Intracranial pressure, conductance to cerebrospinal fluid outflow, and cerebral blood flow in patients with benign intracranial hypertension (pseudotumor cerebri)

Intracranial pressure, conductance to cerebrospinal fluid outflow, and cerebral blood flow were investigated in 14 patients with benign intracranial hypertension (pseudotumor cerebri). Intracranial pressure was increased in 9 patients (20 to 30 mm Hg), borderline in 4 patients (15 to 18 mm Hg), and normal in 1 patient (8 mm Hg). Six patients had plateau waves, and all had B waves in more than 50% of the monitored time. Conductance to cerebrospinal fluid outflow, measured by a lumbo-lumbar perfusion method, was significantly reduced: 0.042 ml X mm Hg-1 X min-1 (+/- 0.004 [SEM]; normal, more than 0.080 ml X mm Hg-1 X min-1). Cerebral blood flow was measured by xenon 133 inhalation and single photon emission computer tomography. Mean hemispheric flow was normal in all cases, averaging 59 +/- 9 ml X 100 gm-1 X min-1. Only 2 patients showed focal low-flow areas. Thus, a disturbance of cerebrospinal fluid circulation seems to be of pathogenetic significance in benign intracranial hypertension.     

颅高压时脑脊液脉动压与脑灌注压相互关系的实验研究

目的　研究颅高压时脑脊液脉动压与脑灌注压的相互变化关系。方法　 14条狗安置硬膜外球囊并注液制成颅高压模型。通过改变球囊内液体量改变颅高压程度和颅内容积。通过压力传感器持续记录脑室内压力、腰椎管内压力及体动脉压。结果　随着颅内压的持续增高 ,脑灌注压逐渐下降 ,脑脊液脉动压相应增高。脑脊液脉动压与颅内压的变化趋势呈现正性线性关系 (r=0 732 2 ,P <0 0 5 ) ,而与脑灌注压的变化趋势呈现负性线性关系 (r=- 0 6 879,P <0 0 5 )。结论　在实验性颅高压中 ,脑脊液脉动压随着脑灌注压的下降而增大 ,两者间呈现负性线性关系。在脑血管自动调节机制受损的情况下 ,脑脊液脉动压的变化可能提供脑血流量改变的信息。     

Regional cerebral oxygen utilization, blood flow, and blood volume in benign intracranial hypertension studied by positron emission tomography

Using PET, we measured regional cerebral oxygen utilization, oxygen extraction, blood flow, and blood volume in five patients with benign intracranial hypertension. No significant differences in regional cerebral function were found between the patients and 15 age-matched normal controls. Cerebral decompression with a lumboperitoneal shunt produced little change in regional cerebral function in one patient studied serially. The raised CSF pressure of benign intracranial hypertension is therefore not associated with any significant deterioration in cerebral oxygen metabolism or hemodynamics.     

Experimental pneumococcal meningitis: Cerebrovascular alterations,brain edema,and meningeal inflammation are linked to the production of nitric oxide

We investigated whether treatment with the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA) and the free radical scavenger superoxide dismutase influences cerebral blood flow changes, brain edema, and cerebrospinal fluid pleocytosis in early experimental pneumococcal meningitis. Compared to untreated infected rats, superoxide dismutase given 3 hours after infection significantly attenuated the increase of brain water content, intracranial pressure, and cerebrospinal fluid white blood cell count, but did not modulate the increase in regional cerebral blood flow. N-Nitro-L-arginine treatment (5 mg/kg intravenously, followed by 5 mg/kg/hour) reversed the increase in regional cerebral blood flow; prevented an increase in brain water content, intracranial pressure, and cerebrospinal fluid nitrite concentrations; and reduced cerebrospinal fluid white blood cell count. With a closed cranial window preparation, N-nitro-L-arginine prevented pneumococci-induced dilatation of pial arterioles. When the effective dose was increased twofold, the effects of N-nitro-Lvarginine became more pronounced but resulted in the death of 4 of 5 rats, probably due to hemodynamic side effects. In primary cultures of rat cerebral endothelial cells, nitrite concentrations increased after pneumococcal stimulation, which could be prevented by NvnitrovLvarginine and cycloheximide. These data suggest that (a) nitric oxide accounts for regional cerebral blood flow changes and pial arteriolar dilatation in the early phase of experimental pneumococcal meningitis; (b) both superoxide radical and nitric oxide are involved as mediators of brain edema and meningeal inflammation; and (c) cerebral endothelial cells can be stimulated by pneumococci to release nitric oxide presumably via the inducible nitric oxide synthase.     

Intracranial volume–pressure relationships during experimental brain compression in primates: 2. Effect of induced changes in systemic arterial pressure and cerebral blood flow

In eight anaesthetized, ventilated adult baboons, the intracranial volume–pressure response was examined at differing levels of raised intracranial pressure during induced changes in systemic arterial pressure and cerebral blood flow. The volume–pressure response is defined as the change in ventricular fluid pressure caused by a volume addition of 0·05 ml to the lateral ventricle. At normal intracranial pressure, the volume–pressure response was unchanged by alterations in systemic arterial pressure and cerebral blood flow. At raised intracranial pressure, however, systemic arterial hypertension rendered the intracranial contents more sensitive to the effects of an addition to the ventricular volume as shown by an increased volume–pressure response. When intracranial pressure was increased, there was a significant linear correlation between the volume–pressure response and both arterial pressure and cerebral blood flow. The clinical implication of this phenomenon is that arterial hypertension in patients with increased intracranial pressure is likely to have a deleterious effect by increasing brain tightness.     

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.     

Regional cerebral blood flow and CSF pressures during Cushing response induced by a supratentorial expanding mass

In order to delineate the critical blood flow pattern during the Cushing response in intracranial hypertension, regional cerebral blood flow was measured with radioactive microspheres in 12 anesthetized dogs at respiratory arrest caused either by expansion of an epidural supratentorial balloon or by cisternal infusion. Regional cerebrospinal fluid pressures were recorded and the local cerebral perfusion pressure calculated in various cerebrospinal compartments. In the 8 dogs of the balloon expansion group, the systemic arterial pressure was unmanipulated in 4, while it was kept at a constant low level (48 and 70 mm Hg) in 2 dogs and, in another 2 dogs, at a constant high level (150 and 160 mm Hg) induced by infusion of Aramine. At respiratory arrest, regional cerebral blood flow had a stereotyped pattern and was largely independent of the blood pressure level. In contrast, concomitant pressure gradients between the various cerebrospinal compartments varied markedly in the 3 animal groups, increasing with higher arterial pressure. Flow decreased by 85-100% supratentorially and by 70-100% in the upper brain stem down to the level of the upper pons, while changes in the lower brain stem were minor, on the average 25%. When intracranial pressure was raised by cisternal infusion in 4 dogs, the supratentorial blood flow pattern at respiratory arrest was approximately similar to the flow pattern in the balloon inflation group. However, blood flow decreased markedly (74-85%) also in the lower brain stem. The results constitute another argument in favour of the Cushing response in supratentorial expansion being caused by ischemia in the brain stem. The critical ischemic region seems to be located rostrally to the oblongate medulla, probably in the pons.     

Treatment of systemic hypertension and intracranial hypertension in cases of brain hemorrhage

We studied the effects of nifedipine, chlorpromazine, reserpine, furosemide, and thiopental on the mean arterial blood pressure, mean intracranial pressure, and cerebral perfusion pressure in 38 patients with increased intracranial pressure resulting from either hemorrhagic cerebrovascular disease or systemic hypertension. These agents are widely used in neurosurgical practice for the treatment of systemic hypertension. Patients were assigned to two groups on the basis of their mean intracranial pressure. Group I comprised 20 patients with a mean intracranial pressure of 20-40 mm Hg (moderately increased ICP group), and Group II consisted of 18 patients with a mean intracranial pressure of greater than 40 mm Hg (severely increased ICP group). Nifedipine, chlorpromazine, and reserpine reduced mean arterial blood pressure by 18-20% in both groups (p less than 0.05 in each). In Group I these agents raised mean intracranial pressure by 10-35% and decreased cerebral perfusion pressure by 20-32% (p less than 0.05 for both), but in Group II these changes were more marked: mean intracranial pressure increased 38-64% and cerebral perfusion pressure decreased 40-54% (p less than 0.01 for both). Furosemide did not significantly reduce mean arterial blood pressure but slightly reduced mean intracranial pressure in each group. Thiopental reduced both mean arterial blood pressure and intracranial pressure in both groups. The effect on intracranial pressure was pronounced in Group II, in which mean arterial blood pressure fell by 18% (p less than 0.05) and mean intracranial pressure decreased 50% (p less than 0.01), whereas in Group I mean arterial blood pressure was reduced by 16% and mean intracranial pressure dropped 23% (p less than 0.05 in each).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral blood flow and metabolism in normotensive and hypertensive patients with transient neurologic deficits

We used positron emission tomography to examine retrospectively the effects of blood pressure on regional cerebral blood flow and oxygen metabolism in seven normotensive and eight hypertensive patients with a history of transient neurologic deficits. In the hypertensive patients, a decrease in regional cerebral blood flow was closely related to blood pressure; these changes were most pronounced in the supratentorial structures, especially the striatum and thalamus. In contrast, the regional cerebral metabolic rate for oxygen was less related to blood pressure. Consequently, the regional oxygen extraction fraction was increased in the hypertensive patients, while regional cerebral blood volume and the regional cerebral blood flow volume ratio were unchanged. Multivariate regression analysis confirmed that hypertension was an independent factor affecting regional cerebral blood flow. The analysis also disclosed that age, sex, hematocrit, smoking, and PaCO2 affected regional cerebral blood flow. These findings suggest that the hemodynamic reserve in hypertensive individuals is reduced, which may predispose them to cerebral ischemia and perhaps stroke, even during small decreases in cerebral perfusion pressure.     

Acute intracranial hypertension

Acute intracranial hypertension is a syndrome with multiple etiologies. Diagnosis and treatment must be performed urgently to save the patient's life and prevent the development of significant disabilities. The appearance of this syndrome is due to intracraincreased volumes and -in turn- the pressure of the intracranial contents, either through an increase in the physiological components (blood, cerebrospinal fluid and brain parenchyma), or through the appearance of a volume in the form of added mass. The underlying brain edema in this condition may be of several types: cytotoxic, vasogenic, interstitial, or hydrostatic. Increased intracranial pressure decreases cerebral perfusion pressure, creating a vicious cycle because of the resulting cerebral ischemia, which progressively increases cerebral blood volume by decreasing resistance and further increases intracranial pressure. Treatment depends on the etiology and will generally require medical and surgical care. Patient management is usually carried out in neurocritical units and involves intracranial pressure monitoring to guide treatment. Correction of all hemostasis disorders is also crucial to patient survival.     

Induced hypothermia in experimental pneumococcal meningitis.

Pneumococcal meningitis resulting from Streptococcus pneumoniae has a death rate of 28% in adults. In severe head injury and stroke, inflammatory changes and intracranial hypertension are improved by induced hypothermia, which also is neuroprotective. We hypothesized that moderate hypothermia ameliorates inflammatory changes in experimental pneumococcal meningitis. Wistar rats were cooled systemically, and meningitis was induced by pneumococcal cell wall components. The increase of regional cerebral blood flow in the meningitis animals was blocked by hypothermia at 6 hours. The reduction of intracranial pressure correlated with temperature. The influx of leukocytes into the cerebrospinal fluid and levels of tumor necrosis factor alpha in the cerebrospinal fluid were decreased. Cooling the animals 2 hours after meningitis induction to 30.5 degrees C was also protective. We conclude that hypothermia is a new adjuvant approach to reduce meningitis-induced changes, in particular intracranial pressure, in the early phase of the disease.     

Perfusion and diffusion magnetic resonance imaging in idiopathic intracranial hypertension

OBJECTIVES: Idiopathic intracranial hypertension (IIH) is characterized by abnormal elevation of intracranial pressure without any underlying etiologic factor. Papilledema is the major clinical finding whereas neuroradiological imaging findings are almost always normal. The aim of this preliminary study was to determine if diffusion and perfusion magnetic resonance imaging in patients with IIH might be beneficial in the management of the disease. MATERIALS AND METHODS: Prospectively, we evaluated standard magnetic resonance, magnetic resonance angiographies and venographies, diffusion and perfusion magnetic resonance findings of 16 patients with IIH and of 16 age-, sex-, and weight-matched normal individuals as a control group. Patients with IIH underwent a detailed neuroophthalmologic examination and lumbar puncture for evaluation of cerebrospinal fluid pressure. Magnetic resonance imaging was performed with 1.5 T equipment. RESULTS: On physical examination, all patients had characteristic papilledema, varying degrees of headache, blurred vision and tinnitus. Cerebrospinal fluid pressure was higher than 250 mm H2O in all patients. A statistically significant decrease in cerebral blood flow in six patients, whereas insignificant increase in two were detected. Cerebral blood volume values were almost similar to normal control group's values. Significant mean transit time prolongation was found in six patients as well. CONCLUSIONS: Idiopathic intracranial hypertension is a clinical syndrome which requires prompt diagnosis and a thorough evaluation. Treatment is crucial for preventing visual loss and improving associated symptoms. It is also important to detect cerebral perfusion changes, as cerebrovascular complications may be associated. Although our patient group is small for statistical evaluation, it is a preliminary study using perfusion and diffusion magnetic resonance which may contribute to IIH management.     

Hipertensión intracraneal aguda

Acute intracranial hypertension is a syndrome with multiple etiologies. Diagnosis and treatment must be performed urgently to save the patient's life and prevent the development of significant disabilities. The appearance of this syndrome is due to intracraincreased volumes and —in turn— the pressure of the intracranial contents, either through an increase in the physiological components (blood, cerebrospinal fluid and brain parenchyma), or through the appearance of a volume in the form of added mass. The underlying brain edema in this condition may be of several types: cytotoxic, vasogenic, interstitial, or hydrostatic. Increased intracranial pressure decreases cerebral perfusion pressure, creating a vicious cycle because of the resulting cerebral ischemia, which progressively increases cerebral blood volume by decreasing resistance and further increases intracranial pressure. Treatment depends on the etiology and will generally require medical and surgical care. Patient management is usually carried out in neurocritical units and involves intracranial pressure monitoring to guide treatment. Correction of all hemostasis disorders is also crucial to patient survival.     

Regional cerebral blood flow and CSF pressures during the Cushing response induced by an infratentorial expanding mass

An experimental study was carried out in eight dogs to investigate whether the Cushing response (CR) during intracranial hypertension is due to pressure per se, tissue distortion, or ischemia in the brain stem. To minimize the effects of rostrocaudal displacement, intracranial pressure was raised by an expanding mass lesion located in the posterior fossa. Regional cerebral blood flow (rCBF) was measured with radioactive microspheres and compartmental cerebrospinal fluid (CSF) pressures were recorded during the CR which was induced by the continuous inflation at a constant rate of an infratentorial epidural rubber balloon in two groups of four dogs. In one group (A) rCBF was measured at the onset of the CR and in the other group (B) at the peak of the systemic blood pressure rise. In the animals of group A blood flow in the mesencephalon, pons and upper medulla oblongata was reduced from control values by 32%, 57% and 85% respectively. In group B blood flow in the same areas did not differ significantly from pre-inflation values. In contrast, the recorded balloon volume, which was assumed to be an index of mechanical distortion of the brain stem, varied considerably at the beginning of the blood pressure rise (from 2.5 to 4.7% of the calculated intracranial space). Similarly, CSF pressure in the posterior fossa at the onset of the CR also varied considerably (from 52 to 117 mmHg). Thus, the large quantitative variations meant that both absolute pressure and tissue distortion were poor predictors of the onset of the CR. The findings suggest that ischemia, rather than brain stem distortion per se or pressure by itself, is responsible for the initiation of the CR. The rise in blood pressure elicited during the CR seems capable of restoring blood flow in the brain stem back to control values.     

Monitoring and interpretation of intracranial pressure

Intracranial pressure (ICP) is derived from cerebral blood and cerebrospinal fluid (CSF) circulatory dynamics and can be affected in the course of many diseases of the central nervous system. Monitoring of ICP requires an invasive transducer, although some attempts have been made to measure it non-invasively. Because of its dynamic nature, instant CSF pressure measurement using the height of a fluid column via lumbar puncture may be misleading. An averaging over 30 minutes should be the minimum, with a period of overnight monitoring in conscious patients providing the optimal standard. Computer-aided recording with online waveform analysis of ICP is very helpful. Although there is no "Class I" evidence, ICP monitoring is useful, if not essential, in head injury, poor grade subarachnoid haemorrhage, stroke, intracerebral haematoma, meningitis, acute liver failure, hydrocephalus, benign intracranial hypertension, craniosynostosis etc. Information which can be derived from ICP and its waveforms includes cerebral perfusion pressure (CPP), regulation of cerebral blood flow and volume, CSF absorption capacity, brain compensatory reserve, and content of vasogenic events. Some of these parameters allow prediction of prognosis of survival following head injury and optimisation of "CPP-guided therapy". In hydrocephalus CSF dynamic tests aid diagnosis and subsequent monitoring of shunt function.     

Blood flow velocities during experimental intracranial hypertension in pigs

Abstract

Objectives: A purely hydraulic mechanism consisting in the pulsatile cuff-compression effect, by the cerebrospinal fluid displacement induced by the arterial pulsation, on the final portion of the bridging veins, has recently been hypothesized. This mechanism is able to maintain the constancy of cerebral blood flow (CBF) within the autoregulatory range, thus implying an exact balance between arterial inflow and venous outflow. In this study, we correlated arterial inflow and venous outflow during an experimentally induced condition of intracranial hypertension in pigs.

Methods: Mock cerebrospinal fluid (CSF) was progressively infused until a condition of brain tamponade was reached. Blood flow velocities at middle cerebral artery and sagittal sinus sites were evaluated simultaneously.

Results: Mean intracranial arterial blood flow velocity (IABFV), mean sagittal sinus blood flow velocity (SSBFV), and pulsatile-IABFV remained almost constant until cerebral perfusion pressure (CPP) dropped below 60–70 mmHg; then, a progressive decrease in mean IABFV and SSBFV, together with an increase in pulsatile-IABFV, was evident.

Conclusion: The strict similarity between mean IABFV and SSBFV patterns suggests that CBF decrement is mainly due to a decrease in the venous outflow, which, in turn, produces an obstacle to the arterial inflow. The correspondent increase in pulsatile-IABFV confirms the presence of a distal outflow obstruction. All these findings point towards a purely hydraulic mechanism underlying the cerebral autoregulation which acts at the level of the so-called Starling resistor.     

Raised intracranial pressure and cerebral blood flow: I. Cisterna magna infusion in primates

Changes in cerebral blood flow during incremental increases of intracranial pressure produced by infusion of fluid into the cisterna magna were studied in anaesthetized baboons. Cerebral blood flow remained constant at intracranial pressure levels up to approximately 50 mm Hg. At intracranial pressure levels between 50-96 mm Hg a marked increase in cerebral blood flow occurred, associated with the development of systemic hypertension and changes in cerebrovascular resistance. Further increases of intracranial pressure led to a progressive fall in cerebral blood flow. Prior section of the cervical cord prevented both the increase in cerebral blood flow and the systemic hypertension. Alteration of cerebral perfusion pressure by bleeding during the hyperaemia in a further group of animals suggested that autoregulation was at least partially preserved during this phase. After maximum hyperaemia had occurred, however, autoregulation appeared to be lost. The clinical implications of these findings are discussed.     

Thoracolumbar intraspinal tumours presenting features of raised intracranial pressure.

Five patients are described in whom a benign or malignant thoracolumbar tumour, producing increased level of cerebrospinal fluid protein, was associated with hydrocephalus or papilloedema or both. A review of the clinical and laboratory features in these and 40 published cases underlines the difficulty in explaining the increased intracranial pressure in such patients. Slow absorption of cerebrospinal fluid as a result of the elevated protein levels or recurrent subarachnoid bleeding may play a part. When patients are discovered to have communicating hydrocephalus or a syndrome resemlbing benign intracranial hypertension, the finding of increased cerebrospinal fluid protein or any symptoms or signs relative to the spine should suggest the possibility of an intraspinal tumour.     

Cerebral venous blood gas tensions in elevated intracranial pressure

Cerebral venous blood gas tensions were correlated with elevated intracranial pressure in spontaneously breathing dogs lightly anesthetized with nitrous oxide/halothane. Intracranial pressure was elevated by infusion of artificial cerebrospinal fluid into a lateral ventricle. Respiration and blood pressure were monitored. The results of these experiments indicate that cerebral venous carbon dioxide tension is increased in association with elevation in intracranial pressure. Moreover, it appears that cerebral venous pCO2 is effectively regulated at a mean of about 52 mm Hg over a wide range of intracranial pressure.     

Bilateral hemispheric reduction of cerebral blood volume and blood flow immediately after experimental cerebral hemorrhage in cats

Acute cerebral circulatory changes following experimental cerebral hemorrhage were investigated in eight cats. The cerebral hemorrhage was produced in the right basal ganglia by introducing arterial blood via a thin catheter, using the systemic arterial blood pressure of the cat as a driving force. Local cerebral blood volume was measured continuously in the bilateral parietotemporal cortexes employing photoelectric apparatuses. Carbon black dilution curves were recorded from the regions, and the mean transit time of blood was calculated. Local cerebral blood flow was estimated from mean transit time and cerebral blood volume. Intracranial pressure was monitored continuously in the right parietal epidural space. Five minutes after cerebral hemorrhage, intracranial pressure increased by 24.0 +/- 6.1 mm Hg, while mean arterial blood pressure increased by only 2.9 +/- 2.0 mm Hg. Cerebral blood volume decreased by 1.60 +/- 0.24 vol% in the hemorrhagic and 1.14 +/- 0.30 vol% in the nonhemorrhagic hemisphere. Cerebral blood flow decreased by 30.0 +/- 4.5 ml/100 g brain/min in the hemorrhagic (initially 64.5 +/- 13.6) and by 30.3 +/- 7.5 ml/100 g brain/min in the nonhemorrhagic (initially 60.9 +/- 6.9) hemisphere. Increased intracranial pressure appeared to be the main cause of the observed cerebral blood volume/flow reduction shortly after experimental hemorrhage in the basal ganglia. Several other factors and mechanisms involved are discussed.