Principles of Neurosurgerv,

edited by Robert G. Grossman. Rosenberg © 1991.

Published by Raven Press, Ltd., New York.

CHAPTER 8

Brain Tumors

Harold F. Young

Incidence, 113
Etiology, 113
General Symptoms and Signs, 114
Tumors of the Glia, 116

Incidence, 116
Astrocytomas and Glioblastomas, 116
Cerebellar Astrocytomas of Childhood, 123
Brainstem Gliomas, 124

Optic Nerve Gliomas, 125
Ependymomas, 126
Oligodendrogliomas, 128

Medulloblastomas, 129
Hemangioblastomas, 132
Papillomas of the Choroid Plexus, 133
Pineal Tumors, 135

Colloid Cysts of the Third Ventricle, 136
Meningiomas, 138
Acoustic Neuromas, 149
Craniopharyngiomas, 152
Primary Central Nervous System Lymphomas, 154
Metastatic Intracranial Tumors, 155
References, 157

INCIDENCE

The results of an autopsy survey by Russell and Rubin-
stein suggest that 9.2 percent of all tumors are in the
brain and that 49 percent of all primary brain tumors are
gliomas (1). Neoplasms that affect brain tissue may be
classified into three categories: primary intraaxial tu-
mors; extraaxial nonparenchymatous tumors, such as
meningiomas; and metastatic tumors. The first group,

the primary intraaxial tumors, arise primarily from par-
enchymatous elements of the central nervous system
(CNS) and account for approximately 50 percent of all
intracranial tumors. Primary intraaxial tumors have an
incidence of about 5 per 100,000 persons per year, and
about 10,000 of such cases occur each year in the United

States. These tumors rarely metastasize outside the CNS,
probably because of the limited life-span of the patient
following diagnosis and treatment. The incidence of met-
astatic tumors to the CNS is clearly increasing, with up

to 65,000 to 70,000 new cases occurring yearly, and will
increase as patients live longer with cancers treated by
chemotherapy. The increased length of survival of these
patients gives longer exposure time for metastatic de-

H. F. Young: Division of Neurological Surgery, Medical Col-

lege of Virginia, Virginia Commonwealth University, Rich-
mond, Virginia 23298.

posits to develop and many cancer patients now die with
CNS involvement. About 80 percent of patients surviv-
ing two years with small-cell carcinoma of the lung have
CNS metastasis (2). Though many of these metastatic
lesions are asymptomatic, they must be considered in
treatment protocols for these patients. Furthermore,
there is experimental evidence that some chemothera-
peutic agents such as 5-fluorouracil may produce tran-
sient disruption of the blood-brain barrier that enhances
the possibility of CNS metastasis (3). In children under

15 years of age, a United States survey conducted be-

tween 1973 and 1976 revealed that CNS neoplasms had
an incidence of 22.2 per million. Cancer was second only
to accidents as a cause of death in children, and brain
tumors ranked second only to leukemia (which had an
incidence of 37.4 per million) (4). In children, tumors
tend to occur in the posterior fossa, rather than in the
supratentorial compartment where adult tumors are
more frequently found.

Geographic differences have been shown in the occur-

rence of tumors; in Japan an unusually high incidence of
pineal tumors has been reported.

ETIOLOGY

Head trauma as the initiator of the growth of brain

tumors has always been a topic of controversy. In 1888,

113

114 / CHAPTERS

Byron Bramwell commented that "amongst the more

direct causes of brain tumor, injury occupies an impor-
tant place" (5). Many authors, including Gowers (6),
Kennedy (7), Parker and Kernohan (8), and Gushing
and Eisenhardt (9), have reported cases supporting the
opinion that prior cerebral injury played a role in the
subsequent development of brain neoplasms. Meningio-
mas have been well documented to grow at the exact site
of previous trauma (10-12).

Retrospective studies, however, may have a serious

recall bias because patients with brain tumors and their
kin may be motivated to recall and report previous head
injuries more completely than do controls (13). Both
Bailey (14) and Wilson (15) denied any significant associ-
ation between head injury and brain tumor. The possibil-
ity that head trauma predisposes to intracranial neopla-
sia was investigated in 2,953 patients who were followed
for a total of 29,859 person years in the course of a pro-

spective study. The observed number of subsequent
brain tumors, 4, did not differ from the expected number
of 4.1 (16). Also, the location and severity of head inju-
ries did not influence the subsequent occurrence of brain

tumors. Trauma and intracranial meningiomas will be

discussed later.

Tumors can be the result of autosomal inheritance,

which is accepted as the origin for the phacomatoses.

These include von Recklinghausen's neurofibromatosis,
Bourneville's tuberous sclerosis, von Hippel-Lindau's
syndrome, and neurocutaneous melanosis. The associa-
tion of cerebral gliomas and neurofibromas in von Reck-
linghausen's syndrome, as well as cerebellar hemangio-
blastomas in familial von Hippel-Lindau's syndrome, is

well established. Medulloblastoma occurring in siblings
has been described in seven reports (17-20). Yamashita,
Handa, and Toyama have suggested that heredity must
play a role in the etiology of medulloblastoma, or was at

least one of several factors (26). Many have suggested
that genetic factors may be related to the pathogenesis of

intracranial gliomas (22-27) and others have docu-
mented radiation-induced gliomas (28).

Some brain tumors undoubtedly have a prenatal ori-

gin. Craniopharyngiomas, medulloblastomas, and sub-
ependymomas belong in this group. The usual midline

location of these tumors, particularly the midline local-
ization of medulloblastomas and subependymomas, is

striking and suggests origin from the pluripotential cells
of the medullary velum in cases of medulloblastoma and
from subependymal cells in cases of subependymoma.
The fact that identical twin brothers can simultaneously

develop symptoms of a subependymoma, proven at

operation, strongly favors a view that this tumor is in-
deed maldevelopmental in origin (22). There are at least
nine case reports of uniovular twins developing proven

brain tumors, including gliomas, meningiomas, medullo-
blastomas, and subependymomas (26).

Suggestive evidence exists of a relationship between

Simian virus 40 (SV-40) and development of a medullo-
blastoma in the cerebellum of children. The incidence of

brain tumors in children in Connecticut increased be-
tween 1960 and 1965, but this increase was not main-
tained after 1965. The mothers of many of these children
had been vaccinated during pregnancy with an antipo-
liomyelitis vaccine which had been contaminated with
Simian virus 40. In Connecticut between 1956 and

1962, 120 children under 20 years of age developed tu-

mors of the central nervous system. Medulloblastomas

accounted for 42 percent of the tumors in children
whose mothers had received the contaminated vaccine,
but in only 18 percent of the children who had not been
exposed to SV-40. Sixty-seven percent of the children

with a medulloblastoma had a history of exposure to

SV-40, compared with 21 percent of the children who

had not been exposed (p < 0.01). It is as yet unknown if
those children of exposed mothers who did not develop
tumors in childhood will do so later in life (29).

Brain tumors have been produced in owl monkeys

inoculated with a human poliomavirus (30). Humans
are a natural host for two polioviruses: JC virus, impli-
cated in progressive multifocal Icukoencephalopathy

(PML), and BK virus, often isolated from the urine of

immunosuppressed patients. Also, an SV-40-related se-
quence in the DNA and extracted from one human

glioblastoma has been observed (31). The finding of such
a viral genome in one human brain tumor does not
prove that a virus is of an etiological importance. Yet,
the proof of viral DNA sequences in a human brain tu-
mor, especially when the virus is known to be oncogenic
in animals, is deserving of further interest.

The etiology of primary brain tumors remains largely

unknown. Brain tumors primarily occur in homo sa-

piens and the carcinogens, such as polycyclic hydrocar-

bons and other compounds, that induce tumors in labo-

ratory animals have not been proven as an etiologic

factor in human brain tumors.

GENERAL SYMPTOMS AND SIGNS

The general symptoms of brain tumors are due to in-

creased intracranial pressure (ICP), traction of the tu-
mor, or brain herniations affecting pain-sensitive intra-

cranial structures—the blood vessels, dura mater, and

cranial nerves. Most of the general symptoms occur only
late in the course of tumor growth and indicate an ad-
vanced stage in tumor progression, except for neuropsy-
chological changes, which may be an early symptom for
brain tumor.

Increase in intracranial pressure may be caused by (1)

the tumor mass, (2) associated cerebral edema, (3) ob-
struction of cerebrospinal fluid (CSF) pathways, (4) ob-
struction of the venous system draining the brain, or (5)
obstruction of the cerebrospinal fluid-absorbing mecha-
nisms. The presence of a tumor mass within the rigid

BRAIN TUMORS / 115

cranium will increase intracranial pressure. If the growth

of the neoplasm is slow, the brain and even the cranium

of young children will compensate to some extent for the
additional mass. When the limits of the compensatory

mechanisms are reached, the symptoms of increased ICP

occur. At times, a small mass may be associated with
severe cerebral edema resulting in increased ICP. In gen-

eral, however, the volume of tumor itself must reach at
least 100 grams before it causes symptoms from in-
creased ICP.

Cerebral edema is clearly a major component of in-

creased ICP in patients with brain tumor. In fact, some

authors claim that it is the edema associated with the

tumor that is the major cause of increased ICP. The most

malignant primary intraaxial tumors, especially meta-
static tumors, are associated with white matter edema.
This is vasogenic edema, resulting from leakage of serum

protein through defects in the capillary endothelium. Ste-
roids are effective in reducing the symptoms and signs of
increased ICP in patients with a brain tumor, generally
coincident with a decrease in edema as seen on computer-

ized tomography (CT), indicating that the edema is a

major cause of increased ICP in some patients with brain

tumor (21).

Tumors in various areas of the brain may cause ob-

struction of CSF flow. Frontal lobe tumors, suprasellar
tumors, and tumors of the anterior third ventricle may

obstruct the foramen of Monro causing enlargement of
the lateral ventricles. Tumors in the temporal lobe may

cause a shift of the brainstem with herniation of the me-
dial temporal lobe into the incisura. Tumors of the poste-
rior third ventricle, quadrigeminal plate, periaqueductal

grey area, and fourth ventricle may cause obstruction of
the aqueduct of Sylvius. Obstruction may also occur at
the foramina of Luschka and Magendie.

Neoplasms occasionally will compress a venous chan-

nel, such as the sagittal or transverse sinus, causing a

decrease in spinal fluid absorption and setting up a cycle
in which increasing pressure further compresses venous

channels. Diffuse meningeal neoplasms, such as carcino-

matosis of the meninges, may cause decreased absorp-

tion of spinal fluid and increased ICP, usually by produc-

ing hydrocephalus. Finally, a chronically elevated CSF
protein may diminish absorption and can result in in-
creased ICP.

The clinician must diagnose the tumor, especially the

primary intraaxial brain tumor, long before these symp-
toms and signs develop in order to cure the patient. Oth-
erwise, treatment will be largely directed toward relief of
intracranial hypertension, with loss of the opportunity to
cure the patient. Late diagnosis of a tumor is similar to
allowing a patient with an expanding post-traumatic he-
matoma to develop a dilated pupil or decerebration. As a

result, as in the late diagnosis of a tumor, the patient will
have sustained a secondary brain insult from increased

ICP or brain herniation that was preventable.

The general symptoms and signs observed in patients

with brain tumors are as follows:

1. Subtle, gradual change in personality and behavior,

irritability, somnolence, or lethargy. These symptoms

are seen very early in frontal lobe tumors or as a sign
of increased intracranial pressure from a posterior
fossa tumor causing hydrocephalus. In children, there
may be deterioration in school performance. These
symptoms often go unrecognized for weeks or
months and are usually more apparent retrospec-

tively upon development of other neurological symp-
toms.

2. Headache. Headache may be a generalized sign of

increased intracranial pressure, or it may localize to
the site of the tumor. It is usually described as a
chronic deep pain rather than the superficial or band-
like sensation of a tension headache. The headache

caused by generalized increase in intracranial pres-
sure usually occurs on a daily basis and is especially
prominent in the morning upon awaking from sleep.

The headache secondary to increased ICP is usually

associated with papilledema. In children, the head-
ache is frequently associated with morning vomiting
without nausea. The upright position or even hyper-
ventilation, by lowering arterial Pco

2

. may lessen the

severity of the headache. At times, the headache local-

izes to the side or the area of the tumor. This most

often occurs when there is local invasion of dura or

bone by the tumor. Gentle tapping of the scalp o%er
the area may aggravate the headache or identify a sen-
sitive area.

3. Vomiting. Vomiting is frequently seen in patients

with increased ICP from a brain tumor. It often oc-
curs with headache, and a vomiting episode may actu-
ally relieve the headache. Vomiting is a particularly

common symptom in children with posterior fossa

brain tumors and is usually described as projectile
vomiting. It usually occurs in the morning upon aris-
ing and is not associated with nausea.

4. Double vision. Diplopia is frequently a symptom of

bilateral sixth nerve palsies. If the palsies are indeed
bilateral, there is no localizing value to the diplopia as
it is a sign of generalized increased ICP.

5. Seizures. Generalized seizures comprise the initial

symptom in about 15 percent of patients with brain
tumors, and occur sometime during the illness in
about 30 percent of patients with brain tumors.
Whether a tumor will produce seizures depends
largely on its location and growth characteristics. The
patients with a tumor in or near the sensorimotor
cortex are more likely to have a seizure than patients

with a tumor in a frontal or temporal pole. Focal and/
or Jacksonian seizures are often associated with a cere-
bral tumor. Most often, the family or witnesses are
alarmed and describe the seizure in terms of a grand

116 / CHAPTERS

mal seizure. A brain tumor should be strongly sus-

pected in any new seizure disorder occurring in an
adult.

The important specific symptoms and signs of the

more common brain tumors will be described in the dis-

cussion of the particular tumor.

TUMORS OF THE GLIA

Incidence

The term neuroglia (nerve-glue, or putty) was intro-

duced by Virchow in 1846 (32). Neuroglial tumors may

be of one cell type or may be mixed. The classification of
gliomas, especially the grading of the astrocytic series, is

.still a subject of debate. The histopathological tissue anal-

ysis, according to the classifications of Burger and Vogel,

is a schema that is gaining increased acceptance by
neuro-oncologists (33,34). Gliomas account for almost
50 percent of all primary brain tumors. The glioblasto-
mas account for 12 to 15 percent of all brain tumors, or
33 percent of all tumors of the glia, and are second only

to meningiomas in frequency among primary brain tu-
mors (35). Some tumors, including cerebral astrocyto-
mas, may be relatively benign and well differentiated in
early stages but later can become highly malignant neo-
plasms.

Astrocytomas and Glioblastomas

The most common type of glioma is the astrocytoma

found in the cerebral hemispheres of adults and in the
cerebellar hemispheres of children (36). There are many

classifications of astrocytomas. Bailey and Gushing dif-
ferentiated only two definite histologic types: the fibril-
lary and protoplasmic (37). Penfield recognized three
types of astrocytomas: pilocystic, gemistocytic, and dif-
fuse (38). The pilocystic type is slow growing and forms

the cystic astrocytoma of the cerebellum. The gemisto-

cytic type is more rapid growing, with multiple small

cysts, and is found only in the cerebrum. The diffuse

astrocytoma is composed of small cells and is generally
found in the cerebrum. Svien and associates suggested
what is apparent to many surgeons, that astrocytomas
appear in various stages of malignancy or anaplasia,
which they graded I to IV (39). The benign astrocytomas

were graded I and II, and the more malignant were
graded III and IV. Glioblastomas are essentially grade IV
astrocytomas in this classification. Other pathologists

grade the astrocytomas as benign or malignant.

Symptoms and Signs

The patient with a tumor of the astrocytoma series,

especially a glioblastoma, may present with a variety of

symptoms, which often are unrecognized for weeks or
months prior to medical attention or correct diagnosis.
Unless the tumor is heralded by a seizure, the patient
often has a very subtle and gradual change in mental

status, which might well be termed psychomotor retar-

dation. This may be noted as a single symptom, such as a

personality or behavior change, apathy, forgetfulness,
dullness, or downgrading in work or school perfor-
mance. As the tumor progresses, often a symptom com-
plex will develop which may include headaches. Unfortu-
nately, these symptoms are often so subtle that they are
ascribed to aging or other events of life and go unrecog-
nized for long periods of time. These symptoms can be
due to a tumor in almost any cerebral location, as cere-
bral gliomas often involve the limbic system, more than
one lobe of the brain, or even both cerebral hemispheres.
There are specific symptoms and signs related to each
area of the brain where the tumor originates and reaches
its maximum size.

Frontal Lobe Intraaxial Tumors

Astrocytomas frequently occur in the frontal lobes

and may spread bilaterally via the corpus callosum (Fig.

1). Tumor infiltration or edema of a frontal lobe, particu-

larly of the right frontal lobe, must involve a fairly large
area of the lobe before headache begins or frank mental
changes occur, although seizures sometimes occur with
minimal cortical involvement. As the tumor increases in
size, bilateral frontal lobe involvement leads to easily
recognizable symptoms of forgetfulness, apathy, and de-
mentia.

Seizures are particularly prone to occur with frontal

lobe gliomas. The tumor may excite the frontal eye field
or the motor cortex, producing a grand mal seizure or
Jacksonian march, with the seizure spreading up or
down the contralateral side of the body. In the course of

an adversive seizure, the eyes deviate toward the tonic-

clonic hand. A tumor growing in the nondominant right
frontal lobe usually will be very large by the time of diag-

nosis, although a tumor in the deep frontal midline may

be quite small and yet produce behavioral deficits or
nonfluent speech disturbance if the tumor involves the
posterior portion of the left third frontal gyrus com-
monly known as Broca's area, which forms part of the

frontal operculum. Because of this, tumors of the left
frontal lobe usually are diagnosed earlier than tumors of

the right frontal lobe.

Temporal Lobe Intraaxial Tumors

The temporal lobe is involved in about one-half of all

the infiltrating neoplasms of the central nervous system.

Lesions of the temporal lobe may produce complex
symptoms including the uncinate seizure, characterized

BRAIN TUMORS / 117

FIG. 1. Deep midline glioblastoma, extending across midline

(arrow), making total removal impossible by operation. Note

surrounding cerebral edema, especially in right cerebral hemi-
sphere.

by the subjective sensation of an odor, usually of an un-
pleasant nature. Uncinate seizures occur primarily with
lesions of the amygdala and the hippocampal gyrus of
either the dominant or nondominant temporal lobe. The
seizure may spread to adjacent areas and psychomotor
seizures may develop. Chewing movements, lip smack-
ing, salivation, and motor automatisms may be part of

the complex.

As the neoplasm enlarges, it may involve Meyer's loop

of the visual pathway in the posterior temporal lobe, pro-
ducing a wedge-shaped defect in the contralateral supe-

rior temporal quadrant visual field. This is because

Meyer's loop contains visual fibers that pass from the
lateral geniculate nucleus of the thalamus to the calca-
rine cortex of the occipital lobe. Only fibers carrying vi-
sual impulses from the inferior retina pass into the ante-
rior temporal lobe.

The temporal lobes are involved in processing of mem-

ory and difficulty with memory, particularly short-term
recall, may occur.

The posterior part of the dominant superior temporal

gyrus, known as Wernicke's area, is concerned with lan-
guage. Some degree of aphasia may be produced by poste-
rior temporal-parietal tumors. The speech output is
characterized by fluency, usually with a high normal or

even excessive output of words per minute.

Parietal Lobe Intraaxial Tumors

The parietal cortex receives, correlates, synthesizes,

and elaborates the primary sensory impulses. It is not

concerned with the cruder sensations, such as recogni-
tion of pain and temperature, which are subserved to a
larger degree by the thalamus. Involvement of the post-
central portion of the parietal lobe produces defects in

gnostic or discrimination of sensation. The patient is un-

able to recognize familiar objects by their weight, size,

shape, or texture (astereognosis). Postural sensitivity is

impaired and the patient may not appreciate the exact
position of his limbs. Although the simple sensory modal-
ities of pain, temperature, and touch are preserved, two-
point discrimination and localization of touch may be
altered. Spatial cutaneous perception may be disturbed

on the contralateral side of the body, and the patient may

be unable to indicate where the touch is applied (atopog-
nosis). When two symmetrical areas of the body are si-
multaneously stimulated, only the stimulus on the nor-

mal side is appreciated (tactile inattention). Usually, the

sensory disorder is more manifest in the distal portions
of the limbs than elsewhere.

Lesions of the parietal lobe may also result in distur-

bance of body awareness, such as unilateral neglect with

a poverty of movement and abnormal positioning of the

limbs, lack of concern over the presence of a one-sided

weakness, or actual denial of hemiparesis (anosognosia).
This usually involves the left body from a right-sided
brain lesion and is again most pronounced in the limbs.
A dressing apraxia is uncommonly observed wherein the
patient has difficulty dressing. One variety of dressing

apraxia is characterized by unilateral neglect. The pa-
tient carefully dresses and grooms one-half of the body,
the side ipsilateral to the cerebral lesion, and completely
ignores the other side. The second variety of dressing
apraxia is exemplified by the patient who is unable to
manipulate an article of clothing in space. This type of
dressing apraxia represents a severe form of visual-spa-

tial disorientation and is seen almost exclusively in cases
with nondominant parietal disorders. A lesion in the an-
gular gyrus of the dominant hemisphere will result in
Gerstmann's syndrome, which is manifest by finger
agnosia, left-right disorientation of the entire body,
agraphia, and acalculia. Lesions of the supramarginal
gyrus may produce an apraxia which is usually asso-
ciated with a hemiparesis.

Visual disturbance caused by parietal lobe involve-

ment is usually a lower quadrant homonymous field de-
fect from involvement of the uppermost fibers of the
visual radiations as they project laterally around the pos-
terior horn of the ventricle. Usually, the hemianopsia is
incongruous. Sometimes images are distorted as to size,
shape, or color (metamorphopsia).

Lesions situated near the sensory cortex may cause

sensory seizures of the contralateral side of the body.
This are usually paroxysmal dyesthesias commonly in-
volving the face. Sensory seizures appear as numbness,
heaviness, or pain in the involved limbs. These sensory
seizures are clinically of localizing value when they as-

118 / CHAPTERS

sume the manifestations of a sensory aura preceding a

Jacksonian convulsion or when they constitute a focal
sensory seizure alone.

Occipital Lobe Intraaxial Tumors

The bccipital lobe and the preoccipital areas (Brod-

mann's 18 and 19) are associated with vision and follow-
ing movements with the eyes. The function of the preoc-
cipital eye fields is to push the eyes toward the opposite
visual field while following movement. The upper lip of
the calcarine fissure in the occipital lobe contains corti-
cal representation of vision from the inferior nasal retina

of the opposite eye and the inferior temporal retina of the
ipsilateral eye. The inferior lip contains corresponding

fibers from the superior retina.

The field defects associated with neoplasms are often

incomplete, progressive in nature, and have gradual or
sloping margins. Occasionally, they are incongruous but,
in general, a lesion of one occipital lobe will cause a con-

tralateral hemianopsia. If the involvement is limited or

localized to the cuneus of the upper lip of the calcarine

fissure, there is a contralateral lower quadrantanopsia. If
the involvement is limited to the lingual or the lower lip
of the calcarine fissure, there is a contralateral upper

quadrantanopsia. A lesion at the occipital pole will

mainly affect central vision; focal lesions of the occipital
lobes may produce localized loss of vision. Occasionally,

sparing of the macula is seen in hemianopsia associated

with involvement of the posterior portion of the occipital

lobe. Patients with lesions peripheral to but not truly

involving the striate cortex may have difficulty with fixa-

tion and maintaining visual attention, and they may lose

following and reflex ocular movements. These uncoor-
dinated movements can best be demonstrated using the
opticokinetic drum. Under normal conditions, the eye

fixes on the object imprinted on the drum and follows it
around the visual field. Jerky, uncoordinated move-

ments are characteristic of destructive lesions of the

preoccipital areas. Patients may also have loss of stereo-

scopic vision, impairment of visual memory and recall,
difficulty in accurate discernment or localization of ob-

jects, disturbances of spatial orientation, and loss of abil-

ity to discriminate with respect to size, shape, and color.

At times, simultagnosia—the inability to perceive more

than one object at a time, or, the ability to recognize

specific details of a picture but not the entire picture—is
found.

Stimulation or irritation of the calcarine cortex may

produce unformed visual hallucinations, such as flashes
of light, in the corresponding field of vision; irritation of
the surrounding areas may cause formed visual halluci-
nations.

Pathology

The histology of the astrocytoma is relevant for the

neurosurgeon performing the operation and for plan-
ning postoperative adjunctive therapy, which usually in-
volves irradiation or chemotherapy. The biological activ-

ity of an astrocytoma appears to be unique to each

patient and is generally related to the actual histology of
the tumor. Low-grade astrocytomas (Grades I and II of
Kernohan) are usually found in younger patients in the
age range of 20 to 40 years. These patients have many
years of useful life after diagnosis and have a normal

immune system (40-44). Whether these tumors cascade
into anaplastic or well-differentiated astrocytomas has
long been discussed. There is no doubt that some con-

tinue to spread slowly as low-grade astrocytomas, eventu-
ally causing death by mass-lesion effect or by infiltrating
vital brain structures. On the other hand, a tumor that
has been demonstrated to be a low-grade astrocytoma by
adequate biopsy or subtotal resection can be found to be
glioblastoma multiforme at the time of reoperation or

death of the patient. Other patients may have a high-

grade astrocytoma that appears to arise de novo as a glio-
blastoma multiforme, with a corresponding rapid and

relentless course. Some patients even have multifocal

gliomas (45).

The glioblastoma multiforme must be regarded as a

heterogeneous tumor in the biological sense. The hetero-

geneity of the tumor, characterized by giant cells, mitotic
activity, pleomorphic pseudopalisading, and neovascu-

larity with hyalinization of blood vessels, has long been
recognized (46). The many genotypically and phenotypi-
cally different cell populations of this tumor have also
been well documented (47). The cell-cycle time may
vary from 25 hours to as long as 58 hours. Hoshino and

associates, using flow cytometry, demonstrated that
glioblastomas have a substantial population of cells in

DNA synthesis and a highly variable distribution of
ploidy, consisting not only of diploid and/or aneuploid,
but also of triploid, tetraploid, and possibly octaploid
populations (48). These investigators, as well as Zuber,
Hamon, and Tribolet, who used the Ki-67 monoclonal

antibody directed against a nuclear antigen present only
in proliferating cells during the G[ S.G

2

and M phases of

the cell cycle, demonstrated a high variability in the pro-

liferating-cell index of gliomas (49). In routine neuro-

pathological study, the grading of gliomas is presently
done on the basis of morphological criteria, such as nu-

clear morphology, vascular proliferation, necrosis, and
mitotic activity although mitoses are not frequently ob-

served. In the future, in vitro and in vivo cell kinetic stud-

ies will need to be done if proper therapeutic strategies
are to be developed.

Other evidence of cellular heterogeneity has been sup-

plied by the Brain Tumor Study Group (50). In this

BRAIN TUMORS

119

study, systemic 1,3-bis (2-chloroethyl)-l-nitrosourea
(BCNU) was identified as the current best chemothera-
peutic agent for patients with anaplastic astrocytomas
and glioblastomas. Less than 50 percent of patients in

the valid study group responded to BCNU given intrave-

nously every 5 weeks. Thus, patients with a glioblastoma
may have a wide variety of responses to chemotherapy or

the response may vary in different areas of the same tu-
mor (51,52). The in vitro drug sensitivity studies per-

formed by Rosenblum and Dougherty at the University

of California at San Francisco also demonstrate the vari-
able drug sensitivity of the glioblastoma (53).

Diagnostic Studies

The diagnostic test of choice for a patient with an as-

trocytoma is enhanced computerized tomography (CT)

or enhanced magnetic resonance imaging (MRI). On
CT, astrocytomas demonstrate a uniform depression of
attenuation values. After the administration of contrast

agent, astrocytomas generally enhance above the pre-

contrast density level. Vascularity and necrosis show
good correlation with contrast enhancement in supra-

tentorial astrocytomas. These tumors are usually

surrounded by zones of decreased attenuation of varying
degrees and extent. Also, there is frequently an inner-
most sharply outlined area with extremely low values,
representing cystic components. Calcification of areas of

the tumor may be seen. Unfortunately, the distribution

of cells of a glioblastoma cannot be inferred from CT
images since the "peritumoral" area and low density

can overestimate or underestimate the extent of the
lesion (54).

MRI studies for tumors generally have a reduced sig-

nal on T,-weighted images and an increasing signal on
increasingly T

2

-weighted images. In gliomas, the compo-

nents and surrounding tissue are often but not always
shown best with T

2

-weighting (Fig. 2).

When the diagnosis of astrocytoma is made by CT or

MRI, cerebral angiography has a limited role for plan-

ning further diagnosis and therapy. Although angiogra-

phy can demonstrate a shift of major cerebral vessels and
tumor stain or neovascularity, this study is often unneces-
sary for surgery.

Operation

The operation for astrocytomas and glioblastomas is

usually limited by the fact that these tumors are neither
circumscribed nor encapsulated. The more necrotic su-

perficial parts of the central tumor are easily resected,

but the more viable periphery and the deep aspects of the

tumor usually fade imperceptibly into normal brain tis-

sue. The blood-brain barrier usually remains intact in

R

FIG. 2. T

2

weighted MRI of left temporal lobe astrocytoma.

Preoperative evaluation of MRI indicated that complete surgi-

cal removal was impossible. Patient has done well two years
following partial lobectomy and irradiation treatment.

the peritumoral area, making it difficult to visualize this
area on CT scan or with the microscope during the oper-
ation. Thus, in nearly every operation, the surgeon must
realize that a cure is not affected by gross radical removal
of the tumor.

At present, there remain four indications for surgery:

(1) to establish the histologicaJ diagnosis and plan adju-

vant treatment by submitting tissue for detailed labora-
tory analysis; (2) to relieve the symptoms and signs of
increased intracranial pressure and thereby lessen me-

chanical brain shift and improve neurological function;

(3) to perform cytoreduction to "buy time" for x-ray
therapy and chemotherapy to take effect; and (4) to re-

duce pressure and change tumor kinetics to make the

tumor more sensitive to radiation and chemotherapy.

These indications remain valid at a time when CT and
MRI scans allow increasingly accurate diagnoses, and
steroids are extremely effective in reducing the signs of
increased intracranial pressure.

Gliomas are associated with cerebral edema which is

often extensive. This vasogenic edema, caused by leak-
age of protein across the defective blood brain barrier, is

the partial cause of the increased intracranial pressure
and neurological defects seen in patients with gliomas.
Brock has shown that even slight local brain compres-

sion over short periods of time gives rise to cerebral

edema and a decrease in regional cerebral blood flow
(55). The cerebral edema and increased ICP should be

reduced by the use of steroid administration three to five
days before the operation. Miller and coworkers, in a

study of methylprednisone treatment of 10 patients with
brain tumors, showed that clinical improvement and re-
duction in periventricular elastance occurred within 24

120 / CHAPTER8

hours of treatment, but that ICP was not significantly

reduced until the second day of therapy (56).

The plateau wave is one of the ICP waveforms ob-

served in patients with increased ICP from various
causes. Matsuda, Yoweda, Handa, and Gotoh found a
remarkable decrease in cerebrovascular resistance dur-
ing the plateau wave, concluding that plateau waves are
caused by marked cerebral vasodilation (57). This sup-
ports the thesis that cerebral blood volume is increased
during the plateau waves. Plateau waves are observed in
brain tumor patients with severe increases in ICP, on a
chronic basis, and may well account for the paroxysmal
systems such as severe headaches with vomiting. Suffi-
cient administration of preoperative steroids will reduce

or abolish these plateau waves as has been shown in pa-

tients having ICP monitoring prior to operation.

Cerebral Metabolism

The neurosurgeon who cares for the patient with a

brain tumor must not only be able to evaluate the patient
clinically and interpret radiological studies, but must

also understand how cerebral metabolic parameters are
altered by surgery.

In patients with brain tumors who do not have clinical

signs of increased ICP, CSF acid-base status and cerebral
gas exchange are almost normal. With increased ICP,
there are changes in cerebral metabolism and cerebral

circulation. Increase in ICP is associated with a decrease
in cerebral blood flow and an increase of lactate concen-

tration and lactate/pyruvate ratio in brain tissue and

CSF (58). A decrease in cerebral venous pH and Po

2

and

an increase in Pco

2

, lactate concentration, and lactate to

pyruvate ratio have been observed with increased ICP.
After reduction of abnormal ICP, a reactive hyperemia

develops with a further increase in the concentration of

lactate and in the lactate/pyruvate ratio in brain tissue

and CSF. This reactive hyperemia is believed to be
caused by cerebral extracellular acidosis. Following an
operation on a patient with a brain tumor, a further de-
crease in brain oxygenation and an increase in brain aci-
dosis has been demonstrated, suggesting an additional
decrease in cerebral blood flow. In this study, the CSF

metabolic acidosis was most pronounced during the sec-
ond and third postoperative days. The degree of CSF
metabolic acidosis was closely related to an altered level

of consciousness and to outcome. In all fatal cases, post-
mortem study revealed cerebral edema (58).

Acidosis may contribute to the development of cere-

bral edema through two different mechanisms. In acido-
sis, cation transport across the cell membrane is im-
paired, causing an increase of sodium in the cells and

subsequent intracellular edema. The other possible

mechanism is that extracellular acidosis causes dilation
of arterioles and an increase of cerebral blood volume,

resulting in increased ICP and extracellular edema

caused by plasma extravasation through the damaged
vessels.

Anesthesia

The choice of anesthetic for a patient with a brain

tumor must take into account the fact that the tumor has
caused many intracranial metabolic and physiologic

changes, the most notably high ICP, even following the

extended use of steroid medication preoperatively (59).

The current anesthetic of choice is a balanced barbitu-

rate-narcotic-N

2

O anesthetic technique, using pentothal

induction and short-acting narcotics such as sublimaze.
The use of moderate hyperventilation to a Pco

2

of about

28 mmHg is helpful in lowering intracranial pressure. In
addition, the use of both osmotic and distal-loop di-
uretics is recommended, with electrolyte monitoring to
recognize and treat serum electrolyte changes. Mannitol
is given in a 20-percent solution at a dosage schedule of 1

gm/kg. Furosemide (Lasix) is then given to promote tu-
bular diuresis; thus, ICP reduction is caused by fluid shift
from the brain into the vascular system.

In patients undergoing operation on the brain, certain

monitoring techniques are routinely employed. Patients

are monitored with electrocardiography and peripheral
arterial and central venous pressure lines, intermittent
arterial blood gases, expiratory CO

2

levels, and urinary

output. A patient placed in any position that might allow

intracranial air embolism should have additional moni-
toring with a precordial Doppler ultrasonic detector and

have a right atrial catheter in place to remove any signifi-
cant air.

Position of the Patient

The position of the patient for operation depends, of

course, on the location of the tumor. The tumor should

be ultimately in clear view and in a position that lends
itself to use of the microscope. Each surgeon has prefer-
ences but, in general, if the microscope is used, then 3-
point cranial fixation is important to prevent move-

ment. The head should always be slightly above the level
of the heart to promote good venous drainage. An unob-
structed airway is of utmost importance, and good com-
munication with the anesthesiologist is essential

throughout the entire operation. The head should never
be turned or fixed in such a manner that would occlude

jugular venous return from the head, regardless of the

type of flexible endotracheal tube used. Armored endo-
tracheal tubes should be used to prevent kinking and

occlusion of the airway.

Generally, the patient is in a recumbent, supine, or

semisitting position. The sitting position is still used for
some posterior fossa operations, but should not be used
without the techniques noted above to detect air embo-

lism. Also, there is risk of cord damage caused by neck

BRAIN TUMORS

121

flexion in the sitting position, especially in elderly pa-
tients with cervical spondylitic ridges. Quadriplegia has
been reported after operations performed in the sitting
position (60). Preoperative testing of the awake patient

to assess the ability of the patient to sit in the operative
position for 15 to 20 minutes without producing neuro-
logical symptoms may be valuable. When a patient dete-
riorates after posterior fossa surgery performed in the
sitting position, tension pneumocephalus should be con-

sidered. As cerebrospinal fluid is evacuated intraopera-

tively, air enters the potential subdural space. With the
closure of the operative wound, air is loculated intracra-

nially and eventually dissects frontally because of the

usual supine position of the patient following surgery.
Nitrous oxide used for anesthesia will rapidly diffuse into
a cavity to equilibrate the partial pressure of N

2

O with

that in the blood. Thus, N

2

O anesthesia may potentiate

tension pneumocephalus by increasing the volume of
intracranial gas (61). This may result in focal deficit or
generalized neurologic deterioration associated with in-
creased ICP. The treatment is twist-drill aspiration of

the air.

Technique

Unless the tumor is small, difficult to locate, or deep

near the midline, surgery for gliomas is generally not

nearly as complicated as surgery for most other brain

tumors. In operations for gliomas, the craniotomy is
placed directly over the tumor that has been localized by
analysis of the preoperative studies and by considering
the appearance of the exposed cortical and vascular anat-

omy. Locating the tumor by ultrasound is rarely neces-
sary. Usually, the cortical incision is placed into, or im-

mediately adjacent and parallel to the sulcus overlying

the tumor, sparing important arteries and veins. Every

effort is taken to avoid the eloquent areas of the brain
serving speech and motor functions. It is best to ap-
proach the tumor through the shortest route possible so
as not to undermine wide cortical areas. Supratentorial
gliomas are generally not well circumscribed and are
without a sharp plane of cleavage between the tumor and
the adjacent sulcus (Fig. 3) or the underlying edematous

white matter. Using magnification, dissection is possible
along the indistinct cleavage planes, and the tumor
usually can be successfully freed grossly from all sides
except along the base. Unfortunately, anaplastic astrocy-
tomas and glioblastomas have a tendency to blend imper-

ceptibly with the subependymal white matter and the
ventricular wall making complete removal difficult or

truly impossible (62-67). The Cavitron Ultrasonic Sur-
gical Aspirator (CUSA) and lasers are important adjunc-
tive instruments in tumor removal. The aspirator allows
rapid, gentle removal of tissue without unnecessary
trauma to the brain. A CO

2

laser is a useful adjunct in

evaporating gliomas.

At the conclusion of tumor removal, the operating mi-

croscope should be used to inspect the tumor bed for any

residual tumor tissue that can be vaporized by the CO

2

laser. Absolute hemostasis must be achieved before clo-
sure.

Enhanced CT or MRI scans are not only the most

useful studies for evaluating the resectability of a supra-

tentorial glioma and in planning the operation, but they
are also the best postoperative tests to assess the amount

of tumor removed during the operation. The initial post-

operative CT or MRI scan should be performed as soon

as possible after the operation.

FIG. 3. Glioblastoma appearing well de-
marcated on surface of brain, but grossly

and microscopically infiltrating brain in the

deep white matter.

122 / CHAPTERS

Outcome

Salcman surveyed the literature and reported the me-

dian survival after operation for 1,561 patients with a
glioblastoma to be 6 months, with only 7.5 percent living
at 2 years (68). All mortality curves converge at 18 to 24
months irrespective of treatment, radiotherapy being the
best adjunctive treatment during the first 18 months
(68,69). Anaplastic astrocytoma has a more protracted
course than glioblastomas multiforme, provided that the
tumor is confined to a unilateral lobar location and ade-
quate treatment is prescribed. Young age at presentation

has been the most significant factor, in addition to histol-

ogy of the tumor, favorably prolonging survival in many

studies of patients with malignant gliomas (70). Retro-

spective reports on the treatment of the gliomas, without
strict histological review by a central pathology group,
are of little value in the discussion of outcome (71). Pro-
spective controlled studies of this tumor by Walker and

the Brain Tumor Study Group are providing data as to
the predictive value of histology, age of the patient, and
neurologic condition of the patient at the time of opera-
tion (50). The data of this group also provide the basis for

present and future chemotherapeutic studies. Unfortu-
nately, one of the most commonly used chemotherapeu-

tic agents for the treatment of patients with anaplastic
astrocytoma, BCNU, is associated with severe pulmo-
nary toxicity (72,73). Thus, it now appears that another
form of therapy, possibly immunotherapy, will be neces-

sary in the treatment of glioblastoma since all current

treatments—operation, irradiation, and chemotherapy
—are self-limiting and each leaves residual malignant
tumor cells leading to recurrence of the tumor symp-
toms. As yet. however, no form of immunotherapy, in-
cluding the once promising LAK-cell therapy, has been

significantly beneficial to patients with malignant brain

tumors (74).

Reopemtion

Following surgery and adjuvant therapy for glioblas-

toma, recurrence usually ensues in months (75). Opera-
tion for recurrence is increasingly being performed.

Though 90 percent of recurrent tumors will be at the site

of the original tumor, effects caused by bilateral and

deep invasive spread rather than mass effect are usually

observed at the time of recurrence (76). More authors are
describing reoperations for recurrent glioblastoma and
the number of patients undergoing reoperation are be-

coming a greater percentage of the total number of pa-

tients having an operation. Unfortunately, there are in-

creasing numbers of reports of patients developing

dissemination of the tumor at the time of recurrence
(77). This is especially true of patients living longer after
multimodality therapy including surgery, conventional

radiotherapy, interstitial radiation therapy, and BCNU

chemotherapy. Thus, new forms of therapy such as in-
terstitial radiation may effectively control the tumor at
the initial site, only to be followed by dissemination of
the tumor to multicentric hemisphere or leptomeningeal
sites. Craniotomy and shunting procedures have often
been implicated in the dissemination of gliomas. Special
precautions to minimize iatrogenic metastases, includ-
ing minimal tumor manipulation and preoperative irra-
diation, will need to be considered in future treatment
protocols for patients with gliomas.

Another indication for reoperation is radiation necro-

sis secondary to whole brain or, more likely, interstitial
irradiation. This latter form of therapy is being increas-

ingly used with definite prolongation of life, but asso-

ciated with a 40 to 50 percent incidence of radiation

necrosis. The necrosis is at times not amenable to steroid

treatment and will require reoperation if the CT or MRI
scans leave the diagnosis in doubt or if the patient's con-
dition deteriorates from mass lesion effect.

Ransohoff and Lieberman have defined the major cri-

teria for reoperation following recurrence (78). Essen-

tially, the recurrence should be causing neurological

symptoms and deficits because of mass effect, the recur-
rence should be in a polar location, and the patient

should have had six good clinical months since the origi-

nal operation. Recently, Ammirati and Harsh with their

associates published a series of patients with anaplastic

gliomas and glioblastomas with a median survival of 36
weeks after reoperation (79,80). Patients undergoing ex-

tensive resection with preoperative Karnofsky ratings of

70 or better have the best chance of benefitting from

reoperation.

Recurrence of a glioma after operation or chemother-

apy may be associated with a cyst. Poisson and co-
workers found a 5 to 8 percent incidence of cystic glio-
mas, and Afra, Norman, and Levin estimated the true
absolute incidence to be 8 to 10 percent in recurrent

malignant gliomas (81,82). In four patients with cystic
recurrence of tumor reported by Levin and associates,

the cyst was accompanied by clinical signs of acutely

increased ICP and aspiration produced prompt re-
lief (83).

Sequential CT or MRI scanning is useful to detect the

positive effect of a treatment plan in clinically stable pa-

tients, nontumor-related causes of clinical deterioration,
early treatment failure as a prelude to reoperation and/or
change in drug protocol, and complications of the treat-
ment plan such as the 20 percent incidence of ventricu-

lar enlargement (84).

Metastasis

There have been only 72 cases reported of metastases

of astrocytomas and glioblastomas, with extraneural me-

tastasis most commonly occurring in adults. The metas-

tases were pulmonary and pleural. Only eight cases devel-
oped without a previous craniotomy, and in another
eight, the extraneural metastasis developed via a sys-
temic shunt (85-87). The reasons for the rarity of this

event are undefined at present. Explanations include the

brief survival of most of these patients, the absence of
lymphatics in the central nervous system (CNS), the lack
of access of the tumor cells to the venous system, and a
systemic immune response that prevents the implanta-
tion of tumor cells in the periphery. The fact that most of
these patients with extra-CNS metastases had undergone
prior operation indicates that the entrance of tumor cells

into the vascular system is an important precursor of

spread outside the CNS (88). Morley has demonstrated

tumor cells in the jugular vein during craniotomy and
probably, as patients live longer, astrocytomas and glio-
blastomas will no longer be considered local diseases of

the brain (89).

Cerebellar Astrocytomas of Childhood

P»:

Incidence

Cerebellar astrocytomas of childhood are regarded as

the least malignant of all gliomas (67). They are the most
common infratentorial tumor in children, with an inci-
dence of 48 percent in Matson's series of brain tumors in
childhood (90). This tumor occurs predominantly in the
first two decades of life.

Symptoms and Signs

The symptoms and signs may be those of increased

intracranial pressure from hydrocephalus or lateral cere-
bellar signs with unilateral motor and cranial nerve defi-
cits, particularly limb ataxia. There may be morning
vomiting, irritability and headache, as in a patient with a

medulloblastoma.

The examination usually reveals papilledema, nystag-

mus, and cranial nerve palsies, especially of the sixth and
seventh cranial nerves. Dysmetria of the ipsilateral limbs

is usually present and the patient has a tendency to fall to

the side of the tumor.

Pathology

It is possible to distinguish between two groups of

childhood Cerebellar astrocytomas: (1) juvenile astrocy-
tomas, according to the classification of Russell and Ru-
binstein, and (2) a group morphologically resembling ce-

rebral astrocytomas, with a poorer long-term prognosis.

Both may be cystic.

Russell and Rubinstein actually divided childhood

BRAIN TUMORS 123

cerebellar astrocytomas into three types: (1) a juvenile

pilocystic type; (2) a juvenile pilocystic type having bun-

dles of glial fibrils separated by spongy areas; and (3) a
diffuse astrocytoma indistinguishable from cerebral as-
trocytomas (1). About 15 percent of cerebellar astrocyto-
mas belong to the latter type. Both in vitro and in vivo
biological differences exist between the two general

types—juvenile and diffuse—of cerebellar tumors. In

particular, bipolar cells are characteristic of the juvenile
astrocytoma; these are preserved during tissue culture
and in transplants (91,92).

Diagnostic Studies

Skull x-rays may show signs of increased ICP. CT or

MRI is of great diagnostic value as it will show a cystic
lesion in a cerebellar hemisphere or in the midline ver-
mis (Fig. 4). Enhanced MRI appears to show the margin
of these tumors very distinctly and, in our experience,

these margins correspond closely with the extent of tu-

mor found at operation.

Operation

Either a midline bilateral craniectomy with removal of

the arch of the atlas or a paramedian approach with uni-

lateral craniectomy can be employed to gain exposure

for cortical incision or needle aspiration. If cystic, the

cyst is drained and the cyst wall mural nodule is found
and removed. It is not necessary to remove the cyst wall.
as this is compressed brain tissue. This is often a most
gratifying procedure and results in relief of symptoms
from increased intracranial pressure and of local cerebel-

lar signs and symptoms. Solid astrocytomas cannot be

completely removed if they invade the brainstem, and
the operation must be confined to removal of the exo-
phytic portion of the tumor. The CO

2

laser is very useful

in evaporating the tumor from the brainstem.

Outcome

Early recurrence is rare after gross total excision. In

general, if there are no new symptoms four to five years

after surgery, one can be optimistic about a cure (93).

However, recurrences leading to death have been re-

ported 20 and 23 years after gross total removal (94),

suggesting the need for longer follow-up studies. Kuhlen-
dahl, Stochdorph, and Hubner found that 8 of their 70
patients with a cerebellar astrocytoma had an astrocy-
toma histologically identical to a cerebral astrocytoma;

all eight patients died within two to four years following

surgery (95).

In a report by Gjerris and Klinhen on cerebellar astro-

cytomas found in 10- to 14-year-old children (93), 70

124 / CHAPTERS

FIG. -4. (A) Sagittal MRI of cystic astrocytoma of vermis of the cerebellum; (B) gadolinium enhanced
axial MRI demarcating the tumor well and aiding in total tumor removal at operation.

percent were juvenile astrocytomas while 30 percent
were diffuse astrocytomas. For children with the juvenile

type of cerebellar astrocytoma, the 25-year cumulative

survival rate was 94 percent, compared with 38 percent
for children with the diffuse type. In the SEER registry,
the 5-year survival of 110 children with cerebellar astro-
cytoma was 91 percent (96).

Brainstem Gliomas

Incidence

Brainstem gliomas tend to occur during childhood

and adolescence. Russell and Rubinstein reported that

77 percent of their patients with a brainstem tumor were
under the age of 20 years, and they noted that brainstem

gliomas comprise a significant portion of the brain tu-

mors of children (1). Brainstem gliomas accounted for

18.7 percent of posterior fossa tumors in Matson's series

(90). At the Hospital for Sick Children in Toronto,

brainstem gliomas comprised 16.1 percent of all brain
tumors and 28.7 percent of all tumors found in the infra-

tentorial region (97).

Symptoms and Signs

These children usually present with cranial nerve pal-

sies, weakness of the arms or legs, sensory changes, and
difficulty with gait. Headache or any symptom of in-
creased ICP is rare.

The examination generally reveals multiple bilateral

cranial nerve palsies, usually involving the sixth and sev-
enth nerves; intranuclear corticospinal tract signs; and
ophthalmoplegia with hyperactive reflexes with Babinski

toe signs. The signs are usually bilateral, but not symmet-
rical. Papilledema is usually not found as hydrocephalus

does not occur early in these tumors.

Pathology

The vast majority of brainstem gliomas originate in

the pons and extend cephalad and caudad for a distance.
This produces a diffuse enlargement of the brainstem. In
the early phase of tumor growth, the tumor infiltrates
between normal neural structures, separating but proba-

bly not destroying them. The cells of brainstem gliomas
are very similar to those of diffuse fibrillary astrocytomas
of the cerebral hemispheres. They may undergo anaplas-

tic changes. Russell and Rubinstein reported that 62.8
percent of these tumors in their series showed changes in
keeping with glioblastoma multiforme (1).

Hoffman, Becker, and Craven have reported a small

group of these tumors that have a distinct biological be-

havior (97). The symptoms in this group begin in early
childhood or even in infancy and the history is usually
long. These tumors fill the fourth ventricle, may extend

up into the cerebellopontine angles, and may mushroom
down over the dorsal surface of the cervical spinal cord.
Pool reported on three patients who had a partially cystic
or nodular infiltrating brainstem glioma that responded
favorably to operative decompression and irradia-
tion (98).

Diagnostic Studies

Patients with brainstem gliomas deserve the most criti-

cal diagnostic studies. A properly performed CT or MRI

A

BRAIN TUMORS / 125

scan may prevent unnecessary posterior fossa opera-

tions. In all cases of brainstem gliomas, the brainstem

appears widened on CT or MRI, and the fourth ventricle

will be abnormal. Most often, the fourth ventricle ap-

pears flattened, with an apparent increase in its trans-
verse diameter, and will be displaced posteriorly. CT sec-
tions thinner than 13 mm are often required to
demonstrate the flattened fourth ventricle (99). Attenua-
tion profiles for brainstem tumors are variable and of no
value for diagnosis, although the most malignant tumors

are believed to show the greater enhancement. The tu-
mor may be of low density and not enhance, low density
with enhancement, isodense without enhancement,
mixed density with enhancement, or increased density
with enhancement. Tumors with increased density,

which appear to fungate into the fourth ventricle or sub-
arachnoid cisterns and enhance strongly with a contrast

agent, are the only lesions that should be considered for
open operation (craniotomy).

Patients who have an enlarged brainstem on MRI or

CT scan, without tumor extension into the ventricle or
subarachnoid spaces, should not require an open opera-

tion. The radiologic study of choice for children and ado-
lescents with hydrocephalus should be MRI, including
axial and sagittal T

r

and T

2

-weighted images (100).

Outcome

In the past, survival for longer than one year was so

uncommon that Matson stated that if a patient was stil

alive 18 months after diagnosis, reinvestigation and sur-

gical exploration was indicated, as some other lesion was

probably present (90). Even today, intrinsic gliomas of
the brainstem have a bad prognosis, and most children
with such tumors have a median survival of less than one

year in most studies, regardless of therapy. In Hoffman

and associates' series of 111 cases, 51 were verified histo-
logically and 32 (62%) of these were Grade III or IV
astrocytomas (97). In this series, there were 10 patients
(8.3%) who had clinical evidence of increased intracra-
nial pressure. Of the 10 patients, 5 had hydrocephalus.
and 5 presented before the age of two with a history of
vomiting and failure to thrive. Of these 10 patients in
Hoffman's series/ 8 had long-term survival, with the lon-

gest survivor alrve 15 years after treatment. Thus, the
clinician should, be aggressive and make every attempt to
treat this subgroup successfully by subtotal surgical exci-
sion and radiotherapy. There are some recent reports of
benefit from combination chemotherapy with 5-flu-
orouracil, l-(2-chlorethyl)-3-cyclohexyl-l-nitrosurea
(CCNU). hydroxyurea, and 6-mercaptopurine for recur-
rent brainstem gliomas (104-106).

Operation

In 1968, Pool strongly suggested that any patient sus-

pected of harboring a brainstem glioma should have an

operation (98). If, following exposure of the brainstem, a

biopsy does not appear to be a safe undertaking, a visual

inspection may nevertheless be helpful in confirming the
diagnosis. An enlarged brainstem with elevation of the
floor of the fourth ventricle, but without exophytic tu-

mor mass, should be viewed as strong evidence for a
brainstem tumor. If there is any evidence by contrast
study of a cyst, stereotactic needle aspiration can be at-
tempted (101-103).

Fortunately, since Pool's 1968 report, CT and MRI

scanning has enabled clinicians to make a more certain
diagnosis prior to operation. Not only will the scan show
the enlarged brainstem as was previously visualized only
on pneumoencephalography, but an enhancing exo-

phytic mass may be seen. As emphasized by Hoffman,

this mass, especially if found in a child with a long clini-
cal history, should undergo surgical resection. At opera-
tion, the solid part of the mass that fungates out of the

dorsal aspect of the brainstem can be safely removed by
microsurgical techniques. Usually, a small portion of the
tumor must be left in the floor of the fourth ventricle and

in the medulla (97).

Optic Nerve Gliomas

Incidence

Optic nerve gliomas comprise 1.7 percent of all intra-

cranial gliomas (107) and up to 7 percent of gliomas in
children (108). They are actually slowly growing, non-

metastasizing neoplasms of the anterior visual pathway.
Seventy-five percent of optic nerve gliomas occur in the
first decade and 90 percent occur in the first two decades
of life, with equal sex distribution (109). These tumors

are present in 1 of 100,000 patients with eye symptoms.

Symptoms and Signs

The clinical presentation depends on whether the tu-

mor is in the orbit or is located intracranially. Intraorbi-
tal gliomas present with painless proptosis, which may
be the only sign, especially in infants. The most common
initial symptom is loss of vision. Bilateral blindness is
unusual, even in advanced cases. In children, visual loss
may present as strabismus or nystagmus. The visual field

defects are variable and nonspecific. Some patients have

scotoma of the central field, but peripheral field defects

are also common. The defects may be dense or mild,

quadrantic, hemianoptic, or irregular. There may be ab-

126 / CHAPTERS

sence of bitemporal hemianopia even when the chiasm is

involved.

Pathology

The pathology of optic nerve gliomas is the subject of

continuing controversy. There is now general agreement
that the optic nerve glioma is an astrocytoma and many
of these tumors, especially in children, have a slow be-
nign biological course. Currently, most authors use the

term "pilocystic astrocytoma of the juvenile type" and
compare the biological behavior of optic gliomas to pilo-

cystic astrocytomas in other parts of the ncuraxis
(110,111). The association of optic nerve gliomas with

neurofibromatosis has been noted at least since 1893.

The relationship between von Recklinghausen's disease
and optic nerve tumors has long been known, and by

1954 approximately 500 cases of glioma of the optic

nerve and chiasm had been reported in the literature,
with 22 percent (108 cases) associated with von Reck-
linghausen's disease. Now the generally accepted inci-

dence of optic nerve glioma in association with neurofi-
bromatosis is approximately 25 percent (112). These

tumors may be multicentric, originating in more than

one locus, or may spread through the chiasm to involve

the opposite optic nerve. No doubt these tumors will be

found more frequently with the increasing use of CT and
MRI scans.

In a series of 84 patients with gliomas involving the

chiasm, only 7 percent had neurofibromatosis and 70

percent of patients with gliomas involving only one optic

nerve had neurofibromatosis (112). Multicentric glio-
mas are frequently associated with neurofibromatosis.
The association with neurofibromatosis doubles the re-
currence rate following the complete excision of an in-

traorbital glioma but does not affect the prognosis follow-

ing irradiation of chiasmal gliomas (113).

A highly malignant optic nerve glioma does occur in

adults and rapidly infiltrates the chiasm and hypothala-

mus, causing death.

Diagnostic Studies

CT and MRI scans are especially useful for intraorbi-

tal pathology and will nearly always document an optic

nerve glioma. This is generally revealed as an enlarged

optic nerve in comparison with the optic nerve of the

normal eye (114). A CT and/or MRI scan should differ-

entiate a glioma of the optic chiasm from a craniopha-

ryngioma by the sharp outline of the craniopharyn-

gioma, which is often cystic and calcified (115). \

Plain skull x-rays should always include views of the

optic foramen. The optic foramen and canal will usually

be enlarged on the side of the tumor.

Operation

Neurosurgeons generally approach the optic nerve

and chiasm by a frontal craniotomy approach over the
orbital roof. The latter can be opened when necessary
and intraorbital contents exposed to remove an optic
nerve tumor. If the tumor is confined to one optic nerve
by clinical examination and radiological studies, opera-
tion for total removal is advised. If at operation the tu-
mor is verified to be confined to one optic nerve, total
excision of the nerve is indicated.

The glioma that invades the optic chiasm or hypothala-

mus is impossible to completely remove. A biopsy
should be done at operation to rule out a craniopharyn-

gioma, which can displace and stretch the optic chiasm,

giving the appearance of an infiltrating neoplasm. A spi-

nal fluid shunt is indicated if the spinal fluid pathways

are blocked.

Outcome

The reports of Oxenhandler and Sayers, as well as Al-

vord and Lofton, confirm these lesions to be neoplasms

and not hamartomas as suggested by Hoyt (116-118).
Therefore, total excision should be done for unilateral
optic nerve gliomas, especially when there is severe vi-
sual loss or blindness. Prognosis for survival is excellent
(116,119,120). Surgical excision is better than irradia-

tion to prevent recurrence of optic nerve gliomas but of

course does not preserve vision (121). About 25 percent

of optic nerve gliomas have already invaded the optic
chiasm at the time of diagnosis and another 5 percent
recur in the chiasm following "complete" intraorbital
excision. There is a stepwise effect of age on outcome,
with an increasing probability of death from tumor
above the age of 20 years, especially obvious in patients

over 50 years of age, half of whom have glioblastoma

multiforme (117).

Ependymomas

Incidence

Ependymomas had an incidence of 1.9 percent of

3,878 histologically verified neoplasms involving the

central nervous system and 3.4 percent of 2,186 gliomas

at the Montreal Neurological Institute during the period

1928 to 1964 (122). In this series, 47 patients had intra-

cranial ependymomas; 64 percent were female. The
average age at admission was 22 years, ranging from a
7-month-old male with a fourth ventricle ependymoma

to a 64-year-old male with a tumor in a similar location.

Posterior, fossa ependymomas are seen more frequently

BRAIN TUMOKS • 127

in children than are supratentorial ependymomas but
represent only 1 percent of tumors in the posterior fossa

in this age group (123). Supratentorial ependymomas
are usually present in the cerebral substance rather than
in the ventricular system (124).

Symptoms and Signs

Headaches are the most frequent complaint, probably

related to obstruction of the fourth ventricle. Vomiting
with the headaches is common. Diplopia, decreased vi-

sion, dizziness, ataxia, or extremity weakness are ob-
served at times. In a young child, the associated hydro-

cephalus may cause the head to enlarge. If there is
herniation of the cerebellar tonsils, cervical pain or stiff-
ness may be present.

Pathology

Although the ependymomas have been subclassified,

the histological grade of the tumor does not appear im-

portant in prognosis (123). There is, however, a clearly

malignant form—the ependymoblastoma (125). The

ependymoblastoma is a highly cellular, embryonal tu-
mor occurring in children, with a notably poor prognosis
and a tendency to subarachnoid spread. The myxopapil-
lary type is generally considered to be intraspinal. The
prognosis of malignant ependymomas is highly variable

but 67 percent of the patients reviewed by Ross and Ru-

binstein had a survival time of 8.8 years (126).

RG. 5. Ependymoma of the fourth ventricle appeared cir-

cumscnbed on surface but had a firm infittrating attachment

to the brainstem, making total removal by operation impossi-
ble.

Diagnostic Studies

Plain skull x-rays may show intracranial calcification,

especially with intraventricular ependymomas. If hydro-

cephalus develops there may be separation of the cranial

sutures, particularly in young children. The principal an-
giographic findings are nonspecific, with avascular
masses usually observed although focal tumor vascular-
ity is found in a minority of cases. Sixty percent of epen-
dymomas of the posterior fossa are associated with sub-
arachnoid extension of the tumor into the cisterna
magna and sometimes into the cervical subarachnoid
space, a point in the differential diagnosis of an ependy-

moma from a medulloblastoma on CT or MRI scan.

Operation

Surgery for an ependymoma should be as radical as

possible but should not proceed if an attempt to remove

the tumor would be likely to damage the brainstem (Fig.

5). Pierluca has noted that, at autopsy, recurrences are

not usually found at the site of tumor remaining in the

brainstem but rather in the cerebellum (127).

Outcome

In the series from the Montreal Neurological Institute,

there was a much poorer prognosis in the younger age
groups, primarily because of the dominant location of
the tumor in the fourth ventricle (122). Of the patients
over 15 years of age, 38.3 percent survived 5 years or
longer following surgery, whereas only 19.1 percent
under 15 years of age survived for the same period. Aver-
age postoperative survival as of 1965 for 7 patients with
grossly complete removal of tumor was 20 years. Hahn,
Shapiro, and Okawara also reported an especially poor

prognosis in patients less than 10 years of age (124). In

the review by Pierluca, the overall survival rate was 33
percent. Of the 25 who died during a period of 8 months
to 17 years postoperatively, the average time of recur-
rence was 2 years, and the average survival time was only
2j years (127).

128 / CHAPTERS

When tumor remains in the brainstem following oper-

ation or is clearly a malignant ependymoblastoma, irra-
diation of the tumor site is urged. Irradiation of the spi-
nal areas is not usually necessary. In the series from the

Montreal Neurological Institute, there were no instances
of spinal seeding (122), but there were cases of tumor
nodules involving the cauda equina in the series of 70
ependymomas of the floor of the fourth ventricle in the
series reported by Pierluca (127).

Oligodendrogliomas

Incidence

Among the gliomas, the oligodendroglioma deserves

special attention. These tumors are reported to represent
between 3 and 7 percent of primary brain tumors (128).
They occur primarily in the third and fourth decades of
life and are found primarily in the frontal lobes.

Symptoms and Signs

The patient with an oligodendroglioma usually has a

long history of headaches or seizures which relate to the
location of the tumor. Since Oligodendrogliomas fre-
quently involve the frontal lobes, personality changes are
common as well. Also, some of these tumors grow along
the walls of the ventricle and may reach the aqueduct or
even the fourth ventricle, causing obstruction of CSF
flow and hydrocephalus. Papilledema is the most com-

mon neurological finding.

Pathology

The oligodendroglioma was described and reported

initially by Bailey and Gushing in 1926 (129). Grossly,

the oligodendroglioma may present by expanding the
cortex or be observed to break through the cortex and

.attach to the meninges. The tumor is red-gray, is gener-

ally firm, and may contain cysts with small necrotic foci.

When cut, the tumor often has areas of gritty calcifica-

tion.

Microscopically, the tumor has been classified into

isomorphic and pleomorphic types, which is of clinical
significance. The isomorphic type is extremely cellular
and uniform in appearance. The cells are closely packed
like cobblestones, each individually "boxed in" by capil-
laries or connective tissue. The cells have regular central

nuclei and clear cytoplasm. The pleomorphic tumors are

much more anaplastic, with increased mitotic figures,

pleomorphic nuclei, focal necrosis, and endothelial vas-

cular changes. This more heterogenous appearance corre-
lates with a much more rapid clinical course.

Oligodendrogliomas are often "mixed" tumors, con-

taining areas of other glial differentiation. Russell esti-

mated that half of all Oligodendrogliomas contain some
component of a second tumor type, the significance of

which is unknown (1). It would seem that more Oligo-
dendrogliomas contain an anaplastic astrocytic compo-

nent than do not. Smith and associates devised a grading
system for Oligodendrogliomas, classifying the tumors

from A through D. They demonstrated a worse progno-
sis for higher-grade tumors (130). Others have not found
this classification system to be prognostically useful
(131,132).

Diagnostic Studies

Up to 65 percent of well-differentiated Oligodendro-

gliomas will exhibit stipplid calcification on plain skull
x-ray. This is the highest percentage of calcification
among all gliomas. Calcification is also highly visible on
the CT scan, which usually localizes the tumor well.
These tumors enhance with contrast and are usually
surrounded by mild to moderate edema. A cystic compo-
nent may be found as well.

Operation

The principles of operation for Oligodendrogliomas

are the same as those for astrocytomas of the cerebrum.
As much tumor as possible should be removed, leaving
the least tumor burden without increasing neurological
deficits. At times, the tumor may appear partially cir-
cumscribed and, with the aid of the microscope, can be
readily removed. Deep tumor involving the peri ventricu-
lar areas is, however, difficult to remove, as there is often

no cleavage plane between tumor and normal tissue.

Outcome

Weir and Elvidge, as well as Zulch and Wechsler, re-

ported that the postoperative survival of patients with an
isomorphic oligodendroglioma was almost twice as long
as that of patients with a pleomorphic tumor (108,133).
Survival was also longer in those patients who had com-

plete removal than in those who had incomplete re-
moval. Though some authors have stated that there is as
yet no proven value of radiation therapy in patients with
Oligodendrogliomas, others strongly point to a beneficial
effect from radiation therapy (131).

The 10-year survival rate for 14 patients with an iso-

morphic oligodendroglioma who received greater than
45 Gy irradiation was 56 percent, versus 18 percent for

11 patients who did not receive postoperative irradiation

(134). In a report by Richmond and McKissock on the

BRAIN TUMORS 129

pleomorphic tumor, no patient survived five years even
when operation was followed by irradiation (135). Thus,
the treatment of choice is radical removal with radiation
therapy (136). The patient with a pleomorphic oligoden-

droglioma should have chemotherapy as well, although

no controlled prospective studies have been reported.

Some patients respond well to BCNU. Oligodendrogli-

oma with metastasis outside the CNS is extremely rare
and, as of 1981, only 12 cases have been documented in
the literature (137).

young children, the head may enlarge from bydro-
cephalus.

The examination will reveal signs of intracranial hy-

pertension such as papilledema and bilateral sixth nerve
palsies. Other cranial nerve deficits, particularly seventh
nerve palsies, may be present. Gait and truncal ataxia is
usually prominent, and nystagmus with lateralizing dys-
metria of the arm and leg may be found. Frequently,

there is hypotonia of the limbs, but hyperreflexia and
Babinski signs are observed as well.

Medulloblastomas

Incidence

The medulloblastoma is a tumor found almost exclu-

sively in children. This tumor represents 15 to 25 percent
of all primary intracranial tumors in children under 16
years of age, but only 1 percent or less of primary brain

tumors in adults. In the SEER Registry, medulloblas-
toma slightly exceeds the incidence of low-grade supra-

tentorial astrocytomas in children, 25 percent versus 23
percent, respectively (96). Eighty percent of all cases of

medulloblastomas occur before the age of 16 and twice

as often in males as in females (138). This fact, plus the

knowledge that not only are CNS metastases common

but extracranial spread occurs to bone, lymph nodes,
testes, skin, pancreas, kidney, liver, intestines, ureter,

and ovaries without predisposing factors such as surgery,
survival, extensive subarachnoid spread, or radiation
therapy, makes the treatment of this tumor a special

challenge (139-142). Eighty percent of adult cases occur
between the age of 21 and 40 years; by 1979 only 13 cases
had been reported presenting after 50 years of age (143).

Symptoms and Signs

Patients with a medulloblastoma usually present with

some variation of the clinical triad of headache, vomit-

ing, and ataxia. Because most medulloblastomas de-

velop in the vermis of the cerebellum and, less often, in
the cerebellar hemispheres, the patient usually presents
with midline cerebellar signs. Children frequently have
morning projectile vomiting without nausea, secondary
to obstructive hydrocephalus. This vomiting may be
transient or disappear for several weeks before returning
with frank cerebellar signs. The child will gradually be-
come ataxic and fall or stumble more than previously

and finally will develop truncal ataxia. As the tumor in-

vades the cerebellum, localizing symptoms such as loss

of coordination will develop. As the brainstem is in-

volved by direct or indirect pressure or invasion, there
will be long-tract signs and cranial nerve deficits. In

Pathology

Neuropathologists have long recognized the capacity

of cerebellar medulloblastomas to differentiate. In 1925,
Bailey and Gushing considered the medulloblastoma to
be a tumor with the potential to develop along spongio-

blastic or neuroblastic lines (37). In 1934, Stevenson and
Echlin proposed that the medulloblastoma arises in the
fetal external granular layer of Obersteiner (144).

Palmer, Kasselberg, and Natsky have identified glial fi-

brillary astrocytic protein (GFAP) in 11 of 13 cases of

medulloblastoma (145). They conclude that medullo-
blastoma is a stem-cell neoplasm with multiple types of

differentiation. In 1983. Rorke proposed a new classifica-
tion system for primitive neuroectodermal tumors.
(PNETs) of which the medulloblastoma is the most com-

mon (146). Under this system. PNETs are separeted into

five groups based on cell differentiation: {1) glial, (2) neu-
ronal, (3) ependymal, (4) multipotential. or (5) without
differentiation. Some authors have found that the degree
of cell differentiation correlates with a significantly pro-

longed recurrence-free period and improved 5-year sur-
vival, but necrosis is associated with a decreased survival
time (147,148).

Diagnostic Studies

Plain skull x-rays in young children may reveal signs

of intracranial hypertension, such as sprung cranial su-
tures which can occur up to the sixth or seventh year
of age.

The CT or MRI scan will show a well-circumscribed

midline enhancing lesion, usually of large size, and any
associated hydrocephalus. This is usually diagnostic for
medulloblastoma but it should be recalled that contrast
uptake in a cerebellar arteriovenous anomaly, particu-

larly in children, may simulate a tumor (149).

Medulloblastomas are slightly hyperdense, with mean

attenuation values nearly 10 Hounsfield (EMI) units
higher than those of astrocytomas (150). Mean posten-

hancement attenuation levels are significantly above

those of astrocytomas. Medulloblastomas are sur-

130 / CHAPTERS

rounded by zones of moderately decreased density, the

outer border of which is not as sharp as in astrocy-
tomas.

Operation and Postoperative Therapy

The therapy for a child with a medulloblastoma re-

mains a challenge. This rapidly growing tumor is often

localized and attached to vital structures and has a well-
recognized tendency to seed within the CNS, especially
within the spinal canal. Microimplants or metastases
have been described as being found at the original opera-
tion (151), though other authors claim CNS spread is the
result of the original operation itself (1). This spread pre-

cludes cure by operation alone. In Cushing's series of
cases treated by operation alone, the maximum survival

was 21 months and averaged 7 months (152).

The current best treatment for medulloblastomas in-

cludes surgery, irradiation, and polychemotherapy

(153). A secondary temporary or permanent spinal fluid
shunting procedure may be indicated to control hydro-
cephalus caused by the tumor (154,155).

Operation on the tumor is indicated to conclusively

establish the diagnosis. CT or MRI scanning may not
definitely differentiate a medulloblastoma from an epen-
dymoma (150). Moreover, surgery will reduce tumor
burden, leaving less mass for radiotherapy and chemo-
therapy. The goal of the operation should be to perform
gross total tumor removal without increasing neurologi-
cal deficits (156). The operation usually requires split-
ting the midline vermis, but this is usually done without

neurologic sequelae. Once the vermis is split, the tumor
is easily seen as a reddish-purple mass that can be re-
moved by suction-aspiration. Intraoperative magnifica-

tion of the tissue interface will allow differentiation of
tumor from brain, as the tumor may well infiltrate into
the cerebral peduncles, cerebellar hemispheres, and floor
of the fourth ventricle. No damage must occur to these
vital structures, as the resultant postoperative ataxia and
loss of coordination would be incompatible with normal

gait or even independent ambulation.

Radiotherapy has been used since 1919 in the treat-

ment of patients with a medulloblastoma. In 1930,

Gushing reported on the first case of whole CNS irradia-
tion for a medulloblastoma (152). Irradiation to the en-

tire central nervous system, including the supraorbital

cranium and brain, using modern equipment and dosim-

etry, can achieve a disease-free interval of five years in 50

to 60 percent of patients. Radiation treatment of the
craniospinal axis (CSA) is technically exacting and re-
quires painstaking attention to detail. Modern radiother-

apy has substantially improved the prognosis for patients
with a medulloblastoma. However, the best outcome

that can be achieved with conventional radiation ther-

apy alone is limited by CNS tolerance levels and proba-
bly has been achieved.

Unfortunately, radiotherapy, although offering a po-

tential for cure, also produces profound late side effects

that are detrimental to the patient, as well as limiting the
potential of other therapies. Though the importance of
x-ray therapy in this tumor cannot be overstated, cer-
tainly the complications should not be underempha-
sized. The size of the target dose is not settled, but Land-
berg and coworkers suggest an absorbed dose of 45 Gy in
not more than 30 fractions over six weeks to the demon-
strated tumor, and 30 Gy in 20 fractions over four weeks
to the subdural space (157). This dosage is well below the
threshold value for serious CNS reactions of 50 Gy in 45

days as reported by Lindgren (104). Using the high de-

gree of precision as outlined above, Landberg and asso-

ciates projected their 10-year survival to b& 53 percent.

Unfortunately, homogenous field radiotherapy has
failed to prevent recurrence of medulloblastoma (158).
For subclinical disease, Leibel and Sheline, at trie Univer-
sity of California, San Francisco, recommend doses from
3,500 to 4,500 rads for the brain, and 3,000 to 4,000 rads
for the spinal cord (159). Additional irradiation can be

given to sites shown by pretreatment scans or myelo-

grams to be involved. The posterior fossa dose is rou-

tinely boosted through opposed lateral fields to a total

dose of about 5,500 rads. The desg is reduced by approxi-

mately 1,000 rads in children of lessThan 2 years of age.
Adjuvant chemotherapy should also be given to patients

with medulloblastoma, at the time of bone marrow re-
covery and before asymptomatic recurrences occur. We

favor this because operation plus irradiation cures about

50 percent of these patients, leaving an equal number

who will suffer recurrences.

Among the most promising protocols advanced thus

far is that published by Venes and associates (160). Al-

though administered to only a small series of children
with a biopsy-proven medulloblastoma, whole neuraxis
radiation was followed by prolonged chemotherapy us-
ing vincristine and cyclophosphamide. The patients re-
ceived intravenous vincristine sulfate (1.5 mg/sq m) alter-
nating weekly with cyclophosphamide (300 gm/sq m) by
mouth. Both vincristine sulfate and cyclophosphamide

have been reported to produce prolonged remission of

the central signs and symptoms of recurrent medulloblas-

toma. Combination therapy with these two agents has
been shown to be effective in the control of childhood

neuroblastoma, a tumor that hi stologically resembles me-
dulloblastoma. The vinca alkaloids are cell-cycle-spe-
cific agents and block mitosis with metaphase arrest. Cy-
clophosphamide is a nitrogen mustard belonging to the

class of alkylating agents. This agent is not cell-cycle-spe-

cific and may act on cells at any stage of the cycle. With

this combination of agents for a period of two years, with
modification of dosage when toxic side effects occurred,

BRAIN TUMORS

131

Venes and coworkers reported no evidence of tumor re-

currence in the follow-up period, which ranged from 16
months to over 7 years.

The use of adjunctive polychemotherapy in cerebellar

medulloblastomas is logical. Duration of therapy at pres-
ent remains empirical. The recurrence rate for medullo-
blastoma appears to peak in the first two years and is

associated with a high percentage of deaths during this
period (161,162). Thus, the use of chemotherapy follow-

ing surgery and irradiation, during the period of aggres-

sive tumor recurrence and before onset of a large tumor

burden, appears to offer the best chance for immediate

and long-term control of medulloblastoma.

Reports of late chemotherapy for recurrent medullo-

blastoma, failing to obtain a long-term remission and

much less a cure, add further support to the concept of

[initial adjuvant chemotherapy for medulloblastoma. In

the report of Crafts and coworkers, 17 patients with re-
current medulloblastoma were treated with a combina-
tion of three drugs: procarbazine, CCNU, and vincris-
tine (163). Significant myelotoxicity, exacerbated by
prior irradiation, compromised therapy. After an initial
response, it was often necessary to reduce the high doses

of CCNU and procarbazine because of bone marrow tox-

icity. Although 10 patients showed an initial response,
on the basis of neurological improvement and decrease

in tumor size by radiological criteria, the median time to
progression was only 45 weeks, without any evidence of

a cure.

A report of Thomas and associates strongly suggested

that initial multimodality therapy for medulloblastoma
is more effective than late chemotherapy of recurrent
medulloblastoma (164). In their series, eight patients
with recurrent medulloblastoma responded to a regimen
consisting of vincristine, BCNU, dexamethasone, and in-
trathecal and intermediate dose intravenous methotrex-
ate (500 mg/m

2

). The median duration of response was

18.8 months. More importantly, four of nine patients

with newly diagnosed medulloblastoma, treated with the
same regimen, were well and disease-free at intervals of
up to 36 months. Intraventricular methotrexate and/or
intravenous BCNU during radiotherapy was associated
with severe toxicity, including three deaths. They recom-
mended against the use of intraventricular methotrexate
and advocated caution in the use of suppressive drugs
during the period of craniospinal radiotherapy. Al-
though this report is encouraging, we recommend with-
holding suppressive chemotherapy until there is clear re-
covery of bone marrow function following radiotherapy.

The role of chemotherapy in the treatment of medullo-

blastoma has not yet been clearly defined. The prelimi-
nary conclusions of the International Society of Pediat-

ric Oncology (165), the Children's Cancer Study Group,

and others indicate that chemotherapy may be useful in
delaying disease recurrence, but will not significantly

prevent recurrence (166). Furthermore, chemotherapy is

most useful in young children in whom there was exten-

sive tumor invasion and incomplete resection (167). fa
one study, there was no significant increase in the recur-.
rence-free period or in the survival rate in 15 patients

receiving adjuvant chemotherapy (168).

Outcome

In general, adult and female patients with a medullo-

blastoma have a better prognosis. Berry and coworkers
noted the five-year survival rate t\) be 60 percent for chil-
dren over five years of age and 48 percent for those under

five years of age (169). Proper therapy now advocates
removal of as much tumor as possible, followed by radia-
tion therapy. In general, gross tumor removal has been

found to produce the best long-term survival. This tu-
mor clearly has a potential for cure (164,170-174).
Operation allows for a great reduction of tumor burden,
without producing mental changes or profound neuro-
logical deficits. Radiotherapy clearly has a role in the
therapy of this tumor. Unfortunately, there are increas-

ing numbers of reports that children who receive irradia-

tion for intracranial tumors exhibit delayed intellectual
and even late endocrinological deficits. Raimondi and

Tomita have shown a significant difference in the mental

and physical development between the medulloblas-

toma and cerebellar astrocytonia groups which cannot

be attributed to hydrocephalus, anxiety, supratentorial

metastasis, or absence from school (175).

Other authors have also stressed postradiation mental

and behavioral disturbances. Hirsch and colleagues re-

ported a series of 57 patients with a medulloblastoma
operated on from 1964 to 1976 (176). The functional
outcome for 11 patients surviving with medulloblas-
toma was compared with that for 18 patients with cere-

bellar astrocytoma; the latter patients did not receive ra-

diotherapy. Only 36 percent of the medulloblastoma
patients had a normal scholastic record, compared with

72 percent of the patients with astrocytoma and 80 per-

cent of the normal control group. An IQ level lower than
70 was seen in patients in whom the medulloblastoma
had been adherent to the brainstem. It was postulated
that the psychological deficit could be caused in part by

malfunction of the thyroid and hypothalamic structures
secondary to irradiation. Other studies have suggested a

correlation between the number of rads delivered to the

hypothalamic axis and a deficit in growth hormone. Sha-
let and associates have demonstrated particularly well

these late effects in children who received cranial irradia-
tion for the treatment of intracranial malignancies (177).

Irradiation may affect the growing spine and lead to axial
growth retardation.

Lastly, spinal fluid markers, such as polyamines, may

132 / CHAPTERS

be useful in predicting the course of therapy in patients
with medulloblastoma (178,1791

Hemangioblastomas

Incidence

Hemangioblastomas are rare, benign, vascular tumors

that may arise anywhere in the body, and that account

for 1.0 to 2.5 percent of all intracranial neoplasms. The
most common site in the CNS is the posterior fossa, espe-

cially the cerebellum, where they comprise 7.3 to 8.8
percent of all posterior fossa tumors (181). Hemangio-

blastomas are thus the fourth most common tumor of

the posterior fossa; 80 percent of these tumors arc lo-

cated in the cerebellar hemispheres (180). They rarely
occur outside of the posterior fossa. Hemangioblastomas
occur both sporadically and as a manifestation of von
Hippcl-Lindau syndrome, characterized by tumors or

tumorlike lesions developing in several organs, including

angiomatosis of the retina (von Hippel disease). In addi-
tion to its association with angiomas of the cerebellum

and retina (originally described by Lindau and von Hip-

pel, respectively), cysts of the pancreas, kidneys, lungs,
liver, epididymis, as well as hypernephroma and
pheochromocytoma, may be present (181). In the von
Hippel-Lindau syndrome, it is rare to find two lesions
within the brain of a single individual, but the entire
spectrum of the syndrome may be found within a family
over several generations. The syndrome is inherited by
an autosomal dominant gene with 10 to 90 percent pene-

trance.

Symptoms and Signs

Patients usually have a long history of minor neurolog-

ical and psychosomatic symptoms prior to presenting
with headaches, dizziness, vomiting, and ataxia—the

usual symptoms of a posterior fossa mass. Headache is

the most common symptom. The most common present-

ing age is in the fourth decade of life, with cases rarely

presenting before puberty or after age 60. Strangely, the
lesion is not manifest at birth or in early life.

The family history is important in the diagnosis of von

Hippel-Lindau syndrome. A positive family history of
vascular tumors in a patient with the above symptoms
strongly suggests a hemangioblastoma, although cerebel-
lar hemangioblastomas more frequently occur sporadi-
cally. Rarely, the lesion may present as a subarachnoid
hemorrhage, a frequent presentation of a spinal heman-

gioblastoma.

The neurological examination most commonly re-

veals papilledema and cerebellar signs, such as horizon-

tal nystagmus, ataxia, slurred speech, and dysmetria. Ba-

binski's sign indicates involvement of the brainstem.

Ocular palsies, including abducens and facial nerve
weakness, are also common. Retinal angiomas are found
in 5 to 20 percent of patients with a cerebellar heman-
gioblastoma and von Hippel-Lindau syndrome.

Pathology

The nodule of the cystic hemangioblastoma is a well-

encapsulated ovoid mass which measures from 1 to 2.5
cm in diameter. It is formed of firm,\dcep red tissue that
has a hemorrhagic appearance on cross section. On histo-

logical examination, it is a highly vascular structure com-

posed predominantly of delicate blood-filled channels
that, in the eye, are primarily capillaries, The interstitial
cells contain nuclei, without mitosis, in abundant cyto-

plasm. The tumor may at times be confused with an

angioblastic meningioma or metastatic hypernephroma.
Exact diagnosis may require electron microscopic exami-
nation that may disclose secretory granules within the
tumor cells, indicative of erythropoietin production.
Generally, collagen is a prominent feature of meningio-
mas and is not present in hemangioblastomas (182).
About 30 percent of hemangioblastomas are solid, with-
out evidence of cyst formation. These forms are not well
demarcated from brain tissue (183).

Diagnostic Studies

A familial history of von Hippel-Lindau syndrome,

plus cerebellar symptoms and signs, will necessitate a CT
or MRI scan and a cerebral angiogram. The CT or MRI
scan will generally demonstrate a cystic lesion, with a
peripherally located contrast-enhancing mural nodule.
The vertebral arteriogram will demonstrate a large cystic
mass with a vascular nodule.

Erythrocytosis has been reported in cases of heman-

gioblastoma. Polycythemia has been reported less often.

The association of these conditions with hemangioblas-
tomas is quite uncommon.

Operation

The operation for cystic hemangioblastoma should

aim for cyst drainage and complete removal of the nod-
ule. The nodule is usually easily located and removed.
Complete removal of the nodule will ensure against re-

currences. Solid cerebral hemangioblastomas diffusely

infiltrate the brainstem and cannot be completely re-

BRAIN TUMORS

133

moved. Deep puncture biopsy or subtotal removal may

result in fatal intraoperative or postoperative hemor-
rhage.

Outcome

The operative mortality rate for cystic hemangioblas-

tomas should be very low, but for solid hemangioblasto-

mas, the mortality rate approaches 25 percent. Radia-

tion therapy has generally not been effective. The
recurrence rate is about 10 percent and relates to incom-
plete removal of the tumor nodule (184). In von Hippel-
Lindau syndrome, hemorrhage may occur in the retinal
lesions, leading to retinal detachment and secondary

glaucoma. Treatment may require laser photocoagula-
tion and even enucleation. Genetic counseling should be
given to patients and families with von Hippel-Lindau

syndrome (185).

Papillomas of the Choroid Plexus

Incidence

Papillomas of the choroid plexus are very rare tumors

that occur in adults and children. They comprise 0.4 to
0.6 percent of all intracranial tumors and 3.9 percent of
all tumors in patients under 12 years of age (186). They
are located in those portions of the ventricles that con-
tain choroid plexus. In adults, they are found in the

fourth ventricle, whereas in children, almost 90 percent

are found in the lateral ventricles and usually are symp-
tomatic before the age of three years. The tumors are rare
in the third ventricle. Those in the fourth ventricle may
extend into the cerebellopontine angle. Some authors
have claimed a higher occurrence in the left lateral ven-
tricle of males, but in most reported series no ventricular

or sex dominance has been observed.

Symptoms and Signs

The symptoms of a choroid plexus papilloma depend

on the patient's age and on the location of the tumor.
Generally, the tumor produces symptoms and signs of
increased ICP. In infants and young children, choroid
plexus papillomas present with a clinical picture of hy-

drocephalus, vomiting, irritability, squint, and enlarging
head. In infants, the fontanelle is full, hyperresonance of
the skull may be present, and usually the patient cannot

adduct the eyes. Older children may develop localizing

signs, such as hemiplegia, hemianopsia, or convulsions,

as their skulls do not expand. There may be asymmetri-
cal enlargement of the ventricles. The rapid and sudden

onset of hydrocephalus and the presence of papilledema
are two features that distinguish hydrocephalus due to a
choroid plexus papilloma from nontumor hydro-
cephalus.

Pathology

Grossly, these tumors appear pink-gray and tufted.

Some are so friable that removal can be difficult. Micro-
scopically, they are papillary with a single layer of co-
lumnar epithelium. They differ from papillary ependy-
momas by the absence of mucin and glia within the

papillae and by the lack of rosette formation and blepha-
roplasts. The pattern is monotonous, with branching fi-
brous stroma radiating from a single point. An ultrastruc-

tural study by Ghatak and McWhortner defined the

individual capillary structures to consist of an orderly
arrangement of epithelial cells, consistently juxtaposed
against a capillary and extracellular space containing
collagen and delicate cell processes (187). They con-
cluded that the fine structural details of the choroid
plexus tumor were essentially the same as those of nor-
mal choroid plexus and thus appeared ideally suited for

an active secreting function. The large size of some of

these tumors could therefore cause overproduction of
CSF and. if absorption pathways were not adequate, ven-

tricular enlargement. Leptomeningeal fibrosis may also

be an important factor in facilitating the development of
hydrocephalus.

It is generally assumed that choroid plexus papillomas

cause an over-production of CSF, as they are usually
associated with ventricular dilatation. Eisenberg and as-
sociates, using the ventricular perfusion technique,
found the CSF formation rate to be four times normal in
a five-month-old child with a choroid plexus papilloma
and hydrocephalus (188). Gudeman and coworkers re-
ported on a 3^-year-old child with bilateral choroid
plexus papillomas (189). Hypersecretion of CSF was re-

duced 50 percent after removing one tumor and, upon
removal of the second papilloma, reduction of ventricu-
lar size occurred; there was no sign of elevated ICP three
months postoperatively.

There is a rare malignant form of choroid plexus pap-

illoma. Dohrman and Collias could find only 22 well-do-
cumented examples in a 1975 report (190). This tumor is
typically located in the lateral ventricle of young chil-

dren. It can metastasize widely to remote areas of the
neuraxis, and cases of extraneural metastasis have been
reported. This tumor can be confused with cellular epen-
dymomas, or even metastatic adenocarcinomas, the lat-
ter, however, being rare in children. Russell and Rubin-

stein, as well as Lewis, have denned the pathological

criteria for malignant choroid plexus papilloma (1,191).

134 / CHAPTERS.

When a choroid plexus papilloma shows invasion of ad-

jacent neural tissue, loss of regular papillary architecture,

and cytological evidence of malignancy or anaplasia, it
should be regarded as a malignant tumor.

Diagnostic Studies

Both ventricular and lumbar cerebrospinal fluid pro-

tein have been reported as elevated (186). Cerebrospinal

fluid protein is usually not elevated in the more common
forms of hydrocephalus.

Plain x-rays of the skull usually show signs of in-

creased ICP. There is widening of sutures in infants and

young children. CT and MRI scans have replaced pneu-
moencephalography and ventriculography as the initial
diagnostic studies. The ventricle harboring the tumor is
usually larger, and there may be a shift of the ventricle
toward the opposite side. The tumors enhance with con-
trast.

An arteriogram will generally show the presence of a

hypertrophied anterior choroidal artery; possibly a "dou-
ble tumor" sign, with one tumor in the trigone and the
other within the temporal or frontal horn; tumor stain at

the trigone; asymmetrical hydrocephalus; and a shift
away from the side of the larger tumor.

Operation

Surgical considerations of lateral ventricle papilloma

include (1) asymmetrical communicating hydrocepha-
lus, (2) expansion of the tumor mass at the trigone with
occlusion and subsequent cystic transformation of either

the temporal or occipital horns, (3) extension of the tu-
mor mass along the choroid plexus through the foramen
of Monro and into the third ventricle, with resultant ob-
struction and progressive dilatation of the lateral ventri-
cle, and (4) extension of the tumor mass through the
choroidal fissure and into the quadrigeminal cistern
from where it may enter the opposite lateral ventricle or

the posterior fossa.

Surgical considerations of fourth ventricle papilloma

are (1) the invariable presence of symmetrical obstruc-
tive hydrocephalus necessitating a spinal fluid diversion
prior to or at the time of tumor removal, (2) determina-
tion of tumor extension into the aqueduct, cisterna
magna, or the pontocerebellar angle, and (3) consider-
ation of the possibility of tumor invasion of the fourth
ventricle or cerebellar hemisphere.

Trigone papillomas are best removed through a tem-

poral parietal bone flap that will give access to the tem-
poral pole anteroinferiorly and the angular gyrus pos-
terosuperiorly. Prior to opening the dura, the encysted
temporal horn can be drained affording immediate de-

compression of the brain. Usually, the gyri are flattened
on opening the dura. A linear cerebrotomy is made
within a sulcus located behind the angular gyrus. A 3- to
4-cm cerebrotomy will allow adequate exposure over the
surface of the tumor. The pedicle of the tumor must

always be identified first. This line of entry of the choroid
arteries and exit of the draining veins is found along the
inferomedial surface of the tumor. The feeding branches
of the anterior choroidal artery enter the tumor at its
posteroinferior medial surface. The vascular pedicle

from the trigone may extend anteroinferiorly along the

choroidal fissure toward the hippocampus superome-
dially, along the choroidal fissure toward the terminal
sulcus and foramen of Monro. The draining veins enter
the subependymal system, penetrate the choroidal fis-
sure to enter the quadrigeminal and galenic system or
may extend downward to enter the supraculminate sys-

tem. Smaller feeding vessels may be, coagulated but
larger feeding arteries should be clipped prior to section.
It is important that the tumor not be remoyed piecemeal

or by morcellation, especially prior to identifying, isolat-

ing, clipping, and severing the pedicle. Raimondi and

Gutierrez strongly recommend every attempt at "en-
bloc" removal of these tumors, regardless of size (192).

A lateral ventricle papilloma that extends into the

third ventricle may not only require the above approach,
but also a cerebrotomy in the frontal lobe if there is lat-
eral ventricle hydrocephalus or an encysted frontal horn.
The foramen of Monro is identified and obliteration of
the perforating feeders to the tumor carried out by pro-
ceeding posteriorly from the foramen of Monro to ap-
proximately the point at which the body of the fornix
ends. After removing the tumor at the foramen of
Monro, the line of dissection can be moved from trans-
ventricular to parasagittal by retracting the frontal lobe
laterally, so as to expose the rostrum of the corpus callo-
sum. A cerebrotomy can be made through the corpus
and extended, if necessary, to the lamina terminalis as
far as the supraoptic recess.

Lateral ventricle papillomas may extend through the

choroidal fissure into the quadrigeminal cistern and con-
tralateral ventricle. They may extend into the quadri-
geminal cistern in "dumbbell fashion" on either side of
the choroidal fissure or expand as a nodule in the
quadrigeminal cistern and subsequently penetrate the
contralateral ventricle through its choroidal fissure.
Thus, the tumor compresses the quadrigeminal plate,
becomes adherent to the commissure of the fornix, and
elevates the splenium of the corpus callosum. Passage of

CSF from the ambient cistern into the quadrigeminal
cistern is obstructed. This tumor receives its blood sup-
ply through the medial and lateral branches of the poste-
rior choroidal arteries on both sides, the quadrigeminal
arteries, and the inferior retrosplenial arteries. It drains

BRAIN TUMORS 135

mainly into the galenic system, the supraculminate sys-
tem, and the anteromedial occipital veins. This tumor
will require a bilateral temporoparietal craniotomy for
removal. Following transventricular tumor removal,
dissection of the remaining tumor is done by the para-
sagittal approach, bilaterally on either side of the falx.
The anterior choroidal arteries must be identified as they
come over or through the tela choroidia and must be
occluded and sectioned. The bridging veins must be care-
fully identified and sectioned.

Posterior fossa papillomas may require an internal-

ized or temporary external spinal fluid shunt procedure

for several days prior to operation. These tumors estab-
lish adhesions within the entirety of the anteroinferior
medullary velum and fastigium. They may extend an-

terolaterally into the lateral recesses of the fourth ventri-

cle. They may also send digital extensions into the floor
of the fourth ventricle or fungate into the cercbellar hemi-
sphere. They will often grow downward, engulfing the

posterior inferior cerebellar artery, and push through the
foramen magnum into the upper cervical canal. Before

dissecting the tumor from the posteroinferior cerebellar
or the vertebral arteries, it needs to be dissected from the
nodulus and uvula of the vermis by displacing the tonsils
laterally and identifying the feeding vessels coming from
the tonsillar and vermian branches of the posterior infe-

rior cerebellar arteries. A cerebellar incision can be made

in a limbic fashion extending from the medial surface of
one tonsil over the nodulus to the medial surface of the
contralateral tonsil, exposing the tania of the fourth ven-

tricle at the calamus scriptorius and permitting isolation
of most of the blood supply of the tumor. Most of this
blood supply is from the tonsillar and retromedullary

portion of the posterior inferior cerebellar arteries. Care

must be taken not to avulse this tumor from the floor of
the fourth ventricle, as the precentral vessels must be
occluded and transected individually.

Outcome

In 1959, Matson and Crofton reported on the results

of surgical management of children with a choroid

plexus papilloma. Seven of 16 patients developed nor-

mally after surgery (186). Raimondi and Gutierrez re-
ported on 23 patients with only 2 deaths, but 12 patients
had persistent postoperative deficits after tumor removal

(192). In 16 of these patients, the hydrocephalus per-
sisted following operation and required a shunt. In a se-
ries of 17 patients, Hawkins reported that 6 were well
following surgery and attending regular school (193).
The survival of children with a malignant choroid plexus
papilloma is about 9 months; x-ray therapy is indicated,

at least to the site of the tumor.

Pineal Tumors

Incidence

Pineal neoplasms are rare, comprising 0.4 to 1 percent

of all intracranial neoplasms (108). The incidence of pi-

neal teratomas and germinomas seems to be much

higher in Japan than elsewhere. In 1963, Araki and Mat-f
sumato, describing a series of surgical cases collected in '
Japan, reported that pineal germinomas accounted for
3.9 percent of 5,714 brain tumors (194). Recently, the
report of the Brain Tumor\ Registry in Japan disclosed
that the incidence of pineal germinomas was 2.1 percent
in 3,802 primary brain tumors. The reason for the higher
incidence of pineal tumors in\Japan is unknown.

Symptoms and Signs \

In Poppen and Marino's series of 45 patients with pi-

nealomas and tumors of the posterior portion of the
third ventricle, they noted three phases in the clinical
progression of these tumors (195). Headaches, with or
without vomiting, characterized the first phase. The sec-
ond phase was characterized by blurred vision, diplopia.
change in mental outlook, ataxia. dizziness, drowsiness,

and the development of the Parinaud syndrome. In the

third phase, papilledema. marked weakness, and varying
degrees of spasticity appeared- Pineal tumors have also

been associated with both precocious and delayed pu-
berty (196). Eye signs represent one of the main manifes-
tations of pineal tumors. Parinaud's syndrome is consid-

ered to be a pathognomonic sign of tumors in this area of
the brain, although other pathology, such as vascular dis-
ease or hydrocephalus from aqueduct obstruction, can
cause the same syndrome. In the case of tumors, Pari-
naud's syndrome is thought to be caused by involvement
of the rostral portions of the superior colliculus. In this

syndrome, the pupils usually are largely dilated and react
poorly to light, and there is paralysis of upward gaze.

With a suprasellar germinoma, pituitary functions will

be disturbed. Some patients will show hypopituitarism,
and others will show an elevation of plasma concentra-
tions of cortisol or luteinizing hormone and follicle-
stimulating hormone. Diabetes insipidus and visual dis-
turbances may also develop.

Pathology

Probably the most generally accepted classification is

that proposed by Russell and Rubinstein. In this classifi-
cation, the most common pineal tumor is the teratoma,
with pinealomas, gliomas, and cysts as the three rarer
types. The essence of this classification is the belief that

136 / CHAPTERS

the majority of the pineal tumors are really of germ-cell

origin, and that pineal tissue itself rarely undergoes ma-

lignant change. The pineal tumor bears close resem-
blance to the seminoma of the testes and dysgerminoma
of the ovary (1,197). In a classical communication pub-
lished in 1947, Freidman observed that many pineal and
suprasellar tumors histologically were identical to cer-

tain testicular and ovarian germ-cell tumors (198). He
proposed the term germinoma to describe them. Pineal
tumors have been reported to metastasize outside the
CNS, and it is particularly the germinoma that does so,
usually spreading initially to the lung (199). The beta
subunit of human chorionic gonadotrophins is elevated
in the plasma of these patients and is useful in diagnosis

and follow-up of these patients.

Operation

There is considerable controversy as to the correct

treatment of patients with pineal tumors. Some surgeons

favor stereotactic biopsy, treatment with a spinal fluid

shunt, and radiotherapy once a tissue diagnosis is ob-

tained. Stereotactic biopsy of third ventricular tumors is
a low-risk procedure; the most common complication is
failure to obtain tissue. With modern stereotactic biopsy,
failure to obtain tissue will decrease (200). This is an

alternative technique for the surgeons not inclined to do

open biopsy or to remove the tumor.

Other surgeons favor removal of the tumor, as the ap-

proaches to the posterior third ventricle are becoming
increasingly refined. Posterior third ventricle tumors
may be approached in several ways (201,202). One ap-
proach is from above the tentorium along the medial
aspect of the occipital lobe or through the corpus callo-
sum. Another approach is via a suboccipital craniec-

tomy, below the tentorium and over the superior cerebel-
lum. This supracerebellar, infratentorial approach is

useful for tumors of the pineal region because the galenic

venous system that caps the dorsal and lateral aspect of
pineal tumors does not obstruct access to the tumor. The
infratentorial supracerebellar approach is not well suited
for tumors with a significant extension above the tento-
rium, or that are growing from the thalamus or corpus
callosum into the third ventricle, or for lateral lesions

(203). Therefore, infratentorial supracerebellar exposure

is useful for midline lesions in the region of the pineal
gland, posterior third ventricle, and superior cerebellar
vermis. This approach affords easy identification of deep
structures, avoids the tributaries of the vein of Galen,
and allows the surgeon access as far as the foramen of
Monro. The medial bridging veins from the cerebellum

to the tentorium can be safely divided as the cerebellum
is separated from the tentorium, exposing the upper

midbrain and posterior third ventricle. The lower mid-

brain and anterior medullary velum are seen as the up-

per vermis is incised or retracted (204,205). The poste-
rior internal cerebral veins may surround or be involved
in the superior aspect of the tumor, and therefore careful
attention must be paid to these vessels as the superior
aspect of the tumor is removed.

Outcome

There is controversy as to the necessity of surgery, as it

has been clearly shown that these\tumors are highly ra-
diosensitive, with long tumor-free \intervals in 55 to 90

percent of patients treated with cranial irradiation (206-

209). In fact, the tumor is so very sensitive to irradiation

that it has been shown to disappear on\CT when as little
as 1,200 rads have been administered to the tumor area.
Adjunctive radiotherapy should be given to all patients
who do not have complete surgical removal of the
tumor.

Neuwelt and associates have reported two patients

with suprasellar germinomas, one with extraneural me-
tastasis via a ventriculoperitoneal shunt and the other
with CNS recurrence and metastasis, who responded to a
combination of cis-platinum, bleomycin, and vinblas-
tine. Both tumors secreted the B

80

subunit of human

chronic gonadotropin, which was a useful marker for
follow-up during remission (20,210).

COLLOID CYSTS OF THE THIRD VENTRICLE

Incidence

Colloid cysts of the third ventricle are uncommon,

accounting for less than 1 percent of all intracranial neo-
plasms. They will be recognized more frequently with

CT and MRI scans, however, which are being increas-
ingly used to evaluate headaches and dementia.

Symptoms and Signs

Generally, there are three forms of presentation (211):

(1) a nonspecific syndrome of increased intracranial
pressure without localizing signs; (2) progressive demen-
tia with or without headache, associated at times with

intracranial hypertension; and (3) paroxysmal attacks

with complete recovery in between.

Headaches are the most common initial complaint,

and may remain the sole complaint. At times, the head-
aches are paroxysmal attacks of pain, usually diagnosed

as migraine attacks. Occasionally, the headaches are re-
lieved by a change in position, such as lying down. De-
mentia, with recent memory loss, and visual symptoms

such as blurring, temporary loss of vision, and diplopia

can occur. Black-out spells, with drop attacks described

BRAIN TUMORS

by the patient as sudden weakness of the legs, have been

observed to be symptoms of colloid cysts of the third

ventricle. Although the neurological examination is fre-

quently normal, papilledema may be present because of
the increased ICP. An organic mental syndrome may be
observed. Ataxia and pyramidal tract signs may be pres-

ent as well.

Pathology

These tumors are well-circumscribed cystic masses,

with a smooth, translucent membrane. This cyst mem-

brane is composed of connective tissue, with a layer of
cuboidal or columnar cells lining the interior surface.
The cyst contains a homogeneous gelatinous liquid.

Diagnostic Studies

CT or MRI is the diagnostic study of choice. These

studies demonstrate a homogeneous, usually hyper-

dense, lesion with a smooth contour attached to the roof
of the third ventricle, generally at the foramen of Monro
although the tumor can also lie more posteriorly or in
the septum pellucidum. There is usually some enhance-
ment after injection of contrast agent. Hydrocephalus of

a variable degree is present in nearly all cases. This has
been noted to be caused not by a block at the foramen of

Monro, but rather by occlusion of the posterior third

ventricle and aqueduct.

Angiography usually shows ventricular dilatation and.

in the majority of cases, classical venous changes caused
by elevation of the proximal portion of the internal cere-
bral vein.

Operation

Various methods have been used for treatment of pa-

tients with colloid cysts of the third ventricle. Some pa-
tients have only had spinal fluid diversion procedures.

Before considering the operative approaches to the third
ventricle, the anatomy must be carefully studied.

The third ventricle is one of the most surgically inac-

cessible areas in the brain, being a narrow, funnel-shaped
midline cavity bounded above by the corpus callosum
and the body of the lateral ventricle, and below by the

sclla turcica, the pituitary gland, and the midbrain. It lies

between the two halves of the thalamus and hypothala-
mus. It is closely related to the circle of Willis and its

branches and to the great vein of Galen and its tributar-

ies. The third ventricle communicates at its anterosupe-
rior margin with each lateral ventricle through the fora-
men of Monro and posteriorly with the fourth ventricle
through the aqueduct of Sylvius. It has a floor, a roof,

and anterior, posterior, and two lateral walls (212).

These landmarks should be studied prior to operation on

a tumor in the third ventricle.

The routes through which the third ventricle can be

reached are: (1) from above, through the foramen of
Monro and roof afterl entering the lateral ventricle
through the corpus callosum or the cerebral cortex; (2)
from anterior, through the lamina terminalis; (3) from
below, through the floor; and (4) from posterior, through
the pineal region or from the posterior part of the lateral

ventricle. Specific operative approaches are indicated de-
pending on whether the turner is located in the anterior
or posterior part of the third ventricle.

The general principles include the following:

1. The craniotomy flap should be placed so as to mini-

mize the need for brain retraction.

2. Incisions in neural tissue and sacrifice of neural struc-

tures should be minimized.

3. Tissue should be removed from within the capsule of

a third ventricular tumor before trying to separate the
capsule from adjacent structures. The most common
cause of tumor appearing to be adherent is not adhe-
sions between the capsule and surrounding struc-
tures, but rather residual tumor within the tumor cap-
sule (213). As the intracapsular contents are removed,

the tumor collapses, thus making it possible to re-

move more tumor through a small opening.

4. Any arteries that pass over the tumor capsule to

neural tissue should be preserved by displacing vessels
off the tumor capsule using a small microdissector.

5. The number of veins sacrificed should be kept to a

minimum. Attempts should be made to displace

veins before obliterating tumor.

6. Any obstruction to the flow of spinal fluid should be

removed if possible. Otherwise, a spinal fluid diver-
sion procedure will be necessary.

The anterior transcallosal approach is useful for le-

sions located in the anterosuperior part of the third ven-

tricle. This approach is easier to perform than the trans-

ventricular transcortical approach if the ventricles are
small. The anterior transventricular transcortical ap-
proach is useful for tumors in the same position if the
tumor has a major extension into the lateral ventricle. It
is imperative that special care be taken to protect the
fornices from damage during the operation.

The transcallosal approach using magnification tech-

niques offers several advantages. Cortical tissue need not
be removed, and this approach is usually not associated
with neurological sequelae, although Jeeves, Simpson,

and Geffen have reported some impairment of the
transfer of tactile information (214). On the other hand,
this approach requires more dissection of the anterior
cerebral arteries.

138 / CHAPTER8

Often the tumor is attached to the tela choroidea of the

anterior third ventricle, and therefore it separates the two

fornices and the two leaves of the septum pellucidum.

This allows further separation of the two fornices at
operation, exposing the tela choroidea of the anterior

third ventricle which can then be divided in the midline
between the two internal cerebral veins. This gives the
surgeon excellent exposure of the anterior third ventricle
and the tumor.

It must be stressed that colloid cysts are not simple to

treat. Some are large and have a wide attachment to the

roof of the third ventricle. Others are located more poste-
riorly and grow into the septum pellucidum. Sometimes

there are dense adhesions between the capsule, choroid
plexus, and deep venous structures, especially the paired
internal cerebral veins. Antunes, Louis and Ganti have
documented postoperative hydrocephalus requiring
shunt procedures in three of eight patients who under-
went a microsurgical transcallosal removal of their col-

loid cysts (215).

Outcome

The results of treatment should be excellent. Antunes

and associates reported on 23 patients with a colloid cyst

(215). Twelve patients did well, two developed seizure
disorders postoperatively, one patient with organic men-

tal syndrome did not improve, one had a hemiparesis,
and another had a severe postoperative memory defect

secondary to fornix section. Four patients died, appar-

ently because of increased intracranial pressure.

MENINGIOMAS

Meningioma as a specific type of tumor was first de-

scribed in 1774 by Antoine Louis, a leading French sur-
geon, in his "Mimoire sur le tumeurs Fongueuse de la
Dure-mere" (216). The tumors arising from the dura

were generally called fongus or fungus for well over a

century; this is how they were referred to by Virchow in

1864 (32), although by that time some authors referred

to them as endotheliomas. The term "meriingioma" was

coined by Harvey Gushing.

Incidence

In historical reviews, meningiomas account for about

14 to 18 percent of all intracranial primary neoplasms.

Combining the brain tumor series of Olivecrona, Zulch,
Bahr and Kernohan and Snipe, the average percentage

of meningiomas was 17.4 percent (108). Meningiomas
occur at any age, but most commonly present in middle
age, with a peak incidence around 45 years of age. Only

about 1 percent of all intracranial tumors in patients

under 20 are meningiomas, and they are therefore rare in

children. Meningiomas are more common in females
than in males, with a ratio of 6:4. In a study of incidental
brain tumors found at autopsy, one-third were menin-
giomas, usually located in the parasagittal region; the
majority were less than 2 cm in size. Most meningiomas
found at autopsy are asymptomatic. Multiple and famil-
ial meningiomas may be found in von Recklinghausen's
disease, but have been reported in persons without neu-
rofibromatosis as well (100,217). \

Etiology

The controversy concerning the relationship between

head trauma and tumors of the brain is particularly perti-

nent when considering the etiology of intracranial me-
ningiomas. Many cases have been cited in which there is
convincing evidence that the site of previous trauma was

the exact location where the tumor subsequently devel-
oped (13,218). Indeed, it was Gushing and Eisenhardt
who stated in 1938 that "of all intracranial tumors in our

experience, the incidence of trauma in the meningiomas

is particularly high. It was recorded in nearly one-third of
the entire number,. . . the direct relation of the blow to
the locus of the ensuing growth is not infrequently so
precise that the conclusion that an etiologic factor in-
volved is inescapable" (9). Meningiomas have definitely

been reported to occur in the exact site of previous

trauma (12) and have been likewise reported follow-
ing radium therapy for a cutaneous malformation
(219-222).

Symptoms and Signs

The average preoperative duration of symptoms for

meningiomas in general is 2'/2 years (1). Meningiomas
are especially noted to cause seizures. In Ramamurthi,
Ravi, and Ramachandran's series of 127 consecutive pa-
tients with a meningioma, a seizure as the initial symp-

tom occurred in 29 percent (223). Of these patients, only

50 percent obtained relief of their seizures following

operation.

Meningiomas, as will be described below, usually pre-

sent with symptoms and signs associated with the area of

the brain where the lesion occurs. For instance, a menin-
gioma of the middle third of the falx classically presents
with focal, contralateral motor or sensory seizures, or

with progressive hemiparesis. Meningiomas may pre-

sent, though rarely, with other symptoms. Hemorrhage

may occur into a meningioma or into the subarachnoid

space (224-227). This is characterized by sudden severe

headache, lethargy, and focal neurological deficit such as

BRAIN TUMORS

159

hemiparesis. Meningiomas associated with hemorrhagic
complications show no predilection for age, sex, or tu-
mor location. Meningothelial, angioblastic, and fibro-
blastic meningiomas have been associated with hemor-
rhage. It is easy to appreciate the potential for
hemorrhage in an angioblastic meningioma because of
the abnormal vasculature. Rarely, a falx meningioma
may present as episodes of transient ischemia caused by

a blood steal from the brain to the highly vascular tumor.
Transient episodes of cerebral ischemia are most often
seen with parasellar meningiomas, as a meningioma of
the medial sphenoid ridge or parasellar region may

narrow or occlude the adjacent carotid artery (228).

Sagittal Sinus and Falx Meningiomas

The most common location for meningiomas is along

the sagittal sinus and falx (6). This is believed to be re-

lated to the abundant pacchionian granulations of this

area. The parasagittal meningioma is at least five times
more common than the falx meningioma, and together

they account for nearly 25 percent of all intracranial
meningiomas (229).

The parasagittal tumor, as strictly defined, attaches to

the superior sagittal sinus and occupies the space be-
tween the falx and the convexity dura, indenting the me-
dial surface of the hemisphere. The sagittal sinus may be
encroached upon or even occluded by invasion of the
tumor which may grow over the hemisphere or down-

ward below the falx. The pericallosal artery and the cor-
pus callosum are then depressed downward by the tumor
mass or associated edema.

Although the falx meningioma may appear to be on

the surface of the brain by CT or MRI examination, at
operation the tumor is hidden beneath the cortical sur-

face. It may arise from the falx or inferior sagittal sinus,

again indenting the medial hemisphere. It may also grow
through the falx and become bilateral or, as it enlarges,
may appear as a parasagittal meningioma.

These tumors tend to occur at the middle one-third of

the sagittal sinus, with the posterior one-third the least

likely site. Some occur at the torcula. Meningiomas that
arise from the anterior one-third are particularly likely to
grow very large before becoming clinically evident.

Headache is the predominant symptom usually fol-

lowed by the insidious deterioration of memory, intelli-

gence, and personality. Tremor and urinary inconti-

nence may also be present.

Meningiomas of the middle third of the sinus often

present with focal epilepsy, usually commencing in the
foot. Spastic weakness of the foot then occurs. The most
posteriorly located tumors may produce prominent sen-
sory findings. Meningiomas of the posterior one-third
may produce homonymous hemianopsia, frequently

unnoticed by the patient until an accident occurs while

driving, or until signs of increased ICP develop. Visual
seizures are uncommon, but occasionally episodes of

scintillating bright lights are mentioned by the patient.

Convexity Meningiomas

Convexity meningiomas constitute about 18 percent

of all meningiomas an\l tend to be concentrated in the

region of the coronal suture. In some series, this is the
largest group of meningiomas. Seizures and focal neuro-
logic deficits are very common, and often the tumor

reaches large size, causing signs of increased ICP.

Sphenoid Ridge Meningiomas

The sphenoid ridge is an important boundary between

the anterior and middle fossae. The lesser curvature

makes up the inner two-thirds of the sphenoid bone over
the anterior clinoid. The greater wing makes up the outer

third, which extends to the pterion. Eighteen percent of

meningiomas are located on the sphenoid ridge and may

grow into the anterior fossa, middle fossa, sylvian fissure,
orbit, or cavernous sinus. Meningiomas of the inner
sphenoid ridge usually involve the optic nerve early in
their growth. There may be a long history of progressive
visual loss: optic atrophy and a temporal field defect may
be present in the affected eye. As the tumor progresses,

the chiasm becomes involved, and both eyes will have

field defects. Involvement of the cavernous sinus leads to
oculomotor paresis or sensory loss in at least the ophthal-
mic division of the trigeminal nerve and eventually in

the other divisions as well. Exophthalmos is common
and may be caused by venous congestion, local tumor

infiltration of the orbit, or hyperostosis.

The tumors of the outer sphenoid ridge may be either

globular or en-plaque. Patients with a globular menin-

gioma usually present with headaches or temporal lobe

seizures. The en-plaque tumor, which is actually a thin
or thick layer of tumor covering the dura, causes unilat-
eral exophthalmos as an initial complaint, followed by
limitation of extraocular movements, decreased visual
acuity, and temporal swelling.

Olfactory Groove Meningiomas

Meningiomas that occupy the midline floor of the an-

terior fossa constitute 18 percent of the meningiomas.

These tumors arise over the lamina cribrosa of the eth-
moid and protrude into the frontal lobes inferiorly and

usually bilaterally. The initial complaint should be anos-
mia, but this is rare. Usually, these tumors become very
large and cause headaches and finally visual failure from

140 / CHAPTERS

either increased ICP or direct encroachment on the optic

nerves. A variety of field defects is seen. This tumor may

produce ipsilateral optic atrophy and contralateral papil-
ledema (Foster-Kennedy syndrome), although this is
rarely seen. Finally, mental deterioration, and bowel and
urinary incontinence may occur.

Suprasellar Meningiomas

Ten percent of meningiomas arise in the midline tu-

berculum sellae. Even when small, the tumors will cause

bitemporal hemianopsia and optic atrophy. Thus, the

usual complaint is painless, or nearly painless, progres-
sive loss of vision, which is usually asymmetrical and
much more severe in one eye than the other. In fact,
there may be complete loss of vision in one eye for years
before visual loss is observed in the opposite eye. If the

tumor grows forward, it may produce anosmia or mental
changes. If it grows posteriorly, there will be oculomotor

and pituitary deficits. In the past, these tumors often

went undiagnosed for years, as the patient's vision deter-
iorated to blindness in one eye. With the advent of CT

scanning, these lesions should be recognized prior to se-
vere visual loss.

Optic Serve Meningiomas

Optic nerve meningiomas fortunately are rare. The

classical presentation is of a central scotoma, breaking
out over time into a peripheral defect in a middle-aged

woman. The visual loss is slow, painless, and progressive.

Opticociliary shunt vessels may be present on fundusco-
pic examination. Optic atrophy eventually develops.
The bilateral form is among the most difficult of all tu-
mors to diagnose before severe loss of vision has oc-

curred. Prior to 1979. only seven patients with histologi-

cally proven bilateral optic nerve sheath meningiomas
had been reported: another two patients with bilateral

signs suggestive of such tumors had been explored on

one side only (230.231).

Posterior Fossa Meningiomas

About 9 percent of meningiomas occur in the poste-

rior fossa. Castellano and Ruggioro have divided these
tumors into five groups (233). The first group includes

the 40 percent of these tumors that arise along the poste-
rior surface of the petrous bone. The tumor involves cra-

nial nerve VIII, and frequently V and VII. Both trigemi-
nal neuralgia and hemifacial spasm have been seen with

a tumor in this location. Ataxia and nystagmus are fre-
quently observed. Finally, as the fourth ventricle is

shifted and the foramina are occluded, hydrocephalus

and increased ICP occur. Often the signs of this tumor
are highly suggestive of acoustic neurinoma.

Another group are those tumors that grow in the re-

gion of the tentorium, comprising 30 percent of poste-

rior fossa meningiomas. These tumors commonly in-
vade venous sinuses and may extend above the
tentorium. These turners usually cause symptoms of in-
creased ICP.

Ten percent of posterior fossa meningiomas arise

from the clivus. They cause posterior headaches, gait dis-
turbances, decreased Wealing, vertigo, dysphagia, and
weakness. Papilledema, nystagmus, lower cranial nerve

palsies, and cerebellar and pyramidal signs are also ob-
served. These signs are sometimes intermittent and remi-
niscent of basilar artery insufficiency or may be confused

with intrinsic brainstem tumors or cerebellopontine an-
gle tumors.

Tumors of the cerebellar convexity comprise a group

of about 8 percent of all posterior fossa meningiomas.
They are usually near the transverse sinus and produce
symptoms of increased ICP and hydrocephalus by dis-
placing the cerebellum forward and obstructing the aque-

duct. Disturbances of gait and cranial nerve signs occur.

The last group of tumors, comprising 8 percent of pos-

terior fossa meningiomas, are located at the foramen

magnum. They account for 1.2 percent of all meningio-

mas. The first case of meningioma at the foramen mag-
num was described by Hallopeau in 1874 (232). There is
some controversy as to tumor location for consideration
as a foramen magnum meningioma. Castellano and
Ruggioro (233), as well as others, considered as foramen
magnum meningiomas only those attached to the dural

edge of the foramen magnum or to the inferior grove of

the clivus. Gushing and Eisenhardt advocated that this

term should be restricted to neoplasms extending into

both the posterior fossa and the cervical spinal canal (9).

The time interval from initial symptom to diagnosis of

a meningioma of the foramen magnum has been re-
ported to range from months up to 13 years. In the past,
this has been a most difficult tumor to diagnose and the
duration of the disease is long. There are no symptoms
pathognomic of a tumor at the level of the foramen mag-
num. A collection of symptoms and signs is commonly
found in association with these lesions. The initial symp-

tom is usually pain in the cervical region, exacerbated by
flexion of the neck, pressure in the neck, coughing, or
straining. Sensory and motor symptoms follow, usually
commencing in one arm and progressing to involve the
remaining limbs. Ataxia and sphincter disturbances are

common. There may be variable and bizarre sensory

dysesthesias. Psychosis and neurosis may coexist, lead-
ing to a diagnosis of hysteria.

The initial examination may show normal results or

only subtle abnormalities in almost half the patients. Pos-

itive findings most commonly include hyperreflexia and
weakness, particularly of one or both upper limbs pro-

gressing to involve the remaining limbs. Clinical findings

BRAIN TUMORS

141

are horizontal nystagmus; palsy of the lower cranial
nerves, generally the hypoglossal; atrophy of the hands;
and intercostal muscle atrophy. Hypesthesia of the sec-
ond cervical dermatome is an important finding when

present. The typical features of the sensory disturbances
are cold dyesthesias, which are considered an early sign
of extramedullary tumor at the foramen magnum. Burn-
ing dyesthesias precede the onset of hypesthesia. Symp-
toms related to the posterior column, such as pseudoc-
tereognosis, otherwise called the piano-playing-fingers
phenomenon, and stereoanesthesia are at times ob-
served. Cerebellar signs and papilledema are un-
common.

Thus, the clinical picture can suggest many other dis-

eases. The confusion with an intramedullary tumor or
syringomyelia is obvious. A foraminal tumor is easily
misdiagnosed as demyelinating disease, degenerative
disease, or cervical spondylosis.

Lateral and Third Ventricle Meningiomas

Meningiomas that arise from the tela choroidea or the

stroma of the choroid plexus of the lateral ventricle con-
stitute only about 2 percent of all meningiomas. These

tumors are rare in the third ventricle, and they usually
occur in the atrium of the lateral ventricle. Only about

100 cases of a meningioma of the ventricles were re-

ported in the English literature between 1900 and 1978,
when Mani and associates reported 22 cases with 13 of

the meningiomas being in the left lateral ventricle (234).

The presenting symptoms of patients with ventricular

meningiomas are nonspecific. Headache is the present-
ing symptom in 40 to 70 percent of patients, followed
closely by hemiparesis in 20 to 60 percent of patients.
Visual changes, memory loss, grand mal seizures, apha-
sia, vertigo, loss of consciousness, and personality

changes have been observed. These tumors have been

observed as a cause of subarachnoid hemorrhage. Also,
xanthochromia suggesting a previous hemorrhage has

been observed in some cases of intraventricular menin-
giomas (235).

Other Sites of Meningiomas

A small number of tumors grow in Meckel's cave, in-

volve the gasserian ganglion, and produce typical trigemi-
nal neuralgia. As the tumor enlarges, it invades the cav-
ernous sinus or spreads into the cerebellopontine

angle.

Pathology

The arachnoidal cell is believed to be the cell of origin

of meningiomas. Ultrastructural analysis reveals many

features of normal arachnoidal cells and meningioma

cells that are identical.

Meningiomas are globular, rarely pancakelike. or en-

plaque, and are usually firmly attached to the dura, with
a sharp demarcation from surrounding brain. Their sur-
faces may be smooth or nodular. Small tumors may
merely indent the brain, but very large tumors may de-
stroy the cortex. Surrounding brain edema is not related
to tumor size, as small tumors may be associated with

massive edema which may produce clinical symptoms

itself. Rarely are meningiomas cystic.

Hyperostosis of the inner table of the skull occurs in

about 5 percent of patients with a meningioma. At times,
the outer table becomes involved and produces a visible
mass, more common in parasagittal tumors. The hyper-

ostosis associated with en-plaque sphenoid wing menin-

giomas may extend into the orbit and temporal fossa.

Microscopically, several histological classifications

have been used for these tumors. The most widely used is

the classification proposed by Courville and adopted by

Russell and Rubinstein. Five categories are designated:
syncytial, transitional, fibrous, angioblastic, and malig-
nant, with gradations often occurring among these
various types (I).

The syncytial or meningotheliomatous type consists

of poorly denned polygonal cells arranged in sheets sepa-
rated by vascular trabeculae. The cytoplasm is homoge-
neous, the nuclei are spheroidal, and collagen reticulin

fibers are sparse and confined to the vascular stroma.

The transitional form, along with the syncytial tumors,
comprises 65 percent of the total pathological spectrum
of meningiomas. A formation of concentrically arranged
cells is characteristic of transitional meningiomas. Cen-
tral hyalinization and deposition of calcium salts pro-

duce psammoma bodies typical of this form of menin-
gioma. The fibroblastic or fibrous type of meningioma is

composed of interlacing bundles of spindle cells, rich in

reticulin and collagen fibers.

Angioblastic meningiomas are highly cellular with

prominent vascular channels and frequent mitoses. The
vessel walls and stroma have abundant reticulin fibers.

These tumors may look like hemangioblastomas by both

light and electron microscopy but differ in gross features
and location. The angioblastic meningiomas tend to be
supratentorial, attached to the dura, cystic, and at times
associated with tumors in other organs.

The incidence of malignant meningiomas is reported

to be 2 to 10 percent of all meningiomas, with a male
predominance—a reversal of the usual gender predilec-

tion of meningiomas. Malignancy can be identified by

various criteria including local invasion of the brain;

atypical histological features, such as high cellularity,
high mitotic rate and poor differentiation; extracranial
differentiation and metastasis; and rapid recurrence. Lo-
cal invasion of bone, dura, or venous sinuses is not a

142 / CHAPTERS

criterion for malignancy, but brain invasion is. Mitotic
figures probably represent rapid growth and not malig-
nancy. On the other hand, cellular progression of a typi-

cal meningioma to that of a spindle-cell sarcoma, or the

cytological appearance of increasing anaplasia, denote
malignancy. A papillary pattern histologically is also a
sign of malignancy; this feature has been particularly
noted in meningiomas in children. The presence of me-

tastasis is an absolute criterion of malignancy (216). The
lung is the most frequent site involved, followed by the

liver and bone. The dissemination is most likely via the
venous system with the parasagitial tumor the most
likely to metastasize. Angioblastic meningiomas account

for a greater number of metastases than their relative
frequency would suggest (236). Dissemination via the

cerebrospinal pathway has been reported in only eight
cases (237). Recurrence of meningiomas, particularly
after incomplete removal, occurs in at least 20 percent of
patients who undergo surgical treatment of their menin-
giomas. Crompton and Gautier-Smith studied recurrent
and falx meningiomas and suggested certain histological
features as pointers to possible early recurrence (238).
These were the presence of mitotic figures, focal necro-

sis, and permeation of the brain by tumor.

Diagnostic Studies

Review of the plain x-ray may be extremely reward-

ing; in about one-half of the cases the diagnosis can be

suspected from the plain x-ray. There may be indirect
evidence of a tumor such as abnormal convolutional
markings, pressure atrophy of the sella turcica, or dis-
placement of physiologically calcified structures; or di-

rect evidence of a meningioma with hyperostosis, in-
creased vascular markings, or tumor calcification.
Hyperostosis is the most frequent sign and most com-
monly involves the inner table of the skull. The menin-
geal vascular groves may be enlarged with abnormal
branching near the tumor. About 10 percent of menin-

giomas show a cloudlike globular calcification or a sim-
ple ringlike outline of the tumor.

Arteriography is most helpful in defining the nature,

location, and extent of the meningioma, as well as its
relationship to important vascular structures. A homoge-
nous but sharply circumscribed tumor stain is frequently
seen, and may persist because of prolonged circulation in
the tumor or because the contrast material actually
leaves the vascular system and enters the extracellular
space. Arteriography remains helpful in the manage-
ment of these tumors as the important vascular supply to

the tumor needs to be visualized before embolization or

surgery can be properly planned.

CT and MRI scans are the most accurate noninvasive

tests for identifying meningiomas. Claveria and asso-
ciates, in an analysis of 71 cases of meningioma diag-

nosed by computerized tomography using a 160 x 160
matrix, concluded that with contrast injection a diagno-
sis of tumor could be made in 96 percent of the cases
(239). The difficult areas to examine by CT for the pres-
ence of a meningioma are the sites adjacent to the calvar-
ium or base of the skull, sych as the parasagittal region,
the tuberculum sella-parasellar area, the optic canal, and
the cerebellopontine angle, because of the superposition

of the density of the tumor and the density of the skull.
MRI is the superior diagnostic test for these tumors be-
cause of the ability to subtract bone from the image. For
meningiomas of the foramen magnum, MRI is clearly

the diagnostic test of choice. Although CT is able to visu-

alize the foramen magnum region well, MRI is better

able to delineate the tumor and differentiate neurologi-

cal structures and cerebrospinal fluid spaces. MRI using
the inversion recovery sequence and gadolinium-diethy-
lene triamine pentoacetic acid (DTPA) contrast medium
will give good definition in over 96 percent of cases. Un-
like CT and myelography, MRI does not show bony arti-
facts. An added advantage of MRI is that vasculature
structures such as the vertebral artery are seen as a void
signal. Most foramen magnum meningiomas occur at

the anterolateral tip of the foramen and the vertebral
arteries are generally encompassed by the tumor. MRI
not only demonstrates the location of the artery in rela-

tion to the tumor and other brain structures but also is
useful in separating the tumor from the vessels.

On CT, meningiomas are usually seen as high-density

areas with well-defined round borders and striking con-
trast enhancement, although the borders may also be
irregular, associated with a variable amount of edema or
cyst formation (240). CT scanning has been suggested by
Vassilouthis and Ambrose as helpful in predicting histo-
logical features of meningiomas (241). In particular, visi-

ble calcium aggregates point to a diagnosis of either tran-

sitional or fibroblastic meningioma. Since most tumors

are surrounded by edema of varying degrees, edema is
not a specific feature of meningiomas. Angioblastic and
syncytial meningiomas show a marked tendency to ex-
hibit low-density, nonenhancing "cystic" areas, or
poorly defined, irregular tumor margins or fringes. The

presence of marked edema, absence of visible calcium

aggregates, and nonhomogeneous contrast enhance-
ment with hypodense areas and poorly defined irregular

borders or fringes point to aggressive or invasive charac-
teristics more commonly found in nonbenign or aggres-
sive meningiomas. New and coworkers, in their report
on CT criteria for malignant meningiomas, described
another CT sign, which they called the mushrooming
pattern (242).

Operation

In 1954, Dr. Frances C. Grant noted, "A meningioma

is a benign tumor, which if it can be completely extir-

BRAIN TUMOBS

143

pated together with its meningeal attachment will not
recur." He further stated in the same paper that "a sub-
total removal without aggravation of existing neurologic

deficit will be more satisfactory to the patient and to his
family than a complete removal and the assurance of a
long life severely crippled" (243). Nearly 30 years later,
these tenets still hold true and should remain foremost in
the mind of every surgeon as the care of a patient with a
meningioma is undertaken.

The preoperative evaluation always has and always

will be critical in the preparation of the patient for opera-
tion. The plain skull x-ray still plays a role in planning

the operation for a patient with a meningioma. The pres-

ence of skull changes produced by the tumor will allow

precise placement of the bone flap. The vascular mark-

ings are important as they can forewarn the surgeon of
potentially severe bleeding, which may accompany
opening of the bone flap. Hyperostosis or tumor in the
bone will alert the surgeon as to the need for cranioplasty

(Fig. 6).

The arteriogram will define the degree of vascularity,

the arterial supply, and venous drainage of the tumor.

Adequate control of the arterial supply and preservation

of normal venous drainage of the brain are among the

most important considerations of the operation. An ex-

tremely vascular tumor may be diagnosed as an angio-
blastic meningioma, or at least alert the surgeon to the
probabilities of severe hemorrhage if the tumor is incised
or debulked piecemeal prior to occlusion of the arterial
supply. The relationship of the major intracranial arter-

ies is critical. A determination must be made whether

these arteries are displaced by or encased in tumor. If the

tumor is displacing the vessels, microsurgical techniques

may allow removal of the tumor from the vessels. If it is

determined the vessels are totally encased by tumor.
then complete tumor removal may be impossible. Preop-

erative planning may then include an extracranial-intra-
cranial vascular anastomosis prior to tumor removal if a
major intracranial vessel is to be compromised by the

operation.

The arterial phase of the arteriogram is of utmost im-

portance for planning methods that may be beneficial in

reducing the blood supply to the tumor. This may in-

volve ligation of the external carotid artery or selective
embolization of the tumor-feeding vessels. There are

some instances in which preoperative embolization of

feeding vessels of the tumor can dramatically reduce in-

traoperative hemorrhage. Placement of emboli directly

into the tumor causes the most effective reduction in

vascularity, thus decreasing blood loss during surgery.

Hieshima and colleagues have shown pathologically

zones of infarction in 10 of 11 tumors embolized and

evidence of decrease in size of some of the tumors on

CT (244).

The venous phase of the arteriogram is as important as

the arterial phase. Although the CT may be able to reveal

patency or occlusion of the sagittal sinus, the venous

arteriogram or direct sinogram is the definitive proce-
dure for determining sagittal sinus patency. The condi-

tion of the sagittal sinus must be determined in all pa-

tients harboring parasagittal faix and tentonal

memngiomas. It is well known that the sagittal sinus can

be safely ligated in only the anterior one-third of its ex-
tent or. in generai only anterior to the coronal suture. If

'• t m mli&M. > &•" - - „

FIG. 6. (A) Enhanced CT scan of asymptomatic patient showing invasion of bone by the frontal convex-
ity meningioma; (B) inner table of bone plate of hypertosis caused by the tumor.

144 / CHAPTERS

tumor only partially invades the sinus posteriorly, every

attempt must be made to completely remove the tumor,

but the sinus and cortical draining veins must be pre-
served. Careful preoperative planning and preparation
of the patient permits reconstruction of the sinus. This
can be done by using the Kapp-Gielchinsky shunt dur-
ing removal of tumor from the sinus and repair of the
sinus by autologous saphenous vein graft (245.246). If

the superior sagittal sinus is completely occluded by tu-

mor, and collateral drainage, usually via the inferior sag-
ittal sinus, is preserved, then the sinus can be safely re-
sected without further increase in neurological deficit.

Equally important is the preservation of the large cor-

tical draining veins, especially from the parietal and oc-

cipital lobes. The approach to the tumor should be

planned so as to preserve these draining veins, or venous
infarction may be produced resulting in cerebral swell-
ing, profound neurological deficit, and seizures.

Preoperative Medications

The patient should be prepared with adequate preoper-

ative anticonvulsant medications, even if the patient had

not had previous seizures. Dilantin and phenobarbital

can be safely used in most patients, although a few will be

allergic to dilantin. The surgeon should be aware of this
fact as dilantin may be the culprit in a persistent postop-
erative fever or rash. Anticonvulsant medication for two
to three days prior to operation is recommended, but
rapid dilantinization can be done if urgent surgery is nec-
essary.

Dexamethasone, in large doses, or a similar steroid for

at least three days preoperatively, and preferably for five

days, will reduce any surrounding brain edema. A grad-

ual reduction of steroids over a similar period postopera-

tively is done depending on the patient's course.

Technique

Adequate exposure is important in every operation. In

most operations for a meningioma, the bone flap should

be a free flap completely detached of its muscular attach-

ments and blood supply. This will lessen the chance of

postoperative epidural hematoma. The bone flap should

be inspected for evidence of tumor invasion, and if this

exists, the bone flap should be discarded or the area of

tumor invasion removed completely by drilling out the

tumor. This at times can be done with an air turbine and
cutting burrs, as the tumor may involve only the inner

surface of the bone. If the bone flap is to be replaced, any

existing vascular groves must be generously waxed or

covered with Avitene.

The bone flap for parasagittal and falx tumors will

usually need to be fashioned so as to cross the midline,
even though the tumor appears unilateral (247). This

permits control of the sagittal sinus by ligation or resec-
tion of the anterior part of the sinus. At times, the tumor
will have a dumbbell extension across the midline, re-

quiring removal. Although slightly more time consum-

ing than a unilateral flap, the bilateral flap can be safely
fashioned by placing burr holes over the midline sinus.
This will protect the sinus from any laceration by the
craniotome or Gigli saw. An alternative, as recom-
mended by Kempe, is the placement of burr holes on

either side of the venous sinus\and then connecting the

holes with a craniotome after freeing the dura and sinus
from the bone (248).

In operations for meningiomas\particular attention

must be paid to the dura. When the dura is exposed,

visual inspection may reveal the extent of the dural in-

volvement with the tumor. Any dura involved with tu-
mor will need to be removed with the tumor, and re-
placed with pericranium, galea, or fascia lata. We do not
favor the use of artificial dura mater, especially silastic
implants, unless absolutely necessary because of adverse
reactions we and others have observed with this material.

Late hemalomas and large granulomatous reactions

forming a mass and requiring reoperation have been re-

ported (249). Therefore, only dura involved by tumor

should be removed as this will require less replacement.
Gentle palpation of the dura and an initial opening over
the lateral margin of a parasagittal or falx meningioma

will show the direction of the dural opening, which
should be made first beyond the firm attachment or in-
vasion of the dura by the tumor. A circumferential dural
opening may decrease blood supply and permits use of
the dura for traction and gentle delivery of this tumor as
it is removed (250).

In the removal of falx, parasagittal, and convexity

meningiomas, it is imperative that the tumor be re-
moved from the brain and not the brain from the tumor.
In falx meningiomas, some gentle retraction of brain is
necessary, but this should never be forceful. Proper pre-
operative use of steroid medication, plus intraoperative
mannitol and anesthetic techniques, will allow the brain
to fall away from the tumor with gentle retraction. Un-

due retraction may tear vessels, lacerate brain, or aggra-
vate cerebral edema, producing a difficult postoperative
course. Mechanical self-retaining retractors, such as the
Leyla retractor, are preferable to manual retraction

which may cause more trauma to the brain.

The bipolar coagulator is an indispensable instrument

for safe control of the feeding arteries and draining veins
of a meningioma. The use of metal clips for hemostasis
may interfere with postoperative CT or MRI scanning.

Microsurgical techniques using the operating micro-

scope are useful in the removal of most meningiomas

and are indispensable for basal tumors involving cranial

nerves or major cerebral vessels. For large parasagittal,
falx, and convexity tumors, loupe magnification is
usually sufficient. Removal of a large tumor requires ap-

BRAIN TUMORS / 145

proaching the tumor from all sides and frequent chang-
ing of the microscope positions becomes cumbersome
and tedious. If the surgeon uses loupes, there is greater

ease in visualizing all sides of the tumor during mobiliza-

tion of the tumor. Rapid excision of any brain tumor as a
primary goal is to be condemned, as speed is not the
essence of the modern operation. Rather, a zone of cleav-
age between brain and tumor is developed by separating
any adhesions by coagulation and cutting feeding ves-

sels. Soft and fragile surrounding brain tissue is carefully

protected by wet telfa strips introduced into the plane of
cleavage. Reduction of tumor mass with ultrasonic aspi-

ration is often necessary to collapse the tumor into a

small mass. In the falx meningioma, the attachment to
the falx should be generously removed, sparing the supe-
rior and inferior sagittal sinuses.

The tumor bed, blood vessels, and dural margins

should be inspected for remaining fragments of tumor.

The dural closure, with or without a graft, should be
water-tight. No tumor bed drains should be necessary,
but a subgaleal hemovac drain is routinely used by many

surgeons to prevent the development of a subgaleal he-

matoma which appears to increase postoperative morbid-

ity. Rather than increase infections in this space, a drain

if removed within 24 hours possibly lessens the chance of
infection from stagnant blood and reduces tension on
the incision.

Basal meningiomas include the olfactory grove, supra-

sellar, medial sphenoid ridge, and petroclival meningio-
mas. Special considerations for surgical removal of these
tumors, and for meningiomas of the tentorium and lat-
eral ventricles, are discussed below.

Olfactory Grove Meningiomas

Durante in 1885 successfully removed an olfactory

grove meningioma (251). This is believed to be the first
successful operation for an intracranial tumor. Success-
ful removal of an olfactory grove meningioma often has
a most gratifying postoperative result. Even when the
tumor is large, there is striking, gradual improvement in
mentation and vision if the optic nerves were com-
pressed by the tumor.

The attachment of these tumors to the floor of the

anterior fossa is over the posterior cribiform plate and
planum sphenoidale. To approach these tumors, a bico-
ronal hairline incision is used. When the tumor is large
and bilateral, a free bifrontal craniotomy flap is pre-
ferred, especially since anosomia is already present in

most cases. Frontal lobe tissue will be found covering the

tumor. This should be gently retracted after the anterior
sagittal sinus is sectioned, so as to expose the superior
aspect of the tumor. If the tumor is large, the frontal
lobes will need to be retracted posteriorly and laterally.
The tumor can then be reduced in size with loop elec-

trodes or the ultrasonic aspirator so as to decompress
and collapse the tumor forward, exposing the anterior
cerebral arteries and their branches. As the tumor is re-
duced in bulk and retracted anteriorly, the optic nerves

will come into view and can be protected. The tumor can

usually be completely removed in this manner. Mac-
Carty recommends cauterizing any osteoma. rather than
vigorous removal which breaks through into the ethmoi-
dal sinuses with resultan rhinorrhea (251).

Tuberculum Sellae Meningiomas

Arteriography is indicated preoperatively to appreci-

ate the relationship of the anterior part of the circle of
Willis to the tumor. The position of the paired anterior
cerebral arteries should be especially noted to aid in pro-
tecting them from damage. Tuberculum sellae menin-
giomas compress the optic nerves and the chiasm posteri-
orly, and generally extend anteriorly over the planum

sphenoidale a few millimeters. These tumors do not ini-

t i a l l y involve the carotid or anterior cerebral arteries.
They may, however, become larger or extend above and

below the optic nerves and chiasm, displacing the inter-

nal carotid artery laterally or the anterior cerebral arter-
ies away from the chiasm. These tumors may be very
adherent to the anterior communicating and anterior ce-
rebral arteries (252).

The usual operative approach is a right frontal craniot-

omy. Some surgeons prefer the approach to be made on
the side of the most severe visual loss as this is the side of
the greatest tumor bulk. Others prefer to approach the
tumor on the side of the most intact optic nerve so as to
always have it in view and to provide protection of the

nerve. The tumor is usually easily reached by a lateral

subfrontal exposure just in front of the sphenoid wing.

This approach has been described by Kempe, MacCarty,

and Poppen (248,253,254). Hunt, Sayers, and Yashon
approach the tumor along the sphenoid wing but also
design the flap so that the anterior falx can be divided if
necessary (255). Symon and Logue also use the unilat-
eral right subfrontal exposure but approach the tumor
along the midline (252,256). The unilateral exposure
should be employed wherever possible, so as to preserve
at least one olfactory nerve. Otherwise, the patient will
be more disturbed postoperatively by loss of the sense of

taste, rather than the anosmia.

The blood supply comes through the dura of the tu-

berculum with very little direct supply from the carotid
or anterior cerebral arteries. The tuberculum tumo:

blood supply can be systematically interrupted by devel-

oping a plane of dissection between the planum sphenoi-
dale, tuberculum, and the tumor. When the basal blood
supply to the tumor is occluded, the tumor will be turned
from an engorged red mass to a pale gray soft tumor,
much easier to decompress and remove. The surgical

146

CHAPTER 8

laser is an excellent adjunct to use for incising the base of

the tumor from the tuberculum. Once the main blood

supply is interrupted, internal decompression of the tu-
mor is essential prior to dissecting the tumor from the

optic nerves and adjacent arteries. Magnification tech-

niques will allow complete removal of the tumor even

though the optic nerves and vessels initially appear ad-
herent to or encased by the tumor. Internal decompres-
sion of the tumor using bipolar coagulation and small
ring currettes or the CUSA must be done carefully be-
cause of the proximity to vital structures. The tumor can
be gently dissected and reflected from the optic nerve

with microdissecting instruments. This tumor does not
invade the optic nerve and can be cleanly and com-
pletely removed from the nerve.

With smaller tumors, the contralateral optic nerve

may be seen just proximal to the optic canal initially or
early in the dissection along the tuberculum. The nerve
forms a useful landmark. The internal carotid artery will

be just beneath it. either slightly medial or lateral de-
pending on the amount of dislocation by the tumor.

With larger tumors, if the contralateral optic nerve is not
easily seen anteriorly, it may be best to proceed along the
initially exposed optic nerve, back to the chiasm and

then, upon freeing the tumor from the carotid and ante-
rior cerebral arteries, proceed forward from the chiasm

dissecting tumor from the opposite nerve as the remain-
ing tumor is rolled anteriorly. Even when the anterior
cerebral arteries are encased in tumor, microdissection
techniques may allow complete removal of tumor from
the vessels. Of course, in doing so, the anterior cerebral
arteries must not be sacrificed in an attempt to com-
pletely remove the tumor (257).

In removing the tumor from the optic chiasm, arach-

noid will eventually be encountered and appear thick-
ened. Just beneath the arachnoid will be the pituitary
stalk, often displaced posteriorly. This should always be
preserved. Meticulous microdissection of tumor from

the stalk may nevertheless result in temporary postopera-
tive diabetes insipidute. Unless the stalk is severed or the
hypothalamus injured, this condition should be tempo-
ran' and easily treated.

At the completion of tumor removal, careful inspec-

tion of the dural attachment at the tuberculum will show
that dura will need to be removed along with any hyper-
ostosis. using a diamond drill. Any troublesome bleeding

encountered in this procedure can usually be controlled

with bone wax or a small amount of Avitene.

Medial Sphenoid Wing Meningiomas

Medial sphenoid wing meningiomas are among the

most difficult of all tumors to completely remove. These

large globular tumors generally form a mass on the me-

dial sphenoid wing, elevating the temporal and frontal
lobes and compressing the optic nerve and chiasm (Fig.

7). They can often be completely removed if the cavern-

ous sinus is not involved. Unfortunately, an en-plaque
meningioma involving the cavernous sinus is difficult to
remove completely, but experienced skull-base surgeons
are reporting increased success with operations done
within the cavernous sinus.

The exposure to these tumors is via a frontotemporal

exposure along the sphenoid ridge. The craniotomy ex-
tends as low as possible to permit a direct view of the
floor of both the temporal and frontal fossae. Bridging

veins from the temporal lobe to the petrosal sinus should

FIG. 7. Medial sphenoid ridge menin-
gioma. Even though the tumor is easily
dissected from the sphenoid ridge, it is

still embedded in the middle sylvian ves-

sels (arrow).

BRAIN TUMORS 147

be occluded by bipolar coagulation, and then sharply

sectioned. The surgeon must have an appreciation of the
relationship of the major vessels with the tumor. If the
vessels are elevated or displaced by the globoid tumor,

the tumor can be first decompressed internally, and then

the outer margins can be removed from the vessels and
optic nerve. If the tumor encases the arteries, the tumor
can be opened and, using microsurgical techniques, of-
ten dissected from the vessels. Exposure is aided by
opening the medial aspect of the sylvian fissure or resect-

ing the tip of the temporal lobe as advocated by Mor-
ley (89).

En-plaque meningiomas invading the frontal basal

bone and air sinuses, as well as the cavernous sinus,
make total removal almost impossible without en-bloc
resection of the orbit and basal frontal bone as described
by Derome and Guiot (258). Even then the tumor may
not be completely resected. It is preferable to remove as
much of the tumor and its extensions by starting laterally

and proceeding medially. When the cavernous sinus is

entered and cranial nerve damage possible, tumor resec-

tion should cease. Bonnal, Andre, Brotchi, and Born
have described the high mortality and morbidity of at-

tempts to totally remove invading medial sphenoid ridge

meningiomas, and the failure to actually accomplish to-

tal removal when it was thought to have been done at the

operation (259). They also pointed out the long survival

enjoyed by patients who did not undergo operations for
removal of this tumor. This is one meningioma, when
incompletely removed, that should receive consider-
ation for postoperative irradiation or gamma knife treat-
ment, especially if symptoms and signs progress.

Petrodival Meningiomas

Petroclival meningiomas were once thought to be in-

operable, and total resection was rarely reported before

1970. Today, with the development and refinements of

microsurgical techniques and approaches, and with the
quantum improvement in neuroradiological imaging,
mortality rates of 0 to 10 percent are now being reported

by outstanding skull-base surgeons, such as Samii and

Sekhar (260,261).

The approach may be retromastoid, pterional, poste-

rior temporal, or combined retromastoid-subtemporal
with division of the transverse sinus. Samii uses a modi-
fied retromastoid-subtemporal approach that preserves
the transverse sinus. A temporal craniotomy is per-
formed, extending it as low as possible to the floor of the

middle fossa and posteriorly to the transverse sinus. A
suboccipital craniectomy is then executed, exposing the
transverse sinus. The mastoid process is completely re-
moved, exposing the full length of the sigmoid sinus
down to the jugular bulb. The petrous pyramid is drilled
away, the superior petrosal sinus coagulated, and the ten-

torium transected in a lateromedial direction. The oc-
cipitotemporal lobe covered by the tentorium is re-
tracted superiorly, and the sigmoid sinus and cerebellum
are retracted medially. The vein of Labbe must be pro-
tected and not traumatized. This approach gives excel-
lent exposure of the cerebellopontine angle, the clival

region, and the craniocervical junction. In tumors that

grow extensively from the clivalregion to the sellar area,
this approach allows excellent visualization of the sellar
and parasellar area because, with the brainstem posteri-
orly and superiorly displaced by the tumor, as tumor is
removed, the surgeon has an unobstructed line of vision
from the cerebellopontine angle to the suprasellar area.
Bleeding must be kept under meticulous control because
it is difficult to tamponade tumor or brainstem bleeding
by pressure.

If the tumor invades the cavernous sinus, complete

removal will be difficult but not impossible. The cavern-

ous sinus can be entered by inferior, anterolateral, or
medial extradural approaches, or by superior or lateral

intradural approaches, because the cavernous sinus can
be viewed as a truncated pyramid. A posterior approach

does not permit easy control of any bleeding from the
intracavernous internal carotid artery. The most impor-
tant cranial nerves passing through the cavernous sinus,
in order of importance, are III. V-I, and VI. When the
tumor invades a cranial nerve and the nerve is healthy
proximal and distal to the area, the invaded segment can
be excised and reconstruction done by direct suture or by
interposition nerve graft. Using the posterior surgical ap-
proach with microsurgical techniques, the immediate

and long-term results should be excellent.

For large anteriorly located tumors, the approach is

more difficult. The transoral-transclival surgical ap-

proach is the most direct operative approach to tumors
ventral to the brainstem and superior spinal cord. For
tumor removal between the clivus and C-3, this ap-
proach allows an extensive anterior exposure for re-
moval of intradural and extradural tumors. Miller and

Crockard have described the successful transoral-trans-

clival removal of anteriorly placed meningiomas at the
foramen magnum (262). The surgeon works seated
above the patient's head. A self-retaining McGarvey
three-ring retractor spreads the upper and lower jaw

widely apart and displaces the tongue and endotracheal
tube caudally. The soft palate is divided, and the incision

is extended on to the hard palate, exposing the posterior
pharyngeal wall. This is incised in the midline, exposing

the lower third of the clivus and cervical spine to the level
of the second cervical vertebra. The lower third of the
clivus, arch of the atlas, odontoid, and part of C-2 are

removed to expose the dura mater. The tumor then can
be completely removed using magnification techniques.
At closure, the dura will need to be grafted using Lyo-
dura and surgical or fibrin glue when necessary; the pha-
ryngeal wall is usually closed in two layers with Vicryl.

148 / CHAPTER8

Prolonged continuous use of a lumbar subarachnoid

drain is often necessary during the immediate postopera-
tive period.

Tentorial Meningiomas

Tentorial meningiomas may be above the tentorium.

below the tentorium, or both above and below. It is neces-
sary preoperatively to make a precise determination of
the site of origin of the tumor by CT scan and angiogra-
phy. Generally, the supratentorial operative approach
allows better visualization of the tumor, facilitates resec-
tion of the infiltrated portion of the tentorium, and per-
mits total excision in one stage. The infratentorial route
should be reserved for tumors with a posterior attach-
ment. When the transverse sinus is involved, a combined
supratentorial and infratentorial approach is pre-
ferred (263).

Lateral Ventricle Meningiomas

A meningioma of the lateral ventricle will usually arise

from the area of the trigone or atrium of the ventricle

and will dilate the temporal horn because of the obstruc-
tion to CSF flow it produces (264).

A temporal craniotomy is used, with a cortical inci-

sion made in the middle third of the middle temporal
gyrus. The posterior third of the superior frontal gyrus

and the supramarginal gyrus must be avoided, especially
in the dominant hemisphere. The cortex and arachnoid
are coagulated and the white mater incised down to the
ependyma of the lateral ventricle. Bipolar coagulation is

used to divide the choroid plexus. The tumor is exposed

but must not be pulled out, for the important anterior
and posterior choroid arteries feeding the tumor will be
torn. Rather, the tumor must be elevated step by step,
exposing the vessels over the medial surface of the tu-
mor, or piecemeal decompression must be done to allow
coagulation of feeding vessels at the tumor margin.
Fixed Lelya retractors are essential during this often me-
ticulous operation, so as not to unduly enlarge the corti-
cal incision. It is essential not to lose control of medial
arteries and veins as they may be impossible to see until
the tumor is completely removed. The ventricles should
be carefully and gently irrigated, looking for any source
of bleeding, especially from the tela choroidea. Dural
closure must be water-tight.

Outcome

The outcome for patients with meningiomas should

be excellent with few exceptions. With CT or MRI scan-
ning available, these lesions should be diagnosed earlier
while still small in size. This is especially true in patients
who have had a seizure or have experienced progressive

visual loss (Table 1). If light perception is lost before

TABLE 1 . The Medical College of Virginia series of patients with intracranial meningiomas compressing the optic nerve

Pre-Op

Post-Op

#

1

2
3
4

5
6
7
8
9

10

1 1

12

Age/sex

64 F
63 M
59 M
51 M
31 F
71 F
23 F
43 F
29 F
54 F
50 M
40 F

symptoms

1 5 years

6 months

1 year

1 5 months

3 years

1 5 years

3-4 months

14 years

9 months

6 years
2 years

1 year

OD"

20/40
20/800
20/40

*

NLP

*

*

20/200

CF"
HM

1

NLP'
HM

OS

C

NLP

HM
HM

20/400
20/70
20/70

NLP

OD

__a

—
—
_^

+
—
—

+
+
+
+

+

OS

+

e

—
—

tr'
tr
tr
+

—

tr
-
-
—

OD

20/20
20/20
20/20

*a

NLP

*

*

20/20
20/50

NLP
NLP

20/400

OS

NLP

20/25
20/200
20/20
20/20
20/400

NLP

*
*
*
«
*

Diagnostic

f

+
+
+
+
+
+
+
+
+
+
+

8

VA = visual acuity

" OD = right eye
° OS = left eye
" - = negative or absent

e

+ = positive

' tr = trace

9

* = visual acuity 20/30 or better pre- and postoperatively

" CF = count fingers

' HM = hand motion

1

NLP = no light perception

Optic pallor

VA

Duration

VA'

CT

operation, it will not be regained postoperatively. Yet
long periods, often over years, of progressive and severe
visual loss are not incompatible with extraordinary post-
operative visual recovery. It appears that the amount of
vision remaining, not the duration of visual loss prior to
operation, determines the postoperative result, in addi-
tion to the technical expertise of the surgeon (265).

In the series of patients with intracranial meningiomas

compressing the optic nerve (see Table 1), by the time of
examination, severe loss of visual acuity was present in
nearly every patient. All patients had dyschromatopsia
demonstrable by color-plate testing, and many had an

afferent pupillary defect with the swinging flashlight test

for optic nerve dysfunction. Definite optic pallor was

observed in 8 of 16 affected eyes. Visual field defects

included a bitemporal depression in five patients, monoc-
ular suppression in five patients, a binasal defect in one
patient, and an incongruous homonymous defect in an-
other patient. Limited gaze of the ocular muscles and
mild proptosis of one eye occurred only in the two pa-
tients with sphenoid wing meningiomas.

Postoperatively, visual acuity improved in 9 of 16 af-

fected eyes (56%), remained the same in 6 of 16 (37%),
and was worse in one patient (#6). Two of four patients
with bilateral visual loss had improvement of visual
acuity in both eyes. A better visual acuity was obtained
in two of eight eyes with definite optic pallor and in two
of four eyes with a trace of paleness of the optic discs.

Visual field deficits distinctly improved in four patients.

It is unfair to compare the results of meningioma sur-

gery done today with those done decades ago by noted
neurosurgeons such as Gushing and Olivecrona. During
nearly all of Cushing's career, only one or two units of

blood could be given as a transfusion, and the hemo-
static electrocautery did not become available until 1927

when it was first used for a craniotomy by Gushing. No

discussion of meningiomas would be complete without
acknowledging one of the classic monographs of medi-

cine. In 1915, Harvey Gushing and Louis Eisenhardt be-
gan a meticulous and scholarly study of meningiomas
which resulted in the monograph, Meningiomas: Their

Classification, Regional Behavior, Life History and Sur-

gical End Results, published in 1938. This remains the

landmark publication on meningiomas. The case histo-
ries and operative drawings are without equal (9).

Future Treatment

Technical advances continue. The ultrasonic surgical

aspirator allows safe removal of the tumor parenchyma

and spares the vascular supply. This is a very useful in-
strument for tumor operations. The surgical laser is be-
ing increasingly applied to brain tumor operations. A
tumor can be incised, excised, or evaporated by a laser.
There is no doubt lasers will have adjunctive roles in

BRAIN TUMORS ••' 149

most operations for brain tumors, particularly menin-

giomas. The higher incidence of meningiomas in women
compared with men, and the rapidly progressive course
of these tumors in some pregnant patients, suggest that
hormones may be involved in the biology of this tumor.

Indeed, Donnell, Meyer, and Donegan have reported a

high concentration of estrogen-receptor protein in some
meningiomas (266). Olson, Beck, Schlechte, and Loh
have reported that hormonal manipulation of meningio-
mas in vitro by tamoxifen stimulated growth in one in-
stance, but the synthetic antiprogestetone RU486 inhib-
ited meningioma growth to some degree (267). Further
research on steroid hormone receptors will be necessary
for developing hormonal therapy for adjuvant therapy

for humans with recurrent or unresectable meningi-
omas.

ACOUSTIC NEUROMAS

Incident

Schwannomas are relatively common tumors com-

prising 8 to 10 percent of all primary intracranial neo-
plasms. Schwannomas generally originate from sensory

nerves, although they have been found in virtually every

site intracranially. including intracerebrally.

The neuroma of the eighth cranial nerve is known by

many names, such as schwannoma of the eighth nerve,

acoustic neuroma, acoustic neurinoma, peripheral
glioma, cerebellopontine angle tumor, and peri neural fi-

broblastoma. In serial sections of unselected temporal

bones, the tumor has been found in its very early stage of

growth in 1 to 2 percent of specimens. The tumor is
usually unilateral, but may be bilateral in type II von
Recklinghausen's disease. Neurosurgeons and otological
surgeons tend to use different surgical approaches to

acoustic neuromas. Otological surgeons, who usually ex-
amine patients with hearing deficits who present early,
frequently diagnose the tumor when the tumor is very
small, less than 1 cm in diameter. Otological surgeons
prefer to remove the small tumors via a translabyrinth-
ine approach. This approach has a high success rate in
preserving brainstem and seventh nerve function, but

destroys the organs of hearing. Thus, any remaining pre-
operative hearing in the affected ear cannot be preserved
or improved by the translabyrinthine operation. Neuro-

surgeons, on the other hand, who more frequently ini-
tially evaluate patients with cerebellopontine symptoms

and signs caused by larger tumors, prefer the suboccipi-

tal transmeatal approach. This approach allows direct

visualization of the vital brainstem structures and allows
preservation of not only the seventh cranial nerve but
potentially the cochlear division of the eighth cranial
nerve as well.

150 / CHAPTER8

Symptoms and Signs

Since these tumors primarily arise from the vestibular

components of the eighth nerve near Scarpa's ganglion
in the internal auditory canal, the vestibular and audi-
tory fibers are usually involved early (268). Auditory
symptoms are the earliest and most striking symptoms
and appear in the form of tinnitus and progressive loss of
hearing. Tinnitus usually precedes dizziness. Vestibular
symptoms are less pronounced and consist of mild per-
sistent episodes of objective or subjective vertigo. The

tumor may become extremely large before seventh cra-
nial nerve symptoms appear. As the tumor grows out of
the porus acousticus and into the cerebellopontine angle,
the fifth cranial nerve or the descending tract of the fifth
nerve in the brainstem becomes compressed by direct
pressure on the brainstem, producing numbness of the
ipsilateral face.

As the tumor enlarges, compression of the adjacent

cerebellar hemisphere or the cerebellar peduncle pro-

duces ataxia, vertigo, and dysmetria of the ipsilateral ex-

tremities. Initial gait ataxia may progress to a tendency
to fall to the side of the tumor. Nystagmus toward the
side of the lesion develops. Further increase in size dis-
places the brainstem, as well as cranial nerves IX, X, and
XI. There may be difficulty in swallowing and talking,

with slurred or nasal speech.

The dislocation of the pons may cause obstruction of

the fourth ventricle, or the tumor may grow upward

through the incisura of the tentorium, obstructing the
flow of spinal fluid and leading to increased pressure sec-
ondary to hydrocephalus. This will cause headaches and

vomiting. Very rarely, a patient will have localized pain
in the retromastoid area.

The very small tumors are still rarely diagnosed be-

cause of the mild early symptomatology. Initial audio-

logical testing is positive for a retrocochlear lesion in
only about one-half of patients harboring a small tumor.

As the tumor becomes larger, a sensorineural hearing
loss can be documented by audiometry and absent calo-

ric responses on the affected side. Caloric testing has
been improved by use of the electronystagmogram.
Hearing loss can frequently be characterized as retro-

cochlear by finding impaired speech discrimination,
type II and type IV Bekesy audiometric responses, and
an absence of recruitment as evidenced by a low, short-
increment sensitivity index (SISI) score. These tests are
being replaced by brainstem evoked-response audiome-
try (269) which, along with MRI, will reveal even the
smallest tumors. MRI distinctly shows the relationship

of the tumor to the adjacent seventh cranial nerve.

The involvement of the seventh cranial nerve pro-

duces a peripheral facial nerve palsy and hypesthesia of
the posterior aspect of the external auditory canal. The
latter has been found in up to 95 percent of cases and is

regarded as a sensitive indicator of facial nerve involve-

ment. As the fifth cranial nerve becomes involved, there
will be loss of the corneal reflex and later hypesthesia

over all three divisions of the trigeminal nerve.

The involvement of the cerebellum and peduncle is

recognized by mild ataxia or dysmetria on the ipsilateral
side. Reflex changes and weakness of the ipsilateral arm
and leg occur when the tumor is veryiarge.

Pathology

The neuroma of the eighth nerve develops primarily

from vestibular branches in the internal auditory canal

near Scarpa's ganglion (268). The tumors are round, ir-
regularly encapsulated, and very firm in consistency.
They measure from 1 cm to 4 cm when they finally fill

the cerebellopontine angle. They appear grossly as dark

yellow or brown in color, with areas of degeneration and •

cysts.

Microscopically, there are firm areas and irregular

softer yellow areas of fatty degeneration. The firm area
consists of elongated Schwann-cell nuclei, arranged in
rows producing typical palisading. Collagen is deposited

in uniform sheets between the cells. In the softer areas,
there are foamy cells sometimes referred to as pseudo-

xanthoma cells.

In type II von Recklinghausen's disease, the acoustic

neuromas are likely to be bilateral and associated with
optic nerve gliomas, intracranial gliomas, and meningio-
mas. The skin may show cafe-au-lait pigmentation, sub-

cutaneous lipomas, and peripheral neuromas. The
eighth nerve tumor in von Recklinghausen's disease,
even when small, is very unlikely to be removed with
preservation of hearing.

Diagnostic Tests

The definitive tests are radiological. Plain x-rays with

Stenver's views and tomography will reveal erosion of

the internal auditory canal in over 75 percent of cases.

The density of the petrous bone on CT may obscure the
smaller tumors in the porus acusticus (270). Therefore,
enhanced MRI of the posterior fossa is now the best sin-
gle radiologic test to define the tumor and its relationship
to the adjacent cranial nerves and brainstem (Fig. 8).
Multiplaner imaging capability undiminished by bony
artifacts represents the major advantage of MRI in the
posterior fossa region. Acoustic nerve tumors and cere-

bellopontine angle (CPA) meningiomas both exhibit low

signal intensity on T,-weighted images, but may be dif-

ferentiated by location. A CPA meningioma usually can
be seen as separate from the vestibular nerve complex,

whereas the epicenter of an acoustic nerve tumor is lo-
cated at that complex. ———

BRAIN TUMORS / 151

R

FIG. 8. Right acoustic neuroma. MRI details relationship of

tumor to the seventh cranial nerve (arrow).

Operation

Total removal of acoustic neuromas is now possible,

especially with early diagnosis and microsurgical tech-
niques. Not only can surgeons usually preserve the func-

tion of the seventh nerve in patients with small acoustic
neuromas, but at times the cochlear nerve can be pre-
served as well, preserving or restoring useful hearing.

The patient can be operated on in the sitting position,

or a reclining or supine position with rotation of the

head. A linear scalp incision is made on the symptomatic
side over the occipital bone. A unilateral retromastoid
craniectomy is carried out, removing bone posterior to
the sigmoid sinus. The basic approach to the tumor by
the suboccipital transmeatal approach has been outlined

by Rand and Kurze (271). The facial nerve is identified

and separated from the tumor in the auditory canal, and
the bulk of the tumor is decompressed. From the lateral

aspect resection proceeds from the posterior direction
down to the pons. Cranial nerves IX, X, and XI are care-
fully identified. Branches of the anterior inferior cerebel-
lar artery are also identified and spared. Superior aspects
of the tumor are resected down to the pons, identifying
the fifth cranial nerve superiorly. The remaining tumor

is dissected clear of the facial nerve. Skillful surgeons
with experience using modern magnification techniques
can usually spare cranial nerve VII. A stimulator at the
lowest possible setting applied at the brainstem origin of

the facial nerve will produce a facial twitch if the nerve is
intact at the end of the operation. If this nerve is sec-
tioned during the operation, it may be repaired at that

time. Since the nerve has been stretched by the tumor, it
is often possible to reanastomose the nerve using micro-
suturing techniques. If this cannot be done, then at a
second operation, a hypoglossal-facial anastomosis can

be done. Some surgeons prefer to use either the phrenic

or accessory nerve for the anastomosis.

If the tumor is extremely large, it may be beneficial to

do a two-stage operation as recommended by Sheptak
and Jannetta (272). At the first operation, an attempt is
made to remove at least 50 to 75 percent of the tumor
and the seventh cranial nerve is tagged. Tumor remain-
ing after the first operation gradually decompresses out

of the pons and comes to lie laterally against the petrous

bone. Upon reoperation 10 to 14 days after the first oper-
ation, tumor is usually found to fill the void left by the
first operation. At the second operation, it may be easier

to identify the arachnoid plane between the brainstem
and the tumor, and dissection is more easily carried out
without disturbing the patient's vital signs during the

operation.

Outcome

In the series reported by Sheptak and Jannetta, of 25

patients with acoustic neuromas who underwent sur-
gery, 78 percent had a good result, returning to normal
activity or full-time employment. Anatomic continuity
of the facial nerve was preserved in 74 percent of pa-

tients, most of whom recovered facial function (272).
When the facial nerve remains anatomically intact at
operation, it may take 2 to 14 months for satisfactory

facial movement to return.

The most frequent immediate postoperative compli-

cation is CSF circulatory problems and has been re-
ported in up to 35 percent of operated patients
(273,274). A CSF leak at the operative site may require
temporary lumbar drainage of CSF. If there is a transient
fifth and seventh cranial nerve paresis, then a temporary
tarsorrhaphy should be done for prevention of potential
corneal irritation.

Recurrence is a problem of incomplete removal. In

MacCarty's series, 15 of 132 patients had subtotal exci-
sions and, of these, five needed reoperation for recur-
rence (275). In a series of 30 patients reported by Oje-
mann, 10 tumors were totally removed. Three of the

tumors which were incompletely resected recurred

within 15 to 24 months after the initial operation (274).

Patients with neurofibromatosis who have bilateral

acoustic neuromas with deafness in one or both ears will

most certainly need speech and hearing training includ-
ing lip reading, as attempts to remove these tumors bilat-

erally will nearly always result in deafness. Acoustic neu-
romas are more frequent in women and may have a
rapidly progressive clinical course in pregnant women.
Neuroma of the acoustic nerve is the other intracranial

152 / CHAPTERS

tumor besides meningioma in which estrogen receptors
have been demonstrated (276).

CRANIOPHARYNGIOMAS

Incidence

Craniopharyngiomas account for approximately 4

percent of intracranial tumors, with 0.5 to 2 percent of
new cases/million population occurring each year. Al-
though one-half of the total cases of Craniopharyngiomas
occur in adults, Craniopharyngiomas account for a
greater percentage of tumors of children: 5 to 13 percent
of all intracranial neoplasms of childhood, with a peak
incidence from 6 to 15 years (277). Craniopharyngiomas
were the most common supratentorial tumor of child-

hood in Matson's tumor series (277). There are marked

differences' in clinical presentation, radiological charac-
teristics, and postoperative outcome between children

and adults.

Symptoms and Signs

Children with a craniopharyngioma usually present

with headaches, vomiting, or visual loss, and psychologi-
cal changes. Diabetes insipidus is rare. Adults usually
present with endocrinological disturbances and visual

field defects.

Examination may reveal visual field defects and often

bitemporal hemianopsia. About 30 percent of children

are found to have papilledema. Small stature is noted in
children. Adults will have endocrine disturbances such

as amenorrhea or loss of libido.

Pathology

These tumors are epithelial in origin and partly cystic

in nature, containing cholesterol crystals and deposits of
calcium. The histological pattern consists of nests of

complex strands of epithelial cells, supported by a vari-

able amount of loose connective tissue stroma.^Since the
anatomical structures in the suprasellar region are nor-
mally devoid of epithelial cells such as those seen in Cra-
niopharyngiomas, the nature and source of these cells
have been the subject of extensive investigation. The pap-
illary histological characteristics of the tumors often
have keratin nodule formations, cholesterol clefts, for-
eign body giant cells, adamantinous elements, and squa-

mous epithelium.

Craniopharyngiomas are now generally considered to

arise either from ectopic embryonic cell rests of enamel
organs, or from residual metaplastic squamous epithe-
lium found in the adenophypophysis and anterior infun-
dibulum. There is evidence for two distinct craniopha-

ryngioma variants, a squamous papillary type and a

classic adamantinous type.

These tumors have a benign microscopic appearance

which belies their malignant clinical behavior, especially—

in childhood. Although usually apparently well circum-

scribed and extracerebral in location, they often show
extension into neighboring brain tissue evoking a vari-
able degree of glial reaction. Islets of tumor cells may be
found in the hypothalamus and in the walls of the third
ventricle. Although only a few Craniopharyngiomas are
found in the third ventricle, most grow around and into
adjacent structures, such as the carotid and anterior cere-

bral arteries, the optic nerves and chiasm, as well as the

hypothalamus, and total operative removal can be ex-
tremely difficult if not impossible, even with modern
neurosurgical techniques.

Diagnostic Studies

Plain x-rays are helpful in children, as approximately

70 percent of cases of craniopharyngioma will have intra-
cranial calcification in an area of an abnormal sella tur-
cica. Craniopharyngioma is the most common tumor to

produce recognizable suprasellar calcification. Signs of

intracranial hypertension, such as sprung cranial su-
tures, may be seen on plain x-ray as well. Calcification is
less common in adults with a craniopharyngioma. CT
and/or MRI scanning is the initial diagnostic test of
choice and, in addition to a well-circumscribed suprasel-

lar tumor which may have attenuation values of both
cyst and calcium, CT or MRI will reveal any hydrocepha-
lus caused by the tumor.

Operation

Patients with a craniopharyngioma can be treated by

one of four modalities: (1) gross total tumor excision, (2)
incomplete tumor removal with radiotherapy, (3) in-

complete tumor removal without radiotherapy, and (4)
cyst evacuation through a burr hole followed by radio-
therapy, repeated cyst aspiration, or installation of radio-
active substances into the cyst.

The location and configuration of the tumor influ-

ences the surgical approach. Wholly intrasellar tumors
can be safely removed by the transphenoidal route. Tu-

mors extending under the temporal lobe are best ap-
proached by a temporal route. The majority of Cranio-
pharyngiomas are located beneath the chiasm and

extend up into the hypothalamus and third ventricle,
down between the clivus and brainstem, and also into
the sella. With this location, some surgeons recommend
an approach along the sphenoid ridge, others advocate a
subfrontal approach, and still others approach the tumor

obliquely over the roof of the orbit or along the
falx (278).

BRAIN TUMORS

Tumor removal may be carried out through a sub-

frontal exposure according to techniques outlined by
Matson and Crigler (277). These authors were able to
totally remove 44 tumors from a group of 74 children
with craniopharyngiomas, without operative mortality
in the 40 patients who had a primary operation only.
Secondary or tertiary operations were associated with in-
creased postoperative morbidity and mortality.

Patterson and Danylevich have described a transcra-

nial approach through the lamina terminalis and sphe-

noid sinus for removal of craniopharyngiomas (279). In
this approach, a small, low unilateral bone flap is made

on the right side (particularly convenient for a right-

handed surgeon) above the orbit, so that it spans the
distance between the falx and temporal line, just above
the orbital ridge. A small strip of 1 cm of the undersur-
face of the frontal lobe is removed to facilitate exposure
of the lamina terminalis behind the optic chiasm. The
tuberculum sellae is removed, the sellar contents visual-
ized, and the lamina terminalis is exposed between the

optic tracts. The tumor is removed by pushing pieces

down and away from the optic chiasm and hypothala-
mus, and toward the sphenoid sinus from where the tu-
mor pieces are extracted. In this method, tumor on the
hypothalamus is removed under direct vision. A unilat-

eral pterional craniotomy is used by many surgeons as it

allows dissection in the parachiasmal spaces.

Regardless of the approach, special care must be taken

not to injure the frontal lobes, optic nerves, chiasm. op-
tic tracts, hypothalamus, or adjacent vasculature. The
risks of operation are real, but recent advances in magni-
fication techniques allow radical, if not complete, re-
moval of these tumors, sparing the all important infun-
dibulum and pituitary stalk.

Outcome

Often the surgeon, even with magnification tech-

niques, is confident of total tumor removal at the end of

the operation, only to find that the follow-up CT or MRI

of the brain reveals some tumor, or that the tumor recurs

(280). In many instances this event is unavoidable since
the tumor is not nearly so discrete from brain tissue as
most surgeons believe. Bartlett has stated that total re-
moval of a craniopharyngioma is impossible (281).
Kempe has stated emphatically that the capsule of a
craniopharyngioma is closely attached to the hypothala-
mus, and that attempting complete removal of the tu-
mor invariably leads to infarction of the hypothalamus
(248). Ghatak, Hirano, and Zimmerman have clearly

demonstrated the local invasiveness of the tumor (282).

Thus, the tumor is not only malignant by location but by
histology as well, as it can actually infiltrate the brain
with nests of cells making operative removal impossible.
This fact is well established in the literature, but too of-

ten ignored in the actual patient with a craniophanim-
gioma, especially at the time of initial diagnosis and
operation.

Bloom reports 5- and 10-year survival rates of 76 and

61 percent, respectively, for patients treated with opera-

tion and conventional radiation therapy at the Royal

Marsden Hospital (283). At the New York Hospital, par-
tial removal of craniopharyngiomas resulted in a recur-

rence rate of 72 percent within 5 years without radiation

therapy, and 41 percent when 3,000 to 4,500 rads were
given following operation (279). These are unsatisfac-
tory results when one considers craniopharyngiomas to
be potentially a biologically benign tumor, although
usually malignant by location. The major problems to
overcome are damage to the frontal, temporal, or hypo-
thalamic areas of the brain. Tumor recurrence is a major

problem, and usually occurs because pieces of the tumor
are left in the hypothalamus. Craniopharygiomas that

are adherent to the hypothalamus in the region of the
tuber cinereum cannot be removed totally with preserva-
tion of the pituitary stalk and with the patient being free
of diabetes insipidus.

When the goal of complete or radical removal of this

tumor is not achieved, the best method of treatment for
the patient is unclear. At the Hospital for Sick Children.
London, even radical removal was associated with at
least 25 percent recurrence (284). It is usually the larger
tumors, greater than 3 cm at initial diagnosis, that are

unable to be removed and thus deserve attention for fur-
ther therapy.

Preliminary observations suggest that radiotherapy

offers an additional therapeutic modality for patients
with residual postoperative tumor. In Shapiro, Till, and

Grant's report, seven patients were treated by incom-
plete removal and deep radiotherapy of 4,000 to 5,500

rads without symptomatic recurrence (284).

If the tumor is cystic, or the recurrence is cystic as it

often may be, then an Ommaya reservoir should be
placed for easy repeated aspiration. Also, this can be
used to instill radioactive substances into the cystic tu-
mor. We and others have used colloidal chromic phos-

phate (colloidal

32

P) intracystic injections successfully to

sclerose the secreting tumor lining and improve the clini-
cal condition of the patient (285-287). We have shown
an in vitro destruction of craniopharyngioma cells by

32

P

(287). A dose of 1 mCi colloidal

32

P per injection will not

injure the optic or oculomotor nerves because of the lim-
ited penetration (approximately 1 mm) of the beta-ra-

diation of

32

P, unless the cyst is very small and the wall

less than 0.5 mm in thickness.

Hoffman and coworkers suggest withholding radio-

therapy in cases of incomplete excision until there is tu-
mor recurrence (288). Certainly, considering the long-
term effects of radiotherapy, it should not be
administered if only a small amount of tumor remains
on the internal carotid artery or hypothalamus. If a large

154 / CHAPTERS

amount of tumor remains, radiotherapy to 5,000 rads

can be administered to the tumor area only. A cystic

recurrence of the tumor can be treated by aspira-
tion along with the injection of

32

P or

198

Au into the

cyst (285).

In children, it has been observed that, following re-

moval of a craniopharyngioma, normal growth may
continue despite lack of growth hormone secretion or

growth hormone therapy. If growth becomes retarded,

exogenous growth hormone can be administered. Fol-

lowing attempts at complete removal, some children will

become very obese or have diabetes insipidus requiring
strict endocrine control.

Future Treatment

Bullard and Signer reported a major breakthrough in

the heterotransplantation of human craniopharyngioma
in athymic "nude" mice (289). Thus, there is now a use-
ful animal model to study the natural history and cell

biology of this tumor.

PRIMARY CENTRAL NERVOUS SYSTEM

LYMPHOMAS

Incidence

Primary central nervous system (CNS) lymphomas

have in the past constituted a rare group of neoplasms.
These are non-Hodgkin's lymphomas, mostly of B-cell
origin. They include reticulum-cell sarcomas, microglio-
mas, and histiocytic lymphomas. These tumors initially
represented less than 1 percent of all primary brain tu-
mors. In the past 10 years, however, the incidence has

tripled in the nonimmunosuppressed population. By

1991. the tumor will be the most common neurological

neoplasm by virtue of the increase in its sporadic occur-
rence and in the acquired immunodeficiency syndrome
(AIDS) population. Three percent of AIDS patients will

develop this tumor either prior to AIDS diagnosis, or
during their subsequent course. Immunological studies
have also suggested a role for Epstein-Barr virus in the
production of lymphomas.

The first description of tumors classified as non-Hodg-

kin's lymphoma of the CNS (NHL-CNS) labeled the tu-
mors "perithelial sarcomas," reflecting their perivascu-
lar location. There was a resemblance between these

brain neoplasms and those tumors of lymph node origin

which had been termed "reticulum cell sarcomas"

(RCS). American authors favored the term "reticulum

c e l l sarcoma," and European authors preferred the term

"microglioma." Other authors considered these tumors
to be two separate but related tumor types. This entire
controversy has become irrelevant, as these tumors are

in fact lymphomas.

The modern classification of non-Hodgkin's lympho-

mas emerged from the separation of systemic lympho-

mas into histological groups with differing prognoses

and the realization that most non-Hodgkin's lympho-

mas were composed of neoplastic B-lymphocytes. The

application of increasingly sophisticated immunological
and molecular genetic methods to lymphoma diagnosis
and classification has given rise to a series of classifica-

tion systems, culminating in the International Working

Formulation sponsored by the National Cancer Insti-
tute.

Diagnostic Studies

Of the roughly 24,000 individuals in the United States

who each year develop NHL, between 2 and 10 percent
will develop neurological involvement. There is a slight
male preponderance at all ages, with a median age at
occurrence of 55 years. Three populations are at risk of
developing NHL-CNS: transplant recipients, patients
with AIDS, and those with congenital immunodeficien-
cies. The patients with NHL-CNS present with four dis-
tinct profiles: (1) solitary or multiple discrete intracranial
nodules, (2) diffuse meningeal or periventricular lesions,
(3) uveal or vitreous deposits (uveitis/vitritis), and (4)
localized intradural spinal cord masses. A febrile upper
respiratory or gastrointestinal illness may precede the ini-
tial neurological symptoms, which frequently are person-
ality changes. These neurological difficulties are similar
to those seen in multiple sclerosis, and in encephalitis of
viral, fungal or parasitic origin. The eye involvement by
lymphoma often accelerates the development of clini-
cally evident deposits in the brain. Eye symptoms such
as obscured, cloudy or blurred vision, or altered visual
acuity accompany lymphoma involving the posterior

segment of the eye, including the vitreous, choroid, and

retina.

Both contrast-enhanced CT and MRI provide delin-

eation of the number and extent of NHL-CNS lesions
within the brain parenchyma. Ten percent of these le-
sions are detectable on contrast CT as hyperdense
deposits within the subcortical white matter, often in
proximity to the ventricular system. Calcification, hem-
orrhage, or cyst formation is uncommon, and suggests
other lesions. The injection of single or double contrast
results in delineation of lesions in over 90 percent of

patients with Jymphomas. CT and MRI usually fail to

detect subarachnoid or vitreal NHL-CNS.

The tumor staging done in this disorder is based on

enhanced CT scanning, CSF examination (in the ab-

sence of intracranial hypertension), and slit-lamp eye
evaluation. As NHL-CNS is a restricted neurological ail-
ment, there is little reason to perform CT scans of the
chest or abdomen, bone marrow biopsy, or surgical ex-
ploration of the abdomen. Stereotactic biopsy may be

BRAIN TUMORS / 155

necessary at times when the above studies fail to give a

histological or immunohistochemical diagnosis.

Treatment

The initial treatment is corticosteroids, which usually

provides a dramatic but short-lived clinical improve-
ment and often complete regression of the lesions. This
responsiveness represents true glucocorticoid cytotoxic-

4ty for lymphoid cells. Radiation therapy clearly pro-

longs survival, and adjuvant chemotherapy trials are un-
derway in at least five centers in the United States.

METASTATIC INTRACRANIAL TUMORS

Incidence

The incidence of metastatic tumor is increasing, pri-

marily caused by two factors: (1) improved length of sur-

vival of patients with cancer, thus increased exposure
time for metastases, and (2) the diagnostic acumen for
single or multiple metastases has been greatly enhanced
by CT and MRI scanning. Also, although unproven in
humans, there is experimental evidence that some che-

motherapeutic agents given for systemic cancer may

produce transient defects in the normal blood-brain

barrier, thus potentially permitting CNS seeding of these

systemic tumors (3).

Brain metastases are the immediate cause of death in

many patients with cancer. At Memorial Hospital in
New York, autopsies of patients who died from systemic

cancer disclosed that 12 percent had brain metastasis, of

which 40 percent were solitary tumors (290). With the
increasing number of these patients, the controversial

aspects of their care must be clarified. Properly man-

aged, many of these patients can be greatly helped and
can enjoy a worthwhile life. In this section, it is our in-
tent to present the neurosurgeon's viewpoint and role in
the management of these patients.

Symptoms and Signs

The symptoms and signs of metastatic brain tumors

are similar to those of other expanding intracranial le-
sions. The tumor may produce a generalized increase in
intracranial pressure, as well as local effects by compres-
sion or destruction of brain tissue in the area of tumor

growth. The generalized increase in intracranial pressure

will result in headache, nausea, and vomiting. Headache
is the single most common presenting symptom of cere-

bral metastases, but is present in only about 50 percent

of cases. The headaches are usually caused by increased

intracranial pressure and are present in the morning
upon awakening. Mental status changes and weakness of

an extremity may be important symptoms. Seizures oc-

cur in only about 15 percent of cases, but especially in

the patients with leptomeningeal metastases. Abrupt on-
set of neurological symptoms suggestive of a stroke may
occur from vessel occlusion by tumor cells or by hemor-
rhage into the tumor, brain, or subarachnoid space. Pa-
tients with melanoma, choriocarcinoma, and with de-
creased platelet counts secondary to chemotherapy may
present with intracranial bleeding.

The examination will reveal papilledema if there has

been a chronic increase in ICP. Mental changes may be
related to the specific area of the brain, but usually there
is a defect in cognitive functioning. Hemiparesis and re-
flex changes are frequently revealed by examination espe-
cially when the tumor involves the motor cortex or the
internal capsule.

Pathology

The most common sources of metastases to the brain

are tumors of the lung, breast, and kidney, and malig-
nant melanoma. Tumors of the gastrointestinal tract,
thyroid, uterus, ovary, pancreas, and prostate, and sarco-
mas infrequently metastasize to the brain. About 50 per-

cent of brain melastases originate from malignancies in

the lung or breast. There is an extremely high incidence

of CNS metastases from small-cell bronchogenic carci-

noma, and the incidence is increased to 80 percent in
patients surviving two years after diagnosis (263). In pa-

tients in whom the primary tumor is initially unknown,
more than one-half are subsequently found to have
bronchogenic carcinoma. Metastases to the brain may
be both leptomeningeal and intracerebral.

The route of spread of metastasis to the CNS is usually

hematogenous, although occasionally the tumor spreads
by direct extension through the bone or via the subarach-
noid space, as in leptomeningeal invasion.

About 75 percent of intracranial tumor deposits are

located within the brain parenchyma, frequently at the

junction of white and gray matter. In some series, a pre-

dominance of parenchymal metastasis has been ob-
served in the distribution of the middle cerebral artery
which has been explained on the basis of laminar flow
(291,292). The cerebellum is another frequent site for
tumor deposits.

Brain metastasis from solid tumors is solitary in about

50 to 65 percent of cases when the diagnosis is made
during life. In autopsy series, the incidence of solitary
metastasis drops to 25 to 40 percent. The lesions are

generally soft, nodular, circumscribed masses, often with
central necrosis. They vary in size, with even the smallest
lesion being associated with severe white-matter edema
of the ipsilateral hemisphere. In addition to solid meta-
static lesions, leukemia and lymphomas are also a major
disease category that invades the CNS. These hemato-

156 / CHAPTER8

logical malignancies usually invade the leptomeninges in

a diffuse or multifocal manner.

There is a wide variability in the interval between the

clinical appearance of the primary cancer and that of the
cerebral metastasis. The cerebral metastasis may be the
first manifestation of a systemic cancer. The symptoms
and findings of cerebral metastasis may appear at the
time of initial evaluation of systemic cancer in the course
of screening studies or many years after the initial diag-
nosis of cancer. The time interval tends to be a function
of the tissue of origin of the metastatic tumor. The aver-
age interval between the diagnosis of lung carcinoma
and the development of brain metastasis is four months,

whereas the interval for breast cancer averages three

years. An excision of a cerebral metastasis may also be
followed by a long latent interval of months or rarely
even years before the primary cancer, which is usually

bronchogenic. is evident.

Vasogenic edema, which predominantly involves the

white matter, is due to leakage of serum proteins and

fluid through blood-vessel walls. This type of edema is
seen with metastatic carcinoma even when the tumor is
very small. Metastatic neoplasms within the brain are

characterized by an absence of a blood-brain barrier to

protein. As demonstrated by standard radionuclides
used for clinical diagnosis, the abnormal permeability to
protein-bound tracers is related to defective capillary en-

dothelium (293). These defective capillaries are found in

the tumor and not surrounding edematous brain. The
presence of defective capillaries probably is sufficient to
explain the associated brain edema. These blood vessels
provide a ready egress for the serum into the extracellu-
lar space of the brain.

In a prospective study by Galicich, Sundareson, Arbit,

and Passe of 33 patients with a solitary brain metastasis,
the second most common cancer to lung cancer was mel-

anoma (294), Tn a series of 1,341 patients with histologi-

cally proven malignant melanoma seen at Duke Univer-
sity Medical Center from 1968 to 1978, 107 patients

developed central nervous system metastasis (295). Male

patients, patients with invasive primary lesions as mea-
sured by Clark's system, and patients with primary le-
sions of the head, neck, or oral mucosa had a higher
incidence of CNS metastasis. A single CNS metastasis
was seen in 48.8 percent of patients, and in 22 percent of

the patients the CNS was the only site of metastasis.

Melanoma occurs in multiple sites in the brain in the

majority of cases (296). An autopsy series reported by

Patel and associates of patients who died with multiple
metastatic melanomas closely detailed the central ner-

vous system involvement (297). The rates of metastasis
were 49 percent for brain, 22 percent for meninges, and

13 percent for medulla and pons. Patel and associates

also correlated autopsy findings with the terminal course

of patients with melanoma. Of 216 patients, 20 percent

died of a CNS complication, second to 39 percent who

died of respiratory failure. Thus, one-fifth of the patients

died from complications of brain metastases, primarily

from hemorrhages and increased intracranial pressure.
All patients with primary head and neck melanoma be-
ing evaluated for surgery should have a CT or MRI be-
cause of the higher incidence of CNS metastases, com-
pared to patients with melanomas of the extremities

(298). Radiation therapy has little to offer patients with

melanoma (299).

Choriocarcinoma is the most malignant of the tumors

of chorionic tissue that arise from fetal tissues and in-
vade the maternal vasculature. The tumor cells metasta-
size by way of the vascular system to all organs, predomi-

nantly to the lungs and brain (300). The incidence of

cerebral metastasis from chorioepithelioma is 20 percent
or more (301). Since tumor cells spread by the vascular

system, tumor invasion of the vessel wall produces de-

generation and then dilation into varices or small aneu-
rysms which result in cerebral or subarachnoid hemor-

rhage. Intracerebral hemorrhage is the first sign of
involvement of the central nervous system. At autopsy,
occlusion of a cerebral artery, probably caused by tumor
emboli, is a commonly observed finding. Also, occlusion

of relatively large arteries has been reported and con-

firmed by operation (302).

Diagnostic Studies

Plain skull films are less valuable in evaluating pa-

tients with metastatic tumors for signs of increased intra-
cranial pressure than patients with primary tumors.

Even the calcified pineal gland may not be shifted be-
cause of bilateral or balancing lesions. The skull x-rays
may reveal bone destruction of the calvarium or base,
but the presence of bone metastases may or may not be
associated with an intracranial parenchymal lesion.

CT or MRI is the single most useful diagnostic test, as

each currently can detect 6- to 10-mm lesions depending
on density and location (303). CT or MRI will also detect
multiple lesions better than any other known method. In
addition, CT or MRI accurately reveals the amount of
edema surrounding a metastatic lesion and is, therefore,
useful for follow-up in the patient being palliated by ste-
roids. Hydrocephalus associated with posterior fossa le-
sions can be evaluated quickly on CT or MRI.

Cerebral arteriography and lumbar puncture are being

used less in the era of scanning. Arteriography will be

necessary at times when the diagnosis remains unclear or
in preparation for stereotactic biopsy or surgical exci-
sion. Lumbar puncture may be indicated after the pres-
ence of an intracerebral (parenchymatous) mass has

been ruled out by CT or MRI in order to make a definite
diagnosis of meningeal carcinomatosis or fungal or bacte-

rial meningitis. The spinal fluid obtained by lumbar
puncture should always have cytology done for malig-

BRAIN TUMORS / 157

nant cells, as well as careful bacteriological cultures for

rare fungi, such as cryptococcus. Tumor markers such as
carcinoembryonic antigen should be measured as well,
because these markers are useful in diagnosis and ther-
apy (304,305).

Operation

In general, management of the patient with metastatic

carcinoma to the brain is almost always palliative, with
cure being the rare exception. The patient with multiple
or deep cerebral lesions, or the patient whose condition

is generally poor with short life expectancy, is best pal-
liated by steroids and x-ray therapy. Steroids are effective

in reducing the associated cerebral edema and intracra-
nial pressure, thereby usually relieving the headaches.
Radiation therapy and/or chemotherapy may slow tu-

mor growth.

There are definite guidelines for operation. In general,

the metastasis should be solitary and surgically accessi-
ble, although surgical removal is sometimes indicated
for multiple lesions which are easily surgically accessible

or in the same operative exposure. The status of the pri-

mary tumor should also be considered. The primary tu-
mor should have been previously successfully treated
(i.e., by pneumonectomy), or treated in the future so at
least to permit long survival. At times, the intracranial
tumor may be symptomatic or life-threatening while the
primary is quiescent; then the metastasis will require im-
mediate operation. Also, there should not be widespread
metastases throughout the body.

Another indication for operation is when the diagno-

sis is unknown. The primary may be unknown and a
tissue diagnosis may be indicated for future therapeutic
management. Also, a solitary lesion in a patient with
cancer does not necessarily indicate a metastasis. The
differential diagnosis includes brain abscess, hematoma,
cerebral infarct, and another tumor such as a menin-

gioma or glioma.

The operation, with adequate steroid preparation, for

a metastatic tumor should be attended by low morbidity
and mortality. These tumors are usually easily located

beneath the cortical surface by mere visual inspection,
gentle palpation, or needle exploration. The tumor is
usually circumscribed, although not truly encapsulated.

It can be microscopically separated from brain tissue. It
is unclear whether there are microscopic cells remaining
after gross removal, but often in a more silent areas of the
brain, a 2- to 3-mm rind of surrounding brain can be
removed and the tumor bed carefully inspected for re-
maining tumor deposits. In various series, tumor re-
moval has been verified as complete at the operative site
in 58 to 75 percent of cases. Even when tumor removal
appears complete, x-ray therapy is standard adjunctive
postoperative therapy.

If a tissue diagnosis is necessary and the patient's con-

dition is poor, then CT- or MRI-guided needle biopsy
can be done. With CT or MRI verification, the needk
can be accurately placed in the tumor and adequate tis-
sue obtained for diagnosis.

Leptomeningeal carcinomatosis has been found in up

to 40 percent of autopsied symptomatic and asymptom-
atic patients with cancer, and may occur with any tumor.
Carcinoma of the breast involves the meninges most fre-
quently. The tumor may occlude the basal cisterns and
spinal meninges, producing a communicating hydro-

cephalus.

The tissue type of the metastasis, if known, should

influence operation. A tumor that is very radiosensitive,

such as lymphoma, can best be treated by radiotherapy

alone, after stereotactic biopsy, but other tumors such as
a hypernephroma or melanoma, being very radioresis-
tant, should be removed when solitary in the brain.

Outcome

The median survival time for series reported since

1970 of patients with a single metastasis, following oper-

ation alone, is five to six months. Thus, the median sur-
vival statistics of surgery alone are approximately the

same or slightly better than radiation therapy alone. In

RansohofFs series of 100 patients treated by combined
modalities of operation plus radiotherapy and/or chemo-

therapy, 38 percent survived 1 year and 13 percent sur-
vived beyond 2 years (306). In other studies of patients
with cerebral metastasis from bronchogenic carcinoma.
the median survival was 6 months, but 45 percent
survived longer than a year, and about 30 percent
were symptom-free neurologically during that time
(199,307-309).

It thus appears that a combined therapeutic approach

affords superior benefit over any one single treatment
modality alone (310-312). As oncologists improve the
longevity of patients with cancer, neurosurgeons will
need to be extremely aggressive to keep pace in knowl-
edge and techniques of polytherapy so as to give the pa-
tient the best opportunity for quality survival following
cerebral metastasis.

Combination chemotherapy does not control CNS

metastases of patients with small-cell bronchogenic carci-
noma. Unfortunately, since metastasis develops in one-
third to one-half of all patients with small-cell cancer,
many advocate prophylactic radiotherapy to the head,
but the efficacy of this approach has not been proven.

REFERENCES

1. Russell DS, Rubinstein LJ. Pathology of tumors of the nervous

system, 4th ed. Baltimore: Williams and Wilkins, 1977.

2. Nugent JL, Bunn PA Jr, Matthews MJ, et al. CNS metastases in