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.     

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     

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.     

Proinflammatory cytokine levels in cerebrospinal fluid from children with acute encephalitis]

Pediatric liver transplant recipients constitute a population characterized by a particularly unpredictable and poor bioavailability of cyclosporin (CyA). Even though several adult studies show that the new oral formulation of CyA, Neoral (NEO), produces better bioavailability and blood level predictability, few data describe its pharmacokinetics in children. We performed a complete analysis of the pharmacokinetics of NEO in ten small children after primary liver transplantation. Three pharmacokinetic profiles were set up with data obtained from tests taken during i.v. administration of CyA, after the first oral NEO dose, and after the last NEO dose before discharge from the hospital. The mean half-lives obtained were 8.1, 7.7, and 6.9 h, respectively, and the bioavailabilities were 22% and 21% for the first and last NEO doses. A large interpatient variability was observed. This was due, in part, to episodes of diarrhea that interfered with the pharmacokinetic evaluation and, in part, to the variability of post-transplant hepatic function. There was a good correlation between CyA trough levels and their related AUCs for both NEO profiles (r = 0.93 and r = 0.74, respectively). We conclude that, even though the pediatric OLT population remains more unpredictable than that of adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability.     

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.     

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.     

Disappearance of blood from cerebrospinal fluid following subarachnoidal hemorrhage (preliminary note)

On the basis of cerebrospinal fluid investigations in 17 patients with subarachnoideal haemorrhage admitted to the hospital in the time period from Nov. 1 1973 to March 15 1975 the authors observed that the blood disappears from the fluid usually 8 days after the onset and they suggest that control lumbar tap and angiography should be performed at that time for possible referral of patients for surgical treatment. From the 8th day on there is no need of administration of drugs increasing blood clotting.     

Diagnostic value of atypical lymphocytes in cerebrospinal fluid from adults with enteroviral meningitis

We have noted two morphologically distinct types of atypical lymphocytes (AL) in the cerebrospinal fluid (CSF) of adult patients with meningitis: one, which we designate type-I AL, with multilobulated nuclei resembling those of the abnormal cells in adult T-cell leukaemia (ATL); and another, type-II AL, characterized by large lymphocytes with basophilic cytoplasm and nuclei containing coarse chromatin. Type-I AL were detected in 25 of 39 patients (64%) with enteroviral and in 11 of 109 (11%) with aseptic meningitis presumed to be caused by other viruses, but not in meningitis resulting from Cryptococcus neofirmans (n = 14), Mycobacterium tuberculosis (n = 19) or acute bacterial infection (n = 49). Type-I AL were not seen in herpes zoster (n = 15) aseptic meningeal reactions (n = 15), or in leptomeningeal carcinomatosis (n = 14). Type-II AL were often present in meningitis of various aetiologies and in aseptic meningeal reactions, but not in leptomeningeal carcinomatosis. The presence of type-I AL in the CSF was found to be indicative of enteroviral meningitis with the highest predictive value (69%), while type-II AL had a lower diagnostic positive predictive value in meningitis of the five aetiologies above. Type-I AL immunostained for CD4, while type-II AL were stained for CD8. The presence of type-I AL in CSF strongly suggests enteroviral meningitis, which warrants careful follow-up without antifungal, antituberculous or antibacterial agents. However, type-I AL, which are likely to be virally transformed lymphocytes, must be distinguished from ATL cells, which frequently involve the meninges.     

病毒性脑炎患儿脑电图与脑脊液分析

目的:观察病毒性脑炎患儿脑电图与脑脊液分析.方法:选取我院5年来收治的病毒性脑炎患者180例,分为三组:健康组、观察组(白细胞数＞10×109/L)和对照组(白细胞数≤10×109/L)各60例,依次进行脑电图和脑脊液分析研究.结果:进行脑电图检查的患者中,脑电图异常率92%,脑脊液异常率49.8%,头颅CT异常率14.6%.进行脑脊液分析的患者中,健康组中脑脊液白细胞数正常或轻度改变者占67.5%.观察组中脑膜受累症状明显(58.9%)51/60,头痛的出现率为(89.9%)58/60,与前两组比较有显著性差异(P<0.05).结论:脑电图与脑脊液检查都对病毒性脑炎患儿都起着至关重要的作用.     

Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension

Spinal cerebrospinal fluid (CSF) leaks are often implicated as the cause of the syndrome of spontaneous intracranial hypotension, but they have rarely been demonstrated radiographically or surgically. The authors reviewed their experience with documented cases of spinal CSF leaks of spontaneous onset in 11 patients including their surgical observations in four of the patients. The mean age of the six women and five men included in the study was 38 years (range 22-51 years). All patients presented with a postural headache; however, most had additional symptoms, including nausea, emesis, sixth cranial-nerve paresis, or local back pain at the level of the CSF leak. All patients underwent indium-111 radionucleotide cisternography or computerized tomographic (CT) myelography. The location of the spontaneous CSF leak was in the cervical spine in two patients, the cervicothoracic junction in three patients, the thoracic spine in five patients, and the lumbar spine in one patient. The false negative rate for radionucleotide cisternography was high (30%). Subdural fluid collections, meningeal enhancement, and downward displacement of the cerebellum, resembling a Chiari I malformation, were commonly found on cranial imaging studies. In most patients, the symptoms resolved in response to supportive measures or an epidural blood patch. Leaking meningeal diverticula were found to be the cause of the CSF leak in four patients who underwent surgery. In three patients these diverticula could be ligated with good result but in one patient an extensive complex of meningeal diverticula was found to be inoperable. Two patients had an unusual body habitus and joint hypermobility, and two other patients had suffered a spontaneous retinal detachment at a young age. In conclusion, spontaneous spinal CSF leaks are uncommon, but they are increasingly recognized as a cause of spontaneous intracranial hypotension. Most spinal CSF leaks are located at the cervicothoracic junction or in the thoracic spine, and they may be associated with meningeal diverticula. The radiographic study of choice is CT myelography. The disease is usually self-limiting, but in selected cases our experience with surgical ligation of leaking meningeal diverticula has been satisfactory. An underlying connective tissue disorder may be present in some patients with a spontaneous spinal CSF leak.