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Cerebrospinal fluid procalcitonin and severe traumatic brain injury in children.

OBJECTIVE: To determine the relationship between cerebrospinal fluid procalcitonin concentration and severe traumatic brain injury in children. DESIGN: Prospective, observational clinical study. SETTING: A multidisciplinary, tertiary-care pediatric intensive care unit. PATIENTS: Twenty-eight patients who required external ventricular drainage for management of severe traumatic brain injury (Glasgow Coma Scale score of <8) and 22 control patients for whom lumbar cerebrospinal fluid evaluation excluded possible meningitis. INTERVENTIONS: Standard intracranial pressure-directed neurointensive care, including intraventricular catheter placement and continuous cerebrospinal fluid drainage, was used to manage patients with severe traumatic brain injury. MEASUREMENTS AND MAIN RESULTS: Demographic data including age, mechanism of injury, time of injury, initial Glasgow Coma Scale score, and outcome were collected. Cerebrospinal fluid procalcitonin concentration was determined by immunoluminometric assay. Initial cerebrospinal fluid procalcitonin concentration (median [range]) in patients with severe traumatic brain injury was increased greater than three-fold vs. controls (0.41 ng/mL [0.15-2.14] vs. 0.12 ng/mL [0.00-0.24], p <.001). Initial cerebrospinal fluid procalcitonin concentration among patients with abusive head trauma (0.31 ng/mL [0.29-0.50]) also was increased vs. controls (p <.05), although this increase was less robust than patients with accidental trauma (0.41 ng/mL [0.15-2.14], p <.001 vs. controls). Additional examination of key demographic and outcome variables with a generalized linear regression model was performed for patients with severe traumatic brain injury. Univariate analysis revealed that both time after injury (p <.01) and abusive head trauma as a mechanism of injury (p <.001) were associated with attenuation of the increased cerebrospinal fluid procalcitonin response after traumatic brain injury. CONCLUSION: Cerebrospinal fluid procalcitonin concentration is increased in children after traumatic brain injury. The attenuated increase in cerebrospinal fluid procalcitonin among victims of abusive head trauma warrants further study because it may reflect impairment of endogenous neuroprotective mechanisms or delay in seeking medical attention. The significance of these observations remains to be determined as future studies elucidate the physiologic and mechanistic properties of procalcitonin.

Journal Article↗

Increased adenosine in cerebrospinal fluid after severe traumatic brain injury in infants and children: association with severity of injury and excitotoxicity.

OBJECTIVES: To measure adenosine concentration in the cerebrospinal fluid of infants and children after severe traumatic brain injury and to evaluate the contribution of patient age, Glasgow Coma Scale score, mechanism of injury, Glasgow Outcome Score, and time after injury to cerebrospinal fluid adenosine concentrations. To evaluate the relationship between cerebrospinal fluid adenosine and glutamate concentrations in this population. DESIGN: Prospective survey. SETTING: Pediatric intensive care unit in a university-based children's hospital. PATIENTS: Twenty-seven critically ill infants and children who had severe traumatic brain injury (Glasgow Coma Scale < 8), who required placement of an intraventricular catheter and drainage of cerebrospinal fluid as part of their neurointensive care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients ranged in age from 2 months to 14 yrs. Cerebrospinal fluid samples (n = 304) were collected from 27 patients during the first 7 days after traumatic brain injury. Control cerebrospinal fluid samples were obtained from lumbar puncture on 21 infants and children without traumatic brain injury or meningitis. Adenosine concentration was measured by using high-pressure liquid chromatography. Adenosine concentration was increased markedly in cerebrospinal fluid of children after traumatic brain injury vs. controls (p < .001). The increase in cerebrospinal fluid adenosine was independently associated with Glasgow Coma Scale < or = 4 vs. > 4 and time after injury (both p < .005). Cerebrospinal fluid adenosine concentration was not independently associated with either age (< or = 4 vs. > 4 yrs), mechanism of injury (abuse vs. other), or Glasgow Outcome Score (good/moderately disabled vs. severely disabled, vegetative, or dead). Of the 27 patients studied, 18 had cerebrospinal fluid glutamate concentration previously quantified by high-pressure liquid chromatography. There was a strong association between increases in cerebrospinal fluid adenosine and glutamate concentrations (p < .005) after injury. CONCLUSIONS: Cerebrospinal fluid adenosine concentration is increased in a time- and severity-dependent manner in infants and children after severe head injury. The association between cerebrospinal fluid adenosine and glutamate concentrations may reflect an endogenous attempt at neuroprotection against excitotoxicity after severe traumatic brain injury.

Adenosine↗

Cytology of equine cerebrospinal fluid.

The cytology of cerebrospinal fluid samples from horses is described. The samples were obtained from 24 normal horses, 35 horses with axonal degeneration and/or spinal cord compression, 29 horses with encephalomyelitis, 14 horses with other lesions of the nervous system, and eight horses with signs of neurologic dysfunction of undetermined origin. (Three of the latter were suspected botulinum intoxications.) Fluid was aspirated from the atlanto-occipital space following general anesthesia or immediately after a lethal dose of barbiturate. In two horses, fluid also was aspirated from the lumbosacral space. Small mononuclear cells were predominant in normal horses, and in most horses with axonal degeneration and encephalomyelitis. Several horses with encephalomyelitis also had neutrophils, eosinophils, and some mitotic figures. Although the cytologic findings were abnormal in many of the horses with disease of the central nervous system, in most horses the cytologic findings were normal.

Animals↗

Multiple sclerosis: activated cells in cerebrospinal fluid in acute exacerbations.

Cerebrospinal fluid (CSF) lymphocytes from three young patients undergoing acute exacerbations of multiple sclerosis were studied by flow cytometry. Using a new method that simultaneously measures cell-surface antigens and the cell-cycle phase, we determined that the CSF lymphocytes in these patients were activated. The majority of the activated cells expressed the OKT4 phenotype, while very few expressed the OKT8 phenotype.

Adolescent↗

Brucella melitensis: an unexpected isolate from cerebrospinal fluid.

A specimen of cerebrospinal fluid was initially handled with 'category 3' precautions because the patient came from Somalia, where tuberculosis and HIV infection are endemic. An isolate from the specimen, initially thought to be a Neisseria species, was subsequently handled on the open bench. It was later identified as Brucella melitensis. Laboratory procedures should allow for the possibility of brucella in such specimens until a positive identification has been made.

Brucella melitensis↗

Neurochemical analysis of cerebrospinal fluid.

The use of cerebrospinal fluid (CSF) analysis for studying in vivo alterations in central neuronal activity requires a relatively sophisticated knowledge of CSF physiology and pathology. Ventriculospinal concentration gradients, circadian rhythms, physical activity, stress, medications, precursor intake, concomitant illness, obstructed CSF circulation, age, and sex alter the baseline neurochemical composition of CSF. Differential probenecid blockade of the egress of acidic monoamine metabolites and cyclic nucleotides from the CSF may complicate interpretations of their accumulations. Degradation of CSF constituents during collection, storage, and analysis may introduce errors in quantification. These sources of CSF variability can be minimized with proper methodolology.

Blood-Brain Barrier↗

Antibodies to herpes-simplex virus in "normal" cerebrospinal fluid.

Thirty samples of cerebrospinal fluid (C.S.F.) obtained during routine myelography were examined for antibodies against herpes-simplex virus (H.S.V.) by antibody-mediated cell-dependent immune lysis. Antiviral antibody was found in the C.S.F. of all ten patients who were subject to recurrent cold sores. Thirteen of the twenty patients who denied or could not recall any previous herpetic infection had a serum antibody, and nine of them also had C.S.F antibody. All patients with C.S.F. antibody also had serum antibody. These results support the suggestion the H.S.V. antibodies may be responsible for maintaining the latency of H.S.V.

Adult↗

[A rare complication of shunt therapy. Metastasis of brain tumors by cerebrospinal fluid drainage].

Shunting of cerebrospinal fluid to extracranial spaces has been a common and effective procedure for symptomatic therapy of hydrocephalus since the fifties. In 1954 the first spreading of tumor cells via a ventriculo-pleural shunt was reported. We are presenting a case of a 10 month old girl with a medulloblastoma of the lower brain stem with spreading of the intracranial tumor through a ventriculoperitoneal shunt. Further 43 cases of the world literature with shunt-associated metastasizing of brain tumors are analysed. The extraneural spreading of tumor cells through shunt tubes must be considered as a possible complication of the shunting procedure.

Cerebellar Neoplasms↗

Cerebrospinal fluid immunoglobulins in children.

Cerebrospinal fluid (CSF) immunoglobulins were measured in 62 normal children, in 9 children with purulent meningitis, and in 10 children with presumptive viral meningitis. The mean values in normal children were IgA 0, IgM 0, and IgG 0.84 +/- 1.4 mg/100 ml (+/- SD). The mean levels of all CSF immunoglobulins were raised in acute bacterial meningitis and were significantly greater than the levels found in viral meningitis. CSF IgM was 0.16 +/- 0.5 mg/100 ml in viral meningitis compared with 2.64 +/- 2.06 mg/100 ml in bacterial meningitis (P less than 0.01). However, these values overlapped to a considerable extent and, generally, measurement of CSF immunoglobulins did not enhance diagnostic accuracy in this group of children.

Cerebrospinal Fluid Proteins↗

The presence of trace amines in postmortem cerebrospinal fluid in humans.

The postmortem levels of biogenic amines in cerebrospinal fluid may represent a useful tool in defining some pathological conditions; no information is available concerning the occurrence of trace amines in postmortem cerebrospinal fluid. Thus, the occurrence of octopamine, synephrine and tyramine were evaluated by using a HPLC system in 20 postmortem samples of cerebrospinal fluid (obtained from 11 males and 9 females) and their levels were compared with those of 20 living subjects (obtained from 11 males and 9 females). The results show that trace amines dramatically increase in the postmortem cerebrospinal fluid (100, 20, and 4 fold increase for tyramine, octopamine, and synephrine respectively). To our knowledge, our data represent the first time trace amines have been identified in postmortem cerebrospinal fluid and the dramatic increase observed for tyramine has the potential of becoming a new tool in forensic science for better defining the time of death.

Amines↗

[Behavior of the indirect immunofluorescence reaction and of cerebrospinal fluid parameters in neurocysticercosis].

Cerebrospinal fluid from 53 patients with clinical evidence of neurocysticercosis and 11 who suffered from several diseases were studied to evaluate the behaviour of indirect immunofluorescence test and some parameters of routine analysis. In neurocysticercosis there were pleocytosis in 88.7% of cases, eosinophilorrachia in 60.3%, hyperproteinorrachia in 71.7% and hypoglucorrachia in 13.2%. The indirect immunofluorescence test was positive in 79.2% of cases but false-positive results were found when the samples showed xanthochromia or erythrocyte contamination. The authors discuss their results in comparison with those in literature and conclude that the immunofluorescent test is sensitive and useful in diagnosis of neurocysticercosis, except when the interferents previously mentioned are present.

Adolescent↗

A unique protein in normal human cerebrospinal fluid.

On analysis of cerebrospinal fluid (CSF) samples from normal volunteer donors by high-resolution zone electrophoresis on agarose gel, an electrophoretically homogeneous protein band consistently appeared in the gamma-globulin region. Application of immunofixation electrophoresis in attempts to identify the band with use of monospecific antibodies against individual human serum proteins and against heavy- and light-chain immunoglobulins as well as polyvalent antisera did not produce a positive immunoprecipitation reaction with the protein band. The serum samples from these subjects did not show similar bands. Therefore, we conclude that this protein band is a normally occurring protein that is unique to CSF.

Adult↗

Atypical nonketotic hyperglycinemia with normal cerebrospinal fluid to plasma glycine ratio.

The diagnosis of nonketotic hyperglycinemia is considered to depend upon the presence of increased cerebrospinal fluid glycine and an increased cerebrospinal fluid to plasma glycine ratio. We studied two siblings who have the neurologic and peripheral biochemical features of the atypical variant of nonketotic hyperglycinemia but have normal cerebrospinal fluid glycine and cerebrospinal fluid to plasma glycine ratios. The proband had reduced liver glycine cleavage system activity of 17% and 21% of mean normal values, confirmed in two independent laboratories. Her lymphoblast glycine cleavage system activity was normal. Nonketotic hyperglycinemia can be present in the absence of increased cerebrospinal fluid glycine. Measurement of liver glycine cleavage system activity is indicated when nonketotic hyperglycinemia is suggested by clinical features and peripheral glycine levels but cerebrospinal fluid glycine is normal.

Adolescent↗

Chicken arachnoid granulations: a new model for cerebrospinal fluid absorption in man.

Cerebrospinal fluid (CSF) absorption was investigated chicken and rat using infusion tests into the cisterna magna. Data were analysed according to a mathematical model by Johnson et al. Results in rat predicted a predominant lymphatic mechanism, which was confirmed by rapid outflow of X-ray contrast media into the olfactoric mucosa. In contrast, dynamics measurements suggested CSF drainage via arachnoid granulations in chicken. CSF spaces along the optic nerve were contrasted radiographically resulting in venous drainage. Electron microscopically, villus-like structures were found at the distal optic nerve connecting the subarachnoid space with accompanying veins, resembling human arachnoid granulations. We hypothesize that CSF absorption through arachnoid villi in microsmatic chicken reflects the situation in man very well.

Animals↗

Ceftriaxone diffusion into cerebrospinal fluid of children with meningitis.

We evaluated the diffusion of ceftriaxone into the cerebrospinal fluid of 27 infants and children with meningitis who were receiving conventional antimicrobic therapy. Ceftriaxone was administered as a single 75 mg/kg dose and was given early or late or both in the course of the illness. Three hours after a dose, the mean cerebrospinal fluid ceftriaxone level was 5.7 micrograms/ml in patients studied early in the course of meningitis and 2.1 micrograms/ml in patients studied later in the illness. Six hours after a dose, the mean cerebrospinal fluid ceftriaxone levels early and late in meningitis were 7.2 and 2.5 micrograms/ml, respectively. The diffusion did not correlate with the leukocyte count or the protein or glucose content of the cerebrospinal fluid. Serial, simultaneous cerebrospinal fluid and plasma ceftriaxone levels were also determined in three additional patients with ventriculo-peritoneal shunt infections and external ventriculostomy drainage. The cerebrospinal fluid ceftriaxone levels in these patients ranged from 0.7 to 8.3 micrograms/ml. Our data indicate that ceftriaxone diffuses sufficiently and consistently into the cerebrospinal fluid to warrant its assessment in the treatment of meningitis.

Adolescent↗

The drainage of cerebrospinal fluid in hydrocephalic rats.

Cerebrospinal fluid plateau pressures and transverse sinus plateau pressures were measured in response to a series of constant-rate infusions into the CSF in 10-day-old control and hydrocephalic H-Tx rats. In control rats the venous pressure increased with CSF pressure but to a lesser extent and around 60% of the total resistance to absorption was due to the concurrent rise in venous pressure with a hydrostatic gradient maintained between CSF and venous blood. In hydrocephalic rats the same infusion rates resulted in an increase in venous pressure which was the same magnitude as the rise in CSF pressure, resulting in zero hydrostatic gradient from CSF to blood. This suggests that CSF drainage does not take place by this route in hydrocephalic rats and that alternative drainage routes must be operating.

Animals↗