COVID-19 Pandemic and Dysbiosis: Can the Ivermectin Hysteria Lead to an Increase of Autoimmune Neuroinflammatory Diseases?

The pandemic caused by the SARS-CoV-2 has made new treatments a goal for the scientific community. One of these treatments is Ivermectin. Here we discuss the hypothesis of dysbiosis caused by the use of Ivermectin and the possible impacts on neuroinflammatory diseases after the end of the pandemic.

Neurological Complications of the COVID-19 Pandemic: What Have We Got So Far?

The recently emerged coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19, is the newest threat to human health. It has already infected more than 54.5 million people worldwide, currently leading to more than 1.3 million deaths. Although it causes a mild flu-like disease in most patients, lethality may increase to more than 20% in elderly subjects, especially in those with comorbidities, like hypertension, diabetes, or lung and cardiac disease, and the mechanisms are still elusive. Common symptoms at the onset of illness are fever, cough, myalgia or fatigue, headache, and diarrhea or constipation. Interestingly, respiratory viruses have also placed themselves as relevant agents for central nervous system (CNS) pathologies. Conversely, SARS-CoV-2 has already been detected in the cerebrospinal fluid. Here, we discuss several clinical features related to CNS infection during COVID-19. Patients may progress from headaches and migraines to encephalitis, stroke, and seizures with leptomeningitis. However, the pathway used by the virus to reach the brain is still unknown. It may infect the olfactory bulb by retrograde neuronal transportation from olfactory epithelium, or it could be transported by the blood. Either way, neurological complications of COVID-19 add greatly to the complex pathophysiology of the disease. Neurological signs and symptoms must alert physicians not only to worst outcomes but also to future possible degenerative diseases.

Painful legs and moving toes.

A 40-year-old woman reported involuntary and irregular movements of her left toes accompanied by pain. This arose following arthroscopy after a sprained left ankle. She had involuntary flexion-extension and abduction and adduction movements of the hallux and the other toes, with reduced pinprick sensation on the skin web between the left hallux and the second toe. Nerve conduction studies confirmed a deep peroneal nerve axonal injury. We diagnosed the syndrome of painful legs and moving toes, provoked by a peripheral nerve injury. Her symptoms have persisted despite pregabalin, gabapentin and amitriptyline.

Postpartum Treatment With Immunoglobulin Does Not Prevent Relapses of Multiple Sclerosis in the Mother.

Multiple sclerosis (MS) is a chronic, neurological, immune-mediated disease that can worsen in the postpartum period. There is no consensus on the use of immunoglobulin for prevention of disease relapses after delivery. We have shown that the controversial beneficial effect of immunoglobulin given immediately after birth could not be observed in patients with MS.

Impacts of environmental tobacco smoke on the onset and progression of multiple sclerosis: a systematic review.

BACKGROUND: Unlike cigarette smoking, environmental tobacco smoke (ETS) has not been as well described as an environmental risk for Multiple sclerosis (MS) nor as a risk factor for disease progression. OBJECTIVE: We systematically reviewed the association between ETS and the risk of onset and/or progression of MS. METHODS: We systematically screened MedLine/PubMed, Science Direct, LILACs, and SciELO searching for publications between January 1st, 2010, and July 5, 2021, with the following keywords: "multiple sclerosis and smoking"; "multiple sclerosis and passive smoking"; "multiple sclerosis and secondhand smoking". RESULTS: Fifteen articles were included in this review, which consisted of systematic reviews with meta-analysis (N = 2), systematic reviews (N = 2), and observational studies (N = 11). Both meta-analyses reported an impact of ETS on MS onset among secondhand smokers. One of the systematic reviews selected two observational studies showing the association between ETS and MS development, and one study that did not find a significant association between ETS and the risk of MS development. The other systematic review identified selected eight articles showing a relationship between ETS and MS. Seven observational studies reported higher odds of MS onset when associated with ETS. Four observational studies did not show a relationship between ETS and MS onset or progression. CONCLUSION: Most articles showed a positive association between ETS exposure and the risk of developing MS. On the other hand, an association between ETS and a higher risk for MS progression could not be established.

ANTECEDENTES: Ao contrário do tabagismo ativo, o fumo passivo (FP) não é tão bem estabelecido como risco para o desenvolvimento de esclerose múltipla (EM) nem como um fator de risco para a progressão da doença. OBJETIVO: Revisamos sistematicamente a associação entre FP e o risco de aparecimento e/ou progressão da EM. MéTODOS: Fizemos uma triagem sistemática nas bases de dados MedLine/PubMed, Science Direct, LILACs e SciELO em busca de publicações entre 1° de janeiro de 2010 e 5 de julho de 2021 com as seguintes palavras-chave: "multiple sclerosis and smoking"; "multiple sclerosis and passive smoking"; "multiple sclerosis and secondhand smoking". RESULTADOS: Quinze artigos foram incluídos nesta revisão, que consistiu em revisões sistemáticas com metanálise (N = 2), revisões sistemáticas (N = 2) e estudos observacionais (N = 11). As metanálises relataram um impacto do FP no surgimento da EM entre fumantes passivos. Um revisão sistemática selecionou dois estudos observacionais mostrando a associação entre FP e desenvolvimento de EM, e um estudo que não encontrou associação significativa entre FP e o risco de desenvolvimento de EM. Outra revisão sistemática identificou oito artigos selecionados mostrando uma relação entre FP e EM. Sete estudos observacionais relataram maiores chances de aparecimento de EM quando associados a FP. Quatro estudos observacionais não mostraram uma relação entre FP e o desenvolvimento ou progressão da EM. CONCLUSãO: A maioria dos artigos mostrou uma associação positiva entre a exposição ao FP e o risco de desenvolver EM. Por outro lado, não foi possível estabelecer uma associação entre FP e maior risco de progressão da EM.

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.

Neuromyelitis optica spectrum disorders with a benign course. Analysis of 544 patients.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) most commonly cause severe disability which is related to disease attacks. However, some patients retain good neurological function for a long time after disease onset. OBJECTIVES: To determine the frequency, demographic and the clinical features of good outcome NMOSD, and analyze their predictive factors. METHODS: We selected patients who met the 2015 International Panel for NMOSD diagnostic criteria from seven MS Centers. Assessed data included age at disease onset, sex, race, number of attacks within the first and three years from onset, annualized relapsing rate (ARR), total number of attacks, aquaporin-IgG serum status, presence of cerebrospinal fluid (CSF)-specific oligoclonal bands (OCB) and the Expanded Disability Status Scale (EDSS) score at the last follow-up visit. NMOSD was classified as non-benign if patients developed sustained EDSS score >3.0 during the disease course, or benign if patients had EDSS score ≤3.0 after ≥15 years from disease onset. Patients with EDSS <3.0 and disease duration shorter than 15 years were not qualified for classification. We compared the demographic and clinical characteristics of benign and non-benign NMOSD. Logistic regression analysis identified predictive factors of outcome. RESULTS: There were 16 patients with benign NMOSD (3% of the entire cohort; 4.2% of those qualified for classification; and 4.1% of those who tested positive for aquaporin 4-IgG), and 362 (67.7%) with non-benign NMOSD, whereas 157 (29.3%) did not qualify for classification. All patients with benign NMOSD were female, 75% were Caucasian, 75% tested positive for AQP4-IgG, and 28.6% had CSF-specific OCB. Regression analysis showed that female sex, pediatric onset, and optic neuritis, area postrema syndrome, and brainstem symptoms at disease onset, as well as fewer relapses in the first year and three years from onset, and CSF-specific OCB were more commonly found in benign NMOSD, but the difference did not reach statistical significance. Conversely, non-Caucasian race (OR: 0.29, 95% CI: 0.07-0.99; p = 0.038), myelitis at disease presentation (OR: 0.07, 95% CI: 0.01-0.52; p <0.001), and high ARR (OR: 0.07, 95% CI: 0.01-0.67; p = 0.011) were negative risk factors for benign NMOSD. CONCLUSION: Benign NMOSD is very rare and occurs more frequently in Caucasians, patients with low ARR, and those who do not have myelitis at disease onset.

Brazilian consensus for diagnosis, management and treatment of hereditary transthyretin amyloidosis with peripheral neuropathy: second edition.

Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ∼ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.

Polineuropatia amiloidótica familiar associada a transtirretina (ATTRv-PN) é uma polineuropatia sensitivo-motora e autonômica hereditária autossômica dominante com mais de 130 variantes patogênicas já identificadas no gene TTR. A ATTRv-PN é uma condição genética debilitante, progressiva e que ameaça a vida, levando à morte em ∼ 10 anos se não for tratada. Nas últimas décadas, a ATTRv-PN se tornou uma neuropatia tratável. Além do transplante de fígado, iniciado em 1990, temos agora 3 medicamentos modificadores de doença aprovados em muitos países, incluindo o Brasil, e muitas outras medicações estão em desenvolvimento. O primeiro consenso brasileiro em ATTRv-PN foi realizado em Fortaleza em junho de 2017. Devido aos novos avanços nesta área nos últimos 5 anos, o Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia organizou uma segunda edição do consenso. Cada panelista ficou responsável por rever a literatura e atualizar uma parte do manuscrito. Finalmente, os 18 panelistas se reuniram virtualmente após revisão da primeira versão, discutiram cada parte do artigo e chegaram a um consenso sobre a versão final do manuscrito.

Update of the Brazilian consensus recommendations on Duchenne muscular dystrophy.

In the last few decades, there have been considerable improvements in the diagnosis and care of Duchenne muscular dystrophy (DMD), the most common childhood muscular dystrophy. International guidelines have been published and recently reviewed. A group of Brazilian experts has developed a standard of care based on a literature review with evidence-based graded recommendations in a two-part publication. Implementing best practice management has helped change the natural history of this chronic progressive disorder, in which the life expectancy for children of the male sex in the past used to be very limited. Since the previous publication, diagnosis, steroid treatment, rehabilitation, and systemic care have gained more significant insights with new original work in certain fields. Furthermore, the development of new drugs is ongoing, and some interventions have been approved for use in certain countries. Therefore, we have identified the need to review the previous care recommendations for Brazilian patients with DMD. Our objective was to create an evidence-based document that is an update on our previous consensus on those topics.

Nas últimas décadas, houve progressos significativos no diagnóstico e no tratamento da distrofia muscular de Duchenne (DMD), considerada a distrofia muscular mais comum na infância. Diretrizes internacionais foram publicadas e revisadas recentemente. Um grupo de especialistas brasileiros desenvolveu um padrão de atendimento baseado em revisão de literatura, com recomendações graduadas pautadas em evidências compiladas em uma publicação dividida em duas partes. A implementação de melhores práticas de manejo ajudou a modificar a história natural desta doença crônica, progressiva, que, no passado, oferecia uma expectativa de vida muito limitada para crianças do sexo masculino. Desde a publicação desse consenso anterior, o diagnóstico, o tratamento com esteroides, a reabilitação e os cuidados sistêmicos ganharam novas possibilidades a partir da divulgação dos resultados de trabalhos originais em algumas dessas áreas. Além disso, as pesquisas e o desenvolvimento de novos fármacos estão em andamento, e algumas intervenções já foram aprovadas para uso em determinados países. Nesse contexto, identificamos a necessidade de rever as recomendações anteriores sobre o manejo dos pacientes brasileiros com DMD. Nosso objetivo principal foi elaborar uma atualização baseada em evidências sobre esses tópicos do consenso.

Idiopathic Hypertrophic Spinal Pachymeningitis: A Case Report.

Idiopathic hypertrophic pachymeningitis is rare cause of neurological symptoms with myelopathy due to spinal cord compression. We report a case of pachymeningitis, which was manifested primarily by tetraparesis after low-energy trauma and recurrence the myelopathy symptoms after 5 years of surgery. The patient, a 19-year-old woman, was subjected to extensive investigation without evidence of any underlying disease. A meningeal biopsy was performed and showed an unspecific inflammatory process with extensive fibrosis of the dura mater. These findings, associated with the exclusion of other causes, suggest idiopathic hypertrophic pachymeningitis.

Wernicke Encephalopathy in COVID-19 Patients: Report of Three Cases.

Encephalopathy has been frequently reported in patients with acute respiratory distress syndrome (ARDS) related to COVID-19, and its etiology remains undetermined. These patients display hypercatabolic state, weight loss, use of diuretics, and dialytic therapy, which represent risk factors for thiamine depletion. The diagnosis of Wernicke encephalopathy (WE) is challenging and based on risk factors for the depletion of thiamine. We reported three cases of patients with COVID-19-related WE treated with intravenous thiamine. All patients responded with immediate neurologic improvement, and two of them had accelerated ventilatory weaning. The cases reported suggest that thiamine deficiency could represent relevant etiology of COVID-19-related encephalopathy.

A New Vision at the Interface of Atrial Fibrillation and Stroke.

Introduction: Current evidence questions the linear sequence traditionally described in atrial fibrillation, blood stasis, intracavitary thrombus, and embolization to the central nervous system. Currently, new perspectives have been described based on questions from the linearly traditional chronology of events; it is within this scope that the article has its objective. Evidences: The association of the two entities is biologically plausible and supported by different cohorts with a higher risk of developing atrial fibrillation, especially in the cardioembolic form. Concepts (temporal dissociation, biological gradient, etc.) determine the existence of other factors associated with cardioembolism, not exclusively by atrial fibrillation. The entire cascade of events associated with myopathy and atrial remodeling can generate damage to the myocyte and amplify the prothrombotic status. It is important to clarify that atrial myopathy can present itself as atrial fibrillation initially or not, but should always be considered thrombogenic in all the contexts of their clinical presentation. Considering atrial heart disease as a cause of embolic stroke, it could explain that one-third of strokes are considered cryptogenic. Conclusions: The traditional model exclusively associating the presence of atrial fibrillation in the genesis of thromboembolism is incomplete. The concept of atrial cardiopathy where cardioembolism occurs in a non-atrial fibrillation dependent manner fits better with current data. The future challenge is to effectively detect the various manifestations of atrial heart disease, generating direct implications for the identification of patients at risk of stroke and also for better management after a cardioembolic event.

Altered expression of microRNAs and B lymphocytes during Natalizumab therapy in multiple sclerosis.

MicroRNAs (miRNAs) are a family of non-translated small ribonucleic acids (RNAs) measuring 21-25 nucleotides in length that play various roles in multiple sclerosis (MS). By regulating gene expression via either mediating translational repression or cleavage of the target RNA, miRNAs can alter the expression of transcripts in different cells, such as B lymphocytes, also known as B cells. They are crucial in the pathogenesis of MS; however, they have not been extensively studied during the treatment of some drugs such as natalizumab (NTZ). NTZ is a humanized immunoglobulin G4 antibody antagonist for integrin alpha 4 (α4) used in the treatment of MS. The drug reduces the homing of lymphocytes to inflammation sites. Integrin α4 expression on the cell surface of B cells is related to MS severity, indicating a critical component in the pathogenesis of the disease. NTZ plays an important role in modifying the gene expression in B cells and the levels of miRNAs in the treatment of MS. In this review, we have described changes in gene expression in B cells and the levels of miRNAs during NTZ therapy in MS and its relapse. Studies using the experimental autoimmune encephalomyelitis (EAE) model and those involving patients with MS have described changes in the levels of microRNAs in the regulation of proteins affected by specific miRNAs, gene expression in B cells, and certain functions of B cells as well as their subpopulations. Therefore, there is a possibility that some miRNAs could be studied at different stages of MS during NTZ treatment, and these specific miRNAs can be tested as markers of therapeutic response to this drug in future studies. Physiopathology, gene expression in B cells and their subpopulations can help understand this complex puzzle involving miRNAs and the therapeutic response of patients with MS.

Latent tuberculosis infection reactivation in patients with multiple sclerosis in use of disease-modifying therapies: A systematic review.

BACKGROUND: Tuberculosis (TB) is an infectious-contagious disease caused by Mycobacterium tuberculosis. This disease can act acutely or in latent form as granuloma. Multiple Sclerosis (MS) is a chronic inflammatory disease more common in the Central Nervous System (CNS). Its treatment involves disease-modifying therapies (DMTs), which can predispose MS patients to a higher risk of infections by interfering in the immune system. Patients undergoing MS treatment could be more susceptible to Latent Tuberculosis Infection (LTBI) reactivation. This study aims to elucidate the possible relationship between MS and LTBI through a systematic review of the literature. METHODS: MEDLINE/PubMed, Cochrane, ScienceDirect, LILACS, and SciELO were systematically reviewed from 2010 to 2020 and Google Scholar from 2015 to 2020 to detect eligible papers. The following keywords were used for this search: "LTBI and MS"; "Multiple Sclerosis and Latent Tuberculosis"; "Multiple Sclerosis and Latent Tuberculosis infection reactivation"; "Multiple Sclerosis and Pulmonary Tuberculosis"; "Multiple Sclerosis and Active Tuberculosis"; "Multiple Sclerosis and Tuberculosis Reactivation" for MEDLINE/Pubmed and ScienceDirect; and "Multiple Sclerosis and Latent Tuberculosis Infection" for Google Scholar, Cochrane, SCIELO, and LILACS. The filter for "review articles," "research articles," and "case reports" was applied in ScienceDirect. RESULTS: Fourteen (14) studies describing the relationship between MS and LTBI were included in qualitative synthesis: case-report (2), prevalence (2), non-systematic review (4), expert consensus (2), and case-control (4) studies. CONCLUSION: The reactivation of LTBI is well understood, but hardly any literature addressed the association between the contagious disease and MS' treatment. The selected articles are observational studies that offer limited data and differ in many aspects detailed over this study. These divergences make it challenging to compare articles' results. Nevertheless, most reports recommend screening for LTBI before starting MS treatment, mainly in high incidence countries.

Neuralgic Amyotrophy: Its Importance in Orthopedics Practice.

The present academic work aims to contribute to an early diagnosis of neuralgic amyotrophy (NA) because of its high prevalence in the population. This disease is a neuromuscular syndrome with unclear etiology; it affects mostly the brachial plexus, causing acute pain in the affected shoulder, paralysis, and disabilities. Considering the importance of an early treatment that can modify the prognosis of the patient, knowing the last updates about the syndrome as its clinical presentation is important. Data analysis was conducted through an online non-systematic review that indicated the epidemiology, pathophysiology, and differential diagnosis and prognosis of NA. Knowledge of the clinical features of NA is not common; however, it is important in orthopedic practice because it requires differentiation from spine pathologies.

Prevalence of multiple sclerosis in key cities of Brazil. A study in Joinville, Southern Brazil.

BACKGROUND: The Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS) has launched an initiative to determine the prevalence of multiple sclerosis (MS) in Brazil, based on key cities deemed representative of their regions in terms of demographic and environmental features. OBJECTIVE: To investigate the prevalence rate of MS in Joinville. METHODS: We reviewed the medical records of all patients who lived in Joinville and met the 2010 McDonald's diagnostic criteria revised for MS on the prevalence day (March 11, 2016). Potential MS patients included individuals treated by all practicing neurologists in the city and the ones found in patients' association and the database of the Municipal Department of Health. Advertisements about the survey were also broadcast on radio and television. Patients who were not living in Joinville on the prevalence day were excluded. All potential MS patients were invited to an in-person diagnostic review, carried out by a panel of experienced neurologists with special expertise in MS on March 11, 2016. RESULTS: The MS prevalence rate was 13.5 per 100,000 inhabitants (95% confidence interval [95%CI] 12.9-14.0/100,000). A total of 51 (66.2%) participants were females, and 26 (33.7%) were males (female to male ratio=1.9:1). Out of the 77 patients, 73 (94.8%) were Caucasians, and four (5.1%) were mixed-race. CONCLUSIONS: Despite its latitude location and European colonization, the prevalence rate was below expectation. The intense internal migration from regions with lower MS prevalence rates to Joinville may have played a role in attenuating the increased risk of MS associated with latitude gradient and European ancestry. Prevalence studies in other cities from Southern Brazil with no significant internal migration and taking part in this broad project may clarify this issue.

Encephalopathy responsive to thiamine in severe COVID-19 patients.

Encephalopathy is one of the most frequent neurological complications of severe Coronavirus Disease 2019 (COVID-19) patients. Cytokine storm and sepsis, hypercatabolic states, the use of furosemide and dialytic therapy represent risk factors for thiamine deficiency and are also found in patients with severe COVID-19. In this retrospective case series, we report clinical and neurological findings of fifteen patients with COVID-19-associated Wernicke Encephalopathy (WE) and their response to treatment with intravenous thiamine. All patients had encephalopathy, with 67% displaying at least one additional sign of classic WE triad (ophthalmoparesis and ataxia). Two patients (13%) had the classic triad. All COVID-19 patients had significant improvement of the neurological manifestations between two to five days after intravenous thiamine administration. Eleven patients (73%) had good neurological outcome at hospital discharge and only two patients (13%) died. This case series suggests that thiamine deficiency may be an etiology of encephalopathy in severe COVID-19 patients and its treatment may represent a safety and low-cost response to reduce the neurological burden.

Evaluation of diagnosis and treatment practices of Brazilian neurologists among patients with multiple sclerosis.

BACKGROUND: Recent changes to the diagnostic criteria for multiple sclerosis (MS) and new medications have had a major impact on the way in which specialists manage the disease. OBJECTIVE: To investigate factors considered by Brazilian neurologists in managing MS, and to identify how these contribute to diagnosis and treatment. METHODS: Potential participants were selected by a steering committee (MS experts who developed this survey). Only MS specialists were included in the study (neurologists who had completed a neuroimmunology fellowship or who were treating more than 30 MS patients). Links to the online questionnaire were distributed between March 2019 and January 2020. This questionnaire was composed of sections with hypothetical MS scenarios. RESULTS: Neurologists from 13 Brazilian states responded to the survey (n = 94). In the clinically isolated syndrome (CIS) scenario, the respondents agreed to treat patients with a high risk of MS diagnosis, whereas in the radiologically isolated syndrome (RIS) half of the respondents opted not to treat, even among high-risk patients. In cases of low-activity relapsing-remitting MS (RRMS), the choice of treatment was distributed among interferon beta, glatiramer acetate and teriflunomide, which were changed to fingolimod and natalizumab, as RRMS severity increased. The topics in which disagreement was found included practices regarding use of disease-modifying therapy (DMT) for pregnant patients and the washout period required for some DMTs. CONCLUSIONS: This study enabled identification of areas of agreement and disagreement about MS treatment among Brazilian neurologists, which can be used to update future protocols and improve patient management.

Patients and neurologists have different perceptions of multiple sclerosis symptoms, care and challenges.

BACKGROUND: Basic steps in the management of patients with Multiple Sclerosis (MS), such as good patient understanding of the disease and active participation in its management are extremely important, as they directly influence treatment adherence and success. Therefore, this study aimed to evaluate the perception of MS patients and neurologists pertaining to the most common disease symptoms, disabilities that impact on quality of life, and patient concerns and difficulties during medical visits, as information that can be used to improve the doctor-patient relationship. METHODS: A cross-sectional study involving two groups: the first composed of neurologists and the second of patients. Participants of the first group were selected by a Steering Committee (15 predetermined neurologists representing each region of Brazil and specialized in MS and neuroimmunological disorders, who also assumed the role of creating the survey and questionnaire). Participants of the second group were selected following dissemination of a questionnaire on the AME's social networks (Amigos Múltiplos pela Esclerose, a non-governmental organization to support patients with MS). Questions about sociodemographic data, disease impact on quality of life, symptoms perception, and concerns and issues regarding disease care were put to both groups. RESULTS: A total of 317 patients and 182 neurologists answered the questionnaires. Significant divergences were found between the perceptions of patients and neurologists in relation to orientation and information given during medical appointments, and also regarding patient participation in treatment and therapy choice. Considering the topic assessing impact on quality of life, more than 70% of neurologists perceived that autonomy to work and travel, and future planning were aspects that most affected patient lives, however, almost 50% of patients reported that disease monitoring did not affect their life in any way. Analysis of data regarding MS symptoms revealed neurologists to consider physical symptoms, such as ambulation issues, imbalance, falls and urinary incontinence, to be those most interfering with patient quality of life, whereas patients considered non-physical symptoms, such as fatigue, pain, cognitive and memory problems to be more significant. Patients with primary progressive MS complained more about ambulation issues, imbalance and falls (p<0.05), when compared to patients with other disease phenotypes. CONCLUSION: Significant differences in disease perception were found in this study. While neurologists tended to overestimate the consequences and symptoms of the disease, for most patients, the disease impact on activities did not appear to be as significant, with more complaints regarding non-physical symptoms. Although neurologists described involving patients in treatment decisions and providing them with appropriate orientation during medical appointments, the opposite was reported by patients. These results may help to improve treatment adherence and disease outcomes by redefining the doctor-patient relationship.

Recommendations by the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and the Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) on vaccination in general and specifically against SARS-CoV-2 for patients with demyelinating diseases of the central nervous system.

The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.