Table Of ContentT he Choroid
Plexus
in Health and
Disease
MARTIN G. NETSKY,
SAMRUAY SHUANGSHOTI,
and collaborators
JOHN WRIGHT & SONS LTD.
BRISTOL
THE UNIVERSITY PRESS OF VIRGINIA
Copyright © 1975 by the Rector and Visitors
of the University of Virginia
First published 1975
ISBN: 0 8139 0521 4
Library of Congress Catalog Card Number: 73-93948
Printed in Great Britain
Printed in Great Britain by John Wright & Sons Ltd.,
at the Stonebridge Press, Bristol
Published in Great Britain by John Wright and Sons Ltd., and distributed solely by them
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Contributors
NORWIN H. BECKER, M.D.
Attending Pathologist, Montefiore Hospital and Medical Center; Associate Professor
of Pathology, Albert Einstein College of Medicine, New York, New York 10461
(Chapter VI)
MILTON W. BRIGHTMAN, Ph.D.
Head, Section on Neurocytology, Laboratory of Neuropathology and
Neuroanatomical Sciences, National Institute of Neurological Diseases and Stroke,
Bethesda, Maryland 20014 (Chapter V)
HELEN F. CSERR, Ph.D.
Assistant Professor of Medical Science, Division of Biological and Medical
Sciences, Brown University, Providence, Rhode Island 02912 (Chapter IX)
SVEN Ο. Ε. EBBESSON, Ph.D.
Professor of Neurosurgery and Anatomy, University of Virginia School of
Medicine, Charlottesville, Virginia 22901 (Chapter VIII)
MARTIN G. NETSKY, M.D.
Professor of Neuropathology, University of Virginia School of Medicine,
Charlottesville, Virginia 22901
RICHARD L. ROVIT, M.D.
Director of the Department of Neurological Surgery, St. Vincent's Hospital and
Medical Center, New York, New York 10011 ; Clinical Professor of Neurosurgery,
New York University School of Medicine, New York, New York (Chapter XVI)
MANNIE M. SCHECHTER, M.D.
Professor of Radiology, Albert Einstein College of Medicine, New York, New York
10461 (Chapter XVI)
DOLORES M. SCHROEDER, Ph.D.
Assistant Professor of Neurosurgery, Department of Neurosurgery,
Charlottesville, Virginia 22901 (Chapter VIII)
SAMRUAY SHUANGSHOTI, M.D.
Assistant Professor of Pathology, Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand
CARL H. SUTTON, M.D.
Assistant Professor of Neurological Surgery, Chief Neurosurgery Section,
V.A. Hospital, University of Miami School of Medicine, Miami, Florida 33152
(Chapter VI)
VIRGINIA TENNYSON, Ph.D.
Associate Professor of Pathology, Division of Neuropathology and Neurology,
Columbia University College of Physicians and Surgeons, New York, New York 10032
(Chapter III)
Preface
A COMPREHENSIVE ANALYSIS OF THE CHOROID PLEXUS is not available in the English
language. Studies on the choroid plexus, its secretions and other properties, however,
have increased greatly in recent years. New technics have brought fresh information
about the choroid plexus, ependyma, and cerebrospinal fluid. The choroid plexus now
is known to absorb and phagocytize as well as to filter and secrete, and the fluid no
longer is viewed merely as a jacket of water protecting the central nervous system.
Light and electron microscopic studies continue to yield new data. The discovery that
some radioactive substances are concentrated by the choroid plexus has awakened
clinical interest, as has the finding that bleeding into the cerebral ventricles may
arise from the plexus not only in children, but also in adults. In this volume, we have
gathered data from widespread sources to elucidate normal structure and function,
and the clinical disorders of the choroid plexus in relation to embryology, anatomy,
chemistry, and physiology.
The word "choroid" or "chorioid" comes from the Greek noun chorion^ meaning
skin. The word is applied generally to vascular membranes, such as the vascular tunic
of the eye. "Plexus" is derived from the Latin word for "a twining", and refers to
interwoven networks of blood or lymphatic vessels, or nerves. The term "choroid
plexus" usually includes three components: epithelium, blood vessels, and connective
tissue. The epithelial covering, also called lamina choroidea epithelialis or choroidal
epithelium, is a modified ependyma derived from the neuropithelium lining the neural
tube. The vascular channels and framework of connective tissue are leptomeningeal
in origin. Ependyma is the lining membrane of the cerebral ventricles and central
canal of the spinal cord. The term was first used by Virchow and comes from the
Greek word for "outer garment".
Some anatomists restrict the term choroid plexus to the stromal connective
tissue and blood vessels. We, however, prefer that "choroid plexus" be used to
mean the combination of choroidal epithelium, blood vessels, and connective
tissue interstitium, because it is thus used by most physicians. The phrase "tela
choroidea" (tela: Latin for "web" or "tissue") is at times used as the equivalent
of our term "choroid plexus". To most authors, however, tela choroidea means
only the roof structures of the 3rd and 4th ventricles, and we shall follow this latter
usage.
Except where indicated, all chapters were written by the principal authors. To save
space, the names of the lower parts of the ventricular system have consistently been
written as 3rd and 4th rather than third and fourth. Terms derived from foreign
languages but used anatomically have not been italicized. The transliteration of
Russian names such as Klosovsky (Klosovskii) and Volgina (Volzhina) is variable,
but we have used the original publication as our authority. The word "mucin" is used
to mean materials stained by the muci-carmine technic and as a brief alternative to
mucicarmine-reactive materials.
A final problem of usage is the restriction of the term "diencephalic" to
a particular portion of choroid plexus in the 3rd ventricle in the embryo, but
to include the entire plexus of the 3rd ventricle when referring to adult structures.
We have avoided this problem here by using "diencephalic choroid plexus" only in
viii Preface (cont.)
discussing the embryo, and "plexus of the 3rd ventricle" in considering the
adult.
We are grateful to Ms Brenda Shifflett for typing the numerous revisions, and to
Ms Anne Russell for most of the photomicrographs.
MARTIN G. NETSKY
SAMRUAY SHUANGSHOTI
Acknowledgments
SOME FIGURES IN THIS PUBLIGATION are taken from our published reports. We are
grateful to the publishers of the journals concerned for permission to reproduce the
figures in this monograph.
Figures 1—2, 3, 4, 5, 6 andF^. II—1, 2, 3, 5, 6, 7, 8, 9, 11, 12 were published by
Shuangshoti and Netsky in the American Journal of Anatomy, 1966. Figures I—7, 8, 10
are taken from the paper by Shuangshoti and Netsky in the Journal of Morphology,
1966. Figures II—4, 10 are from the publication by Shuangshoti and Netsky in
Neurology, 1966. Figures IV—1,2, 3,4, 5, 6, 7, 10, 11 are from the article by Shuangshoti
and Netsky in the American Journal of Anatomy, 1970.
We are grateful to the Archives of Pathology for permission to reproduce Figs. X—4,5,
6, 7, 8, 10 from the article by Shuangshoti, Roberts, and Netsky (1965), and Figs.
XIV—4, 6 from the publication by Shuangshoti, Tangchai, and Netsky (1971). Figures
XII—2, 3, 4, 5, 6, are reproduced by permission of the Amencan Journal of Pathology
from the paper by Shuangshoti and Netsky (1966).
Finally, the publishing firm of Lea & Febiger has given us permission to reproduce
Figs. XIV—1, 10,12 from the Atlas of tumors of the nervous system by Zimmerman, Netsky,
and Davidoff (1956).
M. G. Ν.
S. S.
I
Origin of Choroid Plexus and Ependyma
THE EMBRYOGENESIS OF THE GHOROID PLEXUS is discussed only briefly in most textbooks
of embryology. Various investigators have observed the time of appearance of the
primordia of the choroid plexuses in the lateral and 4th ventricles of animals such as
the pig (Weed, 1917), guinea-pig, rabbit, and rat (Cohen and Davies, 1938; Strong,
1956); others have described the glycogen content of the developing choroidal
epithelium (Weed, 1917), but the full histogenesis was not described. A few workers
using the light microscope have studied material from human embryos incompletely
(Kiszely, 1951 ; Kappers, 1958). Tennyson and Pappas (1964) extensively investigated
the problem electron miscroscopically in material from the rabbit, but did only
limited work on man (Tennyson and Pappas, 1968). A detailed morphologic study
on human material, therefore, has been lacking.
The histogenesis of the choroid plexus in man as given here is based on our previous
investigations of 40 specimens of human embryos and fetuses, ranging from 13 mm
crown-rump (G-R) length ( 4 weeks of gestation) to full term (40 weeks of gestation),
and additional specimens of the choroid plexus from newborn infants up to 1 month
of postnatal life (Shuangshoti and Netsky, 1966a). The gestational age of the embryo,
fetus, or immature or premature infants was calculated from the chart of the National
Pituitary Agency if G-R length or body weight were known. This chart was modified
from data of Streeter (1920).
The first indication of the neuraxis of embryos appears as the neural plate. The
lateral edges of the plate are subsequently elevated to form the neural folds and groove.
The neural folds ultimately join together to form the neural tube lined by tall pseudo-
stratified neuroepithelium (medullary epithelium or matrix cell layer). The individual
epithelial cells are connected to each other toward the luminal borders by terminal
bars. This developing neuroepithelium proliferates actively as evident by numerous
mitotic divisions (Sauer, 1935a, b; Sidman, Miale, and Fedar, 1959; Langman,
Guerrant, and Freeman, 1966). The neural tube is surrounded by layers of mesen-
chymal cells giving rise to the meninges.
The primordium of the choroid plexus is formed by folding of the mesenchyme
in contact with the underlying neuroepithelium of the neural tube. These events
occur in regions where the wall of the neural tube is thin, as in the roofs of
the 3rd and 4th ventricles, and at the junctional groove between the medial
wall of the developing cerebral hemisphere and the roof of the 3rd ventricle
(Fig. I—1). The choroid plexus is present in chordates above Amphioxus, but the
degree of development differs among the various classes of vertebrates (see Chapter
VIII).
3
4 The Choroid Plexus in Health and Disease
parietal organ
pineal
paraphysis post, commissure
I midbrain
cerebellum
X
choroid plexus
/f >K
lateral J hypophysis
ventricle
ant. commissure
velum transversum
Fig. I—1. Drawing of midsagittal section of brain (after Kingsley, 1926), showing the relation
of paraphysis to choroid plexus of the 3rd ventricle and the pineal complex. The paraphysis
projects outside the ventricle and the choroid plexus protrudes into this cavity. The velum
transversum is also part of the choroid plexus. The pineal complex formed by the parietal organ
and the pineal body is located toward the caudal end of the roof of the 3rd ventricle. The
choroid plexuses of the lateral and 4th ventricles are also shown. Note continuity between the
choroid plexuses of the lateral and 3rd ventricle. See also Fig. I—9 (p. 12) for comparison.
A. TIME OF DEVELOPMENT OF CHOROIDAL PRIMORDIA IN MAN
The primordium of the plexus of the 4th ventricle appears first, then the lateral
ventricle, and finally the 3rd ventricle. We found these primordia in embryos at the
6th, 7th, and 8th week of gestation (16, 19, and 23 mm C-R length), respectively.
Other authors differ widely concerning the embryonic age in which the primordia of
the choroid plexuses are first seen. The primordium in the 4th ventricle was said to
appear from 4 to 5 weeks (Streeter, 1912; Jordan and Kindred, 1948; Klosovskii,
1963), and in the lateral ventricle during the 2nd month (Minot, 1892; Heisler, 1907;
Kappers, 1958; Klosovskii, 1963). The primordium in the 3rd ventricle was found
early in the 3rd month of gestation by Frazer (1932), but Klosovskii (1963) asserted
that it appears in the 1st month. Nevertheless, our findings indicate that all primordia
of the major human choroid plexuses (Figs. I—2 to 4) appear no later than the 2nd
month of intrauterine life.
B. PRIMORDIUM OF CHOROID PLEXUS OF LATERAL VENTRICLE
Other terms employed for the choroid plexus of the lateral ventricle are telencephalic
choroid plexus, lateral telencephalic plexus, and plexus of the hemisphere. The
groove formed by the edge of the roof of the 3rd ventricle and the medial wall of the
cerebral hemisphere is the primordium of the choroidal fissure. The mesenchyme in
Origin of Choroid Plexus and Ependyma 5
contact with the neuroepithelium folds along the groove into the lateral ventricular
cavity to begin forming the choroid plexus (Fig. I—2). The choroidal fissure at first
is short, but later considerably elongates and shifts position because of posterior,
inferior, and lateral enlargement, and the extension of the lateral hemisphere. The
choroid plexus is carried along the choroidal fissure into the temporal (inferior) horn
of the lateral ventricle, and the stalk of the plexus lengthens along the fissure. The
pathway of lengthening and extension of the choroid plexus is similar to the course of
the caudate nucleus in man.
Fig. I—2. A coronally sectioned brain from a 7-week-old human embryo (19 mm G-R
length) to show the first indication of the choroid plexus of the lateral ventricle formed by
folding of the neuroepithelium in contact with the mesenchyme into the ventricle. The club-
shaped primordium is covered by tall pseudostratified neuroepithelium. The lining of the
developing telencephalon (upper arrow) is thicker than that covering the primordium of the
plexus (lower arrow). The mesenchymal stroma of the choroid plexus is more vascular than the
primitive leptomeninges around the developing brain. H & Ε ; Χ 24.
The choroid plexus of the lateral ventricle is not developed in cyclostomes but begins
to appear in Selachians and Ganoids and is present constantly in higher species
(Bailey, 1916a). This plexus is highly developed in reptiles and birds, and is more
complex in the latter (Warren, 1905).
The origin of the root of the choroid plexus of the lateral ventricle has been variably
described in the literature. Most textbooks of embryology state only that this choroid
plexus originates in the groove between the junction of the roof of the 3rd ventricle
and the medial wall of the developing hemisphere .
G. PRIMORDIA OF CHOROID PLEXUS OF THIRD VENTRICLE
The number of parts and the location of the choroid plexus of the 3rd ventricle have
been controversial because most investigators consider the velum transversum to be
a definite border between diencephalon and telencephalon. This concept results in
diverse names for the various parts of the choroid plexus of the 3rd ventricle as well
as certain areas of the roof plate of this region. Four choroidal primordia are described
6 The Choroid Plexus in Health and Disease
Fig. I—3. Coronally sectioned brain of the same embryo as in Fig. I—2, illustrating primor-
dium of the paraphysis and choroid plexus of the lateral ventricle in the region of the rostral
end of the roof of the 3rd ventricle. A, The paraphyseal primordium (arrow) folds extraventri-
cularly into the prospective roof of the 3rd ventricle and between the club-shaped primordium
of the choroid plexus of the telencephalon. Η & Ε; χ 11. Β, The neuroepithelium comprising
the paraphyseal primordium is pseudostratified. Η & Ε; χ 600.
by various authors as arising in the diencephalic roof plate. We shall describe these
as reported, and then present our own interpretations.
1. PRIMORDIUM OF VELUM TRANSVERSUM
Toward the rostral end of the roof of the 3rd ventricle, the mesenchyme and under-
lying neuroepithelium fold into the lumen of the neural tube as a transverse ridge,
forming the primordium of the velum transversum (Figs. I—1, 4) in nearly all
vertebrates, including cyclostomes (Bailey, 1916a). This structure is not well formed
in fishes, but is highly developed in amphibians. In Necturus and some tailed amphib-
ians, the velum serves as the principal choroid plexus of the 3rd ventricle (Warren,
1905; Gladstone and Wakeley, 1940). The velum transversum regresses in reptiles
and birds, and is rudimentary in most mammals (Warren, 1905).
Portions of the roof of the 3rd ventricle rostral to the velum transversum were
named paraphyseal arch (Minot, 1901-2; Bailey, 1916a, b; Kappers, 1955), and
those behind the velum transversum were called postvelar arch (Minot, 1901-2),
epiphyseal plate (Streeter, 1912), or dorsal sac (Frazer, 1932). The rostral parts of
the 3rd ventricle in front of the velum transversum were designated as the median
telencephalic ventricle (Kappers, 1950, 1955), and the remaining parts behind the
velum transversum were named the 3rd ventricle.
