Evaluation of enterovirus concentration, species identification, and cerebrospinal fluid parameters in patients of different ages with aseptic meningitis in São Paulo, Brazil.

Human enteroviruses (EV) are the most common cause of aseptic meningitis worldwide. Data on EV viral load in cerebrospinal fluid (CSF) and related epidemiological studies are scarce in Brazil. This study investigated the influence of EV viral load on CSF parameters, as well as identifying the involved species. CSF samples were collected in 2018-2019 from 140 individuals at The Hospital das Clínicas, São Paulo. The EV viral load was determined using real-time quantitative polymerase chain reaction, while EV species were identified by 5'UTR region sequencing. Median viral load was 5.72 log10 copies/mL and did not differ by subjects' age and EV species. Pleocytosis was observed in 94.3% of cases, with the highest white blood cell (WBC) counts in younger individuals. Viral load and WBC count were correlated in children (p = 0.0172). Elevated lactate levels were observed in 60% of cases and correlated with the viral load in preteen-teenagers (p = 0.0120) and adults (p = 0.0184). Most individuals had normal total protein levels (70.7%), with higher in preteen-teenagers and adults (p < 0.0001). By sequencing, 8.2% were identified as EV species A and 91.8% as species B. Age-specific variations in CSF characteristics suggest distinct inflammatory responses in each group.

Targeted analysis reveals alteration in pathway in 5p minus individuals.

Cri du Chat or 5p minus (5p-) syndrome is characterized by a deletion located on the chromosome 5 short (-p) arm and has an incidence rate of 1 in 50,000 individuals worldwide. This disease manifests in disturbances across a range of systems biochemicals. Therefore, a targeted metabolomics analysis was evaluated in patients with 5p- syndrome to help unravel the biochemical changes that occur in this disease. Urine samples were collected from people of both sexes aged 1-38 years old and analyzed by ultra-performance liquid chromatography coupled to mass spectrometry. Student' statistical test, metabolomic pathway analysis and metabolite set enrichment analysis were applied to the data. Alterations of some amino acids and amine biogenics levels were found in Cri du Chat Syndrome individuals. The alteration of most of these metabolites is associated with energy recuperation and glycolysis. In general, we found the catabolism of some metabolic pathways to be affected in 5p- patients.

Cerebrospinal fluid analysis in patients with COVID-19-associated central nervous system manifestations: a systematic review.

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.

Neurofilament light chain in the assessment of patients with multiple sclerosis.

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.

Performance of lactate in discriminating bacterial meningitis from enteroviral meningitis.

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.

FilmArray Meningitis/Encephalitis (ME) panel in the diagnosis of bacterial meningitis.

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.

Diagnosis of neurosyphilis with cerebrospinal fluid pcr: a systematic review

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.

The cerebrospinal fluid in multiple sclerosis: far beyond the bands.

The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency. A more refined evaluation of disease and therapy status can contribute to better therapeutic choices, particularly in escalation of therapies. This is very relevant taking into account the availability of a greater number of drugs for multiple sclerosis treatment in recent years. In this review, we critically evaluate the current literature regarding the most important cerebrospinal fluid biomarkers in multiple sclerosis. The determination of biomarkers levels, such as chemokine ligand 13, fetuin A, and mainly light neurofilament has shown promising results in the evaluation of this disease, providing information that along with clinical and neuroimaging data may contribute to better therapeutic decisions. RESUMO A análise do líquido cefalorraquidiano tem sido empregada para avaliação diagnóstica da esclerose múltipla e a exclusão dos diagnósticos diferenciais. Os achados clássicos refletem a natureza inflamatória da doença, incluindo discreta pleocitose, leve hiperproteinorraquia, aumento da síntese intratecal de imunoglobulina G e, mais tipicamente, a presença de bandas oligoclonais. Nos últimos anos, surgiram novos biomarcadores para esclerose múltipla, e esta busca por marcadores reflete a necessidade de melhor avaliar a atividade e a progressão da doença, bem como a eficácia terapêutica. Uma avaliação mais refinada da atividade da doença e da resposta aos medicamentos pode contribuir para melhores decisões terapêuticas, particularmente no que se refere à troca de medicação. Isto é muito importante nos dias de hoje, quando surgem novas opções medicamentosas. Neste artigo de revisão, avaliamos criticamente a literatura atual referente aos novos marcadores liquóricos na esclerose múltipla. A mensuração destes marcadores, como a quimiocina CXCL13, fetuína A e, principalmente, o neurofilamento de cadeia leve, demonstrou resultados promissores na avaliação da doença, provendo informações que, em conjunto com dados clínicos e de neuroimagem, podem contribuir para melhores decisões terapêuticas.

Neurofilament light chain in the assessment of patients with multiple sclerosis / Neurofilamento de cadeia leve na avaliação de pacientes com esclerose múltipla

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 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.

FilmArray Meningitis/Encephalitis (ME) panel in the diagnosis of bacterial meningitis

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.

The cerebrospinal fluid in multiple sclerosis: far beyond the bands / O líquido cefalorraquidiano na esclerose múltipla: muito além das bandas

ABSTRACT The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency. A more refined evaluation of disease and therapy status can contribute to better therapeutic choices, particularly in escalation of therapies. This is very relevant taking into account the availability of a greater number of drugs for multiple sclerosis treatment in recent years. In this review, we critically evaluate the current literature regarding the most important cerebrospinal fluid biomarkers in multiple sclerosis. The determination of biomarkers levels, such as chemokine ligand 13, fetuin A, and mainly light neurofilament has shown promising results in the evaluation of this disease, providing information that along with clinical and neuroimaging data may contribute to better therapeutic decisions.

RESUMO A análise do líquido cefalorraquidiano tem sido empregada para avaliação diagnóstica da esclerose múltipla e a exclusão dos diagnósticos diferenciais. Os achados clássicos refletem a natureza inflamatória da doença, incluindo discreta pleocitose, leve hiperproteinorraquia, aumento da síntese intratecal de imunoglobulina G e, mais tipicamente, a presença de bandas oligoclonais. Nos últimos anos, surgiram novos biomarcadores para esclerose múltipla, e esta busca por marcadores reflete a necessidade de melhor avaliar a atividade e a progressão da doença, bem como a eficácia terapêutica. Uma avaliação mais refinada da atividade da doença e da resposta aos medicamentos pode contribuir para melhores decisões terapêuticas, particularmente no que se refere à troca de medicação. Isto é muito importante nos dias de hoje, quando surgem novas opções medicamentosas. Neste artigo de revisão, avaliamos criticamente a literatura atual referente aos novos marcadores liquóricos na esclerose múltipla. A mensuração destes marcadores, como a quimiocina CXCL13, fetuína A e, principalmente, o neurofilamento de cadeia leve, demonstrou resultados promissores na avaliação da doença, provendo informações que, em conjunto com dados clínicos e de neuroimagem, podem contribuir para melhores decisões terapêuticas.