A ferritin tracer study of compensatory spinal CSF outflow pathways in kaolin-induced hydrocephalus

Spinal drainage of cerebrospinal fluid (CSF) into the lymphatic system is important in physiological and pathological conditions in both humans and rodents. However, in hydrocephalus and syringomyelia the exact CSF pathway from the central canal into the lymphatic tissue around the spinal nerves remains obscure. We therefore induced syringomyelia and hydrocephalus in 36 Lewis rats by injection of 0.1 ml kaolin into the cisterna magna. At 2, 4 and 6 weeks later cationized ferritin was stereotactically infused into the cisterna magna of controls and into the lateral ventricles of hydrocephalic animals followed by dissection of brain, spinal cord and spinal nerves. CSF pathway and tracer flow were studied by light and electron microscopy. We found that in rats with kaolin-induced CSF outflow obstruction, CSF passes from central canal syringes through ruptured ependyma and dorsal columns into the spinal subarachnoid space, from where it is absorbed along spinal nerves into extradural lymphatic vessels. Taken into account that spinal hydrostatic pressure in humans differs significantly from pressure in animals due to the upright gait, we conclude that spinal compensatory CSF outflow pathways might be of even greater importance in human hydrocephalus.     

Spectral analysis of the CSF pulse wave at different locations in the craniospinal axis.

The frequency spectrum and the amplitude transfer function from arterial pulse pressure to the CSF pulse wave were estimated in the lateral ventricle, cisterna magna and lumbar subarachnoid space of anaesthetised ventilated cats under various conditions: (a) normal status, (b) inhalation of 5% CO2 and (c) saline infusion into the CSF space (0.045 ml/min). The CSF pulse waveforms in the lateral ventricle and cisterna magna were almost identical in all conditions. Inhalation of CO2 and saline infusion increased the values of the amplitude transfer function from blood pressure to the CSF pulse wave in the lateral ventricle and cisterna magna to a similar extent. The CSF pulse in the lumbar sac was remarkably damped under both normal conditions and during CO2 inhalation, but the damping was diminished by saline infusion. During the saline infusion, the spinal canal appeared to function as a low-pass filter to the conduction of the CSF pulse.     

Posterior fossa decompression with tonsillectomy in 104 cases of basilar impression, Chiari malformation and/or syringomyelia

The prime objective in the surgical treatment of basilar impression (BI), Chiari malformation (CM) and/or syringomyelia (SM) is based on the restoration of the normal cerebrospinal fluid (CSF) dynamics at the craniovertebral junction through the creation of a large artificial cisterna magna. A small suboccipital craniectomy has been emphasized to avoid caudal migration of the hindbrain structures into the vertebral canal. Nevertheless, the results showed downward migration of the hindbrain related to that type of craniectomy. The authors present, otherwise, the results of 104 cases of BI, CM and/or SM, whose surgical treatment was characterized by a large craniectomy with the patient in the sitting position, tonsillectomy, large opening of the fourth ventricle and duraplasty with creation of a large artificial cisterna magna. A significant upward migration of the posterior fossa structures was detected by postoperative magnetic resonance imaging.     

Theoretical analysis of the pathophysiology of syringomyelia associated with adhesive arachnoiditis

OBJECTIVE: To apply a theoretical model to analyse the derangement of cerebrospinal fluid (CSF) dynamics in syringomyelia associated with adhesive arachnoiditis. METHODS: An electrical circuit model of CSF dynamics in the spine was used. With this model, the derangement of CSF dynamics in adhesive arachnoiditis was simulated. The effects of various surgical procedures were then analysed, such as syringo-subarachnoid shunting, subarachnoid bypass, and foramen magnum decompression. RESULTS: When CSF flow in the subarachnoid space was obstructed at a certain point, the pressure inside the spinal cord increased in the segment immediately distal to the blockage. This location of increased pressure corresponded to the preferred site of syrinx formation in adhesive arachnoiditis. Syringo-subarachnoid shunting, subarachnoid bypass, and foramen magnum decompression were all effective at reducing this pressure gradient. CONCLUSIONS: Blockage of the spinal subarachnoid CSF pathway produces a relative increase in the pressure inside the spinal cord distal to the blockage point. Repetitive formation of this pressure gradient then induces CSF leakage into the spinal parenchyma, leading to the formation of syringomyelia. Using this model, alternative surgical procedures could be suggested that might be effective in treating this disease.     

Surgical experience of syringomyelia with reference to the findings of magnetic resonance imaging.

We present our surgical experience of 20 patients with syringomyelia, who were divided into two groups based on the findings of magnetic resonance (MR) imaging: a "non-visible cisterna magna" group, in which MR imaging did not reveal cerebrospinal fluid (CSF) in the cisterna magna, and a "visible cisterna magna" group. Patients with non-visible cisterna magna were associated with Chiari malformation (14 patients) or tight cisterna magna (4 patients) and underwent craniocervical decompression. Intradural exploration was performed when CSF movement in the cisterna magna or CSF outflow from the fourth ventricle appeared to be insufficient. It is important to confirm CSF outflow from the foramen of Magendie. Patients with visible cisterna magna were associated with tuberculous meningitis (2 patients) and underwent shunting procedures. Postoperatively, improvement in symptoms and a reduction in syrinx size were demonstrated in all patients except one. Two patients experienced recurrence of symptoms and syrinx dilatation.     

Pharyngeal pain during lateral suboccipital puncture

Oropharyngeal pain was referred by five fully conscious and collaborative patients during lateral suboccipital puncture (LSP) of the cisterna magna, performed for myelography and/or cerebrospinal fluid collection. The anastomotic connections between the lower cranial nerves, the sympathetic nerves and the upper cervical spinal nerves are reviewed, with emphasis on the relationship between the first cervical nerve (C1), the superior cervical ganglion of the sympathetic trunk, and the spinal accessory nerve (nerve XI), and their central connections. The authors conclude that pharyngeal pain during LSP is provoked by the stimulation of afferent visceral fibers of C1, or of the gray communicating branches of the superior cervical ganglion to C1.     

Syringomyelia and Arnold-Chiari syndrome

Many hypotheses concerning pathogenesis of syringomyelia were abandoned because of evidence found in more recent investigations. We should rank among them the "classical" theories of Gardner and Williams based on the assumption that syringomyelic cavities result from directing the fluid from the fourth ventricle to the central canal of the spine in the case of disturbances of circulation of the cerebrospinal fluid in the region of the cranio-spinal junction. The theory of intraspinal pulsation pressure of Greitz may explain the pathogenesis of syringomyelia in the case of obstacles to fluid flow from the cranial cavity to the spinal canal as in patients with Arnold-Chiari syndrome. The origin of Arnold-Chiari syndrome is connected with narrowness in the posterior fossa, particularly with narrowing of the arachnoid spaces. Improvement of clinical condition after surgical restoration of the fluid spaces within the posterior cranial cavity and improvement of cerebrospinal fluid flow in the region of the cranio-cervical junction are factors supporting this opinion.     

Evidence for rapid fluid flow from the subarachnoid space into the spinal cord central canal in the rat

Horseradish peroxidase (HRP) was used as a CSF tracer in Sprague-Dawley rats. One group of rats received an injection of HRP in the cistema magna and a second group was injected in the thoracic spinal subarachnoid space. The animals were sacrificed 0, 10 or 30 min after HRP injection by rapid perfusion with paraformaldehyde and glutaraldehyde. In both groups, there was rapid HRP labeling of brain and spinal cord perivascular spaces. HRP was present in the central canal in a pattern that was not consistent with flow from the fourth ventricle: in both groups there were segments of unlabeled central canal between the fourth ventricle and central canal segments containing HRP. HRP-labeled perivascular spaces were seen in the central gray matter adjacent to the central canal. There was a distinctive pattern of interstitial HRP between perivascular spaces and the central canal. The results suggest that there is a normal flow of fluid from the subarachnoid space, into the perivascular spaces, across the interstitial space and into the central canal. The function of this flow may be to clear metabolites from the interstitial space. The existence of such a flow would add considerable support to the theory that non-communicating syringomyelia develops in segments of central canal isolated by occlusion or stenosis at each end.     

CRANIAL AND SPINAL COMPONENTS OF THE CEREBROSPINAL FLUID PRESSURE-VOLUME CURVE

A quantitative analysis of the contributions of the cranial and spinal compartments to the cerebrospinal fluid pressure-volume curve was made using dogs. The curve was determined by rapid continuous injection of fluid into the cisterna magna with simultaneous measurement of the pressure. Spinal block at the C 1 level was produced by inflation of an epidural rubber balloon allowing the recording of the pressure-volume curve for the isolated cranial system. By subtraction of the two curves obtained, the spinal pressure-volume curve could be calculated. 70 % of the variation in volume within the system was related to the spinal section and 30 % to the cranial section. The intracranial curve represents the effects on the fluid pressure of forced alterations in the volume of the intracranial vascular bed. The spinal compartment has a quantitatively defined and probably mechanically important function as an expansion vessel for the intracranial system.     

Metastatic spinal intramedullary germinoma with elevated cerebrospinal fluid chorionic gonadotropin: a case report

We treated a patient whose unusual recurrent germinoma illustrates the diagnostic value of measuring human chorionic gonadotropin beta subunit (HCG-beta) in cerebrospinal fluid (CSF) and serum. A 25-year-old man with a suprasellar germinoma and ventricular dissemination was treated successfully with systemic chemotherapy and cranial irradiation. Six years later he developed progressive numbness and weakness in both upper extremities. Magnetic resonance imaging (MRI) disclosed an intramedullary spinal cord tumor in the cervical region. The CSF concentration of HCG-beta was elevated and exceeded that in serum. After completion of systemic chemotherapy and spinal irradiation, symptoms subsided and the tumor was no longer evident on MRI. Based on the patient's history and the rapid response of the tumor to treatment, the spinal cord tumor was considered a metastatic intramedullary spinal germinoma representing CSF dissemination via the central canal.     

Changes of frequency spectrum of the CSF pulse wave caused by supratentorial epidural brain compression.

The frequency spectrum of the CSF pulse wave and amplitude transfer function from arterial to CSF pressure were estimated in the lateral ventricle and cisterna magna during the course of supratentorial epidural compression of brain in anaesthetised ventilated cats. Ventricular fluid pressure, the amplitude of spectral components of the CSF pulse and the amplitude of transfer function in the supratentorial compartment were increased in an exponential manner as epidural compression advanced. A transtentorial pressure gradient developed when epidural compression exceeded a critical level. Conduction of the CSF pulse through the tentorial hiatus decreased in an exponential manner when plotted against the transtentorial pressure gradient. Transtentorial conduction of the CSF pulse may serve as a sensitive indicator of the development of tentorial herniation.     

Subarachnoid injection of Microfil reveals connections between cerebrospinal fluid and nasal lymphatics in the non-human primate

Based on quantitative and qualitative studies in a variety of mammalian species, it would appear that a significant portion of cerebrospinal fluid (CSF) drainage is associated with transport along cranial and spinal nerves with absorption taking place into lymphatic vessels external to the central nervous system. CSF appears to convect primarily through the cribriform plate into lymphatics associated with the submucosa of the olfactory and respiratory epithelium. However, the significance of this pathway for CSF absorption in primates has never been established unequivocally. In past studies, we infused Microfil into the subarachnoid compartment of numerous species to visualize CSF transport pathways. The success of this method encouraged us to use a similar approach in the non-human primate. Yellow Microfil was injected post mortem into the cisterna magna of 6 years old Barbados green monkeys (Cercopithecus aethiops sabeus, n = 6). Macroscopic and microscopic examination revealed that Microfil was (1) distributed throughout the subarachnoid compartment, (2) located in the perineurial spaces associated with the fila olfactoria, (3) present within the olfactory submucosa, and (4) situated within an extensive network of lymphatic vessels in the nasal submucosa, nasal septum and turbinate tissues. We conclude that the Microfil distribution patterns in the monkey were very similar to those observed in many other species suggesting that significant nasal lymphatic uptake of CSF occurs in the non-human primate.     

Early changes in cerebrospinal fluid Ca2+ and FFA levels following experimental spinal cord injury

Cerebrospinal fluid (CSF) Ca2+ and free fatty acids (FFA) levels were determined for 4 h following experimental spinal cord (SC) injury in rabbits. The injury was produced by dropping a 20 g weight from 20 cm on exposed dura mater at the C5-C6 level. Samples of CSF were obtained from the cisterna magna from a second laminectomy at the C1 level. A significant decrease in CSF Ca2+ levels was observed 10 and 30 min post-injury; such levels increased above normal values 180 min post-injury. A significant increase in CSF FFA levels was seen from 10 to 240 min post-injury with a peak at 30 min. The early decrease of CSF Ca2+ levels and the concomitant increase in CSF FFA levels seem to confirm in role of Ca2+ in mediating the lipolytic response of the SC tissue to trauma.     

Vasoactive intestinal polypeptide cerebrospinal fluid-contacting neurons of the monkey and cat spinal central canal

Neurons immediately adjacent to the central canal were demonstrated in the cat and monkey to be immunoreactive for the peptide vasoactive intestinal polypeptide (VIP), by means of the peroxidase antiperoxidase method. Most of the cells were found in the thoracic and sacral segments, although a few were present at each level. The thoracic neurons were multipolar and either ependymal or subependymal; they usually had a large, thick dendrite that was oriented radially toward the center of the central canal; this dendrite penetrated through the ependymal layer and ended as a large, fringed podlike process (4-5-microns diameter) along the canal surface in contact with the cerebrospinal fluid (CSF). From the basal surface of the thoracic cell arose several small dendrites and a varicose axon. A few of the thoracic VIP neurons also contained two nuclei. In the sacral cord, the VIP neurons that lie along the central canal were of several types. They were round or multipolar and were either subependymal, within the ependyma, or supraependymal. Many had long dendrites and thin varicose axons stretching for long distances parallel to the cord surface. Other VIP neurons were smaller cells with short, highly branched, varicose processes. Most prominent in the sacral cord of the cat was a massive intricate network of intensely labelled processes extending in parallel along the canal surface. This network contained thick dendrites, highly varicose axons, and small neurons. Electron microscopy demonstrated VIP axons and varicosities containing small round clear vesicles and dense core vesicles. These processes were in desmosomal contact with ependymal cells and in direct contact with the CSF space. VIP processes were also found along the pial surface of the spinal cord at each level. In some cases single axons and bundles of axons arising from the area around the central canal could be traced to terminal fields along the ventral median fissure and the ventral and ventral lateral surface. In summary, the cat and monkey spinal canal is richly innervated by VIP neurons with elaborate processes in contact with the cerebrospinal fluid; further, some of these neurons may also extend axons to the ventral surface of the spinal cord. In these aspects, these cells resemble CSF-containing neurons previously described in lower species.     

Chicken arachnoid granulations: a new model for cerebrospinal fluid absorption in man

Cerebrospinal fluid (CSF) absorption was investigated chicken and rat using infusion tests into the cisterna magna. Data were analysed according to a mathematical model by Johnson et al. Results in rat predicted a predominant lymphatic mechanism, which was confirmed by rapid outflow of X-ray contrast media into the olfactoric mucosa. In contrast, dynamics measurements suggested CSF drainage via arachnoid granulations in chicken. CSF spaces along the optic nerve were contrasted radiographically resulting in venous drainage. Electron microscopically, villus-like structures were found at the distal optic nerve connecting the subarachnoid space with accompanying veins, resembling human arachnoid granulations. We hypothesize that CSF absorption through arachnoid villi in microsmatic chicken reflects the situation in man very well.     

Lymphatic cerebrospinal fluid absorption pathways in neonatal sheep revealed by subarachnoid injection of Microfil

There is mounting evidence that a significant portion of cerebrospinal fluid drainage is associated with transport along cranial and spinal nerves with absorption taking place into lymphatic vessels external to the central nervous system. To characterize these pathways further, yellow Microfil^® was infused into the cisterna magna of 2–7-day-old lambs post mortem to perfuse either the cranial or spinal subarachnoid compartments. In some animals, blue Microfil was perfused into the carotid arteries simultaneously. Microfil was observed in lymphatic networks in the nasal mucosa, covering the hard and soft palate, conchae, nasal septum, the ethmoid labyrinth and the lateral walls of the nasal cavity. Many of these lymphatics drained into vessels located on the lateroposterior wall of the nasopharynx and from this location drained to the retropharyngeal lymph nodes. Additionally, lymphatics containing Microfil penetrated the lateral wall of the nasal cavity and joined with superficial lymphatic ducts travelling towards the submandibular and preauricular lymph nodes. In two cases, lymphatic vessels were observed anastomosing with deep veins in the retropharyngeal area. Microfil was also distributed within the nerve trunks of cranial and spinal nerves. The contrast agent was located in longitudinal channels within the endoneurial space and lymphatics containing Microfil were observed emerging from the mesoneurium. In summary, Microfil distribution patterns in neonatal lambs illustrated the important role that cranial and spinal nerves play in linking the subarachnoid compartment with extracranial lymphatics.     

Ultrastructural observations in experimental hydrocephalus in the rabbit

Changes in the ependyma and periventricular brain tissues of the lateral, 3rd and 4th ventricles and the cervical spinal canal were studied electron-microscopically in young rabbits on the 9th day after injecting kaolin into the cisterna magna. The ependyma of the lateral ventricle overlying the white matter was notably stretched causing increased egress of CSF and disorganisation of the normal architecture of the white matter and capillaries. The neurons and glial cells close to the white matter showed edematous changes. The changes in the ependymal lining and the underlying grey matter were less severe in the dorsal part of the 3rd and the 4th ventricle. The ventral part of the 3rd ventricle was the least affected. The height and the arrangement of the ependymal cells, the surrounding grey matter with narrow interstitial spaces and the absorbing tanycytes seemed to be factors which were responsible for the minimal changes in these regions. The changes appeared to be reversible if the CSF pressure was relieved at this stage. The spinal canal remained unaffected in the majority of our hydrocephalic animals, which could probably be attributed to the type of animal and the degree of hydrocephalus.     

Technique for collecting cerebrospinal fluid in the cisterna magna of non-anesthetized rats

We developed a technique for collecting cerebrospinal fluid (CSF) from the cisterna magna in non-anesthetized adult and young pup rats. In the adults, CSF was collected through a previously implanted guide cannula without previous disruption of the cisterna magna. In the pups, CSF was directly aspirated through a syringe from the cisterna in awake animals without previous surgery. In the adults, the volume of CSF collected varied from 50 to 120 microl, and in pups 7 to 10 days old, it was approximately 25 microl. The technique can easily be done by anyone who is familiar with stereotaxic surgery, and the material needed is cheap and easy to obtain commercially. A simple procedure to calculate the parameters for the implantation of guide cannula in rats other than Wistar ones is also presented.     

Determinants of lumbar CSF protein concentration

Objective To determine factors influencing the wide variation of protein concentration in lumbar cerebrospinal fluid (CSF). Methods Patient variables with potential influence on spinal CSF flow and resorption were measured in different patient settings and compared with albumin and IgG CSF/serum quotients. Results In patients whose diagnostic lumbar puncture produces normal CSF the albumin quotient increased with body mass index (r = 0.408), abdominal circumference (r = 0.399), and body weight (r = 0.317), age-corrected with partial correlation. Body motion before lumbar puncture showed only marginal influence on albumin quotient. In patients with radiculography the albumin quotient decreased with iodine contrast medium elimination from spinal subarachnoid space (r = -0.598) and increased with narrowing of lumbosacral spinal canal (r = 0.515). Conclusion Correlation of albumin quotient with body mass index and related variables may be mediated by spinal CSF resorption, which should be impaired in overweight patients with elevated venous pressure. Negative correlation of albumin quotient with iodine resorption from spinal CSF supports this assumption. Correlation of albumin quotient with narrowing of lumbosacral canal should be due to slowed spinal CSF flow which does increase protein concentration. Tested variables explain part of variation of CSF protein concentration. Other variables like blood-CSF barrier permeability and pulsatile spinal CSF flow should have additional influence. Received: 5 September 2001 Received in revised form: 6 February 2002 Accepted: 7 February 2002     

Cerebrospinal fluid pressure and resistance to absorption during development in normal and hydrocephalic mutant mice

Hydrocephalic mutant mice and matched siblings at different ages were used to measure the pressure and the resistance to drainage of the cerebrospinal fluid (CSF) from the lateral ventricles and from the cisterna magna with glass micropipets. The resting CSF pressure in normal mice increased between 1 to 2 and 4 to 8 days after birth and subsequently decreased between 4 to 8 and 14 days after birth. In hydrocephalic mice the resting pressure was not significantly different from normal in the 1st week after birth, but by 14 days the pressure was significantly higher in hydrocephalic mice. For normal mice, the resistance from the lateral ventricles at 1 to 2 days after birth was 143.9 mm H2O min microliter-1 and it decreased rapidly to 62.0 at 4 to 8 days, and to 21.2 mm H2O min microliter-1 at 14 days. The resistance to absorption from the cisterna magna in normal mice declined from 94.9 to 44.4 and to 26.8 mm H2O min microliter-1 at 1 to 2 days, 4 to 8 days, and 14 days after birth, respectively, suggesting that the absorptive capacity of the subarachnoid outflow sites increased during that period. Thus resistance measured from the lateral ventricles was significantly higher than that from the cisterna magna in the 1st week after birth, suggesting that in immature mice there is a resistance to flow of CSF through the ventricular system. In hydrocephalic mice the resistance measured from the lateral ventricles was higher than for normal animals at 181.5, 106.4, and 103.7 mm H2O min microliter-1 for 1 to 2 days, 4 to 8 days, and 14 days, respectively. Resistance from the cisterna magna in hydrocephalic animals was not significantly different from normal at any age. Thus it is concluded that the hydrocephalus is associated with an obstruction to the flow of CSF from the ventricles.