(Submitted September 11, accepted October 9, 1957.)
ADDRESS: (J.T.L.) 550 First Avenue, New York 16, New York.
PEDIATRICS, March 1958 skull and the appearance of convolutions
on the surface of the cerebral hemispheres
are sometimes said to be secondary to ex-pansion of the brain into a restricted space. The presence of a fluid layer surrounding
the developing brain did not support the
concept of such a simple relationship.
No description of this fluid layer could be found. Its presence in fetal sheep was mentioned by Barron.’ Potter2 stated that the human brain developed in a fluid-filled
space, and found’ that the weight of fluid in the cranial cavity averaged approximately
10% of the weight of the brain in fetuses weighing 250 to 1750 gm. It was not clear
whether these measurements were of extra-cerebral fluid only or whether intraventricu-lar fluid was included; in infants weighing more than 1750 gm the volume of
intra-cranial fluid decreased abruptly to only 1 to 2 ml, suggesting that intraventricular
fluid was not included. Presence of only a small volume of intracranial fluid during late fetal life is supported by a statement of
Scammon4 that the brain of the newborn infant filled the cranial cavity more
com-pletely (97.5%) than that of the adult (92.5%). We were interested in the apparent large
amount of the extracerebral fluid and un-certain whether it lay in the subdural or
subarachnoid space. Its volume was meas-ured in four fetuses by a method excluding the intraventricular fluid and its location
determined in a fifth by dye injection.
jected with protein hormones iodinated with 1-131 (< 150 microcuries per fetus). Three to twenty minutes after injection, the fetuses were frozen in a mixture of acetone and dry ice with an initial temperature of about 0#{176}C,de-creasing to -70#{176}C during a period of 20 to 30 minutes. The entire frozen fetus was then set in moist cotton, frozen to a block, and sec-tioned on a microtome. The bayer of fluid sur-rounding the brain was first noted as an in-cidental finding in each of these preparations. Subsequently its presence in 1 1 fresh,
unin-jected, unfrozen fetuses was regularly observed On direct dissection.
In order to measure the volume of the fluid, four additional fetuses were frozen and sliced
to the midline in the sagittal plane on the microtome. From the remaining bower half of the frozen fetuses the brain substance was readily and cleanly chipped from the frozen
underlying fluid bayer. The ice layer was then
separately chipped from the underlying dura, which remained as an intact glistening
mem-brane lining the skull. The brain and the fluid layer were weighed and the percentage of the intracranial space occupied by each was
calculated.
The location of the fluid layer was
deter-mined in a fifth fetus. A few drops of clear spinal fluid were removed by spinal puncture and replaced by an equal volume of India ink. Diffusion of the ink was hastened by gently squeezing the head a few times. A needle was
‘104 EXTRACORTICAL CEREBROSPINAL FLUID
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Fic. 2. II1IU1III1 fttis: Crowii-rtuip length 1:3c’ni. Estiniated gestatioiial age: 16 tv(’(ks.
(oroIlal sectiotit sl1o%viIlg a layer of fluid l)et%&e1I the brain and calvtLriLIIlI. Iii anothtr
fetlisof the same size, the fluid filled 25 of the imitracraimialspace.
A large orbital space is Prisemit in (1); the corresponding space iii (2) is a HhIid-IIlIe(I anterior projection of the middle fossa,
SPE
406 EXTRACORTICAL CEREBROSPINAL FLUID
space.
FIG. 3. Human fetus: crown-rump length 8 cm. Estimated gestationab age: 12 weeks. Injected
Supratentorial space only.
3). The two differently colored solutions de-fined the position of the meninges.
RESULTS
Weights of the brain and of the layer
of fluid obtained by dissection of four frozen
fetuses indicated that the fluid occupied
from 13 to 26% of the intracranial space (Table I); the larger fetuses had both abso-lutely and relatively larger amounts of fluid. In the largest fetus, which was estimated to be 23 weeks of gestational age, con-volutions were beginning to appear in the cerebral hemispheres (Fig. 1). In this fetus,
fluid filled 26% of the supratentorial space.
In the fetus injected with dye (Fig. 3),
India ink injected into the spinal canal
stained the entire layer of fluid surrounding the brain except for a thin crescent of blue fluid immediately beneath the site of injec-tion of the Evans blue dye and presumably lying in the subdural space. The amount of
blue-stained fluid was approximately equal
to the amount injected. A membrane which
we believe was the arachnoid separated the two colored fluids.
DISCUSSION
A layer of cerebrospinal fluid surrounded the developing brain of normal human fetuses. The presence of this layer mdi-cates that growth of the skull is not
second-ary to pressure on the skull from the
ex-panding brain. A lack of interdependence between growth of skull and brain is also seen in hydranencephaly; in this anomaly,
the head, which may be of normal size
and shape, is filled with cerebrospinal fluid, and only small amounts of brain tissue are
present. Despite the almost complete
ab-sense of brain tissue, the growth of the skull in this anomaly is maintained during fetal life.
Cortical convolutions are also sometimes said to be caused by growth of the brain into a confined space. However, we found
that cortical convolutions appeared in the developing human brain when the organ was surrounded by a thick layer of fluid.
This fluid would give uniform pressure at all points. Even if the brain pressed
di-rectly against the smooth inner surface of the calvarium, folding should not result. Cortical folding is caused by local differ-ences in rates of growth, not by direct pressure. The surface of a balloon blown
up inside a bottle does not become con-voluted.
SUMMARY
A layer of cerebrospinal fluid surrounds
the developing brain of normal human fetuses. The layer was found to occupy 13 to 26% of the intracranial space.
Convo-lutions appeared in the hemispheres while this layer was still present.
Neither growth of the skull nor the
ap-pearance of cortical convolutions is
second-ary to pressure from growth of the brain
into a confined cranial space.
REFERENCES
408
EXTRACORTICAL CEREBROSPINAL FLUID 2. Potter, E. L. : Pathology of the Fetus andthe Newborn. Chicago, Yr. Bk. Pub., 1952, p. 402.
3. Potter, E. L., and Rosenbaum, W. : The normal amount of cerebrospinal fluid present within the skull at birth. Am.
J.
Obst. & Gynec., 45:701, 1943.4. Scammon, R. E.: In Pediatrics, Vol. I, Abt, l.A., ed. Philadelphia, Saunders, 1923, p. 420.
SUMMARIO IN INTERLINGUA
Fluido Cerebrospinal Dc Sito Extracortical In Normal
Fetos Human
In be curso del dissection de un serie de normal fetos human obtenite post abortos legal in Sveda, be observation esseva facite
repetite-mente que be cerebro non replenava be cavitate cranial completemente sed esseva inveboppate
per un strato de fluido clar. Le sito e be con-finios de iste fluido es illustrate in Figuras 1
e 2. Figura 1 demonstra in plus que convobu-tiones cortical appareva a un tempore quando be cerebro non occupava be complete cavitate
cranial. Estimationes volumetric effectuate per pesar glacie abrumpite in appropriate areas de
fetos congelate revelava que be fluido occupa
inter 13 e 26 pro cento del spatio intracranial. Le injection de coborante demonstrava que be fluido occupava un expandite spatio subarach-noide. Figura 3 monstra que tinta de China injicite in be canal spinal coborava be strato de fluido durante que blau de Evans injicite per-cranialmente a in le spatio subdurab remaneva
bocalisate a un area restringite infra be sito de injection.
Iste observationes monstra que ni be cres-centia del cranio ni be apparition del
convobu-tiones cortical resulta secundarimente ab be
