Diagnostic value of determining hemoglobin in cerebrospinal fluid in acute cerebral circulatory disorders

The results of hemoglobin determination in the CSF by the method of fluorescence microscopy in 195 patients speaks in favor of relative diagnostical importance of hemoglobin in the supra fall-out CSF for establishing the character of the stroke. The following circumstances testify to this fact: 1) in an artificial admixture of blood in the CSF in some cases there may be hemolysis of "passing" erythrocytes; 2) in a genuine admixture of blood, tests of hemoglobin in the centrifugate of the CSF may be negative since in some cases the transition of hemoglobin into bilirubin in the subarachmoid space occurs more rapidly than the hemolysis of erythrocytes. Thus, the hemoglobin does not accumulate in the liquid in quantities, sufficient enough to be measured by the existing methods; 3) in a large amount of artificial blood admixture, even without a hemolysis of "passing" erythrocytes the hemoglobin tests in the centrifugate of the CSF may be positive at the expense of hemoglobin of the blood plasma.     

Regional cerebral blood flow and cerebrospinal fluid amino acid analysis in elderly dementia

Regional cerebral blood flow and amino acid concentration in the cerebrospinal fluid were studied in 12 cases of vascular dementia, 12 cases of Alzheimer's disease, 12 cases of chronic alcoholism, and 12 age-matched healthy controls. In vascular dementia, blood flows were decreased in the cerebral cortex, frontal white matter, thalamus, caudate nucleus, and putamen and alpha-aminobutyric acid and glutamic acid concentrations were increased in the cerebrospinal fluid. In Alzheimer's disease, blood flows were decreased in the frontal cortex, parietal cortex, temporal cortex, and frontal white matter and alanine concentration was increased in the cerebrospinal fluid. In chronic alcoholism, blood flows were decreased in the cerebral cortex, thalamus, and putamen and urea, alanine, and glycine concentrations were increased in the cerebrospinal fluid.     

Lumbar cerebrospinal fluid drainage for prevention of cerebrospinal fluid fistulas

Leakage of cerebrospinal fluid may complicate surgical procedures of the temporal bone and skull base. This presentation details experience utilizing 7 days lumbar drainage in an attempt to prevent the occurrence of a postoperative CSF fistula. Thirty-nine patients underwent surgery for various intracranial pathologies and were felt to be at high risk for the development of postoperative CSF fistulae. None of the patients was given prophylactic antibiotics. Ten patients developed clinical and laboratory findings consistent with early meningitis and were treated with appropriate antibiotics. Three patients eventually developed a CSF fistula, with two resolving spontaneously and the third requiring a second surgical procedure to repair the dura (again using lumbar drainage postoperatively). Our conclusions suggest that prophylactic placement of a lumbar catheter in high risk patients increases the likelihood of successful dural closure with an acceptable morbidity. Is these patients routine antibiotic coverage is not indicated.     

Antibiotic pharmacodynamics in cerebrospinal fluid

The CSF half-lives of lipophilic agents, such as quinolones, are similar to those in serum and peak concentrations in CSF are achieved relatively quickly. In contrast, the pharmacokinetics of hydrophilic agents (beta-lactams and vancomycin) in CSF often differ from those in serum. In particular, the half-lives of these agents in CSF tend to be extended, and the time to achieve peak concentrations in CSF is delayed. Hydrophilic antibiotics, such as beta-lactams, penetrate poorly through the BBB, but CSF penetration is significantly increased in the presence of inflammation. In contrast, lipophilic antibiotics, such as quinolones, enter the CSF more efficiently and their penetration is not inflammation dependent. The pharmacodynamic properties of antibiotics in CSF are generally similar to those in other body sites; beta-lactam agents and vancomycin are time-dependent, whereas the quinolones and aminoglycosides are concentration-dependent. However, a notable difference from infections in other sites is that quinolones have a short PAE in CSF and need to continually exceed the MBC for maximal effectiveness. Thus, in CSF, quinolones demonstrate features of both concentration-dependency and time-dependency, evidence that the AUC/MBC is an important predictor of effectiveness. With the exception of quinolones, many antibiotics appear to have prolonged sub-MIC effects and longer half-lives in CSF than in serum, suggesting that dosing intervals longer than those used traditionally would be effective in meningitis. However, this requires clinical verification.     

Hyaluronan in human cerebrospinal fluid

We studied the concentration of hyaluronan in cerebrospinal fluid (CSF) in various diseases and attempted to define its reference interval. A radioassay utilizing cartilage proteins with affinity for hyaluronan was used in determining the concentration of 200 lumbar and 27 ventricular CSF specimens and 11 brain cyst fluids. Molecular weight distributions were determined by gel chromatography and localization in brain tissue by histochemistry. The hyaluronan level of lumbar CSF showed an increase with age; comparatively healthy children had (mean +/- SD) 50 +/- 41 micrograms/L (n = 40) and adults 166 +/- 77 micrograms/L (n = 9); i.e. significantly different values. The highest level was recorded in a patient with meningitis (> 8000 micrograms/L). More than 4000 micrograms/ L was noted in a patient with tumour metastasis in the cerebellum. Significantly elevated levels were especially found with spinal stenosis, head injury and cerebral infarction, but also in inflammatory medical disorders, hydrocephalus and encephalitis. We found no significant increase in multiple sclerosis and some other neurological diseases. Ventricular CSF of adults contained significantly less hyaluronan (53 +/- 73 micrograms/L; n = 16) than lumbar CSF. Hyaluronan in cyst fluids varied from 31 to 25,000 micrograms/L. Weight average molecular weight of hyaluronan in CSF was 2.9-3.0 x 10(5) and in brain tumour cyst fluid 2.4 x 10(6). In search for the origin of hyaluronan in CSF it was found that its concentration in the choroid plexus and leptomeninges was low, but that hyaluronan was accumulated in the superficial layer of the cerebral cortex. Continued screening for hyaluronan in CSF may be valuable in cases of inflammatory diseases, tumours and obstruction to CSF flow.     

Assay of gentamicin in cerebrospinal fluid

A comparison of standard curves obtained from a conventional plate diffusion assay method revealed significant differences when gentamicin standards were made up in different media. Standards made up in distilled water resulted in a curve which differed from that of standards made up in pooled human cerebrospinal fluid by a factor of up to 4. When the assay medium was supplemented with 0-5% sodium chloride, the difference between the two standard curves was reduced to a factor of about 1-5. The curve obtained from standards made up in 150 mM sodium chloride/4-5 mM calcium chloride correlated well with that from standards made up in cerebrospinal fluid. There was no evidence of gentamicin being bound to protein in the cerebrospinal fluid.     

Gram-negative cerebrospinal fluid shunt-associated infections

Twenty hydrocephalic children with cerebrospinal fluid (CSF) shunts over an 11-year period were seen with Gram-negative central nervous system (CNS) infections. Seventeen infections were with single organisms and three were mixed. Sixteen of 20 (80%) of the infections occurred within five months of shunt surgery. Complete shunt removal or replacement in a new site plus systemic and intraventricular antibiotics resulted in a 100% (9/9) cure rate. Systemic and intraventricular antibiotics alone or in combination with incomplete shunt removal generally were unsuccessful. Significant morbidity and mortality were associated with these infections. Of the 18 patients with follow-up data, seven (39%) died with the infection, four (22%) sustained definite CNS damage, three (17%) were retarded after infection but their preinfection status was unknown, and only four (22%) patients escaped without definite sequela. Early recognition and appropriate therapy, hopefully, will improve the current bleak prognosis     

Penicillin transport from cerebrospinal fluid

The passage of penicillin G from cerebrospinal fluid (CSF) was studied by continuous ventriculocisternal perfusion in conscious rabbits. The concentration of penicillin G in the perfusate, collected from the cisterna magna, was 76.5 percent +/- 1.0 (SEM) of that entering the ventricles (having adjusted for normal secretion of CSF). The mean concentration of penicillin G rose 15 percent (p less than 0.005) in the cisternal CSF after probenecid (2 mg per milliliter) was added to the perfusion fluid. We conclude that an active transport system removes penicillin G from the CSF; this mechanism can be inhibited by intraventricular probenecid. Our results are in accord with observations deriving from studies on anesthetized animals given probenecid intravenously or intraperitoneally.     

Neurosyphilis and penicillin levels in cerebrospinal fluid

Because neurosyphilis may progress despite therapy with the recommended penicillin regimens, 15 subjects with positive tests for syphilis in the serum and cerebrospinal fluid (CSF) were studied. All of these patients had CSF pleocytosis. Two received penicillin G (5 and 10 million units per day intravenously, respectively) and 13 received benzathine penicillin G, 3.6 million units per week intramuscularly; treatment lasted four weeks. During intravenous and after intramuscular penicillin therapy, a spinal tap was performed on all subjects; later, assays were done. Of two patients who received intravenous penicillin G, one had 0.3 mug/ml and the other had 2.4 mug/ml penicillin in the CSF. Twelve of 13 patients who received benzathine penicillin G had no detectable penicillin in the CSF; one patient had 0.1 mug/ml penicillin in the CSF.     

Neurotransmitters in cerebrospinal fluid reflect pathological activity

Reduced bone mineral density (BMD), termed diabetic osteopenia, has been reported in patients with insulin-dependent (Type 1) diabetes mellitus (IDDM). To examine BMD in long-term IDDM patients with normal kidney function, but with different degrees of urinary albumin excretion rate (UAER), compared to that of patients with elevated plasma creatinine, 36 IDDM male patients (mean duration 27 years) were subdivided according to UAER (<30, 30-300, >300, >300 mg 24 h(-1) and plasma creatinine 0.120-0.350 mmol l(-1)) and 15 controls were recruited. BMD was measured by dual energy X-ray absorptiometry and UAER by enzyme linked immunosorbent assay. BMD was normal in IDDM patients with normal UAER and reduced in the femoral neck, the trochanter major, and the Wards triangle in patients with increased UAER (p < 0.01, p < 0.05, p < 0.02). BMD correlated to creatinine clearance in both cortical and cancellous bone sites (p < 0.001, p < 0.0001), and inversely to the levels of plasma PTH (p < 0.0005). We conclude that BMD is normal in long-term IDDM male patients with normal kidney function and normal UAER and reduced in patients with increased UAER. Diabetic osteopenia seems to be a progressive phenomenon related to diabetic nephropathy and associated with the decrease in creatinine clearance and with the resulting rise in plasma PTH.     

Cytokine response in cerebrospinal fluid after birth asphyxia

Experimental studies suggest that cytokine-mediated inflammatory reactions are important in the cascade leading to hypoxic-ischemic brain injury. The purpose was to study the content of pro- and antiinflammatory cytokines in cerebrospinal fluid (CSF) of asphyxiated and control infants. Samples of CSF were obtained from 20 infants who fulfilled the criteria of birth asphyxia and from seven newborn control subjects. The concentrations of IL-1beta, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, and granulocyte/monocyte colony-stimulating factor (GM-CSF) were determined with ELISA and of IL-6 using a bioassay. The concentration of IL-6 (pg/mL) was higher in asphyxiated (250, 35-543; median, interquartile range) than in control (0, 0-18) infants (p = 0.001). There was also a significant relationship between IL-6 and the degree of HIE, and between IL-6 and outcome. In addition, the content of IL-8 (pg/mL) was higher (p = 0.009) in the asphyxia group (170, 70-1440), than in the the control group (10, 0-30) and there was an association between IL-8 and degree of HIE. The levels of IL-10, TNF-alpha, GM-CSF, and IL-1beta did not differ between groups. In conclusion, the proinflammatory cytokines IL-6 and IL-8 were markedly elevated in CSF of asphyxiated infants, and the intrathecal levels of these cytokines corresponded to the degree of HIE.     

MR and cerebrospinal fluid enzymes as sensitive indicators of subclinical cerebral injury after open-heart valve replacement surgery

PURPOSE: To evaluate MR imaging and lumbar cerebrospinal fluid enzymes as potential sensitive indicators of cerebral injury after open-heart valve replacement surgery. METHODS: Thirty-four patients with cardiac valvular disease were prospectively entered into this study and then underwent valve replacement or repair under cardiopulmonary bypass using a membrane oxygenator. In 26 patients, MR head images were obtained 12 to 24 hours before surgery; repeat MR images were obtained between 1 and 2 weeks after surgery. In 18 patients, lumbar puncture cerebrospinal fluid was analyzed 24 to 48 hours after surgery; the analyses included measurement of lactic dehydrogenase, creatine phosphokinase, adenylate kinase, and neuron-specific enolase. RESULTS: After surgery, MR imaging showed new ischemic lesions in 15 (58%) of 26 patients: 7 with deep white matter hyperintense lesions; 5 with brain stem, caudate, cerebellar, or thalamic/basal ganglia infarcts; 1 with intraparenchymal hemorrhage; 1 with a subdural hematoma and cortical infarct; and 1 with a corpus callosum lesion consistent with calcium or air. These new ischemic lesions seen on MR images were associated with a focal neurologic deficit in only 4 (27%) of the 15 patients. Neuron-specific enolase and lactic dehydrogenase were abnormally elevated after surgery in 5 (28%) of 18 patients. Adenylate kinase and creatine phosphokinase (brain isozymes) were elevated in one (67%) of the patients. Two (40%) of the five patients with abnormally high neuron-specific enolase or lactic dehydrogenase after surgery also showed a new focal neurologic deficit. CONCLUSIONS: MR imaging is a sensitive measure of subclinical cerebral ischemia after cardiac valve replacement under cardiopulmonary bypass. Cerebrospinal fluid neuron-specific enolase and lactic dehydrogenase are less sensitive than MR imaging for detecting subclinical cerebral ischemia, but these values were elevated after surgery more frequently than was adenylate kinase in our patients.     

Ion concentration in the cerebrospinal fluid in multiple sclerosis

The concentrations of electrolytes Na, K, Ca, Mg, and Cl and trace elements Cu and Zn were determined in the lumbar cerebrospinal fluids of forty patients with multiple sclerosis. Metal ion concentrations were measured using atomic absorption spectroscopy and flame photometry, respectively. Compared with corresponding values obtained from a control group, statistically significant increases in concentration of Na, Cl, Ca, and Zn have been found. Also reported are the results of determinations of ion concentrations in cerebrospinal fluids obtained from patients suffering from diseases other than multiple sclerosis. Possible causes of deviations from the norm are discussed.     

Cultured leptomeningeal cells secrete cerebrospinal fluid proteins

To extrapolate the function of the leptomeninges, we examined the profile of the proteins secreted from the cultured leptomeningeal cells prepared from 1-2-day-old rats. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the medium conditioned with the cultured cells, 20-25 differentially distinctive protein bands were noted. Through several chromatographic procedures (Sephadex G-75, Mono Q, and 7C8-300), altogether 18 proteins were purified to homogeneity, and the partial amino acid sequence of each protein was determined. Homology search revealed that the major proteins included prostaglandin-D-synthase or beta-trace protein, insulin-like growth factor (IGF)-II, IGF-binding protein-2, apolipoprotein E, beta 2-microglobulin, cystatin C, transferrin, peptidyl-prolyl cis-trans isomerase or cyclophilin C, secreted protein acidic and rich in cysteine, ubiquitin, lysozyme C, extracellular superoxide dismutase, and collagen alpha-1 (III). Most of these proteins are known to be the major brain-derived protein constituents of CSF and are thought to play important roles in certain biological events in the brain. Considering the morphological features, the present findings suggest the importance of the leptomeninges as an origin of such proteins in CSF.     

Recurrent meningitis and spontaneous cerebrospinal fluid otorrhea

Five children with recurrent meningitis were surgically confirmed to have vestibular fistula and spontaneous cerebrospinal fluid (CSF) otorrhea. The vestibular fistulas were successfully repaired under general anaesthesia. No complications were found after follow-up for 3-8 years. The etiology of CSF otorhinorrhea, location of fistulas, diagnosis and treatment of spontaneous vestibular CSF otorrhea were discussed.     

Analysis of ceftriaxone and ceftazidime distribution in cerebrospinal fluid of and cerebral extracellular space in awake rats by in vivo microdialysis

In vivo microdialysis was used to estimate the extracellular concentrations of ceftazidime and ceftriaxone, two expanded-spectrum cephalosporins commonly used in the treatment of bacterial meningitis, in two brain regions (the right corpus striatum and the left lateral ventricle_ of awake, freely moving rats. Antibiotics were administered by constant intravenous infusion at 18 mg/h until steady-state levels were reached. Ceftriaxone levels measured at the steady state in the extracellular space of the corpus striatum (0.80 +/- 0.17 micrograms/ml) were statistically equivalent to those obtained in the cerebrospinal fluid of the lateral ventricle (0.71 +/- 0.15 micrograms/ml). The ratios of these levels in the brain to the steady-state levels in plasma were 0.5 +/- 0.1% for both regions. The postinfusion concentrations of ceftriaxone in the brain declined monoexponentially, with an elimination half-life similar to that obtained in plasma. However, the mean antibiotic concentration of ceftazidime in the striatum (2.2 +/- 0.4 micrograms/ml) was lower (P < 0.001) than that in the lateral ventricle (3.8 +/- 0.5% and 4.0 +/- 1.8%, respectively) were higher than those obtained with ceftriaxone. Moreover, the half-life of ceftazidime elimination from plasma was lower than that obtained in the two brain regions. It was concluded that the in vivo microdialysis technique yields useful data on antibiotic distribution in the extracellular space of the brain, that the distribution may not be homogeneous, and that the decay of postinfusion concentrations in the brain may be different from the decay of postinfusion concentrations in plasma.     

Prolactin in human and rat serum and cerebrospinal fluid

Rats treated with haloperidol or bearing subcutaneous implants of prolactin-secreting tumors had elevated CSF prolactin levels compared to those observed in control rats. These levels were commensurate with the increased serum level of prolactin, although there appeared to be an upper limit to the CSF prolactin concentration. Patients with prolactin-secreting pituitary adenomas had elevated CSF hormone levels as compared to patients with non-endocrine neurologic disease. This obtained, regardless of whether the tumor was intra- or extrasellar in its growth. The implications for the route of entry of prolactin into CSF under both normal and abnormal conditions, and the potential role for CSF prolactin as part of a feedback regulatory system on pituitary prolactin release are discussed.