scispace - formally typeset
Search or ask a question

Showing papers on "Cerebrospinal fluid published in 1972"


Journal ArticleDOI
TL;DR: The cavitation of syringomyelia may be produced by cerebrospinal fluid tracking under pressure into the spinal cord from the subarachnoid space along perivascular (Virchow-Robin) spaces.

367 citations


Journal ArticleDOI
TL;DR: The patients with central nervous system involvement who were most likely to survive were those who had received amphoterictn B for four weeks or more and whose cultures of the cerebrospinal fluid converted from positive to negative.

219 citations



Journal ArticleDOI
TL;DR: The spinal dural sac is a dynamic structure, readily changing its capacity in response to prevailing pressure gradients across its walls, which acts as a reservoir for CSF, which moves to and fro through the foramen magnum in Response to changes in cerebral blood flow.
Abstract: During myelography we observed the contrast material in the spinal subarachnoid space while we changed: (1) the intracranial blood volume by CO2 inhalation, hyperventilation, and jugular vein compression; (2) the intra-abdominal and intrathoracic pressure by forced expiration with glottis closed; and (3) the CSF volume by withdrawals and reinjections of fluid. The spinal dural sac enlarges with increases in volume of both intracranial blood and CSF. It partially collapses with reductions in volume of both intracranial blood and CSF. With increases in intra-abdominal and intrathoracic pressure, the thoracolumbar sac partially collapses, while the cervical sac enlarges. From these observations we conclude that the spinal dural sac is a dynamic structure, readily changing its capacity in response to prevailing pressure gradients across its walls. It acts as a reservoir for CSF, which moves to and fro through the foramen magnum in response to changes in cerebral blood flow. By its bladder-like ability to alter its capacity, the spinal dural sac provides the `elasticity' of the covering of the central nervous system.

118 citations


Journal ArticleDOI
TL;DR: Results from perfusion studies at a constant perfusion pressure demonstrated that CSF production rates were similar in both acute and chronic hydrocephalic cats, however,CSF production was affected by changes in perfusion Pressure.
Abstract: Cerebrospinal fluid (CSF) turnover was studied in cats by ventricular perfusion at various time intervals after the intracisternal injection of 175 to 200 mg of kaolin. At seven days, CSF absorptive capacity was minimal and intraventricular pressure was high. During this time interval, the occurrence of quadriplegia in some animals was attributed to microscopic changes observed in kaolin meningitis and also to the elevated intraventricular pressure. After three weeks, when transventricular absorption occurred, CSF absorptive capacity increased, and intraventricular pressure returned to normal. The development of transventricular absorption was accompanied by an increase in water content of periventricular white matter. Results from perfusion studies at a constant perfusion pressure demonstrated that CSF production rates were similar in both acute and chronic hydrocephalic cats. However, CSF production was affected by changes in perfusion pressure.

113 citations


Journal ArticleDOI
TL;DR: A lower turnover rate of dopamine and 5-hydroxytryptamine in both phases of manic-depressive psychosis is indicated, as indicated by the findings of the probenecid experiments.
Abstract: Cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid and homovanillic acid were determined in 37 depressed and 47 manic patients, in 30 other psychiatric patients and in 54 healthy controls. There were no differences in the concentrations of 5-hydroxyindoleacetic acid between the four groups. Manic patients had higher concentrations of homovanillic acid than the other three groups. After loading with probenecid (5 g during 50 h), which blocks the outflow of acid metabolites of monoamines from cerebrospinal fluid, the increase in 5-hydroxyindoleacetic acid levels at a second lumbar puncture was significantly smaller in the manic-depressive patients (about 20%) than in the other two groups (about 60%). The rise in the concentration of homovanillic acid was smaller in manic depressive patients (about 80%) than in the two control groups (about 200%). In a further experiment, methylperidol, a neuroleptic compound which increases the turnover rate of brain dopamine, was administered with probenecid in an attempt to accentuate the differences between the groups. Methylperidol increased the differences between the manic-depressives and the controls for homovanillic acid, and removed the differences for 5-hydroxyindoleacetic acid. These findings indicate a lower turnover rate of dopamine and 5-hydroxytryptamine in both phases of manic-depressive psychosis. — In the probenecid experiments, bipolar depressive patients had lower increases of 5-hydroxyindole acetic acid than cases of unipolar endogenous depression. Treatment with lithium, tricyclic antidepressants and various neuroleptics did not affect the concentrations of 5-hydroxyindoleacetic acid and homovanillic acid. The concentrations of these compounds in cerebrospinal fluid in subjects not premedicated at the second lumbar puncture were relatively unchanged when measured on two occasions at different time intervals.

105 citations


Journal ArticleDOI
TL;DR: Cerebrospinal fluid 5-HIAA, the major metabolite of serotonin, was assayed in a group of five depressed patients and the apparent increase in brain serotonin turnover produced by L-tryptophan in these patients was not accompanied by an improvement in depression.
Abstract: Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin, was assayed in a group of five depressed patients before and during treatment withL-tryptophan, with and without probenecid.L-tryptophan administration was associated with a slight increase in the baseline levels of 5-HIAA, but caused a twofold to threefold increase in the accumulation of 5-HIAA in the cerebrospinal fluid following probenecid administration. The apparent increase in brain serotonin turnover produced byL-tryptophan in these patients was not accompanied by an improvement in depression.

102 citations


Journal ArticleDOI
TL;DR: History, evidence of tissue damage, and thickness of cerebral mantle were considered important, and Antibiotics reduced infection rate from 19% to 3%.
Abstract: Eighty adults with hydrocephalus were treated with a shunt operation. Twenty-four had nonabsorptive hydrocephalus with obstruction at the level of the basal cisterns and 56 had hydrocephalus plus cerebral atrophy without apparent obstruction to the flow of cerebrospinal fluid. Thirty-four patients improved but in only 16 (20%) was the improvement dramatic. The material was analyzed to identify criteria for future case selection. History, evidence of tissue damage, and thickness of cerebral mantle were considered important. Antibiotics reduced infection rate from 19% to 3%.

96 citations


Journal ArticleDOI
TL;DR: The effect of an intravenous injection of ketamine 1.1 mg/kg on the cerebrospinal fluid (c.s.f.) pressure was studied in 20 patients during nitrous oxide-oxygen and relaxant anaesthesia, and results suggest that ketamine must be used with caution in patients with intracranial space-occupying lesions.
Abstract: The effect of an intravenous injection of ketamine 1.1 mg/kg on the cerebrospinal fluid (c.s.f.) pressure was studied in 20 patients during nitrous oxide-oxygen and relaxant anaesthesia. In 11 patients with normal c.s.f. pathways the pressure did not alter significantly, but in 6 of 9 patients with intracranial space-occupying lesions there was a substantial rise in cs.f. pressure. These results suggest that ketamine must be used with caution in patients with intracranial space-occupying lesions.

88 citations



Journal ArticleDOI
TL;DR: The findings suggest that the choroid plexus is responsible for producing neural tube dilatation in hydrocephalus and supports the concept that syringomyelia results from inadequate drainage of cerebrospinal fluid and increased pressure in the spinal cord central canal.
Abstract: ✓ The central canal of the spinal cord was studied with canal occlusion alone, and in experimental (kaolin) hydrocephalus without and with central canal occlusion. Massive dilatation of the canal occurred with kaolin hydrocephalus. Syrinxes extending into the gray and white matter of the cord and communicating with the central canal developed in both the upper and lower spinal cord. The completely isolated central canal (occlusion at the obex and filum terminale) did not dilate, but remained patent. Canal occlusion at the obex and filum terminale completely protected the spinal cord from central canal dilatation or syrinxes in kaolin hydrocephalus. These findings suggest that the choroid plexus is responsible for producing neural tube dilatation in hydrocephalus. It also supports the concept that syringomyelia results from inadequate drainage of cerebrospinal fluid and increased pressure (or pulse pressure) in the spinal cord central canal.

Journal ArticleDOI
TL;DR: A transitory outflow of polymorphonuclear neutrophilic leukocytes (PNL) was found in 70% of the patients with hemorrhagic infarction and lobar hematoma, with a peak three to four days after onset, and the strongest PNL reaction was recorded in CSF from patients with lobarHematoma.
Abstract: Cerebrospinal fluid (CSF) samples obtained by consecutive lumbar puncture of 26 patients with presumed pale cerebral infarction, 66 with presumed hemorrhagic infarction, 16 with lobar hematoma, and 18 with cerebral infarction verified at autopsy, were examined with a cytological method permitting a total and differential cell count A transitory outflow of polymorphonuclear neutrophilic leukocytes (PNL) was found in 70% of the patients with hemorrhagic infarction and lobar hematoma, with a peak three to four days after onset The strongest PNL reaction was recorded in CSF from patients with lobar hematoma In 75% of patients with pale infarction, no PNL or only a few PNL were found In the autopsy group the PNL reaction in the brain as well as in the CSF was stronger in patients with hemorrhagic infarcts than in those with pale infarcts

Journal ArticleDOI
TL;DR: The surface of ependymal cells bordering the brain ventricles, and that of the epithelial cells of choroid plexuses of the cat have been investigated by means of the scanning electron microscope.
Abstract: The surface of ependymal cells bordering the brain ventricles, and that of the epithelial cells of choroid plexuses of the cat have been investigated by means of the scanning electron microscope. The ventricle walls are entirely covered with very long and numerous cilia and no regional differences have been observed regarding their number and disposition. Among the ciliated cells dome-shaped structures are present, possibly containing nervous elements. The ependymal cells of the third ventricle floor are mainly non ciliated but the surface thereof shows numerous small microvilli. Numerous round formations are present among these cells, their nature being difficult to interpret. Also present on the floor are small cells of triangular shape with long and tortuous protrusions, tentatively identified as small neurons. The choroid plexuses have a typical sinuous structure of long tortuous villi rich in cavities and convolutions. Details of the epithelial cells covering the plexus and their surface organization are also reported.

Journal ArticleDOI
TL;DR: Concentrations of rifampin in cerebrospinal fluid were measured after administration of 300 mg of the drug twice daily in 10 patients with probable tuberculous meningitis, and the minimal inhibition concentration for Mycobacterium tuberculosis was exceeded in all patients.
Abstract: Concentrations of rifampin in cerebrospinal fluid were measured after administration of 300 mg of the drug twice daily in 10 patients with probable tuberculous meningitis. The diagnosis was confirmed bacteriologically in only 3 patients. Rifampin was measured in serum and cerebrospinal fluid by a microbiologic assay using a strain of Gaffkya tetragena. Rifampin was present in the cerebrospinal fluid within 2 hours after the drug was first taken in 4 of 10 patients, and at 6 hours, the minimal inhibition concentration for Mycobacterium tuberculosis was exceeded in all patients. The highest concentrations were reached on the second day and subsequently decreased in both serum and cerebrospinal fluid. There was more stability of the concentrations in the cerebrospinal fluid. Rifampin concentrations fluctuated daily in the serum but were stable in the cerebrospinal fluid. Variations in cerebrospinal fluid concentrations among patients were greater than those in serum. All the patients had been treated previou...

Journal ArticleDOI
TL;DR: The data of the two series agree in showing that HCOaformation is a principal feature of CSF formation and that there is a clear homology to the formation of aqueous humor.
Abstract: MAREN, THOMAS H. Bicarbonate formation in cetebrospinal fluid: role in sodium transport and pH regulation. Am. J. Physiol. 222(4) : 885-899. 1972.-Two series of experiments were performed which clarified the role of HCOaformation and movement into cerebrospinal fluid (CSF), and its relation to sodium transport and pH regulation. In the first, the rates of access of HC03, Na+, and Clfrom plasma to CSF were measured in the dogfish Squalus acanthias by means of their isotopes. The rate constant (kin) values for the three ions were 1.9, 0.19, and 0.14 hr-l, respectively. Assuming that these represent net influx, the composition of CSF as secreted has the same sodium concentration as plasma, with HC03much higher and Cllower than plasma. The rate data and the effects of carbonic anhydrase inhibition suggest that HCOsU reaches the CSF by hydroxylation of gaseous COz at the choroid plexus, and probably at glia. The relations among the rates of the three ions show that the movement of HCOShas an important influence on the movement of sodium and of fluid. In the second series, the PCO~ of the fish was elevated fourfold, and the effect upon CSF HCOawas measured. The procedure caused a striking elevation of CSF HC03 concentration, to fourfold normal, in about 3 hr. As a result, pH regulation was maintained in the CSF during a profound respiratory acidosis in the plasma. The rate of HCOaformation in CSF was reduced to half by carbonic anhydrase inhibition. The data of the two series agree in showing that HCOaformation is a principal feature of CSF formation and that there is a clear homology to the formation of aqueous humor.

Journal ArticleDOI
TL;DR: The findings suggest that the appearance of bilirubin in the CSF after subarachnoid hemorrhage may reflect pigment formation in cells which are in intimate contact with the subarachesnoid space.
Abstract: Xanthochromia in the cerebrospinal fluid (CSF) is one of the most helpful indications of a recent subarachnoid hemorrhage.' ,2 The major yellow pigment appearing in the CSF about twelve hours after the bleeding episode is probably bilirubin formed from hemoglobin that has been released from lysed red cells. However, identification and precise measurement of the yellow material in CSF met with considerable difficulty due to the low concentrations of the pigment. Attempts to produce xanthochromia in vitro by incubation of CSF with red blood cells for as long as twenty-six hours failed to produce b i l i r ~ b i n . ~ This suggests that bilirubin formation from hemoglobin in the subarachnoid space requires the participation of a component of brain or tissues surrounding the CSF. Recent observations by Tenhunen et al.4 ,5 have clarified the mechanism by which the heme of red cell hemoglobin is converted to bilirubin in the intact organism. Bilirubin formation is catalyzed by a mixed function oxidase, which is localized in the microsomal fraction of a variety of mesenchymal and epithelial cells. The enzyme system, heme oxygenase (HO), converts heme to equimolar amounts of bilirubin and carbon monoxide and has an obligatory requirement for nicotinamide adenine dinucleotide phosphate (NADPH) and molecular oxygen. It was further noted that HO is stimulated by its substrate, heme. These findings suggest that the appearance of bilirubin in the CSF after subarachnoid hemorrhage may reflect pigment formation in cells which are in intimate contact with the subarachnoid space. In the present investigation, an experimental model of subarachnoid hemorrhage in rats was developed to study microsomal heme oxygenase activity in the brain and in the arachnoid and choroid plexus.

Journal ArticleDOI
TL;DR: A pressor polypeptide was isolated from the cerebrospinal fluid of normotensive and hypertensive patients and Pharmacologically it behaves like angiotensin I.
Abstract: A pressor polypeptide was isolated from the cerebrospinal fluid of normotensive and hypertensive patients. Pharmacologically it behaves like angiotensin I. A very significant correlation (r = 0.83, P < 0.001) was found between the concentration of this polypeptide and the blood pressure of essential hypertensive patients.


Journal ArticleDOI
TL;DR: The morphology of the arachnoid villi and granulations were studied in recently sacrificed dogs and sheep and showed a pressure-dependent "valvular" mechanism which aids in transference of cerebrospinal fluid from the subarACHnoid space to the venous sinus and prevents reflux of blood into the subArachnoids space.
Abstract: The morphology of the arachnoid villi and granulations were studied in recently sacrificed dogs and sheep. Alatex-like material was perfused through the subarachnoid space under near-normal pressure conditions filling open pathways and spaces in the villi. This technique demonstrated that passage of cerebrospinal fluid through the arachnoid villi is at least in part a passive process through open communications. Also, arachnoid villi and granulations show a pressure-dependent "valvular" mechanism which aids in transference of cerebrospinal fluid from the subarachnoid space to the venous sinus and prevents reflux of blood into the subarachnoid space.

Journal ArticleDOI
TL;DR: It is concluded that brain tissue Osm can be successfully measured by the technique described; normal brain Osm is essentially the same as that of CSF or plasma, while in chronic hyperosmolar states, brain Qsm is the sameAs that of plasma or plasma.

Journal ArticleDOI
TL;DR: A correlation was found between the rate of removal from perfusate for the quaternary drugs and their uptake characteristics in vitro and the conclusion was drawn that the investigated amines are eliminated from CSF partly by a carrier mediated process.
Abstract: The elimination from CSF of the quaternary ammonium compounds choline, methylatropine and decamethonium and the tertiary amine atropine has been investigated by ventriculo-cisternal perfusion in anesthetized dogs and rabbits. The elimination of the amines from the perfusate was partly concentration dependent. Further, in the rabbit experiments they decreased the elimination of each other. In the dog 63 per cent of the infused choline was eliminated between the lateral ventricle and cisterna magna at an infusate concentration of 5·10--6M and a rate of 150 μl/min. The corresponding figure for the rabbit was 78 per cent at 30 μl/min. Brain drug concentrations after the experiments revealed that diffusion into the brain contributed to the elimination only to a minor extent. Results were compared to in vitro studies on choroid plexa. A correlation was found between the rate of removal from perfusate for the quaternary drugs and their uptake characteristics in vitro. The conclusion was drawn that the investigated amines are eliminated from CSF partly by a carrier mediated process. One important site of this process is probably the choroid plexus.

Journal ArticleDOI
TL;DR: In this paper, a light and electron microscopic study of the ependymal and subependymal regions of experimental hdrocephalic cats was made, and the major pathological findings were: flattened and outstretched ependyal lining, detachment of ependyanal cells and rarefaction of subependyal areas with increase in the extracellular space.
Abstract: A light and electron microscopic study of the ependymal and subependymal regions of experimental hdrocephalic cats was made. Hydrocephalus was induced by injection of kaolin into the cisterna magna. Cerebrospinal fluid (CSF) turnover was measured in all experimental cats by ventricular perfusion just prior to glutaraldehyde fixation. The cats were sacrificed at 7 (acute hydrocephalus) and at 21 or more days (chronic hydrocephalus) after kaolin. The major pathological findings were: flattened and outstretched ependymal lining, detachment of ependymal cells and rarefaction of subependymal areas with increase in the extracellular space. The significant morphological alterations in acute hydrocephalus, characterized by a marked decreased rate of CSF absorption, were flattening and outstretching of ependymal cells with minimal rarefaction of subjacent tissues. In the acute animal with a measurable amount of CSF absorption, and more clearly, in the chronic animal with higher rates of CSF absorption, detachment of ependymal calls, significant rarefaction of subependymal tissues, and marked increased subependymal extracellular space were the predominant changes. It is concluded that these pathological changes provide the morphologic substrate for transventricular absorption of CSF.

Journal ArticleDOI
TL;DR: No statistically significant difference of the CSF beta‐trace protein concentration could be found between patients suffering from various neurological diseases and healthy controls, with the exception of patients with cerebrovascular disease, where increased concentrations were found around the 5th week after the onset of the stroke.
Abstract: Beta-trace protein constitutes about 7 % of the total cerebrospinal fluid (CSF) protein concentration. In the present study the concentration of beta-trace protein in CSF has been determined in 59 “healthy” controls and in 174 patients suffering from various neurological diseases. The CSF concentration of beta-trace protein was found to increase with age. No statistically significant difference of the CSF beta-trace protein concentration could be found between patients suffering from various neurological diseases and healthy controls, with the exception of patients with cerebrovascular disease, where increased concentrations were found around the 5th week after the onset of the stroke. This increase was especially marked in patients with the most severe signs of a cerebrovascular lesion. Slightly higher CSF beta-trace protein concentrations were found in patients investigated within one month after an exacerbation of multiple sclerosis when compared with multiple sclerosis patients later investigated. A parallelism between increased concentrations of CSF beta-trace protein and the severity of myelin degradation is postulated.

Journal ArticleDOI
TL;DR: The human arachnoids granulation was studied by light microscopy in gapless serial sections after local postmortem perfusion of the subarachnoid space with glutaraldehyde.
Abstract: ✓ The human arachnoid granulation was studied by light microscopy in gapless serial sections after local postmortem perfusion of the subarachnoid space with glutaraldehyde. The smaller granulations are invested in a dural sheath several layers thick which is separated from the body of the granulation by a true subdural space. In larger granulations, there are restricted regions where the body of the granulation protrudes through the dura to enter the venous sinus directly.

Journal ArticleDOI
01 Jan 1972
TL;DR: The concentration of individual proteins in CSF seems to be influenced by the molecular weight of the proteins, and patients with normal, as well as increased, total protein concentrations in CSf seem to have a mechanism favouring the entrance into the CSF of proteins with low molecular weights.
Abstract: The concentrations of 16 different proteins have been determined in unconcentrated CSF and in serum by radial immunodiffusion. The study included 20 patients with different neurological disorders and with total protein concentrations in CSF ranging between 26 and 299 mg per 100 ml. A simultaneous increase of most of the CSF proteins quantitated was found with increased total protein concentrations. A positive, statistically significant correlation between the concentrations of haptoglobin, α2-macroglobulin and β-lipoprotein in CSF, and the total protein concentration in CSF, however, was first obtained when the concentration of the protein in serum was also taken into account.

Journal ArticleDOI
TL;DR: The experimental procedures were based upon the concept that the decrease in inulin concentration occurring during the perfusion was exclusively a function of the volume of newly formed cerebrospinal fluid in the system.
Abstract: ✓ The spinal subarachnoid space of the dog was perfused with an artificial cerebrospinal fluid containing inulin as a tracer. The experimental procedures were based upon the concept that the decrease in inulin concentration occurring during the perfusion was exclusively a function of the volume of newly formed cerebrospinal fluid in the system.

Journal ArticleDOI
TL;DR: It is believed that no bulk absorption of CSF occurs via the choroid plexus, and the inhibiting effect of intra-"ventricular" pressure on CSF production was demonstrated.

Journal ArticleDOI
TL;DR: A comparison between choline in ventricular cerebrospinal fluid from patients with Parkinson's disease and with intention tremor showed no significant differences and the results are discussed in relation to the possible sources of choline.
Abstract: Cerebrospinal fluid from patients with Parkinson's disease and Huntington's chorea has been investigated with regard to the concentration of choline. In Parkinson's disease the choline concentration of lumbar spinal fluid was not different from that of a control group, nor was it related to medication, duration of illness, or severity of symptoms. A comparison between choline in ventricular cerebrospinal fluid from patients with Parkinson's disease and with intention tremor showed no significant differences. Patients with Huntington's chorea had a lower concentration of choline in lumbar spinal fluid as compared with a control group. The results are discussed in relation to the possible sources of cerebrospinal fluid choline.

Journal ArticleDOI
TL;DR: Since the distribution of HRP in brain is determined by diffusion, its use as a tracer for the bulk movement of CSF through nervous tissue is limited and it is, however, an excellent extracellular space marker in electron microscopy.
Abstract: The distribution of intraventricularly injected horseradish peroxidase (HRP) was examined in the ependymal and subependymal tissue of both normal and experimental hydrocephalic cats by light and electron microscopy. At different time intervals after the intracisternal injection of kaolin, the hydrocephalic ventricles were perfused at various intraventricular pressures with mock cerebrospinal fluid (CSF) containing HRP. The uptake and localization of HRP by periventricular brain tissue was studied with respect to transventricular absorption of cerebrospinal fluid. The results of both light and electron microscopic studies have shown that in normal, acute or chronic hydrocephalic cats perfused at either high or low pressure the distribution of HRP is similar. The enzyme was localized mainly to the intercellular spaces, between ependymal cells, glial cells, and in perivascular spaces (in and across the basement membrane of subependymal blood vessels). HRP did not penetrate endothelial tight junctions even in chronic hydrocephalic cats undergoing significant rates of transventricular absorption of CSF. It is concluded that since the distribution of HRP in brain is determined by diffusion, its use as a tracer for the bulk movement of CSF through nervous tissue is limited. It is, however, an excellent extracellular space marker in electron microscopy.

Journal Article
TL;DR: If an immunological mechanism is to be invoked in the initiation of destruction of the basic protein of myelin in MS, then either pathogenic `antibody' must be absorbed in vivo to the target antigen in the central nervous system or the initiating events must be mediated entirely by sensitized lymphocytes.
Abstract: A sensitive gel filtration redioimmunoassay was used to test for antibodies to the basic protein of myelin, the antigen of experimental autoimmune encephalomyelitis, in serum and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and other diseases. Sera and CSF from patients with MS gave results similar to those for controls including subjects with various neurological diseases. Binding of 125I-basic protein by seven-fold concentrated CSF was shown to be due to α-globulin. Free basic protein, as a possible auto-immunogen, was sought in the serum and seven-fold concentrated CSF of patients with MS and controls by competitive inhibition in the radioimmunoassay, but none was demonstrable. If an immunological mechanism is to be invoked in the initiation of destruction of the basic protein of myelin in MS, then either pathogenic `antibody' must be absorbed in vivo to the target antigen in the central nervous system or the initiating events must be mediated entirely by sensitized lymphocytes.