RESUMO
INTRODUCTION: Recent studies suggest the existence of a physiologic basis for bone rarefaction and increased risk for fractures. This study aimed to address anthropometric differences between patients with narcolepsy type 1 (NT1) and type 2 (NT2) and discrepancies in bone mineral content (BMC) as a function of hypocretin-1 (Hcrt-1) measured in cerebrospinal fluid (CSF). METHODS: We have evaluated 31 adult patients (aged 18-65 years) with NT1 and 18 patients with NT2, comparing the groups in terms of anthropometric variables - body mass index (BMI) and waist-to-hip ratio (WHR) - and percentage of bone mineral content (%BMC), measured by bioelectrical impedance analysis (BIA). Statistical analysis assessed the effects of Hcrt-1 levels on CSF, dietary intake, and medication use over these variables. Statistical significance was achieved with a confidence interval of 95 % and p < 0.05. RESULTS: Patients with NT1 presented with higher BMI (32.04 ± 6.95 vs. 25.38 ± 4.26 kg/m2; p < 0.01) and WHR (0.89 ± 0.09 vs. 0.83 ± 0.09; p = 0.02) compared to NT2, in detriment of %BMC, which was lower for NT1 (4.1 ± 1.02 vs. 4.89 ± 0.59; p < 0.01). Hcrt-1 in CSF showed a positive correlation with %BMC (r = +0.48, p < 0.01) and a negative correlation with anthropometric features (BMI: r = -0.54, p < 0.01; WHR: r = -0.37, p = 0.01). There was a correlation between WHR and diary caloric intake (r = +0.42, p < 0.01). CONCLUSION: The evaluation of patients with narcolepsy presupposes a syndromic approach comprising symptoms that go far beyond excessive daytime sleepiness. The integrated follow-up, including nutritional profile and anthropometric features, should add value in reducing morbidity in this population.
Assuntos
Índice de Massa Corporal , Densidade Óssea , Narcolepsia , Orexinas , Humanos , Masculino , Feminino , Adulto , Orexinas/líquido cefalorraquidiano , Estudos Transversais , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/fisiopatologia , Densidade Óssea/fisiologia , Pessoa de Meia-Idade , Adolescente , Relação Cintura-Quadril , Adulto Jovem , IdosoRESUMO
ß-amyloid42 (Aß42) in Alzheimer's disease (AD) and orexin in narcolepsy are considered crucial biomarkers for diagnosis and therapeutic targets. Recently, orexin and Aß cerebral dynamics have been studied in both pathologies, but how they interact with each other remains further to be known. In this study, we investigated the reliability of using the correlation between orexin-A and Aß42 CSF levels as a candidate marker to explain the chain of events leading to narcolepsy or AD pathology. In order to test the correlation between these biomarkers, patients diagnosed with AD (n = 76), narcolepsy type 1 (NT1, n = 17), narcolepsy type 2 (NT2, n = 23) and healthy subjects (n = 91) were examined. Patients and healthy subjects underwent lumbar puncture between 8:00 and 10:00 am at the Neurology Unit of the University Hospital of Rome "Tor Vergata". CSF levels of Aß42, total-tau, phosphorylated-tau, and orexin-A were assessed. The results showed that CSF levels of Aß42 were significantly lower (p < 0.001) in AD (332.28 ± 237.36 pg/mL) compared to NT1 (569.88 ± 187.00 pg/mL), NT2 (691.00 ± 292.63 pg/mL) and healthy subjects (943.68 ± 198.12 pg/mL). CSF orexin-A levels were statistically different (p < 0.001) between AD (148.01 ± 29.49 pg/mL), NT1 (45.94 ± 13.63 pg/mL), NT2 (104.92 ± 25.55 pg/mL) and healthy subjects (145.18 ± 27.01 pg/mL). Moderate-severe AD patients (mini mental state examination < 21) showed the highest CSF orexin-A levels, whereas NT1 patients showed the lowest CSF orexin-A levels. Correlation between CSF levels of Aß42 and orexin-A was found only in healthy subjects (r = 0.26; p = 0.01), and not in narcolepsy or AD patients. This lack of correlation in both diseases may be explained by the pathology itself since the correlation between these two biomarkers is evident only in the healthy subjects. This study adds to the present literature by further documenting the interplay between orexinergic neurotransmission and cerebral Aß dynamics, possibly sustained by sleep.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Narcolepsia , Orexinas , Fragmentos de Peptídeos , Humanos , Orexinas/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Doença de Alzheimer/líquido cefalorraquidiano , Narcolepsia/líquido cefalorraquidiano , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fragmentos de Peptídeos/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Adulto , Proteínas tau/líquido cefalorraquidianoRESUMO
INTRODUCTION: This study explores the interaction between cytokines, cell-mediated immunity (T cells, B cells, and NK cells), and prolonged morphine administration in chronic neuropathic pain patients without cancer-related issues. Despite evidence of opioid immunomodulation, few studies have compared these interactions. METHODS: In a cross-sectional and comparative study, 50 patients with chronic low back radicular pain ("Failed Back Surgery Syndrome") were categorized into intrathecal morphine infusion (IT group, n = 18), oral morphine (PO group, n = 17), and non-opioid treatment (NO group, n = 15). Various parameters, including plasma and cerebrospinal fluid (CSF) cytokine concentrations, lymphocyte immunophenotyping, opioid escalation indices, cumulative morphine dose, and treatment duration, were assessed. RESULTS: CSF IL-8 and IL-1ß concentrations exceeded plasma levels in all patients. No differences in T, B, and NK lymphocyte numbers were observed between morphine-treated and non-treated patients. Higher plasma IL-5 and GM-CSF concentrations were noted in IT and PO groups compared to NO. CSF IFNγ concentrations were higher in PO and NO than IT. Positive correlations included CD4 concentrations with opioid escalation indices, and negative correlations involved NK cell concentrations, CSF TNFα concentrations, and opioid escalation indices. Positive correlations were identified between certain cytokines and pain intensity in IT patients, and between NK cells and cumulative morphine dose. Negative correlations were observed between CSF IL-5 concentrations and pain intensity in IT and PO, and between opioid escalation indices and CSF cytokine concentrations in PO and IT. CONCLUSION: Associations between cytokines, cellular immunity, and prolonged morphine treatment, administered orally and intrathecally were identified.
Assuntos
Analgésicos Opioides , Citocinas , Injeções Espinhais , Laminectomia , Morfina , Humanos , Analgésicos Opioides/administração & dosagem , Citocinas/sangue , Citocinas/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Transversais , Morfina/administração & dosagem , Administração Oral , Laminectomia/métodos , Idoso , Adulto , Dor Pós-Operatória/tratamento farmacológico , Neuralgia/tratamento farmacológico , Síndrome Pós-Laminectomia/tratamento farmacológicoRESUMO
OBJECTIVES: To validate a recently published study in which skin biopsy was reported as a valuable alternative to brain biopsy in diagnosing CSF1R-related disorder (CSF1R-RD). METHODS: Blinded evaluation of skin samples was performed by independent reviewers using light and electron microscopy collected from a group of CSF1R variant carriers (n = 10) with various genotypes (mono and biallelic), different stages of the disease (asymptomatic and symptomatic), and exposed to different therapies (glucocorticoids, hematopoietic stem cell transplantation, and TREM2 agonist), and from a group of healthy controls (n = 5). RESULTS: Biopsies from patients with CSF1R-RD at various disease stages were indistinguishable from controls determined using light microscopy and electron microscopy. DISCUSSION: We found no distinctive axonal pathology in skin biopsies collected from CSF1R variant carriers at all stages of the disease. Our results are consistent with clinical and neurophysiologic features of the CSF1R-RD, in that peripheral nervous system involvement has not been reported. Studies aiming to discover new biomarkers are important, but the results must be validated with larger numbers of patients and healthy controls. Based on blinded light and electron microscopic studies of skin biopsies, there is no evidence that CSF1R-RD is associated with distinctive changes in cutaneous peripheral nerves. This suggests that skin biopsy is not useful in diagnosis of CSF1R-RD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that skin biopsy does not distinguish those with CSF1R-RD, or carriers, from normal controls.
Assuntos
Biomarcadores , Pele , Feminino , Humanos , Masculino , Biomarcadores/líquido cefalorraquidiano , Biópsia , Receptor de Fator Estimulador de Colônias de Macrófagos , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Pele/patologiaRESUMO
Streptococcus suis (S. suis) is a globally prevalent swine pathogen, capable of generating infections in humans who were in contact with the animal or its raw meat. Clinical manifestations range from asymptomatic cases to systemic involvement, with low mortality, but with the possibility of leaving definitive sequelae such as ataxia and hearing loss. There are few case reports, due to lack of knowledge of the disease and its atypical presentation. The objective of this article is to report the case of a man with an occupational history of contact with pigs, who was admitted for meningitis and in whom the isolation of S. suis was obtained in cerebrospinal fluid and paired blood cultures; He completed antibiotic treatment adjusted to bacterial sensitivity, and was left with mild hearing loss as a consequence.
Streptococcus suis (S. suis) es un patógeno porcino prevalente a nivel mundial, capaz de generar infecciones en humanos que estuvieron en contacto con el animal o la carne cruda del mismo. Las manifestaciones clínicas comprenden desde casos asintomáticos hasta compromiso sistémico, con una baja mortalidad, pero con la posibilidad de dejar secuelas definitivas como la ataxia e hipoacusia. Son pocos los reportes de casos, debido al desconocimiento de la enfermedad y a su forma atípica de presentación. El objetivo de este artículo es relatar el caso de un varón con antecedentes ocupacionales de contacto con porcinos, que ingresó por meningitis y en el cual se obtuvo el aislamiento de S. suis en líquido cefalorraquídeo y hemocultivos pareados; completó tratamiento antibiótico ajustado a la sensibilidad bacteriana, quedó con hipoacusia leve como secuela.
Assuntos
Meningites Bacterianas , Infecções Estreptocócicas , Streptococcus suis , Animais , Humanos , Masculino , Antibacterianos/uso terapêutico , Meningites Bacterianas/microbiologia , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/líquido cefalorraquidiano , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/diagnóstico , Streptococcus suis/isolamento & purificação , SuínosRESUMO
OBJECTIVE: There is no firm evidence regarding cerebrospinal fluid (CSF) shunt reimplantation after infection in the pediatric population. The purpose of this study was to compare different criteria and analyze new shunt failure. METHODS: A cross-sectional retrospective multicenter study was performed over 6 years to study patients and each infected shunt at diagnosis, reimplantation, and after reimplantation. The patients were divided into 2 groups: group 1 (G1), reimplantation after negative serial CSF cultures during antibiotic treatment; group 2 (G2), reimplantation after negative serial pancultures after completion of antibiotics. The differences were measured with Mann-Whitney and Χ2 tests; multivariate analysis and associations were calculated using odds ratios (ORs) based on logistic regression. RESULTS: There were 137 shunt infection events in 110 patients: 28 events in G1 and 109 in G2. Significant differences were observed in the diagnosis and reimplantation. Reimplantation dysfunction in G1 was 16 (55.17%) versus 30 (27.78%) in G2 (P = 0.006). The risk of shunt malfunction after reimplantation increased for G1 reimplantation criteria (P = 0.018; OR, 3.34; confidence interval [CI], 1.23-9.05): pleocytosis at diagnosis >17 cells (P = 0.036; OR, 2.41; CI, 1.06-5.47), CSF proteins at diagnosis >182 mg/dL (P = 0.049; OR, 2.21; CI, 1.00-4.89). CONCLUSIONS: G2 reimplantation criteria were related to improved pleocytosis, CSF proteins, and blood neutrophils compared with G1. Mechanical and infectious dysfunction of the new shunt was 3 times more prevalent in G1 than in G2, considering the differences between the groups at diagnosis. Increased parameters of infection at diagnosis were associated with future malfunction more than parameters before reimplantation in both groups.
Assuntos
Derivações do Líquido Cefalorraquidiano , Humanos , Masculino , Feminino , Derivações do Líquido Cefalorraquidiano/efeitos adversos , Estudos Transversais , Estudos Retrospectivos , Pré-Escolar , Criança , Lactente , Equador/epidemiologia , Reinfecção , Reoperação/estatística & dados numéricos , Falha de Equipamento , Adolescente , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/líquido cefalorraquidianoRESUMO
We evaluated the diagnostic clinical performance characteristics (DCPC) of cerebrospinal fluid (CSF) total protein (TP), white blood cell count (WBC), and lactate (LA) with different cutoff points as adjunct biomarkers of confirmed or presumptive symptomatic neurosyphilis (NS) and the impact of HIV infection. From 5,640 participants who underwent lumbar punctures, 236 participants were included, and classified as either people with HIV (PWH) or people without HIV (PWoH) according to the CDC criteria for confirmed NS (n = 42), presumptive NS (n = 74), systemic syphilis (SS) (n = 38), serological diagnosis of syphilis (n = 18), PWH without SS and NS (n = 10), and negative control (n = 72). In PWoH, for presumptive NS, the combination of CSF TP > 45 mg/dL and/or WBC > 5.0 cells/mm3 is valuable for screening, whereas in PWH, it is not recommended for either screening or case-finding NS, however the DCPC were better in the suppressed group. In PWoH, the value of CSF TP > 45 mg/dL is adequate for both screening and confirmation of presumptive NS, subject to prevalence. For WBC count > 20 cell/mm3, the positive predictive value (PPV) of the test is almost perfect, suggesting a confirmatory test. In PWH, CSF TP is an inadequate marker of NS. The WBC count, with cutoffs of > 10 or > 20 cells/mm3, was moderately applicable for screening.As conclusions: CSF WBC count and TP showed distinct DCPC in confirmed or presumptive NS, better in the former. These biomarkers could be included for presumptive NS diagnosis. DCPC of these biomarkers for the diagnosis of NS is greatly affected by HIV co-infection.
Assuntos
Biomarcadores , Infecções por HIV , Neurossífilis , Humanos , Neurossífilis/líquido cefalorraquidiano , Neurossífilis/diagnóstico , Neurossífilis/sangue , Neurossífilis/complicações , Infecções por HIV/complicações , Infecções por HIV/líquido cefalorraquidiano , Masculino , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/sangue , Adulto , Feminino , Pessoa de Meia-Idade , Contagem de Leucócitos , Ácido Láctico/líquido cefalorraquidiano , Ácido Láctico/sangue , Punção Espinal , Proteínas do Líquido CefalorraquidianoRESUMO
BACKGROUND: Oligoclonal bands (OCBs) and Kappa free light chains (FLCs) in the cerebrospinal ï¬uid (CSF) are sensitive markers of intrathecal immunoglobulin (Ig)G synthesis in patients with multiple sclerosis. OBJECTIVE: To evaluate the concordance rate between OCBCs and the Kappa index (KI) in patients with suspected multiple sclerosis (MS). METHODS: Patients with suspected MS were referred to a specialized CSF laboratory as part of their diagnostic investigation. Paired CSF and serum samples were collected and submitted to detection of OCBs and determination of the KI. Positive and negative results were determined with both methods, and the percentage of agreement between them was established. RESULTS: In total, 171 serum and CSF samples from 171 patients were included in the analysis. The mean age of the patients was of 40 ± 14.2 years; 18.9% of them were male, and 81.1% were female. The OCBs and KI presented concordant results in 161 (94.2%) samples: in 74 (43.3%), both were positive, and in 87 (50.9%), both were negative. In 10 cases, the results were discrepant: KI positive/OCB negative in 8 and OCB positive/KI negative in 2 cases. CONCLUSION: The KI and OCBs presented high concordance level. Currently, the detection of OCBs in the CSF is the standard method for MS diagnosis, but it is time-consuming, and its visual interpretation can be difficult. The results suggest that the KI is a good alternative for the detection of intrathecal immunoproduction in cases of suspected MS.
ANTECEDENTES: Bandas oligoclonais (BOCs) e cadeias leves de imunoglobulina (free light chains, FLCs, em inglês) Kappa no líquido cefalorraquidiano (LCR) são marcadores sensíveis da síntese intratecal de imunoglobulina (Ig)G em pacientes com esclerose múltipla (EM). OBJETIVO: Avaliar a taxa de concordância entre BOCs e o índice Kappa (IK) em pacientes com suspeita de EM. MéTODOS: Pacientes com suspeita de EM foram encaminhados a um laboratório especializado em LCR como parte de sua investigação diagnóstica. Amostras pareadas de LCR e soro foram coletadas e investigadas quanto à presença de BOCs e submetidas à determinação do IK. Resultados positivos e negativos foram determinados com ambos os métodos, e estabeleceu-se o percentual de concordância entre eles. RESULTADOS: Ao todo, 171 amostras de soro e LCR de 171 pacientes foram incluídas na análise. A média de idade dos pacientes foi de 40 ± 14,2 anos; 18,9% deles eram do sexo masculino, e 81,1%, do sexo feminino. Resultados concordantes entre as BOCs e o IK foram observados em 161 (94,2%) amostras: em 74 (43,3%), ambos foram positivos, e em 87 (50,9%), ambos foram negativos. Em 10 casos, os resultados foram discrepantes: IK positivo/BOC negativo em 8, e BOC positivo/IK negativo em 2. CONCLUSãO: Observou-se alto nível de concordância entre o IK e as BOCs. A detecção de BOCs no LCR é atualmente o método padrão para o diagnóstico de EM, mas é demorado, e sua interpretação visual pode ser difícil. Os resultados sugerem que o IK pode ser uma alternativa para a detecção de imunoprodução intratecal em casos de suspeita de EM.
Assuntos
Esclerose Múltipla , Bandas Oligoclonais , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Bandas Oligoclonais/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/líquido cefalorraquidiano , Imunoglobulina GRESUMO
Alzheimer's disease (AD) is the most common type and accounts for 60%-70% of the reported cases of dementia. MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in gene expression regulation. Although the diagnosis of AD is primarily clinical, several miRNAs have been associated with AD and considered as potential markers for diagnosis and progression of AD. We sought to match AD-related miRNAs in cerebrospinal fluid (CSF) found in the GeoDataSets, evaluated by machine learning, with miRNAs listed in a systematic review, and a pathway analysis. Using machine learning approaches, we identified most differentially expressed miRNAs in Gene Expression Omnibus (GEO), which were validated by the systematic review, using the acronym PECO-Population (P): Patients with AD, Exposure (E): expression of miRNAs, Comparison (C): Healthy individuals, and Objective (O): miRNAs differentially expressed in CSF. Additionally, pathway enrichment analysis was performed to identify the main pathways involving at least four miRNAs selected. Four miRNAs were identified for differentiating between patients with and without AD in machine learning combined to systematic review, and followed the pathways analysis: miRNA-30a-3p, miRNA-193a-5p, miRNA-143-3p, miRNA-145-5p. The pathways epidermal growth factor, MAPK, TGF-beta and ATM-dependent DNA damage response, were regulated by these miRNAs, but only the MAPK pathway presented higher relevance after a randomic pathway analysis. These findings have the potential to assist in the development of diagnostic tests for AD using miRNAs as biomarkers, as well as provide understanding of the relationship between different pathophysiological mechanisms of AD.
Assuntos
Doença de Alzheimer , Mineração de Dados , Aprendizado de Máquina , MicroRNAs , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/genética , Doença de Alzheimer/diagnóstico , Humanos , MicroRNAs/líquido cefalorraquidiano , MicroRNAs/genética , Biomarcadores/líquido cefalorraquidianoRESUMO
A 30-year-old woman had 5 days of visual hallucinations, nystagmus, memory impairment and mutism. On examination, she was disorientated with reduced attention span, gaze-evoked nystagmus, paratonia and abnormal frontal reflexes. Cerebrospinal fluid (CSF) showed 80 cells, protein 0.41 g/L and glucose 3.2 mmol/L (plasma glucose 5.0 mmol/L). MR scan of the brain showed involvement of limbic and extra-limbic regions and brainstem. Commercial cell-based assays were negative, but tissue-based assays showed neuropil staining, and cell-based assays for anti-metabotropic glutamate receptor 5 (mGluR5) antibodies were positive in serum and CSF. Six months later, she was diagnosed with Hodgkin's lymphoma. This case emphasises the broader clinical spectrum of anti-mGluR5 encephalitis, challenging its initial characterisation as Ophelia syndrome. It underscores the significance of interpreting commercial cell-based assays and advocates for tissue-based assay testing followed by cell-based assay testing in serum and CSF for diagnosing rare autoimmune encephalitis.
Assuntos
Autoanticorpos , Encefalite , Receptor de Glutamato Metabotrópico 5 , Humanos , Feminino , Adulto , Receptor de Glutamato Metabotrópico 5/imunologia , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Autoanticorpos/imunologia , Encefalite/imunologia , Encefalite/diagnóstico , Encefalite/sangue , Doença de Hodgkin/complicações , Doença de Hodgkin/imunologiaRESUMO
This manuscript presents the quantification and correlation of three aspects of Alzheimer's Disease evolution, including structural, biochemical, and cognitive assessments. We aimed to test a novel structural biomarker for neurodegeneration based on a cortical folding model for mammals. Our central hypothesis is that the cortical folding variable, representative of axonal tension in white matter, is an optimal discriminator of pathological aging and correlates with altered loadings in Cerebrospinal Fluid samples and a decline in cognition and memory. We extracted morphological features from T1w 3T MRI acquisitions using FreeSurfer from 77 Healthy Controls (age = 66 ± 8.4, 69% females), 31 Mild Cognitive Impairment (age = 72 ± 4.8, 61% females), and 13 Alzheimer's Disease patients (age = 77 ± 6.1, 62% females) of recruited volunteers in Brazil to test its discriminative power using optimal cut-point analysis. Cortical folding distinguishes the groups with reasonable accuracy (Healthy Control-Alzheimer's Disease, accuracy = 0.82; Healthy Control-Mild Cognitive Impairment, accuracy = 0.56). Moreover, Cerebrospinal Fluid biomarkers (total Tau, A[Formula: see text]1-40, A[Formula: see text]1-42, and Lipoxin) and cognitive scores (Cognitive Index, Rey's Auditory Verbal Learning Test, Trail Making Test, Digit Span Backward) were correlated with the global neurodegeneration in MRI aiming to describe health, disease, and the transition between the two states using morphology.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Doença de Alzheimer/patologia , Disfunção Cognitiva/patologia , Biomarcadores/líquido cefalorraquidiano , Cognição , Envelhecimento , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidianoRESUMO
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.
Assuntos
Infecções por Enterovirus , Enterovirus , Meningite Asséptica , Meningite Viral , Criança , Adulto , Adolescente , Humanos , Lactente , Enterovirus/genética , Meningite Asséptica/líquido cefalorraquidiano , Brasil/epidemiologia , Estudos Retrospectivos , Líquido CefalorraquidianoRESUMO
Acute lymphoblastic leukemia (ALL) is highly associated with central nervous system (CNS) infiltration and can be associated with higher risk of relapse. Conventional cytology (CC) is the traditional method for diagnosing CNS infiltration, although the use of immunophenotyping by flow cytometry (FC) has gained prominence in recent years due to its higher sensitivity. Also, some authors have proposed that CSF contamination by a traumatic lumbar puncture (TLP) could have a clinical impact. This retrospective study accessed the impact of CNS infiltration by CC or FC on overall survival, event-free survival, and relapse rate. In a cohort of 105 newly diagnosed ALL patients, CNS1, CNS2, and CNS3 status were found in 84%, 14%, and 2%, respectively. We found that extramedullary disease at the diagnosis, higher leukocyte counts, and higher blast percentage were associated with a positive CC. Sensitivity and specificity of CC were 53% and 98%, respectively. Three-year overall survival was 42.5%. Conversely, TLP was not associated with a positive CC nor had an impact on relapse rates. In multivariate analysis, a positive CC was associated with an increased relapse rate (HR 2.074, p = 0.037), while its detection by FC did not associate with this endpoint. Survival rates seem to be increasing over the last years by the adoption of a stratified CNS prophylaxis risk strategy. CSF contamination does not represent a major concern according to our report, as it did not increase CNS involvement or relapse rates.
Assuntos
Infiltração Leucêmica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquidiano , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Infiltração Leucêmica/líquido cefalorraquidiano , Adolescente , Idoso , Adulto Jovem , Prognóstico , Taxa de Sobrevida , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Citometria de Fluxo , Imunofenotipagem , Intervalo Livre de DoençaRESUMO
BACKGROUND: Studies have shown that A Disintegrin and Metalloproteinase 10 (ADAM10) is the main α-secretase in the non-amyloidogenic cleavage of the amyloid precursor protein (APP), avoiding the production of amyloid-ß peptide (Aß), one of the pathological hallmarks of Alzheimer's disease (AD). OBJECTIVE: To investigate ADAM10 from cerebrospinal fluid (CSF) and plasma/serum as a potential biomarker for AD. METHODS: A systematic review was carried out in the MEDLINE/PubMed, Web of Science, Embase, and Scopus databases using the terms and Boolean operators: "Alzheimer" AND "ADAM10" AND "biomarker". Citation searching was also adopted. The inclusion criteria were original studies of ADAM10 in blood or CSF in patients with AD. The risk of bias was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The analysis methods were registered in the PROSPERO database (#CRD42021274239). RESULTS: Of the 97 records screened, 17 were included. There is strong evidence for lower levels of ADAM10 in platelets of persons with AD compared to cognitively healthy participants. On the other hand, higher levels of ADAM10 were found in plasma. Regarding CSF, controversial results were found with lower and higher levels of ADAM10 in persons with AD compared to healthy older adults. The differences may be due to diverse reasons, including different sample collection and processing and different antibodies, highlighting the importance of standardizing the experiments and choosing the appropriate antibodies for ADAM10 detection. CONCLUSION: Evidence shows that ADAM10 levels are altered in platelets, plasma, serum, and CSF of individuals with AD. The alteration was evident in all stages of the disease, and therefore, the protein may represent a complementary biomarker for the disease. However, more studies must be performed to establish cut-off values for ADAM10 levels to discriminate AD participants from cognitively unimpaired older adults.
Assuntos
Doença de Alzheimer , Humanos , Idoso , Doença de Alzheimer/diagnóstico , Estudos Transversais , Proteína ADAM10/metabolismo , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores , Secretases da Proteína Precursora do Amiloide/metabolismo , Proteínas de Membrana/líquido cefalorraquidianoRESUMO
Introducción: La infiltración del sistema nervioso central por células malignas constituye una complicación grave de algunas neoplasias hematológicas, principalmente leucemias agudas y linfomas agresivos. Objetivo: Resumir la base científica y la significación clínica de los métodos de estudio del líquido cefalorraquídeo para el diagnóstico y el seguimiento de la infiltración neuromeníngea en pacientes con neoplasias hematológicas. Métodos: Se buscó información durante abril de 2021 en las bases de datos PubMed, ScienceDirect y SciELO. Se seleccionaron las publicaciones en base a su tipología, actualidad, alcance y las limitaciones de los estudios. Conclusiones: El estudio citomorfológico del líquido cefalorraquídeo se considera el método estándar para el diagnóstico y el seguimiento de la infiltración neuromeníngea. La citometría de flujo resulta más sensible para la detección de infiltración oculta que la citología convencional; pero aún existen reservas sobre su significación clínica. Se investiga también la sensibilidad de otros estudios moleculares como el uso de la reacción en cadena de la polimerasa y la detección de biomarcadores(AU)
Introduction: Infiltration of the central nervous system by malignant cells constitutes a serious complication of some hematological malignancies, mainly acute leukemias and aggressive lymphomas. Objective: To summarize the scientific basis and clinical significance of cerebrospinal fluid study methods for the diagnosis and follow-up of neuromeningeal infiltration in patients with hematologic malignancies. Methods: Information was searched during April 2021 in PubMed, ScienceDirect and SciELO databases. Publications were selected based on their typology, timeliness, scope, and study limitations. Conclusions: The cytomorphological study of cerebrospinal fluid is considered the standard method for the diagnosis and follow-up of neuromeningeal infiltration. Flow cytometry is more sensitive for the detection of occult infiltration than conventional cytology, but there are still reservations about its clinical significance. The sensitivity of other molecular studies such as the use of PCR and biomarker detection is also investigated(AU)
Assuntos
Humanos , Neoplasias Hematológicas/líquido cefalorraquidiano , Biomarcadores , Sistema Nervoso Central , Reação em Cadeia da Polimerase , Citometria de FluxoRESUMO
Background: Anti-LGI1 encephalitis is characterized by a pattern of inflammation that predominantly affects the limbic system It is part of the autoimmune encephalitis that attack neuronal surface antigens. It is characterized by the triad of subacute dementia, faciobrachial dystonic crises, and hyponatremia, presenting an excellent response to immunotherapy. The aim of this article is to describe the clinical evolution and functional outcome at 6 months of two patients with anti-LGI1 encephalitis using clinical cases. Clinical cases: Case 1: 62-year-old man with 8-week symptoms manifested by changes in mood, disorientation, and focal motor seizures. Case 2 A 72-year-old woman with a 5-month evolution of rapidly progressive dementia, hyponatremia and bitemporal hyperintensities on MRI. In both, due to clinical suspicion, acute dual immunotherapy with steroid and immunoglobulin was given with substantial improvement. Subsequently, the existence of anti-LGI1 antibodies in cerebrospinal fluid was confirmed. Although both patients received a dose of rituximab during their hospitalization, only the patient in the first case continued biannual doses of rituximab. The second patient was not initially considered to continue long-term immunomodulatory treatment and experienced a relapse. Conclusions: These clinical vignettes present the reader with the classic characteristics of this disease. This can facilitate its recognition and timely initiation of treatment, improving the functional prognosis of patients.
Introducción: la encefalitis anti-LGI1 se caracteriza por un patrón de inflamación que afecta de forma predominante al sistema límbico. Forma parte de las encefalitis autoinmunes que atacan a antígenos de superficie neuronal. Se caracteriza por la tríada de demencia subaguda, crisis distónicas faciobraquiales e hiponatremia, presentando una respuesta excelente a la inmunoterapia. El objetivo de este trabajo es describir por casos clínicos la evolución clínica y resultado funcional a 6 meses de dos pacientes con encefalitis anti-LGI1. Casos clínicos: caso 1: hombre de 62 años con cuadro de 8 semanas, manifestado por cambios en el estado de ánimo, desorientación y crisis focales motoras. Caso 2: mujer de 72 años con una evolución de 5 meses de demencia rápidamente progresiva, hiponatremia e hiperintensidades bitemporales en RMN. En ambos, ante la sospecha clínica, se otorgó inmunoterapia dual aguda con esteroide e inmunoglobulina con mejoría sustancial, posteriormente se corroboró la existencia de anticuerpos anti-LGI1 en líquido cefalorraquídeo. Pese a que ambos pacientes recibieron una dosis de rituximab durante su hospitalización, solo el primer caso continuó dosis semestrales de rituximab. El segundo no fue considerado inicialmente para continuar con tratamiento inmunomodulador a largo plazo y presentó una recaída. Conclusiones: estos casos, presentan al lector las características clásicas de esta enfermedad. Esto puede facilitar su reconocimiento y la instauración oportuna del tratamiento, mejorando el pronóstico funcional de los pacientes.
Assuntos
Doenças Autoimunes do Sistema Nervoso , Demência , Encefalite , Hiponatremia , Encefalite Límbica , Masculino , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Peptídeos e Proteínas de Sinalização Intracelular/uso terapêutico , Autoanticorpos/líquido cefalorraquidiano , Autoanticorpos/uso terapêutico , Encefalite Límbica/tratamento farmacológico , México , Rituximab/uso terapêutico , Recidiva Local de Neoplasia , Encefalite/diagnósticoRESUMO
INTRODUCTION: As disease-modifying therapies become available for Alzheimer's disease (AD), detection of AD in early stages of illness (mild cognitive impairment [MCI], early dementia) becomes increasingly important. Biomarkers for AD in low- and middle-income countries (LMICs) are costly and not widely available; hence, it is important to identify cognitive tests that correlate well with AD biomarker status. In this study, we evaluated the memory alteration test (M@T) to detect biomarker-proven AD and quantify its correlation with neurodegeneration and cerebrospinal fluid (CSF) AD biomarkers in a cohort of participants from Lima, Peru. METHODS: This is a secondary analysis of a cohort of 185 participants: 63 controls, 53 with amnestic MCI (aMCI), and 69 with dementia due to AD. Participants underwent testing with M@T and a gold standard neuropsychological battery. We measured total tau (t-tau), phosphorylated tau (p-tau), and beta-amyloid (ß-amyloid) in CSF, and evaluated neurodegeneration via medial temporal atrophy score in MRI. We used receiver-operator curves to determine the discriminative capacity of the total M@T score and its subdomains. We used the Pearson coefficient to correlate M@T score and CSF biomarkers. RESULTS: The M@T had an area under the curve (AUC) of 0.994 to discriminate between controls and cognitively impaired (aMCI or AD) patients, and an AUC of 0.98 to differentiate between aMCI and AD patients. Free-recall and cued recall had the highest AUCs of all subdomains. Total score was strongly correlated with t-tau (-0.77) and p-tau (-0.72), and moderately correlated with ß-amyloid (0.66). The AUC for discrimination of neurodegeneration was 0.87. CONCLUSION: The M@T had excellent discrimination of aMCI and dementia due to AD. It was strongly correlated with CSF biomarkers and had good discrimination of neurodegeneration. In LMICs, the M@T may be a cost-effective screening tool for aMCI and dementia caused by AD.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/líquido cefalorraquidiano , Peru , Proteínas tau/líquido cefalorraquidiano , Encéfalo , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Neuroimagem , Fragmentos de Peptídeos/líquido cefalorraquidianoRESUMO
Mild cognitive impairment (MCI) is often considered an early stage of dementia, with estimated rates of progression to dementia up to 80-90% after approximately 6 years from the initial diagnosis. Diagnosis of cognitive impairment in dementia is typically based on clinical evaluation, neuropsychological assessments, cerebrospinal fluid (CSF) biomarkers, and neuroimaging. The main goal of diagnosing MCI is to determine its cause, particularly whether it is due to Alzheimer's disease (AD). However, only a limited percentage of the population has access to etiological confirmation, which has led to the emergence of peripheral fluid biomarkers as a diagnostic tool for dementias, including MCI due to AD. Recent advances in biofluid assays have enabled the use of sophisticated statistical models and multimodal machine learning (ML) algorithms for the diagnosis of MCI based on fluid biomarkers from CSF, peripheral blood, and saliva, among others. This approach has shown promise for identifying specific causes of MCI, including AD. After a PRISMA analysis, 29 articles revealed a trend towards using multimodal algorithms that incorporate additional biomarkers such as neuroimaging, neuropsychological tests, and genetic information. Particularly, neuroimaging is commonly used in conjunction with fluid biomarkers for both cross-sectional and longitudinal studies. Our systematic review suggests that cost-effective longitudinal multimodal monitoring data, representative of diverse cultural populations and utilizing white-box ML algorithms, could be a valuable contribution to the development of diagnostic models for AD due to MCI. Clinical assessment and biomarkers, together with ML techniques, could prove pivotal in improving diagnostic tools for MCI due to AD.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/genética , Estudos Transversais , Progressão da Doença , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Aprendizado de Máquina , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidianoRESUMO
PONTOS-CHAVE Quando utilizados na técnica correta, fórcipes e vácuo-extratores apresentam baixos índices de complicações. Para o feto com sinais de hipóxia no período expulsivo, o parto vaginal operatório tem potencial para reduzir a exposição aos fatores intraparto que promovem a encefalopatia hipóxico-isquêmica. Fórcipes médios e/ou rotacionais são opções apropriadas em circunstâncias selecionadas e exigem habilidade e experiência. Os fórcipes são mais resolutivos do que os vácuo-extratores para o parto vaginal operatório, porém são mais associados a lacerações perineais graves. Céfalo-hematoma é mais provável de ocorrer com o aumento na duração da vácuo-extração. Os vácuo-extratores de campânulas flexíveis apresentam taxas maiores de falha, porém apresentam menores incidências de trauma no couro cabeludo do neonato. (AU)