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.

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.

SARS-CoV-2: Should We Be Concerned about the Nervous System?

The COVID-19 pandemic has proved to be an enormous challenge to the health of the world population with tremendous consequences for the world economy. New knowledge about COVID-19 is being acquired continuously. Although the main manifestation of COVID-19 is SARS, dysfunction in other organs has been described in the last months. Neurological aspects of COVID-19 are still an underreported subject. However, a plethora of previous studies has shown that human CoVs might be neurotropic, neuroinvasive, and neurovirulent, highlighting the importance of this knowledge by physicians. Besides, several neurological manifestations had been described as complications of two other previous outbreaks of CoV diseases (SARS ad Middle East respiratory syndrome). Therefore, we should be watchful, searching for early evidence of neurological insults and promoting clinical protocols to investigate them. Our objectives are to review the potential neuropathogenesis of this new CoV and the neurological profile of COVID-19 patients described so far.

Desnutrição e Qualidade de Vida em Pessoas Vivendo com HIV/AIDS / Malnutrition and Quality of Life in People Living with HIV/AIDS

Objetivo: explorar a associação entre o estado nutricional e os aspectos relacionados à qualidade de vida em pessoas vivendo com HIV/AIDS (PVHA) em tratamento antirretroviral. Materiais e Métodos: estudo seccional com uma amostra de 83 pacientes selecionada nos ambulatórios de doenças infecciosas de um instituto de referência para tratamento do HIV/AIDS. Os participantes foram avaliados quanto ao estado nutricional (avaliação nutricional subjetiva global - ANSG) e aos aspectos relacionados à qualidade de vida (questionário Item Short-Form Health Survey -SF-36) por uma fisioterapeuta treinada da equipe multidisciplinar de terapia nutricional. O estudo foi aprovado pelo Comitê de Ética e Pesquisa e todos os participantes assinaram termo de consentimento livre e esclarecido. Resultados: A maioria era do sexo masculino (56,6%), tinha concluído o ensino médio (54,2%), era ativo profissionalmente (54,2%), e ganhava pelo menos um salário mínimo (92,8%). Um terço da amostra tinha desnutrição leve ou moderada, e relatou presença de algum sintoma gastrintestinal. Grande parte dos pacientes apresentava perda de tecido adiposo (65%) e de massa muscular (34,9%) e 40,9% tinham deficiência funcional relacionada ao estado nutricional. Os pacientes classificados como desnutridos, tiveram piores resultados com relação aos componentes da ANSG e menores escores nos domínios da qualidade de vida (capacidade funcional, vitalidade, e limitação por aspectos físicos, emocionais e sociais). Conclusão: A desnutrição parece interferir negativamente na qualidade de vida de PVHA, e o uso de um instrumento de triagem rápida do estado nutricional, como a ANSG, por uma equipe interdisciplinar pode identificar precocemente pacientes que precisam de rápida intervenção nutricional. (AU)

Objective: To explore the association between nutritional status and aspects related to quality of life in people living with HIV/AIDS (PLHA) under antiretroviral treatment. Material and Methods: This was a crosssectional study with a convenience sample of 83 adults. Subjects were randomly selected at the infectious diseases outpatient's clinics at a reference institute for the treatment of HIV/AIDS. Nutritional status (subjective global assessment - SGA) and issues relating to quality of life (questionnaire Short-Form Health Survey Item -SF-36) were assessed by a trained physiotherapist of the nutritional therapy multidisciplinary team. The study was approved by the Research Ethics Committee and all participants signed an informed consent form. Results: Most study subjects were males (56.6%), had completed high school (54.2%), were professionally active (54.2%), with an income of at least one minimum wage (92.8%). A third of the sample had mild or moderate malnutrition and reported presence of some gastrointestinal symptoms. Most patients showed loss of subcutaneous fat (65%) and muscle mass (34.9%), and 40.9% of them had functional impairment related to nutritional status. As expected, patients classified as malnourished showed worse results in relation to SGA components and lower scores in some domains of quality of life (functional capacity, energy, and physical, emotional and social limitations). Conclusion: Malnutrition appears to interfere negatively on PLHA's quality of life, and the use of a rapid screening tool to assess nutritional status, such as SGA, by an interdisciplinary team can early identify patients in need of a quick nutritional intervention. (AU)

Post-cART progressive multifocal leukoencephalopathy era in a Brazilian center.

Progressive multifocal leukoencephalopathy (PML) is lytic infection of oligodendrocytes caused by JC virus (JCV). While PML incidence in developing countries has decreased after the introduction of combination antiretroviral therapy (cART), data in developing countries is scarce and limited to few cohorts. We described the epidemiological and clinical profile of a group of Brazilian HIV infected patients with PML in the cART era. A total of 27 patients were included in the study. The median age at PML onset was 42years (range: 27-67years) and 18 (66.7%) were men. The median CD4+ T cell count at the time of diagnosis was 67cells/mm3 and the median HIV viral load was 27,000copies/ml. Motor deficits were the most common early manifestations (44%). Seizures occurred in 37% of the patients and 9 (33.3%) had PML associated with immune reconstitution inflammatory syndrome (IRIS). Mortality was 33% and lower age at PML onset was associated with survival (p: 0.013). Our results are in accordance with previous published series of PML cases. Factors such as genetic background, regional JCV subtype differences, death from other diseases and underdiagnosis may explain the low prevalence of reported PML cases in developing countries.

Neurological manifestations of Chikungunya and Zika infections.

The epidemics of Chikungunya virus (CHIKV) and Zika virus (ZIKV) infections have been considered the most important epidemiological occurrences in the Americas. The clinical picture of CHIKV infection is characterized by high fever, exanthema, myalgia, headaches, and arthralgia. Besides the typical clinical picture of CHIKV, atypical manifestations of neurological complications have been reported: meningo-encephalitis, meningoencephalo-myeloradiculitis, myeloradiculitis, myelitis, myeloneuropathy, Guillain-Barré syndrome and others. The diagnosis is based on clinical, epidemiological, and laboratory criteria. The most common symptoms of ZIKV infection are skin rash (mostly maculopapular), fever, arthralgia, myalgia, headache, and conjunctivitis. Some epidemics that have recently occurred in French Polynesia and Brazil, reported the most severe conditions, with involvement of the nervous system (Guillain-Barré syndrome, transverse myelitis, microcephaly and meningitis). The treatment for ZIKV and CHIKV infections are symptomatic and the management for neurological complications depends on the type of affliction. Intravenous immunoglobulin, plasmapheresis, and corticosteroid pulse therapy are options.

Neurological manifestations of Chikungunya and Zika infections / Manifestações neurológicas das infecções pelos vírus Zika e Chikungunya

ABSTRACT The epidemics of Chikungunya virus (CHIKV) and Zika virus (ZIKV) infections have been considered the most important epidemiological occurrences in the Americas. The clinical picture of CHIKV infection is characterized by high fever, exanthema, myalgia, headaches, and arthralgia. Besides the typical clinical picture of CHIKV, atypical manifestations of neurological complications have been reported: meningo-encephalitis, meningoencephalo-myeloradiculitis, myeloradiculitis, myelitis, myeloneuropathy, Guillain-Barré syndrome and others. The diagnosis is based on clinical, epidemiological, and laboratory criteria. The most common symptoms of ZIKV infection are skin rash (mostly maculopapular), fever, arthralgia, myalgia, headache, and conjunctivitis. Some epidemics that have recently occurred in French Polynesia and Brazil, reported the most severe conditions, with involvement of the nervous system (Guillain-Barré syndrome, transverse myelitis, microcephaly and meningitis). The treatment for ZIKV and CHIKV infections are symptomatic and the management for neurological complications depends on the type of affliction. Intravenous immunoglobulin, plasmapheresis, and corticosteroid pulse therapy are options.

RESUMO As epidemias provocadas pelo vírus Chikungunya (CHIK) e Zika vírus (ZIKV) têm sido consideradas as ocorrências epidemiológicas mais importantes da América. O quadro clínico da infecção por CHIK caracteriza-se por febre alta, exantema, mialgia, cefaléia e artralgia. Além do quadro clínico típico, manifestações atípicas como complicações neurológicas foram relatadas: meningo-encefalite, mielorradiculopatia, mielorradiculite, mielite, mieloneuropatia, síndrome de Guillain-Barre (GBS), entre outras. O diagnóstico é baseado em critérios clínicos, epidemiológicos e laboratoriais. Em relação aos sinais e sintomas da infecção pelo ZIKV, erupção cutânea (principalmente maculopapular), febre, artralgia, mialgia, cefaléia e conjuntivite são os mais comuns. Algumas epidemias que ocorreram recentemente na Polinésia Francesa e Brasil relataram condições mais severas, com envolvimento do sistema nervoso (GBS, mielite transversa, microcefalia e meningite). O tratamento para ZIKV e CHIK é sintomático, e o manejo das complicações neurológicas dependerá do tipo da afecção. Imunoglobulina venosa, plasmaférese, e pulsoterapia com corticosteróides são opções.

Zika virus-associated neurological disorders: a review.

Zika virus, an arbovirus transmitted by mosquitoes of the Aedes species, is now rapidly disseminating throughout the Americas and the ongoing Brazilian outbreak is the largest Zika virus epidemic so far described. In addition to being associated with a non-specific acute febrile illness, a number of neurological manifestations, mainly microcephaly and Guillain-Barré syndrome, have been associated with infection. These with other rarer neurological conditions suggest that Zika virus, similar to other flaviviruses, is neuropathogenic. The surge of Zika virus-related microcephaly cases in Brazil has received much attention and the role of the virus in this and in other neurological manifestations is growing. Zika virus has been shown to be transmitted perinatally and the virus can be detected in amniotic fluid, placenta and foetus brain tissue. A significant increase in Guillain-Barré syndrome incidence has also been reported during this, as well as in previous outbreaks. More recently, meningoencephalitis and myelitis have also been reported following Zika virus infection. In summary, while preliminary studies have suggested a clear relationship between Zika virus infection and certain neurological conditions, only longitudinal studies in this epidemic, as well as experimental studies either in animal models or in vitro, will help to better understand the role of the virus and the pathogenesis of these disorders.

Viral encephalitis.

While systemic viral infections are exceptionally common, symptomatic viral infections of the brain parenchyma itself are very rare, but a serious neurologic condition. It is estimated that viral encephalitis occurs at a rate of 1.4 cases per 100.000 inhabitants. Geography is a major determinant of encephalitis caused by vector-borne pathogens. A diagnosis of viral encephalitis could be a challenge to the clinician, since almost 70% of viral encephalitis cases are left without an etiologic agent identified. In this review, the most common viral encephalitis will be discussed, with focus on ecology, diagnosis, and clinical management.

Viral encephalitis / Encefalites virais

While systemic viral infections are exceptionally common, symptomatic viral infections of the brain parenchyma itself are very rare, but a serious neurologic condition. It is estimated that viral encephalitis occurs at a rate of 1.4 cases per 100.000 inhabitants. Geography is a major determinant of encephalitis caused by vector-borne pathogens. A diagnosis of viral encephalitis could be a challenge to the clinician, since almost 70% of viral encephalitis cases are left without an etiologic agent identified. In this review, the most common viral encephalitis will be discussed, with focus on ecology, diagnosis, and clinical management.

Embora as infecções virais sistêmicas sejam muito comuns, as infecções virais sintomáticas do parênquima cerebral são raras, mas potencialmente graves. Estima-se que a encefalite viral ocorra em 1,4 casos por 100.000 habitantes anualmente. A localização geográfica é um fator determinante a ser levado em consideração frente aos patógenos transmitidos por vetores. O diagnóstico clínico das encefalites virais pode ser um desafio para o clínico, visto que quase 70% dos casos de encefalite viral ficam sem a identificação do agente viral. Nesta revisão, as encefalites virais mais comuns serão discutidas, com interesse especial sobre os aspectos da ecologia, do diagnóstico e do seu manejo clínico.

Validity of the International HIV dementia scale in Brazil.

HIV-associated neurocognitive disorders (HAND) remain prevalent in highly active antiretroviral therapy (HAART) era. Tests to detect HAND are needed for early diagnosis and treatment. Validity of International HIV Dementia Scale (IHDS) has been determined in different countries. The aims of this study were validate IHDS in a Brazilian cohort of HIV-patients and verify if IHDS can be reliably administered by a non-clinician health professional. One hundred and eighty-seven (187) patients were submitted to a full neuropsychological assessment. IHDS was administered twice to each patient (by a non-clinician and by a neurologist). HAND was diagnosed in 98 individuals (68 on HAART). IHDS had sensitivity of 55% and specificity of 80%. IHDS had fair agreement with neuropsychological tests (k 0.355) and moderate-to-strong agreement between different evaluators (interclass correlation coefficient (ICC) 0.684). HAND is prevalent nowadays. IHDS is quick and easy to administer, but has marginal sensitivity for the detection of HIV cognitive impairment other than dementia.

Validity of the International HIV Dementia Scale in Brazil / Validade da Escala Internacional de Demência pelo HIV no Brasil

HIV-associated neurocognitive disorders (HAND) remain prevalent in highly active antiretroviral therapy (HAART) era. Tests to detect HAND are needed for early diagnosis and treatment. Validity of International HIV Dementia Scale (IHDS) has been determined in different countries. The aims of this study were validate IHDS in a Brazilian cohort of HIV-patients and verify if IHDS can be reliably administered by a non-clinician health professional. One hundred and eighty-seven (187) patients were submitted to a full neuropsychological assessment. IHDS was administered twice to each patient (by a non-clinician and by a neurologist). HAND was diagnosed in 98 individuals (68 on HAART). IHDS had sensitivity of 55% and specificity of 80%. IHDS had fair agreement with neuropsychological tests (k 0.355) and moderate-to-strong agreement between different evaluators (interclass correlation coefficient (ICC) 0.684). HAND is prevalent nowadays. IHDS is quick and easy to administer, but has marginal sensitivity for the detection of HIV cognitive impairment other than dementia.

Distúrbios neurocognitivos associados ao HIV (HAND) ainda são comuns em pacientes usando terapia antirretroviral de alta eficácia (HAART). Testes diagnósticos para detecção de HAND são necessários para diagnóstico e terapia precoces. Nossos objetivos foram validar em uma população brasileira a escala internacional de demência pelo HIV (IHDS), já utilizada em outros países, e avaliar se pode ser confiavelmente aplicada por um profissional não médico. Avaliamos 187 pacientes com uma extensa bateria neuropsicológica. IHDS foi ministrada duas vezes (por médico e não médico). HAND foi diagnosticada em 98 indivíduos (68 em uso de HAART). A IHDS teve sensibilidade de 55% e especificidade de 80%, com pouca concordância com os testes neuropsicológicos (k 0,355) e moderada a forte concordância entre observadores (coeficiente de correlação interclasse (ICC) 0,684). HAND ainda é prevalente nos dias atuais. IHDS é um instrumento rápido e fácil de ser aplicado, mas com baixa sensibilidade para detecção de déficit cognitivo outro que não demência.

Progressive multifocal leukoencephalopathy in a HIV/HTLV co-infected patient.

Many HIV infected patients are at risk for HTLV-I co-infection worldwide. These patients exhibit abnormally high CD4+ T lymphocyte counts that are not a reliable parameter of the immune status. We report a HIV/HTLV co-infected patient who developed progressive multifocal leukoencephalopathy despite of a high CD4+ T lymphocyte count emphasizing that this situation can be observed in regions around the world where HTLV-I infection is prevalent.

Sporothrix schenckii meningitis in AIDS during immune reconstitution syndrome.

Sporotrichosis is a fungal disease usually restricted to the cutaneous and lymphatic systems. Visceral involvement is unusual. To date, only 21 cases of sporotrichosis meningitis have been reported, some of these associated with immunosuppression. According to the reported cases, difficulty establishing the correct diagnosis is almost the rule which, undoubtedly, is associated with a worse prognosis. In this report, two HIV infected patients are described who developed meningitis due to Sporothrix schenckii associated with immune reconstitution inflammatory syndrome. This is the first report of sporotrichosis meningitis associated with immune reconstitution inflammatory syndrome in AIDS patients.