Impact of polypharmacy and the use of medicines associated with the risk of falls in the elderly / Impacto da polifarmácia e o uso de medicamentos associados ao risco de quedas de idosos

Objective: to associate polypharmacy and medication classes with the risk of falls in the elderly. Method: cross-sectional and quantitative study, carried out in a Specialty Medical Outpatient Clinic in the city of São Paulo ­ SP, with 117 elderly people, from March to November 2019. Data collection was carried out by fully transcribing the prescriptions into an individual form and the Downton Falls Risk Scale. To compare the risk of falls with polypharmacy and medication classes, the Mann-Whitney and Chi-Square tests were used. In all comparative analyzes a significance level of 5% and a confidence interval of 95% were used. Results: The risk of falls showed a significant correlation with the number of medications, an average of 5.8 per day (p<0.0001) and the medication classes, antihypertensives (p<0.0001), oral antidiabetics (p=0.027), diuretics (p<0.0001) and antidepressants (p=0.042). Conclusion and implications for practice: therefore, the importance of evaluating factors related to the increased risk of falls is highlighted, for subsequent planning and implementation of strategies to deal with adverse reactions and the measures to be taken to ensure the effectiveness and safety of drug treatment.

Objetivo: associar a polifarmácia e as classes medicamentosas com o risco de quedas em idosos. Método: estudo transversal e quantitativo, realizado em um Ambulatório Médico de Especialidades na cidade de São Paulo ­ SP, com 117 idosos, no período de março a novembro de 2019. A coleta dos dados foi realizada pela transcrição integral dos receituários para um formulário individual e pela Escala de Risco de Quedas de Downton. Para comparar o risco de quedas com a polimedicação e as classes medicamentosas foram utilizados os testes de Mann-Whitney e o Qui-Quadrado. Em todas as análises comparativas foi utilizado um nível de significância de 5% e intervalo de confiança de 95%. Resultados: O risco de quedas apresentou correlação significativa com o número de medicamentos, média de 5,8 ao dia (p<0,0001) e as classes medicamentosas, os anti-hipertensivos (p<0,0001), os antidiabéticos orais (p=0,027), os diuréticos (p<0,0001) e os antidepressivos (p=0,042). Conclusão e implicações para a prática: portanto, ressalta-se a importância da avaliação dos fatores relacionados ao aumento do risco de quedas, para posterior realização de um planejamento e implementação de estratégias no cuidado das reações adversas e nas medidas a serem tomadas para garantir a efetividade e segurança do tratamento medicamentoso.

Review of dengue, zika and chikungunya infections in nervous system in endemic areas / Revisão da infecção por dengue, zika e chikungunya no sistema nervoso em áreas endêmicas

Abstract Dengue, zika, and chikungunya are arboviruses of great epidemiological relevance worldwide. The emergence and re-emergence of viral infections transmitted by mosquitoes constitute a serious human public health problem. The neurological manifestations caused by these viruses have a high potential for death or sequelae. The complications that occur in the nervous system associated with arboviruses can be a challenge for diagnosis and treatment. In endemic areas, suspected cases should include acute encephalitis, myelitis, encephalomyelitis, polyradiculoneuritis, and/or other syndromes of the central or peripheral nervous system, in the absence of a known explanation. The confirmation diagnosis is based on viral (isolation or RT-PCR) or antigens detection in tissues, blood, cerebrospinal fluid, or other body fluids, increase in IgG antibody titers between paired serum samples, specific IgM antibody in cerebrospinal fluid and serological conversion to IgM between paired serum samples (non-reactive in the acute phase and reactive in the convalescent). The cerebrospinal fluid examination can demonstrate: 1. etiological agent; 2. inflammatory reaction or protein-cytological dissociation depending on the neurological condition; 3. specific IgM, 4. intrathecal synthesis of specific IgG (dengue and chikungunya); 5. exclusion of other infectious agents. The treatment of neurological complications aims to improve the symptoms, while the vaccine represents the great hope for the control and prevention of neuroinvasive arboviruses. This narrative review summarizes the updated epidemiology, general features, neuropathogenesis, and neurological manifestations associated with dengue, zika, and chikungunya infection.

Resumo Dengue, zika e chikungunya são arboviroses de grande relevância epidemiológica em todo o mundo. A emergência e reemergência dessas infecções virais transmitidas por mosquitos constituem um grave problema de saúde pública humana. As manifestações neurológicas causadas por esses vírus têm alto potencial de morte ou sequelas. As complicações que ocorrem no sistema nervoso associadas às arboviroses podem representar um desafio diagnóstico e de tratamento. Em áreas endêmicas, casos suspeitos devem incluir encefalite, mielite, encefalomielite, polirradiculoneurite e/ou outras síndromes do sistema nervoso central ou periférico, na ausência de explicação conhecida. Caso confirmado de arbovirose neuroinvasivo é baseado na detecção viral (isolamento ou RT-PCR) ou de antígenos em tecidos, sangue, líquido cefalorraquidiano ou outros fluidos corporais, aumento dos títulos de anticorpos IgG entre amostras de soro pareadas, anticorpo IgM específico no líquido cefalorraquidiano e conversão sorológica para IgM entre amostras de soro pareadas. O exame do líquido cefalorraquidiano pode demonstrar: 1. agente etiológico; 2. reação inflamatória ou dissociação proteico-citológica, dependendo do quadro neurológico; 3. valor absoluto de IgM específica; 4. síntese intratecal de anticorpos IgG específicos (dengue e chikungunya); 5. exclusão de outros agentes infecciosos. O tratamento das complicações neurológicas visa melhorar os sintomas, enquanto a vacina representa a grande esperança para o controle e a prevenção das arboviroses neuroinvasivas. Esta revisão narrativa resume a atualização da epidemiologia, características gerais, neuropatogênese e manifestações neurológicas associadas à infecção pelos vírus da dengue, zika e chikungunya.

Review of dengue, zika and chikungunya infections in nervous system in endemic areas.

Dengue, zika, and chikungunya are arboviruses of great epidemiological relevance worldwide. The emergence and re-emergence of viral infections transmitted by mosquitoes constitute a serious human public health problem. The neurological manifestations caused by these viruses have a high potential for death or sequelae. The complications that occur in the nervous system associated with arboviruses can be a challenge for diagnosis and treatment. In endemic areas, suspected cases should include acute encephalitis, myelitis, encephalomyelitis, polyradiculoneuritis, and/or other syndromes of the central or peripheral nervous system, in the absence of a known explanation. The confirmation diagnosis is based on viral (isolation or RT-PCR) or antigens detection in tissues, blood, cerebrospinal fluid, or other body fluids, increase in IgG antibody titers between paired serum samples, specific IgM antibody in cerebrospinal fluid and serological conversion to IgM between paired serum samples (non-reactive in the acute phase and reactive in the convalescent). The cerebrospinal fluid examination can demonstrate: 1. etiological agent; 2. inflammatory reaction or protein-cytological dissociation depending on the neurological condition; 3. specific IgM, 4. intrathecal synthesis of specific IgG (dengue and chikungunya); 5. exclusion of other infectious agents. The treatment of neurological complications aims to improve the symptoms, while the vaccine represents the great hope for the control and prevention of neuroinvasive arboviruses. This narrative review summarizes the updated epidemiology, general features, neuropathogenesis, and neurological manifestations associated with dengue, zika, and chikungunya infection.

Dengue, zika e chikungunya são arboviroses de grande relevância epidemiológica em todo o mundo. A emergência e reemergência dessas infecções virais transmitidas por mosquitos constituem um grave problema de saúde pública humana. As manifestações neurológicas causadas por esses vírus têm alto potencial de morte ou sequelas. As complicações que ocorrem no sistema nervoso associadas às arboviroses podem representar um desafio diagnóstico e de tratamento. Em áreas endêmicas, casos suspeitos devem incluir encefalite, mielite, encefalomielite, polirradiculoneurite e/ou outras síndromes do sistema nervoso central ou periférico, na ausência de explicação conhecida. Caso confirmado de arbovirose neuroinvasivo é baseado na detecção viral (isolamento ou RT-PCR) ou de antígenos em tecidos, sangue, líquido cefalorraquidiano ou outros fluidos corporais, aumento dos títulos de anticorpos IgG entre amostras de soro pareadas, anticorpo IgM específico no líquido cefalorraquidiano e conversão sorológica para IgM entre amostras de soro pareadas. O exame do líquido cefalorraquidiano pode demonstrar: 1. agente etiológico; 2. reação inflamatória ou dissociação proteico-citológica, dependendo do quadro neurológico; 3. valor absoluto de IgM específica; 4. síntese intratecal de anticorpos IgG específicos (dengue e chikungunya); 5. exclusão de outros agentes infecciosos. O tratamento das complicações neurológicas visa melhorar os sintomas, enquanto a vacina representa a grande esperança para o controle e a prevenção das arboviroses neuroinvasivas. Esta revisão narrativa resume a atualização da epidemiologia, características gerais, neuropatogênese e manifestações neurológicas associadas à infecção pelos vírus da dengue, zika e chikungunya.

Searching for food in a concrete jungle: feeding ecology of a Psittacine assemblage (Aves, Psittacidae) in a major Amazonian city.

The efficient use of food resources is a precondition for wild species´ survival in urban environments. The feeding ecology of animals in tropical cities, however, remains poorly investigated. Here we study the feeding ecology of parrots in Manaus, a major Amazonian city, and compare the results with a parrot assemblage living in undisturbed habitats. We recorded 203 feeding bouts from eight parrot species, which consumed parts of 51 plant species. Parrot diets were dominated by native palm species (Arecaceae). Exotic plants, however, constituted an important portion of the diet of some parrots. Levin's indices, a measure of food niche width, varied from 0.40 to 0.83, indicating an overall tendency to generalist diets. Diet overlap between species was small, indicating broad resource partitioning between members of the assemblage. The diversity of plants consumed in the natural environment was greater than in the urban environment (71 species vs. 52). However, the diversity of plants consumed was similar for parrot species recorded both in natural and urban environments, indicating that occupation of the city does not imply an impoverishment in parrot diets. Creation of municipal protected areas and increasing the city afforestation would provide complementary strategies for Manaus parrot conservation.

Neurobrucellosis.

PURPOSE OF REVIEW: Brucellosis is one of the most common zoonosis worldwide, affecting 500 000 people, annually. Neurobrucellosis incidence is approximately 4%, and it is almost always heterogeneous. As there are no typical clinical features, its diagnosis is frequently misdiagnosing by other infections. RECENT FINDINGS: Neurobrucellosis picture includes meningitis, meningoencephalitis, encephalitis, cranial neuropathies, intracranial hypertension, sinus thrombosis, hemorrhages radiculitis, peripheral neuropathy, myelitis, and psychiatric manifestations. The diagnosis should be based on symptoms and signs suggestive of neurobrucellosis, not explained by other neurological disease, cerebrospinal fluid analysis, a positive Brucella serology or culture, and a response to specific antibiotics, with a significant improvement of cerebrospinal fluid parameters. SUMMARY: Neurobrucellosis can be insidious, and despite its global distribution, it is still unrecognized and frequently goes unreported. The understanding of the current epidemiology is necessary for eradication of the disease in humans, as well as the disease control in animals and prevention based on occupational hygiene and food hygiene.

Neurobrucellosis: the great mimicker.

Neurobrucellosis is caused by bacteria of the genus Brucella and is responsible for several clinical manifestations, making diagnosis challenging. The most common route of infection is through the consumption of unpasteurized or raw dairy products such as fresh milk, butter, and cheese. As neurological complications can develop chronically, they are frequently misdiagnosed as other infections, such as tuberculosis. This report reviews the clinical manifestations, diagnostic approach, treatment, and prognosis of neurobrucellosis, illustrating a case of chronic intracranial hypertension and meningoencephalitis secondary to brucellosis. The clinical presentation of brucellosis can mimic several systemic diseases, resulting in diagnostic delays and clinical complications. A high degree of suspicion is required, and neurobrucellosis should always be considered in the differential diagnosis of chronic meningitis.

Understanding Health Priorities, Behaviors, and Service Utilization Among Brazilian Immigrant Women: Implications for Designing Community-Based Interventions.

Brazilians represent a growing proportion of immigrants in the USA. Little is known about their health or healthcare utilization after their arrival. This study aimed to gather formative data to understand the needs of Brazilian immigrant women to guide public health interventions. We conducted five focus groups with Brazilian women born in Brazil (n = 47) and 13 key informant interviews with representatives from Brazilian-serving organizations. Participants were recruited from churches and social service organizations in the Greater Boston area. Findings revealed that mental health was the most pressing health priority; many attributed high levels of anxiety and depression to worries about undocumented status, separation from social networks, and strenuous work schedules. Occupational health issues were frequently mentioned, including musculoskeletal complaints, skin rashes, and respiratory problems. Domestic violence was also a concern, and many women feared reporting to police due to undocumented status. Most reported good access to medical care and described the quality of healthcare services as superior to that available in Brazil. However, many reported challenges with interpersonal communication with providers, dissatisfaction with a perceived unwillingness from providers to order medical tests or prescribe treatment, and limited access to mental health services. There was agreement that effective intervention strategies should use social media, radio, and group education in churches.

Adherence and barriers to drug therapy: relationship with the risk of falls in older adults / Adhesión y obstáculos con respecto a la terapia medicamentosa: relación con el riesgo de caídas en adultos mayores / Adesão e barreiras à terapêutica medicamentosa: relação com o risco de queda em idosos

ABSTRACT Objective: to verify the association of adherence and barriers to drug therapy with the risk of falls and the sociodemographic, clinical and economic variables. Method: a cross-sectional study, carried out with 117 aged individuals in a Medical Clinic of Specialties for Older Adults in the Southeast region of the city of São Paulo (SP), from March to November 2019. The following scales were applied: Downton Fall Risk, Morisky-Green Test and Brief Medication Questionnaire. Logistic regression was use to verify the association between adherence to the treatment and types of barriers to adherence and the risk of falls. A 5% significance level was used. Results: the older adults with low adherence to the drug treatment presented 5.57 times more chances of having a high risk of falling when compared to those with greater adherence, and those with a barrier in the recall domain had 22.75 times more chances of having a high risk of falling, in relation to the aged individuals without barriers in the recall domain. Conclusion: low and average adherence to drug therapy and the barrier related to the recall domain were associated with high risk of falls in the older adults.

RESUMEN Objetivo: verificar la asociación de la adhesión y los obstáculos con respecto a la terapia con el riesgo de caídas y las variables sociodemográficas, clínicas y económicas. Método: estudio transversal, realizado con 117 adultos mayores en una Clínica Médica Ambulatoria de Especialidades Geriátricas en la región sudeste de la ciudad de San Pablo (SP) entre marzo y noviembre de 2019. Se aplicaron las siguientes escalas: Riesgo de Caídas de Downton, prueba de Morisky-Green y Brief Medication Questionnaire. Se utilizó regresión logística para verificar la asociación entre la adhesión al tratamiento y los tipos de obstáculos con respecto a dicha adhesión y el riesgo de caídas. Se utilizó un nivel de significancia del 5%. Resultados: los adultos mayores con bajo nivel de adhesión al tratamiento medicamentoso presentaron 5,57 más probabilidades de tener un riesgo de caídas elevado en relación con los que presentaron más adhesión, y quienes tuvieron obstáculos en el dominio Recordatorio presentaron 22,75 más probabilidades de tener un riesgo de caídas elevado, en relación con los adultos mayores sin obstáculos en dicho dominio. Conclusión: los niveles bajo y medio de adhesión a la terapia medicamentosa y el obstáculo relacionado al dominio Recordatorio estuvieron asociados al riesgo de caída elevado en los adultos mayores.

RESUMO Objetivo: verificar a associação da adesão e das barreiras à terapêutica medicamentosa com o risco de quedas e as variáveis sociodemográficas, clínicas e econômicas. Método: estudo transversal, realizado com 117 idosos em um Ambulatório Médico de Especialidades do Idoso na Região Sudeste de cidade de São Paulo (SP), no período de março a novembro de 2019. Foram aplicadas as escalas: Risco de Queda de Downton, teste de Morisky-Green e Brief Medication Questionnaire. Para verificar a associação entre a adesão ao tratamento e tipos de barreiras a essa adesão e o risco de quedas, foi utilizada a regressão logística. Foi utilizado um nível de significância de 5%. Resultados: os idosos com baixa adesão ao tratamento medicamentoso apresentaram chance de 5,57 vezes de ter alto risco de queda em relação aos idosos com maior adesão, e aqueles com barreira no domínio recordação apresentaram chance de 22,75 vezes de ter alto risco de queda, em relação aos idosos sem barreira no domínio recordação. Conclusão: a baixa e média adesão à terapêutica medicamentosa e a barreira relacionada ao domínio recordação se associaram a alto risco de queda nos idosos.

[Evidence based guidelines. Diagnosis and management of Guillain-Barré syndrome in ten steps]. / Guía basada en la evidencia. Diagnóstico y manejo del síndrome de Guillain-Barré en diez pasos.

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and in 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.

El síndrome de Guillain-Barré (SGB) es una enfermedad inmunológica del nervio periférico y las raíces nerviosas, poco frecuente, potencialmente mortal y que suele desencadenarse por infecciones. La incidencia del SGB puede aumentar durante el brote de enfermedades infecciosas, tal como se observó en las epidemias del virus Zika en la Polinesia Francesa en 2013 y en América Latina en 2015. El diagnóstico y el manejo clínico del SGB pueden ser complicados ya que su presentación y el curso de la enfermedad son heterogéneos, y actualmente no se cuenta con guías clínicas internacionales. Para respaldar a los médicos, especialmente en el contexto de un brote de una enfermedad infecciosa, hemos desarrollado una guía clínica aplicable en todo el mundo para el diagnóstico y el tratamiento del SGB. La guía se basa en literatura actualizada y el consenso de expertos, y tiene una estructura de diez pasos para facilitar su uso en la práctica clínica. Inicialmente, brindamos una introducción a los criterios de diagnóstico, variantes clínicas y diagnósticos diferenciales del SGB. Los diez pasos luego abordan el reconocimiento y el diagnóstico temprano del SGB, la admisión a la unidad de cuidados intensivos, indicación y selección de tratamiento, seguimiento y tratamiento de la progresión de la enfermedad, predicción del curso clínico, resultados y tratamiento de complicaciones y secuelas.

Guía basada en la evidencia. Diagnóstico y manejo del síndrome de Guillain-Barré en diez pasos / Evidence based guidelines. Diagnosis and management of Guillain-Barré syndrome in ten steps

Resumen El síndrome de Guillain-Barré (SGB) es una enfermedad inmunológica del nervio periférico y las raíces nerviosas, poco frecuente, potencialmente mortal y que suele desencadenarse por infecciones. La incidencia del SGB puede aumentar durante el brote de enfermedades infecciosas, tal como se observó en las epidemias del virus Zika en la Polinesia Francesa en 2013 y en América Latina en 2015. El diagnóstico y el manejo clínico del SGB pueden ser complicados ya que su presentación y el curso de la enfermedad son heterogéneos, y actualmente no se cuenta con guías clínicas internacionales. Para respaldar a los médicos, especialmente en el contexto de un brote de una enfermedad infecciosa, hemos desarrollado una guía clínica aplicable en todo el mundo para el diagnóstico y el tratamiento del SGB. La guía se basa en literatura actualizada y el consenso de expertos, y tiene una estructura de diez pasos para facilitar su uso en la práctica clínica. Inicialmente, brindamos una introducción a los criterios de diagnóstico, variantes clínicas y diagnósticos diferenciales del SGB. Los diez pasos luego abordan el reconocimiento y el diagnóstico temprano del SGB, la admisión a la unidad de cuidados intensivos, indicación y selección de tratamiento, seguimiento y tratamiento de la progresión de la enfermedad, predicción del curso clínico, resultados y tratamiento de complicaciones y secuelas.

Abstract Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and in 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diag nostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology.

Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

The Impact of the COVID-19 Pandemic on the Brazilian Immigrant Community in the U.S: Results from a Qualitative Study.

While an increasing body of data suggests that marginalized groups have been disproportionately impacted by COVID-19, little has been published about the specific impact on Brazilian immigrants in the U.S. We conducted 15 key informant interviews, one of which included two participants (n = 16), with representatives from social service agencies, healthcare, and faith-based organizations serving Brazilian immigrants. Key informants were asked about the community's experiences with COVID-19 testing and treatment, responses to CDC (Centers for Disease Control) guidelines, perceptions about the virus, and the pandemic's impact on physical and mental health. Results suggest that COVID-19 has profoundly impacted Brazilian immigrants' mental and physical health. Key informants perceived that community members faced higher risk of COVID-19 infection due to overcrowded living conditions and over-representation in public-facing and informal (e.g., housecleaning) jobs. They reported barriers to COVID-19-related healthcare services including language, immigration status, and fear of deportation. Brazilian cultural norms surrounding hygiene practices, social distancing, and information distribution have shaped the community's pandemic response. The Brazilian community has faced extensive social, economic, and health ramifications due to the pandemic. While not unique to this community, pre-existing concerns about social disadvantage suggest a particular vulnerability of this population to the virus.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology / Canabinoides em Neurologia - Artigo de posicionamento dos Departamentos Científicos da Academia Brasileira de Neurologia

ABSTRACT Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

RESUMO Os canabinoides compreendem os endocanabinoides, fitocanabinoides e os canabinoides sintéticos e desempenham ações no sistema nervoso central e periférico. Uma quantidade enorme de publicações tem sido lançada nos últimos anos, embora a cannabis seja conhecida por milênios. Os Departamentos Científicos da Academia Brasileira de Neurologia descreveram as evidências do uso médico em suas áreas. A literatura está em constantes mudanças e possíveis novas evidências podem surgir nos próximos dias ou meses. A prescrição dessas substâncias deve ser discutida com os pacientes e suas famílias, com conhecimento sobre eventos adversos e sua eficácia.

Inflammatory Cytokine Patterns Associated with Neurological Diseases in Coronavirus Disease 2019.

Patients with coronavirus disease 2019 (COVID-19) can present with distinct neurological manifestations. This study shows that inflammatory neurological diseases were associated with increased levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, chemokine (C-X-C motif) ligand 8 (CXCL8), and CXCL10 in the cerebrospinal fluid. Conversely, encephalopathy was associated with high serum levels of IL-6, CXCL8, and active tumor growth factor ß1. Inflammatory syndromes of the central nervous system in COVID-19 can appear early, as a parainfectious process without significant systemic involvement, or without direct evidence of severe acute respiratory syndrome coronavirus 2 neuroinvasion. At the same time, encephalopathy is mainly influenced by peripheral events, including inflammatory cytokines. ANN NEUROL 2021;89:1041-1045.

Cerebrospinal fluid findings in neurological diseases associated with COVID-19 and insights into mechanisms of disease development.

OBJECTIVES: To analyze the cerebrospinal fluid (CSF) of patients with SARS-CoV-2 infection and neurological manifestations to provide evidence for the understanding of mechanisms associated with central nervous system (CNS) involvement in COVID-19. METHODS: Patients (n = 58) were grouped according to their main neurological presentation: headache (n = 14); encephalopathy (n = 24); inflammatory neurological diseases, including meningoencephalitis (n = 4), acute myelitis (n = 3), meningitis (n = 2), acute disseminated encephalomyelitis (ADEM) (n = 2), encephalitis (n = 2), and neuromyelitis optica (n = 1); and Guillain-Barré syndrome (n = 6). Data regarding age, sex, cerebrovascular disease, and intracranial pressure were evaluated in combination with CSF profiles defined by cell counts, total protein and glucose levels, concentration of total Tau and neurofilament light chain (NfL) proteins, oligoclonal band patterns, and detection of SARS-CoV-2 RNA. RESULTS: CSF of patients with inflammatory neurological diseases was characterized by pleocytosis and elevated total protein and NfL levels. Patients with encephalopathy were mostly older men (mean age of 61.0 ± 17.6 years) with evidence of cerebrovascular disease. SARS-CoV-2 RNA in CSF was detected in 2 of 58 cases: a patient with refractory headache, and another patient who developed ADEM four days after onset of COVID-19 symptoms. Three patients presented intrathecal IgG synthesis, and four had identical oligoclonal bands in CSF and serum, indicating systemic inflammation. CONCLUSION: Patients with neurological manifestations associated with COVID-19 had diverse CSF profiles, even within the same clinical condition. Our findings indicate a possible contribution of viral replication on triggering CNS infiltration by immune cells and the subsequent inflammation promoting neuronal injury.

Isolated intracranial hypertension associated with COVID-19.

BACKGROUND: Headache is a frequent complaint in COVID-19 patients. However, no detailed information on headache characteristics is provided in these reports. Our objective is to describe the characteristics of headache and the cerebrospinal fluid (CSF) profile in COVID-19 patients, highlighting the cases of isolated intracranial hypertension. METHODS: In this cross-sectional study, we selected COVID-19 patients who underwent lumbar puncture due to neurological complaints from April to May 2020. We reviewed clinical, imaging, and laboratory data of patients with refractory headache in the absence of other encephalitic or meningitic features. CSF opening pressures higher than 250 mmH2O were considered elevated, and from 200 to 250 mmH2O equivocal. RESULTS: Fifty-six COVID-19 patients underwent lumbar puncture for different neurological conditions. A new, persistent headache that prompted a CSF analysis was diagnosed in 13 (23.2%). The pain was throbbing, holocranial or bilateral in the majority of patients. All patients had normal CSF analysis and RT-qPCR for SARS-CoV-2 was negative in all samples. Opening pressure >200 mmH2O was present in 11 patients and, in six of these, > 250 mmH2O. 6/13 patients had complete improvement of the pain, five had partial improvement, and two were left with a daily persistent headache. CONCLUSIONS: In a significant proportion of COVID-19 patients, headache was associated to intracranial hypertension in the absence of meningitic or encephalitic features. Coagulopathy associated with COVID-19 could be an explanation, but further studies including post-mortem analysis of areas of production and CSF absorption (choroid plexuses and arachnoid granulations) are necessary to clarify this issue.

Peripheral facial nerve palsy associated with COVID-19.

COVID-19 pandemic revealed several neurological syndromes related to this infection. We describe the clinical, laboratory, and radiological features of eight patients with COVID-19 who developed peripheral facial palsy during infection. In three patients, facial palsy was the first symptom. Nerve damage resulted in mild dysfunction in five patients and moderate in three. SARS-Cov-2 was not detected in CSF by PCR in any of the samples. Seven out of eight patients were treated with steroids and all patients have complete or partial recovery of the symptoms. Peripheral facial palsy should be added to the spectrum of neurological manifestations associated with COVID-19.

Smell dysfunction in COVID-19 patients: More than a yes-no question.

Anosmia has been recognized as a prevalent and early symptom by many COVID-19 patients. However, most researchers have recorded smell dysfunction solely as present or absent and based on subjective evaluation by patients. We described the results of 57 consecutive COVID-19 patients seen at FIOCRUZ, Rio de Janeiro, Brazil, from April to May 2020. Data about the presence of smell loss, the onset of smell loss and other COVID-19 symptoms such as ageusia and nasal congestion or rhinorrhea were recorded. All patients at the initial consultation and 34 healthy controls underwent the Q-SIT, which is a quick disposable three-item smell identification test, by a trained physician. We compared three groups: healthy controls, COVID+ patients with reported smell loss (COVID w/ SL) and COVID+ patients without smell loss (COVID+ w/o SL). The mean age of patients was 41.4 years (SD ± 10.4), and 54.4% were women. Smell loss was reported by 40.4% of COVID-19 patients. We observed a gradual effect with higher Q-SIT scores in healthy controls, followed by COVID+ w/o SL and COVID+ w/ SL (medians = 3, 2 and 0; respectively, p < 0.001). Anosmia or severe microsmia (Q-SIT≤1) was present in 11.1% (CI: 3.1%-26.1%) of controls, 32.4% (CI: 17.4%-50.5%) of COVID-19 w/o SL and 87% (CI: 66.4%-97.2%) of COVID+ w/ SL (p < 0.001). This study provides evidence that olfactory dysfunction in COVID-19 is common and more prevalent than what is perceived by patients. Q-SIT is a quick and reliable screening test for the detection of smell dysfunction during the pandemics.

Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid.

We report that patients with COVID-19 displaying distinct neurological disorders have undetectable or extremely low levels of SARS-CoV-2 RNA in the cerebrospinal fluid, indicating that viral clearance precede the neurological involvement. This finding points to the need for the development of more sensitive molecular tests and the investigation of other neurotropic pathogens to exclude concurrent neuroinfection.