Cerebrospinal Fluid Volume Changes Research Articles

Brain structural damage in spinocerebellar ataxia type 2. A voxel‐based morphometry study

Voxel-based morphometry (VBM) enables an unbiased in-vivo whole-brain quantitative analysis of differences in gray matter (GM), white matter (WM) and cerebro-spinal fluid (CSF) volumes. We assessed with VBM 20 spinocerebellar ataxia Type 2 (SCA2) patients with mild or moderate cerebellar deficit and 20 age and sex-matched healthy controls. SCA2 patients showed a significant (P < 0.05 corrected for multiple comparison) symmetric loss of GM in the cerebellar vermis and hemispheres sparing lobules I,II, Crus II,VII, and X, and of the WM in the peridentate region, middle cerebellar peduncles, dorsal pons, and cerebral peduncles. The CSF volume was increased in the posterior cranial fossa. No GM, WM or CSF volume changes were observed in the supratentorial compartment. A mild (P < 0.05, >0.01) correlation was observed between the GM and WM loss and severity of the neurological deficit. In SCA2 patients with mild to moderate cerebellar deficit, GM and WM volume loss and CSF volume increase are confined to the posterior cranial fossa.

Chronic hydrocephalus–induced hypoxia: Increased expression of VEGFR-2+ and blood vessel density in hippocampus

Chronic hydrocephalus (CH) is a neurological disease characterized by increased cerebrospinal fluid volume and pressure that is often associated with impaired cognitive function. By and large, CH is a complex and heterogeneous cerebrospinal fluid (CSF) disorder where the exact site of brain insult is uncertain. Several mechanisms including neural compression, fiber stretch, and local or global hypoxia have been implicated in the underlying pathophysiology of CH. Specifically, the hippocampus, which plays a significant role in memory processing and is in direct contact with expanding CSF ventricles, may be involved. Using our model of chronic hydrocephalus, we quantified the density of vascular endothelial growth factor receptor 2 (VEGFR-2+) neurons, glial, endothelial cells, and blood vessels in hippocampal regions CA1, CA2-3, dentate gyrus and hilus using immunohistochemical and stereological methods. Density and %VEGFR-2+ cell populations were estimated for CH animals (2–3 weeks vs. 12–16 weeks) and surgical controls (SC).Overall, we found approximately six- to eightfold increase in the cellular density of VEGFR-2+ and more than double blood vessel density (BVd) in the hippocampus of CH compared with SC. There were no significant regional differences in VEGFR-2+ cellular and BVd expression in the CH group. VEGFR-2+ and BVds were significantly related to changes in CSF volume (P≤0.05), and not intracranial pressure (ICP). The %VEGFR-2+ was significantly greater in CH than SC (P≤0.05), and was significantly correlated with BVd (P≤0.05).These results showed that CH elicited a profound increase in VEGFR-2+ in hippocampus that corresponded to increased BVd. It was unclear whether increased VEGFR-2+ and blood vessel expression was related to focal compression alone or in combination with global ischemia/hypoxia conditions as previously described. These findings suggest that VEGFR-2 may play an adaptive role in angiogenesis after CH-induced hypoxia. Modulation of vascular endothelial growth factor/VEGFR-2+ may be important in developing treatments for hypoxic conditions including hydrocephalus and other forms of cerebral ischemia.

Absence of regional brain volume change in schizophrenia associated with short-term atypical antipsychotic treatment

The first aim of this pilot study was to determine if longitudinal change in caudate volume could be detected in chronic schizophrenic patients after 12 weeks of atypical antipsychotic treatment. A sub-aim of the first aim was to determine if similar results could be obtained from an operator-assisted segmentation tool for volumetric imaging (ITK-SNAP) and voxel-based morphometry (VBM) methods in the caudate. The second aim was to determine if frontal and temporal lobe grey matter, white matter, ventricular and sulcal cerebrospinal fluid volume change could be detected after 12 weeks of atypical antipsychotic treatment with VBM. Ten chronic schizophrenic inpatients, with illness duration averaging 10.6 years, underwent two MRI scans. The first scan was obtained after a mean of 39.4 days of antipsychotic withdrawal. The second MRI was obtained following twelve weeks of atypical antipsychotic treatment. Caudate volume change was first measured with ITK-SNAP. Then the location of grey matter volume change in the caudate was identified with VBM. Finally, the location of frontal and temporal lobe grey matter, white matter, ventricular and sulcal cerebrospinal fluid volume changes were identified with VBM. No longitudinal change in caudate volume or grey matter volume was observed after brief periods of atypical antipsychotic treatment. ITK-SNAP and VBM methods showed very similar results in the caudate. No statistically significant change was identified in the volume of frontal or temporal lobe grey matter, white matter, and lateral, third, or fourth ventricular cerebrospinal fluid. Although the results do not directly show that brief periods of atypical antipsychotic treatment are associated with basal ganglia and cortical volume change, there is much evidence to suggest that such an association exists.

Simple technique of head fixation for image-guided neurosurgery in infants

Dear Editor: I read with interest the technical note by Agrawal and Steinbok [1] describing the technique of head fixation for image-guided neurosurgery in infants entitled “Simple technique of head fixation for image-guided neurosurgery in infants.” However, we have earlier described a novel technique [3] of using plaster of Paris mould for head fixation during stereotactic surgery in 48 patients, which has not been referenced in the present manuscript. We feel that our technique has important points relating to the fixation of head during image-guided surgery in pediatric patients. It has a crucial bearing on the technique and should have been discussed in relation to the technique described by the authors. It is well known that image-guided surgery in pediatric population is evolving and technical standardization for frame fixation is still not firmly established. The differential variations in the thickness of the calvaria in infants and young children as well as the reduced pin pressure provide impedance in the performance of the procedure. Commercially available pediatric pins are not suitable for fear of depressed fracture. The authors’ technique of using an adhesive drape for firm head fixation obviates the problems related to pin fixation. The authors remark that any kind of pin fixation may be hazardous in infants as changes in cerebrospinal fluid volume can potentially decrease the size of the infants’ head and allow for loss of fixation and scalp lacerations. The authors mention that simultaneous use of pins and horseshoe has been attempted [2]. However, we have recently described a novel method of a plaster of Paris mould for rigid frame fixation to the head using pins during stereotactic surgery in 48 patients [3]. It is a useful adjunct that can help mould to the various sizes and shapes of the head. It circumvents the need for a set of pins of varying length and thickness. The Plaster of Paris cast is simple, easily available, not labor-intensive, and is cost-beneficial. The multiple layers of the plaster of Paris provide and imparts a symmetrical, smooth, and even surface for the pin application. The spatial relation of the stereotactic frame to the “virtual head” remains constant during the entire stereotactic procedure. It is ideal for children with a low pain threshold. Prolonged sedation and anesthesia can be avoided. The authors use an adhesive drape over a horseshoe such that the adhesive edge is partly on the head and partly on the horseshoe and the tails of the adhesive drape stuck down inferiorly along the front of the shoulders and the chest. However, the potential variability in the elasticity of the adhesive drape may be a limiting factor in achieving a rigid head fixation and maintaining the accuracy of registration with the image guidance system. They further remark that the head fixation is not absolutely rigid and there is a possibility of relative motion between the head and the horseshoe. In contradistinction, the plaster of Paris cast is snugly fit around the head and the firm setting of the plaster allows for secure placement of the pins and rigid fixation of the head.

Use of acetazolamide to decrease cerebrospinal fluid production in chronically ventilated patients with ventriculopleural shunts

Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been shown to decrease cerebrospinal fluid (CSF) production in both in vivo and in vitro animal models. We report two children with hydrocephalus...

Longitudinal Volumetric Computed Tomographic Analysis of Regional Brain Changes in Normal Aging and Alzheimer's Disease

This study used a semiautomated image analysis technique to quantify the rate and regional pattern of cerebrospinal fluid (CSF) volume changes in the computed tomographic brain examinations of healthy adults and patients with Alzheimer's disease (AD). Longitudinal, within-subject design, with statistical correction for longitudinal method error (eg, head repositioning effects). Palo Alto (Calif) Department of Veterans Affairs Medical Center. The 41 patients with AD were recruited from the Geriatric Psychiatry Research Unit and the National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 35 healthy control subjects were recruited from the local community. Cerebrospinal fluid volumes estimated from computed tomographic scans. Even after accounting for an estimate of method error (eg, head positioning effects) across computed tomographic examinations, the patients with AD showed greater annual CSF volume increases than did the control group. This CSF volume enlargement was not uniform across brain regions of interest; rather, the patients with AD showed disproportionate volume increases in the ventricular system and the sylvian fissures. Greater CSF volume changes in the patients with AD were significantly associated with greater cognitive decline on the Mini-Mental State Examination. Furthermore, younger patients with AD showed more rapid progression on computed tomographic scans than did older patients. The rate of CSF volume enlargement is region specific, with the most marked annual rate of change occurring in the ventricular system and the sylvian fissures. In addition, younger patients show more rapid progression in the ventricular and frontal sulcal brain regions of interest than do older patients.

Variations in pressure-volume index and CSF outflow resistance at different locations in the feline craniospinal axis

Pressure volume index (PVI) and cerebrospinal fluid (CSF) outflow resistance (Ro) were estimated in spontaneously breathing anestheized cats by the bolus injection test under normal conditions and also under abnormal conditions produced by slow infusion of saline into the CSF space. Bolus injections were made separately into the lumbar subarachnoid space, cisterna magna, and lateral ventricle. The mean PVI values in the lumbar sac, cisterna magna, and lateral ventricle under normal conditions were 0.70, 0.71, and 0.64 ml, respectively; not significantly different from each other. Saline infusion lowered PVI significantly at every site; PVI values in the lumbar sac, cisterna magna, and lateral ventricle were 0.54, 0.52, and 0.53 ml, respectively; not significantly different from each other. Indirect values of PVI were calculated from the pressure responses observed at sites other than where the bolus had been injected. These indirect PVI values were always greater than PVI at the injection site under normal conditions, but differences between direct and indirect PVI values were abolished during saline loading of the CSF space. The Ro was estimated under normal conditions in the lumbar sac, cisterna magna, and lateral ventricle to be 81.6, 85.6, and 110.3 mm Hg/ml/min, respectively. The lateral ventricle Ro was significantly higher than at other places. These findings suggest that, when there is no blockage in the craniospinal axis, the pressure response to a bolus change in CSF volume is freely transmitted, direct measurements of PVI are independent of location, and indirect measurements are larger because of "buffering" in the CSF space. When PVI is lowered and buffering capacity is exhausted, these differences between direct and indirect PVI values disappear.

Changes in cerebrospinal fluid volume and cardiovascular functions induced by intraperitoneal injection of hypertonic glucose solution in rats.

The present experiment was undertaken to study the relationship between hemodynamic changes and intracranial hemorrhage induced by intraperitoneal injection of large doses of hypertonic glucose solution in rats. A fifty per cent glucose solution was intraperitoneally injected at a volume of 3.5 ml/100 g b.w. into Wistar rats anesthetized with urethanechloralose. The time span from the start of injection to death was expressed in terms of 100% corrected death time (100% DT) for each rat. Saline that was added to the cerebrospinal fluid in the brain ventricle disappeared gradually from 30% DT up to death. Blood colloid osmotic pressure was slightly elevated temporally 5 minutes (7% DT) after intraperitoneal injection of the glucose solution and returned to the former level 5 minutes later. With regard to hemodynamic changes, a decrease in blood pressure and heart rate began to occur between 5-10% DT. Thereafter, blood pressure and heart rate decreased significantly as compared with the pretreatment period, and the plasma levels of both epinephrine and norepinephrine showed sharply increasing curves as time elapsed after the intraperitoneal injection of the hypertonic glucose solution. It was suggested that the decrease in cerebrospinal fluid and the fall in blood pressure were related to the movement of water from the brain and the flow of body fluid into the hypertonic blood plasma which caused an enlargement of the ventricles due to brain reduction and a change in circulating blood volume. However, questions still remain concerning the mechanisms of the marked increase in plasma catecholamines and bleedings which occurred only in the subarachnoideal space and ventricles.

Volume/pressure relationship of the cerebrospinal space in humans.

Using constant flow rate infusions and compensating for the fluid formed and eliminated, the net volume/pressure (V/p) relationship of the cerebrospinal fluid (CSF) space in humans was investigated in more than 200 patients. Of these, 16 patients constitute a normal reference material. Reference values for the variables characterizing the V/p relationship are reported. The V/p relationship was found to be nonexponential, which is not consistent with the pressure-volume index theory. The reactivity of the vascular bed during induced CSF volume changes had to be taken into account when analyzing the results. There were reasons to believe that the major volume changes during the recording of the V/p relationship took place in the spinal part of the CSF space and that the pressure of minimal elastance corresponded to the spinal epidural venous pressure.

An interpretation of pressure/volume interactions in the craniospinal axis.

A method is presented to help explain the genesis of cerebrospinal fluid (CSF) pressure changes associated with a variety of alterations within the craniospinal system. Translation of the x-axis is used to convert the usual plot of CSF pressure vs. change in CSF volume (CSF P/ΔV curve) to a plot of

An interpretation of pressure/volume interactions in the craniospinal axis

A method is presented to help explain the genesis of cerebrospinal fluid (CSF) pressure changes associated with a variety of alterations within the craniospinal system. Translation of the x-axis is used to convert the usual plot of CSF pressure vs. change in CSF volume (CSF P/ΔV curve) to a plot of CSF pressure vs. total CSF volume (the CSF P/V curve). This translation permits analysis of craniospinal pressure/volume dynamics in terms of the factors that change CSF equilibrium pressure (Peq) or CSF equilibrium volume (Veq) or that alter the shape of the CSF P/V curve. Changes in Peq are produced only by changes in the net CSF flow/pressure relationship. The shape of the CSF P/V curve changes only in response to alterations in mechanical properties of craniospinal tissues. Veq is altered either by changes in the CSF net flow/pressure curve or by variation in mechanical properties of the tissues around the CSF space. Only CSF volume changes alter CSF pressure by movement of a point along a single P/V curve. Volume changes in all other craniospinal compartments alter CSF pressure by changing Peq, by changing Veq, or by changing the shape of the CSF P/V curve. Depending on how tissue mechanical properties are changed, on how other mechanical factors in the craniospinal axis are altered, and on how the net CSF flow/pressure function has been changed, a perturbation of the craniospinal system may selectively alter Peq, Veq, or the shape of the CSF P/V curve. After a perturbation of the craniospinal system, total CSF volume is related to a new CSF P/V curve to generate a new level of CSF pressure. If changes in the net CSF flow/pressure curve or in tissues around the CSF space occur slowly, CSF pressure and volume may not be significantly different from Peq and Veq, whereas if these changes occur rapidly CSF pressure and volume may be markedly different from Peq and Veq. (Neurosurgery, 6: 453-462, 1980)

Bolus versus steady‐state infusion for determination of CSF outflow resistance

For rapid changes in cerebrospinal fluid volume an exponential relationship was demonstrated between CSF pressure and CSF volume in 15 cats. This relationship was valid over a CSF pressure range from 7 to 50 mm Hg and for acute increases of up to 9% to total CSF volume (approximately 13 ml for humans). Our data agree well with previous reports for the cat. A similar relationship has been shown in the dog and in humans. It has been claimed that, given the equations for CSF bulk flow and the exponential relationship between CSF pressure and CSF volume, one can calculate CSF outflow resistance by observing the decay of CSF pressure after a bolus injection into the CSF space. This claim was evaluated in an additional 18 cats. In these animals CSF outflow resistance calculated by the bolus method was compared with resistance calculated by a steady-state infusion method over the CSF outflow resistance range of 74 to 293 mm Hg/ml min-1. Resistance calculated by the bolus method underestimated resistance calculated by the steady-state method, and this underestimate grew larger with increasing resistance. The bolus technique is therefore not a valid method for determining CSF outflow resistance. The explanation offered for these results is that the decay of CSF pressure after a bolus injection into the CSF space occurs not only because of runoff of the injected volume of CSF but also because of "pressure relaxation" of the brain parenchyma around the CSF space. The phenomenon of pressure relaxation was not considered in developing the equation for calculation of CSF outflow resistance by the bolus technique. The time dependency of pressure relaxation allows for a fundamental element of hysteresis within the CSF space. A method of quantifying this element of hysteresis is suggested.

Compartmental analysis of compliance and outflow resistance of the cerebrospinal fluid system.

The distribution of compliance and outflow resistance between cerebral and spinal compartments was measured in anesthetized, ventilated cats by analysis of the cerebrospinal fluid (CSF) pressure response to changes in CSF volume. Cerebral and spinal compartments were isolated by inflating a balloon positioned epidurally at the level of C-6. The change of CSF volume per unit change in pressure (compliance) and change of CSF volume per unit of time (absorption) were evaluated by inserting pressure data from the experimental responses into a series of equations developed from a mathematical model. It was found that 68% of total compliance is contributed by the cerebral compartment while the remaining 32% is contained within the spinal axis. The cerebral compartment accounted for 84% of total CSF absorption. The mechanism for spinal absorption appears to be similar in that no differences were obvious on the basis of pressure dynamics.

DEHYDRATION AND EPILEPSY

To the Editor: —I have noted inThe Journal, April 1, the report on dehydration and epilepsy by Drs. Fetterman and Kumin, concerning twenty-one epileptic patients observed for a period of about one month. I feel that it is dangerous to reduce a patient's fluids to 100 cc. a day; the purposes and objectives of the method are ignored when carried to this extreme degree. The objective is not to subtract fluid to an intolerable degree, from the customary routine of the patient, but to subtract fluid from the patient's body fluid reservoirs. Unless the patient demonstrates actual loss of body weight, there is no subtraction or no real dehydration. A pint, or 500 cc., weighs approximately one pound, and unless water is subtracted from the body tissue reservoirs there will arise no change in cerebrospinal fluid volume or pressure. If the patient receives sufficient liquids in other forms, such