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It was determined from in vitro experiments that the minimal dose of urokinase required to lyse 10 ml of clotted canine blood within a closed space must exceed 10,000 IU. We empirically doubled this minimum effective dose and tested the in vivo safety of injecting 20,000 IU of urokinase every 12 hours for 4 days into the ventricles of six adult mongrel dogs through an implanted catheter-reservoir system. The animals were monitored carefully for local and systemic bleeding by neurological and clinical examination, hematological tests reflecting systemic fibrinolytic status, serial computed tomography, and postmortem histological examinations of the brain, meninges, and peripheral organs. It was found that this intraventricular dose regimen of urokinase did not cause intracranial hemorrhage even though the dogs had recent brain wounds related to transcerebral ventricular catheterization. Mild activation of systemic fibrinolysis, implying passage of the enzyme from ventricle to blood, occurred 4 to 6 hours after each intraventricular injection, but no systemic hemorrhages were seen. This dose regimen also did not cause acute or chronic inflammatory changes in the brain or meninges and did not disturb cerebrospinal fluid circulation.

Quantitative evaluation of radioisotope (RI) cisternography was performed by single photon emission computed tomography (SPECT) in eight patients suspected of chronic hydrocephalus or malfunction of a shunt system, showing symptoms for two to 24 months, and one control patient with cerebrospinal fluid (CSF) leakage ten years after head trauma. Criteria of ventricular dilation by CT scan were satisfied in seven of the eight patients. The patients were given an injection of 1 ml of 1 mCi indium-111 diethylene triamine pentaacetic acid (In-Ill DTPA) via the lumbar route (seven cases) or ventricular catheter (two cases). Regular evaluations were scheduled (4, 7, 10-12, 24, 48 and 72 hours after injection). The region of interest, about 1.3 cm in radius and 0.8 cm in height, was placed in cisterna magna, sylvian cistern, basal cistern, and interhemispheric cistern as well as in the ventricle using a reconstructed image of a horizontal section by SPECT. Clearance curves were calculated with estimated decreasing count of RI each time by the method of exponential regression coefficients. Discrimination of the disease was attempted using the values of constant K of clearance curve and biological half-life time (BHT). Diagnosis of hydrocephalus was satisfactorily made in five patients demonstrating K values lower than 0.04 in all the cisterns expect for the cisterna magna, as well as BHT longer than 18-20 hours. Three of the five patients were treated with ventriculo-peritoneal (VP) shunt (two reconstructions of shunt systems and one VP shunt), and all of the improved. Although the remaining two patients were diagnosed as having hydrocephalus from the study, surgery was not performed, because of complicating psychiatric and malignant gastrointestinal diseases. Each patient diagnosed as Parkinson's disease or Alzheimer's disease showed a higher K value and shorter BHT than those in hydrocephalic patients. This tendency became clearer in the control patient with CSF leakage. Thus quantitative RI cisternography was highly valuable in the discrimination of chronic hydrocephalic from non-hydrocephalic patients with definitive dilation of the ventricles or symptoms similar to normal pressure hydrocephalus. This study may also be useful for estimation of the degree of impairment of CSF circulation.

Present theory holds that pulsatile pressure of cerebrospinal fluid (CSF) is driven by the force of expansion of the choroid plexus. Alternate theories postulating that a possible movement of the brain is involved in pumping CSF have not, to the authors' knowledge, been substantiated heretofore. In this study, in vivo, quantitative magnetic resonance (MR) imaging methods were developed to show reproducible magnitudes and directions of CSF flow. Measurements were obtained with a new MR velocity imaging technique at high resolution (0.4 mm/sec), requiring 64 cardiac cycles per image. Twenty-five healthy volunteers and five patients were studied. Observations of pulsatile brain motion, ejection of CSF out of the cerebral ventricles, and simultaneous reversal of CSF flow direction in the basal cisterns toward the spinal canal, taken together, suggest that a vascular-driven movement of the entire brain may be directly pumping the CSF circulation. The authors describe what they believe to be the first observations and measurements of human brain motion, which occurs in extensive internal regions (particularly the diencephalon and brain stem) and is synchronous with cardiac systole.

It is important for adequate treatment after subarachnoid hemorrhage (SAH) to estimate objectively the disturbed cerebrospinal fluid (CSF) circulation and the intracranial spatial compensatory capacity. This paper reports the results of a preliminary trial to apply infusion studies as a method of quantifying the amount of CSF circulatory disturbance and the elasticity of the brain. The infusion studies (bolus injection, bolus withdrawal and steady-state infusion) were performed in 14 adult SAH patients for a total of 19 times. In 12 patients, studies were carried out under two spinal taps (one for CSF manipulation and the other for a pressure transducer). Two other patients received the tests through ventricular drainage. Pressure changes were recorded by a polygraph and a data recorder, and were later analysed by the methods of Marmarou, et al. and Katzman, et al. to calculate three parameters, namely, pressure-volume index (PVI), CSF outflow resistance (Ro) and CSF formation rate. These parameters were compared with computed tomography (CT) findings, radioisotope cisternographic findings (6 cases) and the effectiveness of therapeutic procedures (external decompression in 4 cases and CSF shunt in 9 cases). PVI values showed statistically significant differences between the decompressed group (44.62±30.33 ml) and nondecompressed group (22.23±9.02 ml) (p

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.

For differentiation of diseases with impaired cerebrospinal fluid circulation and pathological alterations of the midbrain an exact and reproducible sonographic visualization of the brain stem area is of paramount importance. The approach through the anterior fontanelle has proved to be insufficient to accomplish this task. Therefore, we have developed 5 standard sonographic sections enabling detailed study of the brain stem. Typical sonographic views are compared with equivalent anatomical brain sections. To date, 330 infants have been examined using this method, making evaluation of brain stem, aqueduct, fourth ventricle, basilar artery and basal cisterns possible.

The surfaces of the brain offer metabolic and mechanical support to the underlying parenchyma. Mouse, rat, and monkey brains were fixed by immersion in a glutaraldehyde fixative or glutaraldehyde with cetylpyridinium chloride, followed by block staining for complex carbohydrates using alcian blue with OsO4 postfixation, or OsO4 postfixative solution containing ruthenium red, or alcian blue and then ruthenium red-OsO4 treatment. The ependyma in these species had a glycocalyx extending into the ventricular fluid as a finely filamentous network when stained with alcian blue or with alcian blue followed by ruthenium red-OsO4. Mice in the middle age range had stained material in this glycocalyx resembling the hyaluronic acid reported in the ocular vitreous body. Similar material was seen in the arachnoidal space of these mice and in the inner connective tissue matrix of the dura mater. Both the mouse and monkey had a cell-free zone, termed the inner dural matrix zone, between the thick fibrous dura and its innermost cellular layer. This zone contained filamentous and globular alcian blue-stained material. The complex carbohydrates of the mouse ependymal glycocalyx and inner dural matrix zone underwent changes developmentally. Aged rats were injected intraventricularly with latex beads, which, along with extravasated erythrocytes, were seen to adhere to the ependymal glycocalyx. A similar adhesion of erythrocytes was seen in the mouse and monkey ependymal glycocalyx and in the filamentous network of the mouse and monkey inner dural matrix zone. The ependymal glycocalyx, formed in part of complex carbohydrates, is much thicker than previously demonstrated. Some activities related to the ependymal lining of the ventricles, including the movement of cells or particles, the penetration of metabolites or serum-protein fractions (e.g., immunoglobulins), and cell-surface hydration, probably depend in part on complex carbohydrates that provide a sticky, electrically negative, hydrophilic environment. The complex carbohydrates in the inner dural matrix zone might provide mechanical buffering. Complex carbohydrates in the arachnoidal space may help to maintain a loose tissue that needs not only to be hydrated, but also to be open enough to provide cerebrospinal fluid circulation.

✓ A new model for cerebrospinal fluid (CSF) circulation is proposed. Specific activity/time curves for CSF kinetics determined after intraventricular injection of a radiotracer were produced by fitting a biexponential function to data points and developing a two-compartmental model. Calculation of kinetic parameters of the model provides quantitative data about CSF dynamics. The study of each compartment separately and of the intercompartmental relationship is possible with this model. Sequential scan images and graphic plots of the variations of radioactivity in both compartments, derived from this model, add supplementary information in the evaluation of patients. Ventriculography was performed in 80 patients, who fell into four groups: those with normal CSF circulation, hydrocephalus, infantile hydrocephalus, and functioning ventricular shunts. Normal and hydrocephalic patients showed significant differences between the two groups in the means of some numerical parameters calculated from the new model. An increase of intraventricular radioactivity at 24 hours (p < 10−4) and of the volume of Compartment 1 (p < 0.01) with decreased volume of Compartment 2 (p < 10−4) and total flow outside the system (p < 10−3) were found in patients with hydrocephalus. The limiting values for normal patients were also estimated. Communicating and obstructive hydrocephalus could be differentiated by this method; however, no differences in mean values were found relating to the etiology or clinical course of the hydrocephalus. Normal-pressure hydrocephalus and cerebral atrophy produced significantly different mean values for the volume of Compartment 2 (p < 0.01), flow out of the system (p < 0.01), and intercompartmental flow (p < 0.01).

In serial paraffin sections of brainstems fixed by perfusion, ventriculo-cisternal communications in the caudal part of the fourth ventricle are demonstrable in seven species of a total of 27 species, representing Marsupialia, Edentata, Lagomorpha, Rodentia, Ungulata, Carnivora, and Primates, in all of which the lateral apertures of Luschka are well developed. Caudal apertures appear as irregular defects in the taenia of the fourth ventricle with flattening of the roof against the surrounding leptomeninges over the crebello-medullary cistern in the guinea pig, the mulatta monkey, the squirrel monkey and the cynomolgus monkey. In addition, the one capuchin monkey and the one vervet monkey studied have a midline defect in the roof. In the capybara, a circular midline opening through the roof is closed off dorsally by the cerebellar vermis. These caudal and median defects are thought to be ruptures developed late in fetal life due to accumulation of cerebrospinal fluid before egress through lateral apertures of Luschka is established; although they seem to have served their purpose in the fetus and are no longer needed in the adult, they are kept open by continued flow. Study of fetuses from these selected species could prove useful to determine factors concerned with the development of cerebrospinal fluid circulation.

Beschreibung eines im Kindesalter aufgetretenen Meningioms. Der ursachliche Zusammenhang mit einer 6 Jahre vorher operativ gesetzten Durahirnnarbe wird diskutiert. Die Ausdehnung der Geschwulst machte eine Hemispharektomie erforderlich. Einige Monate spater aufgetretene Liquordrucksteigerung war weder durch Plexuskoagulation noch durch Wiederherstellen der Liquorpassage zur hinteren Schadelgrube und den ubrigen basalen Cysternen zu beheben. Sie lies sich erst durch Einbau eines atrioventrikularen Shunts mittels Spitz-Holter-Ventil beseitigen.

Radiology has made several significant contributions to our understanding of head injuries in recent years. Parallel with the development of new techniques has been the growth of accident services and neurosurgical units throughout the country, so that there has been a gradual improvement in our arrangements for the management of these cases. The policy of transferring complicated cases, and those causing the surgeon anxiety, to neurosurgical units is becoming established, a pattern which will undoubtedly increase in the future. Detailed studies will tend to be concentrated in neurosurgical units where there are full neuroradiological facilities. They will be required particularly for the further investigation of complications arising after the immediate acute period is over; for the assessment of specific matters such as continued neurological deficit, prolonged unconsciousness and epilepsy; and for late complications such as chronic subdural haematoma and disturbances of cerebrospinal fluid circulation....

The purpose of this study focuses on the changes of the syrinx volume after posterior reduction and fixation of the basilar invagination (BI) and atlantoaxial dislocation (AAD) with syringomyelia. We retrospectively analyzed the clinical outcome and syrinx volume changes in 71 patients with BI, AAD and syringomyelia treated with the posterior reduction and fixation technique. Clinical improvement was observed in 64 (90.1 %) patients postoperatively; 5 (7.0 %) were stable and 2 (2.8 %) were clinically aggravated. The postoperative Atlantodental interval became normal in 61 patients (86.0 %); showed reduction that was greater than 50 % but not complete in 5 patients (7.0 %); and reduction which was less than 50 % in 5 patients (7.0 %). The size of the syrinx was reduced postoperatively in 66 patients (93.0 %) while no change in the remaining 5 patients (7.0 %). Posterior reduction and fixation of the AAD and BI can effectively enlarge the foramen magnum, improve the cerebrospinal fluid circulation and consequently reduce the volume of the syrinx.

Passage of neuropeptides from the cerebrospinal fluid to circulation depends upon cisternal pressure. When cisternal collecting pressure was kept at — 20 cm, plasma levels of gastrin-17 and somatostatin-14 remained at basal values despite perfusion of high doses of the peptides into the cerebro-ventricular system. Progressive reduction of this pressure above — 15 cm results in a progressive rise of the peripheral concentration of the peptides. Discrimination between central and peripheral action of centrally administered neuropeptides, therefore, possible.

The hydrocephalic brain of a 3-week-old rabbit with a meningoencephalocele is described. The hydrocephalus is caused by obstruction of cerebrospinal fluid circulation in the aqueduct, which is anomalously formed by several minute tubules surrounded by ectopic ependymal cells. The encephalocele is an atrophied part of the right ventricle forced out of the skull by increased CSF pressure. It is suggested that the aqueductal malformation is caused by an ependymal developmental disturbance.

The role of periventricular tissue surrounding the anteroventral third ventricle (AV3V) in mediating drinking behavior induced by angiotensin II was investigated in rats Electrolytic lesions which bilaterally destroyed preoptic-hypothalamic periventricular tissue surrounding AV3V abolished drinking responses normally elicited by intracerebral injections of angiotensin. In another experiment, ventricular obstruction in AV3V had no effect on drinking of a palatable sweet milk solution while the drinking responses induced by peripheral versus central administration of angiotensin were dissociated. Drinking normally induced by lateral preoptic injections of angiotensin was no longer observed when AV3V obstruction prevented drug distribution via cerebrospinal fluid circulation to AV3V periventricular tissue; the driniking response induced by subcutaneous injection of angiotensin was enhanced, however, after placement of the ventricular obstruction. These results, coupled with the earlier observation t that AV3V lesions also abolish drinking induced by subcutaneous angiotensin injection, suggest that, after central or peripheral administration, angiotensin acts on AV3V periventricular tissue to arouse drinking. In contrast to centrally injected angiotensin, peripherally administered angiotensin does not contact receptors by entry and spread in cerebrospinal fluid. After peripheral injection angiotensin may contact sensitive AV3V tissue directly from blood, perhaps via the organum vasculosum of the lamina terminalis, a highly vascularized circumventricular organ within the AV3V which lacks a blood-brain barrier.

Neuropeptides are present in brain tissue as well as in cerebrospinal fluid. Studies from a variety of disciplines have demonstrated that neuropeptides have neuromodulatory activities. Such activities are apparent in the involvement of neuropeptides in the regulation of adaptive, autonomic, and endocrine functions of the brain. Neuropeptides exert their neuromodulating influences by acting as neurotransmitters or as neurohormones. The neurotransmitter function of neuropeptides is associated with their synthesis in situ in brain and anatomical distribution via neuropeptidergic fibre systems. The presence of such neuropeptides in cerebrospinal fluid may be due primarily to drainage into the cerebrospinal fluid compartments, their levels being a reflection of cellular processes such as biosynthesis, release, and metabolism. On the other hand, neuropeptides functioning as neurohormones may be actively delivered into the cerebrospinal fluid from central or peripheral sources. They employ the pathways of cerebrospinal fluid circulation as avenues of transport, and their cerebrospinal fluid levels may be functionally related to neurohormonal activity. In either case the cerebrospinal fluid levels are informative on the neuropeptide climate in brain; thus their determination is meaningful. The methodology for the sensitive and specific determination of neuropeptides is becoming available. Determination of neuropeptides may well be of diagnostic value in clinical practice.

Summary: Three human infants with hypertensive obstructive hydrocephalus were treated with oral doses of digoxin beginning on the 2nd, 7th, and 13th week of postnatal life, respectively. One infant received 0.015 mg/kg/day and two infants were given 0.010 mg/kg/day of digoxin. The drug failed to alleviate any clinical signs of elevated intracranial pressure. Groups of 10-day-old infant rats were acutely digitalized by sc administration of three successive doses of digoxin (3 mg/kg body wt) at 20-min intervals. In the first group electrocardiograms and electroencephalograms were monitored. Additionally, arterial blood pressure was monitored by means of an aortic catheter. The electroencephalographic and cardiovascular response differed from controls only by minor changes in the ECG wave-form (increased amplitude of the QRS and T-waves). In the second group the rate of bulk flow [or cerebrospinal fluid (CSF) formation] was assessed by 5-min intrathecal infusion of 14C-inulin, performed 20 min after the last injection of digoxin. Comparative values for inulin clearance from the CSF system (µl/min) of experimental and control animals were calculated from inulin concentrations in CSF at stated intervals of 15-22, 22-30, 30-45, and 45-60 min after the last dose of digoxin. Rates of CSF formation were depressed to about 50% of control levels at 15 min, reaching a state of complete arrest between 22 and 45 min, and followed by rapid recovery to resting levels at 60 min. In the third experimental group of digitalized infant rats, concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in CSF and brain were assessed 80 min after the last injection of digoxin. Although no significant change in the amounts of 5-HIAA was found in brain tissue, the 5-HIAA concentrations in the CSF of digoxin-treated rats rose to values that were 140% greater than found in controls. An additional group of 10-day-old rats was killed 60 min after se injection of probenecid, 250 mg/kg body wt. Probenecid, a drug which competitively inhibits carrier-mediated transport of 5-HIAA from both the brain and CSF system, increased both brain and CSF concentrations of 5-HIAA by 55 and 432%, respectively. Speculation: We speculate that, although digoxin, in doses not toxic to the cardiovascular system, can completely arrest fluid secretion by the choroid plexus of the rat, its duration of action is too brief, rendering it useless for the treatment of chronic hydrocephalus in man. We also speculate that, despite the presence of efficient transport mechanisms localized to the brain parenchyma as well as the choroid plexus, the circulation of CSF is necessary for efficient elimination of acid metabolites from the central nervous system.

This study is designed to obtain more reliable diagnosis of an impairment of cerebrospinal fluid (CSF) circulation in patients with suspected of hydrocephalus or malfunctions of shunt systems. Such seventeen patients and three control patients (pituitary adenoma; 2, suspected CSF rhinorreal; 1) were included in our study. Twelve male and eight female patients ranged from 18 to 70 year-old (mean 59.5, postoperative follow-up period after a final diagnosis; 2–32 months). Etiologies of the diseases were subarachnoid hemorrhage (4), brain tumor (2), unknown (10), and cryptococcal meningitis(1).

✓ A simple technique for the evaluation of shunt function and cerebrospinal fluid (CSF) circulation in hydrocephalic patients is described. The method utilizes clearance rates of a radionuclide tracer injected into the lateral ventricle via an indwelling frontal catheter which is separate from the shunt apparatus. This permits an accurate assessment of drainage of ventricular CSF via the shunt, or the patency of normal or alternative CSF pathways where the shunt is malfunctioning.

The dynamics of cerebrospinal fluid (CSF) circulation in 20 cases with hypertensive intracerebral hemorrhage was estimated with radioisotope cisternography (RIC) using In-111-DTPA. CT scan was performed simultaneously to observe the changes in the intracranial pathologies. The findings in RIC were classified into four types; normal circulation, ventricular reflux, ventricular stasis, and subarachnoid block over ipsilateral convexity. Among 20 cases examined with RIC in the acute stage, normal circulation was demonstrated in 11 cases (55.0%), ventricular reflux in 1 case (5.0%) and a subarachnoid block over ipsilateral convexity in 8 cases (40.0%). In the subacute stage, 11 out of 17 cases (64.6%) showed normal circulation, 3 (17.7%) ventricular reflux and 3 (17.7%) a subarachnoid block over ipsilateral convexity. Of 8 cases in the chronic stage, 5 cases (62.5%) showed normal circulation, 1 case ( 12.5%) ventricular reflux, 1 case (12.5%) ventricular stasis, and 1 case (12.5%) a subarachnoid block over ipsilateral convexity. Ventricular reflux and ventricular stasis which were demonstrated mainly in the later stage, seemed to be caused by blood in the CSF, because all cases with such abnormalities in RIC had a hematoma in the ventricle at the onset of hemorrhage, and none of the cases without rupture of the hematoma into the ventricle showed such abnormalities. A subarachnoid block over the ipsilateral convexity which was mainly observed in the acute stage and which frequently disappeared in the chronic stage was caused by the mass effect of the hematoma and the surrounding edema, because it was observed only in cases with larger hematomas. In 6 cases which developed ventricular dilatation in the chronic stage, 3 had a normal finding by RIC and the ventricular dilatation was probably caused by brain atrophy after absorption of a hematoma. The other 3 cases showed ventricular stasis by RIC and the disturbance in the CSF circulation may partly contribute to the ventricular dilatation. Thus, follow-up studies by RIC after a hypertensive intracerebral hemorrhage revealed consecutive pathophysiological changes in the CSF circulation in accordance with the intracranial pathological changes.

Hydrocephalus is an important complication of subarachnoid hemorrhage (SAH). We analyzed several factors possibly related to hydrocephalus following SAH in 3521 patients from the International Study on the Timing of Aneurysm Surgery. Hydrocephalus was diagnosed on admission computed tomographic (CT) scans in 15% of patients and was thought to be clinically symptomatic in 13.2% of patients. There was a 5.9% overlap between these groups. Using contingency table analysis, we found the following were significantly related to clinical hydrocephalus: increasing age; preexisting hypertension; admission blood pressure measurements; postoperative hypertension; admission CT findings of intraventricular hemorrhage, a diffuse collection of subarachnoid blood, and a thick focal collection of subarachnoid blood; posterior circulation site of aneurysm; focal ischemic deficits; use of antifibrinolytic drugs preoperatively; hyponatremia; admission level of consciousness; and a low score on the Glasgow outcome scale. Using discriminate factor analysis to predict clinical hydrocephalus, the most important variables in order were the following: CT hydrocephalus, intraventricular hemorrhage, admission level of consciousness, presubarachnoid hypertension, increasing age, subarachnoid blood noted on CT scan, posterior circulation aneurysm site, and hypertension postoperatively (canonical correlation = .399). We conclude that the development of hydrocephalus after SAH is multifactorial. Factors that compromise cerebrospinal fluid circulation acutely (eg, intraventricular hemorrhage, hemorrhage from a posterior circulation site of aneurysm, and diffuse spread of subarachnoid blood) contribute to the development of acute hydrocephalus. These same factors, plus the use of antifibrinolytic drugs preoperatively, are also important in the pathogenesis of clinical hydrocephalus, perhaps by promoting subarachnoid fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

It was determined from in vitro experiments that the minimal dose of urokinase required to lyse 10 ml of clotted canine blood within a closed space must exceed 10,000 IU. We empirically doubled this minimum effective dose and tested the in vivo safety of injecting 20,000 IU of urokinase every 12 hours for 4 days into the ventricles of six adult mongrel dogs through an implanted catheter-reservoir system. The animals were monitored carefully for local and systemic bleeding by neurological and clinical examination, hematological tests reflecting systemic fibrinolytic status, serial computed tomography, and postmortem histological examinations of the brain, meninges, and peripheral organs. It was found that this intraventricular dose regimen of urokinase did not cause intracranial hemorrhage even though the dogs had recent brain wounds related to transcerebral ventricular catheterization. Mild activation of systemic fibrinolysis, implying passage of the enzyme from ventricle to blood, occurred 4 to 6 hours after each intraventricular injection, but no systemic hemorrhages were seen. This dose regimen also did not cause acute or chronic inflammatory changes in the brain or meninges and did not disturb cerebrospinal fluid circulation.

✓ The techniques of Amipaque (metrizamide) computerized tomography (CT) cisternography and Amipaque CT ventriculography are described. Normal, intermediate, delayed, and obstructive cerebrospinal fluid circulation patterns are readily demonstrated by evaluation of ventricular stasis of Amipaque on serial CT scans. Both the morphological and physiological characteristics of intracranial cysts are accurately defined and a diagnostic classification is presented. The functional integrity of ventricular shunts can be appraised using the ventricular persistence of Amipaque as a primary criterion. Other applications of these modalities are described and their place in the neurodiagnostic armamentarium is discussed.

Since the early seventies physical and mathematical models describing the CSF circulation have been developed among which the “Marmarou” model (1973) is the most widely used. Although most models primarily describe the disturbances between formation, storage and absorption of CSF in hydrocephalus, they can also be applied to CSF circulatory disorders resulting from other causes. The model parameters provide information on the rate of CSF formation and absorption (compensatory ability) as well as on the storage capacities (elastance) of the system. The absolute values of these parameters, however, depend largely on the assumptions made in the model equations. For example, the parameters are generally assumed to be unaffected by the type and rate of volume disturbance (volume-pressure test versus infusion test), although the results of Sullivan et al. (1978) and Borgesen et al. (1979) have invalidated this assumption.

1. The syndrome of incisural hippocampal herniation, accompanied by unilateral and then bilateral fixed pupils, deepening coma, respiratory irregularity (Cheyne-Stokes), contralateral hemiplegia, ipsilateral decerebrate posturing, rising blood pressure, and finally renal shutdown, indicates a terminal state that requires immediate relief. 2. Accepted methods of relief by brain shrinkage, dexamethasone, subtemporal decompression, anterior temporal lobectomy, cutting of the tentorium, and even massive uncapping of the skull, have failed in the author's experience to reverse the process when once established. 3. Presentation is made of a rapid and relatively simple inferior horizontal temporal lobectomy, including the hippocampal gyrus, so as to relieve peduncle compression, blockage of cerebrospinal fluid circulation, midbrain haemorrhage, and infarction in the posterior cerebral artery distrubution area. 4. Reports are given of 15 cases out of 30 cases in which operation proved lifesaving, with restoration of normal function in 13. 5. Those patients who died did so in an average of five days, and generally showed either no herniation or continuing evidence of tumour or internal bleeding. 6. Very young patients particularly have an excellent chance of survival, which is seven times better than that of adults in having good to excellent results without operation.

Cerebrospinal fluid (CSF) circulation has been analyzed by metrizamide computed tomography (CT) cisternography in 46 patients. Included were 7 patients without any clinical evidence of impaired CSF circulation, and 39 with hydrocephalus due to various causes. CT cisternography delineated the anatomical structures of the CSF pathways clearly and accurately and enabled us to analyze ventricular filling in a quantitative manner. As a result, a new, more precise CT cisternographic classification of the CSF flow patterns has been established. On the basis of the presence of ventricular reflux and stasis, extent of ventricular filling, and convexity flow of metrizamide, seven groups of flow patterns have been defined.

Much is known about the mechanisms of production and absorption of cerebrospinal fluid (CSF), but there remains little general agreement regarding the specifics of these physiological phenomena.10 In this chapter, the authors will discuss CSF physiology from the bias of the diagnostic imaging studies employed in evaluating hydrocephalus and from a series of experiments utilizing animal models developed by our laboratory.29,33,38,39

The combination of the empty sella syndrome (ESS) and benign intracranial hypertension (BIH) is illustrated by two case histories. The causal relationship between the ESS and the BIH can be explained by two mechanisms. Raised intracranial pressure could produce a herniation of the subarachnoid cistern into the sella turcica, if the diaphragma sellae is incomplete. Alternatively an infarction in a pituitary adenoma could result in both an ESS and cerebrospinal fluid flow obstruction, which could lead to BIH.

Intraventricular hemorrhage in its acute stage was investigated both experimentally and clinically with special emphasis on factors that aggravate its prognosis. In an experimental study, two groups of animals, one with blood clots in the ventricle and the other with liquid blood in the ventricle, were compared in terms of pathophysiological and morphological features. The fatal outcome in the experimental dogs was related to the amount of blood injected and its rate of injection. The injection of non-heparinized blood into the ventricle might have a more delaterious effect on the brain than that of heparinized blood. The following factors were shown to play a significant role in deterioration of the existing disease: 1) the amount of hematoma and the rate of blood injection (or speed of bleeding), 2) intraventricular blood clot formation and its extent, 3) disturbance of cerebrospinal fluid circulation, 4) paraventricular tissue damage, 5) the site and extent of intracerebral hematoma and ventricular perforation and 6) the primary disease and age.

The purpose of this paper is to investigate the pathophysiology of the hydrodynamics in normal pressure hydrocephalus (NPH) and to suggest prognostic criteria by which patients with NPH who may benefit from a shunt can be selected.

THE USE of radioactive isotopes in the treatment of neoplasms has proved to be of considerable value. It is as yet too early to know whether cures can be obtained, but encouraging results have been reported in carcinoma of the prostate,* carcinoma of the cervix,† and malignant pleural and peritoneal effusions.‡ Neoplasms of the central nervous system have been treated by means of pledgets of absorbable gelatin sponge (Gelfoam) impregnated with radioactive gold applied to the tumor bed after surgical removal.9Recently, Lewis10has briefly reported his experience with injection of gold into the subarachnoid space in one patient in a terminal state following recurrence of a glioma. Some brain tumors, such as medulloblastomas and ependymomas of the posterior fossa, tend to spread through the subarachnoid space, following the pathways of cerebrospinal fluid circulation. Although the main mass of tumor may yield to surgical excision, local recurrence and

Systemically ineffective amounts of a cortisol acetate emulsion or pellets of corticosterone or dexamethasone were placed in various regions of the ventricular system of the rat. One or 2 days later the effect on ether-induced ACTH secretion was estimated indirectly by measuring plasma corticosterone changes. Injections of cortisol acetate or implants of dexamethasone were effective in suppressing ACTH secretion when placed into the lateral ventricle but not if placed immediately adjacent to the ventricle. Injections of cortisol acetate into the temporal horn of the ventricle were effective in suppressing ACTH secretion. Implants of corticosterone acetate in the third ventricle were also effective. Implants of this steroid in the tissue immediately adjacent to the third ventricle were effective, but the effectiveness decreased with increasing distances of the implants laterally from the third ventricle. Injections of cortisol acetate into the cisterna cerebellomedullaris were ineffective. It is suggested ...

The intracranial pressure measured as the ventricular fluid pressure (VFP) was recorded continuously via a cannula in the left lateral ventricle of the brain of conscious rabbits 2 days after intracisternal administration of kaolin, known to induce intracranial hypertension. The effect of sympathectomy was studied at various time-periods after bilateral removal of the superior cervical ganglia: (a) During a 2-day recording period following shortly after sympathectomy the VFP of kaolin-treated animals was considerably lower compared to non-sympathectomized, kaolin-treated animals, (b) One week after sympathectomy the VFP was initially lower than in the non-sympathectomized controls. However, it rapidly increased to very high levels, and all animals died within 10 hours after the recording was started, (c) About 2 weeks after sympathectomy the pressure tended to be lower than in the non-sympathectomized control animals. It is suggested that these findings are mainly the result of changes in the intracranial blood volume (although direct effects of the sympathectomy on cerebrospinal fluid circulation can not be excluded). Thus, shortly after sympathectomy–period (a)–when the transmitter is leaking from the degenerating nerves, the intracranial vessels contract and the blood volume decreases. In addition, the intracranial hypertension has probably resulted in a compensatory increase in cerebrospinal fluid absorption and/or reduction in its formation, which will further lower the VFP. Period (b): the denervated vessels dilate and the increased intracranial blood volume will add to the intracranial hypertension caused by the blocked cerebrospinal fluid circulation and the edema produced by the implantation of the pressure cannula. Period (c): the brain vessels have developed a pronounced denervation supersensitivity to circulating catecholamines, the vascular tone is enhanced and the reduced blood volume will tend to lower the VFP.

São apresentados os resultados obtidos com a ventrículo-auriculostomia, com válvula de Holter, no tratamento de 32 pacientes com bloqueio ao trânsito do líquido cefalorraqueano, causado por neoplasia encefálica ou processo inflamatório da leptomeninge ou do epêndima ventricular. Os resultados foram satisfatórios em 20 doentes; 3 não voltaram para contrôle e 9 faleceram. Todos os casos de óbito ocorreram em pacientes com neoplasia encefálica e apenas em um foi relacionado à complicação infecciosa da derivação ventriculovenosa. The results obtained in 32 patients with obstruction of the cerebrospinal fluid circulation caused by cerebral tumors and inflammatory reactions of the leptomeninges or ventricular ependima, are presented. The results were satisfactory in 20 cases; 3 patients did not come back for follow-up and 9 died. All deaths occurred in the group of neoplasms, and only in one case this bad evolution was related to infectious complication of the ventriculo-venous shunt.

The authors describe the techniques of isotope cisternography and ventriculography with high specific activity I131 and Tc99m albumin in children and adult patients. They have studied 35 patients including different type of obstructive and communicating hydrocephalus, microcephalic patients and patients with no intracranial pathology. The value, the limitations, and the potential damage of the test are discussed and the proper use of the two different tracers is assessed.

São apresentados 16 casos de cisticercose encefálica com bloqueio ao trânsito do líquido cefalorraqueano, nos quais foi feita ventrículo-auriculostomia com válvula de Holter. Dos 16 pacientes, 5 faleceram, 10 estão vivos e sem sinais de hipertensão intracraniana e um não foi seguido. Considerando-se o prognóstico reservado da doença, principalmente quando existe hipertensão intracraniana, os resultados podem ser considerados bons. A derivação ventriculovenosa constitui, portanto, valioso método no tratamento da neurocisticercose com dilatação ventricular, causada por bloqueio ao trânsito do LCR. Algumas vêzes a má evolução do caso está relacionada à progressão da própria doença e não à falha no contrôle da hipertensão intracraniana. Sixteen cases of brain cysticercosis with obstruction of cerebrospinal fluid circulation were operated from 1960 to 1965, through ventriculo-auri- culostomy with Holter valve. Five patients died, ten are alive and free of signs of intracranial hypertension and one could not be followed up. Considering the usual bad prognosis of the disease, mainly when increased intracranial pressure is present, the results obtained can be considered good. Therefore, the ventriculovenous shunts are a valuable resource in the treatment of the neurocysticercosis with ventricular dilatation caused by cerebrospinal fluid obstruction either in the intraventricular pathway or in the subarachnoid space. Sometimes the evolution is not satisfatory owing to the progressive course of the disease itself and not as a consequence of a bad control of the increased intracranial pressure.

T HE treatment of brain abscesses in all stages of encapsulation by radical removal of abscess and adjacent softened brain tissue has been reported by several authors. 6,11,14,1~ The reduction in over-all mortality using this method in conjunction with systemic and intraventricular penicillin is a consistent finding in all the reports in the literature. Chorobski and Kunicki 6, in a recent publication reviewing all reported brain abscesses treated by radical removal, state that there were no cases in which meningitis was reactivated by the operation provided antibodies were used. In view of the growing enthusiasm for this type of treatment of brain abscesses, ~ cases are presented with unilateral hydrocephalus secondary to obstruction of the foramen of Monro following removal of a brain abscess. The causal relationship between obstruction in the cerebrospinal fluid circulation and the development of hydrocephalus has been suspected for over half a century and proved experimentally since 1913. The first experi' mental production of hydrocephalus in animals by occlusion of one foramen of Monro by Thomas 2~ was overshadowed by the publications of Dandy 9 at about the same time. Both workers gave adequate experimental proof of the development of hydrocephalus in animals following occlusion of the cerebrospinal fluid pathways. Severe reactions in the ependyma of the lateral ventricles, 3rd ventricle, or aqueduct of Sylvius producing subsequent gliosis and obstruction to the interventricular passages have been occasionally reported. The cause of the ependymitis in some cases has not been determined. 2,12,1s,19,21 In others the gliosis of the ependyma has been secondary to known or suspected meningitis. ~ Burr and McCarthy 4 as early as 1900 attempted to duplicate this picture by injecting irritating substances into the lateral ventricles of experimental animals. They successfully produced ependymitis but unfortunately did not allow their experimental subjects to survive long enough to develop dilatation of the ventricles. The first clearly defined clinical case of unilateral hydrocephalus from obstruction to one foramen of Monro was described by Cushing. s In this presentation Cushing considered the obstruction was secondary to ependymitis, the result of so-called "brain fever" some months previously. The

Spatial resolution remains one of the major problems and goals in spinal imaging. The high spatial resolution afforded by a novel sequence, constructive interference in steady state (CISS), provides a further refinement to MRI, the modality of choice in the investigation of suspected intraspinal pathology. Both complex and subtle abnormalities are more fully elucidated using CISS. It is now used in our institution as an adjunct to conventional imaging sequences in the diagnostic evaluation of complex intraspinal pathology. The anatomical information provided by CISS is of particular value in planning surgical interventions, most notably in the management of intraaxial and extraaxial cystic abnormalities, dysraphic malformations and disturbances of cerebrospinal fluid circulation, including post-traumatic and post-surgical scarring.

A case of acute obstructive hydrocephalus in a patient undergoing an aortic valve replacement is presented. This condition came about as a result of massive left cerebellar hemisphere infarction, probably due to a calcific embolism from the aortic valve. The cerebrospinal fluid circulation was blocked by compression of the fourth ventricle and the Sylvius aqueduct secondary to ischemic edema. Following external ventricular drainage, the hydrocephalus resolved but a neurological deficit secondary to the cerebellar and brain stem infarction became evident. The diagnostic, prognostic and therapeutic implications of this unusual complication following cardiac surgery are discussed.

Objectives To assess the influence of age and sex on ten cerebrospinal fluid (CSF) flow dynamics parameters measured with an MR phase contrast (PC) sequence within the cerebral aqueduct at the level of the intercollicular sulcus. Materials and Methods 128 healthy subjects (66 female subjects with a mean age of 52.9 years and 62 male subjects with a mean age of 51.8 years) with a normal Evans index, normal medial temporal atrophy score (MTA) and without known disorders of the cerebrospinal fluid circulation were included in the study. A phase contrast MR sequence on a 3T MR scanner was used. Ten different flow parameters were analyzed using postprocessing software. Ordinal and linear regression models were calculated. Results The parameters stroke volume (sex: p

The subcommissural organ is an ependymal brain gland that secretes glycoproteins to the cerebrospinal fluid (CSF) of the third ventricle. They condense to form a fibre, Reissner's fibre (RF), that runs along the aqueduct and fourth ventricle and the central canal of the spinal cord. A single injection of an antibody against the secretory glycoproteins of RF into a lateral ventricle of adult rats results in animals permanently deprived of RF in the central canal and bearing a "short" RF extending only along the aqueduct and the fourth ventricle. These animals, together with untreated control animals were used to investigate the probable influence of RF in the circulation of CSF in the central canal of the spinal cord. For this purpose, two tracers, (horseradish peroxidase and rabbit immunoglobulin) were injected into the ventricular CSF. The animals were killed 13, 20, 60, 120 and 240 min after the injection, and the amount of the tracers was estimated in tissue sections obtained at proximal, medial and distal levels of the spinal cord. In rats deprived of RF, a significant decrease in the amount of tracers present in the central canal was observed at all experimental intervals, being more evident at 20 min after the injection of the tracers. This suggests that lacking a RF in the central canal decreases the bulk flow of CSF along the central canal. Turbulences of the CSF at the entrance of the central canal of RF-deprived rats might explain the inability of the regenerating RF to progress along the central canal, as well as the reduced flow of CSF in the central canal of these animals.

The rate at which isotopes descend from the cisterna magna to the lumbar subarachnoid space is highly variable. In monkeys, with and without previous lumbar puncture, transit time was measured. In animals with a previous lumbar puncture, transit times were 10 to 120 minutes; in monkeys without a previous lumbar puncture, transit times were 120 to 180 minutes. In experimental studies of cerebrospinal fluid circulation, the effect of lumbar puncture must be controlled.