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Lipoprotein(a) in the cerebrospinal fluid of neurological patients with blood-cerebrospinal fluid barrier dysfunction.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a recognized pathogenic particle in human plasma, but its presence in the cerebrospinal fluid and its possible role in the central nervous system have not been documented. We tested the hypothesis that apolipoprotein(a) [apo(a)], free or as a component of the Lp(a) particle, can cross the blood-cerebrospinal fluid barrier and be found in the cerebrospinal fluid of patients affected by neurologic pathologies. METHODS: We studied paired cerebrospinal fluid/serum samples from 77 patients with inflammatory (n=20) or noninflammatory (n=34) blood-cerebrospinal fluid barrier dysfunction and without blood-cerebrospinal fluid barrier dysfunction (n=23). We used ELISA to measure Lp(a) concentrations and Western blot and immunodetection to analyze apo(a) isoforms in native and reducing conditions. RESULTS: Entire Lp(a) with either small or large apo(a) isoforms was present in the cerebrospinal fluid of patients with blood-cerebrospinal fluid barrier dysfunction, regardless of its pathogenesis. Multiple linear regression analysis showed that both serum Lp(a) concentration (P=0.003) and cerebrospinal fluid/serum albumin ratio (P<0.001) were predictors of the Lp(a) concentration in cerebrospinal fluid. CONCLUSIONS: Our results demonstrate that Lp(a) can cross a dysfunctional blood-cerebrospinal fluid barrier. The unusual presence of Lp(a) in the cerebrospinal fluid could extend some of its known pathogenic effects to the central nervous system.

Adolescent↗

Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters?

BACKGROUND: Meningitis is a substantial cause of morbidity and mortality in neonates. Clinicians frequently use the presence of positive blood cultures to determine whether neonates should undergo lumbar puncture. Abnormal cerebrospinal fluid (CSF) parameters are often used to predict neonatal meningitis and determine length and type of antibiotic therapy in neonates with a positive blood culture and negative CSF culture. METHODS: We evaluated the first lumbar puncture of 9111 neonates at > or =34 weeks' estimated gestational age from 150 NICUs, managed by the Pediatrix Medical Group, Inc. CSF culture results were compared with results of blood cultures and CSF parameters (white blood cells [WBCs], glucose, and protein) to establish the concordance of these values in culture-proven meningitis. CSF cultures positive for coagulase-negative staphylococci and other probable contaminants, as well as fungal and viral pathogens, were excluded from analyses. RESULTS: Meningitis was confirmed by culture in 95 (1.0%) neonates. Of the 95 patients with meningitis, 92 had a documented blood culture. Only 57 (62%) of 92 patients had a concomitant-positive blood culture; 35 (38%) of 92 had a negative blood culture. In neonates with both positive blood and CSF cultures, the organisms isolated were discordant in 2 (3.5%) of 57 cases. In each case, the CSF pathogen required different antimicrobial therapy than the blood pathogen. For culture-proven meningitis, CSF WBC counts of >0 cells per mm3 had sensitivity at 97% and specificity at 11%. CSF WBC counts of >21 cells per mm3 had sensitivity at 79% and specificity at 81%. Culture-proven meningitis was not diagnosed accurately by CSF glucose or by protein. CONCLUSIONS: Neonatal meningitis frequently occurs in the absence of bacteremia and in the presence of normal CSF parameters. No single CSF value can reliably exclude the presence of meningitis in neonates. The CSF culture is critical to establishing the diagnosis of neonatal meningitis.

Bacteremia↗

Effect of 20% in vitro haemodilution with warmed buffered salt solution and cerebrospinal fluid on coagulation.

We have conducted an in vitro coagulation study consisting of two separate groups of 20 subjects using the thrombelastograph. In the first group, haemodilution was performed with a physiological balanced salt solution similar to plasma, with the exception of calcium, and buffered to a normal pH (Plasmalyte B) at 37 degrees C on blood obtained from consenting volunteers. In the second group, a protein-poor body fluid (cerebrospinal fluid (CSF)) obtained from parturient patients undergoing spinal anaesthesia for Caesarean section was used as the diluent. There were statistically significant differences between the warmed Plasmalyte B treated samples and their untreated controls for all variables measured by the thrombelastograph, except for maximum amplitude, and between the CSF treated samples and their untreated controls for all variables. We conclude that electrolyte and acid-base composition of the diluent fluid had no effect on the observation that crystalloid haemodilution produces hypercoagulability. The marked increase in coagulability produced by addition of CSF cannot be explained on a simple haemodilution basis and confirms previous suggestions of the presence of a procoagulant factor in CSF.

Blood Coagulation↗

Hysteresis in the relationship between cerebrospinal fluid absorption minus formation and cerebrospinal fluid pressure in the dog.

In this study the difference between cerebrospinal fluid (CSF) absorption and formation (A -- F) was measured as a function of CSF pressure in the living and dead dog. We determined this relationship between A -- F and CSF pressure during both increasing and decreasing CSF pressures. A hysteresis effect was identified in 78% of living animals, but was not seen in the dead animals. This suggests that the mechanism of CSF absorption in the living dog is nonpassive and pressure-sensitive.

Absorption↗

Immunofixation to quantify beta 2-transferrin in cerebrospinal fluid to detect leakage of cerebrospinal fluid from skull injury.

beta 2-Transferrin, the desialated form of transferrin normally found only in cerebrospinal fluid (CSF) and aqueous and vitreous humor, is detected by high-resolution immunofixation (IFE). It is not normally found in nasal or aural fluids, saliva, tears, or serum. Detection in nasal fluid has been suggested to document CSF leakage into the nose after skull injury. We measured beta 2-transferrin in 48 samples of CSF. IFE of the CSF was performed on high-resolution agarose gels and stained with Coomassie Blue. beta 2-Transferrin was estimated by quantifying the total transferrin by rate nephelometry and then determining the percentage of transferrin in the beta 2 vs beta 1 region by densitometric scanning of the IFE pattern. We accurately quantified as little beta 2-transferrin as 2.5 mg/L in the CSF samples. The beta 2-transferrin fraction was clearly visible by IFE at concentrations less than 2.5 mg/L, but accurate quantification was difficult. In the samples assayed, the range of beta 2-transferrin was 4.6 +/- 1.9 mg/L. Use of this technique to examine rhinorrhea in a motor-vehicle-accident patient confirmed leakage of CSF into the nasal cavity through a vent in the left olfactory groove.

Adult↗

Are polymorphonuclear leukocytes an abnormal finding in cerebrospinal fluid? Results from 225 normal cerebrospinal fluid specimens.

Although it is often claimed that the presence of a single polymorphonuclear leukocyte (PMN) in the cerebrospinal fluid (CSF) is abnormal, recently some have suggested that a few PMNs are occasionally present in cytocentrifuged differential cell counts of normal CSF. We examined 225 consecutive normal CSF specimens to determine how frequently PMNs occur in normal CSF and to identify factors associated with the presence of PMNs. One or more PMNs were present in 73 cases (32%). The number of CSF PMNs was strongly correlated with the degree of CSF blood contamination and the hematologic PMN count. Of the 163 specimens having 25 red blood cells or less per cubic millimeter, only eight (5%) had three or more PMNs, and these outliers had abnormally high hematologic PMN counts. Of the 36 specimens having 100 red blood cells or more per cubic millimeter, 17 (47%) had six or more PMNs. We conclude that the number of PMNs found on cytocentrifuged differential cell counts is highly dependent on the degree of CSF blood contamination and the patient's hematologic PMN count and that even minimal blood contamination can result in the presence of one to two PMNs in normal CSF.

Cerebrospinal Fluid↗

[Blood-cerebrospinal fluid barrier function and cholinesterase activity in cerebrospinal fluid in degenerative changes of the lumbar spine].

The objective of this study was to determine whether spinal compression associated with degenerative changes of the lumbar vertebral column induces significant alteration in defined cerebrospinal fluid parameters. Serum and lumbar cerebrospinal fluid were studied in 62 patients and 47 age-matched controls. Patients were grouped according to neurologic status, duration of symptoms, and findings in magnetic resonance imaging. Statistically significant elevations in cerebrospinal fluid/serum albumin ratio, acetylcholinesterase, butyrylcholinesterase activity, and total protein concentration were observed in lumbar cerebrospinal fluid of patients. Patients with neurologic deficits did not exhibit significant differences in cerebrospinal fluid parameters compared with patients lacking neurologic signs. No significant differences were detectable between lateral and medial compression. Acute disk herniation led to practically the same biochemical changes as chronic compression. Biochemical analysis of lumbar cerebrospinal fluid offers additional diagnostic information in patients suffering from back or leg pain associated with degenerative changes of the spine. Pathological damage to meningeal and neural tissues can be demonstrated even if neurologic signs or obvious spinal compression are missing in the radiological examination. An elevated cerebrospinal fluid/serum albumin ratio reflects alteration of the blood/cerebrospinal fluid barrier status. Increased acetylcholinesterase and butyrylcholinesterase activity point to pathophysiological impairment of neural tissues or meninges.

Acetylcholinesterase↗

Intravenous probenecid loading. Effects on plasma and cerebrospinal fluid probenecid levels and on monoamine metabolites in cerebrospinal fluid.

Probenecid blocks the active transport from cerebrospinal fluid to blood of homovanillic acid and 5-hydroxyindoleacetic acid, thus increasing cerebrospinal fluid levels of these products of central monoamine metabolism. The half-life in plasma of probenecid given as a single intravenous infusion (40 mg per kilogram of body weight) to patients with either Huntington's chorea or Parkinson's disease averaged about 6.6 hours. In cerebrospinal fluid, peak values for homovanillic acid and 5-hydroxyindoleactic acid occurred in samples collected 8 hours after the 1-hour probenecid infusion was started. Even after 4 hours, however, levels of both monoamine metabolites were significantly increased. There was a positive correlation between cerebrospinal fluid levels of probenecid and the increase in 5-hydroxyindoleacetic acid but not homovanillic acid. Compared with the oral administration of probenecid, the intravenous infusion technique produced more consistent elevations in plasma and cerebrospinal fluid probenecid levels, greater increases in cerebrospinal fluid homovanillic acid values, and fewer gastrointestinal side effects.

Administration, Oral↗

Alpha-2-macroglobulin, albumin, and chymotrypsin inhibitory capacity in cerebrospinal fluid as indices of blood-cerebrospinal fluid barrier.

Concentration of alpha-2-macroglobulin, albumin, and chymotrypsin inhibitory capacity representing mainly alpha-1-proteinase inhibitor were estimated in cerebrospinal fluid in disorders of the central nervous system. While chymotrypsin inhibitory capacity was elevated in all cases with derangement of the blood-cerebrospinal fluid barrier, in 30% of the cases alpha-2-macroglobulin levels were in the normal range. The difference can be attributed to the much larger size of the latter. Better correlation between albumin concentration and chymotrypsin inhibitory capacity (r = 0.84) than between albumin and alpha-2-macroglobulin (r = 0.62) supports the view that the rate of entry of proteins from blood into cerebrospinal fluid is inversely related to their size.

Albumins↗