ABSTRACT
Cerebrospinal fluid hypocretin-1 is proven to be a precise diagnostic marker of narcolepsy Type 1 (NT1). However other characteristics of cerebrospinal fluid and blood parameters have not yet been described. The objective of this study was to evaluate the differences in routine blood and cerebrospinal fluid analyses between NT1 patients and patients suspected of hypersomnia. We collected retrospectively all measures of cerebrospinal fluid hypocretin-1 between 2019 and 2022. This yielded 612 patients out of which 146 were diagnosed with NT1 and the rest (466 patients) were used as a control group. We selected the most relevant routine samples from both blood, plasma and cerebrospinal fluid and compared the two groups. The only significantly different analytes were plasma lactate dehydrogenase and cerebrospinal fluid hypocretin-1. No other differences were found between the groups including thyroid markers, markers of neuroendocrine function, inflammatory markers in blood or cerebrospinal fluid, markers of permeability of the blood brain barrier or metabolic markers in blood samples. We found no significant differences in routine blood or cerebrospinal fluid components, neuroendocrine function, neuroinflammation and metabolic markers. The results reflect that the hypocretin system does not seem to play a chronic major role in regulation of these markers. None of the parameters routinely measured in blood in these patients could differentiate between NT1 and non-NT1 disorders besides CSF-hcrt-1.
Subject(s)
Biomarkers , Narcolepsy , Orexins , Humans , Narcolepsy/cerebrospinal fluid , Narcolepsy/blood , Narcolepsy/diagnosis , Male , Female , Orexins/cerebrospinal fluid , Orexins/blood , Adult , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Middle Aged , Retrospective Studies , Adolescent , Young Adult , L-Lactate Dehydrogenase/blood , L-Lactate Dehydrogenase/cerebrospinal fluid , Case-Control Studies , AgedABSTRACT
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.
Subject(s)
Brain Ischemia/cerebrospinal fluid , Hydrocephalus/cerebrospinal fluid , L-Lactate Dehydrogenase/cerebrospinal fluid , Lactic Acid/cerebrospinal fluid , Subarachnoid Hemorrhage/cerebrospinal fluid , Aged , Biomarkers/cerebrospinal fluid , Brain Ischemia/diagnosis , Brain Ischemia/etiology , Female , Humans , Hydrocephalus/diagnosis , Hydrocephalus/etiology , Hydrocephalus/surgery , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Risk Factors , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/diagnosis , Subarachnoid Hemorrhage/surgery , Time FactorsABSTRACT
PURPOSE: Cerebrospinal fluid (CSF) lactate dehydrogenase (LDH) levels increase in patients with brain injury. We investigated neurologic outcomes associated with CSF LDH levels in out-of-hospital cardiac arrest (OHCA) survivors who underwent target temperature management (TTM). MATERIALS AND METHODS: This was a prospective single-centre observational study from April 2018 to May 2019 on a cohort of 41 patients. CSF and serum LDH samples were obtained immediately (LDH0) and at 24 (LDH24), 48 (LDH48), and 72 h (LDH72) after return of spontaneous circulation (ROSC). Neurologic outcomes were assessed at 3 months after ROSC using the Cerebral Performance Category scale. RESULTS: Twenty-one patients had a poor neurologic outcome. CSF LDH levels were significantly higher in the poor neurologic outcome group at each time point. The area under the curve (AUC) of CSF LDH48 was 0.941 (95% confidence interval [CI], 0.806-0.992). With a cut off value of 250 U/L, CSF LDH48 had a high sensitivity (94.1%; 95% CI, 71.3-99.9) at 100% specificity. CONCLUSIONS: CSF LDH level at 48 h was a highly specific and sensitive marker for 3-month poor neurologic outcome. This may constitute a useful predictive marker for neurologic outcome in OHCA survivors treated with TTM.
Subject(s)
Hypothermia, Induced/methods , Out-of-Hospital Cardiac Arrest/cerebrospinal fluid , Out-of-Hospital Cardiac Arrest/therapy , Adult , Aged , Area Under Curve , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Female , Humans , L-Lactate Dehydrogenase/blood , L-Lactate Dehydrogenase/cerebrospinal fluid , Male , Middle Aged , Out-of-Hospital Cardiac Arrest/blood , Predictive Value of Tests , Prognosis , Prospective Studies , Reproducibility of Results , Sensitivity and Specificity , Survivors , Temperature , Treatment OutcomeABSTRACT
BACKGROUND: Lactate dehydrogenase (LD) exists as 5 isoenzymes (LD-1 through LD-5) that are expressed throughout the body and can be detected in both serum and cerebrospinal fluid (CSF). LD and its isoenzymes have been relatively unstudied in veterinary medicine, although studies in human medicine have demonstrated that changes in total LD activity and atypical isoenzyme patterns can indicate disease processes, including neurologic abnormalities. OBJECTIVES: The purpose of this study was to establish RIs for LD and its isoenzymes in the serum and CSF of clinically healthy dogs. By establishing a definitive RI for this enzyme in healthy canines, further study of the clinical and diagnostic usefulness of LD can be undertaken. METHODS: Serum and atlantoaxial CSF were collected from clinically healthy dogs. Total LD activity was measured spectrophotometrically immediately after collection. Isoenzyme distributions were also determined within 8 hours of collection using the QuickGel LD Isoenzyme technique and a densitometric scanner. RESULTS: The median serum total LD in healthy canines was 69.0 U/L (n = 41; range: 21.0-217.0 U/L), while the median CSF total LD was 10.0 U/L (n = 40; range: 6.0-19.3 U/L). LD-5 is the predominant isoenzyme in canine serum (n = 40), contributing over half of the total enzyme activity. Conversely, in canine CSF (n = 42), LD-1 is the predominant isoenzyme, followed by LD-2 and LD-3. CONCLUSIONS: Knowledge of the distribution and concentration of LD in the serum and CSF of healthy dogs will set the foundation for future studies of canine LD as a potentially clinically useful biomarker.
Subject(s)
Dogs/blood , Dogs/cerebrospinal fluid , L-Lactate Dehydrogenase/blood , L-Lactate Dehydrogenase/cerebrospinal fluid , Animals , Densitometry/veterinary , Electrophoresis/veterinary , Female , Isoenzymes/blood , Isoenzymes/cerebrospinal fluid , Male , Reference ValuesABSTRACT
This study aimed to establish the prognostic utility of lactate dehydrogenase (LDH) levels in the cerebrospinal fluid (CSF) of patients with neoplastic meningitis (NM). Patients with a confirmed diagnosis of NM at a cancer referral center were included. Data on demographic and oncological background, clinical symptoms, diagnostic tests, treatment, and survival were analyzed. In total, 119 patients were included, 74% of whom were females. The mean age was 44.2â¯years at the time of cancer diagnosis and 46.6â¯years at the time between NM diagnosis. Primary cancers were mostly breast cancer, lung cancer, or hematologic malignancies. The mean Karnofsky performance score (KPS) was 65. Frequent clinical symptoms were visual complaints, headache, cranial neuropathy, focal weakness, and decreased awareness. Diagnosis was made based on clinical symptoms, cytological CSF analysis results, and/or magnetic resonance imaging findings. The median overall survival (OS) was 4â¯months (95% CI 2.48-5.52). Prognostic variables associated with a better OS were hematopoietic malignancies, KPSâ¯≥â¯70, absence of meningeal signs, receiving any form of treatment, normal CSF glucose levels, and normal CSF LDH levels. After bivariate analysis, high LDH in the CSF remained statistically significant as a poor prognostic indicator. The LDH level is a useful parameter to assess the prognosis of patients with NM. Other factors associated with the prognosis of these patients were tumor type, CSF glucose levels, performance status, and receiving any form of treatment.
Subject(s)
Biomarkers, Tumor/cerebrospinal fluid , L-Lactate Dehydrogenase/cerebrospinal fluid , Meningeal Carcinomatosis/diagnosis , Meningeal Carcinomatosis/secondary , Adult , Aged , Female , Humans , Karnofsky Performance Status , Magnetic Resonance Imaging , Male , Meningeal Carcinomatosis/mortality , Meningitis/cerebrospinal fluid , Meningitis/diagnosis , Meningitis/etiology , Middle Aged , Prognosis , Retrospective StudiesABSTRACT
An inflammatory response occurring after fatal traumatic brain injury (TBI) initiates time-dependent cascades of acute phase response. This may offer the potential to monitor postmortem biomarker levels of several pro-inflammatory cytokines to gain information about the cause of death and the trauma survival time. Cerebrospinal fluid (CSF) and serum samples were collected from forensic autopsies of 95 adult cadavers after postmortem intervals up to 6 days. The cases were divided according to their cause of death into fatal TBI (n = 46) with different survival times and age- and gender-matching non-TBI fatalities as controls (n = 49). Quantitative marker levels of interleukin-6 (IL-6), ferritin, soluble tumor necrosis factor receptor type 1, C-reactive protein, and lactate dehydrogenase were analyzed using immunoassays. Standardized statistical tests were performed to differentiate causes of death and survival time of TBI cases. The CSF IL-6, ferritin, and LDH levels after TBI were significantly higher than those in the controls (p < 0.001). Only serum IL-6 values showed comparable differences (p < 0.05). Both CSF and serum ferritin levels were discriminative between early and delayed death after TBI (p < 0.05). There were partly distinctive correlations between marker levels in both fluids with rising values after longer survival. There were up to moderate correlation between the marker levels and the postmortem interval due to postmortem hemolysis. However, neither CSF nor serum level ranges were affected by the age or gender of the subjects. This study is the first to measure all five proteins systematically in postmortem trauma cases. Ferritin and IL-6 proved themselves to be interesting postmortem biomarkers to provide specific information on the injury pattern and the survival time of traumatic fatalities. Such forensic investigations could serve as inexpensive and fast laboratory tests.
Subject(s)
Acute-Phase Reaction , Brain Injuries, Traumatic/blood , Brain Injuries, Traumatic/cerebrospinal fluid , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Biomarkers/cerebrospinal fluid , C-Reactive Protein/analysis , Case-Control Studies , Female , Ferritins/blood , Ferritins/cerebrospinal fluid , Humans , Interleukin-6/blood , Interleukin-6/cerebrospinal fluid , L-Lactate Dehydrogenase/blood , L-Lactate Dehydrogenase/cerebrospinal fluid , Male , Middle Aged , Postmortem Changes , Receptors, Tumor Necrosis Factor, Type I/blood , Receptors, Tumor Necrosis Factor, Type I/cerebrospinal fluid , Young AdultABSTRACT
To investigate the protective effects of ginkgo diterpene lactone meglumine injection (GDLMI) on cerebral focal ischemia reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats, and explore its possible mechanism. One hundred and forty male SD rats were randomly divided into sham operation group, model group, ginkgo biloba extract injection (Ginaton, 1.0 mLâ¢kg⻹) group, nimodipine (0.4 mgâ¢kg⻹) group, and GDLMI (5.2, 2.6, 1.3 mgâ¢kg⻹) groups; All of rats received corresponding drugs by tail vein injection 4 days before operation (normal saline in model group and sham operation group). Except the sham operation group, the cerebral ischemic stroke model was established by MCAO method in right brain of the other rats. After 3 h of ischemia, all the animals received intravenous administration again. The neurobehavioral scores of rats after ischemia-reperfusion were evaluated and the infarct rate of brain tissue was observed by TTC staining. The super oxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and lactic acid (LA) contents in brain tissue homogenate and the concentration of Ca2+, glutamate (Glu) and aspartate (Asp), creatine phosphate kinase (CK-BB) and lactate dehydrogenase (LDH) content changes in cerebrospinal fluid were measured. As compared with the sham operation group, the cerebral infarction rate was increased significantly in the model group; the content of MDA and LA in the homogenate of brain tissue was increased, and the content of GSH and SOD was decreased; in cerebrospinal fluid, Ca2+ concentration was decreased, and the content of Glu and Asp, CK-BB and LDH increased significantly. As compared with the model group, the high and medium dose GDLMI groups can significantly reduce the cerebral infarction rate and improve the symptoms of neurological impairment; increase SOD and GSH activity, reduce MDA and LA content in serum; increase Ca2+ concentration in cerebrospinal fluid and decrease the content of neurotransmitter Glu and Asp as well as CK-BB and LDH. GDLMI could obviously improve neurologic impairment in model rats, and the mechanism may be related to recovering the blood brain barrier, scavenging free radicals, decreasing free Ca2+ inflow into the cells and the content of excitatory amino acid in cerebrospinal fluid to improve its protective effect on cerebral ischemia.
Subject(s)
Brain Ischemia/drug therapy , Ginkgo biloba/chemistry , Lactones/pharmacology , Reperfusion Injury/drug therapy , Terpenes/pharmacology , Animals , Aspartic Acid/cerebrospinal fluid , Calcium/cerebrospinal fluid , Creatine Kinase, BB Form/cerebrospinal fluid , Glutamic Acid/cerebrospinal fluid , Glutathione/analysis , L-Lactate Dehydrogenase/cerebrospinal fluid , Lactic Acid/analysis , Male , Malondialdehyde/analysis , Meglumine , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/analysisABSTRACT
BACKGROUND: Lactate dehydrogenase (LDH) exists as 5 isoenzymes in both serum and cerebrospinal fluid (CSF). Human studies have demonstrated that changes in LDH activity can be correlated with a particular disease. OBJECTIVES: Conflicting reports regarding the stability of LDH made it necessary to determine storage conditions before further study of the diagnostic power of this enzyme's activity can be pursued in dogs. The purpose of this study was to optimize measurement of LDH activity and analysis of its isoenzyme profile in canine serum and CSF through proper storage. METHODS: Serum and CSF were collected from 5 healthy dogs. Samples were stored at 22°C, 4°C, or -20°C for up to 2 months. Total LDH activity was measured spectrophotometrically. Isoenzyme profiles were determined using the QuickGel LDH Isoenzyme technique and densitometric scanning. Retention of > 70% LDH activity in stored samples was considered clinically acceptable. RESULTS: Serum and CSF stored at -20°C retained > 85% of the total LDH activity for 4 weeks, although CSF total LDH activity degraded by > 10% within 24 hours of storage. All serum LDH isoenzymes retained > 85% activity for up to 4 weeks at -20°C. CSF LDH isoenzyme activity degraded rapidly, therefore CSF LDH should be evaluated within 72 hours to assure > 75% of LDH isoenzyme activity. CONCLUSIONS: Proper storage at -20°C can optimize detection of total LDH activity and the LDH isoenzyme profile in canine serum and CSF. This information is important for evaluating the potential usefulness of LDH in veterinary medicine.
Subject(s)
Dogs/blood , Dogs/cerebrospinal fluid , L-Lactate Dehydrogenase/metabolism , Specimen Handling/veterinary , Temperature , Animals , Isoenzymes/metabolism , L-Lactate Dehydrogenase/blood , L-Lactate Dehydrogenase/cerebrospinal fluid , Specimen Handling/methodsABSTRACT
Neurosyphilis (NS) caused by Treponema pallidum (T. pallidum) subspecies pallidum, can affect the central nervous system during any stage of the disease. To assess several laboratory parameters for NS diagnosis, we performed a case control study on 42 hospitalized NS patients negative for human immunodeficiency virus (HIV) and 40 syphilis/non-NS patients, excluding NS patients at Xiamen Zhongshan Hospital from June 2010 to June 2011. Multivariate logistic regression model showed that the cerebrospinal fluid white blood cell (CSF-WBC, P = 0.009) levels, the CSF-LDH (P = 0.006) levels, the albumin quotient (P = 0.009) and the IgA index (P = 0.042) were independently associated with high risk of NS. The receiver operator characteristic (ROC) curve analysis revealed that the optimal cut-offs were 10 × 106 cells/L for the CSF-WBC concentration, 19.3 U/L for the CSF lactate dehydrogenase (LDH) concentration, 7.08 for the albumin quotient, and 0.14 for the IgA index. Combining the CSF-WBC level, the CSF-LDH level, the albumin quotient and the IgA index increased the NS diagnosis sensitivity to 97.6%. T. pallidum particle agglutination (TPPA) index significantly correlated with the CSF-WBC (r = 0.453, P = 0.000), the IgA index (r = 0.446, P = 0.000), the albumin quotient (r = 0.262, P = 0.017), and the CSF-LDH (r = − 0.278, P = 0.012), respectively. In addition, there were correlations between the CSF-WBC and the IgA index (r = 0.329, P = 0.003), and between the CSF-WBC and the albumin quotient (r = 0.306, P = 0.005). Our results indicated that simultaneous testing of CSF-WBC levels, albumin quotient, IgA index and CSF-LDH can help predict the likelihood of NS in HIV-negative patients.
Subject(s)
Neurosyphilis/cerebrospinal fluid , Adult , Aged , Albumins/cerebrospinal fluid , Case-Control Studies , Female , HIV Infections , Humans , Immunoglobulin A/blood , Immunoglobulin A/cerebrospinal fluid , Immunoglobulin G/blood , Immunoglobulin G/cerebrospinal fluid , Immunoglobulin M/blood , Immunoglobulin M/cerebrospinal fluid , L-Lactate Dehydrogenase/cerebrospinal fluid , Leukocyte Count , Male , Middle Aged , Neurosyphilis/epidemiology , Odds Ratio , Young AdultABSTRACT
Creutzfeldt-Jakob disease (CJD) is the most frequent human Prion-related disorder (PrD). The detection of 14-3-3 protein in the cerebrospinal fluid (CSF) is used as a molecular diagnostic criterion for patients clinically compatible with CJD. However, there is a pressing need for the identification of new reliable disease biomarkers. The pathological mechanisms leading to accumulation of 14-3-3 protein in CSF are not fully understood, however neuronal loss followed by cell lysis is assumed to cause the increase in 14-3-3 levels, which also occurs in conditions such as brain ischemia. Here we investigated the relation between the levels of 14-3-3 protein, Lactate dehydrogenase (LDH) activity and expression of the prion protein (PrP) in CSF of sporadic and familial CJD cases. Unexpectedly, we found normal levels of LDH activity in CJD cases with moderate levels of 14-3-3 protein. Increased LDH activity was only observed in a percentage of the CSF samples that also exhibited high 14-3-3 levels. Analysis of the PrP expression pattern in CSF revealed a reduction in PrP levels in all CJD cases, as well as marked changes in its glycosylation pattern. PrP present in CSF of CJD cases was sensitive to proteases. The alterations in PrP expression observed in CJD cases were not detected in other pathologies affecting the nervous system, including cases of dementia and tropical spastic paraparesis/HTLV-1 associated myelopathy (HAM/TSP). Time course analysis in several CJD patients revealed that 14-3-3 levels in CSF are dynamic and show a high degree of variability during the end stage of the disease. Post-mortem analysis of brain tissue also indicated that 14-3-3 protein is upregulated in neuronal cells, suggesting that its expression is modulated during the course of the disease. These results suggest that a combined analysis of 14-3-3 and PrP expression pattern in CSF is a reliable biomarker to confirm the clinical diagnosis of CJD patients and follow disease progression.
Subject(s)
Creutzfeldt-Jakob Syndrome/cerebrospinal fluid , Creutzfeldt-Jakob Syndrome/metabolism , Gene Expression Regulation , Prions/cerebrospinal fluid , 14-3-3 Proteins/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , Biomarkers/metabolism , Brain/metabolism , Creutzfeldt-Jakob Syndrome/diagnosis , Creutzfeldt-Jakob Syndrome/enzymology , Disease Progression , Female , Glycosylation , Humans , L-Lactate Dehydrogenase/cerebrospinal fluid , Male , Middle Aged , Prions/metabolism , Up-RegulationABSTRACT
BACKGROUND: Central nervous system (CNS) involvement is common in hemoncologic diseases especially in patients with acute lymphocytic leukemia (ALL). Currently available modalities have limitations in diagnosing CNS involvement in early stages of disease and have a limited prognostic value. Raised cerebrospinal fluid (CSF) total lactate dehydrogenase (LDH) levels can predict CNS involvement in patients with various neurological disorders including CNS leukemia. METHODS: This study was conducted in 23 consecutive freshly diagnosed patients of ALL without any previous CNS disease. Analysis of CSF was done for total LDH, proteins and electrolytes in all the patients before the start of chemotherapy and when the patients were in remission or 6 weeks after chemotherapy whichever was earlier. Twenty-three age and sex matched controls were also studied to set the normal reference range. The results were analyzed statistically by Student's t test and coefficient of co-relation between CSF LDH and protein in patients with raised CSF LDH at the time of presentation was also calculated. RESULTS: CSF LDH was increased in 4 out of 6 patients with signs and symptoms of CNS involvement (Group A) and 3 of these patients also had increased CSF protein levels. 2 out of 17 patients without signs and symptoms of CNS involvement (Group B) had both elevated CSF LDH and protein levels. The increased levels came down to normal reference values after chemotherapy except in one Group A patient in whom CSF LDH remained high. However, no significant change in CSF electrolytes was noted in these patients. CONCLUSION: Raised CSF LDH and CSF protein levels may indicate CNS involvement in patients with ALL.
Subject(s)
Biomarkers, Tumor/cerebrospinal fluid , Central Nervous System Neoplasms/cerebrospinal fluid , Cerebrospinal Fluid/chemistry , Electrolytes/analysis , L-Lactate Dehydrogenase/cerebrospinal fluid , Neoplasm Proteins/cerebrospinal fluid , Precursor Cell Lymphoblastic Leukemia-Lymphoma/cerebrospinal fluid , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/drug therapy , Child , Female , Humans , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Young AdultABSTRACT
Bacterial and aseptic meningitis are characterized by distinctive lactic dehydrogenase isoenzyme patterns. No studies have quantified the dynamics of lactic dehydrogenase isoenzyme distribution during treated bacterial meningitis. We used a retrospective case-series design, and reviewed files of all neonates with bacterial meningitis who attended our pediatric tertiary medical center for 8 years period. We identified neonates in whom a repeated lumbar puncture was indicated. Findings of cerebrospinal fluid analysis, including levels of lactic dehydrogenase isoenzymes, were compared with an age-matched reference group. In two patients with meningitis, lumbar puncture with cerebrospinal fluid analysis was repeated because of inadequate response to treatment or initially obscure etiologic pathogens. Both patients had initially low levels of lactic dehydrogenase-1 and lactic dehydrogenase-2 and high levels of lactic dehydrogenase-4 and lactic dehydrogenase-5, similar to other patients with bacterial meningitis. The distribution pattern of lactic dehydrogenase isoenzyme normalized after adequate antibiotic treatment. In light of the encouraging results in these two patients, further studies are warranted regarding the value of lactic dehydrogenase isoenzyme measurements for follow-up purposes and for evaluations of response to treatment.
Subject(s)
L-Lactate Dehydrogenase/cerebrospinal fluid , Meningitis, Bacterial/enzymology , Pasteurella Infections/enzymology , Streptococcal Infections/enzymology , Anti-Bacterial Agents/therapeutic use , Humans , Infant , Infant, Newborn , Isoenzymes/cerebrospinal fluid , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/drug therapy , Pasteurella Infections/cerebrospinal fluid , Pasteurella Infections/drug therapy , Retrospective Studies , Streptococcal Infections/cerebrospinal fluid , Streptococcal Infections/drug therapy , Time Factors , Treatment OutcomeABSTRACT
Differentiation of bacterial from aseptic meningitis may be difficult. Our aim was to determine the pattern of distribution of lactate dehydrogenase (LDH) isoenzymes in the cerebrospinal fluid (CSF) of patients with bacterial and aseptic meningitis. One hundred and fifty-seven patients with suspected meningitis were enrolled in the study. They were divided into 3 groups according to the culture- or bacterial antigen assay-proven diagnosis and CSF findings: bacterial meningitis (n = 31), aseptic meningitis (n = 65), and non-meningitis (n = 61). Total LDH level and percentages of LDH isoenzymes in the CSF were measured in each patient. Each group showed a distinct LDH isoenzyme distribution pattern, with a statistically significant difference among the groups in the percentages of the various isoenzymes. Compared with the non-meningitis group, total LDH activity in the CSF was high in the aseptic meningitis group (49.82+/-35.59 U/L, P < 0.001) and exaggerated in the bacterial meningitis group (944.53+/-112.3 U/L, P < 0.001). Low LDH-2 levels were unique to bacterial meningitis (P < 0.01), whereas high LDH-3 levels were characteristic of aseptic meningitis (P < 0.05). Both groups had low levels of LDH-1 and high levels of LDH-4 and LDH-5. In conclusion, the LDH isoenzyme pattern may be of clinical diagnostic value in meningitis, particularly when culture results are pending.
Subject(s)
L-Lactate Dehydrogenase/cerebrospinal fluid , Meningitis, Aseptic/cerebrospinal fluid , Meningitis, Aseptic/enzymology , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/enzymology , Adolescent , Body Fluids/enzymology , Child , Child, Preschool , Diagnosis, Differential , Humans , Infant , Infant, Newborn , Isoenzymes/cerebrospinal fluid , Meningitis, Aseptic/classification , Meningitis, Bacterial/classification , Patient SelectionABSTRACT
BACKGROUND: Impaired consciousness without a history of trauma is a common reason for emergency department (ED) visits. Among critically ill patients with a history and physical findings suggestive of a cerebrovascular accident (CVA), it may be difficult to differentiate between a structural and a non-structural cause for their condition. OBJECTIVES: This study was conducted to determine if lactic dehydrogenase (LDH) levels in the cerebrospinal fluid (CSF) of patients with acute non-traumatic neurological disorders could distinguish between structural and non-structural etiologies. MATERIAL AND METHODS: Over a 6-month period, CSF specimens were collected from 54 critically ill patients admitted to the ED with impaired consciousness and findings consistent with a CVA. The patients had moderate to severe impairment of consciousness, had a new motor or sensory deficit, or had meningeal signs of recent onset. CSF-LDH levels were analyzed because CSF levels of the enzyme are typically elevated in meningitis, metastatic cancer, and disorders resulting in ischemic necroses. Patients were excluded if a computed tomography scan showed contraindications to performing a lumbar puncture, if they had a coagulopathy, or if the CSF was xanthochromic or produced visible blood sediment after centrifuging. The data were analyzed according to the patients' admission diagnoses-structural vs. non-structural lesion. RESULTS: Of the samples collected from 54 patients, eight were excluded. Among the 46 patients included in the study, the mean age was 56.1 +/- 2.75 years, mean APACHE II score was 20.93 +/- 0.98, Glasgow Coma Scale (GCS) score was 7.15 +/- 0.49, and mortality was 55% (22 patients). The 30 patients with a structural abnormality had a mean age of 56.7 +/- 3.55 years, GCS score of 7.3 +/- 0.61, APACHE II score of 20.2 +/- 1.1, mortality of 43% (13 patients), and CSF-LDH level of 128.8 +/- 24.8 IU/L (95% confidence interval [CI] 78.1-179.6). The 16 patients with a non-structural (metabolic) disturbance had: a mean age of 55.0 +/- 4.42 years, GCS score of 6.87 +/- 0.86, APACHE II score of 22.2 +/- 1.94, mortality of 56% (9 patients), and CSF-LDH level of 29.8 +/- 2.9 IU/L (95% CI 23.6-36.1). Analysis by Student's t-test was p < 0.05. When the diagnostic value of CSF-LDH level was evaluated using a cutoff point of 40 IU/L, the following results were obtained: sensitivity: 86.7%, specificity: 81.3%, pretest likelihood: 65%, positive predictive value: 90%, negative predictive value: 76%, Likelihood Ratio (LR)+: 4.62, LR-: 0.16 (6.25-fold increase). CONCLUSIONS: In critically ill patients with acutely altered levels of consciousness but without a history of trauma, a CSF-LDH value < or = 40 IU/L is associated with non-structural pathology.
Subject(s)
Consciousness Disorders/enzymology , L-Lactate Dehydrogenase/cerebrospinal fluid , Stroke/enzymology , APACHE , Biomarkers/cerebrospinal fluid , Critical Illness , Cross-Sectional Studies , Emergency Service, Hospital , Female , Glasgow Coma Scale , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective StudiesABSTRACT
Lactate dehydrogenase isoenzymes were profiled in cerebrospinal fluid in patients with acute lymphoblastic leukemia. Cytological examination of patients with central nervous involvement identified isoenzyme 5 which failed to show after selective treatment. The isoenzyme's detection in cerebrospinal fluid without typical cytological characteristics may be regarded as a precursor of such complication. Hence, this may be used as an additional criterion for refinement of cytological evidence employed in diagnosis and prognosis of central nervous involvement in patients with acute lymphoblastic leukemia.
Subject(s)
Biomarkers, Tumor/cerebrospinal fluid , L-Lactate Dehydrogenase/cerebrospinal fluid , Precursor Cell Lymphoblastic Leukemia-Lymphoma/cerebrospinal fluid , Precursor Cell Lymphoblastic Leukemia-Lymphoma/enzymology , Adult , Female , Humans , Isoenzymes/cerebrospinal fluid , Lactate Dehydrogenase 5 , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , PrognosisABSTRACT
The present study investigated cerebrospinal fluid (CSF) biomarkers for estimating degeneration of the central nervous system (CNS) in experimental dogs with GM1 gangliosidosis and preliminarily evaluated the efficacy of long-term glucocorticoid therapy for GM1 gangliosidosis using the biomarkers identified here. GM1 gangliosidosis, a lysosomal storage disease that affects the brain and multiple systemic organs, is due to an autosomal recessively inherited deficiency of acid beta-galactosidase activity. Pathogenesis of GM1 gangliosidosis may include neuronal apoptosis and abnormal axoplasmic transport and inflammatory response, which are perhaps consequent to massive neuronal storage of GM1 ganglioside. In the present study, we assessed some possible CSF biomarkers, such as GM1 ganglioside, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and myelin basic protein (MBP). Periodic studies demonstrated that GM1 ganglioside concentration, activities of AST and LDH, and concentrations of NSE and MBP in CSF were significantly higher in dogs with GM1 gangliosidosis than those in control dogs, and their changes were well related with the months of age and clinical course. In conclusion, GM1 ganglioside, AST, LDH, NSE and MBP could be utilized as CSF biomarkers showing CNS degeneration in dogs with GM1 gangliosidosis to evaluate the efficacy of novel therapies proposed for this disease. In addition, we preliminarily treated an affected dog with long-term oral administration of prednisolone and evaluated the efficacy of this therapeutic trial using CSF biomarkers determined in the present study. However, this treatment did not change either the clinical course or the CSF biomarkers of the affected dog, suggesting that glucocorticoid therapy would not be effective for treating GM1 gangliosidosis.
Subject(s)
Brain/metabolism , Cerebrospinal Fluid Proteins/cerebrospinal fluid , Gangliosidosis, GM1/cerebrospinal fluid , Gangliosidosis, GM1/diagnosis , Nerve Degeneration/cerebrospinal fluid , Nerve Degeneration/diagnosis , Animals , Anti-Inflammatory Agents/therapeutic use , Aspartate Aminotransferases/analysis , Aspartate Aminotransferases/cerebrospinal fluid , Biomarkers/analysis , Biomarkers/cerebrospinal fluid , Brain/physiopathology , Disease Models, Animal , Dogs , G(M1) Ganglioside/analysis , G(M1) Ganglioside/cerebrospinal fluid , Gangliosidosis, GM1/drug therapy , L-Lactate Dehydrogenase/analysis , L-Lactate Dehydrogenase/cerebrospinal fluid , Myelin Basic Protein/analysis , Myelin Basic Protein/cerebrospinal fluid , Nerve Degeneration/drug therapy , Phosphopyruvate Hydratase/analysis , Phosphopyruvate Hydratase/cerebrospinal fluid , Predictive Value of Tests , Prednisolone/therapeutic use , Treatment Outcome , Up-Regulation/physiologyABSTRACT
The aim of the study was evaluation of usefulness of cerebrospinal fluid (CSF) lactate dehydrogenase (LDH) activity assessment in diagnostics of purulent, bacterial meningoencephalitis in adults. The investigations were performed in 17 subjects. In all individuals CSF and plasma LDH activity was estimated during the first 24 hours of hospitalization. Mean CSF LDH activity in patients in very severe clinical state (group I) was 299,11 U/L compared to 163,67 U/L in subjects of group II with moderate and mild course of disease. The difference between mean CSF activities of this enzyme was statistically significant (p<0,001). The obtained results indicate the usefulness of CSF LDH activity assessment in estimation of severity of the patient's clinical state. The magnitude of this activity seems to be also helpful as prognostic marker in purulent, bacterial meningoencephalitis.
Subject(s)
L-Lactate Dehydrogenase/blood , L-Lactate Dehydrogenase/cerebrospinal fluid , Meningitis, Bacterial/diagnosis , Meningoencephalitis/diagnosis , Adult , Female , Humans , Lymphocyte Count , Male , Meningitis, Bacterial/blood , Meningitis, Bacterial/cerebrospinal fluid , Meningoencephalitis/blood , Meningoencephalitis/cerebrospinal fluid , Prognosis , Severity of Illness IndexABSTRACT
The cerebrospinal fluid concentration of Glutamine and Lactate dehydrogenase (LDH) were studied in patients with pyogenic and tubercular meningitis. Significant increase in Glutamine and LDH level (P<0.001) were observed in the test group when compared to the control group. LDH and glutamine may not be useful in differentiating viral from other meningitis. It may act as corroborative evidence of meningitis.
Subject(s)
Brain Abscess/cerebrospinal fluid , Glutamine/cerebrospinal fluid , L-Lactate Dehydrogenase/cerebrospinal fluid , Meningitis/cerebrospinal fluid , Tuberculosis, Meningeal/cerebrospinal fluid , Humans , Meningitis/diagnosisABSTRACT
The cerebrospinal fluid concentration of Glutamine and Lactate dehydrogenase (LDH) were studied in patients with pyogenic and tubercular meningitis. Significant increase in Glutamine and LDH level (P<0.001) were observed in the test group when compared to the control group. LDH and glutamine may not be useful in differentiating viral from other meningitis. It may act as corroborative evidence of meningitis.