Abnormal cerebrospinal fluid-blood flow dynamics. Implications in diagnosis, treatment, and prognosis in normal pressure hydrocephalus.

Increased cerebral blood flow (CBF) has been proposed as responsible for the clinical improvement after cerebrospinal fluid (CSF) shunting in patients with normal pressure hydrocephalus (NPH). In order to determine any abnormal CSF-CBF pressure-flow relationships in NPH, measurements of regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) were made before and after lowering CSF pressure (CSFP) in 15 patients with NPH, and in ten patients with presumed hydrocephalus ex vacuo. Maximal reduction of rCBF and rCBV occurred in the territory of the anterior cerebral artery in NPH but no in dementia due to brain atrophy. Both CBF and rCBV increased after lowering the CSFP by lumbar puncture in patients with NPH. Patients with higher preoperative rCBF and maximal increases in rCBR and rCBV after lowering CSFP showed the most consistent clinical improvement after CSF shunting. Evidence is offered that CBF autoregulation is impaired in NPH. The CBF test assists in both diagnosis and selection of patients for CSF shunting.     

Cerebral blood flow in normal pressure hydrocephalus

A xenon-133 method was used to measure cerebral blood flow (CBF) before and after cerebrospinal fluid (CSF) removal in patients with normal pressure hydrocephalus (NPH). Preliminary results suggested that shunting should be performed on patients whose CBF increased after CSF removal. There was a significant increase in CBF in patients with NPH, which was confirmed by the favorable outcome of 88% of patients shunted. The majority of patients with senile and presenile dementia showed a decrease or no change in CBF after CSF removal. It is suggested that although changes in CBF and clinical symptoms of NPH may have the same cause, i.e., changes in the cerebral intraparenchymal pressure, there is no simple direct relation between these two events. The mechanism underlying the loss of autoregulation observed in NPH is also discussed.     

PET and CBF Studies of Chronic Hydrocephalus: A Contribution to Surgical Indication and Prognosis

The authors investigate whether measurement of cerebral blood flow (CBF) in chronic hydrocephalus is a reliable indicator in selecting patients to undergo ventriculoperitoneal shunting. Global and regional CBF is quantified (Kety-Schmidt one-compartment model) by positron emission tomography in 21 patients. CBF is determined following inJection of 15 0-H2O at three time points 1 week before, 7 days after, and 7 months after shunting. The neurological status of these patients is classified, and cerebrospinal fluid (CSF) dynamics (continuous intracranial pressure [ICP] monitoring and CSF infusion tests) were assessed prior to surgery. Preoperative global CBF values correlate well with clinical outcome. Patients with a significantly lower global CBF value show clinical improvement after 7 months, whereas patients with higher CBF values do not (mean, 33 vs. 45 ml/1 00 ml per minute; p < 0 05). In contrast to conventional methods, including long-term ICP measurement and CSF infusion tests, preoperative global CBF values are discriminating in terms of clinical outcome. Thus, measurement of CBF may be helpful in evaluating the ultimate utility of shunt therapy in chronic hydrocephalus.     

Idiopathic normal pressure hydrocephalus: cerebral perfusion measured with pCASL before and repeatedly after CSF removal

Pseudo-continuous arterial spin labeling (pCASL) measurements were performed in 20 patients with idiopathic normal pressure hydrocephalus (iNPH) to investigate whether cerebral blood flow (CBF) increases during the first 24 hours after a cerebrospinal fluid tap test (CSF TT). Five pCASL magnetic resonance imaging (MRI) scans were performed. Two scans were performed before removal of 40 mL CSF, and the other three at 30 minutes, 4 hours, and 24 hours, respectively after the CSF TT. Thirteen different regions of interest (ROIs) were manually drawn on coregistered MR images. In patients with increased CBF in lateral and frontal white matter after the CSF TT, gait function improved more than it did in patients with decreased CBF in these regions. However, in the whole sample, there was no significant increase in CBF after CSF removal compared with baseline investigations. The repeatability of CBF measurements at baseline was high, with intraclass correlation coefficients of 0.60 to 0.90 for different ROIs, but the median regional variability was in the range of 5% to 17%. Our results indicate that CBF in white matter close to the lateral ventricles plays a role in the reversibility of symptoms after CSF removal in patients with iNPH.     

Cerebral critical closing pressure in hydrocephalus patients undertaking infusion tests

Abstract

Objectives:

Links between cerebrospinal fluid (CSF) compensation and cerebral blood flow (CBF) have been studied in many clinical scenarios. In hydrocephalus, disturbed CSF circulation seems to be a primary problem, having been linked to CBF disturbances, particularly in white matter close to surface of dilated ventricles. We studied possible correlations between cerebral haemodynamic indices using transcranial Doppler (TCD) ultrasonography and CSF compensatory dynamics assessed during infusion tests.

Methods:

We analysed clinical data from infusion tests performed in 34 patients suspected to suffer from normal pressure hydrocephalus, with signals including intracranial pressure (ICP), arterial blood pressure (ABP) and TCD blood flow velocity (FV). Cerebrospinal fluid compensatory parameters (including elasticity) were calculated according to a hydrodynamic model of the CSF circulation. Critical closing pressure (CrCP) was calculated with the cerebrovascular impedance methodology, while wall tension (WT) was estimated as CrCP-ICP. Closing margin (CM) was expressed as the difference between ABP and CrCP.

Results:

Intracranial pressure increased during infusion from 6.7?±?4.6 to 25.0?±?10.5?mmHg (mean?±?SD; P?<?0.001), resulting in CrCP rising by 22.9% (P?<?0.001) and WT decreasing by 11.3% (P?=?0.005). Closing margin showed a tendency to decrease, albeit not significantly (P?=?0.070) due to rising ABP (9.1%; P?=?0.005). Closing margin at baseline ICP was inversely correlated to brain elasticity (R?=?(0.358; P?=?0.038), while being significantly different from zero for the whole duration of the tests (52.8?±?22.8?mmHg; P?<?0.001). Neither CrCP nor WT was correlated with CSF compensatory parameters.

Discussion:

Critical closing pressure increases and WT decreases during infusion tests. Closing margin at baseline pressure may act as an indicator of the cerebrospinal compensatory reserve.     

Normal pressure hydrocephalus. Part 1. Dynamic study of CSF circulation in patients with normal pressure hydrocephalus (author's transl)

To clarify the pathogenesis of normal pressure hydrocephalus (NPH), quantitative measurement of CSF dynamics was attempted using RI techniques. In this study results concerning RI ventriculography and RI transfer test from CSF to plasma were reported. "Barrier ratio" and regional cerebral blood flow study in NPH will be reported elsewhere. Fifty-three patients with chronic communicating hydrocephalus wer devided into two groups. Thus, twenty-seven cases were diagnosed as NPH according to clinical symptoms and signs, and others were considered as mere chronic communicating hydrocephalus without any NPH characteristics. Results are as follows: 1) 169Yb--DTPA ventriculography; In NPH group, there was longer retention of RI injected into lateral ventricle, and RI activity was not detected in the cisterna magna 60 minutes after the injection. These findings show remarkable delay of CSF flow in NPH patients. 2) Transfer test of 169Yb--DTPA from CSF to plasma; Immediately after the RI injection, Transfer ratio of RI activity from CSF to plasma was measured. It was revealed that intraventricular RI was more rapidly transfered to plasma in NPH group compared with in the control group, suggesting accelerated trans-ependymal absorption of RI in NPH group.     

Simultaneous recording of cerebrospinal fluid pressure and middle cerebral artery blood flow velocity in patients with suspected symptomatic normal pressure hydrocephalus.

CSF pressure (intracranial pressure, in one patient lumbar pressure) was monitored continuously for one night in 23 patients with suspected symptomatic normal pressure hydrocephalus (NPH) to identify patients who might benefit from subsequent shunt surgery. In 20 patients middle cerebral artery (MCA) blood flow velocity by means of transcranial Doppler sonography (TCD) and CSF pressure were recorded simultaneously. In three patients transcranial Doppler signals were insufficient. Spontaneous changes in CSF pressure always paralleled changes in the TCD signal. Equivalents of B-waves as well as intermediate waves (in between B- and A-waves), and C-waves could be identified easily and always appeared in phase. The Doppler signal, however, could not be used to evaluate the absolute changes in CSF pressure. Fast Fourier Transform of the Doppler signal was a useful tool to indicate the relative frequency of B-wave equivalents. In five patients the injection of 10ml saline into the ventricle raised intracranial pressure considerably, but hardly affected the MCA blood flow velocity. Continuous TCD monitoring might be useful as a noninvasive screening procedure in patients with suspected symptomatic NPH before continuous invasive CSF pressure measurements are performed.     

Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline values.

Regional cerebral blood flow (CBF) was studied with O(15)-water positron emission tomography and anatomic region-of-interest analysis on co-registered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.     

The relationship of intracranial venous pressure to hydrocephalus

Little is known about intracranial venous pressure in hydrocephalus. Recently, we reported that naturally occurring hydrocephalus in Beagle dogs was associated with an elevation in cortical venous pressure. We proposed that the normal pathway for cerebrospinal fluid (CSF) absorption includes transcapillary or transvenular absorption of CSF from the interstitial space and that the increase in cortical venous pressure is an initial event resulting in decreased absorption and subsequent hydrocephalus. Further analysis, however, suggests that increased cortical venous pressure reflects the effect of the failure of transvillus absorption with increase in CSF pressure on the venous pressure gradient between ventricle and cortex. Normally, the cortical venous pressure is maintained above CSF pressure by the Starling resistor effect of the lateral lacunae. A similar mechanism is absent in the deep venous system, and thus the pressure in the deep veins is similar to that in the dural sinuses. Decreased CSF absorption causes an increase in CSF pressure followed by an increase in cortical venous pressure without a similar increase in periventricular venous pressure. The periventricular CSF to venous (transparenchymal) pressure (TPP) gradient increases. In contrast, cortical vein pressure remains greater than CSF pressure (negative TPP). The elevated periventricular TPP gradient causes ventricular dilatation and decreased periventricular cerebral blood flow (CBF), a condition that persists even if the CSF pressure returns to normal, particularly if tissue elastance is lessened by tissue damage. If deep CBF is to be maintained, periventricular venous pressure must increase. Since the veins are in a continuum, cortical venous pressure will further increase above the CSF pressure. Understanding these principles related to intracranial venous pressure helps in the selection of shunt characteristics that best match the pathologic condition.Presented at the Consensus Conference: Hydrocephalus '92, Assisi, Italy, 26–30 April 1992     

Natural course of intracranial pressure and drainage of CSF after recovery from subarachnoid hemorrhage

Twenty-eight patients were followed 12 months or longer after recovery from subarachnoid hemorrhage (SAH). The examination included spinal infusion test (SIT), clinical evaluation and cerebral computertomography (CT). The results indicate that when resting pressure and drainage of CSF are within normal limits 3 months after the hemorrhage there is little if any risk of developing late communicating hydrocephalus. In this study, most patients with a moderate impaired CSF drainage and/or slightly increased resting pressure 3 months after SAH did not show any increase in the ventricular size or clinical deterioration during the follow-up period. None of the 28 patients developed late communicating hydrocephalus or the clinical picture of normal pressure hydrocephalus.     

Auditory nerve-brain stem evoked potentials in cats during manipulation of the cerebral perfusion pressure

In order to study the effects of various degrees of cerebral ischemia on the auditory nerve-brain stem evoked potentials (BAEP), the cerebral perfusion pressure (CPP), defined as the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP), was systemically manipulated in anesthetized, paralyzed and ventilated cats. The CPP was varied by decreasing MAP, either by hemorrhage or by the infusion of a vasodilating drug, and elevating ICP by infusion of mock CSF into the cisterna magna, or by MAP depression and ICP elevation simultaneously. Even though the lower limit of adequate CPP is considered to be 40 mm Hg, the EEG became isoelectric at an average CPP of 24 mm Hg and the BAEP became isoelectric at an average CPP of 7 mm Hg. These extremely low CPP values of 7-24 mm Hg are far below the range of autoregulation of cerebral blood flow (CBF) so that the brain stem auditory pathway is still capable of generating its electrical response (BAEP) at very low CBF. This is paradoxical since these same regions of the brain have been shown to have the highest levels or regional metabolism as shown by their very high local cerebral blood flow and local glucose utilization.     

CSF galanin and cognition after shunt surgery in normal pressure hydrocephalus

BACKGROUND: "Normal" pressure hydrocephalus (NPH) is associated with injury to neurotransmitter and neuropeptide systems that recovers after surgery. This could be linked to changes in galanin, a neuropeptide with inhibitory effects on basal forebrain cognitive function. OBJECTIVE: To examine changes in CSF galanin concentrations in patients with normal pressure hydrocephalus undergoing shunt surgery, and to investigate the relation between these changes and cognitive functioning. METHODS: Eight patients underwent surgery for idiopathic normal pressure hydrocephalus. Lumbar CSF galanin determinations, cognitive status, and clinical status were quantified before operation and six months after. Cognition was assessed by an extensive battery of tests measuring attention, memory, speed of mental processing, visuospatial function, and frontal lobe function. RESULTS: CSF galanin concentration decreased after surgery. This reduction correlated with improved clinical and cognitive functioning, specifically with attention and visuomotor speed, visuoconstructive and frontal functioning, and clinical status according to the NPH scale, including the sphincter and cognitive components. CONCLUSIONS: The cognitive and clinical improvement after shunt implantation correlated with CSF galanin levels, suggesting that the distribution or function of this agent involves cerebral structures that have some potential for recovery. In this study, galanin was related to several cognitive functions that may be associated with the fronto-subcortical deficits underlying cognitive dysfunction in normal pressure hydrocephalus.     

Chronic hydrocephalus-induced changes in cerebral blood flow: mediation through cardiac effects.

Decreased cerebral blood flow (CBF) in hydrocephalus is believed to be related to increased intracranial pressure (ICP), vascular compression as the result of enlarged ventricles, or impaired metabolic activity. Little attention has been given to the relationship between cardiac function and systemic blood flow in chronic hydrocephalus (CH). Using an experimental model of chronic obstructive hydrocephalus developed in our laboratory, we investigated the relationship between the duration and severity of hydrocephalus and cardiac output (CO), CBF, myocardial tissue perfusion (MTP), and peripheral blood flow (PBF). Blood flow measures were obtained using the microsphere injection method under controlled hemodynamic conditions in experimental CH (n=23) and surgical control (n=8) canines at baseline and at 2, 4, 8, 12, and 16 weeks. Cardiac output measures were made using the Swan-Ganz thermodilution method. Intracranial compliance (ICC) via cerebrospinal fluid (CSF) bolus removal and infusion, and oxygen delivery in CSF and prefrontal cortex (PFC) were also investigated. We observed an initial surgical effect relating to 30% CO reduction and approximately 50% decrease in CBF, MTP, and PBF in both groups 2 weeks postoperatively, which recovered in control animals but continued to decline further in CH animals at 16 weeks. Cerebral blood flow, which was positively correlated with CO (P=0.028), showed no significant relationship with either CSF volume or pressure. Decreased CBF correlated with oxygen deprivation in PFC (P=0.006). Cardiac output was inversely related with ventriculomegaly (P=0.019), but did not correlate with ICP. Decreased CO corresponded to increased ICC, as measured by CSF infusion (P=0.04). Our results suggest that CH may have more of an influence on CO and CBF in the chronic stage than in the early condition, which was dominated by surgical effect. The cause of this late deterioration of cardiac function in hydrocephalus is uncertain, but may reflect cardiac regulation secondary to physiologic response or brain injury. The relationship between cardiac function and CBF should be considered in the pathophysiology and clinical treatment of CH.     

Cerebral blood flow, cerebral metabolism and cerebrospinal fluid biochemistry in brain-injured patients after exposure to hyperbaric oxygen.

A series of head-injured patients, in coma, were treated with hyperbaric oxygen (OHP) at 2.5 atm. Cerebral blood flow (CBF), cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGL), and lactate (CMRL act), and various cerebrospinal fluid (CSF) parameters were measured before and 2 h after the treatment. Pre-OHP and post-OHP average values of arterial blood and CSF lactate, and CMRL act were higher than normal, while CBF, CMRO2 and CSF oxygen pressure (PO2) were lower. CBF tended to increase after OHP in some patients and to decrease in others. This discrepancy and the conflicting results of the literature can be tentatively explained in assuming that there is a different effect of OHP on normal brain circulation as compared to impaired brain circulation. Changes of cerebral metabolic rates were inconsistent and did not relate to changes of CBF, except with repeated studies of the same patient. A correlation was found between the variations of CMRGL and those of arterial blood and CSF glucose content. CSF PO2, CSF acid-base balance, and CSF lactate content did not vary, and arterial PO2 showed a consistent fall. In two patients who were neurologically improved after OHP exposure, the CBF and metabolic changes were not the same.     

Communicating hydrocephalus in adults. Diagnostic tests and results of treatment with medium pressure shunts

In a study of 60 patients with communicating hydrocephalus, sources of error included lumbar cerebrospinal fluid (CSF) leakage, epidural infusion, and cerebrovascular reactions during the CSF infusion test; a high frequency of failing shunts; and initially undetected tumors in the group whose hydrocephalus was idiopathic. Though no sharp distinction could be made between positive and negative diagnositc tests, each variable indicated a certain probability of benefit, ranging from high to low, from shunting. CSF opening pressure in the lateral and sitting positions, the CSF infusion test, and cisternography were helpful in selecting patients for shunting. If clinical improvement was to take place, it did so within 3 months of shunting. Only patients with an opening pressure at or within the upper half of supposedly normal CSF pressure improved from a medium-pressure shunt. Improvement occurred in all patients having pressures of 580 mm H2O or more during an infusion test at a rate of 1.5 ml per minute. Neither preoperative signs and symptoms nor a single electroencephalogram had predictive value.     

Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage.

BACKGROUND: Arterial hypertension is common in the first 24 hours after acute intracerebral hemorrhage (ICH). Although increased blood pressure usually declines to baseline values within several days, the appropriate treatment during the acute period has remained controversial. Arguments against treatment of hypertension in patients with acute ICH are based primarily on the concern that reducing arterial blood pressure will reduce cerebral blood flow (CBF). The authors undertook this study to provide further information on the changes in whole-brain and periclot regional CBF that occur with pharmacologic reductions in mean arterial pressure (MAP) in patients with acute ICH. METHODS: Fourteen patients with acute supratentorial ICH 1 to 45 mL in size were studied 6 to 22 hours after onset. CBF was measured with PET and (15)O-water. After completion of the first CBF measurement, patients were randomized to receive either nicardipine or labetalol to reduce MAP by 15%, and the CBF study was repeated. RESULTS: MAP was lowered by -16.7 +/- 5.4% from 143 +/- 10 to 119 +/- 11 mm Hg. There was no significant change in either global CBF or periclot CBF. Calculation of the 95% CI demonstrated that there is less than a 5% chance that global or periclot CBF fell by more than -2.7 mL x 100 g(-1) x min(-1). CONCLUSION: In patients with small- to medium-sized acute ICH, autoregulation of CBF was preserved with arterial blood pressure reductions in the range studied.     

Regional cerebral blood flow, white matter abnormalities, and cerebrospinal fluid hydrodynamics in patients with idiopathic adult hydrocephalus syndrome.

OBJECTIVES--(1) to evaluate regional cerebral blood flow (rCBF) with single photon emission computed tomography and 99mTc-hexamethylpropyleneamine oxime in patients with the idiopathic adult hydrocephalus syndrome (IAHS); (2) to examine regional cerebral blood flow (rCBF), gait, and psychometric functions before and after CSF removal (CSF tap test); (3) to assess abnormalities in subcortical white matter by MRI. METHODS--Thirty one patients fulfilling the criteria for IAHS (according to history and clinical and neuroradiological examination) were studied. Quantified gait measurements, psychometric testing, and rCBF before and after removal of CSF were obtained. Pressure of CSF and CSF outflow conductance were investigated with a constant pressure infusion method. Brain MRI was used to quantify the severity of white matter lesions and periventricular hyperintensities. In IAHS a widespread rCBF hypoperfusion pattern was depicted, with a caudal frontal and temporal grey matter and subcortical white matter reduction of rCBF as the dominant feature. Removal of CSF was not accompanied by a concomitant increase in rCBF. Significant white matter lesions were detected only in a minority of patients by MRI. An altered CSF hydrodynamic state with a higher CSF pressure and lower conductance was confirmed. IAHS is characterised by an abnormal CSF hydrodynamic state, associated with a widespread rCBF reduction with preference for subcortical white matter and frontal-temporal cortical regions. Furthermore in most patients MRI did not show white matter changes suggestive of a coexistent subcortical arteriosclerotic encephalopathy. At least in the idiopathic group of patients with AHS, measurements of rCBF before and after temporary relief of the CSF hydrodynamic disturbance will not provide additional information that would be helpful in the preoperative evaluation but is suggestive of a preserved autoregulation of rCBF.     

Comparison between the lumbar infusion and CSF tap tests to predict outcome after shunt surgery in suspected normal pressure hydrocephalus

OBJECTIVE: To compare the lumbar infusion test and the cerebrospinal fluid (CSF) tap test for predicting the outcome of shunt surgery in patients with suspected normal pressure hydrocephalus. METHODS: 68 patients with suspected normal pressure hydrocephalus were studied. The absence of preceding history indicated idiopathic disease in 75% of these. All patients were assessed twice with walking and psychometric tests before lumbar infusion test and tap test assessments. The lumbar infusion test was done using a constant infusion rate (0.80 ml/min) and regarded as positive if the steady state CSF plateau pressure reached levels of > 22 mm Hg (resistance to outflow > 14 mm Hg/ml/min). The tap test was regarded as positive if two or more of four different test items improved after CSF removal. As the variability in baseline test results was large, the better of two evaluations was used in comparisons with the results after CSF removal, as well as to evaluate the outcome after shunt surgery. Only patients with a positive lumbar infusion test or a positive tap test had surgery. RESULTS: The results of the CSF tap test and the lumbar infusion test agreed in only 45% of the patients. Of the total cohort, 47 (69%) had positive test results and were operated on; 45 (96%) of these reported subjective improvement, and postoperative assessments verified the improvements in 38 (81%). Improvements were highly significant in walking, memory, and reaction time tests (p < 0.001). Most of the patients improved by surgery (84%) were selected by a positive lumbar infusion test, and only 42% by a positive tap test. Positive predictive values were 80% for lumbar infusion test and 94% for tap test. The false negative predictions in the operated group were much higher (58%) with the tap test than with the lumbar infusion test (16%). CONCLUSIONS: Both the lumbar infusion test and the tap test can predict a positive outcome of shunt operations in unselected patients with suspected normal pressure hydrocephalus. The two tests are complementary and should be used together for optimal patient selection.     

The effect of the excitatory amino acid receptor antagonist dizocilipine maleate (MK-801) on hemispheric cerebral blood flow and metabolism in dogs: modification by prior complete cerebral ischemia

The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist dizociplipine maleate (MK-801) on cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), intracranial pressure and systemic variables was examined in 6 normal dogs (Group I). In 6 additional dogs (Group II), the effects of a prior 11 min episode of complete cerebral ischemia on the response to dizocilipine was studied. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arterial to sagittal sinus O2 content difference. Dizocilipine was administered as a 150 micrograms/kg i.v. bolus followed by a 75 micrograms.kg-1.h-1 infusion for 90 min. Plasma dizocilipine levels were greater than 25 ng/ml for the duration of the infusion. The CSF levels were approximately half the plasma levels. Five minutes after initiation of dizocilipine treatment, Group I dogs experienced a 63% increase in heart rate (P less than 0.01) and an 8% decrease in the mean arterial blood pressure (P less than 0.05). Over the same time interval. CBF increased by 85% (P less than 0.01) and intracranial pressure nearly doubled (P less than 0.05). In addition, dizocilipine treatment in all Group I animals resulted in EEG quasiperiodic bursts of delta-waves and polyspikes on a background of beta-activity. With the exception of the intracranial pressure, the above changes in systemic and cerebral variables persisted for the duration of the drug infusion. Intracranial pressure was no longer significantly elevated after 80 min of drug infusion. Hemispheric CMRO2 was unchanged by dizocilipine in Group I dogs. There was a decrease in the cortical glucose level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with 6 laboratory normals. An identical dose of dizocilipine administered after an 11 min episode of complete cerebral ischemia resulted in no significant changes in either cerebral or systemic variables. The absence of systemic effects in Group II dogs suggests that dizocilipine administration in normal dogs results in a centrally mediated activation of the peripheral sympathetic nervous system. The uncoupling of CBF and CMRO2 observed following dizocilipine treatment is similar to that reported for two other known NMDA antagonists, ketamine and phencyclidine. If administration of dizocilipine results in improved histopathological and neurological outcome following an episode of complete cerebral ischemia, this improvement is unrelated to changes in postischemic CBF or hemispheric CMRO2.     

Lack of relationship between resistance to cerebrospinal fluid outflow and intracranial pressure in normal pressure hydrocephalus

OBJECTIVE: To explore whether calculation of resistance to cerebrospinal fluid (CSF) outflow (Rout) by the lumbar constant rate infusion test in a reliable way predicts the intracranial pressure (ICP) profile in normal pressure hydrocephalus (NPH). METHODS: A prospective study was undertaken including 16 cases with clinical signs of normal pressure hydrocephalus that were investigated with both continuous ICP monitoring and the lumbar constant rate infusion test. Intracranial pressure monitoring was performed for about 24 h, and supplied with a simultaneous lumbar constant rate infusion test at the end of the monitoring period. The pressure recordings were analysed using the Sensometrics Pressure Analyser. Various characteristics of the pressure curves were compared. RESULTS: The continuous ICP recordings were considered as normal (mean ICP<11.5 mmHg) in all 16 cases. The lumbar infusion test showed an apparently abnormal resistance to CSF outflow (Rout) (> or =12.0 mmHg/ml/min) in 12 of 16 cases. There was no relationship between lumbar Rout and mean ICP during sleep. We could not find any relationship between lumbar Rout and number of nightly ICP elevations of 1525 mmHg lasting 0.5 or 1 min. Neither resistance to CSF outflow (Rout) nor mean ICP during sleep was related to the ventricular size. CONCLUSIONS: The results of this prospective study revealed no significant relationship between resistance to CSF outflow (Rout) and the ICP profile in NPH cases. The results also suggest that caution should be made when predicting the ICP profile on the basis of measuring the lumbar CSF pressure for a few minutes duration.