SOME
LIMITATIONS OF THE
HYPOTHESIS
LEWIS
H.
MONRO-KELLIE
WEED
century and a half, the hypothesis that the skull and
of
the vertebral canal form a rigid container for the
bony coverings
central nervous system has occupied the attention of anatomists, physiologists and neurologists. It is a hypothesis which has been gradually
changed in its scope, and even in1 its conception, since its original promulgation by Alexander Monro in 1783. Having been of interest to
many in the course of the first fifty years of its existence, the doctrine
has, in the past three decades, again become the subject of intensive
investigation by workers in intracranial physiology. It is a tenet which
has particularly concerned neurologic surgeons, because on its truth,
or relative untruth, depend many of the critical procedures in the
surgery of the central nervous system. The doctrine has especially
intrigued the scientific curiosity of Harvey Cushing, to whom the academic world owes a vivid presentation of this hypothesis2 that the
contents of the cranium are at all times relatively fixed in volume, and
that variation in any of its three constituent elements must be com¬
pensated by reciprocal variation in the quantity of one or both the
other elements. It is the purpose of this article to assemble anew the
various fractions of evidence which underlie current belief in the truth
of the doctrine, presenting, in part, work already published by me and
detailing new observations which widen the field of knowledge of the
limitations of the hypothesis.
As one superficially examines the bony skeleton, particularly of man
or of other higher vertebrates, one is impressed by the tremendous
gaps in the bony structures constituting the vertebral column and the
bony skull. Were one's knowledge of anatomy confined to skeletal
remains, one would have difficulty in conceiving the skeleton to be an
effective covering for the central nervous system. But as one's
anatomic knowledge advances, one realizes that the many foramina in
the skull are closed by the tough and inelastic dura mater, which
intimately invests all the entering and emerging structures. In the
vertebral canal, somewhat similarly, the intersegmental ligaments form
For almost
a
From the Department of Anatomy, Johns Hopkins University.
1. Monro, Alexander: Observations
on the Structure and Functions of the
Nervous System, Edinburgh, Creech and Johnson, 1783.
2. Cushing, Harvey: Studies in Intracranial Physiology and Surgery, London, Oxford University Press, 1925.
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almost equally tough, though
that the vertebral tube forms a
an
slightly elastic, bridging mechanism, so
complete bony and fibrous investment,
perforated segmentally by nerves and blood vessels. With the dura
cerebri closely applied to the inner surface of the skull, the cranial
box may easily be considered an intact container for the brain, but in
the spinal cord, with the epidural space filled (in the mammals) with a
fatty areolar tissue and a plexus of thin walled veins, the analogies seem
distant; for between the dura mater and the inner fibrous lining of the
mater
vertebral canal, the amount of inelastic fibrous tissue is small, indeed,
and this bridging tissue seems hardly capable of maintaining the spinal
dura in its proper position of distention. Excluding the points of
emergence and entrance of the spinal nerves, the fibrous coverings of
the spinal cord surely may be considered to lack rigidity in one par¬
ticular region—that of the occipito-atlantoid ligament. For here, as has
been known for a century, pulsations of the intradural fluid contents
may be seen under favorable conditions during the life of an animal.
LITERATURE
Such thorough and detailed anatomic conceptions could hardly have
been appreciated by Alexander Monro,1 when, at the end of the eight¬
eenth century, this celebrated Scotch anatomist turned his attention to
the problems of intracranial physiology, and devoted to this sub¬
ject a few of the pages of his epochal monograph "The Structure
and Functions of the Nervous System." Here one finds for the
first time in scientific literature the hypothesis that the blood circulating
within the cranium must at all times be constant in volume. Monro's
own words give a comprehensive idea of his method of reasoning: "as
the substance of the brain, like that of the other solids of our body, is
nearly incompressible, the quantity of blood within the head must be
the same, or very nearly the same, at all times, whether in health or
disease, in life or after death, those cases only excepted, in which water
or other matter is effused or secreted from the blood-vessels; for in
these, a quantity of blood, equal in bulk to the effused matter, will be
pressed out of the cranium." 3
The primary basis for this hypothesis was Monro's anatomic
generalization that the brain is "enclosed in a case of bone" ; 3 and it
followed quite logically that within a rigid container, such as the
cranium, the contents must at all times be of the same volume. Hold¬
ing the brain to be incompressible and being cognizant of the existence
of but one fluid element within the skull-case, Monro assumed that the
quantity of blood could vary in volume only between the venous and
the arterial sides.
3. Monro
(footnote 1,
p.
5).
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Monro's original hypothesis was further developed by George
Kellie,4 whose stimulating report is given in the first volume of the
Transactions of the Medical and Chirurgical Society of Edinburgh in
1824. Kellie attempted experimental and pathologic verification of the
views advanced by Monro. His conclusions, based on observations in
animals and in persons frozen to death, were that a state of bloodlessness did not exist in the brains of animals killed by bleeding, that the
amount of blood in the cerebral veins was not affected by posture or
by gravitation, that congestion of these vessels (particularly on the
venous side) was not found in those conditions in which it might well
be expected (hanging, etc.) and that compensatory readjustments
between the arterial and the venous sides always maintained a con¬
stant intracranial vascular volume. Kellie wrote : "That in the ordinary
state of these parts we can not lessen, to any extent, the quantity of
blood within the cranium, by arteriotomy or venesection ; whereas if the
skull of an animal be trephined then hemorrhage will leave very little
blood in the brain."
With Kellie's apparent verification of Monro's hypothesis, other
workers applied the doctrine to pathologic conditions in man, par¬
ticularly in cases of apoplexy. In these studies, an attempt was made
to determine whether the hemorrhage was compensated for by decrease
in the volume of the intracranial arterial and venous bloods. The
thesis, which quite properly became known as the "Monro-Kellie doc¬
trine," was widely accepted, and interest in it was profound.
Even though the cerebrospinal fluid had been discovered some years
before Monro's publication, and even though Haller5 had given an
accurate, though incomplete, account of this fluid filling and surround¬
ing the central nervous system, Monro was apparently in ignorance ofc
its existence. It was only with Magendie's first adequate description
in 1825 and with his second more comprehensive monograph 7 on the
subject, that knowledge of the cerebrospinal fluid began to spread
beyond Europe. Burrows,8 in 1846, questioned for the first time the
thorough accuracy of the doctrine of fixed intracranial blood volume
and introduced into the conception the relationship of the cerebrospinal
fluid. Burrows repeated many of Kellie's supposedly critical experi¬
ments relating to the effect of posture on the quantity of intracranial
4. Kellie, George: Appearances Observed in the Dissection of Two Individuals; Death from Cold and Congestion of the Brain, Tr. Med.-Chir. Soc.
Edinburgh 1:84, 1824.
5. Haller, A.: Elementa physiologiae corporis humani, 4:204, 1762.
6. Magendie, F.: Recherches sur le liquide c\l=e'\phalo-rachidien,Paris, 1825.
7. Magendie, F.: Recherches anatomiques et physiologiques sur le liquide
c\l=e'\phalo-rachidienou c\l=e'\r\l=e'\bro-spinal, Paris, 1842.
8. Burrows, George: On Disorders of the Cerebral Circulation, London, 1846.
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blood, and in his colored plates is shown an apparent difference between
the intracranial blood volumes of animals, suspended post mortem by
the head or by the tail.
Burrows placed great importance on the cerebrospinal fluid as the
means of replacing blood lost through systemic hemorrhage, for he felt
that exsanguination unquestionably diminished the quantity of intra¬
cranial blood. Burrows was somewhat indefinite regarding the possible
mechanism for such intracranial readjustments as are necessitated by
variations in the volume of cerebral blood. He was unable to decide
whether the vacated space under such conditions was filled with serum
(cerebrospinal fluid?) or was eliminated by "resiliency of the cerebral
substance under diminished pressure" ; but in this expression of doubt
is contained the first suggestion that the volume of the brain may be
altered in accord with physiologic conditions. Summing up Burrow's
contentions, one finds that he was in general accord with the major
thesis that the intracranial volume is at all times fairly constant—a
thesis which necessarily accepts the view that the bony containers of
the central nervous system are rigid, preventing alteration in the total
volume of the tissues and fluids included within them.
After the publication of Burrow's small volume on this subject,
hardly a score of years elapsed before other attempts were made to
ascertain the truth of the important hypothesis by experimental methods.
Donders,0 and Kussmaul and Tenner,10 attempted by direct observa¬
tions through a cranial window, to secure evidence regarding the
constancy or variability of the intracranial vascular volume; their
methods, more reliable than observations on dead animals, did not per¬
mit control of all the factors. The data presented by these workers
hardly justified their conclusion of a variable intracranial blood volume.
Many years later (1896), Hill,11 introducing more rigid methods of
physiologic control, concluded that "the volume of the blood in the
brain is in all physiological conditions but slightly variable."12 But
under these experimental conditions, either by direct observations as
attempted by the earlier investigators or by deductions based on
measurement of intracranial pressures (arterial, venous and cerebro¬
spinal fluid), many factors of necessary control could not be given due
weight.
9. Donders, F. C.: Die Bewegungen des Gehirn und die Ver\l=a"\nderungender
Gef\l=a"\ssf\l=u"\llungder Pia Mater, Schmidt's Jahrb. 69:16, 1851.
10. Kussmaul, Adolf, and Tenner, Adolf: On the Nature and Origin of Epileptiform Convulsions, The New Sydenham Society, 1859.
11. Hill, Leonard: Physiology and Pathology of the Cerebral Circulation,
London, J. & A. Churchill, 1896.
12. Hill (footnote 11, p. 77).
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Dixon and Halliburton 13 studied the general problem of the MonroKellie doctrine in a way but slightly different from that employed by
Hill. Basing their conclusions on the apparently great variations in
intracranial pressures, particularly in the relation of the cerebrospinal
fluid pressure to that in the torcular herophili, they asserted that "the
cranial contents cannot any longer be regarded as a fixed quantity
without the power of expanding or contracting in volume." 14 Such an
assertion necessarily involved extreme modification of the doctrine, if
not definite renunciation. The observations of Dixon and Halliburton
indicated that unquestionably, within the physiologic limits established,
variations in the pressures of cerebrospinal fluid and of cerebral venous
blood could be effected without the exact correspondence in pressure
relationships given by Leonard Hill.
PERSONAL
OBSERVATIONS
the course of investigations to determine what agents, if
would
affect the volume of the brain, McKibben and I 15 ascer¬
any,
tained that the intravenous injection of solutions, the osmotic pressure
of which differed from that of the blood, caused in the living animal
marked alteration in the volume of the brain. It was shown that the
intravenous injection of hypotonie solutions markedly raised the pres¬
sure of the cerebrospinal fluid and increased the volume of the brain,
while the intravenous injection of hypertonic solutions caused lowering
of the pressure of the cerebrospinal fluid and corresponding diminution
in the volume of the brain. With the intravenous injection of strongly
hypertonic solutions, the pressure of the cerebrospinal fluid was fre¬
quently reduced to negative values, so that occasionally negative records
of as great magnitude as the previous positive readings were obtained
in the pressure of the cerebrospinal fluid.
These observations in the living animal caused general recon¬
sideration of the Monro-Kellie doctrine, as the hypothesis of a rigid
container for the nervous system formed a fundamental basis of inter¬
pretation. It was apparent that these alterations in the cerebral volume
and in the pressure of the cerebrospinal fluid, effected by the intra¬
venous injection of solutions of various concentrations, were dependent
on the interchange of water and salts between blood and the nervous
system with its fluids. But the negative pressures in the cerebrospinal
During
13. Dixon, W. E., and Halliburton, W. D.: The Cerebrospinal Fluid: II.
Cerebrospinal Pressure, J. Physiol. 48:128, 1914.
14. Dixon and Halliburton (footnote 13, p. 153).
15. Weed, L. H., and McKibben, P. S.: Pressure Changes in the Cerebrospinal Fluid Following Intravenous Injection of Solutions of Various Concentrations, Am. J. Physiol. 48:512, 1919; Experimental Alteration of Brain Bulk, ibid.
48:531, 1919.
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fluid involved even more the consideration of the accuracy of the MonroKellie thesis. It seemed quite impossible to obtain a negative pressure
in the cerebrospinal fluid unless the bony containers of the central ner¬
vous system served as a rigid mechanism, preventing the direct applica¬
tion of atmospheric pressure to the intracranial contents. Under these
circumstances, it became desirable to reconsider all the variables in the
hypothesis, and to test the conclusion that none of the elements com¬
pletely filling this rigid container was constant in volume. The total
volume of the three elements—blood, cerebrospinal fluid and brain—
But with realization of the
was looked on as relatively constant.
of
alteration
in
brain
volume, it was essential
possibility experimental
to hold that perhaps under conditions of physiologic life, the volume of
the brain itself would vary. Likewise, every evidence at hand indicated
that the quantity of the intracranial blood would not be constant; and
surely there were data enough to lead one to believe that the amount
of cerebrospinal fluid would vary. These factors and these assump¬
tions led McKibben and me to the general conclusion that the intra¬
cranial contents were at all times of a relatively fixed volume and that
the cranial cavity and spinal durai tube were completely filled with
blood, cerebrospinal fluid and nervous tissue; that variations in the
quantity of any one of these three elements might occur, but that these
variations were immediately compensated for by reciprocal changes in
the volume of one or both of the remaining elements.
Realizing that this general, though modified, acceptance of the
Monro-Kellie hypothesis was in many ways based on speculation, and
that belief in the general truth of the doctrine depended almost entirely
on the interpretation of negative pressures experimentally obtained in
the cerebrospinal fluid, I undertook with Hughson 1G a more extensive
study, working toward narrowing the limits of accuracy of the thesis.
In the literature, suggestions as to the importance of the cranial vault
to the general concept had been ventured—first, by Kellie,4 who
noticed that in a trephined animal (dura opened [?]) marked varia¬
tion in intracranial content of blood occurred on changes in posture.
Similarly, Ecker 17 recorded in a trephined animal a marked diminution
in the size of the brain when the carotid arteries were divided. These
16. Weed, L. H., and Hughson, W.: Systemic Effects of the Intravenous
Injection of Solutions of Various Concentrations with Special Reference to the
Cerebrospinal Fluid, Am. J. Physiol. 58:53, 1921; The Cerebrospinal Fluid in
Relation to the Bony Encasement of the Central Nervous System as a Rigid Container, ibid. 58:85, 1921; Intracranial Venous Pressure and Cerebrospinal Fluid
Pressure as Affected by the Intravenous Injection of Solutions of Various Concentrations, ibid. 58:101, 1921.
17. Ecker, Alex: Physiologische Untersuchungen \l=u"\berdie Bewegungen des
Gehirns und R\l=u"\ckenmarks,etc., Stuttgart, E. Schweizerbart, 1843.
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observations, contrasting so strongly with the observations on animals
with intact craniums, suggested the important function of the bony
cranial vault as a factor in the maintenance of the closed box character
of the coverings of the central nervous system.
Two types of experiments were devised by Hughson and me.18 In
the first series, the temporal bone on one side was trephined and the
cranial vault then removed from that side, leaving the dura mater
intact. With this experimental set-up it was possible to record the
pressure of the cerebrospinal fluid in the customary manner and to
administer intravenous injections of strongly hypertonic solutions.
Freely exposed to the atmosphere, the uncovered portion of the cranial
dura mater remained invariably tense, owing to the pressure of the
intracranial contents against it. But freed from the cranial vault over
the one side, the exposed dura could collapse inward on evacuation of
the intracranial contents. Under these conditions, repeated injections
of strongly hypertonic solutions, even in the amount sufficient finally
to kill the experimental animal, failed to reduce the pressure of the
cerebrospinal fluid to negative readings. In every case, the pressure
remained slightly above zero ; the positive reading (usually from 16 to
20 mm. of fluid) was apparently a direct measurement of the height
of the one cerebral hemisphere above the recording needle in the midline of the animal. This type of experiment demonstrated, in Hughson's and my opinion, that the intactness of the cranial vault was
essential for the production of negative pressures in the cerebrospinal
fluid.
The experiments of the second series were of a somewhat similar
nature, with provision made for the initial recording of the negative
pressures in the cerebrospinal fluid and the subsequent exposure of the
dura mater to atmospheric pressure. The experimental procedure
involved first the trephining of the cranial vault under one temporal
muscle, freeing the dura widely over one cerebral hemisphere, and sub¬
sequent sealing of the cranial opening with hard petrolatum and a glass
slide. Under these experimental conditions, measurement of the nor¬
mal pressure of the cerebrospinal fluid could be easily effected ; after
a control period, the animal was given intravenously a large dose of a
strongly hypertonic solution. This injection invariably reduced the
pressure of the cerebrospinal fluid to values of a negative nature. When
these negative pressures we're obtained, the glass slide was abruptly
removed, thereby exposing the cranial dura on one side to atmospheric
pressure. This exposure of the dura mater, which could under these
conditions collapse inward, resulted in the prompt change of the pres¬
sure of the cerebrospinal fluid from its negative value to a positive level,
18. Weed and Hughson (footnote 16, second reference).
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representing again the height of one cerebral hemisphere above the
recording needle. These two series of experiments (Weed and Hughson 19) seemed to demonstrate conclusively the essential accuracy of the
interpretation of the Monro-Kellie doctrine as given by McKibben and
me.
The data indicated that within the physiologic limits tested the doc¬
trine was fundamentally correct, and that the other elements of possible
disturbance to such interpretation were not of sufficient consequence
to interfere with the general soundness of the doctrine.
Thus, a
hypothetic dilatation of the wide venous bed in the spinal epidural space,
the possible stretching of the fibrous bands between the spinal dura and
vertebral canal, the elasticity of the occipito-atlantoid ligament and the
theoretically possible movement of fluid inward along potential perineural channels—all of which factors might be assumed anatomically
and physiologically to prevent strict interpretation of the rigid character
of the coverings of the central nervous system—were not of sufficient
physical importance to vitiate the bony framework of the central
All these potentially active
nervous system as a closed container.
factors seemed to be of theoretical rather than any practical significance
under the conditions of observation. The experiments done with
McKibben and those with Hughson did not give, however, any infor¬
mation regarding these potentialities ; the experiments excluded these
potentialities from any active role in the extreme conditions of the
physiologic procedure, and argued strongly for acceptance of the MonroKellie doctrine as an essentially sound hypothesis.
It seemed, however, that these series of experiments were largely
of a gross nature, and that the means employed were such as to bringout certain maximum variations rather than the minute effects which
might theoretically play a rôle in the normal physical use of the bomcontainers of the nervous system. Slight variations in the intradural
vascular bed or in the epidural tissues would not, under these conditions,
be great enough to interfere with the drastic reduction of the pressure
of the cerebrospinal fluid, achieved by the intravenous injection of
strongly hypertonic solutions. There could, however, not be any doubt
that in the wider sense the Monro-Kellie doctrine was correct. The
gross limitations, through which the doctrine would hold correct, were
established ; but the finer, more minute limitations were not in any way
determined.
For several years after the publication of the results of these
investigations with Hughson, I considered methods of narrowing the
physiologic limits within which the Monro-Kellie doctrine could be
demonstrated to be essentially sound. Many of the suggestions which
19. Weed and
Hughson (footnote 18, charts
1 and
2).
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to me were such as to give but little encouragement, but within
the last two years I have obtained significant data from study of the
changes in pressure of the cerebrospinal fluid, effected by alterations
in the posture of the experimental animal. Some of the data were
presented before the Association for Research in Nervous and Mental
Disease (December, 1927) ; others are now reported for the first time.
For the experimental study of postural changes in the pressure of
the cerebrospinal fluid, a simple tilting table was devised, whereby the
animal, securely fastened to the table, could be abruptly changed from
the horizontal to the vertical positions (head-down, tail-down). It was
necessary to record not only the pressure of the cerebrospinal fluid
during such changes in the animals' positions, but also the intracranial
venous pressure from the sagittal sinus (Weed and Hughson), as well
as the intracranial arterial pressure.
For all these records, simple
apparatus was used, so that the experimental procedure could be carried
out by a small experimental team.
With this set-up, many interesting observations in regard to the
physiology of the cerebrospinal fluid were obtained, but for the
restricted purpose of this discussion, only the pertinent data will be
given. First of all, it became apparent that the clinical observations of
an increase in intracranial tension when lumbar pressure was measured
in the erect rather than in the prone position held also for four-footed
mammals. In the experimental series, with the normal pressure of the
cerebrospinal fluid hovering around an average of 125 mm. of fluid,
abrupt tilting of the animal to the vertical, head-down position occasioned
an increase in the occipital pressure of from 90 to 120 mm. (charts 1,
2 and 3). In forty-four different observations, the average increase
was 104.9 mm. of fluid in this shift from the horizontal to the vertical
position, the extremes being 64 and 167 mm. On the other hand, if
the animal was tilted from the horizontal to the vertical, tail-down posi¬
tion, a decrease of from 60 to 85 mm. occurred in the pressure of the
occipital cerebrospinal fluid (chart 2), the average decrease in twentyfour observations being 74.3 mm. The extreme variations were 115
and 48 mm.
On restoration of the animals to the horizontal position, the pres¬
sures of the cerebrospinal fluid returned ultimately to the same levels
as in the control periods, but not until temporary depressions had
occurred after the vertical, head-down position and temporary elevations
after the vertical, tail-down position (charts 1, 2 and 3). These
increases and decreases from the normal level after such vertical tiltings
consisted of from 10 to 15 mm. of fluid. They persisted usually from
five to seven minutes, with gradual recession, normal levels being cus¬
tomarily restored within ten minutes. These slight differences from
the normal levels of pressure of the cerebrospinal fluid are of siccame
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nificance in indicating the place of absorption of the major portion of
the cerebrospinal fluid and the relation of pressure to the process.
With the vertical, head-down position, the pressure of the intracranial
cerebrospinal fluid is increased; when the animal is restored to the
horizontal position, the pressure of the cerebrospinal fluid is below that
which existed before the tilt to the vertical position. The exact con¬
These obser¬
verse holds when the tilting is in the opposite direction.
vations would seem to indicate that the major absorption of the
cerebrospinal fluid is unquestionably in the head region, and that with
Chart 1 (dog—experiment A 18).—In this and the following charts, the ordirepresent millimeters of Ringer's solution or mercury (carotid pressure) ;
abscissae, time in minutes ; solid black line, cerebrospinal fluid pressure from
nates
occipito-atlantoid manometer ; interrupted line, sagittal venous pressure ; rings and
dashes, brachial venous pressure; solid circles and dashes, carotid arterial pressure.
The animal was in a horizontal position except during the interval marked by the
solid block, in which it was shifted to a vertical, head-down position.
increased pressure in the cranial cerebrospinal fluid an increased
takes place.
Other changes of significance occurred during this tilting process,
particularly in the cerebral venous pressures, as measured in the
superior sagittal sinus (charts 1 and 2). The average increase in
sagittal pressure in the same series of observations, with tilting of the
absorption
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animal from the horizontal to the vertical, head-down position, was 184.1
mm., as compared with an increase of 104.9 mm. in the pressure of the
occipital cerebrospinal fluid. In the converse experiments, on tilting
from the horizontal to the vertical, tail-down position, the average
decrease in sagittal pressure was 79.7 mm., as compared to the average
decrease of 74.3 mm. in the pressure of the occipital cerebrospinal fluid.
The alterations in the systemic venous pressure (chart 3) were not of
significance during this process of abrupt tilting from the horizontal
to the vertical ; similarly, the alterations in the intracranial arterial près-
Chart 2 (dog—experiment A 24).—The animal was in a horizontal position
except during the interval marked by diagonal cross-hatching, in which it was
shifted to a vertical, tail-down position, and during the interval marked by the
solid block, when it was shifted to a vertical, head-down position.
likewise not of real importance in the
discussion. The general observations indicate, therefore, that the pres¬
sure of the cerebrospinal fluid is less affected by postural changes than
is the pressure of the cerebral venous system.
In some animals, the pressure of the cerebrospinal fluid was taken
simultaneously by occipito-atlantoid and lumbar manometers. Under
these conditions, during the control periods when the animal was in the
horizontal position, the occipital and lumbar pressures were at the same
sure
(charts 1,
2 and
3)
were
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levels. When, however, the animal was tilted from the horizontal to
the vertical, head-down position, the increase in the occipital pressure
was far greater than when the durai tube was pierced by only one
needle (chart 3) ; negative pressures occurred in the lumbar manometer.
In one animal, the occipital pressure increased from 120 to 240 mm.,
while the lumbar pressure fell to minus 100 mm. With the animal in
the vertical position, the occipital and lumbar manometers were in the
same vertical plane, side by side.
The fluid in the two manometers
could be seen under these conditions to be at exactly the same level,
though in the experimental set-up the lumbar manometer recorded a
Chart 3 (dog—experiment A 8).-—The animal was in a horizontal position
except during the intervals marked by the solid blocks, in which it was shifted to
a vertical, head-down position.
During the interval, from 57 to 68 minutes, lumbar
puncture was done.
pressure, while the
When the animal
instrument recorded a positive
restored to the horizontal position,
both these manometers showed resumption of normal pressures.
One of the phenomena noted in all these experiments was the
relatively rapid fatigability of the vasomotor system on such abrupt
tiltings to the vertical. In many animals, spontaneous respiration ceased
and vasomotor collapse seemed to occur. Others of the animals seemed
to stand these abrupt changes in posture well, and fatigue in reaction
In one animal (chart 4),
was not apparent, even after many tiltings.
negative
pressure.
occipital
was
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five
carried out in seventypractically absent
the
the
The
of
throughout
period.
magnitude
postural alterations is,
however, of some significance in the general process, as in this animal
the decreases in the pressure of the cerebrospinal fluid were as follows :
40, 70, 60, 48 and 74 mm. The decreases in sagittal venous pressure
for the same tiltings were 65, 69, 59, 45 and 47 mm. Such variations
are, of course, not unexpected in any physiologic reaction, but the curve
indicates a gradual decrease in the pressure of the cerebrospinal fluid,
together with a gradual increase in the sagittal venous pressure.
abrupt tiltings
seven
minutes of
at
five minute intervals
were
experimentation ; fatigue
was
COMMENT
All these data have immediate significance in the limitation of tht
field of accuracy of the Monro-Kellie doctrine. In this series of labora¬
tory mammals (cats and dogs), the average distance between the
occipital recording needle and the last lumbar spine was slightly over
400 mm. The average alterations in the pressure of the cerebrospinal
fluid on tilting from the horizontal to the vertical positions were
104.9 mm. for the head-down position, and 74.3 mm. for the tail-down
position. These alterations in the pressure indicate, therefore, that in
the vertical position the full hydrostatic effect of the column of 400 mm.
of water is not superimposed on the existing normal pressures. For, if
this column were superimposed in its entirety, the pressure of the
occipital cerebrospinal fluid should increase approximately 400 mm.
when the animal is tilted from the horizontal to the vertical, head-down
position ; and, conversely, the decrease should be of the same extent,
giving negative pressures in the cerebrospinal fluid, when the animal
is tilted to the vertical, tail-down position.
Similarly, the magnitude of the alterations in the pressure of the
cerebrospinal fluid in these experimental procedures indicates that the
spinal durai tube does not serve as an absolutely rigid container, for if
the tube were a truly rigid container, the tiltings from the horizontal to
the vertical positions, either tail-down or head-down, should not in any
way affect the pressure of the occipital cerebrospinal fluid, the tube
being to all intents completely filled with fluid. The tilting experi¬
ments with manometers in both occipital and lumbar regions are impor¬
tant here : the second needle serves to vent the tube and permits
dislocation of the spinal fluid as indicated by the greater increase of
pressure in the dependent needle when compared with the lesser increase
in animals without a lumbar opening (chart 3). The fact that alterations
in the pressure of the cerebrospinal fluid do occur in abrupt tilting from
the horizontal to the vertical, even when the tube is not vented, indicates
that the physics of the hydrostatic column of water cannot be directly
applied : the extent of the alterations in pressure, however, demonstrates
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that in many ways the spinal durai tube does act as a partially rigid con¬
tainer. Venting of this tube which thus allows atmospheric pressure
to affect the fluid column through one of the recording manometers,
as in those animals in which simultaneous records of occipital and lumbar
pressures were obtained, shows that a partial vacuum must, under ordi¬
nary conditions, be created within the uppermost portion of the tube,
when the animal is in the vertical position.
These observations lead, therefore, to speculation regarding the
anatomic and physiologic mechanisms which permit, under these condi¬
tions, the partial application of the hydrostatic column to the pressure
of the cerebrospinal fluid when the animals are in the vertical positions.
Two factors of extreme importance seem immediately indicated: (1) the
possible inward collapse of the spinal dura mater, and (2) the alteration
in the intradural venous bed (dilatation or constriction). Reducing the
problem to its simplest form, in the case of the animal tilted from the
horizontal to the vertical, head-down position, with resultant increase in
the pressure of the occipital cerebrospinal fluid of approximately
100 mm., it becomes apparent that this increase in the pressure must
have been due to dislocation of the spinal column of fluid, permitted
by partial collapse of the spinal dura or by dilatation of the intra¬
dural veins in the spinal region. The first of these two factors
might be due to stretching of the small fibrous trabeculae, extending
across the epidural space from the inner surface of the rigid vertebral
column to the outer surface of the dura mater. Such a hypothetic
stretching of fibrous trabeculae might also be accompanied by dilatation
of the veins in the extensive epidural plexus. This stretching would
probably occur to the greatest extent in the lumbar and sacral regions of
the cord, for in these regions the negative pull of the column of water
would, in the vertical position, be most extreme.
The second factor which might play an important rôle in such an
increase in occipital pressure, with the animal in the vertical position,
is the dilatation of the intradural veins in the lower spinal region.
Such a hypothetic dilatation would affect the thin-walled veins transversing the subarachnoid space, the extensive venous bed directly
beneath the pia mater and possibly the venous bed of the spinal cord
itself. This assumed dilatation of veins would decrease the space
occupied by the column of cerebrospinal fluid under normal condi¬
tions, and would, therefore, permit dislocation of the fluid from the
lumbar and sacral regions when the animal is in the vertical, head-down
position. This dislocation would be equivalent to a decrease in the
height of the fluid column ; it would have the same physiologic effect
as inward collapse of the dura mater.
Some information regarding the relative importance of these two
possible factors in allowing a partial hydrostatic effect to be manifested
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in tilting from the horizontal to the vertical positions can be obtained.
The basis for this statement lies in the differences recorded in the
pressure of the cerebrospinal fluid when the animals were tilted from
the horizontal to the vertical, head-down and tail-down positions. In
the former case (tilting from horizontal to vertical, head-down position),
the average increase in occipital pressure was 104.9 mm. of fluid; while
in the latter case (tilting from horizontal to vertical, tail-down position),
the average decrease was 74.3 mm. In both these tiltings, the recordingneedle was in the same place (i. e., through the occipito-atlantoid liga¬
ment in the midline), and the same column of fluid was imposed on the
normal pressure, though in different directions. Were the dilatation
of intradural veins in the uppermost part of the animal the impor¬
tant factor, the decrease when the animal is tilted from the horizontal
to the vertical, tail-down position should be greater than when it is tilted
from the horizontal to the vertical, head-down position. In the former
tilting, the dilatation of the relatively enormous cerebral veins, allowing
outspoken dislocation of the fluid column, would be theoretically possible.
However, with the recorded increase in pressure of the occipital cerebro¬
spinal fluid on tilting from the horizontal to the head-down position
exceeding the decrease on tilting from the horizontal to the vertical, taildown position, it must be assumed that the inward collapse of the dura
mater is the more important factor in such superimposition of hydro¬
static effect on the normal pressure of the cerebrospinal fluid.
The inward collapse of the dura mater, which seems essentially
responsible for the postural dislocation of cerebrospinal fluid, occurs, in
all probability, to a greater extent in the lumbar and sacral regions than
in the thoracic and cervical areas. The evidence for this again depends
on the greater alteration in pressure of the cerebrospinal fluid on vertical
tilting to the head-down position than on tilting to the tail-down position.
In the former case, it seems logical to assume a collapse of the dura
mater against the spinal cord in the region where the spinal cord is
rapidly diminishing in size, whereas, in the latter case, the cervical
enlargement apparently tends to prevent great inward collapse of the
dura mater. The relative sizes of lumbar and cervical portions of the
subarachnoid space would here appear to be responsible.
It seems rational also, on the basis of this argument, to assume that
a theoretically possible compression of veins in the dependent portion
of the nervous system on vertical tilting plays practically no rôle in the
process of dislocation of the fluid. Were such a compression of veins
a factor of significance, the recorded changes in cerebral venous pressure
would not exceed the changes in the cerebrospinal fluid pressure, for
the pressure of the fluid on the outside of the veins would necessarily
have to equal or exceed that within the veins to secure such mechanical
compression. Also, if the veins in the dependent part of the nervous
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the surrounding cerebrospinal fluid on such
vertical tilting, dislocation of spinal fluid would not occur, unless at
the upper end of the vertical system such a dislocation of fluid were
at the same time permitted by other factors.
On the other hand, the major emphasis given in the foregoing para¬
graphs to the importance of inward collapse of the spinal dura mater
does not seem to tell the whole story. The extent of the alterations in
the pressure obtained on each successive tilting in one animal should be
almost exactly the same, were the inward collapse of the dura mater the
entire factor in the process of dislocation of the spinal fluid. This
inward collapse of dura mater, permitted by stretching of the epidural
trabeculae, must be looked on largely as an anatomic phenomenon, and
system
were
compressed by
Chart 4 (dog—experiment A 33).—The animal was in a horizontal position
except during the intervals marked by the solid blocks, in which it was shifted to a
vertical, head-down position.
the process should, therefore, not be subject to greater variation within
the period of experimentation. In the animal the reactions of which are
set down in chart 4, the variations in the alterations of pressure of the
cerebrospinal fluid were considerable ; and these variations, occurring
within five or ten minutes in the same animal, with coincident changes
in the pressures in the superior sagittal sinus, would indicate that the
factor of vasomotor readjustment still had some importance. In conse¬
quence, it is not in any way possible to exclude from this explanation
the theoretical dilatation of the intradural veins in the uppermost por¬
tions of the spinal cord when the animal is in the vertical positions ; this
dilatation must play a rôle of unknown importance in permitting down¬
ward dislocation of spinal fluid.
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CONCLUSIONS
in pressure in the cerebrospinal fluid
lead to the general conclusion that
the mammalian central nervous system is protected in large measure
against changes in pressure due to postural adjustments, as the full
effects of the hydrostatic column of fluid, theoretically possible, are not
superimposed in the vertical position on the normal pressure of the
cerebrospinal fluid. The extent of these variations in pressures, on
abrupt tilting to the vertical positions, are in accord with the clinical
observations by Barré and Schrapf ,20 and by Zylberlast-Zand ;21 in these,
an increase of approximately 200 mm. in pressure of the lumbar cerebro¬
spinal fluid was recorded in man on change from the prone to
the vertical position. Were the central nervous system not held within
a relatively rigid container, the full extent of the hydrostatic column of
fluid should be recorded both in the four-footed animal and in man.
In the laboratory mammals used in these experiments, this column of
fluid measured approximately 400 mm., while in man the analogous dis¬
tance between occiput and last lumbar spine is between 575 and 600 mm.
Roughly, from one third to one fourth of this actual column of fluid
makes its effect felt on postural adjustment; in other words, the spinal
tube of mammals is fairly, though not absolutely, rigid. Within these
physiologic limits, as tested in the experiments on mammals, the spinal
tube does not serve as an absolutely rigid container, yet the effect of the
rigidity of the tube is such that only a fraction of the hydrostatic height
of the contained column of fluid makes itself felt.
This assumption of relative rigidity in the spinal durai tube delimits
again the general accuracy of the Monro-Kellie hypothesis, for in this
doctrine it is necessary to include the spinal tube as well as the cranial
portion. On the basis of these experiments, the Monro-Kellie thesis
may still be assumed to be essentially correct ; but the correctness of
the doctrine does not seem to be as absolute, as in the experiments
recording negative presssures of the cerebrospinal fluid. In these former
observations, the theoretical or actual collapse of the spinal dura against
the spinal cord, and the theoretical or actual dilatation of the spinal
veins, play rôles of relatively small significance, as shown by the extreme
negative pressures so frequently obtained.
There are, of course, other limitations to the Monro-Kellie thesis.
In the recorded literature on the subject, but little mention has been
made of the fact that all the discussions of the doctrine are based on
phenomena of alterations
change in the animal's posture
These
on
20. Barr\l=e'\,J. A., and Schrapf, R.: Sur la pression du liquide c\l=e'\phalo-rachidien,
Bull. m\l=e'\d. Paris 35:63, 1921.
21. Zylberlast-Zand, N.: Sur la modification de la pression du liquide c\l=e'\phalo\x=req-\
rachidien sous l'influence du changement de position du corps et de la t\l=e^\te,Rev.
neurol. 37:1217, 1921.
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the anatomic arrangements in the adult; consideration is not given to
the anatomic disposition in the new-born babe and in other new-born
mammals, where fibrous sutures and fontanels characterize the skull at
the time of birth. The pulsations of the anterior fontanel in the new¬
born babe have been noted for almost 2,000 years, and the elasticity of
these fontanels would, of course, vitiate extreme interpretation of the
accuracy of the Monro-Kellie thesis. As pointed out in other para¬
graphs, however, the elasticity of the occipito-atlantoid ligament in the
adult would similarly affect the absolutely rigid character of the con¬
tainers of the central nervous system ; and in the new-born child the
insertion of such an elastic membrane in a large portion of the cranial
vault would unquestionably tend to have a far greater effect on the
Monro-Kellie hypothesis than would the persistence of a small elastic
window in the occipital region.
It was, of course, extremely important to have Blackfan, Crothers
and Ganz argue so clearly that in children the Monro-Kellie hypothesis
should not be applied with exactness ; but it should not be assumed that
it is possible to discard the thesis entirely in the new-born child and in
young infants. Nanagas'23 experiments on hydrocéphalie kittens are
pertinent to the discussion. In the series of young kittens in the first
few weeks of life, Nanagas created an experimental hydrocephalus by
injecting suspensions of lamp black into the cerebral ventricles or subarachnoid space (Weed24). Following this procedure, the skulls of
these kittens increased enormously in size, the suture lines enlarged and
the fontanels became wide, elastic membranes. The intraventricular
pressure of these hydrocéphalie kittens was approximately 50 per cent
higher than the pressures in the control litter mates. When given
intravenous injections of strongly hypertonic solutions, the intra¬
ventricular pressure of the hydrocéphalie kittens in Nanagas' series was
frequently reduced to negative values. The skull of these kittens, with
such negative pressures existing within the nervous system apparently
collapsed in part, the flat cranial bones coming to over-ride each other
so that a fairly rigid skull was reestablished.
The obtaining of such
in
kittens
would
the
indicate that in the
negative pressures
experimental
new-born mammal the Monro-Kellie doctrine should be looked on as
a fairly potent factor in intracranial physiology.
The limitations here,
much
the
are
to
extreme elasticity of the
greater, owing
however,
—
22. Blackfan, K. L.; Crothers, B., and Ganz, R.: Intracranial Pressure in
the Hydrocephalus of Infancy and Childhood, Proc. A. Research Nerv. & Ment.
Dis., N. Y., December, 1927.
23. Nanagas, J. C.: Experimental Studies on Hydrocephalus, Bull. Johns
Hopkins Hosp. 32:381, 1921.
24. Weed, L. H.: The Experimental Production of an Internal Hydrocephalus,
Contrib. Embryol. no. 44, Carnegie Inst., Washington, 1919, pub. 272, p. 425.
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anterior fontanel and the wide extent of this elastic window, than in the
case of adult animals, in which the whole cranial vault is bony.
That
the intactness of a major portion of the cranial vault is necessary for the
essential working of the closed box character of the containers of the
central nervous system was shown by the experiments done with
Hughson. The question is one merely of the limitations of the MonroKellie thesis rather than of its incorrectness.
In the Monro-Kellie doctrine, then, there exists a hypothesis which
within tested physiologic limits must be considered essentially sound,
though in minor ways the doctrine does not hold. The evidence points
to the cranial cavity as an intact closed container ; in the spinal dura
mater, there exists a fibrous membrane which is not held outwardly
with great rigidity. The spinal region, therefore, constitutes the part
of the central nervous system which is apparently not confined within
an absolutely rigid container ; but the importance of this
part of the
central nervous system is relatively not as great as the cranial portion.
So in almost every physiologic way, the Monro-Kellie doctrine must be
considered essentially correct, though such consideration must be always
subject to special limitation. From the standpoint of intracranial
physiology, as a basis for experimental or surgical procedures, the
doctrine holds; and its importance is great in any clinical procedure.
It is thoroughly stimulating to contemplate again the gradual devel¬
opment and delimitation of this important doctrine of intracranial
anatomy and physiology, for in this doctrine there have been elements of
romance and speculation.
Taking its inception as an explanation of
intracranial physiology logical to its time, Monro 1 limited the doctrine
strictly to the cranium, and being ignorant of the existence of the
cerebrospinal fluid and of the variability of brain volume, he developed
the hypothesis in relation only to the intracranial blood volume. Then,
in Kellie's fascinating studies, there seemed to exist pathologic and
experimental proof of the hypothesis. Again, with the increasing dis¬
semination of knowledge regarding the cerebrospinal fluid, Burrows
was able to add another element to the consideration, and to
accept the
doctrine as a generality, though limiting it in a rather specific way.
The introduction of modern experimental methods, especially the
attempted study of the cerebral blood volume by direct observation
through a cranial window, added but little in the initial researches,
owing to the difficulty of examining more than a local area of the
central nervous system and to the necessity of limiting the obser¬
vations to the relatively large cerebral arteries and veins. But this
method, in the final analysis, must give the information needed ; and it
is of great significance that renewed efforts to this end are now being
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The recent studies by Forbes and Wolff2" are
technically great improvement over the earlier investigations by an
analogous method of direct observation ; with Kubie's introduction of
colored photography into the procedure, data regarding the cerebral
capillary volume will soon be available as well as information regarding
the calibers of the superficial cerebral arteries and veins. All these
methods, to be of final service, must, however, be subject to some type
of calibration or standardization, in order that these observations may be
carefully checked against the physiologic measurements of intracranial
pressures.
With such methods at hand, knowledge regarding the mechanism of
compensation between the three elements filling the cranial cavity may
be had, so that the problem will be taken from the field of speculation
to that of definite physiologic demonstration. However, at present,
it seems thoroughly logical to conclude that in a major way the MonroKellie thesis will, in the future, be held to be essentially correct. The
gradual accumulation of the known limitations of the doctrine will
serve to strengthen the reliance on the major discussion rather than to
weaken it.
carried forward.
a
25. Forbes, H. S., and Wolff, H. G.: Cerebral Circulation: III. The VasoControl of Cerebral Vessels, Arch. Neurol. & Psychiat. 19:1057 (June)
1928. Forbes, H. S.: The Cerebral Circulation: I. Observation and Measurement of Pial Vessels, ibid. 19:751 (May) 1928.
motor
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