2018 international recommendations for MOG-IgG testing, and for other combinations of clinical and laboratory characteristics. RESULTS: Clinical presentations included acute myelitis (n = 48), optic neuritis (n = 36), multifocal encephalomyelitis (n = 4), and brainstem syndrome (n = 3). Twenty-four patients were MOG-IgG positive. Sensitivity and specificity of MOG-IgG test applied to the 2018 international recommendations were 28.4% and 86.7%, while they were 42.1% and 88.6% when applied to DE of unclear aetiology as defined above with two or more among: 1_no periventricular and juxtacortical MS-like lesions on brain MRI; 2_longitudinally extensive MRI optic nerve lesion; 3_no CSF-restricted oligoclonal bands; 4_CSF protein > 50 mg/dl. CONCLUSIONS: Simplified requirements compared to those currently proposed for MOG-IgG testing could facilitate the applicability of the assay in the diagnosis of adults with DEs of unclear aetiology.
Assuntos
Autoanticorpos/sangue , Doenças Desmielinizantes/sangue , Doenças Desmielinizantes/diagnóstico por imagem , Imunoglobulina G/sangue , Glicoproteína Mielina-Oligodendrócito/sangue , Adulto , Idoso , Autoanticorpos/líquido cefalorraquidiano , Estudos de Coortes , Doenças Desmielinizantes/líquido cefalorraquidiano , Feminino , Seguimentos , Células HEK293 , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquidiano , Adulto JovemRESUMO
Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system that commonly manifests as a complex neuropsychiatric syndrome. Antibodies against myelin oligodendrocyte glycoprotein (MOG) are associated with a range of clinical presentations including acute disseminated encephalomyelitis (ADEM), optic neuritis, and transverse myelitis. The concurrence of NMDAR encephalitis and demyelinating syndromes is rare. We describe the case of a 29-year-old male with NMDAR encephalitis and overlapping MOG antibody disease. The aim of this report is to add to the growing knowledge of phenotypic characteristics of overlap syndromes as their clinical and prognostic features may differ from those of single antibody disease.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/sangue , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico por imagem , Autoanticorpos/sangue , Doenças Desmielinizantes/sangue , Doenças Desmielinizantes/diagnóstico por imagem , Glicoproteína Mielina-Oligodendrócito/sangue , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Doenças Desmielinizantes/complicações , Humanos , MasculinoRESUMO
Although Multiple Sclerosis is the most common central nervous system (CNS) inflammatory demyelinating disorder, other CNS inflammatory disorders should be included as diagnostic considerations. Neuromyelitis Optica Spectrum Disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease are less common but share some clinical characteristics, such as optic neuritis and myelitis, which can make a specific diagnosis challenging. However, these disorders have distinctive and generally different clinical phenotypes, prognosis and management. It is imperative to distinguish each from one another, especially since the treatments (not discussed in this review) can be different. The advent of reliable testing for anti-aquaporin-4 for NMOSD and anti-MOG antibodies has helped significantly; however, diagnosis can remain challenging, especially in sero-negative cases. Clinical indicators are important to guide diagnostic work-up. Careful review of the history, neurological exam, imaging, and/or spinal fluid results are essential to making an accurate diagnosis. In this review, we will examine the clinical presentation, diagnosis, and natural history of these inflammatory CNS disorders.