Talk:Book - The Pineal Organ (1940) 26

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

1. &&.

■

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