Dynamic properties of lymphatic pathways for the absorption of cerebrospinal fluid

Recent advances in small, linear-array transducers have opened new avenues for three-dimensional image acquisition from an intracardiac approach. The purpose of this study was to introduce a novel method of image acquisition using toroidal geometry, explore its fidelity of reproduction of three-dimensional cardiac anatomy, and determine whether a whole-heart scan is achievable. Acquisition was accomplished through 360-degree incremental rotation of a rigid endoscope with a side-mounted ultrasound transducer. The procedure was first tested with the use of a gelatin model to define far-field slice resolution with 1.8-degree rotational increments. Comparison of three-dimensional scans of cardiac specimens with corresponding photographs confirmed that toroidal geometry can provide a high-quality display of structures from all sides. We conclude that whole-heart three-dimensional scanning from within the cardiac chambers is possible with toroidal geometry. The quality of depicted anatomy depends on transducer location within the heart, distance from the transducer, density of slices, and image resolution. The potential of intracardiac three-dimensional ultrasound imaging includes detailed spatial evaluation of cardiac morphology, determination of appropriate placement of investigative or therapeutic devices (catheters, closure devices, etc.), and assessment of cardiac function.     

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.     

The usefulness of cerebrospinal fluid tests for neurosyphilis

To determine the usefulness of cerebrospinal fluid (CSF) tests for syphilis at a large academic hospital, clinical and laboratory data on 644 patients in whom such testing was requested over a 12-month period were analysed. In 198 cases (31%) the Treponema pallidum haemagglutination (TPHA) screening test could not be performed because of insufficient fluid. Thirty-eight of the remaining patients were diagnosed as having active neurosyphilis. Examination of 22 files of patients who had a positive TPHA and fluorescent treponemal antibody absorption (FTA-Abs) test together with a negative CSF Venereal Disease Research Laboratory (VDRL) test revealed that other CSF measures indicating disease activity (CSF protein, cells or IgG index) were not utilised optimally. In 10 (45%) of these patients neurosyphilis was not diagnosed despite either abnormal or incomplete CSF biochemical analysis, indicating that if the CSF VDRL is used as the sole marker for disease activity, some cases of neurosyphilis are likely to be missed.     

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.     

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.     

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.     

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.     

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.     

Sanguineous cerebrospinal fluid in recanalized cerebral infarction

To clarify the causal relationship between spontaneous recanalization of the occluded cerebral artery and development of hemorrhagic infarction, 15 patients with internal carotid or middle cerebral arterial axis occlusion were submitted to consecutive lumbar punctures and follow-up cerebral angiography. Consequently, six of seven recanalized patients had sanguineous cerebrospinal fluid (CSF) on the second or third day after ictus, while only one of eight non-recanalized patients had bloody CSF. It was strongly suggested that recanalization might have an initimate relationship with the development of hemorrhagic infarction.     

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.     

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.     

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.     

Effects of blood contamination on cerebrospinal fluid analysis

Data were obtained from 190 cerebrospinal fluid samples collected from both clinically normal and diseased dogs, cats, cows, and horses. Red blood cells, indicating blood contamination, were identified in 115 samples. White blood cells were a rare finding in normal animals. Blood contamination appeared to have little effect on white blood cell numbers even though, in several samples, thousands of red blood cells were identified. An accepted formula to correct for blood contamination was found to be an unreliable method to determine "uncontaminated" values for white blood cells, total protein, or creatine phosphokinase.