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Showing papers on "Cerebrospinal fluid published in 1982"


Journal ArticleDOI
TL;DR: A vascular model which is based on flow in collapsible tubes and changes in vasomotor tone is posited to explain control of pulsatile flow and pulse waveform changes in the cerebrovascular bed and helps to clarify the strong interrelationship between intracranial pressure, cerebral blood flow, and cerebral autoregulation.
Abstract: ✓ Systems analysis of the systemic arterial (SAPW), cerebrospinal fluid (CSFPW), and sagittal sinus (SSPW) pulse waves was carried out in 13 dogs during hypercapnia (5% CO2), intracranial normotension (inhalation of 100% O2), and intracranial hypertension (inhalation of 100% O2 plus an intraventricular infusion). Power amplitude and phase spectra were determined for each wave, and the power amplitude and phase transfer functions calculated between the cerebrospinal fluid (CSF) pressure and systemic arterial pressures, and between the sagittal sinus pressure and CSF pressure. The study indicates that the CSFPW and SSPW were virtually identical when impedance between the cerebral veins and sagittal sinus was minimal, which argues that the CSF pulse was derived from the cerebral venous bed. During inhalation of 100% O2, transmission of the SAPW across the precapillary resistance vessels into the cerebral venous pulse (as represented by the CSFPW) was nonlinear, while transmission across the lateral lacunae i...

152 citations


Journal ArticleDOI
TL;DR: Cerebrospinal fluid flow dynamics were evaluated by 111Indium-diethylenetriamine pentaacetic acid (111In-DTPA) ventriculography in patients with neoplastic meningitis to indicate that cerebrosp spinal fluid flow abnormalities are common in patientsWith neoplasia and that 111In- DTPA cerebro Spinal Fluid flow imaging is useful in characterizing these abnormalities.

138 citations


Journal Article
TL;DR: It is suggested that decreased activity in the central GABAergic and dopaminergic system may be involved in the pathogenesis of depression.

121 citations


Journal ArticleDOI
TL;DR: In 39 parkinsonian patients, CSF somatostatin content was 88.0 ± 4.1 pg per milliliter, which was about 40% less than in controls, and seems to be irreversible, to be present at the onset of symptoms, and to imply an irreparable functional or structural alteration of somatOSTatin-secreting neurons.
Abstract: In 39 parkinsonian patients, CSF somatostatin content was 88.0 ± 4.1 pg per milliliter, which was about 40% less than in controls (147.3 ± 5.1 pg per milliliter). Somatostatin values were unrelated to age, sex, body weight, total CSF protein, immunoglobulin, or cell count in either group. Parkinsonian values were not related to duration of disease, severity, specific signs, or treatment. In contrast to multiple sclerosis, in which CSF somatostatin is low only during relapses, the low somatostatin content of CSF in Parkinson disease seems to be irreversible, to be present at the onset of symptoms, and to imply an irreparable functional or structural alteration of somatostatin-secreting neurons.

119 citations


Journal ArticleDOI
TL;DR: The results support the assumption that S-100 is a reliable index of central nervous system damage and that changes in its concentration could have a prognostic value.
Abstract: S-100 protein was determined by Particle Counting ImmunoAssay in the CSF of patients with various neurological disorders. With a limit of sensitivity of 2.5 micrograms/l this brain-specific protein was detected only in samples from patients with acute damage of the central nervous system, particularly in compression of the spinal cord by tumour, ischaemic disorders, subarachnoid bleeding and haematoma, and viral or suspected viral infections. Our results support the assumption that S-100 is a reliable index of central nervous system damage and that changes in its concentration could have a prognostic value.

106 citations


Journal ArticleDOI
TL;DR: CMOA, although absent in normal CSF, can appear in CSF during acute bacterial meningitis, particularly in patients who recover completely, and is correlated with protein concentrations and microorganisms in the sample of CSF collected at the time of admission.
Abstract: A local defense mechanism in bacterial meningitis was evaluated in humans by measuring complement-mediated opsonic activity (CMOA) in normal and infected cerebrospinal fluid (CSF) with a complement-dependent phagocytic bactericidal assay. CMOA was absent in normal untreated CSF and remained undetectable in 20 samples of CSF from patients with viral meningitis and five samples from patients with acute meningococcemia. In contrast, 15 of 27 samples of CSF from patients with acute bacterial meningitis had a measurable CMOA, which was correlated with protein concentrations (P less than 0.01) and C4 hemolytic activity (P less than 0.001) in the CSF. A favorable outcome of bacterial meningitis was associated with the presence of CMOA in CSF (P less than 0.005). Recovery was also correlated with higher levels of C4 (P less than 0.01) and C3 (P less than 0.05) in CSF and with lower concentrations of microorganisms in the sample of CSF collected at the time of admission (P less than 0.01). Thus, CMOA, although absent in normal CSF, can appear in CSF during acute bacterial meningitis, particularly in patients who recover completely.

101 citations


Journal ArticleDOI
TL;DR: Neuron-specific enolase level was significantly increased in sera from patients with comas resulting from anoxemia, head injury, septic state, cirrhosis and fulminant hepatitis, and the correlation between its level in cerebrospinal fluid and in serum was demonstrated.

97 citations


Journal ArticleDOI
TL;DR: Repeat studies of three patients showed that perturbations of CSF suppressor/cytotoxic cells were dependent on clinical status, adding to the accumulating data that suggest altered immunity in the pathogenesis of MS.
Abstract: To determine if previously reported peripheral blood suppressor cell defects are also found in the central nervous system (CNS) of patients with multiple sclerosis (MS), we studied cerebrospinal fluid (CSF) and peripheral blood lymphocytes from 40 MS patients and 15 patients with other neurological diseases. With an indirect immunofluorescence technique using the OKT series of monoclonal antibodies (OKT4, marking helper/inducer cells, OKT5 and OKT8 marking suppressor/cytotoxic cells, and OKT3 marking all peripheral T cells) we found that MS patients tested in the first 2 wk of exacerbation had invariably diminished CSF suppressor/cytotoxic cells, which was followed by an elevation of these cells in the 3rd wk of exacerbation. Repeat studies of three patients showed that perturbations of CSF suppressor/cytotoxic cells were dependent on clinical status. These observations add to the accumulating data that suggest altered immunity in the pathogenesis of MS.

90 citations


Journal Article
TL;DR: One possible explanation for the stage-related NK suppression seen in the present investigation may be a decreased interferon production combined with immune-complex induced, macrophage-produced prostaglandins which are known to influence the human NK system in a comparable way in vitro.
Abstract: Natural killer cell activity has earlier been shown to be depressed in patients with multiple sclerosis (MS) (Benczur et al., 1980). In the present study, this defect was more clearly characterized in different stages of the disease. By using a single-cell cytotoxicity assay in agarose (Grimm & Bonavida, 1979), in combination with the conventional 51Cr-release, the number of target-binding cells (TBCs) and the fraction of active killer cells therein could be compared with the radioisotope release in the different patient groups. It was found that patients with active and chronic MS showed lower natural killer (NK) activity in the 51Cr-release assay as compared with age and sex-matched controls, in contrast to stable MS patients who were comparable with their control group. The single cell cytotoxicity assay demonstrated that acute MS patients had a decreased number of TBCs in peripheral blood and that they also had a decreased percentage of active NK cells in their TBC fractions. Patients with chronic MS were normal in the single-cell cytotoxicity assay. When cells present in CSF were analysed in acute and chronic MS, few cells were found with target binding capacity and only in two instances out of 13 could any cytotoxicity at all be detected. Patients with other neurological diseases (OND) were found to have detectable NK activity in CSF in six cases out of ten in the single-cell assay. OND patients as a group also had higher peripheral NK activity in the 51Cr-release assay as compared with the control group. When peripheral and CSF cells from MS patients and OND patients were treated with interferon, no increase in TBCs or fraction of killer cells in TBCs was found. In the 51Cr-release assay, comparable increases in cytotoxicity were found in all groups. One possible explanation for the stage-related NK suppression seen in the present investigation may be a decreased interferon production combined with immune-complex induced, macrophage-produced prostaglandins which are known to influence the human NK system in a comparable way in vitro. Additionally, immune-complexes may directly interact with human NK cells as the majority of these are known to express receptors for the Fc portion of IgG.

82 citations


Journal ArticleDOI
James H. Wood1
TL;DR: The individual, somatotopic, chronological, endocrinological, pharmacological, and possible artifactual variations in CSF hormonal composition are presented to facilitate the formulation of clinical protocols and to eliminate possible sources of error.
Abstract: Cerebrospinal fluid (CSF) has been implicated as a conduit in neuroendocrine integration. Evidence suggests that the ventricular CSF may promote the central distribution, enable the dilutional inactivation (sink effect), and facilitate the peripheral delivery of neurally secreted hormones. This discussion of the sites of origin and concentration gradients of CSF hormones and of both physiological and pharmacological variations in the hormonal content of the CSF provides insight into the putative role of CSF in neuroendocrine regulation. Normal or control concentrations of peptides, steroids, and other hormones present in human lumbar CSF are listed to provide a physiological base line to which the CSF hormonal profile of patients may be compared. The individual, somatotopic, chronological, endocrinological, pharmacological, and possible artifactual variations in CSF hormonal composition are presented to facilitate the formulation of clinical protocols and to eliminate possible sources of error.

80 citations


Journal ArticleDOI
TL;DR: It is concluded that, with elevated ICP, CSF drained via pathways that are less evident under normal pressure, as the concentration of RISA on the convexities and in the SSS blood did not significantly differ between the groups.
Abstract: Artificial cerebrospinal fluid (CSF) containing radioisotope iodinated (125I) serum albumin (RISA) and either blue dextran or indigo carmine was given to white New Zealand rabbits over 4 hours. In one group it was given by ventriculocisternal perfusion, in one by ventricular infusion, and in one by cisterna magna infusion. Blood was sampled continuously from the superior sagittal sinus (SSS) or intermittently from the systemic arterial circulation. Removal of CSF from the cisterna magna during the ventriculocisternal perfusion kept the intracranial pressure (ICP) at 0 to 5 torr, whereas ventricular or cisterna magna infusion raised the ICP to 20 to 30 torr and 15 to 20 torr, respectively. In the two groups with raised ICP, an increased concentration of RISA was present in the optic nerves, olfactory bulbs, episcleral tissue, and deep cervical lymph nodes; but this was not found in the group with normal ICP. In all three groups, the concentration of RISA in the SSS blood was the same as in the systemic arterial blood. The concentration gradient of RISA across the cerebral cortex was similar in both the ventriculocisternal perfusion and the ventricular infusion groups. With cisterna magna infusion, the concentration of RISA was the same on the cortical surface and less in the ventricles compared with the ventricular infusion. It is concluded that, with elevated ICP, CSF drained via pathways that are less evident under normal pressure. Drainage of CSF was similar irrespective of whether the infusion site was the ventricles or cisterna magna. It did not appear that acute dilatation of the ventricles during ventricular infusion compromised the subarachnoid space over the surface of the hemisphere, as the concentration of RISA on the convexities and in the SSS blood did not significantly differ between the groups. Transcortical bulk transfer of CSF was not evident with raised ICP.

Journal ArticleDOI
TL;DR: Cerebrospinal fluid obtained from the cisterna magna of conscious unrestrained guinea-pigs was assayed for oxytocin, vasopressin and neurophysin, concluding that the presence of these peptides in CSF reflects activity of extrapituitary terminals and that these terminals are not activated during suckling.
Abstract: Cerebrospinal fluid (CSF) obtained from the cisterna magna of conscious unrestrained guinea-pigs was assayed for oxytocin (OT), vasopressin (AVP) and neurophysin (NP). Basal levels of OT and AVP were approximately 5 and 15 fmol/ml, respectively, whereas NP levels were considerably higher (around 1 pmol/ml); there was no significant differences between males, females and lactating females. In lactating females, simultaneous samples of blood and CSF were obtained during suckling episodes. Despite large increases in plasma OT and NP at milk ejection, CSF levels remained unchanged throughout. Intracerebroventricular injection of 100 fmol OT produced an 8-fold rise in the concentration of this peptide in cisternal fluid within 10 min. Since CSF levels of OT and NP do not change when these peptides are released from the pituitary, we conclude that the presence of these peptides in CSF reflects activity of extrapituitary terminals and that these terminals are not activated during suckling.

Journal ArticleDOI
TL;DR: It is concluded that charge is an important determinant of protein entry into the CSF.
Abstract: Entry of proteins into the cerebrospinal (CSF) from the blood is partially determined by the size of the protein. To determine whether other characteristics of proteins influence CSF entry, proteins or protein fragments were iodinated, inoculated intravenously, and serum and CSF were sampled at later times. The Fc fragment of immunoglobulin G (IgG) did not enter the CSF significantly better than the Fab fragment suggesting that choroidal Fc receptors are not of importance for selective immunoglobulin entry. To determine the role of protein charge on entry, bovine serum albumin [isoelectric point (pI) = 3.9] was chemically altered to provide an albumin with an average pI of 6 (A-6) and another with a pI of 8.5 (A-8). All albumins were of the same size on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A-8 entered the CSF approximately 10-fold better than the native albumin. A-6 was intermediate, entering approximately twofold better. At the time of increased CSF protein concentration during an acute viral encephalitis these differences were narrowed but not eliminated. It is concluded that charge is an important determinant of protein entry into the CSF.

Journal ArticleDOI
TL;DR: A method is described for percutaneous lumbar cerebrospinal fluid (CSF) cannulation and intrathecal infusion and subsequent CSF sampling that should be useful for measuring various aspects of CSF physiology in the laboratory mouse under normal and pathologic conditions.

Journal ArticleDOI
TL;DR: The kinetics of penetration of radioactive [36Cl]-, [22Na]- and [3H]mannitol into the choroid plexus-CSF brain system was investigated in 1-week, 2-week and adult Sprague-Dawley rats and permeability-surface area products (PA) values for 36Cl and 22Na as determined by the fast component of CSF uptake were determined.

Journal ArticleDOI
01 Aug 1982-Cancer
TL;DR: A slightly prolonged CSF methotrexate half‐life suggested a decreased rate of clearance from the CSF, either due to saturation or destruction of the transport mechanisms.
Abstract: A nine-year-old boy with non-Hodgkin's lymphoma inadvertantly received 54 times the standard dose of intrathecal methotrexate (650 mg vs 12 mg). He sustained an immediate and subsequently fatal necrotizing leukoencephalopathy despite an early cerebrospinal fluid (CSF) exchange, intravenous leucovorin and dexamethasone, and supportive care. Following the CSF exchange which removed 78% of the administered dose of methotrexate, the CSF and serum methotrexate levels were 50-100-fold higher than seen following standard therapy. A slightly prolonged CSF methotrexate half-life suggested a decreased rate of clearance of methotrexate from the CSF, either due to saturation or destruction of the transport mechanisms. CSF levels of myelin basic protein and serum levels of lactic dehydrogenase, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, and uric acid were all markedly increased, suggesting both white and grey matter necrosis.

Journal ArticleDOI
TL;DR: Evidence is provided that the choroid plexus contains an active nucleoside transport system of low specificity for nucleosides, and a separate, saturable efflux system forucleosides that is very sensitive to inhibition by NBTI.

Journal ArticleDOI
01 Jul 1982-Cancer
TL;DR: Serial assessment of CSF myelin basic protein levels in patients receiving intrathecal chemotherapy may be useful in the early diagnosis of this disorder.
Abstract: An 11-year-old boy developed a severe myelopathy after an eight-year history of acute lymphoblastic leukemia and numerous courses of intrathecal chemotherapy. Myelin basic protein in the cerebrospinal fluid (CSF) was elevated. Neuropathologic examination disclosed extensive microvacuolar changes in the white matter of the spinal cord. The pathogenesis of myelopathy following intrathecal chemotherapy administered by lumbar puncture includes an early effect on the myelin sheath. Serial assessment of CSF myelin basic protein levels in patients receiving intrathecal chemotherapy may be useful in the early diagnosis of this disorder.

Journal ArticleDOI
TL;DR: A new hypothesis that excess cyclic AMP in the inner ear may be related to endolymphatic hydrops is presented, and the possible role of this second messenger in the regulation of inner ear fluid metabolism is discussed.

Journal ArticleDOI
TL;DR: The present results suggest that the biochemical changes between grade 2 and grade 4 hepatic coma could be due to an inhibition of dopamine beta-hydroxylase, and that the biogenic amines measured in the CSF are of central origin and that their quantification in human lumbar fluid gives new information on the central mechanisms involved in hepatic encephalopathy.

Journal ArticleDOI
TL;DR: The addition of branched-chain amino acids to the infusate may have prevented coma by competing with the aromatic acids for transport across the blood-brain barrier.

Journal ArticleDOI
TL;DR: Arachnoid villi from cynomolgus monkeys subjected to various states of cerebrospinal fluid absorption have been examined with scanning and transmission electron microscopy and the significance of these findings was discussed in relation to CSF absorption and to previously reported ultrastructural studies.

Journal ArticleDOI
TL;DR: A highly significant positive correlation was found between seizure excitability and CSF GABA level, but not between CSF and plasma GABA concentrations.
Abstract: Various studies suggest that alterations in GABAergic function may be connected to epileptic seizures. Low CSF GABA levels have been reported in epilepsy and also febrile convulsions of children. In this study the pentet-razole seizure threshold of dogs was compared with the concentration of GABA in the CSF and blood plasma. A highly significant positive correlation was found between seizure excitability and CSF GABA level, but not between CSF and plasma GABA concentrations.

Journal ArticleDOI
TL;DR: Cerebrospinal fluid gamma-aminobutyric acid (CSF-GABA) was analysed by radioreceptor assay in 16 normal controls and 84 patients with various neurological and psychiatric diseases, finding decreased levels in patients with spinocerebellar degeneration, neuro-Behçet's syndrome and Parkinson's disease and increased levels in Patients with meningitis.
Abstract: Cerebrospinal fluid gamma-aminobutyric acid (CSF-GABA) was analysed by radioreceptor assay in 16 normal controls and 84 patients with various neurological and psychiatric diseases. In patients with spinocerebellar degeneration, neuro-Behcet's syndrome and Parkinson's disease, CSF-GABA levels were decreased. On the other hand, increased CSF-GABA levels were detected in patients with meningitis.

Journal ArticleDOI
TL;DR: Three hours after endotoxin increased protein concentrations in cerebrospinal fluid were seen, results compatible with blood‐brain barrier damage and penetration of other substances; e.g. monoamines released during endotoxinaemia could be expected to have a direct influence on both cerebral blood flow and metabolism.
Abstract: Cerebral blood flow (CBF), cerebral oxygen uptake (CMRO2) and central haemodynamics in anaesthetized dogs with controlled ventilation were studied at intervals for 2 h following an intravenous injection of E. coli endotoxin, 1.0-1.5 mg/kg. CBF showed a 30% decrease within 15 min after the endotoxin administration, while the arterial blood pressure was still not markedly depressed. Autoregulation to arterial blood pressure changes was maintained during endotoxinaemia and the cerebrovascular reaction to changes in arterial carbon dioxide tension (PaCO2) depressed. Normocapnic animals (PaCO2) greater than or equal to 4.0 kPa) showed an increase in CMRO2 of over 40%, that was obvious 1 h after the administration of endotoxin. The intracranial pressure was decreased with 5 min of the administration of endotoxin irrespective of the prevailing arterial blood pressure. Thereafter, it was raised above the control level. Two hours after endotoxin increased protein concentrations in cerebrospinal fluid were seen, results compatible with blood-brain barrier damage and penetration of other substances; e.g. monoamines released during endotoxinaemia could thus be expected to have a direct influence on both cerebral blood flow and metabolism.

Journal ArticleDOI
TL;DR: It is concluded that acetazolamide and furosemide markedly inhibit the transport mechanism(s) in the cat CP that are responsible for CP secretion which represents about 40--60% of the total CSF production and that K transport is also affected.
Abstract: The effect of acetazolamide and furosemide on choroid plexus (CP) production and electrolyte composition of cerebrospinal fluid (CSF) from the cat CP in situ was investigated. Both drugs decreased CSF production by the CP by 50--90% from a control rate of 0.53 microL . min-1 . mg-1 CP within 1.5--2.5 h after the start of drug treatment. The results were similar whether the drug was administered intravenously or applied directly to the CSF side of the CP. A number of experiments in which the effect of administering drugs via the chamber were studied were continued with the drugs removed by washing the preparation with drug-free artificial CSF and the responses measured. The results demonstrated that the effects of acetazolamide and furosemide were reversed during the 1st h following the washout. Both drugs decreased K concentration of nascent CSF when administered intravenously and furosemide also did so when administered on the CSF side of the CP. It is concluded from these and previous data that acetazolamide and furosemide markedly inhibit the transport mechanism(s) in the cat CP that are responsible for CP secretion which represents about 40--60% of the total CSF production and that K transport is also affected.

Journal Article
H W Kreth, L Kress, Hans G. Kress, H F Ott, G Eckert 
TL;DR: Results show that specifically sensitized cytotoxic T cells (CTL) are induced in patients with mumps meningitis, and it is proposed that mumps-specific CTL play an immunopathologic role.
Abstract: Cryopreserved lymphocytes from venous blood and cerebrospinal fluid (CSF) of 10 children with mumps meningitis were tested in 5-hr 51Cr-release assays against uninfected and mumps virus-infected PHA-blasts. Lymphocytes from all patients were cytotoxic to autologous mumps virus-infected target cells, but completely failed to lyse histoincompatible virus-infected PHA-blasts. Cytotoxicity was specific for the infecting virus, and was mediated by E rosette-forming lymphocytes. The effector cells were present over 2 to 3 wk after onset of meningitis. Mumps viral antigens appeared to be preferentially recognized in association with HLA B determinants. The results show that specifically sensitized cytotoxic T cells (CTL) are induced in patients with mumps meningitis. These cells circulate in venous blood and are locally enriched in CSF. Based on clinical observations, it is proposed that mumps-specific CTL play an immunopathologic role.

Journal ArticleDOI
15 May 1982-Cancer
TL;DR: More consistent adherence to the already published recommendation of platelet transfusion immediately prior to LP in patients with low platelets is argued for.
Abstract: Despite knowledge of the bleeding hazard to thrombocytopenic cancer patients undergoing lumbar puncture (LP), a retrospective analysis of physician behavior at one hospital revealed no consistent use of platelet transfusions in patients with less than 20,000 platelets/mm3 on the day of LP. A review of the literature and laboratory cerebrospinal fluid (CSF) data in two institutions, and the performance of an LP experiment revealed that: (1) Batson's epidural venous plexus is an unlikely source and spinal radicular vessels are the most probable source of needle-induced blood in lumbar puncture; (2) the frequency of encountering needle-induced blood at LP is high, 73% (3) the frequency of brushing a nerve root, with the associated risk of lacerating the radicular artery or vein on its surface with the bevel of the LP needle, is high and may be on the order of 26%; and (4) while the passage of an LP needle, obturator in place, through a blood filled vein may carry red cells into a red cell-free medium, this does not always occur. These new considerations argue for more consistent adherence to the already published recommendation of platelet transfusion immediately prior to LP in patients with low platelets. This issue is of particular relevance to the rapidly growing population of thrombocytopenic cancer patients with extended survival on multiple chemotherapeutic regimens requiring lumbar puncture.

Journal ArticleDOI
TL;DR: It is concluded that prolactin has relatively ready access to CSF, especially in comparison to growth hormone, which shows inconsistent plasma patterns after morphine but a late rise following DAMME.

Journal ArticleDOI
01 Nov 1982-Cancer
TL;DR: After intraventricular administration of methotrexate, patients with overt CNS leukemia retained MTX in the CSF significantly longer than patients treated prophylactically, due to abnormal transport of MTX out of theCSF in patients with meningeal disease.
Abstract: A pharmacokinetic study of methotrexate (MTX) administered by the intravenous (IV) and intraventricular (via an Ommaya reservoir) route was performed in 16 children, 13 with acute lymphocytic leukemia (ALL) and three with non-Hodgkin's lymphoma Five children with ALL were treated "prophylactically" for presumed subclinical central nervous system (CNS) leukemia The remaining 11 patients were treated for overt meningeal involvement MTX was administered intravenously at a dose of either 500 mg/m2 or 1500 mg/m2 with one third by rapid intravenous infusion and two thirds intravenously over 24 hours with leucovorin rescue Intraventricular MTX was given in some treatment courses at a dose of 12 mg/m2 At either 500 mg/m2 or 1500 mg/m2, when given only IV, MTX results in a 100 fold higher concentration in plasma compared to cerebrospinal fluid (CSF) The plasma levels are three times higher with the 1500 mg/m2 dose compared to the 500 mg/m2 dose After intraventricular administration of MTX, patients with overt CNS leukemia retained MTX in the CSF significantly longer than patients treated prophylactically This may be due to abnormal transport of MTX out of the CSF in patients with meningeal disease