SARS-CoV-2 Uses CD4 to Infect T Helper Lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as coronavirus disease-2019 (COVID-19). SARS-CoV-2 infects the lungs and may cause several immune-related complications such as lymphocytopenia and cytokine storm which are associated with the severity of the disease and predict mortality . The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is not fully understood. Here we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells in a mechanism that also requires ACE2 and TMPRSS2. Once inside T helper cells, SARS-CoV-2 assembles viral factories, impairs cell function and may cause cell death. SARS-CoV-2 infected T helper cells express higher amounts of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may explain the poor adaptive immune response of many COVID- 19 patients.

Brazilian Consensus for the Treatment of Multiple Sclerosis: Brazilian Academy of Neurology and Brazilian Committee on Treatment and Research in Multiple Sclerosis.

The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more effective and personalized treatment, but the choice and management of disease-modifying therapies (DMTs) is becoming increasingly complex. In this context, experts from the Brazilian Committee on Treatment and Research in Multiple Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology have convened to establish this Brazilian Consensus for the Treatment of MS, based on their understanding that neurologists should be able to prescribe MS DMTs according to what is better for each patient, based on up-to-date evidence and practice. We herein propose practical recommendations for the treatment of MS, with the main focus on the choice and management of DMTs, as well as present a review of the scientific rationale supporting therapeutic strategies in MS.

Brazilian Consensus for the Treatment of Multiple Sclerosis: Brazilian Academy of Neurology and Brazilian Committee on Treatment and Research in Multiple Sclerosis / Consenso Brasileiro para o Tratamento da Esclerose Múltipla: Academia Brasileira de Neurologia e Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla

ABSTRACT The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more effective and personalized treatment, but the choice and management of disease-modifying therapies (DMTs) is becoming increasingly complex. In this context, experts from the Brazilian Committee on Treatment and Research in Multiple Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology have convened to establish this Brazilian Consensus for the Treatment of MS, based on their understanding that neurologists should be able to prescribe MS DMTs according to what is better for each patient, based on up-to-date evidence and practice. We herein propose practical recommendations for the treatment of MS, with the main focus on the choice and management of DMTs, as well as present a review of the scientific rationale supporting therapeutic strategies in MS.

RESUMO O crescent arsenal terapêutico na esclerose múltipla (EM) tem permitido tratamentos mais efetivos e personalizados, mas a escolha e o manejo das terapias modificadoras da doença (TMDs) tem se tornado cada vez mais complexos. Neste contexto, especialistas do Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla e do Departamento Científico de Neuroimunologia da Academia Brasileira de Neurologia reuniram-se para estabelecer este Consenso Brasileiro para o Tratamento da EM, baseados no entendimento de que neurologistas devem ter a possibilidade de prescrever TMDs para EM de acordo com o que é melhor para cada paciente, com base em evidências e práticas atualizadas. Por meio deste documento, propomos recomendações práticas para o tratamento da EM, com foco principal na escolha e no manejo das TMDs, e revisamos os argumentos que embasam as estratégias de tratamento na EM.

Normative values of the Brief Repeatable Battery of Neuropsychological Tests in a Brazilian population sample: discrete and regression-based norms.

Objective Cognitive dysfunction is common in multiple sclerosis. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was developed to assess cognitive functions most-frequently impaired in multiple sclerosis. However, normative values are lacking in Brazil. Therefore, we aimed to provide continuous and discrete normative values for the BRB-N in a Brazilian population sample. Methods We recruited 285 healthy individuals from the community at 10 Brazilian sites and applied the BRB-N version A in 237 participants and version B in 48 participants. Continuous norms were calculated with multiple-regression analysis. Results Mean raw scores and the 5th percentile for each neuropsychological measure are provided, stratified by age and educational level. Healthy participants' raw scores were converted to scaled scores, which were regressed on age, sex and education, yielding equations that can be used to calculate predicted scores. Conclusion Our normative data allow a more widespread use of the BRB-N in clinical practice and research.

Relationship between Expanded Disability Status Scale scores and the presence of temporomandibular disorders in patients with multiple sclerosis.

OBJECTIVES: The objectives of this study were to assess the prevalence of temporomandibular disorders (TMDs) in patients with relapsing-remitting multiple sclerosis (MS) and to investigate whether an association exists between the presence of TMD symptoms and the degree of MS-related disability. MATERIALS AND METHODS: In all, 120 individuals were evaluated: 60 patients with a diagnosis of relapsing-remitting MS and 60 age- and sex-matched controls without neurological impairments. A questionnaire recommended by the European Academy of Craniomandibular Disorders for the assessment of TMD symptoms was administered. For those who answered affirmatively to at least one of the questions, the RDC/TMD Axis I instrument was used for a possible classification of TMD subtypes. The Expanded Disability Status Scale (EDSS) was the measure of the degree of MS-related disability. STATISTICAL ANALYSIS USED: Fisher's exact test was used to analyze the data. ANOVA was used to detect significant differences between means and to assess whether the factors influenced any of the dependent variables by comparing means from the different groups. RESULTS: The prevalence of TMD symptoms in patients with MS was 61.7% versus 18.3% in the control group (CG). A diagnosis of TMD was established for 36.7% in the MS group and 3.3% in the CG (P = 0.0001). There were statistically significant differences between degrees of MS-related disability and the prevalence of TMD (P = 0.0288). CONCLUSIONS: The prevalence of both TMD and TMD symptoms was significantly greater in the MS group. EDSS scores and TMD prevalence rates were inversely related.

Normative values of the Brief Repeatable Battery of Neuropsychological Tests in a Brazilian population sample: discrete and regression-based norms / Valores normativos da Brief Repeatable Battery of Neuropsychological Tests (BRB-N) em uma amostra da população Brasileira: dados discretos e contínuos

ABSTRACT Objective Cognitive dysfunction is common in multiple sclerosis. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was developed to assess cognitive functions most-frequently impaired in multiple sclerosis. However, normative values are lacking in Brazil. Therefore, we aimed to provide continuous and discrete normative values for the BRB-N in a Brazilian population sample. Methods We recruited 285 healthy individuals from the community at 10 Brazilian sites and applied the BRB-N version A in 237 participants and version B in 48 participants. Continuous norms were calculated with multiple-regression analysis. Results Mean raw scores and the 5th percentile for each neuropsychological measure are provided, stratified by age and educational level. Healthy participants' raw scores were converted to scaled scores, which were regressed on age, sex and education, yielding equations that can be used to calculate predicted scores. Conclusion Our normative data allow a more widespread use of the BRB-N in clinical practice and research.

RESUMO Objetivo Disfunção cognitiva é comum em pacientes com esclerose múltipla. Por isto, a Brief Repeatable Battery of Neuropsychological Tests (BRB-N) foi desenvolvida para avaliar as funções cognitivas mais frequentemente alteradas na doença. Entretanto, estão faltando dados normativos desta bateria no Brasil. Assim, nosso objetivo foi fornecer valores normativos contínuos e discretos da BRB-N para a população brasileira. Métodos Foram recrutados 285 indivíduos sadios da comunidade em 10 centros do Brasil e aplicada a versão A em 237 e a versão B em 48 sujeitos. Normas contínuas foram calculadas com análise de regressão múltipla. Resultados Escores brutos médios e 5°percentil para cada subteste são fornecidos, estratificados por idade e nível educacional. Os escores brutos dos sujeitos sadios foram convertidos em escores de escalas e postos em regressão quanto a idade, sexo e educação, fornecendo equações que podem ser usadas para calcular escores previsíveis. Conclusão Nossos dados normativos permitem um uso mais amplo da BRB-N na prática clínica e na pesquisa, fornecendo normas para dados discretos e contínuos. Normas para dados discretos deveriam ser usadas com cuidado e escores demograficamente ajustados são geralmente preferidos quando interpretando dados neuropsicológicos.

Superficial siderosis of the central nervous system is a rare and possibly underdiagnosed disorder.

METHODS: Series of cases collected from Brazilian centers. RESULTS: We studied 13 cases of patients presenting with progressive histories of neurological dysfunction caused by SS-CNS. The most frequent clinical findings in these patients were progressive gait ataxia, hearing loss, hyperreflexia and cognitive dysfunction. The diagnoses of SS-CNS were made seven months to 30 years after the disease onset. CONCLUSION: SS-CNS is a rare disease that may remain undiagnosed for long periods. Awareness of this condition is essential for the clinician.

Superficial siderosis of the central nervous system is a rare and possibly underdiagnosed disorder / Siderose superficial do sistema nervoso central é uma doença rara e possivelmente subdiagnosticada

ABSTRACT Superficial siderosis (SS) of the central nervous system (CNS) is a rare and possibly underdiagnosed disorder resulting from chronic or intermittent bleeding into the subarachnoid space, leading to deposition of blood products in the subpial layers of the meninges. Magnetic resonance imaging (MRI) shows a characteristic curvilinear pattern of hypointensity on its blood-sensitive sequences. Methods Series of cases collected from Brazilian centers. Results We studied 13 cases of patients presenting with progressive histories of neurological dysfunction caused by SS-CNS. The most frequent clinical findings in these patients were progressive gait ataxia, hearing loss, hyperreflexia and cognitive dysfunction. The diagnoses of SS-CNS were made seven months to 30 years after the disease onset. Conclusion SS-CNS is a rare disease that may remain undiagnosed for long periods. Awareness of this condition is essential for the clinician.

RESUMO Siderose superficial (SS) do sistema nervoso central (SNC) é uma doença rara e provavelmente subdiagnosticada, resultante de sangramento crônico no espaço subaracnóide, levando ao depósito de produtos sanguíneos nas camadas meníngeas subpiais. Ressonância magnética (RM) mostra um padrão curvilíneo característico com hipointensidade nas suas sequências sensíveis a sangue. Métodos Série de casos coletados de centros brasileiros. Resultados Apresentamos 13 casos de pacientes com história progressiva de disfunção neurológica causada por SS-SNC. Os achados clínicos mais frequentes destes pacientes foram ataxia progressiva da marcha, perda auditiva, hiperreflexia e disfunção cognitiva. O diagnóstico de SS-SNC foi firmado de sete meses a 30 anos após o início da doença. Conclusão SS-SNC é uma condição rara que pode permanecer sem diagnóstico por longos períodos. O conhecimento desta entidade é essencial ao clínico.

Safety of switching from natalizumab straight into fingolimod in a group of JCV-positive patients with multiple sclerosis.

OBJECTIVE: To assess safety of the switch between natalizumab and fingolimod without a washout period. METHODS: Prospective data on 25 JCV positive patients who underwent this medication switch were collected and analyzed. RESULTS: After a median period of nine months from the medication switch, there were no safety issues to report. The patients had good disease control and no adverse events were reported. CONCLUSION: Washout may not be necessary in daily practice when switching from natalizumab to fingolimod. Expertise on multiple sclerosis management, however, is essential for drug switching.

Safety of switching from natalizumab straight into fingolimod in a group of JCV-positive patients with multiple sclerosis / Segurança na mudança direta de natalizumabe para fingolimode em um grupo de pacientes com esclerose múltipla e positivos para JCV

ABSTRACT Objective To assess safety of the switch between natalizumab and fingolimod without a washout period. Methods Prospective data on 25 JCV positive patients who underwent this medication switch were collected and analyzed. Results After a median period of nine months from the medication switch, there were no safety issues to report. The patients had good disease control and no adverse events were reported. Conclusion Washout may not be necessary in daily practice when switching from natalizumab to fingolimod. Expertise on multiple sclerosis management, however, is essential for drug switching.

RESUMO Objetivo Avaliar a segurança na mudança entre natalizumabe e fingolimode sem período de washout. Métodos Dados prospectivos de 25 pacientes positivos para vírus JC que tiveram sua medicação modificada foram coletados e analisados. Resultados Após uma mediana de nove meses da troca de medicação, não havia aspectos de segurança a relatar. Os pacientes estavam com bom controle da doença e não foram relatados eventos adversos. Conclusão Washout pode não ser necessário na prática diária para a mudança entre natalizumabe e fingolimode. No entanto, expertise no manejo de esclerose múltipla é essencial para esta troca entre medicações.

Real-life experience with fampridine (Fampyra®) for patients with multiple sclerosis and gait disorders.

BACKGROUND: Fampridine is a broad-spectrum voltage-dependent potassium channel blocker that enhances synaptic transmission. The drug has been shown to be able to ameliorate conduction in demyelinated axons, thereby leading to improved gait in patients with multiple sclerosis (MS). OBJECTIVE: To assess the "real-life" efficacy and safety of fampridine prescribed for gait disorders in MS. This was an observational and prospective study carried out at MS Units participating in the Brazilian Multiple Sclerosis Study Group. METHODS: Patients with MS and gait disorders were prescribed fampridine (10 mg twice a day), irrespectively of the degree of disability determined by MS. Neurological disability determined by MS was assessed with the expanded disability scale score (EDSS). Outcomes for efficacy and safety of the drug were evaluated by the 25 foot-walk test and by the adverse events of fampridine. RESULTS: The time taken to walk 25 feet decreased by 20% or more in 62 patients (70%). Twenty-five patients were considered to be non-responders to this treatment. Improvement in walking speed was independent of improvement of disability. Mild or moderate adverse events were reported in 8% of patients. CONCLUSION: Fampridine is an efficient and safe therapeutic option for patients with MS and gait disorders.

No evidence of disease activity in multiple sclerosis patients.

INTRODUCTION: Multiple Sclerosis is a chronic inflammatory demyelinating disease that affects 2.5 million people in the world. NEDA (No evidence of disease Activity) -4 is a new concept related to absence of disease activity in the context of MS. It takes into account the following four parameters: relapses; disability progression; lesion load and brain atrophy. Areas covered: The purpose of this paper is to visit the new emerging concepts of NEDA. Although it is considered important and attractive, there is a lack of uniformity. Expert commentary: Although NEDA-4 embraces important markers of disease activity and degeneration, this definition is still evolving and other parameters apart from the loss of brain volume might be included, especially those related to disability, such as cognitive problems, visual function, fatigue and pain.

Dengue fever in patients with multiple sclerosis taking fingolimod or natalizumab.

Dengue fever is the most prevalent mosquito-borne viral illness in humans. There may be different clinical manifestations of the disease, from mild symptoms to hemorrhagic forms of dengue fever and even neurological complications of this viral infection. Blood cells are usually affected, and thrombocytopenia is the hallmark of the disease. This paper presents 15 cases of dengue fever in patients with multiple sclerosis (MS) taking fingolimod or natalizumab. There were no complications of dengue fever or worse outcomes of MS in these patients, and only four of them needed short-term treatment withdrawal due to lymphopenia.

Cerebrum-cervical arterial dissection in adults during sports and recreation / Dissecção arterial cérebro-cervical em adultos durante prática de esportes e recreação

Dissection of cervical arteries constitutes a medical emergency. Although relatively rarely, activities classified as sports and recreation may be a cause of arterial dissection independently of neck or head trauma. The purpose of the present paper was to present a series of cases of cerebrum-cervical arterial dissection in individuals during or soon after the practice of these sports activities. Methods Retrospective data on patients with arterial dissection related to sports and recreation. Results Forty-one cases were identified. The most frequently affected vessel was the vertebral artery. A large variety of activities had a temporal relationship to arterial dissection, and jogging was the most frequent of these. This is the largest case series in the literature. Conclusion Arterial dissection may be a complication from practicing sports.

A dissecção das artérias cervicais é uma emergência médica. Embora de forma relativamente rara, certas atividades descritas como esportes e recreação podem ser a causa de dissecção arterial independentemente de trauma de crânio ou cervical. O propósito do presente estudo é apresentar uma série de casos de dissecção de artérias cérebro-cervicais em indivíduos durante ou logo após a prática destas atividades desportivas. Métodos Dados retrospectivos de pacientes com dissecção arterial relacionada à prática de esportes e recreação. Resultados Quarenta e um casos foram identificados. A artéria mais frequentemente afetada foi a vertebral. Uma grande variedade de atividades teve relação temporal com a dissecção arterial, sendo a corrida a mais frequente delas. Esta é a maior série de casos da literatura. Conclusão Dissecção arterial pode ser uma complicação da prática de esportes.

Alternatives for reducing relapse rate when switching from natalizumab to fingolimod in multiple sclerosis.

Natalizumab is a therapeutic option for treating multiple sclerosis (MS) and is particularly efficacious for patients with highly active disease. A long washout period has been recommended between withdrawal of natalizumab and start of fingolimod (another option for treating MS). This long washout period has been associated with a significant increase in MS activity. In the present study, a group of 96 patients who were switched from natalizumab to fingolimod had short washout periods between drugs, or monthly corticosteroid pulse therapy if longer washout periods were recommended. This therapeutic approach led to the lowest reported relapse rate so far, among patients with MS switching from natalizumab to fingolimod (8.3%). No complications from short withdrawal were observed in this group of patients.

Cerebrum-cervical arterial dissection in adults during sports and recreation.

UNLABELLED: Dissection of cervical arteries constitutes a medical emergency. Although relatively rarely, activities classified as sports and recreation may be a cause of arterial dissection independently of neck or head trauma. The purpose of the present paper was to present a series of cases of cerebrum-cervical arterial dissection in individuals during or soon after the practice of these sports activities. METHODS: Retrospective data on patients with arterial dissection related to sports and recreation. RESULTS: Forty-one cases were identified. The most frequently affected vessel was the vertebral artery. A large variety of activities had a temporal relationship to arterial dissection, and jogging was the most frequent of these. This is the largest case series in the literature. CONCLUSION: Arterial dissection may be a complication from practicing sports.

Fraqueza muscular adquirida na UTI (ICU-AW): efeitos sistêmicos da eletroestimulação neuromuscular / Muscular weakness acquired in ICU (ICU-AW): effects of systemic neuromuscular electrical stimulation

Com os avanços tecnológicos alcançados atualmente na terapia intensiva e maior sobrevida dos pacientes, outros desafios têm surgido para os profissionais de saúde. Dentre alguns, destaca-se a fraqueza muscular adquirida na UTI (ICU-AW), caracterizada por paresia esquelética e respiratória dos músculos promovendo aumento nas taxas de mortalidade e comprometimento da qualidade de vida. Sua incidência varia de 30% a 60% e tem na síndrome da resposta inflamatória sistêmica (SIRS) e na disfunção de múltiplos órgãos (DMO) sua principal etiologia. Outros fatores de risco como a hiperglicemia, o uso de bloqueadores neuromusculares e sedativos, a imobilidade e a própria ventilação mecânica estão entre os mais comuns. Entre as medidas de combate à ICU-AW, está o conceito de mobilização precoce, bem como despertar diário e controle estreito da glicemia. Nesse contexto, a letroestimulação muscular apresenta-se como recurso de grande valia. Sua principal vantagem está no fato de poder ser empreendida independentemente da cooperação do paciente, e por ser capaz de gerar respostas musculares eficientes, bem como resultados satisfatórios na preservação da massa muscular, condicionamento físico e funcionalidade dos que usam essa ferramenta. Desfechos interessantes têm sido observados em diversos perfis de pacientes, como os de doença pulmonar obstrutiva crônica (DPOC) e traumatismo raquimedular (TRM). No paciente crítico, seu uso tem mostrado redução nos tempos de ventilação mecânica (VM), internação na UTI e maior funcionalidade dos pacientes. A relevância dos efeitos sistêmicos e metabólicos provenientes da eletroestimulação neuromuscular (ENM) tem sido a base para os estudos nos pacientes críticos. Portanto, a ICU-AW é uma realidade no cenário da terapia intensiva e sua prevenção tem dado margem à aparição de novas propostas e ferramentas na prevenção dessas complicações.

With technological advances currently achieved in intensive care and increased patient survival, other challenges have emerged to health professionals. Among some, there is acquired weakness in the ICU (ICU-AW), characterized by skeletal and respiratory muscle paresis promoting an increase in mortality and impaired quality of life. The range of occurrence is 30% to 60% of critically ill patients, and systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction (MOD) are is the main etiology. Other risk factors such as hyperglycemia, the use of neuromuscular blockers and sedatives, immobility and mechanical ventilation are among the most common. Preventing ICU-AW is the concept of early mobilization and daily awakening and tight control of blood glucose. In this context, muscle electrostimulation appears as a great resource. This can be used undertaken regardless of the cooperation of the patient, and be able to generate efficient muscle responses showing satisfactory results in the preservation of muscle mass, physical fitness and functionality of using this tool. Interesting outcomes have been observed in several profiles of patients, such as chronic obstructive pulmonary disease (COPD) and spinal cord injury (SCI). In critically ill patients, its use has shown reduction in mechanical ventilation (MV) days, ICU length and increased functionality of patients. The relevance of the systemic and metabolic effects from the electrostimulation neuromuscular (NMES) has been the basis for studies in critically ill patients. The refore, the ICU-AW is a reality in the setting of intensive care and prevention has given rise to appearance of new proposals and tools in preventing these complications.

Botulinum Neurotoxin Type A in Neurology: Update.

This paper reviews the current and most neurological (central nervous system, CNS) uses of the botulinum neurotoxin type A. The effect of these toxins at neuromuscular junction lends themselves to neurological diseases of muscle overactivity, particularly abnormalities of muscle control. There are seven serotypes of the toxin, each with a specific activity at the molecular level. Currently, serotypes A (in two preparations) and B are available for clinical purpose, and they have proved to be safe and effective for the treatment of dystonia, spasticity, headache, and other CNS disorders in which muscle hyperactivity gives rise to symptoms. Although initially thought to inhibit acetylcholine release only at the neuromuscular junction, botulinum toxins are now recognized to inhibit acetylcholine release at autonomic cholinergic nerve terminals, as well as peripheral release of neuro-transmitters involved in pain regulation. Its effects are transient and nondestructive, and largely limited to the area in which it is administered. These effects are also graded according to the dose, allowing individualized treatment of patients and disorders. It may also prove to be useful in the control of autonomic dysfunction and sialorrhea. In over 20 years of use in humans, botulinum toxin has accumulated a considerable safety record, and in many cases represents relief for thousands of patients unaided by other therapy.

Increased multiple sclerosis relapses related to lower prevalence of pain.

OBJECTIVE: The study aims to investigate the presence of pain amongst multiple sclerosis (MS) patients. METHOD: One hundred MS patients responded to questionnaires evaluating neuropathic and nociceptive pain, depression and anxiety. Statistical analysis was performed using the Mann-Whitney U, Chi-Square and two-tailed Fisher's exact tests and multivariate logistic regression. RESULTS: Women had a statistically higher prevalence of pain (p = 0.037), and chances of having pain after the age of 50 reduced. Women with pain had a statistically significant lower number of relapses (p = 0.003), restricting analysis to those patients with more than one relapse. After the second relapse, each relapse reduced the chance of having pain by 46%. Presence of pain was independent of Expanded Disability Status Scale (EDSS) anxiety, and depression. CONCLUSION: Our findings suggest a strong inverse association between relapses and pain indicating a possible protective role of focal inflammation in the control of pain.