Talk:Book - The Pineal Organ (1940) 25: Difference between revisions

From Embryology
mNo edit summary
 
Line 503: Line 503:
As might be expected, microglial cells are present in the retina and  
As might be expected, microglial cells are present in the retina and  
in the optic nerve, and they have been found in the fibrous plaques of the  
in the optic nerve, and they have been found in the fibrous plaques of the  
human pineal organ.  
human pineal organ.
 
 
 
==CHAPTER 26 STRUCTURE OF THE FULLY DEVELOPED HUMAN PINEAL ORGAN==
 
As previously mentioned, the structure of the pineal body varies
considerably at different ages and in different individuals, and like some
other embryonic and infantile organs which develop up to a certain
degree of perfection and then degenerate, e.g. the pronephros, the greater
part of the mesonephros, and the thymus gland, the pineal body normally
attains its maximum of development before the individual has reached
maturity. This maximum, according to the general estimate, occurs
somewhere between the ages of 5 and 7 years. Signs of degeneration are,
however, frequently evident before this period, and the uniform alveolar
appearance which is present in early infancy usually becomes less pronounced at the end of the second year, and signs of degeneration and
replacement of parenchymal cells by fibroglial tissue are often seen in
quite young children. The parenchymal tissue becomes surrounded by
ingrowths of fibrovascular septa which are continuous externally with
the capsule. These break up the parenchymal tissue into rounded lobes,
as seen in Fig. 264, the pineal body of a child aged 5. This specimen
may, however, be regarded as exceptional with regard to the age at which
degenerative changes, accompanied by ingrowth of thick fibrovascular
septa from the capsule, have taken place, and there are instances in which
the uniform structure of the pineal organ present in the infant is retained
even in advanced age. Speaking generally, however, it is commonly
admitted that, although exceptions occur, there is an increase in the
proportion that the fibroglial constituents have to the parenchyma from
childhood onwards to old age. We shall, therefore, describe first the
structure of the pineal organ as it appears in children between 3 and
6 years of age, in preference to commencing the description of the organ
of adult individuals, in which both the parenchyma cells and the supporting
tissue usually show signs of degeneration.
 
Besides variations in structure due to age changes there are differences
in appearance which are brought out by different methods of preparation,
and we propose, before dealing with the selective actions produced by the
use of special methods of modern technique, to give a short description
of the microscopic appearance of a section of the pineal gland of a child
 
393
 
 
 
I.Lr.S.
 
 
 
394 THE PINEAL ORGAN
 
5 years of age stained by the ordinary harmatoxylin and eosin method.
We shall then endeavour to interpret the appearances seen at this stage
of development and in the organ of adult individuals by a reference to
the earlier stages of embryonic and foetal development and by the microscopic pictures brought out by the use of differential stains. The pineal
organ at this stage is invested by a fibrovascular capsule, derived from
the pia mater and lined internally by a glial stratum. This capsule sends
trabecular containing blood-vessels into the substance of the gland. The
trabecular pass inwards and partially surround the peripheral part of a
 
branched system of
lobules which primarily originate from
the ependymal epithelium of the embryonic
pineal diverticulum.
The epithelial tissue
of the lobules is, however, penetrated
throughout by fine
trabecular of intralobular connective
tissue containing capillary blood-vessels.
The lobular areas between the larger trabeFig. 264. — Tangential Section of the Pineal Gland cu ]^ which grow inof a Child, showing the Fibrous Capsule, Lobes, , - *" , ,
 
and Interlobar Septa. (R. J. G.) ward from the capsule
 
Ca. : capsule. communicate with
 
I.L.S. : interlobular septum. eac h ot her i n the
 
I.Lr. S. : intralobular septum. , ,, ,
 
P. : parenchyma. central part of the
 
gland so that the
lobules as a rule are not completely enclosed in separate compartments, but are continuous with a central mass of parenchymatous tissue
which is more uniform in appearance than the lobulated peripheral zone.
The lobules consist of a supporting glial tissue which has the character of
a fibrillated sponge-work or reticulum enclosing clear intercommunicating spaces. Some of the spaces contain parenchyma cells with vesicular
nuclei, while others appear empty. The reticulum is especially noticeable
beneath the capsule and in relation with the larger trabecular. The cellelements of the reticulum have the appearance of being continuous with
each other, no intercellular septa or intervals ever being visible with the
ordinary methods of preparation. The network thus seems to be formed
 
 
 
 
J-Pa.
 
 
 
THE FULLY DEVELOPED HUMAN PINEAL ORGAN 395
 
of a Plasmodium or spongioplasm within which the nuclei of the cellelements are imbedded. In many of the spaces of the network branched
parenchyma cells containing pale vesicular nuclei are present. The
processes of these cells appear to be :
 
(1) Continuous with processes of similar adjacent cells.
 
(2) Continuous with the matrix of the general neurospongium.
 
(3) Spread out on the perivascular sheaths of the vessels contained
 
in the trabecular or fibrous capsule.
 
 
 
S.D.N.
 
 
 
 
 
 
 
 
 
 
 
*pv
 
 
CT.C.
 
 
 
Pa.C.
 
 
 
Fig. 265. — Section of an Adult Pineal Gland stained by van Gieson's
Method and Eosin, showing the Apparent Continuity of the Reticulum
in which the Parenchyma Cells are embedded ; and also the Relation
of the Parenchyma Cells to the Spaces of the Reticulum and the
Supporting Tissue or Neurospongium. An Interlobular Septum
showing Capillary Blood Vessels and Nuclei of Fibrous Connective
Tissue crosses the Upper Part of the Drawing obliquely. (R. J. G.)
 
 
 
Cp. : capillary vessel.
 
CT.C. : connective tissue cells.
 
Pa. C. : parenchyma cell.
 
 
 
S.D.N. : small darkly stained nucleus.
Sp. : space.
 
 
 
The cells with the pale vesicular nuclei belong to the fully developed
type of pineal or parenchymal cell ; many of the parenchyma cells,
however, are embedded in the spongioplasm, and in this situation the
nucleus is usually smaller and more deeply and uniformly stained than
those of the cells just described. Between these two extreme types, in
young as well as in adult specimens, there are numerous intermediate
forms (Fig. 265), both with respect to the type of the nucleus and the
 
 
 
396
 
 
 
THE PINEAL ORGAN
 
 
 
 
Fig. 266. — Pineal Body. 350.
 
Median vertical section, through the peduncle, of a human pineal body prepared by the Blair-Davis modification of Ranson's pyridin method. The larger,
deeply stained fibres forming a network between the pineal cells are probably
glial, the finer fibrillar in the centre of the photograph are indistinguishable from
nerve-fibres, and possibly represent the axis-cylinders or nerve-fibres reaching
the pineal body from the superior and posterior commissures.
 
 
 
 
Fig. 267. — Pineal Body. 350.
 
Section through the cortical zone of the same specimen as Fig. 266. The
larger fibres forming a network surrounding the pineal cells are probably glial.
The finer fibres between the cells and surrounding the capillary vessels are probably nerves of the sympathetic system.
 
 
 
THE FULLY DEVELOPED HUMAN PINEAL ORGAN 397
 
position of the cell-element, namely, wholly contained within the spongioplasm, protruding from this into a space, or completely extruded into the
space and connected to the surrounding structures merely by fine, tapering processes.
 
In adult specimens, however, when specifically stained for neuroglia,
the distinction between glial cells and the general plasmodium or syncytial
reticulum in which they are imbedded is quite definite, and it is at once
evident that the slender astrocytes and glial fibres in no sense form the
principal constituent of the supporting tissue of the lobules.
 
The former appear as very sparsely scattered branched cells, chiefly of the
astrocyte type (Fig. 272, p. 403), with fine delicate processes lying in a tissue
which when specially
stained by Hortega's
silver impregnation
method is seen to be
principally composed of
branched parenchyma
cells which he believes
to be separate and independent units.
 
By combining the
knowledge gained by
the different specific
methods of silver impregnation with that
obtained by the best
nuclear and cytoplasmic
stains we are able to
distinguish in the parenchymatous tissue of
the adult human pineal organ three principal elements, namely :
 
(1) A glial component, formed by the cell-bodies and slender branched
 
processes of a relatively small number of astrocytes.
 
(2) The parenchyma or pineal cells, distinguished by their large,
 
pale vesicular nuclei. These are much more numerous than
the astrocytes and form the main bulk of the tissue.
 
(3) The mesodermal elements which consist of (a) the fibrous capsule and
 
trabecular, derived from the pia mater, and (b) minute profusely
branched cells which are present beneath the pia mater, in
relation with the perivascular sheaths, and distributed in
the lobules. These are the microglia or mesoglia cells of
Del Rio-Hortega, and are only clearly demonstrable by means
 
 
 
 
Fig. 268. — Pineal Body.
 
 
 
350.
 
 
 
Section through the central region of the same
specimen as Figs. 266, 267. Two types of fibres
are visible, as in Fig. 267. The finer fibres appear
to form a network on the walls of the capillary
vessels.
 
 
 
398 THE PINEAL ORGAN
 
of his silver carbonate process, though their nuclei are recognizable with other methods of staining, especially in glial
plaques.
 
(4) Cells and fibres, which resemble nerve-cells and nerve-fibres
 
but are in many cases only with difficulty distinguished from
the parenchyma and glia cells and the processes of these cells
(Figs. 266, 267, 268).
 
(5) Arterioles, capillaries, and venules.
 
The Parenchyma Cells
 
The form and full extent of the branches of the parenchyma or pineal
cells is only fully revealed by the silver methods of Del Rio-Hortega,
upon whose description the following account is largely based. The
pineal cells of an adult human subject thus shown (Fig. 218, Chap. 22,
p. 317) are characterized by an irregularly shaped body containing a
clear vesicular nucleus. The amount of cytoplasm varies, in some cells
being abundant, in others scanty. The cells thus differ greatly in size.
The cell-body is usually branched, and the branches vary in number,
size, and complexity. Thus the cell may be unipolar, bipolar, or multipolar.
The main branches may give off a group of slender processes which may
subdivide and end freely, or more commonly terminate in club-shaped
swellings implanted on or in the sheath of a vessel wall. The free ends
of the smaller branches are said by Del Rio-Hortega not to communicate
with similar branches of neighbouring pineal cells. The processes of the
cell may be polarized in one direction or they may be distributed irregularly
in any direction. In the former case they are usually directed towards
a vessel lying in the periphery of a lobule, and lie in what is termed the
marginal zone, where they are radially disposed ; in other cases, more
particularly in the centre of a lobule, the cells tend to be multipolar and
stellate in form, the branches appearing to form a plexus ; the terminal
branches of these cells may end in club-shaped swellings on the sheaths
of endolobular vessels, or they may extend to the periphery of the lobule
and become attached to the sheath of an interlobular vessel.
 
Typical branched cells with club-shaped endings are seldom seen in
children below the age of eight years, and the complexity of the branching
and the size of the club-shaped swellings appear to increase with the
advance of age.
 
Although the general form and terminal processes of the pineal cells
can only be clearly demonstrated by means of the silver methods of
impregnation, very little of the structure of the cells and their content is
seen in these preparations ; and in order to form a true estimate of the
nature of these cells it is necessary to adopt special methods which will
 
 
 
THE PARENCHYMA CELLS 399
 
bring out particular characters, such as cytoplasmic granules, vacuoles,
lipoid material, and other contents ; also mitochondria, blepharoplasts,
the centrosome, and Golgi apparatus. Thus by staining frozen sections
with Janus green, small rod-like mitochondria may be demonstrated in
the pineal organ of such animals as the horse, ox, and sheep. The rods
are most abundant around the centrosome and the part of the cell body
which relative to the nucleus is the widest. Occasionally long rods or
chondriocontes have been observed, and one or more thick rods close
to the nucleus arranged in the form of crosses or bundles. Hortega
states that in children the rods are short, while in adults and old subjects
they have become elongated, their elongation coinciding with involutive
changes.
 
The cytoplasm normally has a reticular structure, and frequently
shows vacuoles which may be demonstrated by the use of neutral red.
Lipoid material is also sometimes present. Granules of varying type are
normally present. Some of these have been described as secretory
(Dimitrowa, Rio-Hortega, Pastori, and others). There are also spherules
which have been thought to correspond to the " gliosomes " found in the
central nervous system. Some granules are apparently the result of
degenerative changes and are seen abundantly in the pineal cells of aged
subjects. Pigment granules, usually of small size, but sometimes large,
are found in old subjects, and like the non-pigmented granules mentioned
above are in some specimens due to involutive changes. These granules
are of a yellow-brown colour, and differ considerably from the dark
melanin granules which are also sometimes found in the pineal organ
and may be of morphological interest (see pp. 61-63). These are chiefly
found in the connective tissue elements, trabecular, capsule, and the
surrounding pial tissue.
 
The nucleus of the parenchyma cells of adult subjects is typically
spherical, of large size, and owing to its small chromatin content appears
clear. A well-defined nucleolus is usually present and the nuclear membrane is conspicuous. The nucleus of the parenchyma cells is large,
even in those in which the cytoplasm is scanty and the cell as a whole is
small as compared with the average size of these cells ; and it is also
large when compared with the small deeply stained nuclei of the fibroglial
tissue. Under certain conditions spherular formations described by
Dimitrowa as secretory in nature are present within the nucleus (Fig. 219,
Chap. 22, p. 317). These spherules have been found in the human subject, the ox, lamb, and other animals. They appear as clear droplets
which are stained red by Van Gieson's methods, a grey colour in Weigert
preparations, and pink with saffranin. Dimitrowa regarded the existence
and appearance of these spherules as undoubted evidence of secretory
 
 
 
400 THE PINEAL ORGAN
 
activity, and she believed that the nucleus produces a substance the
chemical composition of which is unknown and which is periodically
discharged into the cytoplasm. The spherules were stated to approach
the nuclear membrane, pass through this into the cytoplasm, and afterwards disappear. The nuclear membrane was then said to be regenerated.
Similar appearances have been described by other authors, e.g. Krabbe,
who reported the presence of the nuclear spherules in the human subject
commencing about the eighth year, reaching a maximum during the
fourteenth year, and persisting in old age. Uemura and Weinberg have
seen the spherules in the pineal body of a child of 4 years and under
3 years of age. The secretory nature of the nuclear spherules has, however, been doubted by many authors, more particularly by Achucarro
and Sacristan, Biondi, Josephy, and Walter. Intranuclear granules and
spherules, wrinkling, outpocketing, and inpocketing of the nuclear
membrane are quite common occurrences in cells with large nuclei in
many structures besides the pineal body. Moreover, the small recesses
between the folds of a wrinkled nuclear membrane may enclose granules
of protoplasm which stain with hematoxylin and the various stains mentioned above in a similar way to the spherules of the parenchyma cells.
Nevertheless the abundant granules which were demonstrated by Hortega
within the nucleus in the cell-body and around the parenchyma cells by
means of his silver carbonate method, in the pineal body of the ox, sheep,
and human subject, must be regarded as histological evidence of a granular
deposit of some stainable substance differing in its chemical composition
from that of the unmodified nucleus and cell-body. Whether the chemical
changes indicated by the presence of these granules is evidence of an
internal secretion seems as yet to be indecisive, and more particularly is
this the case since, as far as we are aware, the presence of the granules
has not been noted in the capillary vessels.
 
The Supporting Tissues of the Pineal Organ
 
In our general description we have already alluded to the fibrous
connective tissue elements comprising the capsule, the trabecular, and
the delicate intercellular connective tissue derived from the sheaths of
the intralobular vessels. Besides the ordinary connective tissue, there
are occasionally seen the branched microglial elements which have been
described in connection with the central nervous system ; these are sometimes present in plaques of glial tissue, and more especially in certain
pathological states. The microglial elements probably enter the tissue
of the pineal body in the same way as they pass into the central nervous
system, namely, as independent units which are first seen beneath the
 
 
 
THE FULLY DEVELOPED HUMAN PINEAL ORGAN 4OI
 
pia mater in the form of small rounded cells, with deeply stained nuclei,
which afterwards assume amoeboid characters and migrate into the deeper
 
 
 
 
Fig. 269. — Pineal Gland of a Woman aged 40. (After R. Amprino.)
 
mm
 
 
 
 
 
 
 
 
1.x *?
 
 
 
> -f) " ,
 
 
 
• » ', '/•
 
 
 
 
t
 
 
 
■ .
r »•
 
 
 
Fig. 270. — Pineal Gland of a Man aged 76. (After R. Amprino.)
 
central parts of the organ, and there may develop a phagocytic function.
There remain to be considered certain non-cellular elements, namely,
a supposed intercellular substance ; forming what has been termed a
26
 
 
 
402 THE PINEAL ORGAN
 
 
 
 
 
 
#
 
 
 
 
 
 
•f
 
 
 
 
 
 
 
 
 
 
 
 
 
4
 
 
 
*► ¥
 
 
 
A B
 
Fig. 271. — A— Pineal Gland of a Newly Born Lamb. B— Pineal Gland of
a Sheep aged 4 years. (After R. Amprino.)
 
glial syncytium ; glial fibres ; and the tortuous thick fibrils which have
been specially described and figured by Amprino (1935) (Figs. 269, 270,
271, 272).
 
An intercellular substance is difficult to demonstrate with certainty,
and possibly in the living subject simply exists as an albuminous semi-fluid
material which everywhere fills the intercellular spaces. It is also probable
that in the preparation of specimens for microscopic examination the
coagulable material present in the interstitial tissue-fluid is concentrated
on the cellular elements and fibres, so as to form on these a continuous
membrane-like covering, such as was described by Held as the " grenz
membran." On the other hand, it is quite possible that a similar process
may occur normally during life and a more solid constituent be separated
out from the more liquid intercellular tissue-fluid, the more solid material
being deposited on the surface of the cellular elements and fibres and
thus forming a continuous membrane-like covering or, when it completely
fills the spaces, an intercellular ground substance. Such a conception is
important in connection with the passage of nutritive material, or possibly
secretory products, into or out of the cell-bodies and their processes —
 
 
 
 
PARIETAL AND
 
 
PINEAL
 
 
NERVES
 
 
*f 1
 
 
HP
 
 
 
 
W x|
 
 
r *\ t
 
 
 
 
#&&.
 
 
 
 
 
 
■
 
 
 
 
 
 
 
403
 
 
 
#
 
 
 
^ I M
 
 
 
*
 
 
 
Fig. 272. — Pineal Gland of a Man aged 40, showing Astrocyte Cells
and Neuroglial Fibres. (After R. Amprino.)
 
or in other words, furnishing the means by which osmotic processes can
take place between the cells and the tissue-fluid.
 
The Nerves of the Parietal Organ and Pineal Body
 
The study of the nerve supply of the human pineal organ necessarily
involves a preliminary consideration of the pineal nerves, commissural
fibres, and the associated ganglia of lower types of animals in which the
parietal sense-organs, pineal sac, and pineal stalk are more highly evolved
than they are in mammals, and in which the nerve tracts have been
definitely traced from their origin in the sensory-cells of the retina of
the pineal eye or the wall of the pineal sac to their termination in the nerve
tracts and ganglia of the brain.
 
A feature of special interest in connection with the nerve supply of
the pineal eye is the bearing that this has upon the question of the bilateral
original of the pineal system, and the closely related problem of the
homology of the pineal organ of birds and mammals with reference to
the " parapineal organ " of cyclostomes and the pineal sac and pineal
stalk of amphibia and reptiles. The nerve supply of the pineal eye and
pineal sac in Sphenodon was specially studied with reference to this
question by the late Professor A. Dendy (191 1, Phil. Trans. Roy. Soc,
Ser. B., Vol. 201, pp. 228-339) (Figs. 183, 184, 185, A, Chap. 20, pp. 259,
260, 261). Unfortunately this important work appears to have escaped
the attention of many modern writers on this subject, owing to the cir
 
 
404 THE PINEAL ORGAN
 
cumstance that only his earlier works have been quoted in many of the
published references to the literature of the pineal system, and these
authors have most probably been unaware of the existence of his later
publications. Dendy, as is well known from his earlier communications,
regarded the pineal eye of Sphenodon as the left pineal organ and the
pineal sac (epiphysis) as the right pineal organ of a paired system which
included the pineal eye and pineal sac, the pineal stalk, and the associated
vessels and nerves. He also considered that the primarily right and left
components of this system have, in the course of evolution, become displaced towards or into the median plane, so that the left organ has become
anterior and the right posterior. The latter or pineal sac of Sphenodon
has also become more degenerate than the left, which is separated off as
the parietal organ and presumably has retained, to a much greater extent,
the original structure of the ancestral pineal eye. In his later memoir,
published in 191 1, Dendy clearly demonstrated that the wall of the pineal
sac of Sphenodon has a nervous structure which is essentially similar to
that of the pineal eye, and that although less highly differentiated it shows,
as in the pineal eye, internal and external limiting membranes, radial
supporting or glial fibres, which are comparable to Miiller's fibres in the
retina of the lateral eyes of vertebrates, also neuro-epithelial cells which
he regarded as sensory in nature, ganglion cells, nerve fibres, and at its
distal extremity pigment cells. In one of his specimens this apical part
was partially constricted off from the main diverticulum so as to form a
thin- walled sac, containing pigment cells in the wall of the main sac.
He regarded this sac as being comparable to the accessory parietal organs
described by Leydig and Studnicka, and as supporting his view that " the
structure of the pineal sac is fundamentally identical with that of the
pineal eye."
 
In cyclostomes (Studnicka, Gaskell, Dendy) there is the same fundamental similarity in structure of the pineal eye and the parapineal organ
as is met with in the pineal eye and the pineal sac or epiphysis of reptiles.
Both in fishes and reptiles there are sometimes two outgrowths, one of
which, Epiphysis I, is anterior, while the other, Epiphysis II, is posterior.
In both fishes and reptiles the anterior epiphysis is usually to the left of the
median plane. In fishes, however, the posterior organ is the more highly
evolved and in cyclostomes it forms the pineal eye, whereas in reptiles the
anterior organ is the more highly evolved and forms the pineal eye or
parietal organ.
 
In Geotria Professor Dendy demonstrated non-medullated nervefibres which apparently arose from the ganglion cells of the retina of the right
or posterior pineal eye ; these converged towards the optic stalk and then,
forming a nerve bundle in the stalk, coursed backwards to end in the right
 
 
 
PARIETAL AND PINEAL NERVES
 
 
 
405
 
 
 
habenular ganglion, the right bundle of Meynert, the ependymal groove
or " subcommissural organ," and, he believed, also in the posterior
commissure (Fig. 134, Chap. 17, p. 188). He likewise traced the connections of the nerve-fibres issuing from the parapineal organ (anterior
or left pineal eye) to the left habenular ganglion, habenular tract, or
superior commissure, and the left bundle of Meynert, which is much
smaller than the corresponding bundle of the opposite side, which receives
the larger pineal nerve coming from the more highly evolved right pineal
eye. In his concluding remarks he states that " the connection of each
of the two sense-organs with the corresponding member of the habenular
ganglion-pair need no longer be questioned " ; and, further, " the
 
 
 
 
Fig. 273.
 
 
-Section through the Vestigial Eye of a Frog Tadpole.
(After Dendy.) (From a photograph).
 
 
 
168.
 
 
 
ep. : epidermis.
p.e. : pineal eye.
 
 
 
?-.s. : roof of skull.
 
v.n. : vestigial stalk and nerve.
 
 
 
marked asymmetry in point of size of the two habenular ganglia and of
the two bundles of Meynert corresponds exactly to the unequal development of the two parietal sense-organs with which they are connected, and
leaves no doubt as to the paired character of the whole system."
 
Without entering further into this highly controversial question, we
may conclude that these observations are highly suggestive of a system
of nerve tracts with commissures passing from the parietal sense-organs
to receptive centres in the brain, which in some respects is comparable
to that of the paired lateral eyes — in other words, a system of afferent
fibres of a sensory nature ; but, as might be expected from the vestigial
condition of the receptive organs in these animals, the fibres are usually
unmyelinated.
 
 
 
406 THE PINEAL ORGAN
 
The nerve-fibres of the functional lateral eyes in the human subject
are unmyelinated until a late period of foetal life, and do not become
myelinated until shortly before birth (Lucas Keene and Hewer, Langworthy, O.R.). In the pineal eye of Geotria and Sphenodon the nerves
remain unmyelinated even in the adult animals, a condition which is to
be expected in organs which even in these species are degenerate and
apparently have little or no function. In other types, for instance in
many reptiles and amphibia, the pineal nerve or tract, though present
in early embryos (Fig. 187, Chap. 20, p. 264, and Fig. 273), usually
disappears later, when the terminal vesicle (parietal organ) becomes
separated from the pineal sac and its peduncle (Beraneck, E., p. 246 ;
Dendy, A., p. 261 ; Klinckowstrom, A. de, pp. 241, 243).
 
The Nerve-fibres and Nerve Cells of the Mammalian Pineal Organ
 
Both in the past and recently, and in addition to the work done on
the nerve supply of the pineal system in fishes, amphibia, and reptiles,
a large amount of work has been devoted to the study of the sensory cells,
nerve cells, and tracts of nerve-fibres belonging to the pineal system in
the human subject and in various types of mammals. This has been
carried out largely with the object of demonstrating an anatomical basis
by which it may be presumed the pineal organ or epiphysis is capable of
being influenced by afferent impulses and can function : either by means
of specific hormones secreted by the pineal cells and carried to distant
organs in the circulating blood or by means of efferent nerves issuing
from the gland and joining the habenular ganglia and other nerve centres
of the brain or the intracranial sympathetic system — exerting through
these systems a direct influence on other organs, e.g. the secretory cells
of the choroid plexuses, or an indirect influence on these cells, by means
of vasomotor nerves regulating the circulation of blood in the vessels of
the organs supplied by them.
 
The anatomical demonstration of the distribution of the nerve-fibres
has been greatly facilitated by the various methods of silver impregnation,
and the definite results obtained by Retzius, Studnicka, Cajal, Pastori,
and other workers have done much to establish the existence and connections of nerve-fibres, which are presumably afferent and efferent and
may form the basis of a reflex mechanism by which it is possible for the
pineal body to be influenced apart from the action of hormones reaching
it through the circulating blood.
 
Theoretically one may postulate the existence of a pineal nerve supply
consisting of a double central and a double sympathetic system, thus :
 
_ , fAfferent nerve-fibres to the pineal body.
 
Central nervous system < „„, n , r , , 1 j
 
[Efferent nerve-fibres from the pineal body.
 
 
 
NERVE SUPPLY OF MAMMALIAN PINEAL ORGAN 407
 
Sympathetic system j Afferent nerve-fibres to the pineal body.
 
[Efferent nerve-fibres from the pineal body.
 
Also one might expect to find in connection with these fibres sensory
or receptive cells and ganglion cells, the latter giving rise to efferent fibres
which leave the pineal organ and pass to such ganglia as the habenular
or optic thalami, or to the plexuses of sympathetic nerve-fibres on the
surrounding blood-vessels. Moreover, one might look for two types of
nerve-cells, a large ganglion-cell belonging to the central nervous system
and a small type of nerve-cell having the characteristics of the sympathetic
system.
 
Actually, it appears that if observations on the pineal system throughout the whole series of vertebrate animals are included, all these different
types of sensory epithelial cells, nerve cells, and nerve-fibres have been
seen and described by competent observers. The pineal system, especially
that of the mammalia, is, however, vestigial in structure and has undergone
marked modifications, and as a consequence the full complement of
nerve cells and nerve-fibres is not found in any one species. Nerve cells,
in particular, are rare, and when present are usually not fully developed.
Such cells have been described as " neuronoid cells " or " amacrine
nerve-cells." Moreover, the existence of typical nerve cells showing both
Nissl granules and axis cylinder process as a normal constituent of the
human pineal organ has been not only doubted but denied by some
recent workers, who regard the occasional occurrence of such cells as
anomalous.
 
There seem, however, to be transitional stages between nerve cells
and typical parenchyma cells, and it is probable that in some cases
branched pineal cells with bulbous extremities have been mistaken for
fully developed nerve cells. True nerve cells, apparently belonging to
the sympathetic system, are occasionally seen on or near the surface of
the organ or in close relation with the vessels contained in the trabecular,
and in our opinion a distinction should be made between these cells and
the transitional or " neuronoid cells " seen in the parenchyma. It is
possible that the latter indicate a stage in the differentiation of true nerve
cells from the indifferent neuro-epithelial cells which form the primary
elements of the developing organ, and which may give rise to neuroglial
cells, parenchyma cells, or very occasionally to either imperfectly or fully
developed nerve cells.
 
The question of whether the parenchyma cells themselves are sensory
in nature and capable of transmitting a sensory impulse from an afferent
pineal nerve to an efferent pineal nerve is one of practical interest. Should
they possess this function, their anatomical connections fully warrant
the assumption that a reflex mechanism may exist within the pineal organ,
 
 
 
408 THE PINEAL ORGAN
 
which is capable of being influenced by impulses reaching it through
its afferent nerve-fibres and transmitting such impulses by efferent fibres
(e.g. sympathetic) to the organs or regions to which these nerves are
distributed.
 
A general survey of the comparative anatomy of the pineal region,
with detailed descriptions of the nerve cells and nerve-fibres of the pineal
system in special types of animals, was published in 1905 by Studnicka
Die Parietalorgane. Oppel. Teil V.), and recent accounts with references
to the literature in such works as UEpiphyse, by J. Calvet, a special article
on the pineal gland by del Rio Hortega in Cowdry's Special Cytology,
Penfield (1928), and various articles such as those by Beraneck, Clarke,
Darkschewitsch, Dendy, Dimitrowa, Herring, Pastori, and others. It will
be realized on studying these contributions to the innervation of the
pineal system that substantial agreement has been reached on the following
points :
 
1. Tracts of nerve-fibres described as the nervus pinealis, nervus
parietalis, tractus pinealis, and tractus habenularis have been traced from
receptive sensory cells or ganglion cells in the retina of the parietal organs
(namely, the pineal eye and end-vesicle of the parapineal organ) and
found to terminate in or traverse the habenular ganglia, the superior and
posterior commissures, and Meynert's bundles. These fibres have been
observed in cyclostomes and other fishes, amphibia, and reptiles. They
may be situated in the stalk of the vesicle, and thus resemble the optic
nerve-fibres of the lateral eyes of vertebrates ; or they may course as an
independent tract through the areolar connective tissue in the neighbourhood of the stalk ; or, after the disappearance of the stalk, they may lie
in the region formerly occupied by the stalk. The nerve-fibres may be
present only in the larval stages or they may persist in the adult animal.
 
2. Similar tracts of nerve-fibres may arise from sensory cells in the
wall of the pineal sac or the epiphysis in elasmobranch and teleostean
fishes, amphibia, reptiles (saurians and snakes), and in mammals. These
fibres terminate for the most part in the posterior commissure, but connections are established in some species also with the internal capsule,
stria; medullares thalami, Meynert's bundles, habenular commissure
and ganglia, and the optic tracts (Darkschewitsch).
 
There is, however, a considerable amount of variation in different
species of mammals, e.g. Herring states that occasional nerve-fibres
may enter the pineal body from the habenular commissure in the cat,
monkeys, and man, but have probable no functional significance ; whereas
in the rat the pineal body is anatomically widely separated from the
habenular commissure, and no nervous connection persists between
them. In the adult rat the pineal body is an isolated organ which lies
 
 
 
NERVE SUPPLY OF MAMMALIAN PINEAL ORGAN 409
 
on the surface of the brain between the cerebral hemispheres and cerebellum. Its only apparent functional connection with the organ is vascular,
and its nerve supply reaches it only in the form of non-medullated fibres
accompanying the blood-vessels (Cajal).
 
The direction in which nerve impulses travel in the fibres connecting
the epiphysis with the habenular ganglia, optic thalami, and the superior
and posterior commissures is difficult to determine in mammalia, owing
to the absence of experimental evidence. It seems, however, to be
generally assumed that impulses travelling from the central fibres coming
from the posterior commissure through the " tractus intercalaris " not
only enter the stalk of the epiphysis, but are also distributed in the
parenchyma of the epiphysis.
 
Pastori states that in some species of mammals (e.g. man and dog)
the nerve-fibres coming from the optic thalami and habenular ganglia
partly decussate in the inter-habenular commissure ; while in other species
of mammals (e.g. the cat) the corresponding nerve-fibres remain homolateral and travel directly from the optic thalamus and habenular ganglion
into the parenchyma of the epiphysis, that is to say, without decussating.
 
On the other hand, the primary direction in which the nerve impulses
travel in the lower classes of vertebrates is apparently from the sensory
cells of the pineal eye, pineal sac, or epiphysis to the central ganglia —
vide Beraneck, Dendy, Gaskell, Klinckowstrom, Studnicka, and others.
Moreover, some writers have supposed that the parenchyma cells of the
human epiphysis may be sensory, or receptor, cells ; and it has also been
suggested that they may be specially sensitive to pressure, and, further,
that they may function in regulating the pressure of the cerebrospinal
fluid, either through the direct action of the sympathetic system on the
choroidal epithelium or by an indirect action on the epithelium through
the choroidal blood-vessels.
 
These considerations suggest that relays of nerve-fibres which originally
carried impulses from the receptive organs of the pineal system to ganglia
of the central nervous system have been either wholly or partially supplanted by nerves which are afferent to the epiphysis, and also that
impulses arising by stimulation of the parenchyma cells of the epiphysis
may be transferred to fibres of the sympathetic system.
 
An anatomical basis which affords support for the latter hypothesis
is furnished by Pastori's recent work on the nervous connections of the
epiphysis. He has demonstrated in the human subject and in the dog
the constant presence of a sympathetic ganglion situated in the membranes just behind the posterior pole of the epiphysis. This ganglion
is connected by a large number of very fine nerve-fibres with the epiphysis,
and also by less numerous but coarser nerve-fibres, which form a definite
 
 
 
410 THE PINEAL ORGAN
 
bundle which joins the plexus of nerve-fibres on the great cerebral vein
and its tributaries. The bundle is the nervus conari of Kolmer. Pastori
describes both the fine and the coarse nerve-fibres as arising from small
sympathetic nerve-cells situated in the ganglion. The fine fibres enter
the epiphysis with the vessels contained in the trabecular.
 
It is thus possible that some of the fibres may be efferent nerves
from the ganglion to the gland, and others afferent from the gland to the
plexus of nerve-fibres on the neighbouring vessels, and that these furnish
a means by which the epiphysis may be influenced by or act upon the
sympathetic system.
 
The Vascular Supply of the Pineal Organ
 
The arteries of the pineal body are derived from the posterior choroidal
branches of the two posterior cerebral arteries. The posterior choroidal
artery on each side enters the transverse fissure of the brain between the
two layers of the tela choroidea, and gives off small branches near its
origin to the pia mater investing the pineal body ; from these branches
numerous arterioles enter the capsule and trabecular of the organ, and
ultimately give off capillary vessels for the supply of the parenchyma.
The capillary net is drained by venules which passing through the
trabecular and capsule unite to form a vessel which joins the great cerebral
vein of Galen. This terminates in the anterior part of the straight sinus.
 
Since a tumour of the pineal organ may by pressure obstruct the great
cerebral vein, it is important to know the exact course of this vessel. It
will be remembered that the internal cerebral vein on each side is formed
in the region just behind the interventricular foramen of Monro by the
union of the anterior choroidal vein with the terminal or striate vein, and
that the two internal cerebral veins course backwards below the fornix
and between the two layers of the tela choroidea or velum interpositum.
Here they receive tributaries from the choroid plexus of the third ventricle
and optic thalami. They unite near the base of the pineal body to form
the great cerebral vein of Galen, which curves upwards in the cisterna
vense magnar cerebri around the splenium of the corpus callosum (Fig.
274). Here after receiving the right and left basal veins and the internal
occipital veins, it opens into the anterior end of the straight sinus, the
latter vessel commencing as a continuation of the inferior sagittal sinus.
It is important to remember also that some of the superior cerebellar
veins run inwards to terminate in the straight sinus or in the internal
cerebral veins.
 
The opening of the right and left basal veins into the great cerebral
vein of Galen has a practical bearing in connection with occlusion of the
great vein, for unless the pressure on the great cerebral vein involves
 
 
 
THE VASCULAR SUPPLY OF THE PINEAL ORGAN 4II
 
its terminal part and the openings into it of these two vessels, any resulting
congestion of the choroidal veins which might result from an obstruction
at the commencement of the vein would be relieved by the anastomoses
between the tributaries of the basal veins and the choroidal veins in the
inferior horns of the lateral ventricles. For detailed description of the
 
 
 
 
Fig. 274. — Diagram showing the Principal Tributaries and Relations of
the Great Vein of Galen, and the position occupied by a Pineal Tumour.
 
 
 
anatomy of these veins in connection with the production of hydrocephalus the reader should consult articles by Dandy and Blackfan
(1914), Stopford (1926, 1928), and Bedford (1934).
 
Since no lymphatic vessels are present in the central nervous system
of which the pineal organ is a part, it is probable that secretory or waste
products contained in the tissue-fluids of the pineal body would, like the
cerebrospinal fluid, be absorbed directly into the venous system through
perivascular channels which are in communication with the tissue spaces.
 
 
 
CHAPTER 27
 
RELATIONS OF THE ADULT PINEAL ORGAN
 
Some of the more important relations are seen in Fig. 276, which
is an X-ray photograph of a patient aged 50, showing a calcified pineal,
and Fig. 1, p. 2, also of a calcified pineal organ. Fig. 277 is from a section
of the pineal region made in the median sagittal plane, and Fig. 278 a transverse section of a brain containing a tumour in the pineal region. Fig. 274
 
 
 
 
Fig. 275. — Radiographs of Skull, showing Calcification in the Choroid
 
Plexus.
 
also shows diagrammatically the position of the great cerebral vein, basal
vein, and internal occipital vein to the pineal body ; the relations that a
pineal tumour growing backwards beneath the tentorium cerebelli would
have to the splenium of the corpus callosum ; the junction of the great
cerebral vein with the inferior sagittal sinus to form the straight sinus,
and the convolutions and sulci on the adjacent tentorial surface of the
brain. The falx cerebri, tentorium, and falx cerebelli, the cerebellum
 
412
 
 
 
RELATIONS OF THE ADULT PINEAL ORGAN 413
 
and pons Varolii are not represented in the diagram. The drawing
can thus show the internal occipital vein which lies above and external
to the tentorium. Here it issues from the parieto-occipital fissure ;
near its termination it crosses the
free border of the incisura tentorii
and joins the great cerebral vein
between the splenium of the corpus
callosum above and the pineal body
which lies below and internal to it.
In this position it would be in
direct relation with a pineal tumour.
Fig. 279, a transverse and approximately vertical section, gives a
notion of the parts in close relationship to the pineal body very
different from that obtained from
Fig. 278, since it passes through
 
the posterior part of the fornix and FlG - 276.— Lateral Radiograph of the
 
Skull of a Patient, aged 50, showing the Typical Appearance of
Calcification cf the Pineal Gland.
 
 
 
 
great cerebral vein, which lie above,
the pulvinares of the optic thalami,
which are lateral, and the superior
colliculi and aqueduct, which lie
 
 
 
below. The close relation of the
 
 
 
cavity of the lateral ventricle, choroid plexus, fimbria, and tela choroidea
are also readily
appreciated in this
section.
 
The exact position and relations
of the pineal body
are specially well
seen in Fig. 280.
It is approximately
conical in form,
slightly flattened
from above downwards, and averages about 8 mm.
in length. The
base of the gland is
directed forwards
 
and slightly upwards. Its position, which is very constant, is primarily
determined by that of the superior or habenular commissure and the
 
 
 
 
Fig. 277. — Median Sagittal Section of Brain.
 
 
 
414
 
 
 
THE PINEAL ORGAN
 
 
 
posterior commissure, which lie respectively in its superior and inferior
peduncles. The body lies in the groove between the superior colliculi
of the quadrigeminal plate, and the apex is directed backwards and
slightly downwards. The organ receives a partial covering of pia mater,
which is derived from the lower layer of the tela choroidea or velum
interpositum. The anterior third or half of its upper surface is covered
by the layer of ependyma which forms the floor of the dorsal diverticulum
or suprapineal recess. This is continuous with the ependyma lining the
 
 
 
 
Fig. 278. — Transverse Section of a Brain containing a Tumour of the
 
Pineal Organ.
 
 
 
cavity of the third ventricle, and is reflected anteriorly over the superior
commissure and into the pineal recess. The roof of the superior pineal
recess is continuous with that of the third ventricle, and has numerous
choroidal villi hanging downwards from it and resting on the upper
surface of the pineal body. The posterior two-thirds or half of the upper
surface is covered by the lower layer of the tela choroidea which is firmly
adherent to its capsule. It is in close relation with the great cerebral
vein which separates it from the corpus callosum and commissural fibres
of the fornix. The splenium projects backwards beyond the apex of the
pineal body. The nerve-fibres of the splenium course outward and
 
 
 
RELATIONS OF THE ADULT PINEAL ORGAN 415
 
backward over the roof and lateral wall of the posterior horn and hinder
part of the inferior horn of the lateral ventricle ; in this situation they
form a thin lamina, the " tapetum," inside the fibres of the optic radiation.
The latter consist of afferent and efferent fibres which connect the lower
visual centres of the lateral geniculate body and superior colliculus with
the occipital cortex. It is said that no commissural fibres belonging to
 
 
 
 
Fig. 279. — Transverse Section of Brain showing Relations of Pineal Body.
 
 
 
Aq. S. : aqueduct of Sylvius.
 
C.C. : corpus callosum.
 
Ch. P. : choroid plexus.
 
C.N. III. : third cranial nerve.
 
F. : fornix, beneath which is the great
transverse fissure.
 
H.M. : hippocampus major.
 
I.C. : internal capsule.
 
I.C.L.V. : inferior horn of lateral ventricles.
 
L.G.B. : lateral geniculate body.
 
L.V. : lateral ventricle.
 
the visual area of the cortex cross in the corpus callosum. So far as we
are aware, little is known about the function of the fibres of the tapetum
and the fibres of the forceps major which cross in the splenium of the
corpus callosum, and injury to these fibres does not appear to give rise
to any definite symptoms or disability.
 
The under surface of the pineal body is typically separated from the
groove between the superior colliculi by a fold of pia mater, which forms
 
 
 
M.G.B. : medial geniculate body.
 
N.P. : nuclei pontis.
 
O.M.N. : oculo-motor nucleus and
 
medial longitudinal fascicle.
Op. T. : optic thalamus.
R.N. : red nucleus.
S.C. : superior colliculus.
S.C.P. : superior cerebellar peduncle
 
(brachium conjunctivum).
S.N. : substantia nigra.
V.M.C. : vena magna cerebralis.
 
 
 
416 THE PINEAL ORGAN
 
a recess called the subpineal cul de sac of Reichert. This may reach
forward as far as the posterior commissure or it may become obliterated
by adhesions. The lateral surfaces are also covered with pia mater which
 
 
 
 
Fig. 280. — Drawing of a Medial Longitudinal Section through the Pineal
Region of a Human Subject showing the Relations of the Pineal
Organ to the Corpus Callosum, Fornix, Great Cerebral Vein, Dorsal
Diverticulum, and Choroid Plexus, Superior and Posterior Commissures, Quadrigeminal Plate, and the Membranes and Blood-vessels
at its Posterior Pole. (R. J. G.)
 
 
 
Aq. C. : aqueductus cerebri.
 
Cbl. : cerebellum.
 
C.C. : corpus callosum.
 
Ch. P. : choroid plexus.
 
D.D. (S.P.R.) : dorsal diverticulum
 
(superior pineal recess).
Ep. : ependyma.
F. : fornix P.B. : pineal body.
 
 
 
P.C. : posterior commissure.
 
O.T. : optic thalamus.
 
R.P. : recessus pinealis.
 
S.C. : superior commissure.
 
Spl. : splenium.
 
5. Col. : superior colliculus.
 
Teg. : tegmentum.
 
V .CM. : gr. vein of Galen.
 
 
 
V. III. : third ventricle.
may be continued backward from the sides and apex of the organ as a
fold which contains between its layers vessels, nerves, and the ganglion
conari (Kolmer, Lowy, and Pastori). The nerve-fibres are described as
being of two kinds — " fine," which are the more numerous, and " coarse,"
 
 
 
RELATIONS OF THE ADULT PINEAL ORGAN 417
 
both sets of fibres belong to the sympathetic system. This fold has been
described as the posterior ligament (Calvet), whereas the reflections at
the side are styled the lateral ligaments. In some cases the body and apex
of the pineal organ are completely surrounded by a plexus of vessels
lying in the subpial tissue and containing calcareous concretions. In
old subjects this tissue is often very dense and thick, so that considerable difficulty may be experienced in freeing the body from its
surroundings.
 
At the base of the organ are the superior and inferior peduncles and
an intermediate or lateral peduncle (Calvet) which connects the pineal
body with the medial surface of the thalamus. The superior peduncle
contains medullated nerve-fibres belonging to the superior or habenular
commissure, and the inferior peduncle conveys similar fibres of the
posterior commissure ; between the two commissures is the pineal recess.
 
The superior peduncle is continued forward on each side as the
habenula (Fig. 281). This forms the inner boundary of the trigonum
habenulae, and anteriorly is continuous with the taenia thalami, which
marks the lateral limit of the roof of the third ventricle and the line along
which the ependyma on the lateral wall of the ventricle leaves the medial
surface of the thalamus. The habenular ganglion is situated in relation
with the posterior and median part of the optic thalamus, beneath the
trigonum habenulae. It receives afferent fibres from the stria medullaris
thalami, which if traced backwards divide into two bundles, of which one
joins the ganglion of the same side while the other crosses in the habenular
commissure to the ganglion of the opposite side. The stria medullaris
is connected in front with the anterior pillar of the fornix, these fibres
being derived from the cells in the hippocampal cortex, whereas a ventral
bundle of fibres comes from a collection of cells in the anterior perforated
substance. It is believed, therefore, that in the human subject the
habenular commissure is chiefly composed of decussating fibres belonging to the olfactory system and that each habenular ganglion receives
relays of fibres from the olfactory organ of both the right and left side.
In lower vertebrates, however, such as the cyclostomes, in which definite
pineal sense-organs are present, the habenular ganglia receive afferent
fibres which arise in the ganglion cells of the retinae of the pineal eyes,
and in the human subject some of the fibres of the habenular commissure
appear to terminate in the basal part of the pineal body (see p. 408).
 
The posterior commissure : in spite of the position of the posterior
commissure, as seen in median longitudinal sections of the brain, being
so familiar and such a valuable landmark, it has been found difficult to
trace its connections with certainty, and there is considerable difference
of opinion with regard to the origin of its fibres. Most authors are,
27
 
 
 
418 THE PINEAL ORGAN
 
however, agreed that in the human subject some of its fibres arise in the
nucleus interstitialis or nucleus of origin of the median longitudinal
 
 
 
 
w
 
 
 
N.C
fCh.Pi 1
 
 
 
F. 1
V.M.C!
 
 
 
S. — V.M.C. 2
 
 
 
 
 
 
Th.
B.
 
 
 
 
Fig. 281. — Pineal Region Viewed from Above.
The upper part of the right hemisphere of the brain has been removed and
the right lateral ventricle opened by removal of portions of the corpus callosum
and the roof of the posterior and inferior cornua. A part of the fornix and tela
choroidea were then cut away so as to expose the pineal body, habenular region,
and superior colliculus. The pineal body of the adult lies between 5 and 6 cm.
directly below the supero-medial border of the hemisphere, and its apex is 1 cm.
in front of the posterior end of the splenium of the corpus callosum. The great
cerebral vein lies in the velum interpositum (T. Ch.) between the pineal body
below and the fornix and corpus callosum above.
C. : cerebellum. O. Th. : optic thalamus.
 
Ch. PI 1 and 2 : choroid plexus. P.B. : pineal body.
 
C.S. : colliculus superior. 5. : splenium of corpus callosum.
 
F. 1 and 2 : fornix. V.B. : vena basilaris.
 
N.C. : nucleus caudatus. V.M.C. 1 and - : vena magna cerebralis.
 
(Original : R. J. G.)
 
fasciculus, and that the decussating fibres have connections through this
tract with the nuclei and nerve-fibres of the eye muscles. The com
 
 
RELATIONS OF THE ADULT PINEAL ORGAN 419
 
missure also appears to contain fibres which originate or end in nuclei
situated in the tectum opticum.
 
In cyclostomes, e.g. Petromyzon, in addition to fibres which are
associated with the pineal system, fibres of the posterior commissure
arise from cells which are widely scattered through the dorso-caudal
part of the thalamus and tectum opticum. In Geotria, the Australian
lamprey, according to Dendy the larger of the two organs, the right
parietal organ (Epiphysis II or posterior pineal organ) is connected
by a well-defined tract, the pineal nerve with the right habenular ganglion,
and also sends fibres to the posterior commissure and right bundle
of Meynert ; whereas the smaller deeply placed left parietal organ
(Epiphysis I or parapineal organ of Studnicka) is joined by a few short
fibres with the left habenular ganglion which lies immediately beneath
it, and also sends fibres to the posterior commissure and the left bundle
of Meynert. The morphology of the pineal tract and of the habenular
commissure in cyclostomes is discussed on p. 193. Briefly summarized
it may be stated that two organs or pairs of organs have been considered
by some authors to be comprised in the pineal system, of which the anterior
organ or Epiphysis I is related to the habenular ganglia and the habenular
commissure, and the posterior organ or Epiphysis II is connected with
the posterior commissure. It is this Epyphysis II in a modified form
which is said to be represented by the epiphysis of amphibia ; the pineal
sac or epiphysis of reptiles ; and the epiphysis of birds and mammals.
 
Having considered the immediate relations of the pineal body and
the principal connections of the habenular and posterior commissures,
it will be advantageous to examine the structures which lie around the
pineal zone, and which are liable to be compressed by a tumour originating
in these regions, or would have to be borne in mind when approaching
the organ with the object of removing a tumour. A glance at the transverse section (Fig. 279) will show the relations of the tela choroidea with
its contained vessels to the transverse fibres and fimbria; of the fornix
and also the connection of the latter with the body of the corpus callosum.
Overlapping the fimbria of the fornix on each side is the choroid plexus,
which projects into the lateral ventricle. The size, vascularity, and
density of the plexus varies considerably in different individuals. In the
specimen drawn the lateral ventricle is of moderate size, but in cases of
obstruction to the aqueduct of Sylvius the ventricle may be greatly distended or, if emptied, the walls may be collapsed. On either side of the
pineal body is the pulvinar of the optic thalamus. This is separated from
the pineal body, superior colliculus, and superior brachium by pia mater
containing blood-vessels. Lateral to the pulvinar is the internal capsule,
passing between the caudate and lenticular nuclei and coursing down
 
 
420 THE PINEAL ORGAN
 
ward into the crura cerebri. Immediately beneath the pineal body is the
roof of the aqueduct, containing the tecto-spinal and tecto-bulbar nuclei.
Around the aqueduct is the central grey matter and below it the various
nuclei of the third nerve, the nuclei of the fourth nerve, and the medial
longitudinal fasciculi (Fig. 279, p. 415), which if traced downwards are
found to be connected on each side with the superior olive, the nucleus
of the sixth cranial nerve, and that of the vestibular nerve. Ventral to
the nuclei of the third nerve are the red nuclei, the decussation of the
rubro-spinal tract, and the substantia nigra ; while dorso-lateral to the
red nucleus is the medial lemniscus. Ventral to the red nuclei is the
substantia nigra and near the outer borders of this are seen the medial
geniculate bodies. Passing upwards round the outer side of the crus
cerebri are the posterior cerebral and superior cerebellar arteries, with the
fourth nerve running ventrally and forwards between them. The basal
vein also, as mentioned previously, occupies the recess between the crus
cerebri and medial geniculate body on the inner side, and the tail of the
caudate nucleus, inferior horn of the lateral ventricle, choroidal fissure,
fimbria, and hippocampus are on the outer side. Finally the apex of the
pineal body is seen in a medial section (Fig. 280) to be in close relation
to the superior vermis of the cerebellum, and if the organ is enlarged it
may exert direct pressure on this and the superior peduncles or brachia
conjunctivae. Should a tumour of the pineal body enlarge forward into
the third ventricle it may exert pressure on the interpeduncular and
subthalamic regions and upon the optic thalami laterally.
 
 
 
CHAPTER 28
 
THE FUNCTIONS OF THE PINEAL BODY
 
We do not propose to deal at length with the controversial question of the
function of the mammalian pineal organ, which has been very fully discussed in publications specially concerned with the endocrine glands ;
nor do we propose in this section to discuss the various functions attributed
to the pineal organs of fishes, amphibia, and reptiles, which we have already
alluded to (pp. 6, 46, 230) ; but from the practical standpoint of whether
the use of pineal extracts as a therapeutic measure should be continued or
should be discontinued, we believe that the present time is ripe for a
short review of the principal results which have been obtained from
recent experimental work on the function of the pineal gland in birds
and mammals.
 
The evidence which is often contradictory may be classified under
two principal headings, namely :
 
A — The results of experimental work on animals.
B — Observations on the human subject.
 
A. Experimental Work on Animals. — The biochemical aspect of this
subject has been fully dealt with in numerous articles in the physiological
and pharmaceutical journals and is beyond the scope of the present
treatise ; we shall therefore limit our description to the consideration of
the general results of experimental work under the following categories :
 
1. The results of pinealectomy.
 
2. The effects of feeding with pineal substance and injection of
 
pineal extracts.
 
3. The influence of pineal grafts.
 
In the consideration of each of these subdivisions we shall allude first
to results which are deemed to be of a positive character and afterwards
to those which are negative. We shall also limit ourselves to a brief
discussion on the more important and typical results which have been
obtained by authoritative workers, and we shall not attempt to make a
complete record of the numerous papers of an indecisive nature which
have been published on this subject, references to which will be found
in the larger monographs dealing with the organs of internal secretion
and the principal journals on endocrinology.
 
421
 
 
 
422
 
 
 
THE PINEAL ORGAN
 
 
 
Pinealectomy
 
Assuming that the pineal organ exerts an inhibitory influence on body
growth and the development of the sexual organs, perhaps the most
striking positive results which have been obtained in support of this
view were those described by Foa in 19 12 and Izawa in 1922. Foa performed the difficult operation of removing the pineal gland in young
chicks between the ages of 5 and 7 weeks. The mortality was large and
only a small number of chicks survived. After a period of 3 months
the latter showed that the general development of the body had been
much more rapid in the experimental birds than in the controls, and also
 
 
 
 
Fig. 282. — A — Crest, and B — Testicle of a Cock from which the Epiphysis
had been removed three months previously ; a — crest, and b — testicle
of a Normal Control Specimen of the Same Age.
 
The development of the experimental animals was much more rapid than the
controls, and the development of the secondary sexual characters (crow, crest,
spurs) was equally precocious.
 
(After Foa ; redrawn from UEpiphyse, J. Calvet.)
 
that the development of the secondary sexual characters had been more
precocious and active in the experimental animals, namely, the growth of
the comb and spurs and the early occurrence of crowing (Fig. 282).
Moreover, at the age of 10 to 12 months Foa examined the testicles of the
pinealectomized birds and found that they were not only increased in
size, but also showed that the general increase was due to the hypertrophy
of both the interstitial tissue and the seminiferous tubules. He obtained
similar results by repeating these experiments on rats and mice and
another series of young chicks. In the latter series he noted that the
size was not so markedly influenced as in the first series, and also that
pinealectomy had no effect on hens.
 
 
 
PINEALECTOMY 423
 
Izawa performed pinealectomy on 36 chickens ranging from 4 to 5
weeks of age, and besides these 1 1 others of the same age and weight
as those operated on were used for comparison. Aseptic precautions
were taken, and no cases of infection occurred. Most of the experimental
animals died shortly after the operation. Only four — three males and
one female — survived the operation for any length of time. These were
fed under the same conditions as the control animals and the effects
observed. Compared with the controls, the pinealectomized animals
showed a retarded growth for a few weeks following the operation, but
about a month later they grew more rapidly than the controls, their
body-weight becoming greater and their legs longer than those of the
controls. In the two males whose pineal bodies were completely removed,
the rapid development of the comb and the premature crow deserve
special notice, and Izawa stated that they gave evidence of sexual instinct
31 and 50 days earlier than the controls. There was also a marked increase
in the size of the testes.
 
In the female pinealectomized bird there was a remarkable increase
in the size of the ovary and of the Fallopian tube, the latter showing a
great increase in the length of the tube with increase in the width of its
ampullary portion, which was described as voluminous, while the Fallopian
tubes in the control were not only short but uniformly slender throughout
their whole length.
 
Zoia and Horrax also report positive results following pinealectomy.
The latter states that pinealectomized hens tend to breed earlier than
controls of the same age and weight ; on the other hand, Sarteschi reports
that pinealectomized hens dislike to copulate. Izawa gives tables showing
the exact weight and size of the various organs and parts of the animals
experimented on, and of the controls. From the statistical side it should
be borne in mind that the results obtained by Izawa, striking as they
appear to be, were based on only three cases, two male and one female,
and that the controls were individuals matched with regard to age and
weight with the experimental animal rather than of average size and
weight.
 
Positive results following pinealectomy have also been recorded
by Urechia and Gregoriu, Hoffmann, Zoia, Clemente, Izawa, and
Yokoh in young rats and chickens, namely, general increase in the
growth of the body and increase in the size and weight of the
genital glands in both males and females. Hoffmann also found in
three pinealectomized rats a decided enlargement of the vesicular
seminales.
 
Horrax, 19 16, experimenting with rats and guinea-pigs, found acceleration of spermatogenesis in the pinealectomized animals.
 
 
 
424 THE PINEAL ORGAN
 
Pinealectomy Resulting in Negative or Regressive Effects
 
Kolmer and Loewy destroyed the pineal gland by cauterization in
immature rats weighing 50 grm. They obtained negative results and
verified histologically that the destruction of the organ was complete.
 
Cristea practised epiphysectomy in 30 male chicks, 12 of which
survived, and in place of increased growth showed a rapid retardation
of both general development and of secondary sexual characters.
 
Foa's experiments, previously mentioned, were negative with respect
to chicks of the female sex.
 
Dandy, who experimented on dogs, came to the following conclusions :
 
1. Following the removal of the pineal he observed no sexual pre
cocity, or indolence ; no adiposity or emaciation ; no somatic
or mental precocity or retardation.
 
2. The experiments seemed to yield nothing to sustain the view
 
that the pineal has any active endocrine functions of importance
either in very young or adult dogs.
 
3. The pineal is not essential to life and seems to have no influence
 
on the animals' well-being.
 
Demel performed epiphysectomy on rams aged 4 weeks, of which
four survived. These showed a diminished growth, they became timid,
their fleece was poor and diminished in amount, their horns grew very
slowly and in two of them the horns were shed. The testicles were as
large as those of the healthy rams or definitely larger (positive change).
The hoofs were defective and there was an increase in the body temperature, which was raised by more than 1 ° C.
 
As a counter-test, Demel fed these animals for three months with
" epiglandol." They rapidly recovered, attained the weight of the
control rams, and developed the normal amount of fat and their horns.
Demel came to the conclusion that the pineal played a role in the regulation of temperature and in producing hypertrophy of the testicles. He
considered that it had no effect on the secondary sexual characters. But,
since as is well known, the development of these is associated with the
development of the genital organs, it is difficult to believe that the one
system could be affected without the other. It is possible also that the
rise of temperature and poor condition of the experimental animals might
have been due to concomitant injury of the meninges and other important
parts, and the subsequent improvement in their condition to recovery
from this, quite apart from the action of epiglandol.
 
Negative results were also obtained in lower vertebrates, e.g. frog
tadpoles, by Atwell and E. R. Hoskins and M. Hoskins. In those animals
 
 
 
PINEALECTOMY WITH NEGATIVE EFFECTS 425
 
which survived complete destruction of the pineal body by means of a
thermocautery, nothing abnormal was observed in their development.
 
In one of the most recent publications on the effects of pinealectomy,
namely, by L. G. Rowntree in the Practitioners' Library of Medicine and
Surgery, 1938, Chapter 5, this author summarizes the general results of
this operation in the following words : " Pinealectomy in the hands of
many investigators has led consistently to negative results ; in the rat
(Foa, Horrax, Kolmer, Loewy, del Castillo, Renton and Rushbridge,
Anderson and Wolf) ; in the rabbit (Exner and Boese) ; in the dog
(Dandy) ; and in the chick (Badertscher). Positive results have been
claimed in the rat by Izawa and Yohoh ; in the guinea-pig (Horrax and
Clemente) ; and in the chick (Foa, Zoia, and Clemente). The most
common results of pinealectomy are said to be : premature development
of secondary sexual characters in the male ; enlargement of the gonads,
overgrowth of the body, and obesity. Anderson and Wolf, after a critical
analysis of the several papers submitted, expressed the opinion that the
data submitted do not justify the conclusions reached."
 
 
 
The Effects of Feeding with Pineal Substance and the Injection of
 
Pineal Extracts
 
Precocious sexual and mental development and early somatic development when occurring in the human subject are usually interpreted as
indicating pineal deficiency or hypopinealism. If this opinion is correct,
one would expect that feeding with pineal substance or the injection of
pineal extracts would produce a condition of retarded sexual and mental
development and deferred somatic maturity. The effect of feeding
experiments, however, appears in many instances to be just the reverse,
namely, in place of inhibition of growth of the sexual organs and of the
body, there is often a rapid sexual and somatic development. There are,
however, a considerable number of experiments which have given results
which appear to confirm the general opinion of the restraining influence
of the pineal and which may, according to Calvet, be regarded as positive
in nature, whereas the accelerating and stimulating influence may be
regarded as negative.
 
Positive Effects. — Sisson and Finney obtained a retardation of growth
in young rats by feeding with the epiphysis of the calf. Priore found that
repeated injections of pineal extracts produced a definite retardation of
development in young male rabbits. M'Cord and Allen dissolved the
desiccated powder of the pineal in water containing living Amblystomes [
 
1 The type of this group of tailed amphibians is the Mexican axolotl, which is the
permanent larval form of a salamander from the United States, Amblystoma tigrimon.
 
 
 
426 THE PINEAL ORGAN
 
and obtained a retardation of metamorphosis. This result is, however,
counterbalanced by the results of experiments published by M'Cord in
1 91 7, in which he states that : "In unicellular organisms (paramoecia)
pineal extract increases the rate of reproduction to more than double that
of the controls " ; and " in larval forms (Ranidce) both growth and
differentiation are hastened."
 
Berblinger, experimenting on young rats, injected alcoholic and watery
extracts of the epiphyses of oxen subcutaneously, and also administered
the pineal by way of the alimentary tract. He obtained positive results
in most, but in some there was an increase in size.
 
Calvet also experimented on immature white rats, using epiphyseal
extracts obtained, fresh, from entire horses, geldings, and mares. These
were ground aseptically in a mortar and mixed with equal parts of physiological serum. The animals received daily injections of this solution for
8 days, and were killed two days after the injections had been discontinued. The testicles were slightly smaller than those of the controls,
but the size of the animals remained practically the same as the controls.
 
Negative Results. — M'Cord fed young chickens and guinea-pigs with
food containing a mixture of desiccated pineal gland and lactose. The
control animals received a similar food containing the same amount of
lactose but without the pineal. In both cases there was an acceleration
of growth in the experimental animals. At the end of two weeks the
guinea-pigs fed with pineal substance showed an increase in weight of
100 per cent., as compared with an increase of 77 per cent, in the controls.
The author, however, noted that the action was variable (Fig. 283), and
that if young animals were fed with epiphyses obtained from aged oxen,
there was a diminution in weight.
 
Negative results, namely, acceleration of development and increase of
weight, have also been obtained by Roux in frog tadpoles, Calvet in
tadpoles of Alytes, M'Cord (previously mentioned) in Ranidce, by
feeding with desiccated epiphysis, and also by Calvet with daily injections
of Epiglandol into immature rats, 1 c.c. of Epiglandol being equal to
0-02 grm. of the fresh gland. The injected animals killed three weeks
after weighed 34 grm., while the largest of the controls weighed only
31 grm. Notwithstanding this somatic increase, the testicles were not
hypertrophied and macroscopically appeared even smaller than those
of the controls ; moreover, microscopical sections showed no appreciable
change in structure.
 
In discussing the various results of these experiments depending on
the use of desiccated epiphysis or extracts of the epiphysis, Calvet puts
forward the suggestion, based on the biochemical researches of Fenger
and Roux, that since phosphoric acid, calcium, magnesium, sodium, and
 
 
 
EFFECTS OF FEEDING WITH PINEAL EXTRACTS 427
 
other inorganic elements are present in the desiccated epiphysis it is
possible that the power to influence growth may be due to the action
of these chemical constituents rather than on the supposed action of a
hormone.
 
Robinson reports further feeding experiments carried out by M'Cord
on young animals using fresh pineal glands, with resulting early precocity
and adiposity ; Hoskins' results were almost completely negative. Kozelka
also obtained negative results with pineal implants in chicks ; whereas
increased rate of growth has been claimed by Dobowik ; and in the rat
 
 
 
 
 
 
 
i <
 
 
 
Fig. 283. — A — Control Bird, and B — Experimental Chick nourished with
a Desiccated Extract of the Epiphysis, obtained from young Oxen.
 
The experimental chick is diminished in size ; feeding with the extract has,
therefore, in this instance retarded growth.
 
(Redrawn from Calvet, after M'Cord.)
 
 
 
Lahr found no influence on body-growth in either sex, but retardation
of gonadal development in both male and female animals. Robinson
further records the experimental work of Hanson on the effects on the
offspring of intraperitoneal injections of pineal extracts in successive
generations of parent rats. In succeeding generations up to the fifth
he obtained increasing retardation of growth, with acceleration in gonadal
development, precocity, " dwarfism," and macrogenitalismus precox
being the outstanding results.
 
Incidentally it may be mentioned here that observations on the human
subject seem to indicate that in those cases in which excessive premature
growth of the body has been associated with mental and sexual precocity,
the ultimate stature and body-weight of those individuals who have lived
to adult life is below the average height and weight.
 
In an interesting article by H. Lisser in Bedside Diagnosis, 1928,
 
 
 
428 THE PINEAL ORGAN
 
W. B. Saunders, Philadelphia, the author, refers to certain cases of hypergenitalism in preadolescent males combined with premature union of the
epiphyses of the long bones. The principal signs being : premature and
excessive development of the genital organs ; premature change of voice,
associated with rapid and excessive development of the body in general ;
the mental development, although somewhat precocious, not keeping
pace with the general precocity, and in addition to the above-mentioned
well-recognized group of symptoms, under the heading of skeletal changes,
Lisser states that " the boy is large for his age, as if he were becoming a
giant, but the excessive output of testicular secretions hastens epiphyseal
unification, and the premature union of the epiphyses transposes a misleading and transitory gigantism into a final height which is not excessive
and which may indeed incline to a mild form of dwarfism. Roentgenograms on such boys will reveal a bone age in advance of their chronological
age as an additional proof of precocity."
 
It seems possible that this explanation of premature bodily growth
associated with excessive testicular secretion and premature union of the
epiphyses may account for some of the apparently contradictory results
of experimental work on the effects of feeding with pineal substance or
extracts, or injections of pineal extracts, namely: in some retardation
or arrest of growth, " dwarfism," while in others there has been excessive
growth. It must be borne in mind, however, that in a large proportion
of the clinical cases that have been recorded in which these symptoms
have been present there is no proof of their having been connected either
directly or indirectly with the pineal organ.
 
The Influence of Pineal Grafts
 
Calvet experimented on three rats belonging to the same litter. These
animals received every second day one-half epiphysis of an entire adult
horse, which was introduced into the subcutaneous tissue of the dorsal
region with aseptic precautions. The control animal received a portion
of muscle or cerebral substance of equal weight from the horse and
suffered the same traumatism as the experimental animals. The grafts
commenced on the 15th November, 1932, and ceased on the 10th
December. The weight of the control rat, which at the commencement
of the experiment was 38 grm., reached 62 grm. The others treated
with the epiphysis weighed 40 grm. at the commencement, decreased
3 grm. from their original weight. The normal rat increased 3 cm. in
length, while the size of the grafted animals remained stationary.
 
Moreover, the migration of the testicles was arrested in the grafted
animal, and microscopic sections of the testicle showed a true atrophy,
 
 
 
INFLUENCE OF PINEAL GRAFTS 429
 
whereas the testicles of the normal rat had migrated into the scrotum
and showed active spermatogenesis. Calvet repeated the same experiment
on a number of rats and young guinea-pigs and obtained practically the
same results.
 
Grafts carried out on adult males were without effect on either growth
or the testicles.
 
Hblldobler and Schultze obtained acceleration of metamorphosis
with increase of weight after implantation of a small piece of the epiphysis
of the ox at the root of the tail in the larva of the toad, their results are
opposed to those of Calvet and are classed by him as negative. On the
other hand, the same experiment was repeated by Romeis, who was
unable to confirm the result of the last-mentioned observers.
 
Correlation of the Pineal Gland with the Genital Glands and
other Endocrine Organs
 
An interesting observation which appears to indicate an interrelationship of the pineal organ and the genital glands was made by Jean Calvet,
namely, that the parenchyma cells in the pineal gland of the bullock
are less numerous than in that of the bull, and also that the neuroglial
tissue is relatively more abundant in the castrated than in the entire
animal. This observation is of considerable importance and if confirmed
by subsequent investigations on similar lines with a detailed record of
the age of the animals from which the epiphyses were obtained would
be of real value in establishing the existence of a definite interrelationship
between the pineal gland and testicles.
 
Biach and Hulles (19 12) found in cats which had been castrated when
very young that 7-8 months after there was an atrophy of the parenchyma
of the pineal, and he also stated that the epiphysis of the ox was smaller
than that of the bull. Calvet also weighed the epiphyses of geldings and
oxen and compared these with the weights of the pineal body in stallions
and bulls. The results were variable, the glands being sometimes larger
in the castrated than in the entire animals, but the weight of the pineal
glands of the stallions and bulls was on the whole greater than in the
castrated animals and they were more developed.
 
Aschner (191 8),' moreover, has confirmed the observations of Calvet
with regard to the predominance of neuroglial fibres and fewer nuclei
of the parenchyma cells of the pineal gland in the ox as compared with the
bull, and has noted the same differences in dogs, cats, rabbits, and guineapigs.
 
1 Aschner, B., Die Blutdriisenerkrangimgen des Weibes. (Wiesbaden, 191 8.) Physiologic der Hypophyse. Handbuch der inneren Sekretion, II, Liefkabitzsch.
 
 
 
CHAPTER 29
 
PATHOLOGY OF PINEAL TUMOURS
 
The various pathological conditions which arise in and around the pineal
gland can be discussed in relation to the actual lesion itself, in relation to
the local changes produced inside the cranium, and in relation to the
somewhat variable general skeletal and endocrine changes which are
sometimes associated with such pathological conditions.
 
General Pathology. — The pineal gland may undergo simple hypertrophy. This was described by Virchow as occurring in an infant. It
has also been observed in association with other pathological conditions,
such as myxoedema and polyglandular dysfunctions, and has also been
described in a case of general cerebral hypertrophy.
 
Laignel has observed and described a case in which atrophy of the
gland was found.
 
The other pathological conditions arising in and in the region of the
pineal may be classified as follows : (1) cysts ; (2) cholesteatomata ;
(3) teratomata ; (4) pinealomata ; (5) pineoblastomata.
 
1. Cysts. — Cysts of various types have been described in relation to
the pineal. They are usually simple cysts without any associated tumour
growth. Often they may be found to project into and obliterate the
third ventricle and to compress the corpora quadrigemina. They almost
invariably give rise to hydrocephalus by blockage of the aqueduct.
 
No rule can be formulated as to the age incidence of such growths,
since they have been described both in the new-born and in the aged.
Such cysts are commonly single, but may be multiple. They are lined
with flattened cells and contain fluid which is occasionally discoloured
from recent haemorrhage. These cysts are very seldom accompanied by
any changes of the pubertas precox type.
 
2. Cholesteatomata. — These tumours occur in the region of the pineal ;
they are firm in consistency, the cut surface being yellowish-white and
waxy in appearance. On section they can be seen to be composed of
lamellated waxes or scaly material enclosed in a wall of stratified squamous
cells concentrically arranged. Such cells may be multinucleated. The
waxy material consists of desquamated cells and cholesterol crystals.
 
Cholesteatomata occur anywhere in the brain, but more especially
 
430
 
 
 
PATHOLOGY OF PINEAL TUMOURS 43I
 
do they occur near the midline. They are regularly connected with the
meninges. Bostroem concludes that all cholesteatomata arise from
embryonal epidermal inclusions.
 
3. Teratomata. — These tumours arise exclusively in young males
from 4 to 16 years of age, and are associated with precocious sexual
development, hirsutes, and sometimes with adiposity and general overgrowth.
 
These complex teratcmata are of moderate size ; they may be solid
or cystic, and are usually circumscribed. They give rise to marked pressure signs. They may consist almost entirely of hair, sebaceous material,
epidermoid cysts, cartilage, calcific grains, fat tissue and non-medullated
nerve-fibres, and smooth muscle. l A small layer of normal pineal tissue
may be found beside and unusually compressed and displaced by the
tumour. They are firm in consistency, irregular and knobbly on the
surface, often with elongated shreds of tela choroidea adherent to the
upper and posterior surface.
 
Their nature and origin is obscure, but of interest ; they are probably
derived from embryonic vestiges. The dermal structures, such as hair
and sebaceous glands, require an ectodermal tissue for their development,
which may possibly reach the pineal gland by the same developmental
disturbances that give rise to cholesteatomata. It must also be remembered
that in certain reptiles and fishes the pineal is a well-developed organ
which passes through a minute foramen in the skull and reaches the surface.
Alternatively these may develop by pseudogestation from a fertilized filial
polar body.
 
4, 5. Pinealomata and Pineoblastomata. — Tumours arising from the
pineal gland tend to resemble the structure of the developing pineal at
some definite stage of its development. The more primitive the type
that is found in these tumours, the more rapidly growing and more
invasive is the growth. The primitive type of such tumours is termed
pineoblastoma. The course is usually short. If the tumour cells resemble
more the adult type of pineal structure, they are slow growing, less
invasive, are less liable to haemorrhage, and less vascular, and the tumour
is termed pinealoma.
 
Pineoblastomata : these tumours are usually soft, with a tendency to
 
1 Transversely striated muscle fibres have also been found in teratomata of the pineal
gland, and very occasionally in the normal gland, more especially in the ox, as described
by Nicolas and Dimitrowa (Fig. 284;. Striated muscles fibres have, moreover, been
observed by Hammer in the epiphysis of a human foetus aged 5 months, and cells which
have been described as "myoid" in the adult human organ. They have been found
chiefly in the vascular connective tissue septa or trabecular, and usually appear as isolated
fibres, as in the specimen described by Dimitrowa. In some cases the nucleus is central
and the general appearance of the fibres is intermediate between that of the striped and
unstriped types of muscle-fibres.
 
 
 
432 THE PINEAL ORGAN
 
infiltrate into the surrounding tissue — the hemispheres, the cerebellum,
and the third ventricle — and tend to obliterate the aqueduct. Cysts are
often present and areas of haemorrhage occur. The surface is irregular
and lobulated ; cysts may be seen on the cut surface.
 
Microscopically there is a marked variation in the type and arrange
 
 
 
Fig. 284. — A Transversely Striated Muscle-Fibre from the Epiphysis of
Bos taurus. (After Dimitrowa.)
 
ment of cell found. The cells are arranged in a mosaic with streams of
small cells deeply staining in character and enclosing nests of larger cells
with vesicular nuclei and larger masses of clear cytoplasm, bearing a
strong resemblance to the parenchyma cells of the mature pineal body.
Giant cells are not an uncommon feature in various areas of these tumours ;
they are more common in the vicinity of the calcified plaques, which are a
frequent feature of such growths.
 
 
 
PATHOLOGY OF PINEAL TUMOURS 433
 
Pinealomata : the other main type is that which more closely approximates to the adult or mature type of pineal. They are slower in growth
and less invasive. Haemorrhages and cysts are less common. Microscopical section shows an alveolar pattern ; the cells are chiefly of the
large vesicular type, and are separated by strands of fibrous tissue.
 
Thus we see the importance of recognizing the developmental stages
 
 
 
P.M
 
 
 
 
c.t. cap.
 
 
 
Fig. 285. — Section through Pineal Body showing a Central Cavity, the
Wall of which is stained deeply and contains numerous Corpora
Arenacea.
 
 
 
Art. : artery.
 
Cav. : central cavity.
 
C. Ar. : corpora arenacea.
 
c.t. cap. : connective tissue capsule.
 
Ep. : ependyma.
 
gl. sh. : glial sheath.
 
 
 
Pig. : pigment.
 
P.M. : pia mater.
 
Ps. Ep. : pseudo-epithelium.
 
V. : vein.
 
ves. : vessel.
 
 
 
(Drawn from a specimen in Professor Barclay-Smith's collection at King's College,
 
London.)
 
 
 
through which the pineal passes when attempting to understand the
histology of these tumours.
 
General Changes. — The associated changes in the brain are due to
direct displacement and invasion of the brain substance. The cerebellum
is often invaded. The growth extends beneath the tentorium and invades
the cerebellum both in the midline and in either of the lateral lobes.
 
The midbrain is pressed upon, and especially the corpora quadrigemina. This distortion gives rise to the characteristic eye signs and
may also occlude the aqueduct of Sylvius. Occlusion of the aqueduct
may also be brought about by direct invasion of the third ventricle by
the growth. The outcome of these changes is that the whole ventricular
 
28
 
 
 
434 THE PINEAL ORGAN
 
system above the aqueduct becomes distended and internal hydrocephalus
results. Pressure on the vein of Galen by the growth may also play a
part in the development of the hydrocephalus.
 
The floor of the third ventricle is depressed. The hypophysis is
pressed upon and the hypothalamus distorted. It is this change as well
as the direct invasion which occurs which probably accounts for the
changes in growth and sexual development and other hypothalamic
signs which are sometimes seen. Extension may occur into the cerebral
hemispheres by direct invasion.
 
Haemorrhage occurs into these growths, and terminally haemorrhage
into the ventricles is not an uncommon finding. Changes are also found
around the medulla, there usually being a very well-developed pressure
cone.
 
 
 
CHAPTER 30
 
SYMPTOMATOLOGY OF PINEAL TUMOURS
 
Enlargements of the pineal gland usually present clinically a welldefined syndrome. Owing to the anatomical position, enlargements of
the gland cause pressure on structures which give rise to clear-cut clinical
symptoms and hence are quite early recognizable.
 
The symptoms can best be considered under three headings : (1) Focal
 
 
 
Pineal
gland
 
 
 
 
Fig. 286. — Anatomical Relationships of the Pineal Gland.
 
— those due to the lesion itself. (2) Local — the changes brought about
within the central nervous system. (3) General — the somatic changes
which sometimes accompany such enlargements.
 
1 . Focal Signs. — The focal signs which may be produced by tumours
are due in the main to the anatomical position of the gland (see Fig. 286).
It is because of its relationship to the superior corpora quadrigemina
that the eye signs produced are so characteristic.
 
435
 
 
 
436 THE PINEAL ORGAN
 
The aqueduct of Sylvius lying below the gland is very liable to be
occluded and produce a severe degree of internal hydrocephalus when
pressed upon by a pineal tumour.
 
The cerebellum lies immediately posterior to the pineal and is often
invaded by growths arising in that neighbourhood.
 
A contributory factor in the production of the internal hydrocephalus
is the fact that the vein draining the choroid plexuses — the vein of Galen —
is very liable to be compressed, with the result that engorgement of the
 
 
 
 
Fig. 287. — Schematic Representation of the Various Ways in which a
Pineal Tumour may extend and cause Pressure Symptoms : (1) on the
Corpora Quadrigemina ; (2) on the Aqueduct of Sylvius and Midbrain ;
(3) downwards on the Cerebellum, causing Cerebellar Symptoms ; (4) on
the Midbrain Thalamic and Subthalamic Regions ; and (5) on the
Cerebral Hemisphere.
 
choroid plexuses is produced and possibly an increased secretion of the
cerebrospinal fluid.
 
Tumours which arise in the pineal may extend in various directions,
and Fig. 287 illustrates the common methods of extension.
 
Eye Signs. — Tumours may extend into the corpora quadrigemina
and oculomotor region and produce a clinical syndrome which is characterized by loss of pupillary reaction to light, reaction to accommodation, and
upward, downward, and lateral movement of the eyes, in that order of
 
 
 
SYMPTOMATOLOGY OF PINEAL TUMOURS 437
 
development. It is extremely common to find that the light reflex is absent
and the patient unable to look upward.
 
To understand this clearly it is necessary to visualize the arrangement
of the oculomotor nuclei (Fig. 288). It will be remembered that the
nuclei of the Illrd, IVth, and Vlth nerves lie in about one continuous
line on either side of the aqueduct just below the corpora quadrigemina,
together with the medially placed nuclei. Various functions have been
mapped out for the several parts of the nucleus. In Fig. 288 it will be
seen that the Edinger-Westphal nucleus (A) is the most anterior, and is
concerned with control of the pupillary and ciliary muscles ; the dorsi
 
 
/-- Bird Ventricle
 
 
 
A
 
 
 
^v Central
 
|V\ ..--Nucleus
 
 
 
- B
 
 
 
- C
 
 
 
Fig. 288. — Diagram showing Arrangement of Oculomotor Nuclei.
 
lateral nucleus (B) is concerned with upward movements ; the ventromedial nucleus (C) is concerned with downward movement ; the central
nucleus with movements of divergence. The small caudal nucleus (D)
may be concerned again with pupillary reaction.
 
Thus it will be seen that pressure exerted from in front and above
the nuclei will give rise first to absence of light reflex, then to loss of
accommodation and loss of upward and downward movement. In clinical
practice it is the lateral movements which persist for the longest period.
 
Ear Signs. — Should the inferior corpora quadrigemina be pressed
upon, then deafness, unilateral or bilateral, complete or partial, may result.
 
 
 
438 THE PINEAL ORGAN
 
Cerebellar Signs. — Extension occurs into the cerebellum. This may
be into either hemisphere or directly in the midline.
 
Nystagmus is very common ; there is often giddiness and incoordination, with a tendency to swerve to the side most affected, or, if in
the midline, a tendency to fall backward. There is weakness, adiadochokinesia, intention tremor in the arms, and usually a grossly ataxic
gait. Rombergism may be present. The cerebellar involvement will in
some cases also give rise to a dysarthric speech, usually staccato in type.
 
Other cerebellar signs may be present. On extension of the hands
there is a tendency to fall away on the side of the lesion. The pastpointing test may show deviation.
 
The reflexes may be diminished or absent on one or both sides and the
limbs atonic, but usually the pyramidal involvement predominates.
 
Pyramidal and Sensory Signs. — The pyramidal tracts and medial
lemnisci may be affected. Involvement of the pyramidal tracts gives
rise to increase in tone on the affected side, weakness, increased deep
reflexes, absent abdominal reflexes, and an extensor plantar response.
The sensory changes take the form of a hemianesthesia, as all the sensory
fibres at the level of the corpora quadrigemina have joined the medial
lemniscus.
 
Signs of Third Ventricle Involvement. — The somatic changes sometimes
associated with pineal tumours have been referred to involvement of the
hypothalamus and third ventricle.
 
Disturbed temperature regulation has been reported in a few cases
of pineal tumour. The hypothalamus is probably concerned in the control of body temperature, and the case reports show that there may be
rise of temperature of an irregular type without any apparent source of
infection and with no corresponding rise in pulse-rate. The controlling
centre in the hypothalamus itself or its efferent pathway may be damaged.
Polyphagia, polyuria, and glycosuria have also been observed, and are
probably due to hypothalamus involvement.
 
Signs of Involvement of the Cerebral Hemispheres. — As a pineal tumour
grows, extension occurs upwards into the hemispheres. It is of necessity
a deep extension, and the motor cortex and sensory cortex are not usually
involved. The optic radiations, however, pass near by on their way to
the occipital cortex, and these may be cut through and a right or left
homonymous hemianopia result.
 
2. Local Signs. — Owing to the site of the lesion, signs due to raised
intracranial pressure manifest themselves early in the course of the
tumour growth. Headaches are severe and continuous, and are associated
with vomiting. Mental lethargy and reduction in mentality may be
early signs, as may also giddiness. Loss of vision occurs from the effects
 
 
 
SYMPTOMATOLOGY OF PINEAL TUMOURS 439
 
of papilledema, which is usually very marked and presents itself as a very
early sign. Epileptiform fits also occur.
 
Signs are produced in the cranial nerves as the result of the raised
intracranial pressure. The third ventricle is commonly affected, and
double vision and strabismus are frequently present. The Vlth nerve is
also involved. There is paralysis of the external rectus on either or both
sides, with a convergent strabismus. The olfactory nerve is not affected.
The Vth nerve may be affected, giving rise to a weakness of the muscles
of mastication and sometimes sensory loss on that side of the face. .
 
Facial paralysis is seen quite commonly, and is either produced by
the local extension of the growth or from damage to the nerve resulting
from the raised intracranial pressure.
 
Deafness is common, and has already been mentioned.
 
The nerves IX, X, XI, and XII are not usually affected ; only if the
cerebellum is extensively invaded will they be pressed upon and give
rise to their characteristic physical signs.
 
3. General Signs. — Pineal tumours associated with general somatic
changes are almost confined to the male sex. The disturbances of growth
associated with pineal tumours affect chiefly the genital organs, but are
often associated with adiposity and sometimes with general and symmetrical overgrowth.
 
Hypertrophy of the penis and testes, with growth of pubic hair and
precocious sexual instinct, have been observed with most tumours classed
as teratornata, as well as with simple, benign, and malignant tumours.
The testicles show a marked increase in the size and number of the interstitial cells. The breasts enlarge, and one case has been reported of a
secretion of colostrum in a boy aged 4, associated with testicular enlargement.
 
Increase of hair occurs also on the lips and chin and in the axillae.
Deepening of the voice may take place.
 
The adiposity which occurs has been observed with all varieties of
pineal tumours, and cannot be distinguished clinically from hypophyseal
obesity — probably because, as already pointed out, it is in both cases due
to hypothalamic involvement. The adiposity is proximal in distribution ;
it is marked over the shoulders and pelvic girdles, with considerable
enlargement of the breasts. The buttocks, thighs, and abdomen also
show heavy deposits of fat.
 
Physiological experiments seem to point to the fact that injection of
pineal extracts in chicks and guinea-pigs causes a general increase in
size, with genital overgrowth and sexual precocity, but the evidence is
still not completely convincing.
 
The possibility is that the pineal gland normally facilitates growth in
 
 
 
440 THE PINEAL ORGAN
 
general, and sexual development in particular. Acceleration of these
functions occurring in the course of pineal tumours may therefore be
interpreted as hyperpinealism. In the absence of further data, obesity
and hypertrichosis may be considered as part of the general and sexual
overgrowth, but the hypophyseal failure must be considered as a possible
contributing factor in the adiposity.
 
A close relationship evidently exists between the pineal and testicular
functions, which are probably not antagonistic in nature, but as yet there
are insufficient data to define the relationship between the pineal organ
and the ductless glands, and hence of its relationship to the gonads.
Moreover, in quite a number of cases there are no signs whatever of any
sexual abnormalitv.
 
 
 
CHAPTER 31
 
OPERATIVE TECHNIQUE
 
Although it is possible to operate on the pineal using local infiltration
of the scalp and some scopolamine and morphine, yet it is preferable,
in the author's opinion, to use rectal avertin, local infiltration of the scalp
with J per cent, novocain, and to follow with intratracheal gas and oxygen.
The reasons for using intratracheal gas and oxygen are that it is desirable
to have the patient completely quiet while the deep approach to the pineal
is proceeded with, and that if the patient stops breathing, oxygen or
 
 
 
■ ■
 
 
 
 
Fig. 289. — Drawing showing the Skin Incision and Site for the Burr Holes
in the Bone so as to Expose the Posterior two-thirds of the Cerebral
Hemisphere.
 
carbondioxide can be given, a very desirable precaution when operating
near the brain-stem, where slight deflections in either direction may press
or drag upon the respiratory centre.
 
There are only two approaches to the pineal gland which are of any practical value, and both demand a large right occipito-parietal osteoplastic flap.
 
1. Dandy's Operation. — This is the method of choice, and is based
on experimental operative procedure performed on dogs. After preliminary infiltration of the scalp with novocain, a large occipito-parietal
scalp flap is fashioned (Fig. 289) and bleeding controlled. Some five
 
441
 
 
 
442
 
 
 
THE PINEAL ORGAN
 
 
 
burr holes are made in the skull at the periphery of the scalp incision and
these burr holes are joined by means of a Gigli saw, which is inserted
by a special curved introducer (Fig. 290). After the saw has been introduced, the bone between the burr holes is cut on the bevel, the introducers acting as a protector to the underlying dura mater and brain
(Fig. 291). When all the burr holes have been united with the exception
of the lowest two, the osteoplastic flap can be elevated and fractured
across its narrow and thinned-out base ; it is then hinged outwards on
the temporal muscle. Bleeding vessels in the dura mater are underrun
 
 
 
 
Fig. 290. — Useful Gigli Saw
Guide.
 
 
 
Fig. 291. — The Method of Introducing a Gigli Saw between Two
Burr Holes.
 
 
 
with silk sutures, while those occurring in the bone are controlled with
Horsley's bone wax. If there is a considerable increase of the intracranial pressure this can be diminished by the administration of 20 c.c.
of hypertonic saline (15 per cent.) at the commencement of the operation,
but as a rule this is not necessary because adequate reduction of the intracranial pressure may be produced by tapping the lateral ventricle. It is
a remarkable fact that although an internal hydrocephalus causes gradual
destruction of cerebral tissue, yet this hydrocephalus is advantageous to
the surgeon when removing a pineal tumour ; otherwise it would be
impossible to retract the posterior part of a normal hemisphere without
causing some permanent damage. When the fluid from the ventricle
is withdrawn in a case of internal hydrocephalus, the flattened-out hemisphere can be retracted without further damage ensuing.
 
A flap of dura mater is turned outwards on top of the osteoplastic
 
 
 
OPERATIVE TECHNIQUE 443
 
flap (Fig. 292) and bleeding from the cut surface of the dura is controlled
with silver clips. As the mesial margin of the flap extends almost to the
superior sagittal sinus, there are numerous bleeding vessels which will
require ligature ; some of the smaller ones may be dealt with by silver
clips. The lateral ventricle is then tapped at the junction of its body
and descending horn, the cerebrospinal fluid being allowed to flow away
over the brain ; the needle is left in situ for as long as possible to ensure
complete evacuation of the ventricle.
 
The next step is to divide any cerebral veins which may be running
 
 
 
 
Fig. 292. — The Method in which the Osteoplastic Flap is raised and turned
outwards : Flap of Dura Mater is then turned outwards and the
Lateral Ventricle tapped.
 
from the upper part of the hemisphere into the superior sagittal sinus.
There are five or six of these veins, and they can be secured between fine
ligatures or silver clips. Care should be taken to avoid injury to the vein
which drains the Rolandic area of the brain, otherwise a transient hemiplegia may result.
 
After the cerebral veins have been divided the whole of the posterior
extremity of the hemisphere is to be retracted to such an extent as to
expose the falx cerebri (Fig. 293). Continued retraction will bring the
inferior longitudinal sinus into view, and beneath it the corpus callosum
(Fig. 294). To obtain an adequate exposure of the splenium of the
corpus callosum, it is often advisable to divide the inferior longitudinal
 
 
 
444
 
 
 
THE PINEAL ORGAN
 
 
 
sinus between silver clips, and then slit up the lower border of the falx
for half an inch or more with a curved tenotomy knife (Fig. 295). The
splenium of the corpus callosum is then incised in the midline and the
tumour exposed. Any bleeding that may be encountered in this procedure
is checked by the diathermy point. The most important structure in
relation to the tumour is the great vein of Galen, which lies under the
fornix. This vein and its tributaries should be carefully preserved.
 
 
 
 
Fig. 293. — The Exposure of the Corpus Callosum. The Ligated Cerebral
Veins can be seen as they enter the Superior Sagittal Sinus.
 
The tumour is carefully prised out of its bed by means of a curved dissector, such as Adson's. It may be that the third ventricle is opened while
the tumour is dissected out of its bed, but this does not matter (Figs.
294, 296). Absolute hsemostasis is essential, and all bleeding points are
controlled by the application of silver clips or the use of the diathermy
point.
 
The tumour bed must be quite dry before completing the operation.
The posterior part of the cerebral hemisphere is allowed to fall back
into place, and the dura mater united with one or two tethering sutures.
Drainage by means of a fine corrugated rubber dam is often necessary
 
 
 
OPERATIVE TECHNIQUE
 
 
 
445
 
 
 
 
Fig. 294. — The Posterior Part of the Cerebral Hemisphere is retracted
so as to expose the corpus callosum.
 
 
 
 
Fig. 295. — The Inferior Surface of the Falx has been divided, together
with the Inferior Sagittal Sinus. The Posterior End of the Corpus
Callosum has been divided, exposing the Pineal Tumour.
 
for a day or so. The osteoplastic flap is replaced and the scalp approximated by two layers of sutures. The head is covered with a firm bandage,
and the patient nursed flat for the first three days and then allowed a
 
 
 
44-6 THE PINEAL ORGAN
 
pillow. With the depletion of cerebrospinal fluid during the operation,
it is necessary to balance this by an adequate intake, and therefore after
the operation a continuous rectal saline infusion is instituted. A purge
is given on the second day after operation, and if there is much headache
a lumbar operation is performed. The stitches are removed on the tenth
day, and the patient is subsequently allowed to get out of bed.
 
2. Van Wagenen's Operation.— The second method of surgical
approach is that devised by van Wagenen, in which the tumour is attacked
 
 
 
 
Fig. 296. — Section through
the Brain showing the
Exposure and Incision
of the Corpus Callo
SUM.
 
 
 
Fig. 297.
 
 
-The Actual Removal of a Pineal
 
Tumour.
 
 
 
through the median wall of the lateral ventricle. It is an easier method
and the route is less vascular, and the tributaries of the great vein of
Galen can be more easily seen and dealt with. The disadvantage, however, is that it leaves some permanent disturbance of function in the form
of hemiplegia and homonymous hemianopia.
 
The first part of the operation is very similar to Dandy's approach —
an osteoplastic flap is fashioned and turned outwards (Fig. 298). The
dura mater is incised and a flap turned downwards. A reversed L-shaped
incision about 6 cm. in length is made in the cortex, extending from the
posterior end of the superior temporal lobe gyrus upward and slightly
backward, ending in the lobus parietalis superioris. This incision is
 
 
 
OPERATIVE TECHNIQUE
 
 
 
447
 
 
 
gradually deepened by means of the diathermy cautery, using the cutting
and coagulating currents alternately, and its edges retracted by small
flange retractors covered with moist lint. The incision is deepened until
the dilated lateral ventricle is opened (Fig. 299). The wound can now be
retracted sufficiently to enable the surgeon to see the bulging medial wall
of the ventricle covered in part by the choroid plexus. If the choroid
plexus is well developed and extends over the medial wall of the ventricle
 
 
 
 
Fig. 298. — Van Wagenen's Approach
to the Pineal showing the Outline of the Osteoplastic Flap
and the Site of the Incision in
the Cortex.
 
 
 
Fig. 299. — Sectional view of the
approach to a Pineal Tumour
through a dilated lateral
 
Ventricle.
 
 
 
in the region of the bulging pineal tumour, it may be coagulated with
the diathermy point. The medial wall of the ventricle is then gently
incised and the pineal tumour exposed and gradually separated from its
connections (Fig. 300). Absolute haemostasis is procured, and a small
piece of rubber dam is inserted into the incision in the brain for drainage.
The dura mater is replaced and held in position by a few anchoring
stitches. The osteoplastic flap is accurately put back in its original
position, and the scalp united by a double layer of interrupted sutures,
and a firm dressing then applied. The drainage wick is removed after
twenty-four hours and the stitches on about the tenth day.
 
 
 
448 THE PINEAL ORGAN
 
Whichever method of operation is adopted, it is a wise precaution to
give the patient some post-operative X-ray therapy, as it is impossible
to be quite sure that every particle of the tumour has been removed, and
pineal tumours for the most part are radiosensitive.
 
 
 
 
Fig. 300. — Actual Exposure of a Pineal Tumour through the Lateral
 
Ventricle.
 
 
 
Ventricular puncture may be necessary during convalescence if the
intracranial pressure becomes increased.
 
In some cases where the pineal tumour is very large it may be
advisable to perform a partial lobectomy of the occipital lobe in order to
give the surgeon a better method of approach.
 
 
 
CHAPTER 32
 
CLINICAL CASES
 
The following clinical cases have come under observation and treatment
since 1919.
 
Case 1. — Elsa B., aged 26, was admitted to hospital under the late Sir
David Ferrier, in May, 1919, complaining of headache and vomiting. Up to
a year prior to admission the patient was a cheerful individual who was employed
in a laundry, and was very keen on tennis. Gradually she lost interest in her
work and gave up all games. For a month previous to her admission to hospital
she had attacks of vomiting, and was unsteady while walking.
 
On Examination. — The patient appeared rather depressed, but was quite
keen to cooperate in the hope that something could be done to relieve her
symptoms. She walked with a staggering gait, but there did not seem to be
any tendency to fall to either side. She had a good sense of smell. The visual
fields were complete. Bilateral papilloedema was present, more marked on
the right side — right, four diopters ; left, three diopters. The pupils were
dilated and did not react to light or accommodation. There was loss of conjugate upward movement of the eyes. There was weakness of the right Vlth
nerve and bilateral nerve deafness. The other cranial nerves appeared normal.
There was a fine lateral nystagmus to the right. Ataxia was marked and
Romberg's sign was positive. The diagnosis of a pontine or pineal tumour
was made, and a subtentorial decompression advised.
 
Operation. — On 15th May, 1919, a large subtentorial decompression was
performed under ether anaesthesia ; there was marked increase of the intracranial pressure, but no tumour was discovered. The wound was closed
without drainage. Healing was sound and the stitches were removed after
ten days. The patient rapidly improved after the operation, the vomiting
stopped completely, and the papilloedema subsided. However, a month after
the operation the decompression area began to bulge (Fig. 301), and the
papilloedema returned. The patient began to go downhill and died two months
after her operation.
 
An autopsy was performed and the brain removed entire and hardened.
No obvious tumour could be seen. After the hardening process was complete,
several sections were made through the entire brain, and a pineal tumour was
discovered.
 
Pathology. — The tumour was situated between the splenium of the corpus
 
callosum and the quadrigeminal plate of the midbrain, both these parts being
 
invaded by an ingrowth of the tumour (Fig. 302). Its maximum transverse
 
diameter in the section examined was 17 mm. and its vertical measurement
 
29 449
 
 
 
450
 
 
 
THE PINEAL ORGAN
 
 
 
15 mm. There was no definite capsule, the growth being limited by the tissues
with which it came into contact. Thus it was covered laterally by vascular
 
 
 
 
Fig. 301. — Photograph of Case i, showing Bulging through a Sub-tentorial
 
Decompression.
 
pia mater, and where it was invading nerve-tissue this was pushed aside and
compressed, the original covering having been either partially or completely
destroyed. The aqueductus cerebri had been flattened by pressure, its roof
 
 
 
 
Fig. 302. — Case i. Brain after Removal, show Position of Pineal Tumour.
 
being almost in contact with the floor except in the centre, where in the position
of the median groove in its floor the section showed a triangular space with the
apex directed downwards. The single layer of cubical epithelium which lines
 
 
 
CLINICAL CASES 45I
 
the duct was retained on the right side, but had disappeared for the most part
on the left side, where it was replaced by an ingrowth of vascular glial tissue.
In the nerve-tissue of the splenium and quadrigeminal plate which surrounded
the growth there was a considerable increase in the number and size of the
blood-vessels. Many of these contained thrombi, in which there was a relatively
very high proportion of lymphocytes as compared with red blood-corpuscles.
The walls of the vessels were thickened, and there was a considerable nuclear
proliferation in surrounding glial tissue.
 
The surface of the tumour was very irregular and in places lobulated. The
central parts were broken down, an irregular cavity being present in the lower
part of the section, with spaces running out from the main cavity into the central
axes of the lobules, where the destruction of tissue was less complete. The
 
 
 
Ca.
 
 
 
 
Fig. 303. — Case i. Small Cyst in Base of Tumour containing
Choroidal Villi.
Ca. : calcareous body. C.V. : choroidal villus,
 
central axes of the lobules showed a canal which was in some places lined by
flattened epithelial cells, external to which was a layer of condensed glial tissue
continuous with that of the tumour. These spaces were for the most part
empty, but occasionally contained a small amount of cell debris or degenerated
blood-corpuscles. They probably represent remnants of the lumen of the
original pineal outgrowth which had become cystic.
 
The tumour cells were loosely arranged in a lobular manner around these
cystic spaces, the lobules being separated by vascular ingrowths from the surface. Two principal types of cell were present : the majority had spherical
nuclei, deeply stained with hematoxylin, and surrounded by a small amount of
feebly stained cytoplasm. Among these were larger cells with a feebly stained
round or oval nucleus. They appeared to belong to the supporting glial tissue,
which in some places formed a trabecular network similar to that seen in the
normal gland. No mitotic figures appeared to be present, though in some parts
the cells were of small size and closely packed together, suggesting an active
proliferation. In the upper part of the tumour there were extensive areas of
necrosed tissue showing an irregular fibrinous network containing degenerated
red blood-corpuscles and leucocytes, which were intersected by strands of
degenerated glial tissue.
 
A small cyst lined by ependyma and containing choroidal villi was present
at the base of one of the lobules in the lower part of the tumour (Fig. 303).
 
 
 
452 THE PINEAL ORGAN
 
This was probably a remnant of the dorsal diverticulum, which was present
during foetal life and projects backwards over the pineal body from the posterior
part of the roof of the third ventricle. This figure should be compared with
Fig. 304, which represents a small cyst, lined by cylindrical ependymal cells,
found in the substance of the epiphysis of an ox.
 
 
 
 
Fig. 304.
 
 
 
-Small Cyst, lined by Cylindrical and Irregularly Shaped
Ependymal Cells, in an Epiphysis of Bos taurus.
 
 
 
Some of the ependymal cells send processes outward towards the periphery.
(After Dimitrowa, 1901.)
 
Case 2. — Harry P., aged 12, was admitted to hospital in October, 1923,
with a history of constant headaches for nearly two years. He had been fitted
with various glasses without any benefit. Four months before admission he
had his tonsils and adenoids removed, as it was thought that this treatment
might alleviate the headaches.
 
On Examination. — The patient was thin, and inclined to be irritable. There
was no sign of pubertas praecox. The pupils reacted sluggishly to light and
accommodation, and there was bilateral papilloedema of 4-5 diopters in each
eye. The visual fields were normal. There was complete paresis of upward
gaze and some weakness of the right Vlth nerve. The hearing on the right side
was somewhat diminished. The other cranial nerves were normal. There was
a slight lateral nystagmus to the right. The gait was somewhat ataxic and
Romberg's sign was positive. There was very slight weakness of the right
arm. All the deep reflexes were normal.
 
Radiographs revealed a calcified pineal body and some opening up of the
sutures of the skull. After the boy had been in hospital for a week attacks of
vomiting and sweating commenced, and it was thought that the condition
might possibly be due to a tuberculoma. This diagnosis was supported by the
fact that although the boy had a good appetite, he put on no weight and remained
exceedingly thin. However, owing to the very definite paresis of upward
gaze, it was decided that the more probable diagnosis was that of pinealoma.
 
Operation. — Under rectal ether and local anaesthesia a large osteoplastic
 
 
 
CLINICAL CASES 453
 
flap was turned down over the right parieto-occipital region. The lateral
ventricle was tapped, but owing to the poor condition of the patient no further
exploration was carried out. The patient never really rallied, and died three
days later.
 
At autopsy the pathologist unfortunately cut into the brain, and exposed a
large but somewhat fragmentary vascular pineal tumour. Microscopically
there was a definite mosaic arrangement of the cells, with one or two giant cells
surrounded by a definite layer of small cells. It was unfortunate that the
brain was not hardened before it was sectioned.
 
Case 3. — Hilda H., aged 25, was admitted to hospital on 30th October,
1930, complaining of headaches, sickness, and occasional attacks of double
vision. The headaches were not continuous, but occurred spasmodically,
the patient being quite free from them for several weeks at a time. The headaches first commenced about two years previously. A month before admission
to hospital she became unsteady in her gait and could not see to mend her
clothes. She was seen as an out-patient, and was found to have bilateral papilledema, and admission was recommended.
 
On Examination. — The patient was found to be well-nourished and quite
cheerful and very keen to get well in order that she could go back to her work.
 
There was bilateral papilledema, four diopters of swelling in the right eye,
and three diopters in the left. The pupils reacted sluggishly to light and
accommodation. The visual fields were full. There was weakness of both
Vlth cranial nerves. There was limitation of upward gaze, which increased
while under observation in hospital. An X-ray examination showed some
increase in the meningeal grooves in the skull, which was significant of increased
intracranial pressure. There was no sign of calcification of the pineal gland.
There was some ataxia on walking, but this on the whole was slight. There
was a fine lateral nystagmus to the right, and slight deafness in the right ear.
Rombergism was present. The deep reflexes were slightly increased on the
right side of the body. There were no other neurological symptoms. The
diagnosis of tumour of the pineal gland was made, and a supratentorial approach
was advised.
 
Operation. — On 21st November, 1930, under intratracheal gas and oxygen
anaesthesia combined with local infiltration, a large occipito-parietal osteoplastic
flap was turned down on the right side. The dura mater was very tense, and
to relieve the intracranial pressure the right lateral ventricle was tapped. The
dura mater was incised and the cerebral hemisphere was carefully retracted ;
several cerebral veins required to be secured by silver clips, as they entered the
superior longitudinal sinus. On exposing the falx cerebri, a little more retraction brought the corpus callosum into view. Two silver clips were placed on
the inferior longitudinal sinus and the falx was divided between them. The
corpus callosum was then divided longitudinally, and a large tumour of the
pineal gland was exposed. An attempt to remove this with the diathermy knife
failed owing to excessive bleeding from the great vein of Galen and its tributaries. When the bleeding was more or less under control the condition of the
patient was so very poor that the osteoplastic flap was replaced and the scalp
wound closed. A blood transfusion of 400 c.c. of citrated blood was given
immediately the patient returned to the ward. The condition of the patient
 
 
 
454 THE PINEAL ORGAN
 
rapidly improved and next day she was talking quite happily. There was wellmarked lateral nystagmus to the left and right.
 
Thirty-six hours after the operation the patient became drowsy and then
unconscious, with a pulse-rate of 50. The upper part of the scalp wound was
opened, the bone flap removed, and the lateral ventricle tapped. Some 40C.C
of cerebrospinal fluid were withdrawn. The patient rapidly improved after
this, but by the tenth day after operation, when the stitches were removed,
there was considerable bulging of the scalp in the region of the wound ; 200 c.c.
of a 15 per cent, sodium chloride solution were given intravenously. This
worked like a charm, and the bulge completely disappeared for four days,
when it became more tense again. As a further operation for the complete
 
 
 
 
Fig. 305. — Case 3.
 
 
 
Showing Bulging of Decompression Area in the Right
Occipitoparietal Region.
 
 
 
removal of the tumour was refused by the patient, it was decided to give a
course of X-ray treatments. Four treatments were given at two- weekly intervals,
the applications being given over the decompressed area. This kept the patient
quite fit, the papilloedema subsided, and the patient was able to go home.
 
On re-admisson. — She was readmitted in May, 193 1, with bulging of the
decompression area and an increase in the papilloedema (Fig. 305). Operation
was again refused and a further course of X-ray treatment was given. The
patient was discharged in June, 193 1, in an improved condition ; the papilloedema
was subsiding again and the cerebral hernia was less. She died quite suddenly
in August, 1 93 1, but no autopsy was obtainable.
 
Case 4. — Albert P., aged 23, was admitted to hospital under the care of
Dr. Worster-Drought, on 9th October, 1931, complaining of headaches,
drowsiness, dizziness, and a constant " vacant " feeling. He was quite well
 
 
 
CLINICAL CASES
 
 
 
455
 
 
 
until three months ago, when he first complained of occipital headache, which
had persisted ever since. Soon after the headaches began he became drowsy
and had attacks of " vacancy," during which he would sit or stand motionless
for as long as half an hour. He slept well and ate well. Apart from headaches
he did not feel ill. He had noticed dimness of vision on occasions. He had
had several attacks of giddiness, in one of which he fell downstairs. He had
only vomited once prior to admission. He had grown fatter during the last
three months.
 
On Examination. — The patient was found to be somewhat slow in his
movements. He weighed 12 st. i lb. A
considerable amount of subcutaneous fat was
noticeable (Fig. 306).
 
Cranial nerves. — The pupils were equal,
but reaction to light and accommodation was
slow. The visual fields were normal to rough
tests. Bilateral papilloedema was present ; five
diopters in the right and four in the left. There
was no nystagmus, and the ocular muscles
were normal. Speech was slow, and ponderous, and the whole attitude was slow and
heavy ; he never smiled, and the facial
expression seemed lost.
 
Sensation to cotton-wool and pin-pricks
was quite normal. The cold tube felt hot on
the right side of the trunk from the acromion
process to the midline nearly down to the
umbilicus. All limb reflexes were normal.
The gait was slow, but with no obvious defect.
Co-ordination, finger-nose test, was poor.
Rombergism was slight. The heart, lungs,
etc., were normal, and the blood-pressure
100 85. An X-ray examination made on 16th
October, 1931, showed that the sella turcica
was enlarged and erodefl, and the pineal body
calcified. Cushing's thermic reaction was
negative. The blood-sugar curve was normal.
The visual fields were constricted. The
cerebrospinal fluid showed : total protein 0-03
per cent. ; globulin, no excess. The Wassermann reaction was negative.
 
First Operation. — Air ventriculography was carried out on 31st October,
1931, under local anaesthesia. A small trephine was made in the right parietal
bone and a cannula passed into the ventricle ; 200 c.c. of ventricular fluid were
withdrawn and 140 c.c. of air introduced (Fig. 307).
 
The ventricular fluid was clear and colourless, cells 1 per c.mm. There
were no red corpuscles. Total protein was 0-015 P er cent. There was no
excess of globulin, and the Wasserman reaction was negative. The patient
was very drowsy after the ventriculography.
 
 
 
 
Fig. 306. — Case 4. Photograph of Patient suffering
from a Pineal Tumour.
 
The vacant expression in
this patient is well marked.
 
 
 
456 THE PINEAL ORGAN
 
Second Operation. — On 5th November, 1931, a right subtemporal decompression was carried out under local anaesthesia. Considerable intracranial
pressure was found. The patient stood the operation well, but afterwards
became more drowsy and gradually got weaker. He suddenly collapsed and
died on 21st November, 193 1. He had been running a high temperature for
three days. The wound had quite healed and was healthy.
 
Pathology. — A post-mortem examination was carried out by Dr. Carnegie
Dickson. The body was that of a well-nourished, well-developed young adult
male, with little of note externally except that the figure showed a tendency to
the female type. There was marked general flattening of the convolutions,
more especially of the left hemisphere, which appeared to be slightly larger
 
 
 
 
Fig. 307. — Case 4. Radiograph after Ventriculography, showing Dilated
Lateral Ventricles and Area of Pineal Tumour just beneath the
Corpus Callosum.
 
 
 
than the right. The larger surface veins were somewhat dilated and the
Pacchionian bodies about the vertex were numerous and prominent. Over the
central portion of the base, e.g. over the pons and the interpeduncular space
and dilated infundibulum, there was some thickening of the pia arachnoid.
 
On horizontal section of the brain at the level of the upper surface of the
corpus callosum, the lateral ventricles were found to be very considerably
dilated, especially the left, and the section at this level passed through a pearly
" epidermoid " or " cholesteatomatous " tumour to the left side of the middle
line, just posterior to the central point of the hemisphere, and occupying
roughly the normal position of the left optic thalamus, which was displaced
 
 
 
CLINICAL CASES 457
 
by the tumour forwards and outwards. This tumour had evidently arisen from
the pineal region, the tumour lying mostly to the left side of this, pushing
downwards the corpora quadrigemina and lamina quadrigemina and compressing the subjacent aqueduct of Sylvius, thus producing the hydrocephalus. The body of the pineal gland was still present, about the size of a
small cherry-stone, and apparently more or less independent of the tumour,
which, however, was in contact with its upper and left surface. The central
portion of the pineal was removed for section, and the remaining sides of the
gland sewn together to preserve the continuity of the specimen. The tumour
was about the size of a large walnut or small plum, and it reached and pushed
downwards and backwards the upper and anterior part of the cerebellum.
 
On the right side of the brain, just external to the dilated posterior ventricular horn, there was considerable softening and haemorrhage due to the compression, and the cerebrospinal fluid had evidently ruptured outwards at this
point during the removal of the specimen. The right optic thalamus showed
considerable bulging into the dilated right lateral ventricle, suggesting the
possibility that this also contained tumour, but on cutting into it, this was disproved and it was found to be due merely to pressure displacement by the
tumour to the left side, pushing it towards the right and upwards. Sections of
the tumour itself had a glistening, pearly white iridescence, suggestive of the
presence of cholesterol. Horizontal sections at a lower level showed much the
same appearance, with dilatation of the ventricles, including the third ventricle,
thus producing the prominent infundibulum as seen from below.
 
Histological Examination — Sections from various parts of the pearly tumour
showed it to be a typical epidermoid consisting of a series of cysts or tumours,
showing a concentric laminated appearance due to the production from the
periphery inwards of squamous epithelium The outer or formative layer in
most of these cysts is much degenerated or has largely disappeared, i.e. is now
more or less inactive. Where it persists it shows a tendency to the production
of multinucleated plasmoidal squamous cells. Here and there, however, the
formation of outward budding and the production of further small cysts at the
periphery of the main mass persist. The central portions of the cysts consist
of desquamated epithelial cells and debris, including cholesterol crystals.
 
Sections of the pineal itself show at some parts more or less normal pineal
structure, but at others there is distinct proliferation, with the production of
what may be considered a simple pinealoma, involving more especially the larger
pineal cells, and with little or no proliferation of the so-called " small lymphocytelike " cells.
 
The adenomatous cells are somewhat loosely arranged, the stroma varying
in amount and in some parts being scanty and containing numerous thinwalled blood-vessels.
 
Case 5. — George W., aged 32, came under observation in March, 1932,
complaining of giddiness and some difficulty in walking. The patient was a
bank clerk, and was able to do his work until February, 1932, when he had an
attack of influenza which kept him in bed for three weeks. On getting out of
bed he found he was very unsteady on his feet and could not stand alone. He
was treated with tonics and massage, but did not improve.
 
 
 
458 THE PINEAL ORGAN
 
On Examination. — When seen on ioth March, 1932, he appeared to be
somewhat dull and listless. His pupils were dilated and reacted sluggishly
to light. There was bilateral papilloedema, there being five diopters of swelling
in the right eye and four in the left. Except for slight bilateral deafness, the
other cranial nerves appeared normal. There was a slight lateral nystagmus to
the right. Rombergism was marked, and the patient was quite ataxic. The
deep reflexes were normal, and there was no impairment to sensation.
 
Lumbar puncture revealed a clear colourless cerebrospinal fluid under
pressure ; there were no abnormal constituents. The day following the lumbar
puncture the patient was incontinent three times, and there was a well-marked
lateral nystagmus. Also for the first time there was limitation of upward gaze
and a definite weakness of the right sixth cranial nerve. Both lower limbs
became spastic two days later. Radiographs of the skull revealed a midline
calcified pineal shadow. This case was looked upon as a typical pinealoma, and
removal was advised.
 
Operation. — On 21st March, under avertin and local anaesthesia, a large
 
right occipito-parietal osteoplastic flap
was turned down, the lateral ventricle
tapped, and the dura mater opened.
Bleeding was reduced to a minimum by
the application of silver clips and the
use of the diathermy knife. The falx
was exposed and the inferior longitudinal
sinus severed between the clips. The
inferior border of the falx was divided
to the extent of half an inch. The
splenium of the corpus callosum was
split with a curved diathermy knife and
a large pineal tumour exposed. Large
FlG „ 308.— Case 5. Actual Size vdns could be seen surroun di ng the
of Pineal Tumour after Removal. .... . , °
 
tumour. An incision into the tumour
 
was made with the diathermy knife, and a definite capsule appeared to cover
the tumour. With a curved dissector the tumour was shelled out of its capsule.
The bleeding, which was not great, was controlled by the use of diathermy.
The retracted cerebral hemisphere was replaced and covered by dura mater.
A small piece of corrugated rubber tubing was inserted into the region of the
tumour and brought out through the upper part of the wound. The bone flap
itself was removed, as it was thought that as the capsule had been left behind it
would be advisable to give a course of X-ray treatment later. The patient stood
the operation very well.
 
The following day the right ventricle was tapped and 30 c.c. of blood-stained
cerebrospinal fluid were withdrawn. The drainage tube was removed after
forty-eight hours. The fifth day following operation lumbar puncture was
performed — the fluid was under slight pressure and blood-stained. From this
day recovery was uneventful, and the patient left hospital a month after the
operation.
 
The tumour was about the size of a plum (Fig. 308) and was quite hard in
consistency. Histologically the tumour was a typical pinealoma.
 
 
 
 
CLINICAL CASES 459
 
Subsequent History. — At the end of May, 1932, the patient was given a course
of X-ray treatment ; he seemed very well, and was able to go back to his office
in September, 1932 ; he was able to walk quite well. There was no papilledema,
but still some lateral nystagmus to the right. The patient had a bad attack of
influenza in December, 1932, which was followed by pneumonia which proved
fatal in four days. Every effort was made to obtain an autopsy, but this was
refused by the relatives.
 
Case 6. — Harry F., aged 27, was admitted to hospital on 5th February,
r 935j complaining of headaches. The duration of the present headache was
about three weeks, but he had had a similar bout of headaches one year previously. The headaches were mostly occipital, but sometimes were on top of
the head, mostly on the right side. They lasted for a quarter of an hour, and
were worse in the morning. On two occasions he had vomited in the last three
weeks, and frequently was nauseated without vomiting. He had double vision
for moderately distant objects, which was getting worse. Movement of the
eyes was painful. He suffered from giddiness two or three times a week,
mostly when standing. There was no tendency to fall to one side more than
to the other. There was no deafness, no noises in the head, no loss of power
in any part of the body, and no unconscious attacks. There was no difficulty
in speech, but he experienced difficulty in swallowing. There was no urinary
trouble. He sometimes had numbness at the back of the head, but did not
suffer from pins-and-needles in the extremities.
 
There was no previous history of ear trouble or of trauma. The patient
had fainted once five years ago, and had had Vincent's angina three years ago.
 
On Examination. — On examining the fundi on 12th February, 1935, the
edge of the left disc was less distinct than that of the right. Papilloedema
on the left side was in sharp contrast to a lesser amount on the right. The
veins in both fundi were distinctly enlarged.
 
On 19th February a stereoscopic X-ray examination of the skull showed a
small rounded shadow of calcified pineal, a linear shadow situated at a certain
distance from the rounded shadow and quite close to the right temporal bone.
 
On 24th February examination of the fields showed no abnormality. The
patient continued to complain of severe headaches, and diplopia was still
present.
 
Operation. — Ventriculography was performed on 7th March. Both lateral
ventricles were very dilated (Fig. 309). The patient was given avertin
anaesthesia with gas, oxygen, and ether. A large flap was turned down over
the right occipito-parietal region. The dura was quite tense, and the lateral
ventricle was therefore tapped and some 80 c.c. of fluid withdrawn. The dura
mater was then incised and the occipital pole of the brain was retracted outwards. The inferior border of the falx was now incised after having clipped
the inferior sagittal sinus by means of silver clips. The splenium of the corpus
callosum was pushed upwards by the underlying tumour ; the splenium was
cut through with a knife and the tumour exposed. It was a vascular tumour
and a portion was removed with punch forceps. It was considered impossible
to remove the tumour owing to the great vascularity, and therefore the occipital
pole of the brain was replaced and the dura held together by three interrupted
sutures ; the bone flap was removed and the scalp united by a double row of
 
 
 
460 THE PINEAL ORGAN
 
interrupted sutures. The patient stood the operation very well, and after three
weeks deep X-ray therapy was given through the defect in the skull made by
removal of the bone flap.
 
The portion of tissue removed showed a typical pineal tumour, with plenty
of large cells (Fig. 310).
 
 
 
 
Fig. 309. — Radiograph after Ventriculography, showing Dilated
Lateral Ventricle.
 
Subsequent progress. — The patient was discharged from hospital two months
later, but the stigmata of the pineal tumour, due to pressure on the corpora
quadrigemina, still persisted.
 
The patient was admitted on 19th October, 1935, for a second course of
deep X-ray therapy ; but this did not have a very beneficial effect, and the
 
 
 
 
 
 
 
 
 
 
Fig. 310. — Case 6. Histological Appearance of Pineal
Tumour ( ■ 32).
 
patient left hospital very little improved by this treatment. We were informed
that he died a month afterwards at his home, no autopsy being obtained.
 
Case 7. — Herbert O., aged 23, was admitted to hospital on 4th March, 1935,
complaining of double vision, which was first noticed some six weeks prior to
admission. The onset had been gradual and seemed to follow a series of head
 
 
CLINICAL CASES 461
 
aches. The patient blamed his left eye, as he said the false image was to the
left of the real one. There had been no vomiting or blurring of vision. His
speech was normal and memory good. He had had no fits.
 
On Examination. — The pupils were equal and reacted to light. There was
absence of accommodation and of the upward and downward movements of
the eyes. There was some slight ptosis of the left eye and some rotary nystagmus.
 
The cranial nerves appeared normal, with the exception of some weakness
of the right Vllth, IXth, and Xllth. There was no sensory loss in the arms,
but some slight intention tremor. Reflexes were increased in the arms, but
were equal on the two sides. There was no weakness of the legs and no sensory
loss. Knee and ankle-jerks were brisk and the plantars were extensor in type.
There was bilateral papilloedema — right three diopters, left four diopters.
 
 
 
 
Fig. 311. — Case 7.
 
 
 
Photograph of Brain, showing Position of Pineal
 
Tumour.
 
 
 
Lumbar puncture gave a clear, colourless fluid with a pressure of 270 mm.
Cells . . . . . . . . . . 10 per c.mm.
 
 
 
Protein
 
Chlorides
 
Globulin test
 
Sugar
 
Culture
 
Wassermann reaction
 
 
 
50 mg. per 100 c.c.
 
710 mg. per 100 c.c.
 
Negative
 
Within normal limits
 
Sterile
 
Negative
 
 
 
A radiograph of the skull was normal except for some erosion of the posterior
clinoid processes. The visual fields were normal.
 
The patient gradually became comatose and paralysed down the right
side of the body, and died on 10th March, 1935, some six days after his admission, without any operation being contemplated.
 
 
 
462 THE PINEAL ORGAN
 
Post- Mortem Examination. — At autopsy there was bilateral pulmonary
collapse and enlargement of the heart. A very large tumour was found in the
pineal region (Fig. 311). The photograph reveals the right half of the brain,
showing a tumour 2-J- in. in diameter occupying almost the whole of the third
ventricle, and extending forwards to the anterior commissure and below to the
tuber cinereum. The tumour is infiltrating the superior corpora quadrigemina
 
 
 
 
Fig. 312. — Case 7. Low-power Picture of Histological Section of the
 
Pineal Tumour.
 
 
 
 
 
 
 
 
Fig. 313. — Case 7. High-power Picture of Histological Section of the
 
Pineal Tumour.
 
and the midbrain, extending to the interpeduncular space and the upper border
of the pons. The point of origin of the tumour is not obvious, but from the
mode of extension forwards into the third ventricle, and the direction of infiltra
 
 
CLINICAL CASES 463
 
tion downwards and forwards into the midbrain, it would seem that the tumour
arose in the pineal gland, which is no longer distinguishable.
 
Histology. — Sections show a cellular tumour intersected by numerous
capillaries. Some areas show the characteristic carrot-shaped cells arranged
in circles, with their long, protoplasmic processes forming a fibrillary network
in the centre (pseudo-rosettes) (Figs. 312, 313).
 
Case 8. — Henry B., aged 11, came under observation on 4th July, 1935,
with a history of more or less constant headaches for two years. However, he
was free for some weeks at a time. A week prior to admission he had repeated
vomiting attacks which could not be stopped with any kind of treatment.
 
On Examination. — He was a well-built and well-nourished boy, and quite
intelligent. He complained of double vision and inability to look upwards
beyond the horizontal plane. The pupils did not react to light, but reacted
quite well to accommodation. The visual fields were normal. There was slight
weakness of the right external rectus. There was bilateral papilledema, more
marked on the right side. The rest of the cranial nerves appeared normal.
There was no loss of sensation in the body and the deep reflexes were normal.
The cerebrospinal fluid was under tension, the manometric reading being 250.
The fluid was clear and colourless and did not contain any abnormal constituents.
 
A radiograph of the skull (Fig. 314) revealed definite hammer markings
owing to the increased intracranial pressure. The Wassermann reaction in
the blood and cerebrospinal fluid was negative.
 
Four days after admission the patient was found to develop skew deviation
of the eyes on looking at objects in front of him, and the double vision became
constant.
 
Operation. — A ventricular puncture was performed and 100 c.c. of air
injected into the lateral ventricle. Ventriculography revealed bilateral dilatation of the lateral ventricles. A diagnosis of pineal tumour was made, and a
large osteoplastic flap was turned down over the right occipito-parietal region.
The lateral ventricle was tapped and the occipital pole of the brain retracted
outwards through the opening in the skull. The splenium was cut through
revealing a large pineal tumour. A portion was removed for examination and
the operation was terminated. The general condition of the patient improved
somewhat and the wound healed well.
 
The microscopical examination revealed an undifferentiated form of
pinealoma (Fig. 315).
 
Subsequent Progress. — After three weeks, deep X-ray therapy was given to
the pineal region through three ports of entry, some nine treatments being given,
and the boy was discharged on 1st September with very slight papillcedema
and slight ataxia. On writing to the patient three months later from the followup department it was found that the boy had died in his sleep six weeks after
leaving hospital and no post-mortem examination was held.
 
Case 9. — The specimen was obtained from a brain supplied to the Anatomy
Department of King's College, London. No history of the case was available.
A median longitudinal section of the brain showed a cyst which occupied the
centre of the pineal body and compressed the quadrigeminal plate of the midbrain. The aqueductus cerebri was also compressed, but it was not completely
 
 
 
464 THE PINEAL ORGAN
 
obstructed, and there was no marked distension of the third or lateral ventricles
(Fig. 316). The pia mater around the pineal body and neighbouring parts was
considerably thickened.
 
The pineal cyst was removed for microscopical examination and serial
longitudinal sagittal sections were cut and stained with hematoxylin and eosin
and with picro-indigo-carmine.
 
These showed that the cavity of the cyst was formed by the breaking down
of the central part of the pineal body. Its wall showed, in a modified form,
the structure of the pineal gland (Fig. 317, A). There was a pseudo-epithelial
stratum lining the cavity, the tissue immediately bounding the lumen being
fibrillar and glial in nature. A middle zone, which formed the major part of
 
 
 
 
Fig. 314. — Case 8. Radiograph
demonstrating hammer marking owing to the increased
Intracranial Pressure due to
a Pineal Tumour.
 
 
 
Fig. 315. — Case 8. Histological
Picture showing Appearance of
a Pineal Tumour ( 320).
 
 
 
the thickness of the cyst wall, showed typical parenchymatous pineal cells.
These were of small size, but had relatively large nuclei ; they were imbedded
in a loose glial network, which forms the supporting tissue throughout the whole
thickness of the cyst wall.
 
There were some irregular plaques of calcareous deposit in the wall of the
cyst, and corpora arenacea were abundant in the surrounding membranes,
but were not present in the actual wall of the cyst.
 
Lying dorsal to the pineal body was a tubular diverticulum of the ependyma,
which extended the whole length of the pineal body (Fig. 318). It opened
into the third ventricle at the suprapineal recess, and contained groups of
choroidal villi, which projected into its lumen (Fig. 317, B). This represents
the persistent dorsal sac which is present in foetal life, and is formed as a tubular
outgrowth from the roof of the posterior part of the third ventricle. It would
probably have contributed to the secretion of the cerebrospinal fluid. Should
its opening have become blocked, it might have given rise to a thin-walled
cyst, which would have differed from the pineal cyst described above in having
 
 
 
CLINICAL CASES
 
 
 
465
 
 
 
 
Fig. 316. — Mesial Section of the Brain, showing Large Pineal Cyst lying
between the splenium of the corpus callosum and the corpora
Quadrigemina.
 
 
 
t»
 
 
 
 
 
 
Ca.
 
 
 
Gli.
 
 
 
 
 
C.V.
 
 
 
Fig. 317. — Case 9.
 
 
 
A — Section through the wall of the pineal cyst shown in Fig. 316. The lumen
of the cyst lies below ; it is lined by a layer of condensed glial tissue, no
ependymal epithelium being visible. The middle zone is formed of a
degenerate tissue containing few parenchyma cells and showing numerous
spaces. In the upper part of the section is the fibrous capsule.
 
Gli : glial tissue. Gl. st. : glial stratum. Lum. : lumen.
 
B — Portion of the wall of the dorsal diverticulum or suprapineal recess which
lay above the pineal cyst. It shows sections of corpora arenacea and choroidal
villi.
 
Ca. : corpus arenaceum. Cv. : choroidal villi.
 
a wall lined with ependymal epithelium, and most probably containing tufts
of choroidal villi projecting into its lumen.
 
Pineal cysts lined by ependyma also occur, and vary in size from small
microscopic cysts such as that shown in Fig. 304, in which the lining
30
 
 
 
466 THE PINEAL ORGAN
 
epithelium is columnar in type, to larger cysts which are formed, as is
indicated by septa projecting into the lumen, by the coalescence of adjacent
smaller cysts. The lining membrane in the larger cysts, found in old
 
 
 
 
Fig. 318. — Case 9. Drawing of a Longitudinal Section of the Pineal Cyst,
and the Suprapineal Recess above it, D.D. (R. J. G.)
 
A. : anterior end. P. cyst. : lumen of the pineal cyst.
 
C.V. : choroidal villi projecting into P. : posterior end.
the lumen of the diverticulum.
 
 
 
subjects, is formed by flattened cells which have been described as
" pseudo-ependymal." Whether these cells are responsible for the
secretion of the fluid which fills the cyst or whether this fluid is derived
from the vessels supplying the gland appears to be undetermined. 1
 
1 Further information on the development and nature of pineal cysts will be found in
an article by Eugenia R. A. Cooper in the J. Anat., 67, 1932-3, p. 28.
 
 
 
CHAPTER 33
 
GENERAL CONCLUSIONS
 
The surgery of the pineal organ, although yet in its infancy, may be said
to be advancing rapidly owing to the fact that neurological diagnosis
becomes more established and more accurate each year.
 
The symptomatology tends to be more definite : there is usually a
severe degree of raised intracranial pressure, associated with headache,
vomiting, papilledema, epileptiform fits, and some cranial nerve paralysis.
The eye signs are definite, with loss of pupillary reaction and failure of
upward movement of the eyes.
 
Operations for the removal of pineal tumours have become standardized ; and even if the complete removal cannot be undertaken, a postoperative course of deep X-ray therapy will complete the cure, as the
majority of pineal tumours are radio-sensitive.
 
Morphology
 
1. The pineal system, including the parietal eye, its nerves, and the
related cerebral ganglia is one of the most ancient sensory systems of
the vertebrate phylum. The existence of a parietal sense-organ being
plainly indicated in certain of the primitive ostracoderm fishes by the
presence of a pineal plate, showing either a complete pineal canal or a
pineal pit on the inner surface of the plate. The canal and plate are well
seen in the examples of Anaspida and Cephalaspida, which are found in
strata ranging from the lower Silurian 1 to the Devonian eras and in specimens of Pterichthys and Bothriolepis belonging to the Order Antiarchi,
found in upper Devonian strata.
 
2. In these fishes there is definite evidence that the parietal eye
coexisted with other sensory organs of the head, namely : the lateral
eyes, the olfactory organs, and the vestibular or static organs ; and also
that these had approximately the same relative positions to each other
and the parietal foramen or pit that they have in the heads of living
cyclostomes and other vertebrates.
 
3. The closure of the outer or superficial end of the parietal canal by
a thin plate of bone in certain examples indicates that in these specimens
 
1 The Silurian Epoch has been estimated by Barrell to embrace a period from
390,000,000 to 460,000,000 years ago.
 
467
 
 
 
468 THE PINEAL ORGAN
 
regression of the organ had already commenced, and that it had ceased
to function as a visual organ.
 
4. In some palaeozoic fishes, e.g. Pholidosteus, Rhinosteus, and
Titanichthys, bilateral pineal impressions are visible, either (a) on the
dorsal or outer aspect of the pineal plate, or (b) on its inner or intracranial
surface. Moreover, evidence of the bilateral nature of the pineal system
is also present in existing species. Thus in some species in which two
separate parietal eyes are present, e.g. Petromyzon or Geotria, each eye
is connected by its own nerve with the habenular ganglion of the same side ;
and when the two parietal organs differ in size there is a corresponding
difference in size of the habenular ganglion and also of the fasciculus
retroflexus of Meynert of the two sides.
 
5. In those animals in which there is normally only one parietal
sense-organ or an unpaired epiphysis, the normal connections of the
basal part of the stalk of the parietal organ or of the epiphysis with the
right and left habenular ganglia and posterior commissure are bilateral.
Moreover, the occasional occurrence of accessory parietal sense-organs
and indications of coalescence of two retinal placodes, or of two lenses
in a single eye, may also be regarded as evidence pointing to a primary
bilateral origin of the system. Bifurcation of a single pineal stalk into
two terminal vesicles has also been observed as a variation in different
classes of vertebrates, more particularly in fishes (Cattie) ; in amphibia
(Cameron) ; in reptiles (Spencer, Klinckowstroem) ; in birds, e.g.
Emys europea (Nowikoff ) ; and among mammals several instances in
human embryos.
 
6. The development of two separate pineal diverticula, in the median
plane and in the interval between the habenular commissure and the
posterior commissure, seems to be a rare occurrence, although two
terminal vesicles which have arisen from a common stalk may lie one
behind the other. If one parietal vesicle only is developed and it is later
cut off from its stalk of origin, the latter is usually displaced backwards
so that the epiphysis lies behind the parietal eye. Apart from the paraphysis, which originates anterior to the velum transversum, diverticula
arising from the roof of the third ventricle in front of the habenular
commissure are developed from the dorsal sac or postvelar arch, and give
rise to the suprapineal recess or are an outgrowth from the choroid plexus.
Neither the paraphysis nor diverticula originating from the postvelar
arch are epiphyseal in nature.
 
7. The parietal eye, which seems to have attained its maximum
development in certain extinct amphibia, reptiles, and mammal-like
reptiles, and the epiphysis or pineal body usually show signs of regression
in specimens of mature living species. The most important of these
 
 
 
GENERAL CONCLUSIONS 469
 
indications are : (1) the frequent absence or disappearance during the
later stages of development of the nerve or nerves connecting the parietal
eye or epiphysis with the central nervous system ; (2) excessive development of pigment in or around the retinal cells, or development of pigment
in the lens or cornea ; (3) degeneration of the retinal epithelium of the
parietal organ ; in the epiphysis of anamniota degeneration of the lining
epithelium of the pineal stalk ; or in the pineal organ of adult birds,
degeneration of the epithelium lining the follicles, accompanied in some
cases by obliteration of the lumen of the follicles ; and in the pineal organ
of adult mammals frequent degeneration of the parenchyma cells. The
degree of degeneration of the parenchyma cells in adult mammals varies
both in different individuals and in different parts of the organ in the same
individual. In the latter case it is common to find areas in which the
parenchyma cells have disappeared altogether and been replaced by
neuroglial plaques or bands. These often break down in the centre to
form cysts, and deposits of calcareous salts are frequently seen in the
walls of the cysts or in the trabecular or capsule. See Figs. 221, A, B, C,
2 %5> 317? and 318.
 
8. In addition to the evidence in some extinct and living vertebrates
of a single pair of pineal organs which are united, either partially in the
stem of a Y-shaped organ bearing two terminal vesicles, or completely
fusion having taken place throughout the whole length of the stalk which
terminates in a single composite vesicle, there are indications, according
to certain authors, of the existence of two pairs of parietal organs arranged
serially, one pair lying in front of the other. Thus in the Palaeozoic fish
Bothriolepis (Fig. 319), Patten describes, in addition to the median eye
tubercle situated on the pineal plate between the two orbital cavities, a
pair of bilateral impressions which are visible only on the internal aspect,
and are present on the deep surface of the post-orbital plate (Fig. 320).
These he believed lodged a pair of posterior median or parietal eyes.
The three impressions or pits form a triangular group disposed in a
similar manner to the median eyes of many invertebrates, and, more
particularly, the triplacodal entomostracan eye which is found in certain
Branchiopods, e.g. Apus and Branchipus (Figs. 248, 250), and in the
" carp louse " Argulus foliaceus, which is typical of many other crustaceans. Another interpretation of the meaning of these two impressions
is given on p. 472 by Stensio, who suggests that they are produced by
the attachment of paired muscles of the lateral eyes. The existence and
exact position of two pairs of retinal placodes which will give rise to the
median eyes of vertebrates and which lie one in front of the other on each
side of the open medullary plate, has not, we believe, been definitely
established, nor is there agreement with respect to their exact position
 
 
 
470
 
 
 
THE PINEAL ORGAN
 
 
 
__^ „-n h op
 
~-~-p orb pi.
 
 
 
 
relative to the pair of placodes which give origin to the lateral eyes.
Thus, Patten assumes that two pairs of retinal placodes which become
incorporated in the roof of the third ventricle and give rise to the
parietal eyes of vertebrates lie in front of those for the lateral eyes in a
position which he describes as typical, in the development of Arachnids
(Figs. 257, 258, 259), whereas Locy in his account of two pairs of
 
p pi , n h " accessor y " or pineal eyes in
 
Acanthias, figures these as
lying behind the placodal pits,
which will develop into the
optic vesicles of the lateral eyes
(Fig. 143). Moreover, the
intermediate stages between
the first appearance of the
two pairs of rudiments for the
accessory eyes and the outgrowth of the pineal diverticulum in the later stages do not
appear to have been definitely
established by Locy. The
appearance, however, of symmetically arranged sensory
placodes or pigment spots
formed in series around the
margin of the medullary plate
(Figs. 257, 258, 259), or head
region (Fig. 19) in invertebrates suggests the possibility
that one pair of a series of
simple eyes being more
favourably placed for the reception of visual impressions
than the others — e.g. at the
 
 
 
 
Fig. 319. — Dorsal Aspect of Bothriolepis
canadensis, showing the nasohypophyseal
Opening, Lateral Orbits, Pineal and Postorbital Plate, and the Cephalic Appendages WHICH HAVE RECENTLY BEEN SHOWN TO
 
be True Pectoral Fins. (After Patten.)
 
n.h. op. : naso-hypophyseal opening.
 
orb. : orbital cavity.
 
p.f. : pectoral fin.
 
p. orb. pi. : postorbital plate.
 
p. pi. : pineal plate.
 
 
 
antero-lateral margins of the
head on each side — becomes more highly evolved than those in front of
or behind this pair The more favourably situated pair, it may be assumed,
gains the ascendancy over the others and becomes the principal pair,
whereas the less favourably situated ocelli retain their primitive simple
character and tend to degenerate. If this is the case, and if as is
commonly believed both the lateral and median eyes of vertebrates have
been evolved from the simple eyes of a lowly organized type of invertebrate, the discrepancy which exists with regard to the position of the
 
 
 
GENERAL CONCLUSIONS
 
 
 
471
 
 
 
median or accessory placodes relative to the optic pits for the lateral eyes
in vertebrates may be readily explained.
 
The presence of the two impressions on the deep aspect of the posteromedian plate of Bothriolepis described by Patten has recently (1929-1930)
been confirmed by Stensio, who gives an illustration (Fig. 321) of the
same two pits in Aster olepis, an allied genus. He suggests that the pits
are produced by the attachment of one or several of the recti muscles of
 
 
 
 
po
 
 
 
P''^W J><>V P ek
 
 
v pp
 
 
 
Fig. 320. — Dorsal Aspect of the Ocular and Olfactory Plates of Bothriolepis ENLARGED. (AFTER PATTEN.)
 
A part of the olfactory and rostral plates has been removed on the left in order
to expose the deeper-lying sclerotic plates. Between the lateral eyes is the quadrangular parietal plate, nearly perforated by a deep conical pit opening inward
and covered externally by a thin, lens-like tubercle, beneath which was the parietal
eye. On the deep aspect of the post-orbital (post median) plate are two similar
pits, which Patten believed were occupied by a pair of posterior parietal eyes.
 
 
 
a.s. pi. : anterior sclerotic plate.
le. : lateral ethmoid.
Is. pi. : lateral sclerotic plate.
me. : mesethmoid.
 
0. : corneal opening.
 
01. : site of primitive olfactory organ.
p.e.t. : parietal eye tubercle.
 
 
 
po. pi. : postorbital plate.
 
p.p. : position of paired pits on inner
 
aspect of po. pi.
p.s. pi. : posterior sclerotic plate.
r. : rostrum.
rs. : shelf plate on inner surface of
 
rostrum.
 
 
 
the lateral eye on each side ; a supposition which appears much more
probable than Patten's hypothesis ; more especially since the investigations of Stensio and others into the general anatomy of these fishes have
definitely proved that the cephalic appendages of Bothriolepis, Asterolepis
ornata, and allied genera — which were at one time thought to closely
resemble the cephalic appendages of the Merostomata, e.g. Eurypterus
— are true pectoral fins, consisting of two segments, each of which
contains inside the dermal bony exoskeleton, an axial cartilaginous
endoskeleton, which in Bothriolepis was provided with a perichondral layer
 
 
 
472
 
 
 
THE PINEAL ORGAN
 
 
 
 
of lime-bearing tissue, intermediate between true bone and calcified
cartilage. The endoskeleton in the specimen described did not
participate either in the axial articulation or in the articulation between
the two segments of the fin, since both these articulations were
formed solely by the dermal bones. In the proximal articulation the
inner ends of the dermal bones embraced the neck, of the processus
brachialis of the anterior ventro-lateral plate ; the opening in the dermal
bones of the appendage which surrounded the process is called the axial
foramen, and besides enclosing the head or condyle of the processus
brachialis transmitted vessels and nerves to the appendage. The intermediate position in a direct line of descent between fishes and the invertebrate Merostomata, which was claimed for the Antiarchi (Bothriolepis,
 
Pterichthys), is thus not confirmed by
recent work. This Order being now
considered to belong definitely to the
fishes, their appendages being true
pectoral fins and their resemblance to
the large paddle-like appendages of
the Merostomata (Eurypterus or
Pterygotus) being functional rather
than structural.
 
9. The theory that a higher race
of animals which was " predominant "
arose directly from a lower race in
the geological period which immediately preceded it, must, in the light
of modern knowledge, be radically modified, since it is evident that the
common ancestor of two highly differentiated and in many respects
divergent classes must have been of a much simpler type than either of
the two classes under consideration. Moreover, the divergence of the
two classes must have taken place long before dominance of one class
over the other could have existed as a factor in their evolution.
Certain points of similarity in particular organs or systems seem to
have been preserved in the two divergent classes, although even these
when critically examined are found to present modifications in detail ;
and the modifications or divergences are in general more pronounced
in the phylogenetically older races and in adult animals as compared with
their larval or embryonic stages. To take a concrete instance, the difference between the compound faceted eye of an arthropod and the inverted
eye of an adult vertebrate is very great, and since the upright faceted eyes
of certain arthropods were already highly evolved in some trilobites which
were living in the Upper Cambrian period and since median eye tubercles
have been found in both larval and adult specimens of Trinucleus and
 
 
 
Fig. 321. — Intracranial Surface
of postmedian plate of
asterolepis ornata. (after
Stensio.)
 
 
 
GENERAL CONCLUSIONS 473
 
other closely related forms of trilobites, it is evident that the distinction
between median eyes and lateral eyes had occurred at a very early date
and that the time required to produce the differentiation of the complex
faceted eyes must place the actual origin of the lateral eyes of arthropods
at a still earlier period.
 
The degree of differentiation of the lateral eyes of invertebrates varies
greatly in different classes, and the divergence from the simpler types is
greater in the adult animal than in the larva and in the more highly
organized types of animal than in the more primitive.
 
Now the earliest known fossil vertebrates, the ostracoderms, agree
with the invertebrate Eurypteridae in possessing both lateral and
median eyes, and they were contemporary with each other, living in
the sea under much the same conditions and in the same geological
period. Comparisons were therefore made between the ostracoderms
and the eurypterids, and between the living representatives of these
two extinct classes, the cyclostomes, which are the direct descendants
of the ostracoderms and certain of the more primitive types of
cartilaginous fishes on the one hand, and the land scorpions, spiders,
Limulus, and certain of the Crustacea on the other ; all of which
resemble each other in possessing lateral and median eyes in the same
relative positions with regard to each other and other organs in the
head.
 
It will be unnecessary to refer to more than two or three of the more
salient points which have recently been settled by a critical examination
of the alleged similarities between the ostracoderm fishes and the
eurypterids. One of these apparent similarities was the possession in
Cephalaspid fishes of an exoskeleton which seemed to closely resemble
the chitinous exoskeleton of eurypterids and Xiphosura. Now the
exoskeleton of the fishes, whether it consists of denticles, scales, scutes,
or " armour plating," consists of an outer layer of epidermal bone or of
enamel, which covers a dermal bony stratum, or osteodentine ; and it
will be recalled that in the development of a tooth the formation of the
enamel is at the inner or deep end of the enamel cells or ameloblasts ;
further, the increase in thickness of the enamel is by the laying down of
new layers on the superficial surface of those which have already been
deposited ; and also that the dentine which is formed on the surface of
the dermal papilla by the odontoblasts is layed down in the reverse direction to the enamel, namely, from without inwards, the increase in thickness
of the dentine being due to its formation at the outer or superficial ends
of the odontoblasts. The shields or plates forming the armour plating
of the ostracoderm fishes are of the nature of a vaso-dentine, and the
 
 
 
474 THE PINEAL ORGAN
 
rhombic scales on the posterior part of the body, in some examples, e.g.
Pteraspis (Fig. 322), were coated on their superficial aspect by an enamellike layer. In the formation of the chitinous exoskeleton of an arthropod,
however, there is a secretion of a cuticular nature from the outer ends of
the columnar hypoblast cells or deric epithelium, this becoming condensed
forms a hard chitinous shell on the surface of the hypoblast. The shell
thus consists of a thickened and hardened cuticle and differs both structurally and chemically from enamel and osteodentine. Chitin is a nitrogenous and carbohydrate substance allied in its composition to horn ;
it may be impregnated with lime salts, but no true Haversian systems,
such as those present in bone, are found in it. Increase in size of the
animal including its appendages is obtained by a series of moults (ectdyses)
in which the hardened cuticle undergoes softening and is cast off; the
 
 
 
 
Fig. 322. — Lateral Aspect of Pteraspis rostrata, an Ostracoderm Fish
characterized by the absence of pectoral or pelvic flns, a hypocercal
Tail, Large Plates or Scutes covering the Head and Anterior Part
of the Body, and Rhombic Scales covering the Remaining Part of the
Body and Tail.
 
The pineal plate is not perforated in P. rostrata, but in some specimens a
pit is present on its internal surface. In P. monmouthensis a complete perforation
is found. (E. Ivor White.)
 
growth of the animal taking place chiefly in the intervals between the
moults ; whereas the increase in size of vertebrates which possess an
exoskeleton is similar to that of the skull, a continuous process, taking
place partly along the lines of suture between the plates and in the case
of dermal bones which have sunk beneath the surface of the skin also
by deposit of new bone on the surface of the old, and absorption of bone
on the internal surface.
 
Another important distinction between the fishes and the palaeostracan
arthropods is the existence of median dorsal and caudal fins in the former,
as compared with the long, tapering caudal spine of the Xiphosura, as
well as the presence in some, e.g. Asterolepis, Remigolepis, Bothriolepis,
of a cartilaginous endoskeleton, having the structure of a true pectoral
fin inside the bony plates forming the exoskeleton. Finally the existence
of a notochord (Fig. 238, p. 341), and the vertebrate position of the heart
and main blood-vessels relative to the alimentary canal are fundamental
 
 
 
GENERAL CONCLUSIONS 475
 
differences which serve to place the ostracoderms definitely among the
fishes, and not, as was formerly supposed, in an intermediate position
within the direct line of descent of the vertebrates from a highly differentiated ancestral arthropod, such as Limulus, or a species resembling
any other of the living arachnids.
 
Summary of Observation on the Development and Structure of the
Human Pineal Organ
 
1. The pineal diverticulum first appears in human embryos of approximately 15 mm. length.
 
2. The apex of the diverticulum is primarily directed forwards.
 
3. The pineal outgrowth lies a short distance in front of the posterior
commissure, and sometimes presents a constriction subdividing it into
an anterior and posterior segment.
 
4. The whole thickness of the neural wall participates in the formation of the pineal evagination.
 
5. In some specimens there is an indication of the anterior segment
being subdivided into right and left lobes.
 
6. The " anterior lobe " first described by Krabbe appears in embryos
of about 22 mm. length as several neuro-epithelial buds which grow forward into the surrounding connective tissue.
 
7. A well-marked supra-pineal recess (dorsal sac) is present at the
22-mm. stage.
 
8. Transverse grooves, which are produced by folding of the roof
of the aqueductus cerebri in the region of the posterior commissure,
represent temporary infrapineal recesses.
 
9. Between the third and fourth months of foetal life there occurs
an active proliferation of cells derived from the inner or ependymal
zone of the pineal diverticulum. These grow outward in the form of
cords, the component cells of which are arranged radially round a central
axis which is destitute of nuclei. This is accompanied by a simultaneous
ingrowth of vascular processes of mesenchyme.
 
10. A special mass of proliferating cells growing from the anterior
wall of the main diverticulum gives rise to the solid anterior lobe of
Krabbe, whereas the cords which grow from the fundus of the diverticulum form the principal solid part of the posterior lobe. The cavities
at the base of the stalk and that of the posterior diverticulum appear to
open out, and their lumina thus become incorporated in the cavity of
the third ventricle, whereas the cavity of the main or anterior diverticulum,
which may be cut off as the " cavum pineale," usually disappears.
 
11. The neuro-epithelial cells give rise to (1) the glia lining the fibrous
capsule and covering the trabecular, (2) the parenchyma cells, and (3) the
 
 
 
476 THE PINEAL ORGAN
 
neuroglial cells (astrocytes). The surrounding connective tissue and
ingrowing vascular mesenchyme form the fibrous capsule and the connective tissue basis of the septa and finer trabecular, including the contained vessels. Many of the sinusoidal vessels in the central part of the
pale vascular areas, which are seen in the earlier stages of development,
disappear, leaving only a very fine capillary plexus in the parenchymatous
tissue of the lobules.
 
12. The parenchymatous tissue in the adult consists of a reticulum
of branched pineal cells, among which are a few neuroglial cells, chiefly
of the astrocyte type. The " alveolar " appearance which is sometimes
seen in adult specimens is due to the persistence of primary neuroepithelial cords, cross-sections of which appear as rosettes.
 
13. Cells and nerve-fibres belonging to the sympathetic system accompany the vessels entering and leaving the pineal organ ; and medullated
nerve-fibres connect the habenular and posterior commissures with the
parenchymatous tissue, but the exact mode of termination of their axons
with regard to the pineal cells is not certain. True ganglion cells belonging
to the central nervous system and having an axis cylinder process, although
described by some authors, appear to be very rarely seen in the human
pineal gland, but transitional forms exist, which are intermediate between
true nerve ceils and parenchymatous cells. These are described as
" neuronoid."
 
The experimental and clinical evidence with respect to function of
the mammalian pineal body is at the present time too conflicting to allow
of any definite conclusions being drawn. We know that before the age
of puberty, more especially in boys, pineal tumours have sometimes
been associated with premature growth in size of the body, precocious
development of the genital organs, and the early appearance of secondary
sexual characters. But it seems probable that certain other factors have
been involved in the production of these symptoms — more particularly
pressure, either direct or indirect, of the pineal tumour on neighbouring parts of the brain, such as the hypothalamus and pituitary
region, combined with the irritative reflex effects produced by increased intracranial tension — and that the symptoms are not directly
attributable to disturbance of any special function possessed by the
pineal body itself. Moreover, a considerable number of cases have
been reported in which sexual precocity and macrogenitosomia have
been present but there has been no pineal tumour, and the reverse
condition in which a pineal tumour has been present in young
boys but unaccompanied by the Pellizzi syndrome. Further, that
although some cases of premature development of the breasts in
girls and gynecomastia in males have been reported, these con
 
 
GENERAL CONCLUSIONS 477
 
ditions appear to have been absent in the majority of cases of pineal
tumour.
 
An accurate knowledge of the immediate anatomical relations of the
pineal body, is essential in order to clearly distinguish the symptoms due
to implication of neighbouring parts and those due to a supposed special
function of the pineal gland. Some of the structures in close relation
with the pineal body are : the aqueduct of Sylvius, the quadrigeminal
plate, the geniculate bodies, the nuclei and nerve tracts of the ventral
part of the midbrain, the thalamencephalon, the hypothalamus and
" portal system " of vessels supplying the pituitary gland, the cerebellum,
and the related intracranial nerves and blood-vessels. The mere enumeration of these parts which are liable to be involved in a growth of the pineal
body will indicate that when the pressure symptoms are eliminated from
the total " symptom complex " accompanying the growth of such tumours
there is little left in support of the contention that the human pineal gland
has a regulating influence on the normal development of the body and the
genital organs, and more especially in the direction of inhibiting or retarding their growth.
 
In Fig. 323 we have tried to show in a diagrammatic manner the
general distribution of the different types of median and lateral eyes in
the animal kingdom. We have not attempted to include in this scheme
any of the aberrant forms of eye such as those met with on the back of
the Chitons, or " coat-of-mail shells," or invertebrate eyes with inverted
retina; such as those on the back of Oncidium or at the edge of the mantle
in Pecten, since these are not specially concerned in the phylogeny of
either the paired median or paired lateral eyes of vertebrates, and although
of great interest in showing how special organs are sometimes evolved in
anomalous situations in adaption to special needs, they do not assist in
tracing the general evolution of the eyes of vertebrates. We hope that
the diagram will be of some assistance in showing graphically how very
far removed the more highly organized classes of living vertebrates are
from the highly organized living invertebrates ; and, although the form
and dimensions of the " tree " are not intended to accurately represent
the periods of time which have elapsed since the divergence of the various
classes took place in the course of evolution, that it will give some indication of the way in which certain of the simple types have persisted to the
present day without, it may be presumed, having undergone marked
modifications in general form and structure, while others have diverged
from the primary simple type, but have nevertheless retained some of
their older traits, which appear either in a simple form in the early larval
condition, or may be present in the adult, in a modified and highly differentiated form. We have limited the term " parietal eye " to the parietal
 
 
 
478 THE PINEAL ORGAN
 
sense-organ of vertebrates, and designated the median eyes of invertebrates as such, or as frontal, triplacodal, or entomostracan eyes. We do
not, however, wish it to be inferred that we consider the parietal senseorgan of vertebrates has arisen quite independently of the median eyes
 
 
 
EPIPHYSIS SHOWS EVIDENCE OF DEGENERATION
IN ADULT ANIMALS. PARIETAL EYE ABSENT
 
 
 
PARIETAL EYE WELL DEVELOPED
 
P NERVE ENDS IN R HABR GANGLION
 
IN L.VIVIR, PINEAL SAC LARGE
 
PARIETAL EYE WELL DEVELOPED P NERVE
 
ENDS IN L. HABR GANGLION: WALL OF
 
PINEAL SAC HIGHLY DIFFERENTIATED
 
PARIETAL FORAMEN LARGE
LARGE ORBITAL CAVITIES
 
 
 
Parietal foramen well
developed. paired lateral
orbital cavities.
 
 
 
EPIPHYSIS PRESENT
 
PARfETAL EYE ABSENT. TUBULAR
EPIPHYSIS WITH EXPANDED
TERMINAL VESICLE
 
 
 
PARIETAL EYES WELL
DEVELOPED. PAIRED
LATERAL EYES WITH
INVERTED RETINA AND
ECTODERMAL LENS
 
 
 
TORNARIA LARVAE ..HEMICHORDA
WITH EYE-SPOTS/ UROCHORDA
ON APICAL PLATE CEPHALOCHORDA J J
 
 
 
PAIRED MEDIAN EYES AND PAIRED LATERAL EYES
ARE SOMETIMES PRESENT, OF UPRIGHT TYPE
 
 
 
EXTINCT BRANCHES OF
NO TRACES ARE LEFT
 
 
 
 
EPIPHYSIS WELL DEVELOPED IN YOUNG
BIRDS FOLLICULAR EPITHELIUM DEGENERATES
IN OLDER BIRDS AND THE CAVITIES OF THE
FOLLICLES TEND TO BECOME OBLITERATED
PARIETAL EYE ABSENT
 
 
 
STALKED. LATERAL EYES, OF COMPOUND
AND HIGHLY DIFFERENTIATED, UPRIGHT
TYPE! ENTOMOSTRACAN OR TRIPLACODAL
M OF MEDIAN EYE
 
 
 
CYCLOSTOM
 
 
 
MEDIAN PAIRED EYES AND LATERAL
PAIRED EYES LENS SINGLE
RETINA UPRIGHT OR INVERTED
 
 
 
AN FRONTAL OCELLI AND
RAL FACETED EYES OF
ILE TYPE
 
 
 
simple uprighteyes
 
types of simple upright eyes,
lateral; dorsal; on edge of
mantle, having ectodermal
cellular lens & inverted
retina. highly differentiated
eyes in cephalopods.
 
 
 
TROCHOPHORE LARVAE WITH EYESPOTS ON APICAL PLATE
 
 
 
SIMPLE OCELLI OR PIGMENT SPOTS,
 
OF UNICELLULAR OR MULTICELLULAR TYPES.
 
 
 
Fig. 323. — Scheme indicating the General Distribution of Different
Types of Median and Lateral Eyes in the Animal Kingdom.
 
 
 
of invertebrates. Further, we have used the term " parietal eye " in the
singular although, as explained elsewhere, it may represent in some cases
one member of a pair of median eyes or in other cases be formed by the
fusion of the right and left members of a pair of primarily bilateral
organs.
 
 
 
EVOLUTION OF THE PARIETAL ORGAN
 
 
 
479
 
 
 
CLASSES OF ANIMALS E- OIFFERENT
SEQUENCE OF GEOLOGICAL PERIODS b ESTIMATED NUMBER OF YEARS TYPES OF EYE
 
 
 
iRY, PLEISTOCENE 6 PLEIOCENE
 
 
 
TERTIARYqliGOCENE & EOCENE —
 
 
 
GREAT MAMMALS
 
 
 
SECONDARY or MEZOZOIC
 
$5,000,000 TO 240,000,000
 
 
 
JURASSIC
 
155. OOO.OOO TO 195,000.000
 
 
 
TRIASSIC
 
190,000,000 TO 240,000,000
 
 
 
PE RM I AM
 
 
 
PRIMARY
 
or
 
PALEOZOIC
 
2/5,000,000 TO 700000 000
 
 
 
215. OOO, OOO TO 280, OOO, OOO
 
 
 
CARBONIFEROUS
 
2 SO OOO.OOO To 33U.OOOOOO
 
 
 
370, 000,000
 
DEVONIAN
 
360. OOO, OOO TO 420 OOO. OOO
 
 
 
SILURIAN
 
 
 
3 90.000 OOO TO 46OOOOO00
 
 
 
ORDOVICI AN
 
 
 
480,000,000 TO 590 OOO.OOO
 
 
 
CAMBRIAN
 
550,000 OOO TO 700,000,000
 
 
 
ARCHAEAN
 
 
 
MAMMALS
 
BIRDS
 
GREAT REPTILES
 
LARGE PARIETAL FORAMEN
or IMPRESSION IN SOME
REPTILES & AMPHIBIANS,
MAMMAL-LIKE REPTILES
LAST TRILOBITES
 
GREAT AMPHIBIA
 
 
 
LAND SCORPIONS
 
STEGOCEPHALIA
MAILED FISHES
 
 
 
MARINE SCORPIONS
 
EXISTENCE OF PAIREO-EYES OF
VERTEBRATES PRESUMED
 
FIRST FISHES & INSECTS
 
 
 
VERTEBRATES APPEAR
 
 
 
INDICATIONS OF
MEO'AIN &-LATERAL PAIRED-EYES
OF INVERTEBRATES
 
FIRST TRILOBITES
 
EXISTENCE OF PAIRED-EYES PRESUMEO
(WORMS. CRUSTACEANS. MOLLUSCS)
 
EVOLUTION OF PHOTO-RECEPTIVE ORGANS
 
INVERTEBRATES
 
 
 
Fig. 324 t — Geological Chart indicating the Order in which Organs Sensitive
to Light and various Types of Eye have been evolved, and also the
Estimated Age in which the Different Classes of Animals have been
found. (Modified from Scheme and Data published by Gaskell and

Latest revision as of 11:27, 7 August 2020

CHAPTER 25

THE HUMAN PINEAL ORGAN Development and Histogenesis

The stages in development of the derivatives of the primary ependymal elements of the brain and spinal cord, which we have described in Chapter 22, are of great importance in connection with the study of the structure of the fully developed pineal body. In the early phases of development it was shown by Cajal that the ependymal cells extend through the whole thickness of the wall of the neural tube, as is seen in Golgi preparations of the chick embryo at the third day of incubation. At a later stage, when the width of the neural tube has increased, there is a tendency for the central part or body of the cell, which contains the nucleus, to separate from its attachment to either the internal or the external limiting membrane, or it may lose its connection with both of these membranes. In the latter case the cell is said to be liberated, and it may form a branched neuroglial cell of the astrocyte or oligodendric type. In those cases in which the attachment of the inner end of the cell element to the internal limiting membrane is retained, the cell may develop into a definitive ependymal cell, lining either the central canal of the spinal cord or a ventricle of the brain (Fig. 261, a), whereas if the internal connection is lost (Fig. 261, c) and the cell body remains anchored to the external limiting membrane or to the glial membrane covering the pial sheath of vessels penetrating the substance of the brain or spinal cord, the cell may differentiate into a subpial astrocyte, e.g. the cells or fibres of Bergmann, in the molecular layer of the cerebellum, or into a fixed " vascular " astrocyte, as contrasted with the free unattached type, which appears to be connected by its processes with those of neighbouring astrocytes. Besides these three principal types, intermediate forms are frequent : thus, one large process of an astrocyte provided with an expanded foot-plate may preserve its attachment to the sheath of a vessel, while the other small branched processes appear in Golgi preparations to end in free extremities.

There is, however, a considerable amount of doubt as to whether the apparent continuity of the neuroglial cell-elements is a true uninterrupted connection of one glial cell with another, since many of the modern neurologists hold the view that both the glial cells and the nerve cells

381


382 THE PINEAL ORGAN

are independent units. The discussion of this interesting and fundamentally important problem presents many difficulties, and we do not propose to enter into the question here, since, apart from its general bearing on the structure of nervous tissue, it does not specially affect the study of the pineal organ ; for, whether the processes of the glial cells are merely in contact or are continuous with each other, there seems to be a functional continuity in the framework as far as support is concerned. At this point it will be necessary to refer to the view which was originally taken by His with respect to the origin of neuroglia cells and neuroblasts. He believed that the medullary plate is primarily formed



Fig. 261. — Transverse Section through the Spinal Cord of a Ten-day Chick Embryo, showing the Supporting Cells. (After Lenhossek, 1895O

a. : ependymal cell. c. : astroblast, or displaced epithelial

b. : supportive spongioblast. cells.

of undifferentiated cells which give rise to " germinal cells " and " spongioblasts." The former in his opinion gave rise to neuroblasts and ultimately to nerve cells, whereas the spongioblasts developed into the supporting neuroglial tissue and ependyma. The germinal cells or the cells next the internal limiting membrane which are undergoing mitosis give rise to two daughter cells, both of which, he thought, migrated outward through the spongioblasts into the mantle zone, where they could be distinguished by their large size and pale vesicular nucleus, and were spoken of as " neuroblasts." Schaper, in 1897, contended that the germinal cells gave origin to both neuroblasts and spongioblasts, and that the indifferent cells which resulted from their division were capable of


THE HUMAN PINEAL ORG AN— DEVELOPMENT 383

producing either neuroglia cells or nerve cells even after the outward migration of the indifferent cells from the internal limiting membrane had already occurred. Whether an actual migration of whole cells takes place or simply an outward movement of the nucleus along a protoplasmic strand which has grown out as a process from the body of the cell is a much debated question, but we are inclined to believe that the latter alternative is the correct interpretation of the changed position of the nuclei. The migration by amoeboid movements of microglial cells has, however, been definitely proved and recorded on cinematograph films.

It has been demonstrated by Cajal that at an early period of embryonic life the spongioblasts send out a process which on reaching the external limiting membrane expands into a conical swelling or foot-plate, while the inner end, retaining its attachment to the internal limiting membrane, develops one or more processes resembling cilia which project into the central canal or a ventricle of the brain (Fig. 223, Chap. 22, p. 322, and Fig. 261). The foot-plate at the outer end is in relation with the vessels of the pia mater outside the external limiting membrane, and it is believed that it serves to absorb material from the blood for the nourishment of the nerve tissue, for in the earlier stages of development the latter does not possess the rich blood supply which it has in late embryonic stages and in foetal life. In these later stages, when the central area of the nerve tissue has become vascularized, foot-plates are developed on those processes of the neuroglia cells which come into relation with the sheaths of ingrowing vessels (Fig. 220, p. 318), and it is said that with further evolution there is a tendency for the sub-pial expansions to disappear and eventually for the attachment of the inner end of the cell to the internal limiting membrane to be lost. Branched lateral processes from the body of the cell have in the meantime been developed, and eventually one or more thick processes of the cell which have become attached by a foot-plate to the sheath of a vessel constitute what are known as its vascular processes, while the others, namely, the dendritic processes, either end freely or communicate with similar processes of adjoining neuroglia cells. The foot-plates on the vascular processes of the neuroglia cells are somewhat like the club-shaped expansions of the parenchyma cells of the pineal body (Fig. 218, Chap. 22, p. 317), and it is possible that serving as points of attachment, the latter have the same function as the foot-plates, namely, that of absorbing nourishment from the blood circulating in the vessel to which the expansion is attached.

In both neuroglial and pineal parenchyma cells the terminal expansions are frequently conical or trumpet-shaped, but the expansions of the neuroglial processes more often have the form of flat oval plates applied to the surface of the vascular sheath (Fig. 262), whereas the ends of the


384 THE PINEAL ORGAN

processes of the pineal cells are more typically club-shaped and the cells

usually give off several processes each of which terminates in an expansion.

At a later period of foetal development, and especially at about the



Fig. 262. — Footplate of Neuroglial Cell attached to Sheath of Blood Vessel : Rabbit. (After Penfield.)

The drawing shows two rows of cells of the oligodendroglia type ; these are situated between myelinated fibres of the cerebral white matter. One large fibrous astrocyte is seen above two oligodendroglial cells. Gliosomes stained by the method of Del Rio-Hortega are seen in relation with the cell-bodies and processes of both types of cell.

time of birth, small cells with few and slender processes are developed between the medullated fibres of the white matter in the brain and spinal cord. These are termed oligodendrocytes, and their small round nuclei,


THE HUMAN PINEAL ORGAN — DEVELOPMENT 385

lying in rows between parallel nerve-fibres, have long been recognized in specimens stained with the ordinary nuclear dyes such as iron haematoxylin. The appearance of these small cells in rows between the nervefibres is strongly suggestive of multiplication by amitotic division, more especially as mitotic figures are not often seen at this stage of development and the nuclei frequently lie in pairs. It also seems possible that they represent a modified or immature form of astrocyte rather than a distinct type, the modification from the usual astrocyte form into the interfascicular type of cell found in the white matter being due to the presence of the medullated white fibres, which limit the expansion and formation of processes in certain directions. The existence of transitional forms between the oligodendrocytes and the astrocytes among the cells in the aforementioned rows is an additional point in favour of this interpretation. Oligodendrocytes are also found in relation with large nerve-cells, such as those in the anterior cornua of the spinal cord and the pyramidal cells of the cortex cerebri (Fig. 263). These are often spoken of as satellite cells or perineuronal cells, whereas the oligodendrocytes found between the medullated nerve-fibres of the white matter in the brain and spinal cord are known as interfascicular cells. The small round granules lying in or on the processes of both types of oligodendrocyte which are termed gliosomes are believed to be concerned in the formation of the myelin sheath of nerve-fibres, and the relation of the perineuronal and interfascicular oligodendrocytes to the nerve cells and nerve-fibres suggests an homology of the oligodendrocytes of the central nervous system with the ganglionic capsular cells and the cells of the sheath of Schwann in the peripheral nervous system. The small branched cells with acidophil granules which are found in relation with the parenchyma cells of the pineal body possibly represent oligodendrocytes in this organ.

The mode of development of neuroglial fibres and the question of the existence of an intercellular substance we shall discuss later in the description of the structure of the normal pineal organ and the changes which it undergoes in disease or as a result of involution, but, as we have thought it advantageous to allude to some of the characteristic features of neuroglial tissue in the central nervous system before entering on the description of the pineal organ itself, so also we think that it will be profitable to discuss now the structure and some of the principal modifications of the normal ependyma of the brain and spinal cord, and the changes which it undergoes in disease or as a result of degeneration.

In the fully developed pineal organ the definitive ependyma is limited to the cells lining the pineal recess, but under certain conditions remnants of the original ependymal lining of the primary cavity of the pineal diverticulum or of its secondary outgrowths may persist as the lining

25 X^^l


386


THE PINEAL ORGAN



Fig. 263.

A — Oligodendrocytes in relation with pyramidal cell of cerebral cortex : human. B — Microglial cell, in relation with nerve-cell of grey matter. C — Fibrous astrocyte, showing perivascular feet and gliosomes. D — Protoplasmic astrocyte, also showing perivascular expansions and gliosomes.

F. As. : fibrous astrocyte. OL., OL.D. : oligodendrocytes.

Gl. : gliosome. P. As. : protoplasmic astrocyte.

M. Gl. : microglial cell (mesoglia). P.V. Exp. : perivascular expansion.

N.C. : nerve cell. Sp. : spines.

(After Penfield and Cone, redrawn from Cowdry's Special Cytology.)


THE HUMAN PINEAL ORGAN — DEVELOPMENT 387

membrane of one type of pineal cyst, and it seems possible that even after the full development of the organ has been attained and all traces of the original cavity have disappeared, certain cells which resemble the embryonic spongioblasts or primary ependymal cells retain the power of differentiating into either ependyma or neuroglia. This supposition may also apply to the development of ependymal cells lining the cavities in certain cases of syringomyelia, but when epithelium is found lining cysts in the pineal body or the cavities in the grey matter of the spinal cord it is usually of an irregular type — pseudo-ependymal — and the typical ependyma of the tall columnar form is seldom seen. The variations which occur in the normal ependyma and choroidal epithelium of the ventricles and central canal of the spinal cord are very considerable. These changes in the structure and form of the epithelium are related to varying mechanical and other conditions which are present in different parts of the brain and spinal cord. Thus the lining epithelium may be modified in one situation to form a sensory epithelium, e.g. the retina of the lateral eyes, and in another to form a secretory organ, as in the choroidal epithelium of the ventricles ; and since ependyma enters largely into the composition of the pineal organ as a whole, we propose to give a short summary of the morphology and functions of the ependyma in general, with the view of gaining a better insight into the structure and possible functions of this tissue as it occurs in the epiphysis of mammals. The morphology of the ependyma has been specially studied by Agduhr and Studnicka, and the following brief note is largely based on Agduhr's account of the ependyma in Penfield's Cytology of the Nervous System.

The ependyma is seen in its simplest form in the central nervous system of Amphioxus and of cyclostomes, in which the supporting tissue of the central nervous system is said to be wholly epithelial throughout life. The term " ependyma," as usually understood, is applied to the epithelial lining of the ventricular cavities of the brain and central canal of the spinal cord, but in the embryonic condition in all vertebrates, before the development of nerve cells and nerve-fibres, it extends through the whole thickness of the wall of the neural tube and takes part in the formation of the internal and external limiting membranes. Later, when the differentiation of this wall into zones has taken place, the term " ependyma " is often applied to the inner zone, which consists of several layers of spongioblasts, or " primary ependymal cells." This inner zone at a later stage is seen to be further differentiated into the definitive ependyma, glioblasts or astroblasts, and neuroblasts. Still later, the supporting function of the neuroglial tissue is supplemented by the ingrowth of vessels with their connective tissue sheaths.


388 THE PINEAL ORGAN

From the morphological standpoint it must be remembered also that the lining membrane of outgrowths from the cerebral vesicles is homologous with the ependyma, and thus the epithelial lining of the following parts is ependymal in origin : the olfactory lobes ; the optic vesicles, including the pigment and sensory layers of the retina ; the infundibulum of the hypophysis ; the choroidal epithelium ; the paraphysis ; the epiphysis and the subcommissural organ ; also the lamina terminalis and the roof and floor-plates of the brain and spinal cord. The shape, the structure, and the function of the ependymal cells in these different situations varies. Thus the cells may be flattened, cubical, or columnar in form. They may be club-shaped, flask-shaped, or bottleshaped. They may be specialized in form, as in the hexagonal pigment cells, or rod and cone cells of the retina ; they may be glandular in type, as in the choroidal epithelium or in the paraphysis. They are, in some situations, devoid of cilia, in others they possess well-defined cilia, having minute rod-like particles or blepharoplasts at their bases, and their free ends converging to a point from the wide basal or ventricular end of the cell. The cells may be close together or separated by an interval. The basal ends of the cells may be joined by intercellular bridges so as to form an internal limiting membrane or separated so that the spaces between the cells open into the ventricular cavities or central canal of the spinal cord.

Large intra- and inter-ependymal nerve cells have been demonstrated by Agduhr (1922) in the ependyma lining the central canal of the spinal cord in the human subject and in various mammalian animals. These cells frequently end in a club-shaped process which projects into the central canal and resembles the club-shaped projections of the sensory cells described by Dendy and Studnicka in the parietal organ of cyclostomes and fishes. These cells have been beautifully demonstrated by the Nissl method of staining, and Agduhr has shown connections (synapses) between peripheral processes of intra-ependymal cells and the processes of cells lying in the nerve substance external to the ependyma.

The Functions of the Ependyma

These may be enumerated in the following order : Generative. Supporting.

Lining membrane for protection and limitation of the nerve-tissues. Causation of currents in the cerebrospinal fluid by means of its

cilia. A membrane concerned in dialysis and filtration, or serving as a

limiting barrier.


THE FUNCTIONS OF THE EPENDYMA 389

Secretory.

Pigment formation.

Special sense.

Receptive cells concerned in reflex mechanisms. The generative capacity has already been referred to in connection with the differentiation from it of spongioblasts, neuroblasts, and the definitive ependyma, as has also the supportive character of the early ependymal elements. The limiting function of the definitive ependymal layer is, moreover, obvious, and the supposed action of the cilia in producing movement of the cerebrospinal fluid is well known. The special problems concerning dialysis, filtration, and the formation of a barrier to the passage of certain fluids or substances, whether normal or extraneous, into the cerebrospinal fluid are familiar to neurologists.

The secretory function of the modified ependymal epithelium which covers the choroidal plexuses is well established, and is definitely proved by inferences made in cases of obstruction to the outflow of cerebrospinal fluid from the ventricles and by direct observation of secretion of the fluid on the surface of the choroid plexus — in the human subject by Mott and Cushing, and in animals by Dandy and Blackfan. It is generally thought that the ependyma in other situations has a limited power of secretion of cerebrospinal fluid, but normally only to a very small extent. The question of the power of the ependymal cells to absorb cerebrospinal fluid has been studied by Nahagas and others. According to Nanagas a very small amount of cerebrospinal fluid may be absorbed through the ependyma lining the ventricles of the brain in normal animals (kittens), and evidence obtained from post-mortem examinations shows that obliteration of the lumen of the central canal of the spinal cord, which sometimes occurs in old age, is not followed by distension of the cana below the obstruction.

We have already considered the formation of pigment in the outer layer of the retina, in nerve tissues, and in the epidermis, and it will thus be only necessary to recall its frequent presence in the parenchyma cells and fibro-glial tissue of the pineal body : a condition which may be partly due to degenerative changes setting in at an early age, before degeneration has commenced in the nerve tissues as a whole, either as a result of disease or old age ; or it may in part be due to an hereditary trait, which has been preserved from the remote period when it may be inferred pigment was normally present in large quantity in the parietal sense-organ of our reptilian ancestors.

The possible function of the ependyma as a sensory layer containing receptive nerve-cells which are concerned in reflex action is strikingly suggested by Agduhr's demonstration of nerve cells in the ependyma


390 THE PINEAL ORGAN

lining the central canal of the spinal cord and brain stem in animals and the human subject. The existence of nerve cells in the ependyma which are connected by their peripheral processes with nerve cells in the adjacent grey matter suggests that impulses originating in the ependyma may be transmitted to ganglion cells in the grey matter of the spinal cord or brain stem. Whether the impulses are transferred to the cortex of the brain and give rise to a conscious sensation or not, it seems quite possible and even probable that they may originate reflex actions.

The function of the subcommissural organ, which is developed as a thickening of the ependyma below the posterior commissure and inferior peduncle of the pineal body (Fig. 185, B, p. 261), is not known, nor is that of Reissner's fibre, which is developed in relation with the subcommissural organ (Fig. 134, p. 188).

Microglia

Any investigation into the structure and pathology of an organ such as the pineal body, which is derived as an outgrowth from the central nervous system would be incomplete without a reference to the nature and origin of microglia as it occurs in the cerebrospinal system generally. The microglia or mesoglia is sometimes alluded to as the " third element " in the composition of nervous tissue. This name was originally given by Cajal (1913) to a group of small non-nervous elements which were afterwards differentiated by the special staining methods of Del RioHortega into oligodendrocytes and microglia, the former neuroglial in nature, the latter mesodermal. Hortega accordingly proposed to restrict the application of the term " third element " to the microglia, and allocate the oligodendrocytes to the neuroglial constituents or " second element." Thus, of the three constituents of nerve tissue excluding the connective tissue and vessels, the " first element " comprises the nerve cells ; the " second element " the neuroglia, including both astrocytes and oligodendrocytes ; and the " third element " is represented by the microglia. The microglia cells are small branched elements with minute nuclei of irregular form which stain deeply by Nissl's method ; the ordinary nuclear dyes such as hematoxylin ; and the silver carbonate method of Del Rio-Hortega which also brings out clearly the cell-body and processes. The latter are irregular in form and size and are characterized by small thorn-like spines. The cells have phagocytic properties and are under certain conditions capable of amceboid movements. Thus, according to the descriptions of Hortega, during the migratory phase in the development of the microglia, throughout the nervous tissue, it consists of roundish cells with pseudopodia, the various shapes of which indicate the motility of the cells. " After this initial phase the cells become branched,


DEVELOPMENT OF MICROGLIA 391

and when they take up their positions in the tissue they have small dark nuclei, surrounded by scanty cytoplasm prolonged into two or more thin, wavy, branched processes beset with spines which end freely, that is, they are not anastomosed among themselves nor are they connected with the neuroglia elements." He also holds the view that in a broad sense the microglia of the central nervous system represents from the functional standpoint the reticulo-endothelium of mesodermal tissues. It has been known to fix certain colloids to phagocytose erythrocytes and cellular debris, and it is believed to be concerned in the elimination of substances resulting from metabolism and degeneration of nerve cells. Thus, it is found to participate actively in inflammatory and destructive processes involving the central nervous system, and as a result of the motility of the cells and their increase in size under pathological conditions they assume various forms, becoming rod-like, lamellar, or rounded in shape, and frequently contain fat granules.

Development of Microglia

The microglia, according to the description of Del Rio-Hortega, does not appear until the last period of embryonic life. In foetuses at term and in new-born animals it is abundant both beneath the pia mater and spreading inward along the course of the vessels of the brain and cerebellum. It is developed later than the neuroglia, at the time when the vessels of the pia mater have reached their full development. The cells which give rise to the microglia are believed to be mesodermal in origin and are first visible immediately beneath the pia mater on the surface of the brain and spinal cord ; they are found also in relation with the tela choroidea of the third ventricle below the corpus callosum and fornix, and also beneath the pia mater covering the white matter of the cerebral peduncles. It is also abundantly formed in connection with the vascular folds of the tela choroidea inferior and on the surface of the cerebellum.

Originating as a layer of rounded or flattened cells beneath the pia on the surface of the brain, the microglial cells afterwards develop pseudopodia and migrate deeply into the substance of the white and grey matter, and eventually they reach the ependyma lining the ventricles or central canal of the spinal cord.

The cells beneath the pia are at first rounded, cuboidal, or flattened ; they increase in size and develop irregular bulbous processes ; later, when they reach their ultimate destination, they become fixed and dendrites are formed, on which later the characteristic spines are developed. The cells are said by Hortega to lie in the neuroglia, and their processes do not communicate with each other.


392 THE PINEAL ORGAN

The nuclei in the early stages of development are easily visible in specimens stained with the ordinary nuclear dyes. They form two or three layers beneath the pia and resemble the nuclei of lymphocytes and proliferating endothelium, and in cases of injury or disease may be readily mistaken for these.

The microglia cells having attained their full development become " fixed " and are described as being in the resting condition. They are found throughout the nervous system in the grey and white matter, being, however, more abundant in the grey matter than in the white. It is probable that the normal number of cells is maintained during adult life by amitotic division of the nuclei, although mitotic figures have occasionally been seen (Del Rio-Hortega). Having reached their full development and entered the resting phase, in a fixed position, they may retrace their stages of development in reverse order ; the processes gradually thickening and becoming shorter, until they assume the form of pseudopodia, and the body becomes rounded. This process of devolution is seen in cases of injury to the brain, when the cells having assumed amoeboid characters, migrate towards the focus of inflammation, hsemorrhage, or degeneration and there act as phagocytes, engulfing leucocytes, erythrocytes, and broken-down nerve tissue. Their function is, therefore, similar to that of leucocytes and the cell-elements of the reticuloendothelium, and before the ordinary methods of staining were supplanted by the special methods of staining with silver carbonate, the appearances were interpreted as those of inflammation as it occurs elsewhere in the body generally and attended by the accumulation of leucocytes and proliferation of endothelium.

Relations of Microglia to Nerve-cells and Vessels

Microglial cells, like oligodendrocytes, are found as satellite cells of large neurones, such as the Purkinje cells of the cerebellar cortex. They may be associated either with the body of the cells or with its processes. They may be distinguished from oligodendrocytes by their small, deeply stained, and irregularly shaped nuclei and by the spines on their processes. Microglia cells are also found in relation with the adventitia of the vessels lying in the white or grey matter.

As might be expected, microglial cells are present in the retina and in the optic nerve, and they have been found in the fibrous plaques of the human pineal organ.

Retrieved from ‘https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:Book_-_The_Pineal_Organ_(1940)_25&oldid=417064’
Powered by MediaWiki