RESUMO
OBJECTIVE: To evaluate: (1) the distribution of gray matter (GM) atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and relapsing-remitting multiple sclerosis (RRMS); and (2) the relationship between GM volumes and white matter lesions in various brain regions within each disease. METHODS: A retrospective, multicenter analysis of magnetic resonance imaging data included patients with MOGAD/AQP4+NMOSD/RRMS in non-acute disease stage. Voxel-wise analyses and general linear models were used to evaluate the relevance of regional GM atrophy. For significant results (p < 0.05), volumes of atrophic areas are reported. RESULTS: We studied 135 MOGAD patients, 135 AQP4+NMOSD, 175 RRMS, and 144 healthy controls (HC). Compared with HC, MOGAD showed lower GM volumes in the temporal lobes, deep GM, insula, and cingulate cortex (75.79 cm3); AQP4+NMOSD in the occipital cortex (32.83 cm3); and RRMS diffusely in the GM (260.61 cm3). MOGAD showed more pronounced temporal cortex atrophy than RRMS (6.71 cm3), whereas AQP4+NMOSD displayed greater occipital cortex atrophy than RRMS (19.82 cm3). RRMS demonstrated more pronounced deep GM atrophy in comparison with MOGAD (27.90 cm3) and AQP4+NMOSD (47.04 cm3). In MOGAD, higher periventricular and cortical/juxtacortical lesions were linked to reduced temporal cortex, deep GM, and insula volumes. In RRMS, the diffuse GM atrophy was associated with lesions in all locations. AQP4+NMOSD showed no lesion/GM volume correlation. INTERPRETATION: GM atrophy is more widespread in RRMS compared with the other two conditions. MOGAD primarily affects the temporal cortex, whereas AQP4+NMOSD mainly involves the occipital cortex. In MOGAD and RRMS, lesion-related tract degeneration is associated with atrophy, but this link is absent in AQP4+NMOSD. ANN NEUROL 2024;96:276-288.
Assuntos
Aquaporina 4 , Atrofia , Autoanticorpos , Substância Cinzenta , Imageamento por Ressonância Magnética , Glicoproteína Mielina-Oligodendrócito , Neuromielite Óptica , Substância Branca , Humanos , Feminino , Aquaporina 4/imunologia , Neuromielite Óptica/patologia , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/imunologia , Masculino , Glicoproteína Mielina-Oligodendrócito/imunologia , Adulto , Atrofia/patologia , Substância Cinzenta/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/imunologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Autoanticorpos/sangue , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/imunologia , Adulto JovemRESUMO
MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease; AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis; brain and cord MRI at least 6 months from relapse; and Expanded Disability Status Scale (EDSS) score on the day of MRI. Brain white matter T2 lesions, T1-hypointense lesions, cortical and cord lesions were identified. Random forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred and sixty-two patients with MOG-antibody disease [99 females, mean age: 41 (±14) years, median EDSS: 2 (0-7.5)], 162 with AQP4-neuromyelitis optica spectrum disorder [132 females, mean age: 51 (±14) years, median EDSS: 3.5 (0-8)], 189 with multiple sclerosis (132 females, mean age: 40 (±10) years, median EDSS: 2 (0-8)] and 152 healthy controls (91 females) were studied. In young patients (<34 years), with low disability (EDSS < 3), the absence of Dawson's fingers, temporal lobe lesions and longitudinally extensive lesions in the cervical cord pointed towards a diagnosis of MOG-antibody disease instead of the other two diseases (accuracy: 76%, sensitivity: 81%, specificity: 84%, P < 0.001). In these non-acute patients, the number of brain lesions < 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, P < 0.001). An EDSS < 3 and the absence of longitudinally extensive lesions in the cervical cord predicted MOG-antibody disease versus AQP4-neuromyelitis optica spectrum disorder (accuracy: 76%, sensitivity: 89%, specificity: 62%, P < 0.001). A workflow with sequential tests and supporting features is proposed to guide better identification of patients with MOG-antibody disease. Adult patients with non-acute MOG-antibody disease showed distinctive clinical and MRI features when compared to AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis. A careful inspection of the morphology of brain and cord lesions together with clinical information can guide further analyses towards the diagnosis of MOG-antibody disease in clinical practice.
Assuntos
Esclerose Múltipla , Neuromielite Óptica , Feminino , Humanos , Neuromielite Óptica/patologia , Estudos Retrospectivos , Glicoproteína Mielina-Oligodendrócito , Estudos Transversais , Aquaporina 4 , Esclerose Múltipla/diagnóstico por imagem , Autoanticorpos , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Encephalitis is an inflammation of the cerebral parenchyma manifested by acute symptoms such as fever, headaches, and other neurological disorders. Its etiology is mostly viral, with herpes simplex virus being a frequent etiological agent in children. The development of neurological sequelae is a serious outcome associated with this infection. OBJECTIVE: To assess the general prevalence and types of neurological sequelae in children after a case of acute viral encephalitis caused by HSV. METHODS: This systematic review and meta-analysis was developed following the PRISMA guidelines. The literature search was carried out in the MEDLINE, Embase, SciELO, LILACS, Cochrane, CINAHL, PsycINFO, and Web of Science databases. Studies were included of children with confirmed HSV infection and that presented a description of neurological sequelae associated with that infection. For the meta-analysis of general prevalence and of the types of neurological sequelae a random effects model was used. RESULTS: Of the 2827 articles chosen in the initial search, nine studies were included in the systematic review and meta-analysis. The general prevalence of neurological sequelae was 50.7% (95% CI 39.2-62.2). The most frequent sequelae were related to mental disability, with a 42.1% prevalence (95% CI 30-55.2); on the other hand, the least frequent sequelae were those related with visual impairment, with a 5.9% prevalence (95% CI 2.2-14.6). The included studies presented regular quality and substantial heterogeneity. CONCLUSION: Even with antiviral therapy, half of patients will develop some type of disability.
Assuntos
Encefalite por Herpes Simples , Encefalite Viral , Encefalite , Herpes Simples , Humanos , Criança , Simplexvirus , Herpes Simples/complicações , Progressão da Doença , Encefalite/complicações , Encefalite por Herpes Simples/complicaçõesRESUMO
Myelin oligodendrocyte glycoprotein (MOG) is a unique CNS-specific mammalian protein that is expressed on the surface of compact myelin and oligodendrocyte cell bodies. MOG is an accessible target for autoantibodies, associated with immune-mediated demyelination in the central nervous system. The identification of MOG reactive immunoglobulin G antibodies (MOG-IgG) helps to distinguish a subgroup of patients from multiple sclerosis and other CNS disorders, reducing the risk of clinical misdiagnosis. The development of the cell-based assays (CBA) improved the detection of clinically meaningful MOG-IgG binding to conformational MOG expressed in the cell membrane surface. In this review, we describe factors that impact on the results of CBA, such as MOG conformation, protein glycosylation, addition of fluorescent tags, serum dilution, secondary antibodies, and data interpretation.
Assuntos
Esclerose Múltipla , Neuromielite Óptica , Animais , Aquaporina 4 , Autoanticorpos , Humanos , Imunoglobulina G , Esclerose Múltipla/diagnóstico , Glicoproteína Mielina-Oligodendrócito , Projetos de PesquisaRESUMO
OBJECTIVE: To explore levels of astrocytopathy in neuromyelitis optica spectrum disorder (NMOSD) by measuring levels of the astrocytic enzyme glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), an established astrocytic biomarker known to be associated with disease activity in multiple sclerosis. METHODS: Cerebrospinal fluid concentrations of GS and GFAP were measured by ELISA in patients with NMOSD (n=39, 28 aquaporin-4 (AQP4)-Ab-seropositive, 3 double-Ab-seronegative, 4 myelin oligodendrocyte glycoprotein (MOG)-Ab-seropositive and 4 AQP4-Ab-seronegative with unknown MOG-Ab-serostatus), multiple sclerosis (MS) (n=69), optic neuritis (n=5) and non-neurological controls (n=37). RESULTS: GFAP and GS concentrations differed significantly across groups (both p<0.001), showing a similar pattern of elevation in patients with AQP4-Ab-seropositive NMOSD. GS and GFAP were significantly correlated, particularly in patients with AQP4-Ab-seropositive NMOSD (rs=0.70, p<0.001). Interestingly, GFAP levels in some patients with double-Ab-seronegative NMOSD were markedly increased. CONCLUSIONS: Our data indicate astrocytic injury occurs in some patients with double-Ab-seronegative NMOSD, which hints at the possible existence of yet undiscovered astrocytic autoimmune targets. We hypothesise that elevated GS and GFAP levels could identify those double-Ab-seronegative patients suitable to undergo in-depth autoimmune screening for astrocytic antibodies.
Assuntos
Astrócitos , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Glutamato-Amônia Ligase/líquido cefalorraquidiano , Neuromielite Óptica/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: MOG-IgG-associated optic neuritis, encephalitis and myelitis (MONEM) is a recently recognized group of inflammatory central nervous system (CNS) disorders distinct from multiple sclerosis and neuromyelitis optica spectrum disorders. Limited data are available regarding the predictors of relapse in this condition. OBJECTIVE: We aimed to evaluate the longitudinal serostatus of patients with MOG-IgG and to correlate serostatus with long-term clinical outcomes. METHODS: Of 574 consecutive patients who presented with demyelinating inflammatory CNS disorders, we included 31 patients who were MOG-IgG-positive. Patients with MOG-IgG were followed up from 2011 to 2017 at the School of Medicine, University of São Paulo, Brazil. RESULTS: Relapsing disease occurred in 23 out of 31 patients (74%), while 8 (26%) exhibited a monophasic course. All monophasic patients, as well as the majority of relapsing patients, became seronegative during clinical remission. Patients exhibiting disease activity in the last 2 years were more likely to remain positive, with higher medium titres than those found in patients in clinical remission. CONCLUSION: MOG-IgG patients usually present with a relapsing course, and the risk of relapse was associated with longitudinally persistent MOG-IgG seropositivity. In contrast, patients who experienced a single attack became spontaneously seronegative for MOG-IgG during long-term follow-up.
Assuntos
Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Encefalite/imunologia , Imunoglobulina G , Glicoproteína Mielina-Oligodendrócito/imunologia , Mielite/imunologia , Neurite Óptica/imunologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Adulto JovemRESUMO
OBJECTIVE: To evaluate cerebrospinal fluid (CSF) cytokine profiles in myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG+) disease in adult and paediatric patients. METHODS: In this cross-sectional study, we measured 27 cytokines in the CSF of MOG-IgG+ disease in acute phase before treatment (n=29). The data were directly compared with those in aquaporin-4 antibody-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) (n=20), multiple sclerosis (MS) (n=20) and non-inflammatory controls (n=14). RESULTS: In MOG-IgG+ disease, there was no female preponderance and the ages were younger (mean 18 years, range 3-68; 15 were below 18 years) relative to AQP4-IgG+ NMOSD (41, 15-77) and MS (34, 17-48). CSF cell counts were higher and oligoclonal IgG bands were mostly negative in MOG-IgG+ disease and AQP4-IgG+ NMOSD compared with MS. MOG-IgG+ disease had significantly elevated levels of interleukin (IL)-6, IL-8, granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor, interferon-γ, IL-10, IL-1 receptor antagonist, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α as compared with MS. No cytokine in MOG-IgG+ disease was significantly different from AQP4-IgG+ NMOSD. Moreover many elevated cytokines were correlated with each other in MOG-IgG+ disease and AQP4-IgG+ NMOSD but not in MS. No difference in the data was seen between adult and paediatric MOG-IgG+ cases. CONCLUSIONS: The CSF cytokine profile in the acute phase of MOG-IgG+ disease is characterised by coordinated upregulation of T helper 17 (Th17) and other cytokines including some Th1-related and regulatory T cells-related ones in adults and children, which is similar to AQP4-IgG+ NMOSD but clearly different from MS. The results suggest that as with AQP4-IgG+ NMOSD, some disease-modifying drugs for MS may be ineffective in MOG-IgG+ disease while they may provide potential therapeutic targets.
Assuntos
Aquaporina 4/líquido cefalorraquidiano , Citocinas/líquido cefalorraquidiano , Imunoglobulina G/líquido cefalorraquidiano , Esclerose Múltipla/líquido cefalorraquidiano , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquidiano , Neuromielite Óptica/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/terapia , Adulto JovemRESUMO
BACKGROUND: The Centers for Disease Control and Prevention (CDC) currently recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment and slow emergence of antimicrobial resistance. Since 2013, the prevalence of reduced azithromycin susceptibility increased in the United States; however, these strains were highly susceptible to cephalosporins. We identified a cluster of Neisseria gonorrhoeae isolates with high-level azithromycin resistance, several of which also demonstrated decreased ceftriaxone susceptibility. METHODS: Eight N. gonorrhoeae isolates collected from 7 patients on Oahu, Hawaii, seen 21 April 2016 through 10 May 2016 underwent routine Etest antimicrobial susceptibility testing by the Hawaii Department of Health. All demonstrated elevated azithromycin minimum inhibitory concentrations (MICs) >256 µg/mL and elevated ceftriaxone MICs (≥0.125 µg/mL). Isolates were sent to the University of Washington and CDC for confirmatory agar dilution testing; sequence data were sent to CDC for analysis. All patients were interviewed and treated, and when possible, partners were interviewed, tested, and treated. RESULTS: All isolates had azithromycin MICs >16 µg/mL and 5 had ceftriaxone MICs = 0.125 µg/mL by agar dilution. All isolates were ß-lactamase positive and were resistant to penicillin, tetracycline, and ciprofloxacin. Genomic analysis revealed genetic relatedness. No patients reported recent travel or antibiotic use, and no male patients reported male sex partners. All patients were successfully treated. CONCLUSIONS: This cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility and high-level azithromycin resistance may bring the threat of treatment failure in the United States with the current recommended dual therapy one step closer.
Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Ceftriaxona/farmacologia , Busca de Comunicante , Farmacorresistência Bacteriana Múltipla , Gonorreia/microbiologia , Gonorreia/transmissão , Neisseria gonorrhoeae/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Ceftriaxona/uso terapêutico , Ciprofloxacina/farmacologia , Quimioterapia Combinada , Feminino , Gonorreia/tratamento farmacológico , Havaí , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neisseria gonorrhoeae/enzimologia , Neisseria gonorrhoeae/genética , Penicilinas/farmacologia , Tetraciclina/farmacologia , Adulto Jovem , beta-Lactamases/metabolismoRESUMO
BACKGROUND: Myelin oligodendrocyte glycoprotein (anti-MOG) antibody was reported in anti-aquaporin-4 (anti-AQP4) seronegative neuromyelitis optica spectrum disorders (NMOSD) patients. OBJECTIVES: To describe clinical phenotypes associated with anti-MOG. METHODS: Seventy consecutive Thai patients with inflammatory idiopathic demyelinating central nervous system disorders (IIDCD) who were previously anti-AQP4 seronegative were tested for anti-MOG. RESULTS: Anti-MOG was positive in six patients, representing 20.7% of the IIDCD anti-AQP4 seronegative patients with a non-multiple sclerosis phenotype, and most had relapses. All first presented with optic neuritis with good visual recovery after treatment. CONCLUSIONS: Anti-MOG positive patients may have manifestations that mimic NMOSD but differ in their course and prognosis from anti-AQP4 positive NMOSD.
Assuntos
Autoanticorpos/sangue , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/imunologia , Neurite Óptica/imunologia , Aquaporina 4/imunologia , Biomarcadores/sangue , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/fisiopatologia , Neurite Óptica/diagnóstico por imagem , Neurite Óptica/tratamento farmacológico , Neurite Óptica/fisiopatologia , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Estudos Retrospectivos , Testes Sorológicos , Tailândia , Resultado do Tratamento , Visão Ocular , Adulto JovemRESUMO
Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders.
Assuntos
Esclerose Múltipla/metabolismo , Neuromielite Óptica/metabolismo , Células Th17/metabolismo , Animais , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/patologia , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/patologia , Células Th17/efeitos dos fármacosRESUMO
To elucidate immunopathogenetic roles of aquaporin-4 antibodies in the cerebrospinal fluid (CSF) of neuromyelitis optica spectrum disorders (NMOSD), we analyzed aquaporin-4 antibody titers, cellular and inflammatory markers in the CSF collected from 11 aquaporin-4 antibody seropositive patients. The CSF aquaporin-4 antibody levels during attacks (but not in sera) closely correlated with pleocytosis, inflammatory cytokines including interleukin-6 that can regulate antibody-producing plasmablasts, and glial fibrillary acidic protein levels in the CSF. The amount of aquaporin-4 antibodies present in the central nervous system may have therapeutic implications, as it is associated with astrocyte injury and inflammatory responses during NMOSD attacks.
Assuntos
Aquaporina 4/imunologia , Autoanticorpos/líquido cefalorraquidiano , Neuromielite Óptica , Doença Aguda , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/sangue , Neuromielite Óptica/líquido cefalorraquidiano , Neuromielite Óptica/imunologia , Adulto JovemRESUMO
In neuromyelitis optica (NMO), astrocytes become targets for pathogenic aquaporin 4 (AQP4)-specific antibodies which gain access to the central nervous system (CNS) in the course of inflammatory processes. Since these antibodies belong to a T cell-dependent subgroup of immunoglobulins, and since NMO lesions contain activated CD4(+) T cells, the question arose whether AQP4-specific T cells might not only provide T cell help for antibody production, but also play an important role in the induction of NMO lesions. We show here that highly pathogenic, AQP4-peptide-specific T cells exist in Lewis rats, which recognize AQP4268-285 as their specific antigen and cause severe panencephalitis. These T cells are re-activated behind the blood-brain barrier and deeply infiltrate the CNS parenchyma of the optic nerves, the brain, and the spinal cord, while T cells with other AQP4-peptide specificities are essentially confined to the meninges. Although AQP4268-285-specific T cells are found throughout the entire neuraxis, they have NMO-typical "hotspots" for infiltration, i.e. periventricular and periaqueductal regions, hypothalamus, medulla, the dorsal horns of spinal cord, and the optic nerves. Most remarkably, together with NMO-IgG, they initiate large astrocyte-destructive lesions which are located predominantly in spinal cord gray matter. We conclude that the processing of AQP4 by antigen presenting cells in Lewis rats produces a highly encephalitogenic AQP4 epitope (AQP4268-285), that T cells specific for this epitope are found in the immune repertoire of normal Lewis rats and can be readily expanded, and that AQP4268-285-specific T cells produce NMO-like lesions in the presence of NMO-IgG.
Assuntos
Aquaporina 4/metabolismo , Sistema Nervoso Central/imunologia , Encefalomielite Autoimune Experimental/imunologia , Imunoglobulina G/imunologia , Neuromielite Óptica/imunologia , Linfócitos T/metabolismo , Animais , Aquaporina 4/genética , Astrócitos/imunologia , Astrócitos/patologia , Linhagem Celular , Sistema Nervoso Central/patologia , Encefalomielite Autoimune Experimental/patologia , Humanos , Interferon gama/metabolismo , Interleucina-17/metabolismo , Neuromielite Óptica/patologia , Nervo Óptico/imunologia , Nervo Óptico/patologia , Ratos Endogâmicos Lew , Linfócitos T/patologiaAssuntos
Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/classificação , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Autoanticorpos/sangue , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/sangue , Humanos , Esclerose Múltipla/sangue , Esclerose Múltipla/classificação , Esclerose Múltipla/imunologia , Neuromielite Óptica/sangue , Neuromielite Óptica/classificação , Neuromielite Óptica/imunologiaRESUMO
BACKGROUND: Longitudinally extensive transverse myelitis (LETM) is a characteristic manifestation of neuromyelitis optica (NMO). However, not all patients with LETM are positive for aquaporin-4 (AQP4) antibodies. We evaluated the characteristics of idiopathic isolated LETM negative for AQP4 antibodies. METHODS: From the National Cancer Center registry of inflammatory diseases of the central nervous system, patients with LETM as an initial manifestation and follow-up for at least two years were enrolled. Their medical records and MRIs were reviewed retrospectively. AQP4 antibody was confirmed by three different validated methods at least three times. Cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) levels were measured to investigate astrocyte damage. RESULTS: Among 108 patients with first-ever LETM, 55 were positive for AQP4 antibodies (P-LETM) and 53 were consistently negative. Of them, seven were later diagnosed with seronegative NMO, and four were positive for MOG antibodies. The remaining 42 patients (N-LETM) showed several features distinct from P-LETM: male predominance, older age of onset, milder clinical presentation, spinal cord confinement and absence of combined autoimmunity. CSF GFAP levels were not increased in N-LETM but were markedly elevated in P-LETM. CONCLUSIONS: Idiopathic isolated N-LETM is not that rare among first-ever LETM, and has many features distinct from P-LETM where astrocytic damage is evident.
Assuntos
Aquaporina 4/imunologia , Mielite Transversa/sangue , Mielite Transversa/fisiopatologia , Sistema de Registros , Adolescente , Adulto , Idade de Início , Autoanticorpos/sangue , Feminino , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/imunologia , Mielite Transversa/líquido cefalorraquidiano , Mielite Transversa/classificação , Fatores Sexuais , Adulto JovemRESUMO
We report a patient with neuromyelitis optica (NMO) presenting anti-myelin-oligodendrocyte glycoprotein (MOG)-seropositive, in whom biomarkers of demyelination and astrocyte damage were measured during an acute attack. A 31-year-old man developed right optic neuritis followed by longitudinally extensive transverse myelitis, fulfilling the criteria for definite NMO. He was anti-MOG-seropositive and anti-aquaporin-4 seronegative. The myelin basic protein level was markedly elevated whereas glial fibrillary acidic protein was not detectable in cerebrospinal fluid during an acute attack. His symptoms quickly improved after high-dose methylprednisolone therapy. This case suggests that NMO patients with anti-MOG may have severe demyelination in the absence of astrocyte injury.
Assuntos
Anticorpos Bloqueadores/uso terapêutico , Astrócitos/patologia , Doenças Desmielinizantes/patologia , Glicoproteína Mielina-Oligodendrócito/antagonistas & inibidores , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/patologia , Neuromielite Óptica/terapia , Adulto , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Metilprednisolona/uso terapêutico , Mielite Transversa/complicações , Fármacos Neuroprotetores/uso terapêuticoRESUMO
BACKGROUND: Association of leukoencephalopathy and atypical mycobacteriosis has been rarely reported. We present a case that is relevant for its unusual presentation and because it may shed further light on the pathogenic mechanisms underlying reversible encephalopathies. CASE REPORT: We report the case of a Hispanic 64-year-old woman with cognitive decline and extensive leukoencephalopathy. Magnetic resonance imaging revealed white-matter lesions with increased water diffusivity, without blood-brain-barrier disruption. Brain biopsy showed tissue rarefaction with vacuolation, mild inflammation, few reactive astrocytes and decreased aquaporin water-channel expression in the lesions. Six months later, she was diagnosed with atypical mycobacterial pulmonary infection. Brain lesions resolved after antimycobacterial treatment. CONCLUSION: We hypothesize leukoencephalopathic changes and vasogenic edema were associated with decreased aquaporin expression. Further studies should clarify if reversible leukoencephalopathy has a causal relationship with decreased aquaporin expression and atypical mycobacterial infection, and mechanisms underlying leukoencephalopathy resolution after antimycobacterial treatment. This article may contribute to the understanding of pathogenic mechanisms underlying magnetic resonance imaging subcortical lesions and edema, which remain incompletely understood.
Assuntos
Leucoencefalopatias/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Antibacterianos/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Feminino , Humanos , Leucoencefalopatias/etiologia , Leucoencefalopatias/patologia , Pneumopatias/diagnóstico , Pneumopatias/microbiologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Micobactérias não Tuberculosas , Substância Branca/patologiaRESUMO
A 44-year-old man presented with severe right visual loss. The right fundus examination showed marked optic disc oedema associated with partial macular star. Serological blood tests for infectious agents were all negative. Serum aquaporin-4 antibody was negative but anti-MOG (myelin oligodendrocyte glycoprotein) was positive. Magnetic resonance revealed extensive lesion in right optic nerve. There was no visual improvement after intravenous therapy. Patient had no further attacks after follow-up. Optic disc oedema with macular star is found in several infectious and non-inflammatory disorders, but it has not been reported in optic neuritis (ON) associated with autoantibodies to myelin oligodendrocyte glycoprotein (anti-MOG).
RESUMO
Two patients with longitudinally extensive myelopathy were initially biopsied for suspected spinal cord tumors. Both patients were later diagnosed with neuromyelitis optica spectrum disorders (NMOSD) supported by their AQP4-seropositivity. Pathological review of both biopsies revealed demyelinated lesions with thickened vessel walls and tissue rarefaction. Immunohistochemical staining demonstrated findings compatible with acute NMOSD lesions in one case while the other case exhibited findings consistent with chronic NMOSD lesions. A pre-biopsy differential diagnosis of longitudinally extensive spinal cord tumors should include NMOSD. Specific biopsy features, such as cystic changes with vascular wall thickening and astrocyte injury, should raise suspicion for NMOSD.
Assuntos
Aquaporina 4/imunologia , Autoanticorpos/análise , Neuromielite Óptica/imunologia , Neoplasias da Medula Espinal/patologia , Medula Espinal/imunologia , Adolescente , Biomarcadores/análise , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/patologia , Valor Preditivo dos Testes , Medula Espinal/patologiaRESUMO
BACKGROUND: Myelin-oligodendrocyte glycoprotein antibody (MOG antibodies) was found in various demyelinated diseases. This is the first report of a patient with longitudinally extensive transverse myelitis with an extremely high titer of MOG antibodies after an influenza infection. This case supports the view that MOG antibodies are linked to longitudinally extensive transverse myelitis and that influenza infection might trigger the MOG antibodies. CASE PRESENTATION: A 32-year-old healthy male developed high fever, dysesthesia and paraesthesia below the C2 area, muscle weakness of the bilateral lower extremities, and urinary retention ten days after an influenza type A infection. Magnetic resonance imaging revealed a longitudinal lesion in the spinal cord extending from C2 to the spinal conus. There were no lesions in the brain or optic nerves. Established cell-based immunoassays revealed that he was positive for MOG antibodies (titer = 65,536) and negative for anti-aquaporin 4 antibodies (AQP4 antibodies). He fully recovered after steroid pulse therapy followed by 60 mg prednisolone. CONCLUSION: This is the first report of influenza A-associated longitudinally extensive transverse myelitis with a high titer anti-MOG antibodies. Our case report supports a relationship between anti-MOG antibodies and longitudinally extensive transverse myelitis, which was triggered by influenza infection. Further studies are needed to establish the clinical significance of anti-MOG antibodies for diagnosis, treatment, and prognosis.
Assuntos
Vírus da Influenza A/patogenicidade , Influenza Humana/complicações , Glicoproteína Mielina-Oligodendrócito/imunologia , Mielite Transversa/imunologia , Adulto , Autoanticorpos , Humanos , Masculino , Mielite Transversa/etiologiaRESUMO
Therapeutic plasma exchange (TPE) can improve disability recovery after neuromyelitis optica spectrum disease (NMOSD) attacks, but its effectiveness and safety in Latin-American patients with access barriers and diverse ethnicity is underexplored. We carried out a retrospective cohort study with NMOSD patients that underwent TPE. 84 NMOSD attacks in 68 patients were evaluated. Despite a median 25-day delay from symptom onset to TPE, 65,5% of patients showed significant improvement. Adverse events occurred in 39% of patients, usually transitory and with no fatalities.