RESUMEN
The purpose of this study is to investigate the diagnostic and prognostic role of cerebrospinal fluid (CSF) biomarkers in the diagnostic work-up of glucose transporter 1 (GLUT1) deficiency. Reported here is a systematic review according to PRISMA guidelines collecting clinical and biochemical data about all published patients who underwent CSF analysis. Clinical phenotypes were compared between groups defined by the levels of CSF glucose (≤ 2.2 mmol/L versus > 2.2 mmol/L), CSF/blood glucose ratio (≤ 0.45 versus > 0.45), and CSF lactate (≤ 1 mmol/L versus > 1 mmol/L). Five hundred sixty-two patients fulfilled the inclusion criteria with a mean age at the diagnosis of 8.6 ± 6.7 years. Patients with CSF glucose ≤ 2.2 mmol/L and CSF/blood glucose ratio ≤ 0.45 presented with an earlier onset of symptoms (16.4 ± 22.0 versus 54.4 ± 45.9 months, p < 0.01; 15.7 ± 23.8 versus 40.9 ± 38.0 months, p < 0.01) and received an earlier molecular genetic confirmation (92.1 ± 72.8 versus 157.1 ± 106.2 months, p < 0.01). CSF glucose ≤ 2.2 mmol/L was consistently associated with response to ketogenic diet (p = 0.018) and antiseizure medications (p = 0.025). CSF/blood glucose ratio ≤ 0.45 was significantly associated with absence seizures (p = 0.048), paroxysmal exercise-induced dyskinesia (p = 0.046), and intellectual disability (p = 0.016) while CSF lactate > 1 mmol/L was associated with a response to antiseizure medications (p = 0.026) but not to ketogenic diet.Conclusions:This systematic review supported the diagnostic usefulness of lumbar puncture for the early identification of patients with GLUT1 deficiency responsive to treatments especially if they present with co-occurring epilepsy, movement, and neurodevelopmental disorders. What is Known: ⢠Phenotypes of GLUT1 deficiency syndrome range between early epileptic and developmental encephalopathy to paroxysmal movement disorders and developmental impairment What is New: ⢠CSF blood/glucose ratio may predict better than CSF glucose the diagnosis in children presenting with early onset absences ⢠CSF blood/glucose ratio may predict better than CSF glucose the diagnosis in children presenting with paroxysmal exercise induced dyskinesia and intellectual disability. ⢠CSF glucose may predict better than CSF blood/glucose and lactate the response to ketogenic diet and antiseizure medications.
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Biomarcadores , Errores Innatos del Metabolismo de los Carbohidratos , Humanos , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/sangre , Pronóstico , Errores Innatos del Metabolismo de los Carbohidratos/diagnóstico , Errores Innatos del Metabolismo de los Carbohidratos/líquido cefalorraquídeo , Niño , Ácido Láctico/líquido cefalorraquídeo , Ácido Láctico/sangre , Glucemia/análisis , Dieta Cetogénica , Preescolar , Transportador de Glucosa de Tipo 1/genética , Glucosa/líquido cefalorraquídeo , Proteínas de Transporte de Monosacáridos/deficienciaRESUMEN
We investigated the agreement between the jugular bulb (JB) and cerebrospinal fluid (CSF) lactate levels. The study was conducted from July 2021 to June 2023 as a prospective observational cohort study at a single center. The right jugular vein was accessed, and the placement of JB catheter tip was confirmed using lateral cervical spine X-ray. A lumbar catheter was inserted between the 3rd and 4th lumbar spine of the patient. Lactate levels were measured immediately, 24 h, 48 h, and 72 h after ROSC. In patients with a good neurological prognosis, kappa between JB and CSF lactate levels measured immediately, at 24 h, 48 h, and 72 h after ROSC were 0.08, 0.36, 0.14, - 0.05 (p = 0.65, 0.06, 0.48, and 0.75, respectively). However, in patients with a poor neurological prognosis, kappa between JB and CSF lactate levels measured immediately, at 24 h, 48 h, and 72 h after ROSC were 0.38, 0.21, 0.22, 0.12 (p = 0.001, 0.04, 0.04, and 0.27, respectively). This study demonstrated that JB lactate levels exhibited significant agreement with arterial lactate levels, compared to CSF lactate levels. Therefore, this should be considered when using JB lactate to monitor cerebral metabolism.
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Venas Yugulares , Ácido Láctico , Paro Cardíaco Extrahospitalario , Humanos , Ácido Láctico/líquido cefalorraquídeo , Masculino , Femenino , Persona de Mediana Edad , Anciano , Paro Cardíaco Extrahospitalario/líquido cefalorraquídeo , Estudios Prospectivos , Pronóstico , Biomarcadores/líquido cefalorraquídeoRESUMEN
OBJECTIVES: To evaluate the performance of GeneXpert MTB/RIF (Xpert) for tuberculous meningitis (TBM) and to identify additional indicators to improve diagnostic accuracy. METHODS: An accuracy study was conducted. During 2011-2019, 243 TBM with 140 non-TBM in three TB-designated facilities in China were enrolled. Microbiological evidence of M tuberculosis (Mtb) in CSF was used as the reference. Additional indicators were identified by Boosted-Classification and Regression Tree (CART), the improvement of diagnostic performance was evaluated by ROC. RESULTS: The diagnostic sensitivity of Xpert was 71.1 % for definite TBM, and 5.5 % for probable/possible TBM. The positive rate of Xpert was improved with cerebrospinal fluid (CSF) increasing volume and was associated with CSF color (yellow). The additional indicators obtained by CART were CSF lactate and glucose and increased the sensitivity to 96.1 % (definite TBM) and 84.6 % (probable/possible TBM). CONCLUSIONS: The diagnostic performance of Xpert was satisfactory in definite TBM and would significantly be improved by the additional use of CSF lactate and glucose.
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Mycobacterium tuberculosis , Sensibilidad y Especificidad , Tuberculosis Meníngea , Humanos , Tuberculosis Meníngea/diagnóstico , Tuberculosis Meníngea/microbiología , Tuberculosis Meníngea/líquido cefalorraquídeo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Femenino , Adulto , Masculino , Persona de Mediana Edad , China , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Adulto Joven , Líquido Cefalorraquídeo/microbiología , Adolescente , Anciano , Ácido Láctico/líquido cefalorraquídeoRESUMEN
INTRODUCTION: Ventriculoperitoneal shunt (VPS) infection is a severe complication. Early diagnosis could help to decrease morbidity and treatment costs. Lactate has been used for the diagnosis of other central nervous system infections. The aim of this study is to determine the usefulness of lactate for the diagnosis of VPS infection. METHODOLOGY: Retrospective cohort study. Lactate was measured in patients who consulted with VPS dysfunction between May 2019 and May 2022. Mean were compared according to culture results. A Receiver Operating Characteristic (ROC) curve was performed to determine the appropriate cut-off point. RESULT: Lactate has a high negative predictive value but a low positive predictive value for the diagnosis of ventriculitis.
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Ácido Láctico , Derivación Ventriculoperitoneal , Humanos , Derivación Ventriculoperitoneal/efectos adversos , Estudios Retrospectivos , Femenino , Masculino , Ácido Láctico/líquido cefalorraquídeo , Niño , Preescolar , Lactante , Estudios de Cohortes , Adolescente , Ventriculitis Cerebral/líquido cefalorraquídeo , Ventriculitis Cerebral/diagnósticoRESUMEN
Despite numerous studies in human patients and animal models for phenylketonuria (PKU; OMIM#261600), the pathophysiology of PKU and the underlying causes of brain dysfunction and cognitive problems in PKU patients are not well understood. In this study, lumbar cerebral spinal fluid (CSF) was obtained immediately after blood sampling from early-treated adult PKU patients who had fasted overnight. Metabolite and amino acid concentrations in the CSF of PKU patients were compared with those of non-PKU controls. The CSF concentrations and CSF/plasma ratios for glucose and lactate were found to be below normal, similar to what has been reported for glucose transporter1 (GLUT1) deficiency patients who exhibit many of the same clinical symptoms as untreated PKU patients. CSF glucose and lactate levels were negatively correlated with CSF phenylalanine (Phe), while CSF glutamine and glutamate levels were positively correlated with CSF Phe levels. Plasma glucose levels were negatively correlated with plasma Phe concentrations in PKU subjects, which partly explains the reduced CSF glucose concentrations. Although brain glucose concentrations are unlikely to be low enough to impair brain glucose utilization, it is possible that the metabolism of Phe in the brain to produce phenyllactate, which can be transported across the blood-brain barrier to the blood, may consume glucose and/or lactate to generate the carbon backbone for glutamate. This glutamate is then converted to glutamine and carries the Phe-derived ammonia from the brain to the blood. While this mechanism remains to be tested, it may explain the correlations of CSF glutamine, glucose, and lactate concentrations with CSF Phe.
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Encéfalo , Glucosa , Fenilalanina , Fenilcetonurias , Humanos , Fenilcetonurias/metabolismo , Fenilcetonurias/líquido cefalorraquídeo , Glucosa/metabolismo , Adulto , Masculino , Fenilalanina/líquido cefalorraquídeo , Fenilalanina/sangre , Fenilalanina/metabolismo , Femenino , Encéfalo/metabolismo , Ácido Láctico/líquido cefalorraquídeo , Ácido Láctico/metabolismo , Ácido Láctico/sangre , Adulto Joven , Glutamina/metabolismo , Glutamina/líquido cefalorraquídeo , Glutamina/sangre , Glucemia/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: After neurosurgery, intracranial infection is a common complication with high rates of clinical impairment and death. Traditional diagnostic approaches are time-consuming. Early and correct diagnosis improves infection control, treatment success, and survival. Novel markers are used to diagnose and classify post-neurosurgical meningitis (PNM) to overcome the difficulties of diagnosing postoperative intracranial infections and avoid the drawbacks of existing diagnostic measures. The objective was to investigate the diagnostic value of ß-2 transferrin (ß-2TF) and transferrin (TF) in the cerebrospinal fluid (CSF) for the identification of intracranial infection after neurosurgery. METHODS: Owing to their symptoms and laboratory results, 168 patients with suspected intracranial infection after neurosurgery were divided into 3 groups: post-neurosurgical bacterial meningitis (PNBM; n = 61), post-neurosurgical aseptic meningitis (PNAM; n = 45), and non-PNM (n = 62). We measured lactate (LA), ß-2TF, and TF levels in the CSF. RESULTS: CSF LA levels were significantly higher in the PNM, PNBM, and PNAM groups compared with the non-PNM group ( P < .05). The CSF ß-2TF level in PNM, PNBM, and PNAM were statistically higher than those in non-PNMs ( P < .05). CSF TF levels in the PNBM group were statistically higher than those in the PNAM and non-PNM groups ( P < .05). The PNBM and non-PNM receiver operating curve (ROC) analysis indicates that the cutoff values for the combination (LA, ß-2TF, TF) was 0.349, and the area under the curve (AUC) was 0.945 ( P < .0001), with 92.86% sensitivity and 92.98% specificity. The PNAM and non-PNM ROC analysis indicates that the cutoff values for the combination (LA, ß-2TF, TF) was 0.346, and the AUC was 0.962 ( P < .0001), with 89.29% sensitivity and 90.24% specificity. The PNM and non-PNM ROC analysis indicates that the cutoff values for the combination (LA, ß-2TF, TF) was 0.609, and the AUC was 0.941 ( P < .0001), with 96.36% sensitivity and 82.83% specificity. A Glasgow Coma Scale score ≤8, LA, ß-2TF/TF ratio, length of hospital stay, intensive care unit admission, poor surgical wound, and craniotomy were associated with poor outcomes ( P < .05). LA and ß-2TF were independent risk factors for intracranial infection. CONCLUSION: Postoperative cerebral infections can be identified using CSF ß-2TF as a particular marker protein. CSF TF helps distinguish PNBM from PNAM. Combining CSF LA with them improves diagnostic speed, sensitivity, and accuracy. LA and ß-2TF were independent risk factors for cerebral infection.
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Meningitis Bacterianas , Neurocirugia , Humanos , Transferrina , Procedimientos Neuroquirúrgicos/efectos adversos , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/etiología , Meningitis Bacterianas/líquido cefalorraquídeo , Craneotomía/efectos adversos , Ácido Láctico/líquido cefalorraquídeo , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Curva ROCRESUMEN
BACKGROUND: Cerebral microdialysis (CMD) has become an established bedside monitoring modality but its implementation remains complex and costly and is therefore performed only in a few well-trained academic centers. This study investigated the relationship between cerebrospinal fluid (CSF) and CMD glucose and lactate concentrations. METHODS: Two centers retrospective study of prospectively collected data. Consecutive adult (>18 years) acutely brain injured patients admitted to the Intensive Care Unit between 2010 and 2021 were eligible if CSF and CMD glucose and lactate concentrations were concomitantly measured at least once. RESULTS: Of 113 patients being monitored with an external ventricular drainage and CMD, 49 patients (25 from Innsbruck and 24 from Brussels) were eligible for the final analysis, including a total of 96 measurements. Median CMD glucose and lactate concentrations were 1.15 (0.51-1.57) mmol/L and 3.44 (2.24-5.37) mmol/L, respectively; median CSF glucose and lactate concentrations were 4.67 (4.03-5.34) mmol/L and 3.40 (2.85-4.10) mmol/L, respectively. For the first measurements, no correlation between CSF and CMD glucose concentrations (R2 <0.01; p = 0.95) and CSF and CMD lactate concentrations (R2 =0.16; p = 0.09) was found. Considering all measurements, the repeated measure correlation analysis also showed no correlation for glucose (rrm = -0.01; 95% Confidence Intervals -0.306 to 0.281; p = 0.93) and lactate (rrm = -0.11; 95% Confidence Intervals -0.424 to 0.236; p = 0.55). CONCLUSIONS: In this study including acute brain injured patients, no correlation between CSF and brain tissue measurements of glucose and lactate was observed. As such, CSF measurements of such metabolites cannot replace CMD findings.
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Encéfalo , Glucosa , Adulto , Humanos , Estudios Retrospectivos , Microdiálisis , Encéfalo/metabolismo , Glucosa/líquido cefalorraquídeo , Ácido Láctico/líquido cefalorraquídeoRESUMEN
Bacterial meningitis is a serious complication after neurosurgery and has a high mortality rate. Early diagnosis and timely treatment are crucial or will have disastrous consequences. The classic triad of bacterial meningitis lacks sensitivity and specificity. Therefore, the diagnosis of post-neurosurgical bacterial meningitis relies on cerebrospinal fluid. But traditional cerebrospinal fluid parameters are not completely reliable in diagnosing post-neurosurgical bacterial meningitis. Previous studies have found that CSF lactate concentration is related to bacterial meningitis. But, after the craniocerebral operation, the cerebrospinal fluid of most patients is bloody. Whether red blood cells interfere with diagnosing PNBM based on lactate concentration is limited. In the current study, we further analysis on whether red blood cells interfere with diagnosing PNBM based on lactate concentration. This study aimed to investigate the value of cerebrospinal fluid lactate concentrations in post-neurosurgical bacterial meningitis. A prospective observational study was performed on 62 patients at Kunshan First People's Hospital's intensive care unit affiliated with Jiangsu University. We found that erythrocytes do not affect cerebrospinal fluid lactate, and elevated lactate concentrations can be used as a marker for postoperative bacterial meningitis.
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Meningitis Bacterianas , Complicaciones Posoperatorias , Humanos , Ácido Láctico/líquido cefalorraquídeo , Meningitis Bacterianas/diagnóstico , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Sensibilidad y Especificidad , Estudios ProspectivosRESUMEN
Meningitis is a critical public health problem demanding immediate diagnosis and effective treatment due to high mortality rates. Cerebrospinal Fluid (CSF) lactate concentration is a promising test to distinguish bacterial from viral meningitis. This study aimed to assess the performance and usefulness of CSF lactate as a biomarker to differentiate between bacterial and viral meningitis, and to determine its optimal level to differentiate between them. This prospective study included 50 patients, presented to Abbassia Fever Hospital with clinical findings consistent with meningitis. Patients were divided into two groups: Group1 included 30 patients with bacterial meningitis. Group 2 included 20 patients with viral meningitis. CSF lactate and other conventional CSF parameters were recorded. For CSF culture, Streptococcus pneumoniae was identified in 53.3% of the bacterial meningitis group. The polymerase chain reaction (PCR) indicated that S. pneumoniae was present in 26/50 (52%) and 3/50 (6%) patients were PCR negative. Among bacterial meningitis patients, S. pneumoniae was the most pervasive organism 26/30 (86.7%). The mean CSF lactate level was 9.3 mmol/l ±5.0 (2.2-17.6). There was a statistically significant strong agreement (Kappa=0.957) between types of meningitis diagnosed by PCR, culture, and CSF lactate at cutoff level of 7.2 mmol/L. This cutoff value was the best to differentiate between bacterial and viral meningitis. The validity of CSF lactate as a differentiating tool showed sensitivity, specificity, positive predictive value, and negative predictive value of 93.3%, 100%, 100%, and 90.9%, respectively. In conclusion, CSF lactate could be a valuable, sensitive, specific, and rapid marker for identifying the most dangerous bacterial causes of CNS infection, especially S. pneumoniae. CSF lactate can be routinely used as an early biochemical warning marker and a useful point-of-care test. CSF lactate at cutoff level of >7.2 mmol/L can accurately detect S. pneumoniae, the most prevalent organism in Egypt.
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Meningitis Bacterianas , Meningitis Viral , Humanos , Ácido Láctico/líquido cefalorraquídeo , Estudios Prospectivos , Diagnóstico Diferencial , Meningitis Viral/diagnóstico , Meningitis Viral/líquido cefalorraquídeo , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Bacterianas/microbiología , Biomarcadores , Sensibilidad y EspecificidadRESUMEN
Objective: This retrospective case-control study aimed to investigate the relationship between cerebrospinal fluid (CSF) biomarkers and subarachnoid hemorrhage (SAH) and cerebral hemorrhage (CH) and to determine whether these biomarkers can predict the risk of hemorrhage. Methods: Patients diagnosed with SAH and CH at Chongqing University Central Hospital between January 2020 and April 2022 were included in this study. CSF-adenosine deaminase (ADA), CSF-lactate (Lac), and CSF-lactate dehydrogenase (LDH) were measured, and their associations with hemorrhage risk were analyzed using multivariable logistic regression models. The predictive value of these biomarkers was evaluated using receiver operating characteristic (ROC) analysis. Results: A total of 114 SAH patients, 105 CH patients, and 53 healthy controls were included in this study. The multivariable analysis revealed that hypertension, CSF-ADA, and CSF-Lac were independent risk factors for SAH, while hypertension and CSF-LDH were independent risk factors for CH. The ROC analysis demonstrated that the combination of CSF-ADA and CSF-Lac had the highest predictive value for SAH (area under the curve = 0.938), while CSF-LDH had the highest predictive value for CH (area under the curve = 0.946). Conclusion: CSF biomarkers, specifically CSF-ADA, CSF-Lac, and CSF-LDH, are valuable predictors of SAH and CH. These biomarkers may assist in diagnosing and managing hemorrhagic stroke in clinical settings.
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Hemorragia Cerebral , Hemorragia Subaracnoidea , Humanos , Estudios de Casos y Controles , Estudios Retrospectivos , Biomarcadores , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/complicaciones , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico , Ácido Láctico/líquido cefalorraquídeoRESUMEN
INTRODUCTION: Pyruvate dehydrogenase complex (PDH) deficiency (Online Mendelian Inheritance in Man # 312170) is a relatively common mitochondrial disorder, caused by mutations in the X-linked PDHA1 gene and presenting with a variable phenotypic spectrum, ranging from severe infantile encephalopathy to milder chronic neurological disorders.Isolated peripheral neuropathy as predominant clinical presentation is uncommon. RESULTS: We report on a patient, now 21 years old, presenting at the age of 2 years with recurrent symmetric weakness as first symptom of a PDH deficiency. Neurophysiological evaluation proving a sensory-motor polyneuropathy with conduction blocks and presence of elevated cerebrospinal fluid proteins, suggested a chronic inflammatory demyelinating polyneuropathy. The evidence of high serum lactate and the alterations in oxidative metabolism in muscle biopsy pointed toward the final diagnosis. After starting nutritional supplements, no further episodes occurred. A hemizygous mutation in PDHA1 (p.Arg88Cys) was identified. This mutation has been previously described in five patients with a similar phenotype. A three-dimensional reconstruction demonstrated that mutations affecting this arginine destabilize the interactions between the subunits of the E1 complex. CONCLUSION: We summarize the clinical and genetic characteristics of one patient with PDH deficiency presenting isolated peripheral nervous system involvement. This study highlights that the diagnosis of PDH deficiency should be considered in children with unexplained peripheral neuropathy, even with features suggestive of acquired forms, especially in case of early onset and limited response to treatment. A simple analysis of lactic acid could help to target the diagnosis.In addition, we suggest that the residue Arg88 is the most frequently involved in this specific phenotype of PDH deficiency.
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Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa , Humanos , Ácido Láctico/líquido cefalorraquídeo , Ácido Láctico/uso terapéutico , Mutación , Fenotipo , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/diagnóstico , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/tratamiento farmacológico , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/genéticaRESUMEN
BACKGROUND: Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far. OBJECTIVE: To analyze systematically the CSF profile in COVID-19. METHODS: Retrospective analysis of 150 lumbar punctures in 127 patients with PCR-proven COVID-19 and neurological symptoms seen at 17 European university centers RESULTS: The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72-50.8]), which was present in 58/116 (50%) samples from patients without pre-/coexisting CNS diseases (group I). QAlb remained elevated > 14d (47.6%) and even > 30d (55.6%) after neurological onset. CSF total protein was elevated in 54/118 (45.8%) samples (median 65.35 mg/dl [45.3-240.4]) and strongly correlated with QAlb. The CSF white cell count (WCC) was increased in 14/128 (11%) samples (mostly lympho-monocytic; median 10 cells/µl, > 100 in only 4). An albuminocytological dissociation (ACD) was found in 43/115 (37.4%) samples. CSF L-lactate was increased in 26/109 (24%; median 3.04 mmol/l [2.2-4]). CSF-IgG was elevated in 50/100 (50%), but was of peripheral origin, since QIgG was normal in almost all cases, as were QIgA and QIgM. In 58/103 samples (56%) pattern 4 oligoclonal bands (OCB) compatible with systemic inflammation were present, while CSF-restricted OCB were found in only 2/103 (1.9%). SARS-CoV-2-CSF-PCR was negative in 76/76 samples. Routine CSF findings were normal in 35%. Cytokine levels were frequently elevated in the CSF (often associated with BCB dysfunction) and serum, partly remaining positive at high levels for weeks/months (939 tests). Of note, a positive SARS-CoV-2-IgG-antibody index (AI) was found in 2/19 (10.5%) patients which was associated with unusually high WCC in both of them and a strongly increased interleukin-6 (IL-6) index in one (not tested in the other). Anti-neuronal/anti-glial autoantibodies were mostly absent in the CSF and serum (1509 tests). In samples from patients with pre-/coexisting CNS disorders (group II [N = 19]; including multiple sclerosis, JC-virus-associated immune reconstitution inflammatory syndrome, HSV/VZV encephalitis/meningitis, CNS lymphoma, anti-Yo syndrome, subarachnoid hemorrhage), CSF findings were mostly representative of the respective disease. CONCLUSIONS: The CSF profile in COVID-19 with neurological symptoms is mainly characterized by BCB disruption in the absence of intrathecal inflammation, compatible with cerebrospinal endotheliopathy. Persistent BCB dysfunction and elevated cytokine levels may contribute to both acute symptoms and 'long COVID'. Direct infection of the CNS with SARS-CoV-2, if occurring at all, seems to be rare. Broad differential diagnostic considerations are recommended to avoid misinterpretation of treatable coexisting neurological disorders as complications of COVID-19.
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COVID-19/líquido cefalorraquídeo , Adulto , Barrera Hematoencefálica , COVID-19/complicaciones , Proteínas del Líquido Cefalorraquídeo/líquido cefalorraquídeo , Citocinas/líquido cefalorraquídeo , Europa (Continente) , Femenino , Humanos , Inmunidad Celular , Inmunoglobulina G/líquido cefalorraquídeo , Ácido Láctico/líquido cefalorraquídeo , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/etiología , Bandas Oligoclonales/líquido cefalorraquídeo , Estudios Retrospectivos , Punción Espinal , Síndrome Post Agudo de COVID-19RESUMEN
Neoplastic cell infiltration into the central nervous system (CNS) is a serious complication of hematological neoplasms. Cytomorphology (CM) and flow cytometry (FC) have been used to detect meningeal infiltration. The association between CSF findings with the results of CM and FC is still poorly understood. We retrospectively evaluated CSF findings in 72 patients with hematological neoplasm and meningeal infiltration detected either by CM or FC. We compared CSF cell count, total protein concentration, and lactate concentration according to the type of hematological neoplasm. We also compared these CSF findings according to the FC and CM results (FC + CM + , FC + CM-, and FC-CM +). The proportion of patients with positive FC was higher than with CM (FC - 91.7%; CM - 63.9%). Thirty-five (48.6%) patients with meningeal infiltration had normal CSF cell count, normal total protein concentration, and normal lactate concentration. The proportion of cases in which these CSF parameters were normal did not differ according to the type of hematological neoplasm. The positivity of CM was significantly higher in patients with > 3 cell/mm3 (P = 0.015) but the positivity of FC was not significantly different between patients with > 3 cell/mm3 or ≤ 3 cells/mm3. Patients with positive CM had more CSF cells (P = 0.0005) and higher lactate concentration (P = 0.0165) than patients with negative CM. The absence of CSF changes in cell count and total protein and lactate concentrations does not exclude the presence of meningeal infiltration. Although CM is considered the gold standard, the probability of positive CM is low in patients without CSF abnormalities in these parameters. Patients with hematological neoplasm with suspected meningeal infiltration should be investigated with both methods.
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Neoplasias Hematológicas/líquido cefalorraquídeo , Neoplasias Hematológicas/diagnóstico por imagen , Neoplasias Meníngeas/líquido cefalorraquídeo , Neoplasias Meníngeas/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/líquido cefalorraquídeo , Niño , Preescolar , Femenino , Citometría de Flujo/métodos , Humanos , Lactante , Ácido Láctico/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Scrub typhus is one of the most common causes of meningo-encephalitis in endemic areas of the Indian subcontinent. Numerous studies have established the reliability of cerebrospinal fluid lactate for differentiation of bacterial meningitis from aseptic meningitis. However, there are no reported data on the predictive value of cerebrospinal fluid lactate in scrub typhus meningitis. We thus conducted a cross-sectional study to examine the diagnostic accuracy of cerebrospinal fluid lactate in the differentiation of different causes of acute meningitis. Over two years, we studied 119 patients, with almost equal gender distribution, whose mean age was 43.58 (±18) years and their overall mean duration of fever was 11.7 (±21.0) days. Commonest clinical features overall were neck stiffness; values of cerebrospinal fluid lactate were lowest in aseptic meningitis, followed by scrub typhus, TB and bacterial meningitis. We conclude that cerebrospinal fluid lactate levels may be a useful adjunct to clinical features and laboratory investigations to differentiate between bacterial, viral, tubercular and scrub meningitis.
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Ácido Láctico/líquido cefalorraquídeo , Meningitis Aséptica/diagnóstico , Meningitis Bacterianas/diagnóstico , Tifus por Ácaros/diagnóstico , Adulto , Estudios Transversales , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Meningitis Aséptica/líquido cefalorraquídeo , Meningitis Bacterianas/líquido cefalorraquídeo , Persona de Mediana Edad , Orientia tsutsugamushi , Reproducibilidad de los Resultados , Tifus por Ácaros/líquido cefalorraquídeo , Tuberculosis Meníngea/líquido cefalorraquídeo , Tuberculosis Meníngea/diagnósticoRESUMEN
Listeria rhombencephalitis (L. rhombencephalitis) is an uncommon form of central nervous system infection caused by Listeria monocytogenes (LM). It often occurs to immunocompetent individuals. Here, we described the case of a 45-year-old female patient without medical histories, who presented for high-grade fever, headache, and focal neurological manifestations. She was initially empirically diagnosed with acute disseminated encephalomyelitis (ADEM) because of clinical symptoms, acute clinical course, and neuroimaging. However, the biochemical analysis of cerebral spinal fluid (CSF) questioned the diagnosis of ADEM. The final diagnosis of L. rhombencephalitis was based on CSF culture for LM. Thus, L. rhombencephalitis should be preferentially and empirically considered for a patient with significantly elevated lactic acid and moderately increased red cells in CSF at early time, accompanied with rapidly progressive neurological dysfunctions involved in the brain stem.
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Encefalitis/diagnóstico , Encefalomielitis Aguda Diseminada/diagnóstico , Fiebre/diagnóstico , Cefalea/diagnóstico , Ácido Láctico/líquido cefalorraquídeo , Listeria monocytogenes/patogenicidad , Biomarcadores/líquido cefalorraquídeo , Diagnóstico Diferencial , Encefalitis/líquido cefalorraquídeo , Encefalitis/patología , Encefalomielitis Aguda Diseminada/líquido cefalorraquídeo , Encefalomielitis Aguda Diseminada/patología , Femenino , Fiebre/líquido cefalorraquídeo , Fiebre/patología , Cefalea/líquido cefalorraquídeo , Cefalea/patología , Humanos , Listeria monocytogenes/aislamiento & purificación , Imagen por Resonancia Magnética , Persona de Mediana Edad , Rombencéfalo/diagnóstico por imagen , Rombencéfalo/metabolismo , Rombencéfalo/patologíaRESUMEN
Lactate is produced from anaerobic glycolysis, which occurs in most tissues in the human body. Blood lactate is tested in most physiologically unwell patients in the Emergency Department and helps to guide treatment and prognosis. Cerebrospinal fluid (CSF) lactate, however, is not often measured. Various central nervous system (CNS) conditions lead to a rise in CSF lactate, including acute neurological infection, stroke, seizures and mitochondrial pathologies. This article discusses the utility and limitations of CSF lactate, highlighting specific clinical situations where it can help in the diagnosis of CNS infections and unexplained encephalopathy.
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Enterovirus/aislamiento & purificación , Ácido Láctico/líquido cefalorraquídeo , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Viral/líquido cefalorraquídeo , Encefalomiopatías Mitocondriales/líquido cefalorraquídeo , Infecciones Estafilocócicas/líquido cefalorraquídeo , Adulto , Biomarcadores/líquido cefalorraquídeo , Encefalopatías/líquido cefalorraquídeo , Encefalopatías/diagnóstico , Infecciones del Sistema Nervioso Central/líquido cefalorraquídeo , Infecciones del Sistema Nervioso Central/diagnóstico , Femenino , Humanos , Masculino , Meningitis Bacterianas/diagnóstico , Meningitis Viral/diagnóstico , Persona de Mediana Edad , Encefalomiopatías Mitocondriales/diagnóstico , Infecciones Estafilocócicas/diagnósticoRESUMEN
Cerebrospinal fluid (CSF) changes are significant for antemortem diagnoses of some neurological diseases. The aim of this study was to evaluate if the concentration of L-lactate in CSF could be used to differentiate healthy from encephalitic cattle. Cerebrospinal fluid samples from healthy cattle (n = 10) and from those naturally affected by rabies (n = 15), bovine herpesvirus type 5 meningoencephalitis (n = 16), histophilosis (n = 6), or bacterial encephalitis (n = 4), including 1 case of listeriosis, were collected and analyzed. Physical, biochemical (i.e., protein and glucose), and cellular analyses were performed in fresh samples. L-lactate, electrolytes (sodium, potassium, and chloride), calcium, and magnesium concentrations were measured in CSF samples that were kept frozen. L-lactate concentrations were also measured in plasma. Analysis of variance was used for comparison between groups and receiver operating characteristic analysis was performed considering L-lactate in CSF of healthy versus encephalitic cattle. The CSF L-lactate concentration was significantly higher in cattle with bacterial encephalitis than in healthy cattle; however, it did not differ between viral and bacterial encephalitis. The calcium concentrations were lower in cattle with encephalitis. L-lactate concentration in CSF > 3.6 mmol/L can be accepted as a cut-off value to indicate encephalitis. Thus, L-lactate in CSF is important for the diagnosis of encephalitis in cattle. Despite the small number of cases of bacterial encephalitis, it is suggested that L-lactate was not important for the differentiation between viral and bacterial encephalitis. Additional studies with a greater number of observations are necessary to clarify this, specifically in cases of listeriosis.
Les modifications du liquide céphalorachidien (LCR) sont importantes pour le diagnostic antemortem de certaines maladies neurologiques. Le but de cette étude était d'évaluer si la concentration de L-lactate dans le LCR pouvait être utilisée pour différencier les bovins en bonne santé des bovins encéphalitiques. Des échantillons de LCR provenant de bovins en bonne santé (n = 10) et de sujets infectés naturellement par la rage (n = 15), de méningoencéphalite à BoHV-5 (n = 16), l'histophilose (n = 6), ou d'encéphalite bactérienne (n = 4), notamment un cas de listériose ont été collectés et analysés. Des analyses physiques, biochimiques (protéines et glucose), et cellulaires ont été effectuées dans des échantillons frais. Les concentrations de L-lactate, d'électrolytes (Na+, K+, et Cl−), de calcium (Ca), et de magnésium ont été mesurées dans des échantillons de LCR maintenus congelés. Les concentrations de L-lactate ont également été mesurées dans le plasma. Une analyse de variance a été utilisée pour la comparaison entre les groupes et une analyse ROC (Receiver Operating Characteristic) a été réalisée en considérant le L-lactate dans le LCR de bovins en bonne santé par rapport à des bovins encéphalitiques. La concentration de L-lactate dans le LCR était significativement plus élevée chez les bovins présentant une encéphalite bactérienne que chez les bovins en bonne santé. Cependant, elle ne différait pas entre les bovins présentant une encéphalite virale et bactérienne. Les concentrations de Ca étaient plus faibles chez les bovins atteints d'encéphalite. Une concentration de L-lactate dans le LCR > 3,6 mmol/L peut être acceptée comme valeur seuil indiquant une encéphalite. Ainsi, le L-lactate dans le LCR est important pour le diagnostic de l'encéphalite chez les bovins. Malgré le petit nombre de cas d'encéphalite bactérienne inclus, il a été suggéré que la concentration de L-lactate dans le LCR dans la présente étude n'était pas une méthode de diagnostic important dans la différenciation entre l'encéphalite virale et bactérienne chez les bovins. Des études supplémentaires comportant un plus grand nombre d'observations sont nécessaires pour clarifier cet aspect, en particulier dans les cas de listériose.(Traduit par les auteurs).
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Enfermedades de los Bovinos/líquido cefalorraquídeo , Encefalitis/veterinaria , Ácido Láctico/líquido cefalorraquídeo , Animales , Infecciones Bacterianas/líquido cefalorraquídeo , Infecciones Bacterianas/veterinaria , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Bovinos , Enfermedades de los Bovinos/diagnóstico , Encefalitis/líquido cefalorraquídeo , Encefalitis/microbiología , Encefalitis/virología , Virosis/líquido cefalorraquídeo , Virosis/veterinariaRESUMEN
BACKGROUND: Concentrations of soluble amyloid-ß (Aß) oscillate with the sleep-wake cycle in the interstitial fluid of mice and cerebrospinal fluid (CSF) of humans. Further, the concentration of Aß in CSF increases during sleep deprivation. Stress and disruption of the circadian clock are additional mechanisms hypothesized to increase CSF Aß levels. Cortisol is a marker for stress and has an endogenous circadian rhythm. Other factors such as glucose and lactate have been associated with changes in sleep-wake activity and/or Aß. OBJECTIVE: In this exploratory study, we used samples collected in a previous study to examine how sleep deprivation affects Aß, cortisol, lactate, and glucose in plasma and CSF from healthy middle-aged adults (Nâ=â11). METHODS: Eleven cognitively normal participants without evidence of sleep disturbance were randomized to sleep deprivation or normal sleep control. All participants were invited to repeat the study. Cortisol, lactate, glucose, and Aß were measured in 2-h intervals over a 36-h period in both plasma and CSF. All concentrations were normalized to the mean prior to calculating mesor, amplitude, acrophase, and other parameters. RESULTS: One night of sleep deprivation increases the overnight concentration of Aß in CSF approximately 10%, but does not significantly affect cortisol, lactate, or glucose concentrations in plasma or CSF between the sleep-deprived and control conditions. CONCLUSION: These data suggest that sleep deprivation-related changes in CSF Aß are not mediated by stress or circadian disruption as measured by cortisol.
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Péptidos beta-Amiloides/líquido cefalorraquídeo , Ritmo Circadiano/fisiología , Privación de Sueño/líquido cefalorraquídeo , Sueño/fisiología , Estrés Fisiológico/fisiología , Estrés Psicológico/líquido cefalorraquídeo , Adulto , Cognición/fisiología , Femenino , Glucosa/líquido cefalorraquídeo , Humanos , Hidrocortisona/líquido cefalorraquídeo , Ácido Láctico/líquido cefalorraquídeo , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The pathophysiology of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) has not been fully evaluated. The aim of this study was to evaluate the dynamics of lactate and lactate dehydrogenase (LDH) in carotid cisternal cerebrospinal fluid (CSF), and to discuss their effectiveness as markers of early brain injury (EBI) and DCI following aSAH. PATIENTS AND METHODS: Among 91 consecutive aSAH patients treated between January 2012 and March 2019 at National Hospital Organization Beppu Medical Center, 19 patients (20.9%) were eligible for this retrospective study. Concentrations of lactate and LDH in carotid cisternal CSF within 14 days after onset of aSAH were evaluated. RESULTS: Six of the 19 patients (31.6%) had a history of DCI. Both lactate and LDH levels in carotid cisternal CSF were significantly higher in the DCI group than in the non-DCI group on postbleeding day (PBD) 1-2, 3-4, and 5-6. Interestingly, neither lactate nor LDH levels in blood differed significantly between DCI and non-DCI groups on PBD 1-2. CONCLUSIONS: Lactate and LDH concentrations in carotid cisternal CSF may vividly reflect the EBI and may thus represent predictive biomarkers of DCI following aSAH.
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Isquemia Encefálica/líquido cefalorraquídeo , Hidrocefalia/líquido cefalorraquídeo , L-Lactato Deshidrogenasa/líquido cefalorraquídeo , Ácido Láctico/líquido cefalorraquídeo , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Anciano , Biomarcadores/líquido cefalorraquídeo , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiología , Femenino , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/etiología , Hidrocefalia/cirugía , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico , Hemorragia Subaracnoidea/cirugía , Factores de TiempoRESUMEN
PURPOSE: The detection and quantification of metabolites relevant for the diagnosis of fatal metabolic disorders by proton magnetic resonance spectroscopy (1H-MRS) was recently demonstrated. This prospective study aimed to compare the concentrations of beta-hydroxybutyrate (BHB), glucose (GLC), and lactate (LAC) derived from both biochemical analyses and 1H-MRS for the diagnosis of fatal metabolic disorders. METHODS: In total, 20 cases with suspected fatal metabolic disorders were included in the study. For the agreement based on thresholds, the concentrations of BHB and GLC in the vitreous humor (VH) from the right vitreous and in cerebrospinal fluid (CSF) from the right lateral ventricle were derived from 1H-MRS and biochemical analyses. The predefined thresholds for pathological elevations were 2.5 mmol/l for BHB and 10 mmol/l for GLC based on the literature. In addition, concentrations of the same metabolites in white matter (WM) tissue from the corona radiata of the right hemisphere were analyzed experimentally using both methods. To enable the biochemical analysis, a dialysate of WM tissue was produced. For all three regions, the LAC concentration was determined by both methods. RESULTS: The conclusive agreement based on thresholds was almost perfect between both methods with only one disagreement in a total of 70 comparisons due to the interference of a ferromagnetic dental brace. The differences in the concentrations between both methods showed high standard deviations. Confidence intervals of the bias not including 0 were found in CSF-GLC (- 3.1 mmol/l), WM-GLC (1.1 mmol/l), and WM-LAC (- 6.5 mmol/l). CONCLUSION: Despite a considerable total error attributable to both methods, MRS derives the same forensic conclusions as conventional biochemical analyses. An adaptation of the protocol to reduce the detected errors and more data are needed for the long-term validation of MRS for the diagnosis of fatal metabolic disorders. The production of WM dialysates cannot be recommended due to high glycolytic loss.