RESUMO
BACKGROUND: Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis. OBJECTIVE: With the support of the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN) and the Brazilian Society of Child Neurology (Sociedade Brasileira de Neurologia Infantil, SBNI), a consensus on the diagnosis and treatment of AIE in Brazil was developed using the Delphi method. METHODS: A total of 25 panelists, including adult and child neurologists, participated in the study. RESULTS: The panelists agreed that patients fulfilling criteria for possible AIE should be screened for antineuronal antibodies in the serum and cerebrospinal fluid (CSF) using the tissue-based assay (TBA) and cell-based assay (CBA) techniques. Children should also be screened for anti-myelin oligodendrocyte glucoprotein antibodies (anti-MOG). Treatment should be started within the first 4 weeks of symptoms. The first-line option is methylprednisolone plus intravenous immunoglobulin (IVIG) or plasmapheresis, the second-line includes rituximab and/or cyclophosphamide, while third-line treatment options are bortezomib and tocilizumab. Most seizures in AIE are symptomatic, and antiseizure medications may be weaned after the acute stage. In anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the panelists have agreed that oral immunosuppressant agents should not be used. Patients should be evaluated at the acute and postacute stages using functional and cognitive scales, such as the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Modified Rankin Scale (mRS), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CONCLUSION: The present study provides tangible evidence for the effective management of AIE patients within the Brazilian healthcare system.
ANTECEDENTES: Encefalites autoimunes (EAIs) são um grupo de doenças inflamatórias caracterizadas pela presença de anticorpos contra antígenos neuronais e gliais, que ocasionam sintomas psiquiátricos subagudos, queixas de memória e distúrbios anormais do movimento. A maioria dos pacientes é jovem, e o atraso no tratamento está associado a pior prognóstico. OBJETIVO: Com o apoio da Academia Brasileira de Neurologia (ABN) e da Sociedade Brasileira de Neurologia Infantil (SBNI), desenvolvemos um consenso sobre o diagnóstico e o tratamento da EAIs no Brasil utilizando a metodologia Delphi. MéTODOS: Um total de 25 especialistas, incluindo neurologistas e neurologistas infantis, foram convidados a participar. RESULTADOS: Os especialistas concordaram que os pacientes com critérios de possíveis EAIs devem ser submetidos ao rastreio de anticorpos antineuronais no soro e no líquido cefalorraquidiano (LCR) por meio das técnicas de ensaio baseado em tecidos (tissue-based assay, TBA, em inglês) e ensaio baseado em células (cell-based assay, CBA, em inglês). As crianças também devem ser submetidas ao rastreio de de anticorpo contra a glicoproteína da mielina de oligodendrócitos (anti-myelin oligodendrocyte glycoprotein, anti-MOG, em inglês). O tratamento deve ser iniciado dentro das primeiras 4 semanas dos sintomas, sendo as opções de primeira linha metilprednisolona combinada com imunoglobulina intravenosa (IGIV) ou plasmaférese. O tratamento de segunda linha inclui rituximabe e ciclofosfamida. Bortezomib e tocilizumab são opções de tratamento de terceira linha. A maioria das crises epilépticas nas EAIs são sintomáticas, e os fármacos anticrise podem ser desmamadas após a fase aguda. Em relação à encefalite antirreceptor de N-metil-D-aspartato (anti-N-methyl-D-aspartate receptor, anti-NMDAR, em inglês), os especialistas concordaram que agentes imunossupressores orais não devem ser usados. Os pacientes devem ser avaliados na fase aguda e pós-aguda mediante escalas funcionais e cognitivas, como Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Modified Rankin Scale (mRS), e Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CONCLUSãO: Esta pesquisa oferece evidências tangíveis do manejo efetivo de pacientes com EAIs no sistema de saúde Brasileiro.
Assuntos
Consenso , Encefalite , Humanos , Encefalite/diagnóstico , Encefalite/terapia , Encefalite/imunologia , Brasil , Criança , Adulto , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/terapia , Técnica Delphi , Autoanticorpos/sangueRESUMO
BACKGROUND: Autoimmune encephalitis (AE) consists of a group of acquired diseases that affect the central nervous system. A myriad of phenotypes may be present at the onset. Due to the heterogeneity of clinical presentations, it is difficult to achieve uniformity for the diagnostic and therapeutic processes and follow-up strategies. OBJECTIVE: To describe a series of patients diagnosed with AE in a resource-limited public hospital in southern Brazil and to analyze therapeutics and outcomes. METHODS: We retrospectively reviewed the electronic medical records of patients diagnosed with AE at the Hospital de Clínicas de Porto Alegre from 2014 to 2022. Data collected included clinical presentation, neuroimaging, cerebrospinal fluid testings, electroencephalogram, autoantibodies, treatments, outcomes, follow-up time, degree of neurological impairment, and mortality. RESULTS: Data from 17 patients were retrieved. Eleven cases were classified as definite AE and 6 as possible AE. Autoantibodies were identified in 9 patients. Timing for diagnosis was impacted by the high costs associated with autoantibody testing. Most patients became functionally dependent (82.4%) and most survivors remained with autoimmune-associated epilepsy (75%). Five patients died during hospitalization, and one after a 26-month of follow-up. CONCLUSION: In this resource-limited hospital, patients with AE had a worse clinical outcome than that previously described in the literature. Development of epilepsy during follow-up and mortality were greater, whilst functional outcome was inferior. Autoantibody testing was initially denied in most patients, which impacted the definitive diagnosis and the use of second-line therapies.
ANTECEDENTES: A encefalite autoimune (EA) consiste em um grupo de doenças adquiridas que afetam o sistema nervoso central. OBJETIVO: Descrever uma série de pacientes diagnosticados com EA em um contexto de atenção terciária à saúde com recursos limitados e analisar a terapêutica e os resultados. MéTODOS: Revisamos retrospectivamente os prontuários eletrônicos de pacientes diagnosticados com EA no Hospital de Clínicas de Porto Alegre de 2014 a 2022. Os dados coletados incluíram apresentação clínica, neuroimagem, exames de líquido cefalorraquidiano, eletroencefalograma, autoanticorpos, tratamentos, resultados, tempo de acompanhamento, grau de comprometimento neurológico e mortalidade. RESULTADOS: Dados de 17 pacientes foram coletados. Onze casos foram classificados como EA definitivo e seis como EA possível. Autoanticorpos foram identificados em nove pacientes. O tempo para o diagnóstico foi afetado pelos altos custos associados ao teste de autoanticorpos. A maioria dos pacientes tornou-se funcionalmente dependente (82,4%), e a maioria dos sobreviventes permaneceu com epilepsia autoimune associada (75%). Cinco pacientes faleceram durante a internação, e um após 26 meses de seguimento. CONCLUSãO: No hospital em questão, os pacientes com EA tiveram um desfecho clínico pior do que o previamente descrito na literatura. O desenvolvimento de epilepsia durante o acompanhamento e a mortalidade foram maiores, enquanto o desfecho funcional foi inferior. Os testes de autoanticorpos foram inicialmente negados para a maioria dos pacientes, o que impactou o diagnóstico definitivo e o uso de terapias de segunda linha.
Assuntos
Doenças Autoimunes do Sistema Nervoso , Encefalite , Epilepsia , Doença de Hashimoto , Humanos , Estudos Retrospectivos , Saúde Pública , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/terapia , AutoanticorposRESUMO
A number of studies have shown that oxidative stress is related to the pathogenesis of several immunological diseases, such as Hashimoto's thyroiditis (HT), although there is no plausible mechanism to explain it. Thus, we aimed at hypothesizing and providing some possible mechanisms linking oxidative stress to autoimmunity aspects and its implications for HT, as well as adjuvant therapeutic proposals to mitigate the deleterious effects. Our hypothesis is that deficient eating habits, autoimmune regulator gene predisposing gene, dysbiosis and molecular mimicry, unfolded proteins and stress in the endoplasmic reticulum, and thymus involution appear to be the main potential factors leading to HT oxidative stress. Likewise, we show that the use of minerals selenium and zinc, vitamins D and C, as well as probiotics, can be interesting adjuvant therapies for the control of oxidative damage and poor prognosis of HT. Further clinical trials are needed to understand the real beneficial and side effects of these supplements.
Assuntos
Doença de Hashimoto , Humanos , Doença de Hashimoto/terapia , Doença de Hashimoto/patologia , Estresse Oxidativo , Suplementos NutricionaisRESUMO
Autoimmune encephalitis (AE) comprises a group of diseases mediated by antibodies against neuronal cell surface or synaptic antigens, such as ion channels or neurotransmitter receptors. New clinical syndromes and their associated antibodies were and are still being characterized over the last two decades. The fact that their main clinical features are interdisciplinary, - encompassing neuropsychiatric symptoms, cognitive dysfunction, epileptic seizures, movement and sleep disorders - has led to a surge of interest in this field. Some of these diseases present with a well-defined syndrome, being recognizable on clinical grounds. Correct diagnosis is important since AE are potentially treatable diseases, despite their severity. On the other hand, an increasing number of neuronal antibodies being described casts doubt upon the way we should utilize antibody testing and interpret results. In this article we review, summarize and update the current knowledge on antibody mediated encephalitis.
Assuntos
Encefalite , Epilepsia , Doença de Hashimoto , Autoanticorpos , Encefalite/diagnóstico , Encefalite/terapia , Epilepsia/diagnóstico , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/terapia , Humanos , Convulsões/diagnósticoRESUMO
AIM: Rheumatic manifestations are common in patients with Hashimoto's thyroiditis (HT). Since previous reports on the prevalence of arthritis in this disease may have a rheumatology referral bias, we sought to establish the prevalence of undifferentiated inflammatory arthropathy (UIA) in unselected HT patients as seen in an endocrinology clinic. METHODS: Cross-sectional study of 92 consecutive HT patients and no definite rheumatic disease from the Endocrinology Division, Hospital Universitario de Caracas diagnosed by the presence of anti-thyroid peroxidase antibodies (n = 68) or typical ultrasonographic findings (n = 24). Undifferentiated inflammatory arthropathy was defined as combination of morning stiffness and joint pain with ≥2 characteristics of inflammatory joint pain. The study was revised and approved by the Ethics Committee of our hospital and all patients signed an informed consent form. RESULTS: Twenty-three patients (25%; 95% CI 16-34) met the criteria for UIA. Joints most commonly affected were the knees, hands and ankles and the most common pattern was oligoarticular (82.6%). In the multivariate analysis, variables associated to the presence of UIA were the presence of myalgia (odds ratio [OR] = 19.41; 95% CI = 2.38-158.38) and Raynaud's phenomenon (OR = 4.32; 95% CI = 1.01-18.60). No association was found with demographics, duration of disease, comorbidities or thyroid function status. CONCLUSIONS: Almost 1 in 4 patients with HT had no definite rheumatic disease present with UIA. An early identification of concurrent arthritis in HT patients is necessary for thorough differential diagnosis and prompt treatment initiation to halt potential joint damage and disability.
Assuntos
Artrite/epidemiologia , Endocrinologia , Doença de Hashimoto/epidemiologia , Ambulatório Hospitalar , Adulto , Artrite/diagnóstico , Artrite/imunologia , Artrite/terapia , Estudos Transversais , Feminino , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Doença de Hashimoto/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Venezuela/epidemiologiaRESUMO
The disorders of the central nervous system associated with cancer by remote immune-mediated mechanisms are a heterogeneous group. These disorders encompass the classic paraneoplastic disorders and the recently recognized autoimmune encephalitis associated with antibodies against neuronal cell surface or synaptic proteins that occur with or without cancer association. In the last decade, the new surge of interest in neuronal diseases associated with anti-neuronal antibodies led to the rapid discovery of new forms of disease that have different manifestations and were not previously suspected to be immune mediated. The recognition of these syndromes is important because it may lead to early detection of an underlying malignancy and prompt initiation of treatment, improving chances for a better outcome.
Assuntos
Doenças do Sistema Nervoso Central/sangue , Encefalite/sangue , Doença de Hashimoto/sangue , Síndromes Paraneoplásicas do Sistema Nervoso/sangue , Anticorpos/sangue , Doenças do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso Central/patologia , Doenças do Sistema Nervoso Central/terapia , Detecção Precoce de Câncer , Encefalite/complicações , Encefalite/patologia , Encefalite/terapia , Doença de Hashimoto/complicações , Doença de Hashimoto/patologia , Doença de Hashimoto/terapia , Humanos , Neurônios/metabolismo , Neurônios/patologia , Síndromes Paraneoplásicas do Sistema Nervoso/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/patologia , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Sinapses/metabolismo , Sinapses/patologiaRESUMO
Hashimoto's encephalopathy is a rare disease, with a reported prevalence of 2.1 per 100 000. Clinical manifestations include confusion, decreased state of consciousness, cognitive deficit, seizures, myoclonus, ataxia, and focal neurological deficits. Due to the wide variety of signs and symptoms, clinical diagnostic suspicion is essential. Diagnosis is based on three pillars: the presence of neurological clinical manifestations after ruling out other causes of encephalopathy. 2) Presence of increased antithyroid antibodies. 3) Significant clinical improvement after the administration of immunomodulation. The treatment of Hashimoto's encephalopathy pursues two objectives: to control the autoimmune process and to control the complications of the disease. Although in most cases recovery is complete with treatment, the risk of relapse can range from 12.5 to 40% in follow-ups to 2 years.
La encefalopatía de Hashimoto es una enfermedad rara. Se reporta una prevalencia de 2,1 por cada 100 000 habitantes. Entre las manifestaciones clínicas se describen confusión, disminución del estado de consciencia, déficit cognitivo, convulsiones, mioclonus, ataxia y/o déficits neurológicos focales. Debido a la amplia variedad de signos y síntomas, la sospecha clínica diagnóstica es fundamental. El diagnóstico se basa en tres pilares: la presencia de manifestaciones clínicas neurológicas, con la exclusión de otras causas de encefalopatía; presencia de anticuerpos antitiroideos aumentados; una mejoría clínica notable luego de la administración de inmunomoduladores. El tratamiento de la encefalopatía de Hashimoto tiene dos objetivos: controlar el proceso autoinmune y controlar las complicaciones de la enfermedad. Aunque en la mayoría de los casos la recuperación es completa con el tratamiento, el riesgo de recaídas puede oscilar entre 12,5 a 40% en seguimientos a dos años.
Assuntos
Autoanticorpos/imunologia , Encefalite/terapia , Doença de Hashimoto/terapia , Fatores Imunológicos/uso terapêutico , Encefalite/diagnóstico , Encefalite/fisiopatologia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/fisiopatologia , Humanos , Recidiva , Resultado do TratamentoRESUMO
Autoimmune encephalitis are one of the emergent causes of subacute changes in the level of consciousness, behavior, cognitive impairment and seizures, mainly in young people. They are a consequence of inflammation or dysfunction of parts of the brain caused by antibodies against specific brain antigens, usually located in the limbic system, resulting in clinical presentation as a limbic encephalitis. The objectives of this article are to show the clinical presentation, complementary studies and treatment of this entity, considering that the patient's prognostic depends on a high level of clinical suspicion, and on an early initiation of immunosuppressive therapy. We did a nonsystematic review of the literature on autoimmune encephalitis between 2005 and 2017. We conclude that the prevalence of autoimmune encephalitis is increasing, even surpassing infectious causes of encephalitis in developed countries. Clinical presentation includes sub-acute cognitive and behavioral impairment, with or without alterations in consciousness and seizures. Fever and inflammation of the cerebrospinal fluid are less common than in the infectious causes but psychiatric symptoms are more frequent. There are specific clinical presentations according to the particular type of antigen/antibody present, which also determines the association with cancer, constituting a paraneoplastic syndrome only in some cases. Immunosuppressive therapy has been standardized in steps, and should be initiated early to improve prognosis.
Assuntos
Encefalite , Doença de Hashimoto , Diagnóstico Diferencial , Encefalite/classificação , Encefalite/diagnóstico , Encefalite/terapia , Doença de Hashimoto/classificação , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/terapia , HumanosRESUMO
Autoimmune encephalitis are one of the emergent causes of subacute changes in the level of consciousness, behavior, cognitive impairment and seizures, mainly in young people. They are a consequence of inflammation or dysfunction of parts of the brain caused by antibodies against specific brain antigens, usually located in the limbic system, resulting in clinical presentation as a limbic encephalitis. The objectives of this article are to show the clinical presentation, complementary studies and treatment of this entity, considering that the patient's prognostic depends on a high level of clinical suspicion, and on an early initiation of immunosuppressive therapy. We did a nonsystematic review of the literature on autoimmune encephalitis between 2005 and 2017. We conclude that the prevalence of autoimmune encephalitis is increasing, even surpassing infectious causes of encephalitis in developed countries. Clinical presentation includes sub-acute cognitive and behavioral impairment, with or without alterations in consciousness and seizures. Fever and inflammation of the cerebrospinal fluid are less common than in the infectious causes but psychiatric symptoms are more frequent. There are specific clinical presentations according to the particular type of antigen/antibody present, which also determines the association with cancer, constituting a paraneoplastic syndrome only in some cases. Immunosuppressive therapy has been standardized in steps, and should be initiated early to improve prognosis.