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.

Rabies virus circulation in a highly diverse bat assemblage from a high-risk area for zoonoses outbreaks in the Brazilian Amazon.

Bats are the second most diverse order of mammals and play a central role in ecosystem dynamics. They are also important reservoirs of potentially zoonotic microorganisms, of which rabies virus is the most lethal among the bat-transmitted zoonotic pathogens. Importantly, recent outbreaks of human rabies have been reported from the Brazilian Amazon. Here we present a survey of bat species and rabies virus (RABV) circulation in a bat assemblage in the Marajó region, northern Brazil. Using data from mist-net captures and bioacoustic sampling, 56 bat species were recorded along the Jacundá River basin over a 10-day expedition in November 2022. For the investigation of RABV, we used the direct fluorescent antibody test (DFAT) and the rapid fluorescent focus inhibition test (RFFIT). In total, 159 bat individuals from 22 species were investigated for RABV. Five adults of the common vampire bat, Desmodus rotundus, showed RABV-specific antibodies in serum samples. Additionally, we report on local residents with injuries caused by D. rotundus bites and the occurrence of colonies of non-hematophagous bats from different species roosting inside human residences. This scenario raises concerns about the risks of new cases of human rabies and other zoonotic diseases associated with bats in the region and highlights the need for epidemiological surveillance and mitigation measures to prevent outbreaks of emerging infectious diseases.

When dissident bodies proclaim their places as dissonant bodies. / Quando corpos dissidentes proclamam seus lugares como corpos diz-sonantes.

This essay aims to present the concept of dissonant bodies and give visibility to these bodies in the field of public health from anti-colonial and queer perspectives. These bodies are often considered dissidents. Their existence is considered abject, disposable, and marginalized by neoliberal and necropolitical society. It is presented as another possibility in the face of the logic and political strategies of hegemonic reproduction of capital-life and health policies. It debates tensions of new possibilities and alternatives of other modes of existence and inclusive worlds, in which all lives are considered, in their singularities and differences, radically equal in the validation of their ways of living.

O objetivo deste ensaio é apresentar o conceito de corpos diz-sonantes e dar visibilidade a esses corpos no campo da saúde coletiva, a partir de perspectivas anti-coloniais e queers. São corpos muitas vezes considerados dissidentes, cujas existências consideradas abjetas, descartáveis e marginalizadas, pela sociedade neoliberal e necropolítica são apresentadas como outras possibilidades frente às lógicas e estratégias políticas de reprodução hegemônica da vida-capital e nas políticas de saúde. Debate tensionamentos de novas possibilidades e alternativas de modos outros de existências e de mundos inclusivos, em que todas as vidas sejam consideradas, em suas singularidades e diferenças, radicalmente iguais na validação dos seus modos de viver.

Phenotypic/Genotypic Profile of Children with Neuronal Ceroid Lipofuscinosis in Southern Brazil.

INTRODUCTION: Neuronal ceroid lipofuscinoses (CLNs) are a group of lysosomal storage disorders of genetic origin, characterized by progressive neurodegeneration and intracellular accumulation of autofluorescent lipopigment. Thirteen genes related to CLNs are currently described, showing genetic and allelic heterogeneity, most of them with an autosomal recessive pattern. Due to the few descriptions of cases related to CLNs in Brazil, it is necessary to describe the phenotypic and genotypic characteristics of these patients. This study aims to evaluate the genotypic profile and correlate it with the phenotypic characteristics of patients with CLN in a children's hospital. METHODS: This study was performed as a descriptive cross-sectional study with analysis of medical records, imaging, and laboratory tests of patients who had a confirmed molecular diagnosis of CLN. RESULTS: The sample consisted of 11 patients from nine families with different subtypes of CLNs (CLN2, 5, 6, 7, and 8), with CLN2 being the most prevalent in the study. A total of 16 mutation variants were identified in genes associated with the five CLNs described in this study, with typical and atypical clinical phenotypes depending on the subtype and its variants. CONCLUSION: Novel mutations identified in the patients in this study showed phenotypes of rapid and severe progression in the CLN2 patient and similar characteristics in CLN6 and CLN7 patients, as previously described in the literature.

Neurodevelopmental disorder associated with gene ARF3: A case report.

We present a case study of a patient exhibiting acquired microcephaly along with global developmental delay and drug-resistant epilepsy. Brain magnetic resonance imaging revealed distinctive features, including a Z-shaped morphology of the brainstem, volumetric reduction of white matter, diffuse thinning of the corpus callosum, and partial fusion of the cerebellar hemispheres at their most cranial portion. Whole-exome sequencing uncovered a pathogenic variant in the ARF3 gene c.200A>T, p.(Asp67Val). The neurodevelopmental disorder associated with the ARF3 gene is exceptionally rare, with only two previously documented cases in the literature. This disorder is characterized by global developmental delay and brain malformations, particularly affecting the white matter, cerebellum, and brainstem. It can also manifest as acquired microcephaly and epilepsy. These phenotypic characteristics align with Golgipathies, underscoring the significance of considering this group of conditions in relevant clinical contexts. In cases where a Z-shaped morphology of the brainstem is observed, ARF3-associated disorder should be included in the list of differential diagnoses.

Effects of superparamagnetic iron oxide nanoparticles (SPIONS) testicular injection on Leydig cell function and sperm production in a murine model.

In the domain of medical advancement, nanotechnology plays a pivotal role, especially in the synthesis of biocompatible materials for therapeutic use. Superparamagnetic Iron Oxide Nanoparticles (SPIONs), known for their magnetic properties and low toxicity, stand at the forefront of this innovation. This study explored the reproductive toxicological effects of Sodium Citrate-functionalized SPIONs (Cit_SPIONs) in adult male mice, an area of research that holds significant potential yet remains largely unknown. Our findings reveal that Cit_SPIONs induce notable morphological changes in interstitial cells and the seminiferous epithelium when introduced via intratesticular injection. This observation is critical in understanding the interactions of nanomaterials within reproductive biological systems. A striking feature of this study is the rapid localization of Cit_SPIONs in Leydig cells post-injection, a factor that appears to be closely linked with the observed decrease in steroidogenic activity and testosterone levels. This data suggests a possible application in developing nanostructured therapies targeting androgen-related processes. Over 56 days, these nanoparticles exhibited remarkable biological distribution in testis parenchyma, infiltrating various cells within the tubular and intertubular compartments. While the duration of spermatogenesis remained unchanged, there were many Tunel-positive germ cells, a notable reduction in daily sperm production, and reduced progressive sperm motility in the treated group. These insights not only shed light on the intricate mechanisms of Cit_SPIONs interaction with the male reproductive system but also highlight the potential of nanotechnology in developing advanced biomedical applications.

Characteristics of Opsoclonus-Myoclonus Syndrome in Patients of the Largest Pediatric Hospital in Latin America.

BACKGROUND: Opsoclonus-myoclonus syndrome (OMS) is a rare neuroinflammatory disorder characterized by ataxia, opsoclonus, and myoclonus. Clinical diagnosis of OMS has been challenging; therefore, we sought to determine the clinical and treatment profiles of patients with OMS at the largest pediatric hospital in Latin America. METHODS: We analyzed the data of patients diagnosed with OMS between 2010 and 2020 at Pequeno Principe Hospital (Brazil) to determine the corresponding clinical profile more accurately. RESULTS: Of the approximately 50,000 visitors to our pediatric neurology department from 2010 to 2020, 10 patients with OMS were observed. Five nontumor cases included three parainfectious and two idiopathic cases. The median time from symptom onset to diagnosis was 34 days. All patients with diagnostic OMS criteria in the idiopathic, nontumor group underwent whole-exome sequencing, with potentially pathogenic mutations identified in two cases. Nine patients were treated with methylprednisolone pulse, followed by oral steroids; eight received one or more intravenous immunoglobulin treatments; and six received azathioprine and cyclophosphamide. Complete symptomatic recovery was observed in only one patient. CONCLUSIONS: OMS diagnosis remains challenging. Diagnostic suspicion is necessary to improve the management of these patients and allow early immunosuppressive treatment. Paraneoplastic etiology is the most prevalent. In idiopathic patients who do not respond to immunosuppressive treatment, tests, such as whole-exome sequencing, may reveal a differential diagnosis. Genetic alterations that increase the risk of tumors may be an important clue to the pathophysiology of OMS.

Psychobehavioral factors and family functioning in mucopolysaccharidosis: preliminary studies.

Introduction: Mucopolysaccharidoses (MPS) constitute a group of progressive and multisystemic inherited metabolic diseases that profoundly affect both the mental health of patients and the wellbeing of their families. This study aims to evaluate the impact of MPS on family functioning and related factors. Methods and results: Twenty-five patients with MPS, including types I (n = 4), II (n = 11), IIIB (n = 2), IVA (n = 3), and VI (n = 5), and their families participated in this study. The mean patient age was 13 years [standard deviation (SD): 7.7 years]. Behavioral and emotional problems were noted in 9.1% of all patients. While the type of MPS did not directly influence mental problems, the presence of neuronal involvement did (p = 0.006). Patients with MPS III exhibited difficulties primarily in emotional areas, conduct, hyperactivity, and peer problems. Importantly, both patients with MPS II and those with MPS III experienced a significant impact on communication [mean scores for communication domain: MPS II, 35.6 (SD: 24.3); MPS III, 35.0 (SD: 22.6)]; poorer communication was directly linked to worse adaptive behavior (p = 0.012), and worse adaptive behavior was associated with lower quality of life (p = 0.001). Quality of life and caregiver burden among family members did not significantly differ across MPS types; however, higher caregiver burden was negatively associated with quality of life (p = 0.002). Concerning family functioning, the most impacted domains included independence, intellectual/cultural orientation, activity/recreation, and expressiveness. Domain scores did not vary based on MPS type, treatment, or neurological involvement. Quality-of-life scores were positively associated with the cultural/intellectual domain score. Conclusion: The impacts of quality of life and family extend beyond clinical characteristics and MPS type, strongly influenced by patient cognition and communication, as well as type of family functioning, especially those with greater cultural/intellectual skills of their family members. A multidisciplinary approach addressing the broader needs of individuals with MPS becomes essential. Techniques aimed at improving communication, including prompt interventions such as speech therapy and augmentative and alternative communication strategies, can contribute to overall family functioning improvement.

O trabalho de fisioterapeutas da Atenção Básica em Saúde brasileira - construindo caminhos para o enfrentamento da pandemia da Covid-19

Introdução: A Atenção Básica em Saúde (AB) tem papel importante no cuidado de usuários com Covid-19, na prevenção de agravos, na escuta e acolhimento inicial, diagnósticos, condutas e encaminhamentos precoces, bem como na reabilitação e continuidade do cuidado de pessoas com sequelas da doença, tanto no âmbito físico, psíquico e social. No Brasil, embora as condutas de gestão de crise política possam ter tido impacto direto no descontrole da pandemia e com enormes quantidades de usuários em estado grave de contaminação com número elevado de óbitos, a AB possui equipes multiprofissionais que incluem o fisioterapeuta para o cuidado da população, com papel preponderante no enfrentamento da pandemia. Objetivos: Dessa forma, este ensaio acadêmico busca trazer à cena a atuação de fisioterapeutas na AB para prevenção, promoção, cuidado continuado, ações territoriais e reabilitação de usuários com Covid-19, bem como suas consequências biopsicossociais, com enfoque na integralidade do cuidado e ações coletivas no território. Métodos: Apresentamos as possibilidades de ferramentas, ações e práticas de atuação do profissional fisioterapeuta no enfrentamento da pandemia na Atenção Básica. Resultados e Conclusões: O fisioterapeuta da Atenção Básica tem um papel preponderante em todas as fases da pandemia da Covid-19, desde a promoção da saúde e prevenção de contaminação e de contágio, tratamento na fase aguda e o cuidado na Covid Longa.

Correction: Wet market biosecurity reform: Three social narratives influence stakeholder responses in Vietnam, Kenya, and the Philippines.

[This corrects the article DOI: 10.1371/journal.pgph.0001704.].

Factors associated with interprofessional collaboration in Primary Health Care: a multilevel analysis.

Working with an interprofessional focus is increasingly necessary, in view of the growing complexity of the population's health needs. This study aims to assess interprofessional collaboration and the teamwork climate in primary health care (PHC) and determine whether there is a relationship between these two variables. The AITCS-II instrument was used to measure interprofessional collaboration, while to diagnose teamwork climate, the ECTE instrument was used, a version adapted to the SUS context of the Teamwork Climate Inventory instrument. These two instruments were applied online together with a questionnaire for the sociodemographic characterization of the 544 participants, who belonged to 97 Family Health Strategy (FHS) teams in a Brazilian municipality. The obtained data were submitted to a multilevel analysis. A positive correlation was observed between interprofessional collaboration and three of the four teamwork climate factors. The better the work climate, the better the interprofessional collaboration in the corresponding team, and this characteristic stands out in relation to other individual analyzed characteristics.

Factors associated with interprofessional collaboration in Primary Health Care: a multilevel analysis / Fatores associados à colaboração interprofissional na Atenção Primária à Saúde: uma análise multinível

Abstract Working with an interprofessional focus is increasingly necessary, in view of the growing complexity of the population's health needs. This study aims to assess interprofessional collaboration and the teamwork climate in primary health care (PHC) and determine whether there is a relationship between these two variables. The AITCS-II instrument was used to measure interprofessional collaboration, while to diagnose teamwork climate, the ECTE instrument was used, a version adapted to the SUS context of the Teamwork Climate Inventory instrument. These two instruments were applied online together with a questionnaire for the sociodemographic characterization of the 544 participants, who belonged to 97 Family Health Strategy (FHS) teams in a Brazilian municipality. The obtained data were submitted to a multilevel analysis. A positive correlation was observed between interprofessional collaboration and three of the four teamwork climate factors. The better the work climate, the better the interprofessional collaboration in the corresponding team, and this characteristic stands out in relation to other individual analyzed characteristics.

Resumo Trabalhar com foco interprofissional é cada vez mais necessário, tendo em vista a crescente complexidade das necessidades de saúde da população. Este estudo tem como objetivo avaliar a colaboração interprofissional e o clima de trabalho em equipe na atenção primária à saúde (APS) e verificar possível relação entre estas duas variáveis. Para mensurar a colaboração interprofissional foi utilizado o instrumento AITCS-II, enquanto para o diagnóstico do clima de trabalho em equipe foi utilizado o instrumento ECTE, versão adaptada para o contexto SUS do instrumento Teamwork Climate Inventory. Esses dois instrumentos foram aplicados on-line juntamente com um questionário para caracterização sociodemográfica dos 544 participantes, pertencentes a 97 equipes da Estratégia Saúde da Família (ESF) de um município brasileiro. Os dados obtidos foram submetidos a uma análise multinível. Foi observada uma correlação positiva entre a colaboração interprofissional e três dos quatro fatores do clima de trabalho em equipe. Quanto melhor o clima de trabalho, melhor a colaboração interprofissional na equipe correspondente, e essa característica se destaca em relação às demais características individuais analisadas.

Quando corpos dissidentes proclamam seus lugares como corpos diz-sonantes / When dissident bodies proclaim their places as dissonant bodies

Resumo O objetivo deste ensaio é apresentar o conceito de corpos diz-sonantes e dar visibilidade a esses corpos no campo da saúde coletiva, a partir de perspectivas anti-coloniais e queers. São corpos muitas vezes considerados dissidentes, cujas existências consideradas abjetas, descartáveis e marginalizadas, pela sociedade neoliberal e necropolítica são apresentadas como outras possibilidades frente às lógicas e estratégias políticas de reprodução hegemônica da vida-capital e nas políticas de saúde. Debate tensionamentos de novas possibilidades e alternativas de modos outros de existências e de mundos inclusivos, em que todas as vidas sejam consideradas, em suas singularidades e diferenças, radicalmente iguais na validação dos seus modos de viver.

Abstract This essay aims to present the concept of dissonant bodies and give visibility to these bodies in the field of public health from anti-colonial and queer perspectives. These bodies are often considered dissidents. Their existence is considered abject, disposable, and marginalized by neoliberal and necropolitical society. It is presented as another possibility in the face of the logic and political strategies of hegemonic reproduction of capital-life and health policies. It debates tensions of new possibilities and alternatives of other modes of existence and inclusive worlds, in which all lives are considered, in their singularities and differences, radically equal in the validation of their ways of living.

Brazilian autoimmune encephalitis network (BrAIN): antibody profile and clinical characteristics from a multicenter study.

Background: The frequency of antibodies in autoimmune encephalitis (AIE) may vary in different populations, however, data from developing countries are lacking. To describe the clinical profile of AIE in Brazil, and to evaluate seasonality and predictors of AIE in adult and pediatric patients. Methods: We evaluated patients with possible AIE from 17 centers of the Brazilian Autoimmune Encephalitis Network (BrAIN) between 2018 and 2022. CSF and serum were tested with TBAs and CBAs. Data on clinical presentation, complementary investigation, and treatment were compiled. Seasonality and predictors of AIE in adult and pediatric populations were analyzed. Results: Of the 564 patients, 145 (25.7%) were confirmed as seropositive, 69 (12.23%) were seronegative according to Graus, and 58% received immunotherapy. The median delay to diagnosis confirmation was 5.97 ± 10.3 months. No seasonality variation was observed after 55 months of enrolment. The following antibodies were found: anti-NMDAR (n=79, 54%), anti-MOG (n=14, 9%), anti-LGI1(n=12, 8%), anti-GAD (n=11, 7%), anti-GlyR (n=7, 4%), anti-Caspr2 (n=6, 4%), anti-AMPAR (n=4, 2%), anti-GABA-BR (n=4, 2%), anti-GABA-AR (n=2, 1%), anti-IgLON5 (n=1, 1%), and others (n=5, 3%). Predictors of seropositive AIE in the pediatric population (n=42) were decreased level of consciousness (p=0.04), and chorea (p=0.002). Among adults (n=103), predictors of seropositive AIE were movement disorders (p=0.0001), seizures (p=0.0001), autonomic instability (p=0.026), and memory impairment (p=0.001). Conclusion: Most common antibodies in Brazilian patients are anti-NMDAR, followed by anti-MOG and anti-LGI1. Only 26% of the possible AIE patients harbor antibodies, and 12% were seronegative AIE. Patients had a 6-month delay in diagnosis and no seasonality was found. Findings highlight the barriers to treating AIE in developing countries and indicate an opportunity for cost-effect analysis. In this scenario, some clinical manifestations help predict seropositive AIE such as decreased level of consciousness, chorea, and dystonia among children, and movement disorders and memory impairment among adults.

Brazilian experts' consensus on the treatment of infantile epileptic spasm syndrome in infants.

BACKGROUND: Infantile epileptic spasms syndrome (IESS) is a rare but severe condition affecting children early and is usually secondary to an identifiable brain disorder. It is related to psychomotor deterioration in childhood and epilepsy in adult life. Treatment is challenging as infantile spasms may not respond to most antiseizure medication, and relapse is frequent. OBJECTIVE: To evaluate the literature regarding treatment of IESS and provide a practical guidance to a healthcare system with limited resources. METHODS: An expert committee from the Brazilian Society of Child Neurology reviewed and discussed relevant scientific evidence in the treatment of IESS regarding the drugs available in Brazil. RESULTS: Oral prednisolone and vigabatrin are the most common drugs used as first-line therapy; they are efficient and affordable therapy as both are available in the Brazilian unified health system (SUS, in the Portuguese acronym). Intramuscular adrenocorticotropic hormone (ACTH) presents similar efficacy as oral prednisolone but has a higher cost and is not available in Brazil. Other antiseizure medications such as topiramate, levetiracetam, or benzodiazepines have limited response and are prescribed as adjuvant therapy. If the health service has nutritionists, a ketogenic diet should be implemented for those not responding to hormonal and vigabatrin treatment. Epilepsy surgery is mainly indicated for patients with focal lesions that do not respond to pharmacological therapy. CONCLUSION: Early treatment of IESS with efficient drugs is feasible in our country. Using standard protocols increases the odds of achieving complete cessation in a shorter time and decreases relapse.

ANTECEDENTES: A síndrome do espasmo epiléptico infantil (IESS) é uma condição rara, mas grave, que afeta crianças precocemente e geralmente é secundária a um distúrbio cerebral identificável, estando relacionada a deterioração psicomotora na infância e a epilepsia na vida adulta. O tratamento é desafiador, pois os espasmos infantis podem não responder à maioria dos medicamentos anticrises e as recidivas são frequentes. OBJETIVO: Avaliar a literatura sobre o tratamento de IESS e fornecer uma orientação prática para um sistema de saúde com recursos limitados. MéTODOS: Um comitê de especialistas da Sociedade Brasileira de Neurologia Infantil revisou e discutiu evidências científicas relevantes no tratamento da IESS em relação aos medicamentos disponíveis no Brasil. RESULTADOS: Prednisolona oral e vigabatrina são os fármacos mais comumente usados como terapia de primeira linha; são eficientes e acessíveis, já que ambos estão disponíveis no sistema único de saúde brasileiro (SUS). O ACTH intramuscular apresenta eficácia semelhante à prednisolona oral, mas tem custo mais elevado e não está disponível no Brasil. Outros medicamentos anticonvulsivos, como topiramato, levetiracetam ou benzodiazepínicos, têm resposta limitada e são prescritos como terapia adjuvante. Se o serviço de saúde tiver nutricionista, deve-se implementar dieta cetogênica para aqueles que não respondem ao tratamento hormonal e vigabatrina. A cirurgia de epilepsia é indicada principalmente para pacientes com lesões focais que não respondem à terapia farmacológica. CONCLUSãO: O tratamento precoce da IESS com fármacos eficazes é factível em nosso meio. O uso de protocolos padronizados aumenta as chances de alcançar a cessação completa em um tempo menor e diminui a recaída.

Wet market biosecurity reform: Three social narratives influence stakeholder responses in Vietnam, Kenya, and the Philippines.

In 2020, Covid-19 led to global policy statements promoting bans and reforms to wet markets in Asia and Africa to prevent future pandemics. We conducted a comparative, exploratory qualitative study in 2021 in three countries (Kenya, Vietnam and the Philippines) to understand the social and political dimensions to biosecurity reform at wet markets. This included 60 key informant interviews and rapid ethnographic research in 15 markets, as well as a review of policy documents and online media articles. We found no evidence that the rhetoric of pandemic spillover that emerged in 2020 had any influence on policy or reform efforts apart from those related to Covid-19 infection control. Rather, we identified three main narratives that frame the problem of biosecurity and preferences for reform. The first, a human health narrative, questioned global framings about pandemic risk, viewed markets as sources for food security rather than disease, emphasized the need to strengthen the control of endemic diseases, and conceptualized health through the lens of 'freshness' rather than biomedical categories. A second modernization narrative approached biosecurity as part of a broader process of socio-economic development that emphasized infrastructural gaps, spatial arrangements, cleanliness and a conflict between reform and economic interests. A third narrative centered on local livelihoods and the tension between local market stakeholders and biosecurity and modernization efforts. This final narrative called into question the appropriateness of certain regulations and policies, including bans and closures, emphasized the importance of preserving cultural heritage and highlighted the need for collective political action to resist certain veterinary policies. In conclusion, wet market biosecurity strategies occur in the context of three contrasting narratives that emphasize different aspects of health and risk, and reflect different worldviews and interests. Within this context, there is a need for local government to strengthen market management and biosecurity in ways that enhance the agency of market stakeholders and strengthen local livelihoods and food security as part of a pluralistic and democratic politics.

Brazilian experts' consensus on the treatment of infantile epileptic spasm syndrome in infants / Consenso de especialistas brasileiros sobre o tratamento da síndrome dos espasmos infantis em lactentes

Abstract Background Infantile epileptic spasms syndrome (IESS) is a rare but severe condition affecting children early and is usually secondary to an identifiable brain disorder. It is related to psychomotor deterioration in childhood and epilepsy in adult life. Treatment is challenging as infantile spasms may not respond to most antiseizure medication, and relapse is frequent. Objective To evaluate the literature regarding treatment of IESS and provide a practical guidance to a healthcare system with limited resources. Methods An expert committee from the Brazilian Society of Child Neurology reviewed and discussed relevant scientific evidence in the treatment of IESS regarding the drugs available in Brazil. Results Oral prednisolone and vigabatrin are the most common drugs used as first-line therapy; they are efficient and affordable therapy as both are available in the Brazilian unified health system (SUS, in the Portuguese acronym). Intramuscular adrenocorticotropic hormone (ACTH) presents similar efficacy as oral prednisolone but has a higher cost and is not available in Brazil. Other antiseizure medications such as topiramate, levetiracetam, or benzodiazepines have limited response and are prescribed as adjuvant therapy. If the health service has nutritionists, a ketogenic diet should be implemented for those not responding to hormonal and vigabatrin treatment. Epilepsy surgery is mainly indicated for patients with focal lesions that do not respond to pharmacological therapy. Conclusion Early treatment of IESS with efficient drugs is feasible in our country. Using standard protocols increases the odds of achieving complete cessation in a shorter time and decreases relapse.

Resumo Antecedentes A síndrome do espasmo epiléptico infantil (IESS) é uma condição rara, mas grave, que afeta crianças precocemente e geralmente é secundária a um distúrbio cerebral identificável, estando relacionada a deterioração psicomotora na infância e a epilepsia na vida adulta. O tratamento é desafiador, pois os espasmos infantis podem não responder à maioria dos medicamentos anticrises e as recidivas são frequentes. Objetivo Avaliar a literatura sobre o tratamento de IESS e fornecer uma orientação prática para um sistema de saúde com recursos limitados. Métodos Um comitê de especialistas da Sociedade Brasileira de Neurologia Infantil revisou e discutiu evidências científicas relevantes no tratamento da IESS em relação aos medicamentos disponíveis no Brasil. Resultados Prednisolona oral e vigabatrina são os fármacos mais comumente usados como terapia de primeira linha; são eficientes e acessíveis, já que ambos estão disponíveis no sistema único de saúde brasileiro (SUS). O ACTH intramuscular apresenta eficácia semelhante à prednisolona oral, mas tem custo mais elevado e não está disponível no Brasil. Outros medicamentos anticonvulsivos, como topiramato, levetiracetam ou benzodiazepínicos, têm resposta limitada e são prescritos como terapia adjuvante. Se o serviço de saúde tiver nutricionista, deve-se implementar dieta cetogênica para aqueles que não respondem ao tratamento hormonal e vigabatrina. A cirurgia de epilepsia é indicada principalmente para pacientes com lesões focais que não respondem à terapia farmacológica. Conclusão O tratamento precoce da IESS com fármacos eficazes é factível em nosso meio. O uso de protocolos padronizados aumenta as chances de alcançar a cessação completa em um tempo menor e diminui a recaída.

Predictive factors of genetic diagnosis and real-life impact of next-generation sequencing for children with epilepsy.

OBJECTIVE: Identify the predictive variables of genetic pathogenic results and the impact of test results on epilepsy diagnosis and management. METHODS: Analytical observational design evaluated 130 patients with epilepsy that had performed genetic testing over January 2017 to July 2022. RESULTS: There was a gradual increase in the number of exams performed over the years. The frequency of pathogenic results was 34% (n = 44/130), 8 altered genes with 54% (n = 24/44) of the results. The tests were more positive in patients with developmental delay and/or regression (p = .01). None of the other factors analyzed were associated with higher diagnostic yield. The age at onset of epilepsy brought diagnostic yield to the test (p = .041). Patients with negative genetic test had a reduction in the number of electroencephalograms performed before and after the test (respectively, 3.80 ± 6.37 and .84 ± 1.67; p < .001). SIGNIFICANCE: Facing a large proportion of patients with unexplained epilepsy have a genetic cause a genetic test has the potential to reduce the use of unnecessary diagnostic tests, improve patient outcomes by identifying targeted treatments, and provide families with genetic counseling and risk assessment. But an early genetic testing can be crucial to reach these goals. Even in cases where the genetic test is negative, the study suggests that it still has important implications for patient care and management.

Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS): new cases, systematic literature review, and associations with CSF1R-ALSP.

CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS). The former is increasingly recognized, and disease-modifying therapy was introduced; however, literature is scarce on the latter. This review analyzes BANDDOS and discusses similarities and differences with CSF1R-ALSP.We systematically retrieved and analyzed the clinical, genetic, radiological, and pathological data on the previously reported and our cases with BANDDOS. We identified 19 patients with BANDDOS (literature search according to the PRISMA 2020 guidelines: n = 16, our material: n = 3). We found 11 CSF1R mutations, including splicing (n = 3), missense (n = 3), nonsense (n = 2), and intronic (n = 2) variants and one inframe deletion. All mutations disrupted the tyrosine kinase domain or resulted in nonsense-mediated mRNA decay. The material is heterogenous, and the presented information refers to the number of patients with sufficient data on specific symptoms, results, or performed procedures. The first symptoms occurred in the perinatal period (n = 5), infancy (n = 2), childhood (n = 5), and adulthood (n = 1). Dysmorphic features were present in 7/17 cases. Neurological symptoms included speech disturbances (n = 13/15), cognitive decline (n = 12/14), spasticity/rigidity (n = 12/15), hyperactive tendon reflex (n = 11/14), pathological reflexes (n = 8/11), seizures (n = 9/16), dysphagia (n = 9/12), developmental delay (n = 7/14), infantile hypotonia (n = 3/11), and optic nerve atrophy (n = 2/7). Skeletal deformities were observed in 13/17 cases and fell within the dysosteosclerosis - Pyle disease spectrum. Brain abnormalities included white matter changes (n = 19/19), calcifications (n = 15/18), agenesis of corpus callosum (n = 12/16), ventriculomegaly (n = 13/19), Dandy-Walker complex (n = 7/19), and cortical abnormalities (n = 4/10). Three patients died in infancy, two in childhood, and one case at unspecified age. A single brain autopsy evidenced multiple brain anomalies, absence of corpus callosum, absence of microglia, severe white matter atrophy with axonal spheroids, gliosis, and numerous dystrophic calcifications.In conclusion, BANDDOS presents in the perinatal period or infancy and has a devastating course with congenital brain abnormalities, developmental delay, neurological deficits, osteopetrosis, and dysmorphic features. There is a significant overlap in the clinical, radiological, and neuropathological aspects between BANDDOS and CSF1R-ALSP. As both disorders are on the same continuum, there is a window of opportunity to apply available therapy in CSF1R-ALSP to BANDDOS.

Factors related to the waiting time for scheduling an oral biopsy in Brazil: a multilevel analysis.

BACKGROUND: Timely diagnosis of oral cancers is critical, and performing biopsies of oral lesions with suspected malignancy is a crucial step in achieving this goal. The waiting time for the diagnosis may be related to the progression and prognosis of malignant neoplasms. OBJECTIVE: The aim of this observational, cross-sectional, national-level study was to identify the factors associated with the waiting time for scheduling an oral biopsy, based on the identification of its need. METHODS: We used secondary data from the Brazilian public health system, obtained from the 2nd cycle of the National Program to Improve Access and Quality of Dental Specialty Centers (PMAQ-CEO). The study outcome was the waiting time for scheduling an oral biopsy, starting from the identification of the need for the exam. We analyzed individual and contextual variables using multilevel statistical analysis. RESULTS: In 51.8% of DSC the waiting time for scheduling a biopsy was non-immediate; in 58.1% of CEOs, the sum of the weekly workload of dentists working in the Stomatology specialty is up to 20 h per week; in terms of coverage, 67.1% of the CEOs have only municipal coverage and 34.0% are references for up to 12 oral health teams in primary health care; only the coverage variable remained significant in the multivariate model (p < 0.05). Of the contextual variables, none of the variables remained significant (p > 0.05). When these were analyzed together, only the coverage remained significant (p < 0.05); CONCLUSION: Our analysis indicates that the waiting time for scheduling an oral biopsy is longer in CEOs that cover only one municipality and is not related to contextual factors.