RESUMO Antecedentes: O comprometimento do sistema nervoso central (SNC) pode ocorrer em pacientes com COVID-19. O papel do exame do LCR nesses casos ainda não foi precisamente estabelecido. Objetivo: Foi realizada uma revisão sistemática dos achados do LCR em pacientes com COVID-19 e comprometimento do SNC. Métodos: Os parâmetros do LCR, incluindo análises citológicas e bioquímicas, RT-PCR para o SARS-CoV-2, além de outros marcadores liquóricos, foram registrados e analisados em pacientes com as seguintes síndromes: acidente vascular cerebral, encefalopatia, encefalite, síndromes inflamatórias, crises epilépticas, cefaleia e meningite. Resultados: Aumento de leucócitos e/ou aumento da concentração de proteína foram encontradas em 52,7% dos pacientes com encefalite, 29,4% dos pacientes com encefalopatia e 46,7% dos pacientes com outras síndromes inflamatórias (P<0,05). A RT-PCR em LCR para identificação SARS-CoV-2 foi positiva em 17,35% dos pacientes com encefalite e menos de 3,5% dos pacientes com encefalopatia ou síndromes inflamatórias (P<0,05). A produção intratecal de imunoglobulinas foi encontrada em apenas 8% dos casos. Mais de 85% dos pacientes apresentavam aumento de citocinas e quimiocinas no LCR. Foi identificado aumento do neurofilamento de cadeia leve (NfL) em 71% e da proteína Tau em 36% dos casos. Conclusão: Alterações inflamatórias leves e inespecíficas foram frequentes em pacientes com manifestações neurológicas do SNC associadas à COVID-19. O aumento de biomarcadores de neurodegeneração sugere a possibilidade de dano neuronal, com consequências de longo prazo ainda desconhecidas.

ABSTRACT Background: Central nervous system (CNS) symptoms may occur in patients with acute COVID-19. The role of CSF examination in these patients remains to be established. Objective: A systematic review of CSF findings relating to COVID-19 was carried out. Methods: CSF parameters, including cytological and biochemical analyses, SARS-CoV-2 RT-PCR and other CSF markers, were recorded and analyzed among patients with acute COVID-19 and one of the following CNS syndromes: stroke, encephalopathy, encephalitis, inflammatory syndromes, seizure, headache and meningitis. Results: Increased white blood cells and/or increased protein concentration were found in 52.7% of the patients with encephalitis, 29.4% of the patients with encephalopathy and 46.7% of the patients with inflammatory syndromes (P < 0.05). CSF RT-PCR for SARS-CoV-2 was positive in 17.35% of the patients with encephalitis and less than 3.5% of the patients with encephalopathy or inflammatory syndromes (P < 0.05). Intrathecal production of immunoglobulins was found in only 8% of the cases. More than 85% of the patients had increased CSF cytokines and chemokines. Increased CSF neurofilament light chain (NfL) and CSF Tau were found in 71% and 36% of the cases, respectively. Conclusion: Non-specific inflammatory CSF abnormalities were frequently found in patients with COVID-19 CNS syndromes. The increase in neurodegeneration biomarkers suggests that neuronal damage occurs, with long-term consequences that are still unknown.

RESUMO Antecedentes: O comprometimento do sistema nervoso central (SNC) pode ocorrer em pacientes com COVID-19. O papel do exame do LCR nesses casos ainda não foi precisamente estabelecido. Objetivo: Foi realizada uma revisão sistemática dos achados do LCR em pacientes com COVID-19 e comprometimento do SNC. Métodos: Os parâmetros do LCR, incluindo análises citológicas e bioquímicas, RT-PCR para o SARS-CoV-2, além de outros marcadores liquóricos, foram registrados e analisados em pacientes com as seguintes síndromes: acidente vascular cerebral, encefalopatia, encefalite, síndromes inflamatórias, crises epilépticas, cefaleia e meningite. Resultados: Aumento de leucócitos e/ou aumento da concentração de proteína foram encontradas em 52,7% dos pacientes com encefalite, 29,4% dos pacientes com encefalopatia e 46,7% dos pacientes com outras síndromes inflamatórias (P<0,05). A RT-PCR em LCR para identificação SARS-CoV-2 foi positiva em 17,35% dos pacientes com encefalite e menos de 3,5% dos pacientes com encefalopatia ou síndromes inflamatórias (P<0,05). A produção intratecal de imunoglobulinas foi encontrada em apenas 8% dos casos. Mais de 85% dos pacientes apresentavam aumento de citocinas e quimiocinas no LCR. Foi identificado aumento do neurofilamento de cadeia leve (NfL) em 71% e da proteína Tau em 36% dos casos. Conclusão: Alterações inflamatórias leves e inespecíficas foram frequentes em pacientes com manifestações neurológicas do SNC associadas à COVID-19. O aumento de biomarcadores de neurodegeneração sugere a possibilidade de dano neuronal, com consequências de longo prazo ainda desconhecidas.

ABSTRACT Background: Central nervous system (CNS) symptoms may occur in patients with acute COVID-19. The role of CSF examination in these patients remains to be established. Objective: A systematic review of CSF findings relating to COVID-19 was carried out. Methods: CSF parameters, including cytological and biochemical analyses, SARS-CoV-2 RT-PCR and other CSF markers, were recorded and analyzed among patients with acute COVID-19 and one of the following CNS syndromes: stroke, encephalopathy, encephalitis, inflammatory syndromes, seizure, headache and meningitis. Results: Increased white blood cells and/or increased protein concentration were found in 52.7% of the patients with encephalitis, 29.4% of the patients with encephalopathy and 46.7% of the patients with inflammatory syndromes (P < 0.05). CSF RT-PCR for SARS-CoV-2 was positive in 17.35% of the patients with encephalitis and less than 3.5% of the patients with encephalopathy or inflammatory syndromes (P < 0.05). Intrathecal production of immunoglobulins was found in only 8% of the cases. More than 85% of the patients had increased CSF cytokines and chemokines. Increased CSF neurofilament light chain (NfL) and CSF Tau were found in 71% and 36% of the cases, respectively. Conclusion: Non-specific inflammatory CSF abnormalities were frequently found in patients with COVID-19 CNS syndromes. The increase in neurodegeneration biomarkers suggests that neuronal damage occurs, with long-term consequences that are still unknown.

ABSTRACT Background Neurosyphilis is difficult to be diagnosed. CSF VDRL is the gold standard, but its sensitivity is low. Cerebrospinal fluid (CSF) PCR for the detection of Treponema pallidum DNA has been evaluated; however, its diagnostic value is still poorly understood. Methods Here we performed a systematic review including articles that assessed the diagnostic sensitivity of CSF PCR in patients with syphilis and neurosyphilis. The CSF PCR sensitivity and specificity of different PCR assays was assessed in patients with neurosyphilis with or without HIV coinfection and in patients with syphilis with no central nervous system (CNS) manifestations. Results Eighteen studies evaluating 703 patients were included. The PCR sensitivity for neurosyphilis was 73.9% among HIV negative and 37.5% among HIV infected patients, having varied from 62.2% to 100% with different PCR assays. The sensitivity of CSF VDRL CSF was 68% in the same population. The specificity of CSF PCR was 93%. CSFPCR was positive in16.4% of the patients with primary and secondary syphilisand 28.9% of patients with latent syphilis. None of the syphilis cases without neurological manifestations were positive with CSF VDRL. Conclusion CSF PCR seems to be at least as sensitive as CSF VDRL, with good specificity. In addition, CSF PCR may potentially reveal early neuroinvasion in patients withsyphilis with no CNS symptoms. Future studies are still needed to assess the potential clinical value of detecting T. pallidum DNA in CSF in syphilis cases prior to the development of CNS symptoms.

ABSTRACT The precise diagnosis of bacterial meningitis is essential. Cytological and biochemical examination of cerebrospinal fluid (CSF) are not specific. Conventional methods for bacterial meningitis lack sensitivity or take too long for a final result. Therefore, other methods for rapid and accurate diagnosis of central nervous system infections are required. FilmArray meningitis/encephalitis (ME) panel is a PCR multiplex for simultaneous and rapid identification of 14 pathogens, including 6 bacteria, 7 viruses, and Cryptococcus. We evaluated 436 CSF samples submitted to FilmArray ME Panel. Among them, 25 cases were positive for bacteria, being Streptococcus pneumonia the most frequent (48 %). Among positive cases for bacteria, 60 % were positive only with FilmArray. All the bacterial meningitis cases in which the only positive test was FilmArray had CSF findings suggestive of bacterial meningitis, including neutrophilic pleocytosis, increased CSF protein and lactate, and decreased CSF glucose. These findings suggest that FilmArray may increase the diagnostic sensitivity for bacterial meningitis.

RESUMO A esclerose múltipla (EM) é uma doença autoimune, inflamatória e degenerativa do sistema nervoso central. A degeneração axonal é deflagrada pelo processo inflamatório e é o substrato patológico da incapacidade na EM. As intervenções terapêuticas reduzem a inflamação retardando a neurodegeneração e a progressão da incapacidade. A neurodegeneração é avaliada pelo quadro clínico e pela ressonância magnética. Estas mensurações não suficientemente acuradas, havendo necessidade de novos biomarcadores. Diversos biomarcadores têm sido estudados e, até o presente, o mais promissor é o neurofilamento de cadeia leve (NfL). O mesmo é um componente do citoesqueleto que é liberado no líquido cefalorraquidiano após injúria axonal. No presente estudo nós revisamos o conhecimento atual acerca do NfL na EM, síndrome clinica isolada e síndrome radiológica isolada, discutindo criticamente como a determinação deste biomarcador pode contribuir na tomada de decisões clínicas.

ABSTRACT Multiple sclerosis (MS) is an autoimmune, inflammatory, and degenerative disease of the central nervous system. Axonal degeneration is triggered by inflammation and is the pathological substrate of progressive disability in patients with MS. Therapeutic interventions can reduce inflammatory activity, thus delaying neurodegeneration and the progression of disability. Disease activity and neurodegeneration are assessed mainly through clinical evaluation and magnetic resonance imaging. These measures lack sensitivity and accuracy, so new biomarkers are necessary. Several markers have been studied and to date the most promising is neurofilament light (NfL), a component of the axonal cytoskeleton, which is released into cerebrospinal fluid (CSF) following axonal damage. In the present study, we review the current knowledge about CSF NfL determination in MS, clinically isolated syndrome, and radiologically isolated syndrome, and critically discuss how CSF NfL measurement may contribute to therapeutic decision-making in these patients.

RESUMO Objetivo: O objetivo deste estudo foi avaliar a estabilidade, em 12 horas, de parâmetros citológicos e bioquímicos do liquor. Métodos: Amostras de líquido cefalorraquidiano (LCR) foram aliquotadas em cinco diferentes tubos e armazenadas em temperatura ambiente. A primeira alíquota foi imediatamente analisada e as demais, analisadas após 2, 4, 6 e 12 horas. Para avaliação citológica, foram incluídas amostras com pelo menos 20 leucócitos/mm3. Foi realizada análise de variância dos resultados e a comparação da interpretação clínica dos resultados nos diferentes tempos. Resultados: Não houve redução significativa no número de leucócitos e hemácias por análise de variância (ANOVA). A interpretação clínica da citologia não resultou em resultados diferentes em nenhum dos tempos avaliados. Não houve variação significativa dos parâmetros bioquímicos. Conclusão: Os resultados sugerem que o armazenamento de amostras de LCR por 12 horas em temperatura ambiente não compromete significativamente a interpretação clínica. Estudos futuros deverão avaliar o comportamento desses parâmetros em amostras com contagens de células mais próximas aos valores limítrofes.

ABSTRACT Objective: The aim of this study was to evaluate the stability, in 12 hours, of cytological and biochemical parameters of the cerebrospinal fluid (CSF). Methods: Cerebrospinal fluid (CSF) samples were aliquoted into five different tubes and stored at room temperature. The first aliquot was immediately analyzed and the others analyzed after 2, 4, 6 and 12 hours. For cytological analysis, samples of at least 20 leukocytes/mm3 were included. Analysis of variance of the results and the comparison of the clinical interpretation of the results at the different times were performed. Results: There was no significant decrease in the number of leukocytes and erythrocytes by the analysis of variance (ANOVA). The clinical interpretation of the cytology did not result in different results in any of the evaluated times. There was no significant variation in the biochemical parameters. Conclusion: The results suggest that the storage of CSF samples for 12 hours at room temperature does not significantly compromise clinical interpretation. Future studies are still required in order to evaluate the behavior of these parameters in samples of cell counts closer to boundered values.

RESUMEN Objetivo: El objetivo de este estudio fue evaluar la estabilidad, en 12 horas, de parámetros citológicos y bioquímicos del líquido cefalorraquídeo (LCR). Métodos: Muestras del LCR fueron alicuotadas en cinco viales diferentes y almacenadas a temperatura ambiente. La primera alícuota fue inmediatamente analizada y las demás, analizadas tras 2, 4, 6 y 12 horas. Para la evaluación citológica, se incluyeron muestras con al menos 20 leucocitos/mm3. Se realizó el análisis de la varianza (ANOVA) de los resultados y la comparación de su interpretación clínica en los diferentes tiempos. Resultados: No hubo reducción significativa en el número de leucocitos y hematíes por ANOVA. La interpretación clínica de la citología no mostró resultados diferentes en ningún de los tiempos evaluados. No hubo variación significativa de los parámetros bioquímicos. Conclusión: Los resultados sugieren que el almacenamiento de muestras de LCR por 12 horas a temperatura ambiente no compromete significativamente la interpretación clínica. Nuevos ensayos deben evaluar el comportamiento de eses parámetros en muestras con recuentos de células más cercanas a los valores limítrofes.

ABSTRACT The cytological and biochemical examination of cerebrospinal fluid (CSF) has been used for the presumed diagnosis of bacterial meningitis until the final microbiological results are achieved. We assessed the ability of CSF lactate in comparison with other CSF parameters to discriminate bacterial and enteroviral community acquired meningitis. We included 1,187 CSF samples of acute community-acquired meningitis, being 662 cases of bacterial and 525 of enteroviral meningitis. Lactate concentration (mg/dL), leukocyte count/mm3, protein (mg/dL), and glucose (mg/dL) were compared between bacterial and viral meningitis. Receiver operator characteristic (ROC) curves were used to assess diagnostic performance. CSF leukocytes, CSF protein and CSF lactate were significantly higher in bacterial meningitis cases (P<0.0001). CSF glucose was significantly lower in bacterial meningitis cases (P<0.0001). CSF lactate showed the best predictive ability with an area under the curve of 0.944 (95% CI 0.929 – 0.959). Considering a cut off of CSF lactate of 30 mg/dL, the sensitivity and specificity for bacterial meningitis were 84.1% and 99%, respectively. In the cytological and biochemical CSF analysis, CSF lactate was the most accurate marker for bacterial meningitis.

RESUMO O uso de anticoagulantes e de agentes antiplaquetários tem aumentado nos últimos anos. A realização de punção lombar diagnóstica em pacientes utilizando tais medicamentos representa um desafio, em função dos riscos de complicações hemorrágicas ou trombóticas, estas últimas em pacientes que interrompem o tratamento para a realização do procedimento. Não há ainda estudos controlados nem diretrizes específicas nesta área. Neste artigo de revisão, algumas recomendações são feitas, levando-se em conta aspectos farmacológicos destas medicações, o risco de complicações trombóticas de acordo com a doença de base, e a urgência na coleta do líquor. A avaliação cuidadosa destas informações e uma monitorização neurológica rigorosa visando a detecção e o tratamento precoce de complicações podem reduzir o risco de sequelas neurológicas decorrentes de hemorragia. Uma decisão individualizada e uma efetiva comunicação entre o médico assistente e o responsável pela realização da punção lombar é essencial para minimizar potenciais riscos.

ABSTRACT The use of anticoagulants and antiplatelet agents has largely increased. Diagnostic lumbar puncture in patients taking these drugs represents a challenge considering the opposing risks of bleeding and thrombotic complications. To date there are no controlled trials, specific guidelines, nor clear recommendations in this area. In the present review we make some recommendations about lumbar puncture in patients using these drugs. Our recommendations take into consideration the pharmacology of these drugs, the thrombotic risk according to the underlying disease, and the urgency in cerebrospinal fluid analysis. Evaluating such information and a rigorous monitoring of neurological symptoms after lumbar puncture are crucial to minimize the risk of hemorrhage associated neurological deficits. An individualized patient decision-making and an effective communication between the assistant physician and the responsible for conducting the lumbar puncture are essential to minimize potential risks.

RESUMO Objetivos Moléculas inflamatórias e fatores neurotróficos estão implicados na modulação dolorosa, contudo, seu papel nas cefaleias primárias não é claro. O objetivo do presente estudo foi comparar níveis de biomarcadores séricos na migrânea e cefaleia do tipo tensional. Métodos Este foi um estudo transversal, no qual foram avaliados níveis de adiponectina, quimiocinas e fatores neurotróficos em pacientes com migrânea e cefaleia do tipo tensional. Sintomas depressivos e ansiosos, o impacto e a frequência da cefaleia e alodínea foram registrados. Resultados Foram incluídos 68 pacientes com migrânea e 48 pacientes com cefaleia do tipo tensional. A alodínia cutânea (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), e adiponectina (p = 0.017) foram maiores na migrânea, independentemente de sintomas depressivos e ansiosos, frequência e impacto da cefaleia. Conclusões Níveis de CCL3/MIP-1α, CCL5/RANTES e adiponectina foram maiores na migrânea do que na cefaleia do tipo tensional, sugerindo papeis distintos destas moléculas na fisiopatologia destas duas cefaleias primárias.

ABSTRACT Objectives Inflammatory molecules and neurotrophic factors are implicated in pain modulation; however, their role in primary headaches is not yet clear. The aim of this study was to compare the levels of serum biomarkers in migraine and tension-type headache. Methods This was a cross-sectional study. We measured serum levels of adiponectin, chemokines, and neurotrophic factors in patients with migraine and tension-type headache. Depression and anxiety symptoms, headache impact and frequency, and allodynia were recorded. Results We included sixty-eight patients with migraine and forty-eight with tension-type headache. Cutaneous allodynia (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), and ADP (p = 0.017) were significantly higher in migraine than in tension-type headache. The differences occurred independently of anxiety and depressive symptoms, frequency and impact of headache, and the presence of pain. Conclusions This study showed higher CCL3/MIP-1α, CCL5/RANTES, and ADP levels in migraine in comparison with tension-type headache. Our findings suggest distinctive roles of these molecules in the pathophysiology of these primary headaches.