Effect of hypertonic solutions on the blood-brain barrier.

The effect of hypertonic urea and saline on the blood-brain barrier of the dog was quantitatively measured by the indicator diffusion technique. Urea appeared to stimulate glucose transport into the brain, while the diffusionary loss of fructose was enhanced. Hypertonic saline affected the diffusionary loss of the test sugars in a similar manner, but had no effect on glucose transport. The blood-brain barrier alterations were not reversible, but did decrease somewhat with time.

Early management and decision making for the treatment of myelomeningocele.

A program for early selection and treatment of the infant with myelomeningocele was developed at the University of Oklahoma Health Sciences Center in 1977. Over a 5-year period, 69 babies were evaluated, 36 babies were recommended for early vigorous treatment. Of the 33 babies for whom only supportive care was recommended, five were initially treated at the parents' request, two underwent delayed vigorous treatment, one was subsequently treated by "crisis management," one moved and did not return for follow-up, and 24 received only supportive care. All 24 babies died between 1 to 189 days of age (mean 37 days). The involvement of several physicians and paramedical support personnel is considered essential for this approach of early selection and treatment. Continued support and regular follow-up is necessary for any baby who receives only supportive care. Parents retain legal custody. Although ethical concerns make any approach difficult, the method presented is considered to be the best alternative available at this time.

Blood-brain barrier: a definition of normal and altered function.

The anatomical component of the blood-brain barrier (BBB) has been shown to be the cerebral capillary. These capillary endothelial cells are connected by continuous tight intercellular junctions and under normal conditions do not demonstrate transendothelial channels or pinocytotic vesicles. The rate that substances penetrate the BBB is related to molecular size, lipid solubility, and the presence of a specific carrier-mediated transport system. This latter mechanism for transendothelial passage is utilized for the movement of a wide variety of biologically important compounds such as sugars, amino acids, and organic acids. In certain pathological conditions, the permeability of the BBB is altered so that normally excluded plasma proteins and fluid enter the brain extracellular space, with the subsequent development of cerebral edema. In other abnormal conditions, alterations in the specialized transport systems operating across the cerebral capillary result in adverse changes in cerebral and neurotransmitter metabolism. An understanding of the unique properties of the BBB and of the changes that occur in pathological conditions has allowed the development of rational therapeutic strategies for a wide variety of diseases of the central nervous system.

Intraventricular pneumocephalus secondary to subcutaneous emphysema: a case report.

Intraventricular tension pneumocephalus is an unusual complication of surgically treated hydrocephalus. This is a life-threatening complication requiring prompt diagnosis and treatment. A case is presented wherein tension pneumocephalus developed as a result of cervicocranial subcutaneous emphysema in the presence of a ventriculoperitoneal shunt.

Quantitative anatomy of the thoracolumbar epidural space.

Quantitative measurements of the epidural space between T-7 and L-4 were made in the sagittal and coronal planes utilizing x-ray films made after the injection of iodized oil into the epidural space in the low thoracic and upper lumbar areas. These data reveal a 1-mm ventral epidural space and a 2-mm lateral epidural space, with a sawtooth shape to the dorsal epidural space measuring between 1.1 and 2.9 mm at the rostral lamina and between 3.8 and 6.5 mm at the caudal lamina. Additionally, five patients with chronic pain were studied by computed tomography of T-8 to T-12, with confirmation of the sawtooth shape of the dorsal epidural space. Computed tomography showed the measurements of the epidural space at the rostral lamina to vary between 1.3 and 1.6 mm and those at the caudal lamina/interlaminar space to range from 6.9 to 9.1 mm.

Cystic optic glioma.

A pilocytic astrocytoma of the optic nerve, chiasm, hypothalamus, or third ventricle is a relatively common tumor of childhood. This case report illustrates such a tumor, originating from this location, which is unusual because of the association with two very large cystic extensions into the middle cranial fossa and into the third ventricle. The massive size and extent of this tumor and cysts was demonstrated on a magnetic resonance imaging (MRI) scan, with gadolinium enhancement. This case illustrates a novel macroscopic appearance for a pilocytic glioma of the anterior third ventricle. The purpose of this report is to alert clinicians to the varied morphology this tumor may present as we apply increasingly our improved radiological, operative, and histopathological techniques.

Choroid plexus Na+/K+-activated adenosine triphosphatase and cerebrospinal fluid formation.

The quantitative relationship between intraventricular fluid formation and choroid plexus Na+/K+-activated (transport) adenosine triphosphatase (ATPase) was studied in rabbit and dog by perfusing the ventricular system with a solution containing ouabain (10(-8) to 10(-3) M). The effect of ouabain in the same range of concentrations on ATPase activity was also measured by the release of inorganic orthophosphate from in vitro choroid plexus tissue. Normally, about 20 to 25% of ATPase activity in lateral ventricle plexus is Na+/K+-activated, and this component is almost completely inhibited by ouabain in a concentration of 10(-4) M. At this concentration, the rate of intraventricular cerebrospinal fluid (CSF) formation is decreased some 70 to 80% in dog and rabbit. The results of this study suggest that a portion of the intraventricular fluid formation is insensitive to cardiac glycoside inhibition and that either there are two different mechanisms responsible for choroid plexus fluid formation or there is a significant non-ATPase dependent extrachoroidal source of CSF.

The effect of apnea on brain compliance and intracranial pressure.

The effect of 2 minutes of apnea during endotracheal intubation on intracranial pressure (ICP), compliance, and cerebral blood volume (CBV) was studied in 19 adult dogs during normo-, hypo-, and hypercapnia. The compliance was measured from the cisterna magna in response to an intrathecal bolus injection (pressure-volume index). CBV was monitored by radiolabeled red blood cell activity. These measurements were made before and after 2 minutes of apnea. At normocapnia (pCO2 of 35-40 mm Hg), a period of apnea resulted in an increase in ICP from 9.6 to 26.3 mm Hg, a decrease in compliance from 0.051 to 0.020 ml/mm Hg (60%), and an increase in CBV of 0.26 ml (9.6%). When the animals were hypocapnic (pCO2 of 24-28 mm Hg), ICP increased from 12.8 to 19.6 mm Hg, compliance fell from 0.041 to 0.029 ml/mm Hg(29%), and CBV increased 0.07 ml (3.1%). Hypercapnia (pCO2 of 50-58 mm Hg) before apnea resulted in an increase in ICP from 21.5 to 47.1 mm Hg, a decrease in compliance from 0.032 to 0.015 ml/mm Hg (52%), and an increase in CBV of 0.41 ml (13.4%). These results suggest that hyperventilation (hypocapnia) before intubation limits the adverse decrease in brain compliance and increase in ICP by reducing changes in cerebral blood volume.

Formation of cerebrospinal fluid. Relation of studies of isolated choroid plexus to the standing gradient hypothesis.

After a brief summary of current views on the origin of cerebrospinal fluid (CSF) and the processes underlying its elaboration, the author discusses studies of isolated choroid plexus in extracorporeal perfusion systems and flux chambers. The results suggest that transependymal water flow is secondary to the electrically silent pumping of sodium. The author presents evidence in support of the standing gradient hypothesis as the structural basis of CSF secretion.

Fluid flow performance of a new siphon-control device for ventricular shunts.

Most available cerebrospinal fluid diversion systems utilize differential-pressure valves that often induce overshunting, resulting in complications due to the siphoning of fluid from the ventricular system when the patient is in the erect position. A new siphon-control device (SCD) was tested alone and in combination with four types of differential-pressure valves with low, medium, and high opening pressures (namely PS Medical, Heyer-Schulte, Cordis-Hakim, and Codman valves). The valve inlet and outlet pressures were measured at several fluid inflow rates between 2.0 and 50.0 ml/hr. Inlet pressure and valve resistance were determined when the outlet pressures of the differential-pressure valve or SCD were varied between 0 and -60 cm H2O. Of the differential-pressures valves tested, none provided protection against siphoning without the distal connection of the SCD. The SCD allowed all differential-pressure valves tested to maintain atmospheric pressure regardless of the outlet pressure. The SCD performs in a manner similar to the older anti-siphon device, but with some improvements in design and construction. The results of this investigation suggest that the increased resistance due to the inline SCD is not functionally significant when added to the conventional valve systems with low opening pressure.

Effect of mannitol and furosemide on blood-brain osmotic gradient and intracranial pressure.

The effect of mannitol (1.0 gm/kg) and furosemide (0.7 mg/kg), alone and in combination, on the blood-brain extracellular fluid and cerebrospinal fluid (CSF) osmotic gradient, elevated intracranial pressure (ICP), CSF and serum osmolality, and urine output was studied in 26 mongrel dogs. Mannitol and furosemide, when used together, produced a greater (62.4% versus 56.6%) and more sustained (5 hours versus 2 hours) fall in ICP than mannitol alone. This correlated with a prolongation of the reversal of the blood-brain osmotic gradient (-3.4 to + 38.5 mOsm/kg) and a rate of urine formation 15 times control values. There was a transient but not significant fall in serum Na+ with the combined treatment, but the arterial pressure did not vary from pretreatment levels. The results from this present study suggest that the distal loop diuretics in a dose of less than 1.0 mg/kg act synergistically with mannitol by causing preferential excretion of water over solute in the renal distal tubule, and thereby sustaining the osmotic gradient initially established by the mannitol infusion. It is possible, but unlikely in the doses used, that the additive effect of furosemide on reducing ICP in the presence of mannitol is due to interference with CSF formation or Na+ and H2O movement across the blood-brain barrier.

Benzodiazepine receptors and cerebrospinal fluid formation.

There is autoradiographic evidence that peripheral-type benzodiazepine ligands bind with high affinity to the membranes of choroid plexus tissue. In this study, the binding of a 4'-chloro analog of diazepam (Ro 5-4864) to rabbit choroid plexus and cerebral cortex was accomplished utilizing an in vitro radioactive assay method. A kinetic analysis of this binding revealed a relatively high affinity of this ligand (KD) for peripheral binding sites in plexus tissue (KD = 16.1 nM/mg protein). There was a 4.6-fold greater density of binding sites (total receptor density (Bmax) = 2.3 pmol/mg) in choroidal membrane as compared to cortical tissue (Bmax = 0.5 pmol/mg). In 40 rabbits in which a ventricular perfusion system was used, the rate of cerebrospinal fluid (CSF) formation was observed to decrease some 48% in the presence of 10(-4) M Ro 5-4864, although some inhibition of secretory activity was still noted at a CSF concentration of 10(-8) M. The choroid plexus tissue levels of adenosine 3',5'cyclic monophosphate (cAMP) and adenosine triphosphatase (ATPase) were not affected by 10(-4) M Ro 5-4864. The results of this study support the notion that the specific benzodiazepine peripheral binding sites in choroid plexus serve to modulate CSF formation. The mechanism of action is poorly understood but does not involve the transport ATPase system or the second messenger cAMP.

Cranial hemophilic pseudotumor. Case report.

Hemophilic pseudotumor is a rare complication of hemophilia occurring in 1% to 2% of individuals with a severe factor VIII or IX deficiency. This pseudotumor has been defined as a progressive cystic swelling involving muscle that is produced by recurrent hemorrhage and may be accompanied by roentgenographic evidence of bone involvement. The case is presented of a 12-month-old child with mild factor VIII deficiency (10% of normal factor VIII activity), who developed a pseudotumor of the skull.

Effect on intracranial pressure of furosemide combined with varying doses and administration rates of mannitol.

The first part of this study investigated the combined use of furosemide and mannitol in the treatment of elevated intracranial pressure (ICP). Two groups of dogs were studied to determine if renal excretion of mannitol was altered in the presence of furosemide. No significant difference in excretion was noted between the two groups. Fifteen animals were used in other studies to identify the most advantageous sequence of administration of furosemide and mannitol. Infusion of mannitol followed by furosemide 15 minutes later resulted in the most profound and sustained ICP reduction. The effect on ICP reduction of varying the mannitol dose was observed in studies using single doses of 0.5 gm/kg, 0.75 gm/kg, and 1 gm/kg. The larger mannitol dose, resulting in a greater blood-brain osmotic gradient, proved to be the most efficacious in ICP reduction. A further 15 animals were used in investigations to determine whether changing the rate of delivery of the most effective mannitol dose (1 gm/kg) influenced resultant ICP reduction. The results indicated that rapid administration (2 ml/kg/min) produced higher peak serum concentrations of mannitol and more profound lowering of ICP than the same dose delivered at slower rates.

Blood-brain barrier restoration following cold injury.

Cerebral blood flow (CBF), 113mIndium-DPTA, and 14C-glucose extraction were measured simultaneously in rat brain from 2 to 58 days following a thermal insult. In the early stage of a cold induced lesion (2 days), the blood-brain barrier (BBB) was disrupted with resulting leakage and diffusionary loss of both glucose and indium-DPTA. The adjacent, nonnecrotic brain showed similar but more subtle changes. In both areas, CBF was markedly reduced. CBF and augmented loss of glucose and Indium-DPTA continued in the epicenter of the lesion for up to 58 days postinjury while the BBB function in the brain areas surrounding the lesion returned toward normal. These findings were consistent with observation of disruption of BBB activity and of immature brain capillaries during the reparative period.

Pediatric syringomyelia.

Syringomyelia was first recognized as a disease process some 400 years ago. The process of cystic dilation of the spinal cord is unpredictable and may result in a delay of many decades before the symptoms and signs of neurologic and orthopedic changes become apparent and commensurate with the observed cystic changes within the spinal cord. The syringomyelic process is usually associated with trauma, tumor, or congenital abnormalities at the craniocervical junction or along the spinal neuraxis. Several theories have been proposed as to processes involved in the development of spinal cyst formation, although none are completely compatible with the observed clinical pathology of syrinx development. Magnetic resonance imaging has markedly improved our ability to study the anatomy and natural history of syrinx formation, but to date, our understanding of the process remains imprecise. In view of the limited understanding of the pathophysiology of this disease process, it is not surprising that a variety of treatment regimens have been proposed and their efficacy remains difficult to fully evaluate.

Shunt-related brain abscess and ascending shunt infection.

We report the fifth case of shunt-related brain abscess. Two prior cases have been associated with colonic perforation and infection with gram-negative enteric organisms. These cases strongly suggest that ascending shunt infection is possible despite bulk cerebrospinal fluid flow in the opposite direction and add to our understanding of shunt infections.

The importance of shunt valve position in flow characteristics of the Medtronic PS Medical Delta valve.

This study was conducted to document the extent to which flow depends on valve position in relation to head-pressure reference. Medtronic PS Medical Delta valves (contour model, performance levels 0.5, 1.0, 1.5, and 2.0) were studied in a bench test designed to evaluate flow rates with respect to valve position in relation to the head-pressure reference postion. The valves were connected to an "infinite" reservoir by the standard inlet catheter. An initial head (proximal) pressure was selected for each valve based on package insert data. The position of the inlet catheter tip was fixed at this starting head pressure, thus making the inlet catheter tip position the reference for relative head pressures on the valve assembly. When the valve body is positioned above this level, the effective head pressure is lowered, and when the valve body is positioned below this level, the effective head pressure is raised. Flow was established with the siphon control portion of the valve body located on the same horizontal level as the inlet catheter tip (the reference head pressure or "0" position). A standard silastic catheter was attached to the outlet of the valve, and its length was fixed at 50 cm for all valves (-50 cm H(2)0). The distal end of the outlet catheter was connected to a fraction collector, and 1-minute samples (five replicates) were collected for gravimetric determination of flow rate. The valve assembly was then moved in 1-cm increments through the range of 4 cm above to 8 cm below the head-pressure reference position. Samples were collected from each position (4 cm to -8 cm) relative to the inlet catheter tip. Flow rate, in milliliters/hour, was plotted against both relative position (4 cm to -8 cm) and absolute head pressure (in centimeters of water). Each of the valves tested was shown to have a linear relationship between flow and position relative to the inlet catheter tip (or absolute head pressure). The average increase in flow per centimeter of displacement of valve from catheter tip was 16.5 ml/hr/cm (range 14.4-17.6 ml/hr/cm). Once the inlet catheter tip is fixed in position, it serves as a pressure reference. Movement of the valve above this level results in a net decrease in effective head pressure, and movement below this position results in a net increase in effective head pressure. Thus, the positioning of shunt valves in locations different from this pressure reference position should be performed only with the knowledge that significant increases in outflow rate may occur when the valve body is positioned lower than the inlet catheter tip. This increase in outflow rate is not the result of siphoning or a defect in the antisiphon device but instead the result of a net increase in effective head pressure.

Spina bifida occulta: early clinical and radiographic diagnosis.

Tethered cord syndrome (TCS) is produced by traction of the lumbosacral spinal cord. Clinically, patients with tethered cord syndrome present with various combinations of neurologic, orthopedic, and cutaneous abnormalities. These abnormalities are often subtle. Early diagnosis, and treatment when indicated, is essential to prevent progressive and frequently irreversible neurological deterioration. Early diagnosis is aided by a high degree of clinical suspicion. Plain spine films are useful in the preliminary evaluation of suspected dysraphism. When plain film abnormalities are present, magnetic resonance imaging (MRI) has been found to be the single most effective procedure for both initial diagnosis and pre-operative evaluation of patients with myelodysplasia.