Brazilian consensus recommendations on the diagnosis and treatment of autoimmune encephalitis in the adult and pediatric populations.

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.

A wide spectrum of neurological manifestations in pediatrics patients with the COVID-19 infection: a case series.

Neurological symptoms in COVID-19 patients can also be found in the pediatric population, but they are usually described as mild symptoms. Herein, we described a case series of four pediatric patients with severe and highly heterogeneous central and peripheral nervous system manifestations. The objective was to report neurological manifestations of COVID-19 in children and adolescents. The design is case series. The participants are four children and adolescents with confirmed COVID-19. The main outcome and measures are as follows: Clinical data were gathered from electronic medical records, and data of all neurologic symptoms were checked by a trained neurologist. We reported four pediatric patients with COVID-19 and different neurologic symptoms. Case 1 was a 16-year-old girl with a sensory and motor polyradiculopathy with RT-qPCR for COVID-19 and dengue both detected in CSF that improved after appropriate treatment. Case 2 was a 15-year-old boy with Guillain-Barre syndrome and had good response after using human immunoglobulin. Case 3 was a 5-year-old girl with acute intracranial hypertension that improved after going through lumbar puncture and using acetazolamide. Case 4 was a 2-month-old male infant with focal epileptic seizures that recovered after antiepileptic treatment. We highlight the need to consider different neurologic manifestations as part of the COVID-19 clinical spectrum.

Electrical status epilepticus during sleep in patients with congenital Zika virus syndrome: An unprecedented clinical finding.

BACKGROUND: Brazil experienced a disproportionately higher rate of microcephaly cases in November 2015 with evidence of a causal link with Zika virus (ZIKV) infections during pregnancy. Epilepsy is a major neurological feature seen as part of congenital Zika virus syndrome (CZVS). Different seizure types and electroencephalographic (EEG) abnormalities have been described in association with this syndrome. However, clinical and neurophysiological features of epilepsy seen in children with CZVS are not fully understood. METHODS: We evaluated children with CZVS showing an EEG pattern of electrical status epilepticus during slow-wave sleep (ESES). Information on gender, age of onset of seizures, head circumference at birth, gross motor function at the time of diagnosis, of clinical and EEG aspects of seizures, EEG features and response to drug treatment was assessed. RESULTS: Our case series included four patients. They were diagnosed with epilepsy between one month to 18 months of age and showed an ESES pattern at the age of three. They presented with a wide range of epileptic symptoms, but all experienced tonic seizures. Multiple drug treatment was the management approach for three patients; however, they showed poor response to treatment with conventional drugs used in the treatment of ESES. CONCLUSIONS: Children with CZVS may develop an EEG pattern of ESES. Clinicians and neurologists should be aware of this neurological presentation to improve the management of these patients.

Clinical Features and Inflammatory Markers in Autoimmune Encephalitis Associated With Antibodies Against Neuronal Surface in Brazilian Patients.

Acute encephalitis is a debilitating neurological disorder associated with brain inflammation and rapidly progressive encephalopathy. Autoimmune encephalitis (AE) is increasingly recognized as one of the most frequent causes of encephalitis, however signs of inflammation are not always present at the onset which may delay the diagnosis. We retrospectively assessed patients with AE associated with antibodies against neuronal surface diagnosed in reference centers in Northeast of Brazil between 2014 to 2017. CNS inflammatory markers were defined as altered CSF (pleocytosis >5 cells/mm3) and/or any brain parenchymal MRI signal abnormality. Thirteen patients were evaluated, anti-NMDAR was the most common antibody found (10/13, 77%), followed by anti-LGI1 (2/13, 15%), and anti-AMPAR (1/13, 7%). Median time to diagnosis was 4 months (range 2-9 months). Among these 13 patients, 6 (46.1%) had inflammatory markers and when compared to those who did not present signs of inflammation, there were no significant differences regarding the age of onset, time to diagnosis and modified Rankin scale score at the last visit. Most of the patients presented partial or complete response to immunotherapy during follow-up. Our findings suggest that the presence of inflammatory markers may not correlate with clinical presentation or prognosis in patients with AE associated with antibodies against neuronal surface. Neurologists should be aware to recognize clinical features of AE and promptly request antibody testing even without evidence of inflammation in CSF or MRI studies.

Prevalência de doenças autoimunes em pacientes com síndrome de Down / Prevalence of autoimmune diseases in Down syndrome patients

Introdução: Diversas doenças podem acometer pacientes com síndrome de Down (SD), dentre elas as doenças autoimunes (DAI). Quando comparados à população geral, pacientes com SD apresentam maior risco para desenvolvimento de DAI. O objetivo do estudo foi avaliar a prevalência de DAI em pacientes com SD. Métodos: Estudo retrospectivo. Foram avaliados prontuários de 71 pacientes atendidos no ambulatório universitário de SD. Foram pesquisadas: tireoidite de Hashimoto (TH), doença de Graves (DG), doença Celíaca (DC), alopecia areata (AA), vitiligo, leucemia e diabetes mellitus tipo I (DMI). Diagnóstico de TH foi considerado quando T4 livre normal ou baixo, TSH elevado, presença de anticorpos antitireoideanos e ultrassonografia de tireoide compatível com TH. Diagnóstico de DG foi considerado quando T4 livre normal ou elevado, TSH suprimido e anticorpo antirreceptor de TSH positivo. A DC foi diagnosticada quando anticorpo antendomísio IgA positivo e biópsia intestinal compatível com DC. AA e vitiligo foram considerados quando presença de lesão de pele diagnosticada por dermatologista. Alterações no hemograma e biópsia de medula óssea foram considerados para diagnóstico de leucemia e hiperglicemia com anticorpo anti-GAD positivo foram considerados para DMI. Resultados: A prevalência de DAI foi 18,3%. TH foi encontrado em 6 pacientes; DG em 2 pacientes; DC em 4 pacientes; AA em 2 pacientes; vitiligo em 1 paciente e leucemia em 1 paciente. Nenhum paciente apresentou DMI. Conclusão: A prevalência de DAI neste estudo foi maior comparado à prevalência de DAI na população em geral. Recomenda-se rastreio regular destas doenças nos pacientes com SD.

Introduction: Several diseases can affect patients with Down syndrome (DS), among them autoimmune diseases (AID). As compared to the general population, patients with DS are at increased risk for development of AID. The aim of this study was to evaluate the prevalence of AID in patients with DS. Methods: A retrospective study. We analyzed the records of 71 patients treated in a university outpatient unit of DS. We surveyed for Hashimoto’s thyroiditis (HT), Graves’ disease (GD), celiac disease (CD), alopecia areata (AA), vitiligo, leukemia and diabetes mellitus type I (DMI). Diagnosis of HT was considered when free T4 was normal or low, TSH was high, presence of anti-thyroid antibodies, and thyroid ultrasound compatible with TH. GD was diagnosed when free T4 was normal or elevated, TSH was suppressed, and anti-TSH receptor was positive. CD was diagnosed when anti-endomysium IgA was positive and intestinal biopsy was compatible with CD. AA and vitiligo were considered in the presence of skin lesions diagnosed by a dermatologist. Changes in blood count and bone marrow biopsy were considered for diagnosis of leukemia, and hyperglycemia with positive anti-GAD were considered for DMI. Results: The prevalence of AID was 18.3%. HT was found in 6 patients, DG in 2, DC on 4, AA in 2, vitiligo in one, and leukemia in one patient. No patient had DMI. Conclusion: The prevalence of AID in this study was greater than in the general population. Regular screening of these diseases in patients with DS is recommended.