Most of the site will reflect the ongoing surgical activity of Prof. Munir Elias MD., PhD. with brief slides and weekly activity. For reference to the academic and theoretical part, you are welcome to visit
neurosurgery.tv
Neurosurgical Perspective
The pineal gland is at a site to which all surgical approaches are treacherous
and where mass lesions produce interesting clinical syndromes. It has an
extensive histopathology disproportionate to its diminutive size. Until fairly
recently, not much was known of the gland's significance, and there seemed to be
little reason for neurosurgeons to trouble themselves with attempting to
understand its physiology.
Zoologists and comparative anatomists had long postulated a photoreceptor
function for the pineal by analogy to phylogenetically lower species. It was not
until recent times, with the advent of radioimmunoassays that detect pineal
products and staining techniques that define the complex interconnections
between the organ and its near and distant neighbours, that the physiology and
clinical importance of the pineal were understood.
The emerging picture confirms many of the pineal's postulated functions but also
suggests a far broader influence than previously imagined. It seems that the
pineal is indeed a photoreceptor organ, synchronizing many of the hormonal and
neurobehavioral activities of the organism to circadian variations in
environmental light; however, there is far more to pineal physiology. The known
and probable influences of the gland continue to become more diverse. Pineal
physiology provides insight not just into one small part of the brain, but into
its integration with the entire nervous system.
Historical Perspective
So small and remote as to be easily overlooked in a rapid
perusal of the cerebrum, the pineal gland has been a source of fascination for
philosopher and physician alike since its discovery by Herophilus in 300 H.C.
Galen dubbed the gland konareion (conarium in Latin), meaning "shaped like a
pinecone." Descartes believed that the pineal's central location uniquely
qualified it to be the "seat of the soul." To those for whom the anatomic
situation was too suggestive not to postulate a psychic link, the pineal was the
"sphincter of the mind."
Evolution of Techniques to Study the Pineal
Science began to make inroads in pineal physiology with
early anatomic studies of animals such as fish and amphibians, which also
possess pineal glands but in more superficial locations adjacent or in close
proximity to visual structures. The human pineal is buried deep within the
brain, far from the surface where it might interact directly with sources of
light. Therefore, its photoreceptor function was not appreciated until
anatomists could trace pathways from the optic apparatus to the pineal and
comparative anatomists determined that the organ monitoring environmental photic
information was the same in lower animals and humans. Only then did awareness of
the link between this gland and photoperiodic homeostasis begin to emerge.
The efferent arm of pineal function was elucidated later, more than 50 years
ago, with the isolation and demonstration of melatonin, "the pineal factor that
lightens melanocytes." The essential link between melatonin action and
photoperiodicity was described shortly thereafter.
For 4 decades, isolation and assay techniques for a long list of biosynthetic
precursors, intermediaries, neurotransmitters and peptide hormones have
overwhelmed an entire scientific journal devoted to pineal research. Although
the volume of data renders impossible, for the moment, the assemblage of a
comprehensive summary of pineal physiology. it clearly establishes the gland's
central role in coordinating vertebrate physiology.
The pineal is studied at the chemical level by analysis of its products and of
interactions between these and others isolated from organs throughout the body.
Individual pineal cells from a variety of species are subjected to chemical and
physical manipulations. The isolated pineals of subhuman species have been
examined and purified homogenates used in a variety of culture and tissue
experiments. In vivo experiments are most frequently done in rats and lower
animals but also in primates. Human in vivo studies are becoming increasingly
feasible with improved techniques for chemical analysis and imaging of the
nervous system.
Much of what is known about
pineal physiology is learned from manipulations of exposure of an organism to
light - the major influence on pineal physiology. Comparison of physiologic
parameters before and after pinealectomy provides clues to the organ's function.
For a variety of reasons,
frequently ethical ones, relatively few studies of pineal physiology have been
done on human beings. Much of the available information about how the pineal
operates and what its functions are is derived from animal studies, cell
cultures, and tissue preparations. The precise significance of many experimental
findings for humans is nebulous. Many of the functions ascribed to the human
pineal are based on extrapolations from in vitro and nonhuman data.
Phylogenetic Clues to Pineal
Function
Comparisons among species
provide important clues to the pineal's role in humans. Phylogenetically, the
gland has been primarily a photoreceptor organ. Throughout vertebrate species it
is closely related to the optic apparatus. Some species have cortical and
medullary portions of the pineal: the significance of this is unknown.
Pineal volume does appear to
correlate with variations in hormonal activity. Species with larger pineals
(relative to total organism size) tend to be homoeothermic (vs. heterothermic)
and to have diurnal physiologic cycles (vs. nocturnal). Tropical animals tend to
have smaller pineals than those adapted to living in temperate climates, where
seasonal variations in temperature and daily duration of sunlight make
reproductive timing more critical.
The pineal is present in all
vertebrates. In lower species its location is often more superficial and its
association with photoreceptor function is more obvious. Through evolution. the
pineal changed from a photoreceptor organ to one associated with an organism's
interactions with the light-dark cycle.
Analogies between mammalian and
amphibian photoreceptors (anatomic, chemical or functional) are not identities.
Interesting and exciting theories about human pineal function are frequently
extrapolated from animal research or even from in vitro tissue or cell culture
preparations. Cautious appraisal of pineal data from nonhuman studies is
warranted to avoid over- or underestimation of the gland's importance in humans.
The pineal arises as an
evagination of the neuroepithelial roof of the third ventricle, between the
habenula and the posterior commissure in the second month of gestation.
Neuroepithelial cells become pinealocytes, whereas mesenchymal cells become the
connective tissue strands, fibroblasts and vessels of the gland. The pineal
develops from two lobes that fuse. The gland's orientation changes from vertical
to horizontal. Innervation of the gland is completed in the prenatal period.
At birth there are two types of
pinealocyte which are distinguishable to approximation 3 years of age. Type I
pinealocytes are S-100-positive and neuron-specific enolase-negative; type II
pinealocytes are enolase-positive. S-100-negative, and melatonin negative. At
birth. type I cells predominate. but by 1 year of age, they are outnumbered by
type II cells.
Secretory activity, specifically
of the primary pineal product melatonin, varies throughout the course of
development. Serum melatonin levels increase from the third postnatal month to
preschool age. They then decline steadily from preschool age until sexual
maturity. This pattern raises the interesting possibility that, contrary to
previous beliefs, the gland's effects on development are not necessarily related
to sexual maturation. The pineal reaches its adult size by age 4 years and
undergoes no significant histologic changes from childhood to adulthood.
Regional Gross Anatomy
The anatomic location of the
pineal with respect to nearby neural and vascular structures accounts for the
difficulty in surgical access as well as for the neurological symptoms that may
accompany mass lesions arising in the gland. From the physiologic perspective,
the pineal is well situated to serve as the hub of a system of input, feedback
and regulation among numerous diverse brain regions.
Also called the epithalamus, the
pineal is located in the posterior most portion of the epithelial roof of the
third ventricle. The posterior commissure is found posteroinferiorly. Anteriorly
the gland is in continuity with the habenular trigone and the striae medullaris
thalami. The posterior portion of the corpus callosum, the splenium overlies the
pineal.
Although the gland is suspended
in the pineal recess, a CSFfilled cistern contiguous with the quadrigeminal
cistern, the gland itself is not bathed in spinal fluid but rather is surrounded
by a pial layer. Because the organ is solid, the substances it produces are
probably not primarily released directly into the third ventricle but rather
into the vascular system.
Major vascular structures lying
in proximity to the pineal or passing by it are the medial posterior choroidal
arteries (the major feeders to the gland) and numerous perforators. Ample venous
outflow seems to facilitate the distribution of synthesized substances. Drainage
is into the vein of Galen via the internal cerebral veins: the veins of
Rosenthal are situated just lateral and superior to the pineal. Behind the gland
is the precentral vein of the cerebellum.
Microscopic Anatomy
Microscopically the pineal
appears as clusters of parenchymal cells enclosed by bands of connective tissue
of variable thickness that consist of fibrous astrocytes and other cell types.
The pineal is surrounded by a capsule and is composed of lobules with separating
connective tissue septae. Astrocytes are shown to be abundant by glial
fibrillary acidic protein (GFAP) staining and form a barrier between vessels and
pinealocytes.
There are many different cell
types in the gland. In addition to supporting, neuronal, and endothelial cells,
the stroma is made up of pinealocytes, which themselves may be subdivided by
histologic and electron microscopic, and increasingly by biochemical and
functional, criteria.
Pinealocytes make up 90 percent
of the parenchyma of the gland. In sub mammalian species, they are derived from
photoreceptor cells. In vertebrates there are thought to be two types of pineal
cells, light and dark, so named on the basis of their responsiveness or
unresponsiveness to light input at the retina, The existence of these two types
in humans remains controversial.
Parenchymal pineal cells are
thought to belong to the system of amine precursor uptake and decarboxylation
(APUD) cells. They stain positively for neuron-specific enolase.
Pinealocytes are characterized
by their prominent nuclei and nucleoli. Each pinealocyte has several cytoplasmic
processes, which terminate in club-shaped endings on perivascular spaces and
which may provide a means for communication between pinealocytes.
Because it produces substances
chemically related to neurotransmitters, contains synaptic vesicles, secretes
its products in response to stimulation of receptors on its cell membrane and
originates in the ectoderm, the pinealocyte can be considered a "paraneuronal"
cell. Kappers considers the pineal "a true endocrine organ" because
pinealocytes, although derived from neuroectoderm, are not neurons.
In lower animals, pinealocytes
morphologically resemble retinal photoreceptor cells. Some of the pinealocytes
in these species have processes that resemble axons and many of them
immuno-stain positively for gamma-aminobutyric acid (GABA).
Glial cells, primarily fibrous
astrocytes, appear to serve both supportive and metabolic roles in the pineal,
as they do in all central nervous system tissue. Staining with S-100 suggests
that microglial cells are also present.
The endothelial cells that make
up the vascular supply to the pineal do not have the tight junctions
characteristic of the bloodbrain barrier: the pineal is thus rightly considered
to be a circumventricular organ. Although parasympathetic, commissural. and
peptidergic fibers have been demonstrated in the pineal. the only fibers with
known physiologic significance in the gland are general visceral afferent
sympathetics originating in the superior cervical ganglion and reaching the
pineal via the nervi conarii. These postganglionic sympathetic fibers receive
descending input from hypothalamic nuclei, particularly the suprachiasmatic
nucleus (SCN), which receives direct input from retinal ganglion cells.
Unmyelinated fibers travel through connective tissue in discrete bundles. In
some animals all the sympathetic input reaches the pineal as unmyelinated fibers
travelling with venules and arterioles, which vascularize the gland. There is
also questionable parasympathetic innervation, possibly arriving via the
habenula and posterior commissure. Neurotransmitters reach pineal cells not
across a synaptic cleft but by diffusion after release from varicosities some
distance away. Other cell and tissue types found in the pineal include fibrous
connective tissue, skeletal muscle and lymphocytes.
Acervuli, corpora arenacea, or
pineal calcifications, the familiar and important pineal landmarks seen on skull
roentgenography and computed tomography (CT) of the head are still incompletely
understood. Calcium accumulates along plasmalemma and intracellularly in
pinealocytes. This may be the basis of calcium deposition, which occurs in an
organic matrix produced by pinealocytes. The calcareous concretions grow along
growth zones and are composed of calcium, magnesium and ammonium ions as well as
calcium carbonate. The growth process is thought to be age- and sex-independent
and is probably related to the gland's secretory activity.
Although the etiology of these
concretions is not known, two theories have been proposed. In the first a
carrier protein is thought to be released into intracellular vacuoles. In the
second there is decreased drainage of tissue fluid from the gland. Acervuli are
seen in 3 percent of pineals by age 1 year, in 7.1 percent by age 10, and in 33
percent by age 18.
The functional significance of
pineal calcifications is unknown. Recent CT studies of pineal calcifications
have attempted to correlate their presence with diseases such as schizophrenia.
Another incompletely understood
phenomenon is the formation of benign pineal cysts. These mass lesions, which
can reach proportions sufficient to result in clinical symptoms and signs, are
thought to result either from degeneration of foci of gliosis within the gland
or from sequestration of CSF during pineal development. Why this happens remains
unknown. In a recent radiologic review, Golzarian et al. reported a 2,4 percent
incidence in 500 consecutive magnetic resonance imaging studies. Pineal cysts
can be found in 25 to -40 percent of subjects studied at autopsy.
