Reduction of cerebrospinal fluid pressure by hypocapnia: changes in cerebral blood volume, cerebrospinal fluid volume and brain tissue water and electrolytes. II. Effects of anesthetics

Part I of these studies (Artru, 1987) examined how cerebral blood volume (CBV), CSF volume, and brain tissue water and electrolytes determined CSF pressure during 4 h of hypocapnia in sedated dogs. The three groups reported were: hypocapnia (PaCO2 20 mm Hg) with no intracranial mass (group 1), intracranial mass (epidural balloon, CSF pressure 35 cm H2O) but no hypocapnia (group 2), and intracranial mass with hypocapnia used to lower CSF pressure (group 3). It was found that in dogs with an intracranial mass (group 3) the CSF pressure-lowering effect of hypocapnia was sustained for 4 h due to improved reabsorption of CSF, decrease of CSF volume to offset reexpansion of CBV and no increase in the sum of CSF volume and CBV. The present Part II studies (groups 4-8) examine the effects of anesthetics on CSF pressure during conditions like those used for group 3, namely, intracranial mass present and hypocapnia used to lower CSF pressure. When halothane or enflurane were used for anesthesia, the CSF pressure-lowering effect of hypocapnia was not sustained. CSF pressure increased from 17.3 +/- 4.7 and 19.0 +/- 4.1 cm H2O, respectively (mean +/- SD), at 10 min to 50.3 +/- 12.8 and 43.2 +/- 12.8 cm H2O, respectively at 4 h. Increase of CSF pressure was associated with increased resistance to reabsorption of CSF (Ra) and increase in the sum of CSF volume and CBV. With halothane the intracranial volume increase was comprised chiefly of cerebral blood and with enflurane the intracranial volume increase was comprised chiefly of CSF. When isoflurane, fentanyl, or thiopental were used for anesthesia, the CSF pressure-lowering effect of hypocapnia was sustained. Ra did not increase and the sum of CBV and CSF volume remained reduced.     

Human cerebrospinal fluid somatostatin in neurologic disease

Concentrations of somatostatin-like immunoreactivity (SLI) were examined in human cerebrospinal fluid (CSF). To validate the assay it was shown that CSF which had been run over a somatostatin immunoaffinity column showed no interference with binding of synthetic standards. Reversed phase HPLC showed that the immunoreactive material coeluted with SS14 and SS28 as well as a higher molecular weight precursor. Concentrations of human CSF SLI were stable at both room temperature and 4 degrees C for up to 72 h while repeated freezing and thawing resulted in a significant loss of immunoreactive material after the 3rd repetition. In normal control patients less than 55 years of age, CSF SLI was 54.7 +/- 1.9 pg/ml, while in those older than 55 CSF SLI was 56.2 +/- 2.2 pg/ml. Febrile infants had significantly higher levels (75.4 +/- 7.3) pg/ml. CSF SLI was normal in patients with aseptic meningitis (54.4 +/- 3.4 pg/ml), suggesting that increased CSF protein and white cell counts do not affect concentrations. Concentrations of CSF SLI were significantly increased in intervertebral disc disease (65.1 +/- 5.6 pg/ml), intrinsic spinal cord pathology (101.0 +/- 23.9 pg/ml), central nervous system tumors (78.0 +/- 7.8 pg/ml) and acute cortical damage of varied etiology (277.8 +/- 81.6 pg/ml). Patients with pseudotumor cerebri had concentrations of 43.2 +/- 2.5 pg/ml. Concentrations of CSF SLI were significantly reduced (P less than 0.01) in multiple sclerosis (38.8 +/- 5.5 pg/ml) and old cortical pathology (23.2 +/- 3.9 pg/ml). Serial CSF analysis in patients with acute CNS lesions, suggest that CSF SLI may be a neurochemical marker of acute pathology, as the initially elevated levels fell to or below normal with resolution of the pathologic process.     

Subarachnuid cerebral hemorrhage treated with unequal volume of cerebrospinal fluid replacement

Objective To asscss the effcct and safely of treatment with unequal volume replacement of cerebrospinal fluid(CSF) in cases of subarachnosd hemorrhage(SAH). Background 48 cases of SAH were seleeted which comply to the diagnostic standard set bh the 2nd National meeting of cerebro-vascular diseases and confirmed by CT and CSF examination. Randomly 24 cases were treated as above called treated cases and the other 24 cases as control. Method Treated Treated cases, after successful spinal puncture, 5to 10 ml of CSF were withdrawn. Normal saline were replaced but the volume were 2ml less than the amount withdraw. This is repeated until 6-10ml were withdrawn. The last injeetion of normal saline was aeeompanied with 5mg of dexamethasonum. Cases treated replacement were between 1 to 4times. Result After replacement intracranial pressure (ICP) were generally lowered and headache immediately lcssened or relieved. No further bleeding or herniation of brain occurred. Discussion At present the replaccment of CSF are generally of equal volame. This may cause recurrent bleeding or herniation of brain. After unequal volume replacement, great fluctuation of ICP bu comparison may be lowered. In treated cases duration of headache cerebral vasospasm(CVS), ocurance of hydrocephlus were generally less than the control cases(p＜0.05). No intracranial infection in treated casea. Conelusion Unequal volume replacement of CSF in treatment of SAH is effeetive. It is safer than equal volume replacement     

Intracranial cerebrospinal fluid measurement studies in suspected idiopathic normal pressure hydrocephalus,secondary normal pressure hydrocephalus,and brain atrophy

OBJECTIVE: To investigate intracranial cerebrospinal fluid (CSF) distribution in patients with a clinical diagnosis of idiopathic normal pressure hydrocephalus (INPH). METHODS: 24 patients with a clinical diagnosis of INPH were studied. Control groups comprised 17 patients with secondary normal pressure hydrocephalus (SNPH), 21 patients with brain atrophy, and 18 healthy volunteers. Ventricular volume (VV) and intracranial CSF volume (ICV) were measured using a magnetic resonance based method and the VV/ICV ratio was calculated. RESULTS: The SNPH group showed a marked increase in the VV/ICV ratio compared with the healthy volunteers (37.8% v 15.6%, p < 0.0001). The brain atrophy group showed a significant increase in ICV compared with the healthy volunteers (284.4 ml v 194.7 ml, p =0.0002). The INPH group showed an increase in ICV (281.2 ml, p = 0.0002) and an increase in the VV/ICV ratio (38.0%, p < 0.0001). Fifteen of 24 INPH patients underwent shunting; 11 improved and four did not. CONCLUSIONS: The results suggest that INPH patients have brain atrophy in addition to hydrocephalic features. This may help to explain the difficulties encountered in the diagnosis and the unpredictable response rate to shunt surgery in INPH patients.     

CT measures of cerebrospinal fluid volume in alcoholics and normal volunteers

Cranial computed tomography (CT) scans were obtained in 46 male chronic alcoholics and 31 normal male volunteers. Automated methods were used to estimate the cerebrospinal fluid (CSF) volume in various intracranial zones. Measures of the ventricular fluid volume, the volume of fluid in cortical areas on CT sections at the level of the ventricles, and the sulcal fluid volumes on two convexity sections were computed. The alcoholic group, excluding subjects with chronic liver disease, had significantly more fluid than the control group on all sulcal measures. The group difference on the ventricular measure fell short of significance. Within the alcoholic group, no significant correlation was found between the number of years of alcoholism and any fluid measure when normal age effects were taken into account. A striking degree of variability in the sulcal volumes was observed within the alcoholic group, with many subjects showing normal values while a large group showed markedly elevated values. Further studies will be necessary to determine the significance of these variations.     

Intracranial pressure,its components and cerebrospinal fluid pressure–volume compensation

Clinical measurement of intracranial pressure (ICP) is often performed to aid diagnosis of hydrocephalus. This review discusses analysis of ICP and its components' for the investigation of cerebrospinal fluid (CSF) dynamics. The role of pulse, slow and respiratory waveforms of ICP in diagnosis, prognostication and management of hydrocephalus is presented. Two methods related to ICP measurement are listed: an overnight monitoring of ICP and a constant‐rate infusion study. Due to the dynamic nature of ICP, a ‘snapshot’ manometric measurement of ICP is of limited use as it might lead to unreliable results. Therefore, monitoring of ICP over longer time combined with analysis of its waveforms provides more detailed information on the state of pressure–volume compensation. The infusion study implements ICP signal processing and CSF circulation model analysis in order to assess the cerebrospinal dynamics variables, such as CSF outflow resistance, compliance of CSF space, pressure amplitude, reference pressure, and CSF formation. These parameters act as an aid tool in diagnosis and prognostication of hydrocephalus and can be helpful in the assessment of a shunt malfunction.     

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.     

Changes in cranial CSF volume during hypercapnia and hypocapnia.

Magnetic resonance imaging was used to measure the effect of inhalation of 7% CO2 and hyperventilation with 60% O2 on human cranial cerebrospinal fluid volume. During CO2 inhalation there was a reduction in the cranial CSF volume ranging from 0.7-23.7 ml (mean 9.36 ml). The degree of reduction in cranial CSF volume was independent of the individual subject's increase in end-expiratory pCO2 or mean arterial blood pressure, in response to hypercapnia. During hyperventilation with high concentration oxygen the cranial CSF volume increased in all subjects (range 0.7-26.7 ml, mean 12.7 ml). The mean changes in cranial CSF volume, induced by hypercapnia and hypocapnia, were very similar to the expected reciprocal changes in cerebral blood volume.     

Changes in the arterial fraction of human cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography.

Hypercapnia induces cerebral vasodilation and increases cerebral blood volume (CBV), and hypocapnia induces cerebral vasoconstriction and decreases CBV. Cerebral blood volume measured by positron emission tomography (PET) is the sum of three components, that is, arterial, capillary, and venous blood volumes. Changes in arterial blood volume (V(a)) and CBV during hypercapnia and hypocapnia were investigated in humans using PET with H(2)(15)O and (11)CO. Arterial blood volume was determined from H(2)(15)O PET data by means of a two-compartment model that takes V(a) into account. Baseline CBV and values during hypercapnia and hypocapnia in the cerebral cortex were 0.034+/-0.003, 0.038+/-0.003, and 0.031+/-0.003 mL/mL (mean+/-s.d.), respectively. Baseline V(a) and values during hypercapnia and hypocapnia were 0.015+/-0.003, 0.025+/-0.011, and 0.007+/-0.003 mL/mL, respectively. Cerebral blood volume changed significantly owing to changes in PaCO(2), and V(a) changed significantly in the direction of CBV changes. However, no significant change was observed in venous plus capillary blood volume (=CBV-V(a)). This indicates that changes in CBV during hypercapnia and hypocapnia are caused by changes in arterial blood volume without changes in venous and capillary blood volume.     

Dynamics of the cerebrospinal fluid and the spinal dura mater

During myelography we observed the contrast material in the spinal subarachnoid space while we changed: (1) the intracranial blood volume by CO₂ inhalation, hyperventilation, and jugular vein compression; (2) the intra-abdominal and intrathoracic pressure by forced expiration with glottis closed; and (3) the CSF volume by withdrawals and reinjections of fluid. The spinal dural sac enlarges with increases in volume of both intracranial blood and CSF. It partially collapses with reductions in volume of both intracranial blood and CSF. With increases in intra-abdominal and intrathoracic pressure, the thoracolumbar sac partially collapses, while the cervical sac enlarges. From these observations we conclude that the spinal dural sac is a dynamic structure, readily changing its capacity in response to prevailing pressure gradients across its walls. It acts as a reservoir for CSF, which moves to and fro through the foramen magnum in response to changes in cerebral blood flow. By its bladder-like ability to alter its capacity, the spinal dural sac provides the `elasticity' of the covering of the central nervous system.     

Variations of homovanillic acid levels in ventricular cerebrospinal fluid

We studied the nycterohemeral variations of homovanillic acid (HVA) in ventricular cerebrospinal fluid (CSF) in 24 patients undergoing monitoring of intracranial pressure as part of the normotensive hydrocephalus (NTH) work-up. CSF samples were obtained every 4 h in each patient. The mean individual values of HVA in the ventricular CSF ranged from 133 to 421 ng/ml, and they could not be correlated to any clinical feature. The intraindividual levels of HVA were stable throughout 24 hours, with a variation coefficient inferior to 10% in 63% of cases, and inferior to 20% in all the patients.     

Arginine vasopressin levels in cerebrospinal fluid in neurological disease

Levels of arginine vasopressin have been measured in the blood and cerebrospinal fluid of patients with benign intracranial hypertension and raised intracranial pressure, patients with other neurological diseases and in normal control subjects. There was no difference in blood levels in each of the 3 groups (mean ± SEM, 2.8 ± 0.5, 2.5 ± 0.25, 2.53 ± 0.4 pg/ml). However, levels of arginine vasopressin in the cerebrospinal fluid in patients with benign intracranial hypertension and other neurological diseases were higher (mean ± SEM, 0.64 ± 0.05, 0.61 ± 0.04 pg/ml), than in the control group (0.49 ± 0.06), but not different from each other. The origin of arginine vasopressin in cerebrospinal fluid is uncertain and a number of possibilities are discussed.     

Changes in human cerebral blood flow and cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography.

Hypercapnia induces cerebral vasodilation and increases cerebral blood flow (CBF), and hypocapnia induces cerebral vasoconstriction and decreases CBF. The relation between changes in CBF and cerebral blood volume (CBV) during hypercapnia and hypocapnia in humans, however, is not clear. Both CBF and CBV were measured at rest and during hypercapnia and hypocapnia in nine healthy subjects by positron emission tomography. The vascular responses to hypercapnia in terms of CBF and CBV were 6.0 +/- 2.6%/mm Hg and 1.8 +/- 1.3%/mm Hg, respectively, and those to hypocapnia were -3.5 +/- 0.6%/mm Hg and -1.3 +/- 1.0%/mm Hg, respectively. The relation between CBF and CBV was CBV = 1.09 CBF0.29. The increase in CBF was greater than that in CBV during hypercapnia, indicating an increase in vascular blood velocity. The degree of decrease in CBF during hypocapnia was greater than that in CBV, indicating a decrease in vascular blood velocity. The relation between changes in CBF and CBV during hypercapnia was similar to that during neural activation; however, the relation during hypocapnia was different from that during neural deactivation observed in crossed cerebellar diaschisis. This suggests that augmentation of CBF and CBV might be governed by a similar microcirculatory mechanism between neural activation and hypercapnia, but diminution of CBF and CBV might be governed by a different mechanism between neural deactivation and hypocapnia.     

Normal cerebrospinal fluid pressure in the newborn

Lumbar CSF pressure (CSFP) was measured on 61 occasions, in 49 babies undergoing lumbar puncture as part of a septic screen, by means of Gaeltec pressure transducers. In normal circumstances, intracranial pressure (ICP) has the same value. Measurements were made when the baby was horizontal and quiet, with the head deflexed. For acceptance of the measurement, it was essential for the CSF to be clear and to show pressure pulses with respiration, heartbeat and jugular occlusion. The mean CSFP and standard deviation were 2.8 +/- 1.4 mm Hg (3.8 +/- 1.9 cm water), with a normal range of 0 to 5.7 mm Hg (0 to 7.6 cm water). This value is similar to previous reports of CSFP measured invasively in infants, but is much lower than the "ICP" established noninvasively. No relationship was found between birthweight, gestational age, current weight, postmenstrual age, or postnatal age and CSFP.     

Plasma and cerebrospinal fluid gamma-aminobutyric acid in neurological disorders.

In 49 patients with various neurological disorders plasma and CSF gamma-aminobutyric acid (GABA) concentrations were determined by radioreceptor assay. The CSF GABA concentration of 127 +/- 47 pmol/ml (range: 65-275; n = 52) was independent of the age, the sex and the intake of various drugs including benzodiazepines, baclofen and antidepressants. Patients with diverse neurological disorders such as multiple sclerosis, ischaemic strokes, intracranial tumour and polyneuropathies had similar CSF GABA levels. The mean plasma GABA concentration was 309 +/- 79 pmol/ml (range: 179-498; n = 44). The correlation between the GABA concentrations of CSF and plasma was very poor (r = 0.18; n = 44). Therefore plasma GABA is not a suitable indicator for CSF GABA.     

An experimental study of acute subarachnoid haemorrhage in baboons: changes in cerebral blood volume, blood flow, electrical activity and water content.

Subarachnoid haemorrhage following transection of the posterior artery was produced in 10 baboons. Cerebral blood volume (CBV) decreased transiently after subarachnoid haemorrhage. Two basic patterns of intracranial pressure (ICP) were observed; in one ICP returned to normal but in the other it remained elevated. In this latter group four out of five animals showed an increase in CBV above the original level. There were delays in sensory conduction (measured using somatosensory evoked potentials) bilaterally; those on the contralateral side to the bleed were correlated with ICP whereas other factors are implicated on the ipsilateral side. Initial flow reduction and restoration of cerebral blood flow were both correlated with water content.     

Cerebrospinal fluid absorption mechanism--based on measurement of CSF flow rate in shunt tube

The cerebrospinal fluid (CSF) absorption mechanism in cases of hydrocephalus was investigated on the basis of measurements of CSF flow in a shunt tube after ventriculo-peritoneal shunt surgery, monitoring of intracranial pressure, CT findings, radioisotope cisternography, cerebral blood flow, EEG, PSP tests and changes in neurological findings. The subjects were 6 males and 7 females aged from 18 to 70. CSF flow rates in the shunt tubes were between 0.01 and 1.93 ml/min. Calculating the daily volume of CSF flow, the subjects were divided into two groups: Group A (8 patients) with a volume of less than 150 ml/day (0.01-0.25 ml/min), and Group B (5 patients) with between 150 and 500 ml/day (0.01-1.93 ml/min). Monitoring of intracranial pressure prior to the shunt operation was performed in 10 cases. These pressure values ranged between 4 and 25 mmHg (mean: 7-8 mmHg), and there was no difference between the two groups. The pre-and post-operative radioisotope cisternography findings indicated improvement of ventricular dilatation, periventricular lucency and ventricular reflux. After the shunt operations, there was neurological improvement in 6 of the 8 Group A cases but only in 2 of the 5 Group B cases. Considering the CSF flow volumes of the two groups, it appears that in Group A the shunt tube is not the main CSF circulation pathway. This could mean that resistance to CSF absorption in the cerebrospinal space has decreased after the shunt operation and there has been recovery of the physiological CSF absorption pathways. In other words, neurological improvement can be expected in this group A.     

Changes in the intracranial volume-pressure relations and visual evoked potentials produced by stabilized and compensated additional volume]

The experiment was carried out on 17 cats with intracranial volume-pressure relations changed by means of an epidural balloon of 1.0 ml volume (group I--12 cats) and 0.5 ml (group II--5 cats). The duration of compression exerted by the balloon was 360 min. The intracranial pressure, volume-pressure responses, resistance to cerebrospinal pressure resorption and visual evoked potentials were determined at intervals of 60 minutes. In group I pressure exerted by 1 ml balloon was followed by changes of volume-pressure relations and visual evoked potentials which increased with duration of the experiment. In group II the changes were noted only in the volume-pressure responses and resistance to CSF resorption at the time of balloon volume rise from 0 to 0.5 ml. Maintenance of this balloon volume in the cranial cavity caused no further changes of volume-pressure parameters or visual evoked potentials during 360 minutes of the experiment.     

Resistance to drainage of cerebrospinal fluid: clinical measurement and significance

By infusing saline intrathecally at a constant rate until a new steady-state cerebrospinal fluid (CSF) pressure is attained, one can estimate clinically the apparent resistance (Ra) to drainage of CSF in mm saline/ml./minute. This intrathecal saline infusion test (ITSIT) was performed 36 times on 29 patients with diverse intracranial problems, and the results were analysed and, in most cases, compared with the pneumoencephalogram and the isotope cisternogram. The ITSIT is a safe, simple test to estimate Ra, but factors which are difficult to control (occult leaks from the subarachnoid space; independent fluctuations of CSF pressure) limit its reliability and clinical usefulness. If closely correlated with the clinical syndrome, the pneumoencephalogram, and the isotope cisternogram, an ITSIT may identify decisively the patient who needs a shunt. In addition the ITSIT offers another method by which to investigate the pathophysiological mechanisms of the various states of intracranial hypertension. Results from the test performed on four patients with intracranial hypertension of unknown cause (pseudotumor cerebri) suggest that the underlying mechanism in this condition is probably an impediment to normal CSF drainage.     

Cerebrospinal fluid outflow and intracranial pressure in hydrocephalic patients with external ventricular drainage

Klein O, Demoulin B, Jean Auque RT, Audibert G, Sainte‐Rose C, Marchal J‐C, Marchal F. Cerebrospinal fluid outflow and intracranial pressure in hydrocephalic patients with external ventricular drainage.
Acta Neurol Scand: DOI: 2010: 122: 140–147.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background and purpose – The aim of this study was to monitor the 24 h cerebrospinal fluid (CSF) outflow and intracranial pressure (ICP) in hydrocephalic adult patients with external ventricular drainage (EVD). Patients and methods – Twelve patients (5M/7F) aged 30–69 years suffering from acute hydrocephalus requiring EVD were admitted in the neuro‐intensive care unit. The CSF collecting bag was continuously weighted using a high‐precision scale, the filtered output of which was fed at 1 Hz to a computer and converted to flow (Q′ext_csf). ICP was also recorded. Results – One patient was excluded because more than 80% of the Q′ext_csf data were rejected by the system. The mean ± SD Q′ext_csf and ICP were respectively 7.5 ± 3.4 ml/h (range 1.6–12.1 ml/h) and 12.4 ± 2.7 mmHg. Two patterns of Q′ext_csf were identified: a continuous profile and a discontinuous one with numerous bursts frequently associated with manoeuvres such as cough or chest physiotherapy. The short‐term variations of Q′ext_csf and ICP were usually unrelated. Conclusion – The study stresses the important inter and intra‐subject variability of Q′ext_csf in patients with EVD. The mean Q′ext_csf is lower than the reference production rate (21 ml/h), raising the question of persistent CSF absorption and/or depressed secretion. The independent changes of Q′ext_csf and ICP on the short term is likely to be explained by the pressure–volume characteristics of the intracranial space.