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PubMed1997

Apolipoprotein E in cerebrospinal fluid in 85-year-old subjects. Relation to dementia, apolipoprotein E polymorphism, cerebral atrophy, and white matter lesions.

OBJECTIVE: To further elucidate the pathogenetic role of apolipoprotein E (Apo E) in degenerative brain disorders, we analyzed cerebrospinal fluid (CSF) levels of Apo E in 85-year-old subjects with dementia disorders. DESIGN: Survey. SETTING: Community. PARTICIPANTS: Population-based sample of 27 demented (12 with Alzheimer disease [AD]; 13, vascular dementia [VAD]; and 2, other types of dementia) and 35 nondemented individuals. MAIN OUTCOME MEASURES: Cerebrospinal fluid levels of Apo E, Apo E polymorphism, and brain atrophy and white matter lesions (WMLs) measured by computed tomography (CT) of the brain. Dementia was defined according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria; AD, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria; and VAD, National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neuroscience criteria. RESULTS: The mean (+/- SD) CSF levels of Apo E were lower in the AD (2.6 +/- 1.5 mg/L; P < .02) and VAD groups (2.5 +/- 0.9 mg/L; P < .002) than in the nondemented group (3.8 +/- 1.7 mg/L). Cerebrospinal fluid levels of Apo E decreased with increasing severity of dementia and with increasing temporal cortical and central frontal atrophy. In nondemented individuals, CSF levels of Apo E decreased with increasing degree of WMLs. Cerebrospinal fluid levels of Apo E were not influenced by the Apo E4 isoform. CONCLUSIONS: Whether our finding of an association between low CSF levels of Apo E and dementia disorders (both degenerative, such as AD, and vascular, such as VAD) is related to the pathogenesis of these disorders or is a secondary consequence of the disease process remains to be established. Although statistical correlations do not give direct evidence of causal relations, the correlations between CSF level of Apo E and severity of dementia and cortical atrophy suggest that CSF level of Apo E follows the disease process.

Aged↗
PubMed2000

Cost analysis of enteroviral polymerase chain reaction in infants with fever and cerebrospinal fluid pleocytosis.

BACKGROUND: Infants with fever and cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital for parenteral antibiotic therapy for potential bacterial meningitis pending results of CSF culture. Published estimates suggest that 90% of all episodes of meningitis are caused by enterovirus. Enteroviral polymerase chain reaction (ePCR) has a sensitivity of 92% to 100% and a specificity of 97% to 100% in CSF. OBJECTIVE: To compare a management strategy using ePCR with current practice to determine potential savings by allowing earlier discharge. METHODS: Decision analysis comparing 2 strategies for the care of a retrospective cohort of infants with fever and CSF pleocytosis: standard practice vs ePCR testing of all CSF samples. Model assumptions include the following: (1) standard practice patients continue parenteral antibiotic therapy until CSF cultures are negative at 48 hours, (2) patients with positive ePCR results would be discharged after 24 hours, (3) patients with positive ePCR results have a negative CSF culture, and (4) costs are calculated from actual patient charges with a cost-to-charge ratio of 0.65. SUBJECTS: All infants aged 28 days to 12 months admitted to an urban teaching hospital with fever, CSF pleocytosis, and a negative CSF Gram stain from January 1996 through December 1997. OUTCOME MEASURE: Total cost of hospitalization. RESULTS: A total of 126 infants were identified. One hundred twelve (89%) were discharged with a diagnosis of aseptic meningitis; 72% of these cases occurred during the peak enterovirus season (June to October). Three of 3 patients with positive CSF cultures had bacterial growth within 24 hours of admission. Mean length of stay for patients with aseptic meningitis was 2.3 days (SD, +/-1.4 days). Total cost of hospital care for all 126 infants was $381,145. In our patient population, total patient costs would be reduced by the ePCR strategy if enterovirus accounts for more than 5. 9% of all meningitis cases. Varying the sensitivity of the ePCR assay from 100% to 90% changes the "break-even" prevalence from 5.8% to 6.5%. Total cost savings of 10%, 20%, and 30% would occur at an enteroviral meningitis prevalence of 36.3%, 66.7%, and 97.1%, respectively. CONCLUSIONS: Enteroviral PCR analysis of CSF for infants admitted to the hospital with meningitis can result in cost savings when the prevalence of enteroviral meningitis exceeds 5.9%. Limiting use of ePCR to the enterovirus season would increase cost savings. A prospective study is needed to validate these results. Arch Pediatr Adolesc Med. 2000;154:817-821

Boston↗
PubMed2003

Neopterin, biopterin, and nitric oxide concentrations in the cerebrospinal fluid of children with central nervous system infections.

We measured neopterin, biopterin and nitric oxide (NO) concentrations in the cerebrospinal fluid of pediatric patients with central nervous system (CNS) infectious diseases. The nitric oxide and neopterin concentrations were significantly elevated in encephalitis patients, especially in two cases with serious neurological sequelae, while the biopterin levels were not elevated. The bacterial meningitis patients, on the contrary, had high cerebrospinal fluid concentrations of neopterin and biopterin, but not of NO. Although these findings are preliminary, it may suggest that cerebrospinal fluids nitric oxide would be a useful marker to prospect neurological prognoses in the CNS infections.

Biomarkers↗
PubMed2004

[Catecholamine levels in plasma and cerebrospinal fluid of neurosurgical patients with normal and elevated intracranial pressure].

OBJECTIVE: Catecholamine levels in the plasma and cerebrospinal fluid of 21 neurosurgical patients with hydrocephalus and with normal and elevated intracranial pressure were determined prospectively in a clinical study. METHODS: The study comprised 11 patients with normal intracranial pressure (8 female, 3 male, group 1) and 10 patients with elevated intracranial pressure (6 female, 4 male, group 2). The patients underwent a ventriculo-peritoneal shunt operation, external ventricular drainage or ventriculocisternostomy. The measuring times were set as follows: time 1: pre-operative; time 2: intra-operative; time 3: post-operative. The anaesthetic for the operations was administered as a total intravenous anaesthesia with propofol and alfentanil, muscle relaxation being achieved with rocuronium bromide or cis-atracurium. RESULTS: Measurements of the catecholamine levels (adrenaline, noradrenaline and dopamine) at the three set times revealed an intra-operative fall compared to the initial pre-operative value and a rise in the catecholamine level again after the operation. It is likely that this largely reflects the course of the anaesthetic. The fall in the plasma catecholamine level was much slighter in group with elevated intracranial pressure. But in the group of patients with elevated intracranial pressure the catecholamine levels found in the plasma were much higher than those of the patients without elevated pressure. In the case of adrenaline, it was possible to demonstrate a statistically significant difference at the three measuring times. This suggests that especially the analyzed adrenaline level in the plasma could take on the role of a marker in cases of elevated intracranial pressure. In group 2, with elevated intracranial pressure, the catecholamine levels in the cerebrospinal fluid (CSF) were considerably higher than those in group 1, but the difference did not reach the significance level. The lack of correlation between the catecholamine values in the plasma and CSF described in the literature (comparison of the corresponding values at time 2) was confirmed for noradrenaline and dopamine in patients with elevated intracranial pressure (group 2). In both groups of patients there was a CSF plasma gradient for dopamine at time 2, i. e. the dopamine level was higher in cerebrospinal fluid than in the plasma. CONCLUSION: The study shows that even a slight rise in intracranial pressure without clinically detectable ischaemia may result in elevated plasma and CSF catecholamine levels. Although catecholamine values are not routine parameters, they can be used in developing procedures to protect the brain in neurosurgical patients.

Adult↗
PubMed1979

Neuropeptide hormones in cerebrospinal fluid. Experimental and clinical aspects.

Neuroendocrinologists are now realising that the brain-pituitary relationships in man are more complex than they had previously thought. It seems that the brain is also a gland, whereas the pituitary produces neuropeptide hormones which work in the brain. Since most substances which carry information between those two neuroendocrine partners are present in cerebrospinal fluid, it is natural to assume that cerebrospinal fluid has an important role as a carrier of molecular signals between the brain and pituitary. Whether or not the analysis of cerebrospinal fluid neuropeptide hormones will give more information about the brain activity in neurological and psychiatric patients is not yet known exactly despite some promising new findings.

Brain Chemistry↗
PubMed1988

Measurement of immunoreactive myelin basic protein peptide (45-89) in cerebrospinal fluid.

To measure myelin basic protein (MBP)-like material in cerebrospinal fluid, we compared two radioimmunoassays, both using the same antiserum to MBP but one using peptide (45-89) as the radioligand and standard (peptide assay), and the other using purified MBP as the radioligand and standard (MBP assay), with respect to their diagnostic sensitivity. Cerebrospinal fluid specimens from 185 patients with definite multiple sclerosis (MS) (n = 27), possible MS (n = 63), probable MS (n = 24), and other neurological disease (n = 71) were analyzed using both assays. The diagnostic sensitivity of the peptide assay was significantly better than that of the MBP assay in those with definite MS (sensitivity 59% and 30%, respectively); there was no significant difference in specificity. The peptide assay also showed better correlation with disease activity than the MBP assay: 14 patients classified as having active MS showed significantly higher sensitivity (78.6% versus 38%, p less than 0.04) when compared to patients with inactive disease. The MBP assay showed no significant difference between these two groups. Besides the increase in sensitivity, the actual molar concentrations of immunoreactive MBP detected using this peptide assay were considerably higher than those found using the MBP assay. These results show that the use of MBP antisera capable of recognizing epitopes present in the carboxyl half of MBP peptide (45-89) results in more sensitive detection of immunoreactive MBP when used with MBP peptide (45-89) as radiolabeled ligand in the assay.

Humans↗
PubMed2004

5-Hydroxyindoleacetic acid and homovanillic acid concentrations in cerebrospinal fluid in patients with Alzheimer's disease, depression and mild cognitive impairment.

In this study we investigated the cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in Alzheimer (AD) patients (n=75), patients with mild cognitive impairment (MCI, n=9) and patients with depression (n=7). CSF HVA was significantly elevated in AD with depression (Geriatric Depression Scale, 15 point version GDS>5) in comparison to AD without depression (p<0.05, ANOVA) and CSF HVA showed a significant positive correlation with the GDS score of AD-patients (p=0.03, Spearman Rho: 0.38, Spearman Rank Correlation). In the group of AD patients CSF 5-HIAA was positively correlated with cerebrospinal fluid beta-amyloid 1-42 (Abeta42), p<0.05, Spearman Rho: 0.3, Spearman Rank Correlation, but not with CSF tau. Additionally, there was a significant positive correlation between cerebrospinal fluid 5-HIAA and HVA in the group of AD patients (p<0.0001, Rho: 0.47, Spearman Rank correlation). Neither 5-HIAA nor HVA in CSF could differentiate between mild cognitive impairment, depression and AD. The results of this study support the hypothesis that the serotonergic system plays a role in the course of AD. They further suggest an important role of dopamine metabolism in depression within AD patients.

Aged↗
PubMed1990

[The significance of isoelectric focusing of unconcentrated cerebrospinal fluid in the detection of oligoclonal zones in multiple sclerosis].

In a group of 31 patients with a confirmed diagnosis of multiple sclerosis the authors assessed the presence of oligoclonal abnormality of gammaglobulins in cerebrospinal fluid. Specimens of non-concentrated cerebrospinal fluid were examined by two separating methods which use as a vehicle polycryamide gel: isoelectric focusing and a modified electrophoretic technique. By isoelectric focusing an oligoclonal state was proved in 71%, the finding was doubtful in 16.1% and negative in 12.9%. The applied electrophoretic separation revealed an oligoclonal state in 58.1%, the finding was doubtful in 25.8%, negative in 16.1%. In cerebrospinal fluid where isoelectric focusing did not prove an oligoclonal finding, the latter was not detected by electrophoresis either. The method of isoelectric focusing is obviously more sensitive than mere electrophoretic separation. In common practice, it is, however, better to use electrophoresis in vehicles which positively influence the separation process, best in a polyacrylamide gel. Only when the finding is negative or doubtful and there is urgentclinical suspicion, it is suitable to supplement the examination by isoelectric focusing.

Adult↗
PubMed1988

Cerebrospinal fluid levels of quinolinic acid in Huntington's disease and schizophrenia.

The concentration of the endogenous excitotoxin quinolinic acid was determined in the cerebrospinal fluid of drug-free patients suffering from Huntington's disease or schizophrenia (control group). In both diseases, quinolinic acid concentrations were highly variable (less than 4-48 nM) but the mean levels for each disease group were not significantly different from each other or from the quinolinic acid concentration of normal cerebrospinal fluid. Analysis of steady-state cerebrospinal fluid quinolinic acid concentration is unlikely to be of value as a diagnostic tool in Huntington's disease.

Adolescent↗
PubMedDate not supplied

The local effect of pH changes in the cerebrospinal fluid on the ventrolateral areas of medulla oblongata and on the spinal cord surface on the activity of cardiac and vertebral sympathetic nerves.

Application of acid cerebrospinal fluid at pH 6.8 to the ventral surface of the medulla oblongata in cats increased the arterial blood pressure and the activity of the vertebral nerve and enhanced respiratory modulation of the vertebral and cardiac nerves. Alkaline cerebrospinal fluid at pH 7.7 applied to the ventral surface of the medulla oblongata increased the arterial blood pressure without changes in the sympathetic nerve activity. When the spinal cord was superfussed with artificial acid cerebrospinal fluid at the Th1 level the activity of the vertebral nerve and cardiac nerve increased and the arterial blood pressure rose. The authors discuss the possibility of regulation of the activity of sympathetic neurons in the medulla and spinal cord by means of direct action of pH and pCO2 on the neurons, or through an indirect effect mediated by superficial chemoreceptors of the medulla oblongata. The role of local changes of the brain blood flow in the mechanism of these results is discussed as well.

Animals↗
PubMed1995

Cerebrospinal fluid corticotropin and cortisol are reduced in infantile spasms.

Infantile spasms respond to ACTH, and levels of the hormone in cerebrospinal fluid of untreated infants with this disorder were found to be lower than in age-matched controls. In this study we analyzed cerebrospinal fluid cortisol and ACTH using improved immunoassays in a larger cohort of infants with infantile spasms. Analysis of 20 patients and 15 age-matched controls revealed significantly lower levels of both ACTH and cortisol in the cerebrospinal fluid. These data, combined with the efficacy of ACTH and glucocorticoids for infantile spasms, support an involvement of the brain-adrenal-axis in this disorder.

Adrenocorticotropic Hormone↗
PubMed1987

[Quasi-normal cerebrospinal fluid in patients with acquired immunodeficiency syndrome and cryptococcal meningitis].

We report eight patients with cryptococcal meningitis and a cerebrospinal fluid characterized by few or no white blood cells and chemistries that may be near normal. In four of these patients, only testing for cryptococcal antigen allowed the initial diagnosis. Seven of the patients had a certain diagnosis of AIDS. Six have died. Autopsies performed in two cases indicated a poor meningeal inflammatory response. Contrary to the findings in most immunodeficient patients, in AIDS cryptococcal meningitis may present with few cellular or biochemical abnormalities in the cerebrospinal fluid. In AIDS patients presenting with headache and fever or change in mental status, examination of the cerebrospinal fluid should not be limited to routine studies.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Changes in magnesium concentration in the serum and cerebrospinal fluid of neuropathic rats.

BACKGROUND: Central sensitization of neuropathic pain is associated with an influx of extracellular calcium via the opening of N-methyl-D-aspartate (NMDA) receptor-gated ion channels, which are usually blocked by magnesium plugs. As magnesium-deficient rats develop a mechanical hyperalgesia and intrathecal or intraperitoneal magnesium suppresses neuropathic pain, the magnesium concentrations in serum and cerebrospinal fluid may be altered in neuropathic pain. We therefore compared the magnesium concentrations in serum and cerebrospinal fluid of neuropathic rats with those in injured rats without symptoms of neuropathic pain and normal rats. METHODS: Mechanical allodynia was induced in male Sprague-Dawley rats by tight ligature of the left lumbar fifth and sixth spinal nerves. The threshold of paw withdrawal was evaluated by the up-down method using withdrawal response to stimulus with a von Frey filament on the third, seventh and 14th days. Rats with a threshold of less than 4 g were selected as the symptomatic group and compared with an asymptomatic group, an unoperated control group and a sham-operated group. On the 16th day, the Mg2+ concentrations in serum and cerebrospinal fluid were measured. RESULTS: The magnesium concentrations in the serum and cerebrospinal fluid of symptomatic neuropathic rats did not differ from those in the injured rats without symptoms of neuropathic pain, sham-operated rats and normal rats. CONCLUSION: Our results suggest that physiologic homeostasis is maintained by active transport through the blood-brain barrier despite the activation of NMDA receptor-gated ion channels. However, rats with neuropathic pain may be in a magnesium-deficient condition at the effector site, such that magnesium treatment can decrease neuropathic pain.

Animals↗
PubMed1996

Cerebrospinal fluid distribution of opioids after intraventricular & lumbar subarachnoid administration in sheep.

The study of opioid distribution in blood and cerebrospinal fluid (CSF) is required to understand pharmacokinetic-pharmacodynamic relationships following lumbar intrathecal (it) and intracerebroventicular (i.c.v.) administration, and to investigate the contributions of spinal or supraspinal sites of action. The sheep model developed for pharmacokinetic study of analgesics allows atraumatic sampling of plasma and CSF after drug administration by the intravenous (i.v.), i.c.v., and it routes in an unanesthetized animal. Five adult female sheep were prepared with femoral vascular catheters, lumbar it and epidural cannulae, i.c.v. cannulae, and cisterna magna cannulae. Hydromorphone, methadone, naloxone, and [14C] sucrose were injected and collected by two methods: 1) injection into the i.c.v. cannula with lumbar CSF samples collected via the lumbar cannula and 2) injection into the lumbar cannula and cisternal CSF samples collected via ventriculocisternal cannula. Hydromorphone, morphine, and [14C] sucrose were detected at 90-105 min in lumbar CSF after i.c.v. injection. Hydromorphone and [14C] sucrose were detected in i.c.v. cerebrospinal fluid at 50 min after lumbar i.t. injection. Methadone was not detected in i.c.v. cerebrospinal fluid after i.t. injection, nor was methadone significantly detected in lumbar CSF after i.c.v. injection. These data indicate that i.c.v. and i.t. administration of lipophilic opioids produces CSF distributions different from those of hydrophilic opioids. This suggests that lipophilic opioids such as methadone or naloxone exert their effects predominantly on tissues near the site of injection. The study of i.t. and i.c.v. opiate administration and CSF pharmacokinetics may therefore have direct clinical implications.

Analgesics, Opioid↗
PubMed2005

Cerebrospinal fluid leaks of temporal bone origin: etiology and management.

BACKGROUND: Cerebrospinal fluid (CSF) leaks of the temporal bone region require surgical treatment as they pose life-threatening risks such as meningitis. AIM: The aim of the study was to determine the surgical outcome depending on different operation techniques and grafts. METHOD: We performed a retrospective review of 28 cases of CSF leaks, operated in our department from 1983 to 2002. After a mean follow-up of 8 years, patients were interviewed concerning otorrhea or rhinorrhea and meningitis. In this context, our management of CSF leaks is presented. RESULTS: The CSF leak had arisen spontaneously (n = 3), traumatically (n = 6) or postoperatively (n = 19). The surgical CSF leak repairs were performed via a transmastoid (n = 13), a middle fossa (n = 11) or a combined (n = 4) approach. Surgical outcome was independent on the used graft. CSF leak could be sealed in 25 of 28 cases. Only 3 patients suffered from recurrences. Meningitis or other complications did not occur. CONCLUSIONS: Comparing different techniques and grafts, there were no differences in the surgical outcome.

Cerebrospinal Fluid Otorrhea↗
PubMed1999

Unchanged levels of interleukins, neopterin, interferon-gamma and tumor necrosis factor-alpha in cerebrospinal fluid of patients with dementia of the Alzheimer type.

Several histopathological studies suggest that amyloidogenesis in dementia of the Alzheimer type is accompanied by activated glia and glia-derived cytokines, leading to chronic, self-propagating, cytokine-mediated molecular and cellular reactions. As studies regarding inflammatory changes in cerebrospinal fluid of patients with dementia of the Alzheimer type has been inconclusive, we set up a prospective study to assess cerebrospinal fluid levels of interleukin-1beta, interleukin-6, interleukin-10, interleukin-12, soluble interleukin-2 receptor, interferon-gamma, tumor necrosis factor-alpha and neopterin in 20 patients with dementia of the Alzheimer type and 20 age- and sex-matched controls. Comparing both groups, no significant differences in concentrations and specific activities could be revealed. An additional 22 patients were included to enlarge the study population. No statistically significant differences were shown comparing patients (n=42) with the control group (n=20). We conclude that the immune-mediated inflammatory changes found in histopathological studies are not reflected in cerebrospinal fluid of patients with dementia of the Alzheimer type. Probably, cytokine production appears very localized in the central nervous system, not allowing representative detection in cerebrospinal fluid. Further studies assessing cytokine levels in various regions of central nervous system of patients with dementia of the Alzheimer type will be of interest to confirm this hypothesis.

Aged↗
PubMed1988

[Diagnostic value of aspartate aminotransferase in the cerebrospinal fluid].

As datum, the range of aspartate aminotransferase in the cerebrospinal fluid of adults was determined on the basis of 153 fluid samples and compared with the values obtained from 356 neurological patients. A significant increase in enzyme activity was established in respect of CVI, polyneuropathy, acute encephalitis, and SAB. It was possible to eliminate any dependence of the aspartate aminotransferase activity on serum activity, total protein, and cell count. The increase in activity of aspartate aminotransferase in the cerebrospinal fluid is thus identified as an independent pathological fact, and thus it can be incorporated in diagnostic routine more particularly in the diagnosis of CVI disorders.

Aspartate Aminotransferases↗
PubMed1996

Traumatic cerebrospinal fluid leakage: risk factors and the use of prophylactic antibiotics.

Cerebrospinal fluid (CSF) leakage following head trauma is often difficult to diagnose, but is of considerable importance in view of the possibility of fistula formation and meningitis. It is unclear whether specific clinical or radiological signs point to an increased risk of CSF leakage. Previous studies have been largely anecdotal and uncontrolled, leading us to perform a retrospective control study comparing the clinical and radiological features of patients with overt CSF leakage, and those without. Of the 293 patients studied, 115 had clinical CSF leakage and 170 did not, with incomplete documentation in eight patients. The group with CSF rhinorrhoea had significantly greater incidence of periorbital haematoma (chi square = 8.642). This suggests that patients with head injuries and features of periorbital haematoma are at greater risk of unobserved dural tear and delayed CSF leakage. Frontal and ethmoid fractures in particular were also associated with CSF leakage (chi square = 5.46). The use of prophylactic antibiotics was studied. There was a significantly greater incidence of meningitis in the group which received prophylactic antibiotics (p = 0.024). There was no significant difference in the incidence of meningitis in those patients with CSF fistulae treated by surgical or conservative methods.

Adolescent↗