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Cerebrospinal fluid shunts.

Cerebrospinal fluid (CSF) shunt technology has undergone rapid advances in the past two decades. As a result, pediatricians and other primary care physicians are being asked with increasing frequency to provide care for persons with CSF shunts. Familiarity with the more common shunts is a prerequisite to intelligent management of shunt related problems. Physicians providing daily care must have carefully documented hospital records and operative notes available to them as well as information detailing the safe evaluation of shunt patency and function if they are to manage patients with CSF shunts properly. In addition, parents and guardians must be alerted to signs and symptoms related to shunt malfunction.

Cerebrospinal Fluid Shunts↗

[Detecting infectious agents in central nervous system inflammation by cerebrospinal fluid analysis].

Cerebrospinal fluid analysis is the method of choice in CNS infection and provides the basis for appropriate treatment. Due to the proximity of CSF and CNS, the infectious agent may be detected directly by microscopy or antigen or nucleic acid detection--the latter by polymerase chain reaction--in native CSF or after culture. Furthermore, intrathecal antibody synthesis against the infectious agent may identify the cause of infection. This indirect antigen detection method requires correction for a systemic antibody response and a blood-CSF barrier disturbance. The following text gives an overview of appropriate detection methods and their relevance to the most important CNS infections.

AIDS Dementia Complex↗

Successful treatment of a patient with a 13-year history of post-traumatic rhinorrhea due to malabsorption of cerebrospinal fluid.

Chronic cerebrospinal fluid (CSF) leaks associated with skull base fractures are rare but intractable and patients may be subjected to numerous operations. We present a 30-year-old man with a 13-year history of chronic CSF rhinorrhea following a cranial trauma. Computed tomography (CT) showed a bone defect in the planum sphenoidale. CT cisternography revealed a leak from the defect and CSF malabsorption. The absence of symptoms of CSF malabsorption may be attributable to external leakage of excess CSF. After closing the leak via the extended transsphenoidal approach we placed a ventriculoperitoneal shunt for occult hydrocephalus. We discuss the clinical symptoms of chronic CSF leakage and present therapeutic strategies dictated by the mechanisms underlying the leak.

Adult↗

Endonasal endoscopic repair of cerebrospinal fluid rhinorrhea.

Cerebrospinal fluid (CSF) rhinorrhea implies a communication between the subarachnoid space and the upper respiratory tract. Trauma and postoperative defects are the more common causes of CSF rhinorrhea. The authors review their results with endoscopic repair of skull base defects associated with CSF rhinorrhea involving the paranasal sinuses. A total of 10 patients, 7 males and 3 females, were treated under endoscopic vision from 1997 to 2001. The causes of CSF rhinorrhea were traumatic (7), postoperative (2) and spontaneous (1). Four patients had the diagnosis and the site confirmed after intrathecal fluorescein-saline injection. The obliteration of the CSF leak was achieved with fat free, mucoperichondrial, or mucoperiostal free grafts taken from the middle or inferior turbinate and kept in place by fibrin glue. Primary closure was obtained in 10 patients and one patient developed a recurrence 14 months later. The repair of the CSF rhinorrhea by endonasal endoscopic surgery is safe, very effective and is a valid alternative to the cranial approach.

Adolescent↗

Computed tomography and cerebrospinal fluid leak.

Cerebrospinal fluid (CSF) rhinorrhea is a serious condition which if untreated may lead to meningitis. Detection of the leak site at surgery may be difficult without prior accurate radiological localization of the leak and at times repeat operation has been required. Clinical and radiological localization of the leak is not always easy and many different tests have been tried. Prior to computed tomography (CT), the most common combination of radiological tests were plain films and tomograms of the skull and CSF isotope studies. Although CT scanning may be helpful in assessing a patient with CSF rhinorrhea, it is most effective when combined with intrathecal Metrizamide. The combination of Metrizamide and CT was first reported in 1977 and several case reports and small series of cases have since been reported. The purpose of this article is to review the value of CT especially when used in combination with Metrizamide in the patient with CSF leak and also to discuss the technique of the combined study and to show its value with illustrative cases.

Adult↗

Isoelectric focusing followed by silver staining. A suitable method for routine investigation of cerebrospinal fluid proteins.

Cerebrospinal fluid (CSF) and serum samples from 361 consecutive patients were investigated. The protein pattern of each sample was examined by isoelectric focusing (IEF) of unconcentrated CSF followed by silver staining and by agar gel electrophoresis of concentrated CSF stained with amido black. 347 paired samples were compared. The results were the same in 83% of the samples. Discordant results were found in 10% of the samples. and in 7% additional information was achieved by one of the methods. IEF was superior to agar gel electrophoresis for the identification of oligoclonal immune reactions of the central nervous system. Tau globulin increase was seen in a few CSF samples, more often with IEF and then associated with other changes of the pattern. IEF of unconcentrated CSF followed by silver staining only requires 20 microliters CSF, while 3-4 ml CSF is needed for the agar gel electrophoretic method. It was concluded that IEF has several advantages compared to agar gel electrophoresis and is suitable as a routine method in clinical laboratories.

Adolescent↗

Biofilm-related infections of cerebrospinal fluid shunts.

Cerebrospinal fluid (CSF) shunts carry a high risk of complications. Infections represent a major cause of shunt failure. Diagnosis and therapy of such infections are complicated by the formation of bacterial biofilms attached to shunt surfaces. This study correlated the pathophysiology and clinical course of biofilm infections with microscopical findings on the respective shunts. Surface irregularities, an important risk-factor for shunt colonisation with bacteria, were found to increase over time because of silicone degradation. Scanning electron-microscopy (SEM) documented residual biological material (dead biofilm), which can further promote extant bacterial adhesion, on newly manufactured shunts. Clinical course and SEM both documented bacterial dissemination against CSF flow and the monodirectional valve. In all cases, biofilms grew on both the inner and outer surfaces of the shunts. Microscopy and conventional culture detected all bacterial shunt infections. Analyses of 16S rDNA sequences using conserved primers identified bacteria in only one of three cases, probably because of previous formalin fixation of the samples.

Adolescent↗

Cerebrospinal fluid concentrations of S-adenosylmethionine, methionine, and 5-methyltetrahydrofolate in a reference population: cerebrospinal fluid S-adenosylmethionine declines with age in humans.

Cerebrospinal fluid concentrations of S-adenosylmethionine, methionine, and 5-methyltetrahydrofolate were measured in 80 children and young adults in whom there was no disturbance of the methyl transfer pathway. Cerebrospinal fluid was collected under standardized conditions and analyzed by high-performance liquid chromatography. S-Adenosylmethionine, but not methionine nor 5-methyltetrahydrofolate, concentrations declined sharply during the first year of life. There was no correlation between concentrations of S-adenosylmethionine and methionine or 5-methyltetrahydrofolate. Reference ranges for the three metabolites are given.

Adolescent↗

Human cerebrospinal fluid peptidomics.

Cerebrospinal fluid (CSF) has frequently been extensively studied to explore several different central nervous system (CNS) disorders because it contains proteins, enzymes, hormones, neuropeptides and neurotransmitters that play critical regulatory roles in many different physiological processes. Individual neuropeptidergic systems in CSF have been studied. In theory, peptidomics offers a bird's-eye, comprehensive and systems-level approach to analyze all of the peptidergic systems that have been expressed in CSF at any given time. In this study, low molecular mass (M(r) < 5 kDa) peptides were isolated by ultrafiltration. The isolated peptides, with or without trypsin digestion, were preferentially enriched with a solid-phase extraction cartridge, and the peptides were separated with capillary liquid chromatography and analyzed with on-line quadrupole time-of-flight mass spectrometry (MS). In this proof-of-principle study, the 20 representative MS-characterized peptides were shown to be derived from 12 proteins, among which four proteins, amyloid-like protein 1, secretogranin I, granin-like neuroendocrine peptide precursor and neurosecretory protein VGF, have been shown elsewhere to be either associated with CNS disorders or to play a central role in the CNS. The long-term goals of this peptidomics study are to monitor the changes (amount; modifications) of CSF peptides, clarify the aberrant processing of large intact protein precursors, elucidate the molecular mechanisms of CNS disorders and find biomarkers. This analytical method is effective for the analysis of the human lumbar CSF peptidome.

Adult↗

Characteristics of an inhibitor of the Na+/K+ pump in human cerebrospinal fluid.

Human cerebrospinal fluid (CSF) inhibits the Na+/K+ pump in human red cells and the activity of purified Na+/K+-ATPase (Halperin, J. A., Shaeffer, R., Galvez, L., and Malavé, S. (1985) Proc. Natl. Acad. Sci. U.S. A. 80, 6102-6104, 1983; Halperin, J. A., Martin, A. M., and Malavé, S. (1985) Life Sci. 37, 561-566. We describe here some properties of the CSF inhibitor of the Na+/K+ pump. Active material was extracted from human CSF with 50% methanol and then concentrated and desalted by ultrafiltration. This extract inhibited, in a dose-dependent manner, the ouabain-sensitive influx of K+ into human red cells and the activity of purified Na+/K+-ATPase. Partial separation of the inhibitory activity was achieved by gel filtration and reverse-phase high performance liquid chromatography. Inhibition of both pump and enzyme was specific in that other red cell membrane transport systems or enzymes examined were not influenced by CSF extracts. Dialysis and ultrafiltration experiments indicate that the molecular weight of the inhibitor is approximately equal to 600. The inhibitory activity is sensitive to proteolytic enzymes indicating that the inhibitor might be a small peptide. In the presence of CSF extract the K0.5 for external K+ to stimulate the Na+/K+ pump increased from 1.4 to 3.1 mM, suggesting that the CSF inhibitor competes with external K+ for stimulation of the pump. We estimate that the concentration of the inhibitor in CSF might be approximately equal to 50 pg/ml, a value close to the concentration of other active peptides found in human CSF.

Cerebrospinal Fluid Proteins↗

Steroid hormones and steroid hormone binding globulins in cerebrospinal fluid studied in individuals with intact and with disturbed blood-cerebrospinal fluid barrier.

We measured in simultaneously withdrawn cerebrospinal fluid (CSF) and serum samples from 56 endocrinologically grossly normal patients the concentrations of several lipophilic unconjugated steroids [i.e. dehydroepiandrosterone (DHEA), androstenedione, cortisol, progesterone, testosterone] and their hydrophilic counterparts, i.e. DHEA-sulfate, or hydrophilic binding proteins, i.e. albumin, sex hormone-binding globulin (SHBG) and corticosterone-binding globulin (CBG). CSF levels of total (i.e. free plus protein-bound) DHEA, androstenedione, cortisol, progesterone, and testosterone were found to be in the 0.02-2 nM range and only cortisol reached levels approximately 20 nM. These values were of the same order of magnitude as the reported and calculated free serum levels of these steroids. In patients with disturbed (abnormally leaky) blood-CSF barrier (BCB) function, CSF levels of these steroids were not different from those with intact BCB, in contrast to DHEA-sulfate, CBG and SHBG whose CSF levels were significantly elevated, that is similar (i.e. 2-5) fold as those of albumin. In vitro demonstrated low affinity (micromolar) interactions of steroids with neuronal membrane-bound neurotransmitter receptors should be considered in perspective to the here reported finding that steroids occur in vivo at best in nanomolar concentrations in the CSF. Whether in other extracellular fluid compartments of the brain higher levels of steroids than in CSF can accumulate is as yet not clear. Very probably, pathological production or excessive dosage of steroids that are negligibly bound to SHBG or CBG will produce CSF and brain levels in the near micromolar range.

Blood-Brain Barrier↗

Cerebrospinal fluid hydromechanics in adult patients with benign noncommunicating hydrocephalus: one-hour test shunting and balanced cerebrospinal fluid infusion test to select patients for intracranial bypass operation.

Cerebrospinal fluid (CSF) pressure and absorption were determined in 12 patients with benign noncommunicating hydrocephalus. An extracorporeal communication of plastic tubing between the ventricular system and the lumbar subarachnoid space was established to imitate the hydromechanical condition after an intracranial bypass operation. This extracorporeal shunt, which in effect was an externalized Torkildsen shunt, served first as a test shunt for 1 hour and then as a route for the constant rate CSF infusion test. The total CSF absorptive capacity was thus determined under a condition of balanced CSF pressure between the proximal and distal compartment. Four patients, whose tests showed normal CSF pressure and absorption, were selected for intracranial bypass operation. Follow-up examination showed a normal clinical condition, reduction of the ventricular system, normal CSF pressure, and normal CSF absorption in all 4 patients. The other 8 patients, whose tests indicated impaired CSF absorption, were treated by ventriculoatrial shunting. The tests were valid in selecting patients for intracranial bypass operation.

Adolescent↗

Studies on homocarnosine in cerebrospinal fluid in infancy and childhood. Part II. Homocarnosine levels in cerebrospinal fluid from children with epilepsy, febrile convulsion or meningitis.

To clarify the pathophysiological role of homocarnosine in the cerebrospinal fluid (CSF) in children, homocarnosine levels in CSF were determined in patients with epilepsy (32 cases), febrile convulsion (5 cases) and meningitis (42 cases) with a high speed amino acid autoanalyzer (Hitachi Co.). Mean homocarnosine levels in CSF of controlled epileptic children, uncontrolled epileptic children and febrile convulsion cases were 0.61 +/- 0.25 mumol/dl, 1.03 +/- 0.37 mumol/dl and 1.09 +/- 0.04 mumol/dl, respectively. High homocarnosine levels in CSF of children with uncontrolled epilepsy or febrile convulsion may indicate the reduced turnover rate from homocarnosine to GABA. In patients with meningitis, the unconscious states were accompanied by significantly lower homocarnosine levels in CSF (0.39 +/- 0.20 mumol/dl) than those in the patients with clear conscious states (0.9 +/- 0.31 mumol/dl, however, in patients with clear conscious states homocarnosine in CSF were almost the same as those of normal children (0.89 +/- 0.23 mumol/dl). These data suggest that homocarnosine in CSF might be related to the convulsive tendency and consciousness.

Adolescent↗

Suppression of cerebrospinal fluid (CSF) production by a Na+/K+ pump inhibitor extracted from human cerebrospinal fluid.

A low molecular weight compound (about 600 daltons) extracted from human cerebrospinal fluid, and sensitive to proteolytic enzymes, has been shown to mimic the specific inhibitory effects of cardiac glycosides on the Na+/K+ pump of erythrocytes. The compound, which was labelled CSF-inhibitor (CSF-I) and reconstituted in artificial rabbit CSF, was used to study its effects on the rate of CSF formation in rabbits. Three groups of adult New Zealand white rabbits of either sex, anesthetized with ketamine and xylazine, and artificially respired were subjected to ventriculocisternal perfusions. Baseline rates of CSF formation were obtained during the first 2 hours of perfusion when plain rabbit CSF was used as the perfusate. Thereafter, the animals were perfused for an additional 2 to 3 hours with either plain rabbits CSF (controls), rabbit CSF containing 10(-6) M ouabain (group 2) or CSF-I (group 3). The rate of CSF formation in control animals was observed to gradually decline with time (about 7.5% in 4 hours). The addition of ouabain to the perfusate caused an abrupt and marked 43% decline in the rate of formation while the addition of CSF-I resulted in a 57% decline. These results suggest that the peptide CSF-I which is present in human CSF may act as an endogenous regulator of CSF production.

Animals↗