Effects of mannitol and furosemide on the rate of formation of cerebrospinal fluid

The inhibitory effects of two different diuretic agents—mannitol and furosemide—on the rate of production of cerebrospinal fluid (CSF) were examined in cats by ventriculocisternal perfusion; each animal served as its own control. In 26 cats, mannitol effected as much as an 89% decrease in CSF formation as the serum osmolality was raised from 311 to 336 mosmol/liter by intravenous mannitol infused at rates from 2 to 10 mg/kg/min. The degree of decrease was a linear function of the rise in serum osmolality. Furosemide was shown to reduce CSF production by as much as 94% when intravenous doses of 0.87 to 20.3 mg/kg were used in 25 animals. The decrease was dependent on the natural logarithm of the dose. Intraventricular furosemide at concentrations of 0.06 to 0.24 mg/ml was very effective in 10 cats, without causing saluresis or diuresis. This effect was also linearly related to the natural logarithm of the concentration.     

Inhibition of cerebrospinal fluid formation by omeprazole

Omeprazole, a specific inhibitor of H(+)-K(+)-activated ATPase, gave a dose-dependent inhibition of CSF production as determined by cerebroventriculocisternal perfusions in the rabbit. The reduction was 35% when the perfusate concentration of omeprazole was 10(-6) M and 25% after an intravenous dose of 0.2 mg/kg of omeprazole, respectively. A similarly substituted benzimidazol (H178/42) without H(+)-K(+)-ATPase-inhibiting properties did not affect CSF production at a perfusate concentration of 10(-5) M. Omeprazole in a concentration of 2 x 10(-4) M and more caused a significant but variable reduction in total and Na(+)-K(+)-ATPase activity in choroid plexus homogenates. However, in concentrations of 2 x 10(-5) M and less, no effect on total or Na(+)-K(+)-ATPase activity was obtained. Nor did omeprazole (2 x 10(-4) M) influence HCO3-ATPase. Choline uptake in isolated choroid plexus was significantly reduced by 86% in the presence of acid-pretreated omeprazole 2 x 10(-3) M, but was not affected by 2 x 10(-5) M omeprazole (intact or acid-pretreated). Thus, the mechanism for the marked inhibitory influence of omeprazole on CSF production is not yet evident. In doses causing even a 50% reduction of CSF production, no side effects were observed in contrast to Na(+)-K(+)-ATPase inhibitors such as ouabain.     

How to assess cerebrospinal fluid flow rate

The kinetics of cerebrospinal fluid can be analyzed equally well with velocity imaging and 3D T2-weighted flow sensitive sequences. These techniques constitute a valuable evaluation for intracranial and spinal CSF obstructive pathology.     

Method and clinical significance of cerebrospinal fluid spectrophotometry

The results of the spectrophotometric analysis of 932 cerebrospinal fluid specimens are presented. The specimens were obtained from 95 patients with subarachnoid and intracerebral hemorrhages, 75 patients with traumatic head injuries, 40 patients with infectious diseases of the central nervous system, 302 patients with cerebrovascular accidents and 302 patients suffering from a variety of diseases such as multiple sclerosis, herniated intervertebral discs and vasomotor headache. Normal cerebrospinal fluid is colourless and shows a spectrophotometric absorption characterized by a flat curve with decreasing absorption from 350 to 650 nm. In disease states Oxy-Hemoglobin, Met-Hemoglobin and Bilirubin can be identified in cerebrospinal fluid. These pigments, when present in cerebrospinal fluid, change the spectrophotometric curve due to their specific absorption spectra. According to the quantitative relationship between the pigments and their chronological order of appearance in the cerebrospinal fluid, typical spectrophotometric patterns have been delineated. The spectrophotometric absorption curve of a hemorrhage due to rupture differs from that of a diapedetic hemorrhage. Moreover, tap bleeding results in an absorption curve which can be differentiated early from that of a subarachnoid hemorrhage. Finally, artifacts due to desinfectants can easily be identified. It is concluded that the spectrophotometric analysis of cerebrospinal fluid gives helpful information in subarachnoidal-hemorrhage, subdural and intracerebral hematoma, in contusions of the brain, carcinomatosis of the leptomeninx, spinal tumor and meningoencephalitis of unknown origin.     

The effect of furosemide and bumetanide on cerebrospinal fluid formation

Complete inhibition of carbonic anhydrase maximally reduces CSF flow 40–60%³⁴. We have confirmed that CSF flow in rabbits may be maximally decreased in this way by acetazolamide 30 mg/kg i.v., but have found only about 20% reduction from control after furosemide at 50 mg/kg i.v. This effect of furosemide is consistent with specific but partial inhibition of carbonic anhydrase of choroid plexus (and perhaps other sites of CSF secretion) based on the affinity of furosemide for carbonic anhydrase. Bumetanide, with 7 times lower affinity for carbonic anhydrase and 14–40 times higher inhibition of renal electrolyte transport processes than furosemide^2,18,30, did not decrease CSF flow.     

Comparison of radio-iodinated serum albumin and blue dextran as indicators to measure rate of formation of cerebrospinal fluid.

The characteristics of two nondiffusible indicators, ¹²⁵I-labeled albumin (RISA-125) and blue dextran, were compared by using them simultaneously to measure rate of formation of cerebrospinal fluid (CSF) in in vitro experiments and in a series of ventriculocisternal perfusion experiments in rhesus monkeys. Mean CSF formation calculated from the dilution of RISA-125 was 37.6 μl/min (±0.74 sem); the CSF formation calculated from the corresponding dilution of blue dextran was 37.1 μl/min (±0.70 sem). The difference is not statistically significant. As measured by counts per minute, the concentration of RISA-125 in aliquots of a dilute RISA-125 solution varied considerably. In the in vitro experiments, simulated CSF formation calculated from these counts varied around the mean by more than ± 10% at the 95% confidence limits. Counting variability is probably related to the low energy levels of the ¹²⁵I isotope. Cerebrospinal fluid formation calculated from the dilution of blue dextran had one-tenth the coefficient of variation of that calculated from the dilution of RISA-125. We have concluded that blue dextran is preferable to RISA-125 to measure the rate of formation of cerebrospinal fluid in the experimental setting because it is easier to detect accurately small changes of CSF formation with blue dextran.     

Effect of 5-hydroxytryptamine on the rate of cerebrospinal fluid production in rabbit

Infusion of 5-hydroxytryptamine in mock cerebrospinal fluid of rabbits lowered cerebrospinal fluid production dose-dependently by nearly 30%. The effect was amplified in the presence of the monoamine oxidase inhibitor, nialamide. The 5-hydroxytryptamine-induced inhibition was partly counteracted by ketanserin, and further addition of practolol completely blocked the reduction in cerebrospinal fluid formation, suggesting that both 5-hydroxytryptamine receptors and beta 1-adrenergic receptors were involved in the response mediated by both the secretory epithelium and the vascular bed of the plexus.     

The effects of aluminum chloride on the rate of secretion of the cerebrospinal fluid

The claim that AlCl3 could produce 100% inhibition of cerebrospinal fluid secretion was investigated using ventriculocisternal perfusion in the rabbit, and it was shown that a large part of this inhibition was an artefact due to a pH sensitivity of Blue Dextran, used as an indiffusible marker, caused by AlCl3. Thus the true inhibition found by us, using [3H]labeled markers, was about 33% and usually only partly reversible. Penetration of 22Na from blood into the perfused ventricles was partially inhibited by AlCl3. The effects of some other acid buffer systems, namely acetate and phosphate, on rate of secretion were measured; the results were highly variable. When mean arterial pressure was measured, it was found to be unaffected by AlCl3 but elevated with acetate and phosphate buffer mixtures.     

The proliferation rate of T and B lymphocytes in cerebrospinal fluid

Summary An immunocytochemical method is presented by which individual proliferating T and B lymphocytes can be detected in the cerebrospinal fluid (CSF) of patients with inflammatory and neoplastic diseases of the central nervous system. The absolute numbers of proliferating T and B lymphocytes were approximately equal, so that only a minority of the strongly prevailing T-cell population proliferates in the CSF during the immune process. The highest proliferation (25.7%) was found within the small subset of activated, i.e. cytoplasmic immunoglobulin-containing, B lymphocytes. This provides further evidence that these cells are not the terminally differentiated plasma cells of classical cytology but progenitor cells capable of further proliferation. B-cell lymphomas could be easily identified. The detection of abnormally proliferating cell subsets could help in the differentiation of opportunistic infection from leukaemic infiltration     

The cerebrospinal fluid production rate is reduced in dementia of the Alzheimer's type.

OBJECTIVE: To evaluate the production rate of CSF in patients with differing disease states. METHODS: The authors measured the production rate of CSF in three groups of patients: five patients with PD below age 60 (aged 51 +/- 4 years, mean +/- SD), nine with PD over age 60 (aged 69 +/- 6 years, mean +/- SD), and seven with dementia of the Alzheimer's type (AD) (aged 72 +/- 9 years, mean +/- SD). This method, based on the Masserman technique, employs ventricular rather than a lumbar access to the CSF space. Furthermore, the volume of CSF removed during the procedure is only 3 mL rather than 10 mL. RESULTS: These measurements indicate that the mean rate of CSF production in patients with PD under age 60 was 0.47 +/- 0.13 mL/minute, in patients with PD aged 60 or older the mean rate was 0.40 +/- 0.12 mL/minute, and in patients with AD the mean rate was 0.20 +/- 0.06 mL/minute. CONCLUSION: These results indicate that the rate of CSF production in patients with PD is normal, and that the rate of CSF production in patients with AD is markedly reduced.     

Sources of error in measuring cerebrospinal fluid formation by ventriculocisternal perfusion.

Ventriculocisternal perfusion is regarded as a precise method of measuring the rate of formation of cerebrospinal fluid (CSF) but it possesses inherent potential sources of error. Using the technique to measure CSF formation rate in the rhesus monkey, we have observed rate changes when none were expected. Most puzzling has been the steady decline of CSF formation rate at 4 percent each hour during the final five hours of a seven hour perfusion although variables known to affect CSF formation remained stable. In addition, alterations in rate caused by artefacts were observed in experiments in which craniospinal blood volume was changed by sudden changes of either PCO2 or central venous pressure. Mobilisation or sequestration of incompletely equilibrated CSF is believed responsible. In other experiments, a small increase of intracranial pressure produced by increasing outflow resistance was quickly followed by an apparent reduction of CSF formation. We have concluded that to assess accurately the effect a variable has on the rate of CSF formation, one must control perfusion time and craniospinal blood volume as well as intracranial pressure.     

IgE in the cerebrospinal fluid

The level of IgE in the cerebrospinal fluid (CSF) was determined by particle counting immunoassay. With a limit of sensitivity of 0.2 IU/ml, this immunoglobulin was detected neither in CSF of non-neurological patients (n = 27) nor of patients with sciatica (n = 13). IgE was present in samples from some patients with either multiple sclerosis (MS) or various infections of the central nervous system. In these cases, an IgE index [CSF IgE/serum IgE: CSF albumin/serum albumin] was calculated as 0.29 (SD 0.12). This value is not abnormal as the mean IgG and monomeric IgA indices are 0.45 and 0.34, respectively. Therefore, the IgE detected in most of the CSF samples was not locally produced. However, most patients with tuberculous meningitis had clearly an increased IgE index suggesting a local biosynthesis, but we failed to detect any IgE antibody activity against purified protein derivatives.     

Idiopathic hypotension of the cerebrospinal fluid

A case of spontaneous hypotension of the cerebrospinal fluid (CSF) is reported. A 32 years-old woman was complaining of intense orthostatic headaches. CT scan showed slit ventricles and the spinal tap showed a pressure of the CSF too low to be measured. A sample of clear CSF could only be obtained by aspiration. The patient's status improved without drugs by simply staying in bed for one week. Few similar cases have been reported. The mechanisms of this disorder still remains unknown.