56 2 Diseases Mainly Affecting the Brain and its Coverings

Intracranial Hypertension and Brain Tumors

Definition:
An elevation of intracranial pressure (intracranial hypertension) may be
caused by various types of intracranial process, particularly brain tumors.
In addition to the focal signs produced by the underlying process itself, in-
tracranial hypertension manifests itself initially by headache, then by pro-
gressive impairment of consciousness and vegetative signs such as vomit-
ing, bradycardia and arterial hypertension. The objective findings include
papilledema, oculomotor palsy, pupillary abnormalities, disturbances of
respiration and other vital functions, and, finally, coma, when the elevated
intracranial pressure has led to herniation through the tentorial notch or
the foramen magnum (p. 223).

Signs of Intracranial orrhages, coronary hypoperfusion,

Hypertension and Pseudotumor
Cerebri
The main signs of intracranial hyper-
tension are listed in Table 2.10.
paresthesias in the hands and feet,
headache, and cerebral edema. Im-
mediate descent and treatment for
intracranial hypertension (see below)
are essential for recovery.

| Altitude Sickness
Too rapid ascent may be associated
with pulmonary edema, retinal hem-

Table 2.10 Clinical manifestations of intracranial hypertension

Subjective Headache (diffuse and persistent, most severe in the morning), vo-
miting (fasting, projectile), apathy
Signs of im- Confusion, respiratory disturbance, bradycardia, hypertension, cere-
pending bellar fits (opisthotonus and extensor spasms of arms and legs), di-
herniation lated pupils
Ocular findings Papilledema (may appear within hours), enlarged blind spot, at-
tacks of amblyopia, oculomotor palsy, occasionally abducens palsy
Skull radiograph Increased digitate markings, enlarged sella turcica with demineral-
ized dorsum sellae, diastasis of sutures in children
CT/MRI Slit ventricles (when elevation of ICP is due to cerebral edema), pe-
riventricular signal change, possible causative lesion (e.g., tumor,
hemorrhage)
EEG Diffusely abnormal, nonspecific
Lumbar Contraindicated when a dangerous elevation of ICP is suspected!
puncture Pressure over 200 mmH2O; may be normal, however, if CSF flow is
blocked at the occipitocervical or spinal level

Mumenthaler, Neurology 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.
All rights reserved. Usage subject to terms and conditions of license.
Mumenthaler, Neurology 2004 Thieme

Table 2.11 Causes of intracranial hypertension

Category Specific entities Clinical features Remarks

Intracranial mass Brain tumor, subdural hema-
toma, intracerebral hematoma
Infection Encephalitis, meningitis
Traumatic brain injury Contusion, brain edema, intrace-
rebral hematoma
Impairment of Intraventricular tumors, aque-
cerebrospinal fluid ductal stenosis, malresorptive
resorption hydrocephalus
Focal neurological and neuropsychologi-
cal deficits, headache
Fever, meningism E.g., neurobrucellosis,
syphilis
Progression of brain edema, focal
seizures
Headache (possibly ictal), vomiting; in Intermittent elevation of
malresorptive hydrocephalus spasticity cerebrospinal fluid pres-
of legs, urinary incontinence, psycho- sure, prior subarachnoid

Intracranial Hypertension and Brain Tumors

organic syndrome hemorrhage or meningitis
Elevation of cerebro- E.g. in polyradiculitis, spinal Lumbar puncture yields cerebrospinal
spinal fluid protein tumors (esp. schwannoma) fluid with elevated protein
Toxic processes Lead poisoning, insecticide Psycho-organic syndrome, anemia, lead
poisoning line (on gums)
Iatrogenic Steroids, oral contraceptives,
tetracycline
Altitude sickness On rapid ascent Headache, pulmonary edema, retinal Descend immediately!
hemorrhage, angina pectoris
Pseudotumor cerebri Usually affects obese young women; A diagnosis of exclusion;
slit ventricles, often papilledema see Table 2.12
Empty sella syndrome CT shows an apparently empty sella May be associated with
turcica containing air visual disturbances

57
58 2 Diseases Mainly Affecting the Brain and its Coverings
| Pseudotumor Cerebri (Benign
Intracranial Hypertension)
Cases of intracranial hypertension
that are not due to any of the entities
listed above or to any other discern-
ible organic intracranial process are
designated as pseudotumor cerebri or
benign intracranial hypertension.
This diagnosis of exclusion is most
commonly made in obese young
women. The neurological examina-
tion and neuroimaging studies are
normal except for papilledema, an
enlarged blind spot, and (occasion-
ally) very narrow cerebral ventricles
(slit ventricles). The cerebrospinal
fluid is under elevated pressure but of
normal composition. The clinical fea-
tures are summarized in Table 2.12.
Causative factors are found in only
about three-quarters of cases of intra-
cranial hypertension not associated
with an intracranial space-occupying
lesion (see above). Approximately
one-quarter are associated with otitis
media. Other causes include neuro-
Table 2.12 Characteristics of pseudotu-
mor cerebri
Usually diffuse headache
Young women
Often obese
Relatively common in pregnancy
Vomiting (moderately common)
Dizziness and tinnitus (common)
Nystagmus (moderately common)
Papilledema (common)
Enlarged blind spot
Slit ventricles on CT
Elevated cerebrospinal fluid pressure
Mumenthaler, Neurology 2004 Thieme
All rights reserved. Usage subject to terms and conditions of license.
syphilis and vitamin A deficiency
(246a).
Spontaneous recovery is the rule, and
recurrence is rare. 8 % of these pa-
tients suffer permanent visual im-
pairment as a consequence of papill-
edema; the risk is particularly high in
patients concomitantly suffering
from arterial hypertension. Gradual
shrinkage of the blind spot on visual
field testing is an excellent indicator
of a positive response to treatment.
Treatment
Serial therapeutic lumbar punc-
tures. If cerebral edema is present,
high-dose dexamethasone or pred-
nisone should be given intrave-
nously at first, and then orally.
Mannitol or furosemide, 40 mg i.v.
b.i.d. or t.i.d., may also be given. A
commonly used treatment is with
the carbonic anhydrase inhibitor
acetazolamide, 250750 mg/day.
Obese patients should be put on a
reducing diet.
| Empty Sella Syndrome
The subarachnoid space may extend
into the sella turcica in the presence
or absence of intracranial hyperten-
sion when the diaphragma sellae in-
adequately separates the intrasellar
and suprasellar compartments. CT re-
veals a seemingly empty sella with
Hounsfield values approximating
those of air. In cases of pseudotumor
cerebri, an empty sella is associated
with a higher frequency of visual
disturbances.
| Brain Tumors
(97c, 221b, 520a, 851a)
Epidemiology
One in 10,00020,000 people will de-
velop a brain tumor. Perhaps an addi-
 Intracranial Hypertension and Brain Tumors
tional one-quarter of this number
harbor an asymptomatic cerebral me-
tastasis of a malignant tumor else-
where in the body. Primary brain tu-
mors are much more common among
psychiatric inpatients (prevalence
1 %) than in the general population. In
an epidemiologic study performed at
the Mayo Clinic over a period of
40 years, the overall incidence of
brain tumors was 19.1 per 100,000
persons per year (778a).
Causes
Brain tumors are thought to result
from the interaction of a nonlocalized
humoral factor with a local factor re-
lated to embryonic histogenesis,
which is responsible for the typical
locations of various particular types
of tumor, and for the overall in-
creased occurrence of brain tumors in
the vicinity of the neural groove. Ge-
netic factors also play a role; thus, the
loss of tumor suppressor genes
through mutation seems to play a
role in the generation of glioblastoma
multiforme. Trauma contributes to
the generation of brain tumors ex-
ceedingly rarely, if at all.
Table 2.13 General characteristics of brain tumors
Symptoms and signs:
Headache (early symptom in one-
third)
General signs of intracranial hy-
pertension (vomiting, bradycardia
not always present)
Epileptic seizures (initial symptom
in one-fourth)
Neuropsychological changes
(apathy, irritability, memory impair-
ment)
Mumenthaler, Neurology 2004 Thieme
All rights reserved. Usage subject to terms and conditions of license.
59
| General Clinical Manifestations
of Brain Tumors
General Characteristics
The general characteristics of brain
tumors are listed below and summa-
rized in Table 2.13.
> The symptoms and signs are
steadily progressive. (N.b., so may
be those of inflammatory and
(more rarely) vascular processes,
while a sudden hemorrhage into a
tumor may produce sudden, apo-
plectiform manifestations.)
> Headache is common (steady, dif-
fuse, often both day and night with
diminution over the course of the
day); it may be an early symptom
in ca. one-third of cases.
> Signs of intracranial hypertension
may be present (see Table 2.10).
> Mental changes may include irrita-
bility, fatigability, memory impair-
ment, and general and focal
psycho-organic syndromes.
> Epileptic seizures are more com-
monly generalized than focal, and
are the first symptom in ca. one-
fourth of all cases.
Course Objective findings
Steady progression Focal neurologic deficits
(exception: acute
onset due to hemor-
rhage into tumor)
Neuropsychological and
psychopathological abnor-
malities
Cranial nerve palsies
(sometimes)
papilledema (common)
60 2 Diseases Mainly Affecting the Brain and its Coverings
Focal signs and symptoms. These
usually appear sooner or later in the
course of the illness, accompanied by
the general manifestations described
above. They may provide a clue to the
localization of the tumor.
Falsely localizing symptoms and
signs. These may result from shifting
of intracranial structures due to mass
effect.
| Diagnostic Evaluation
Imaging Studies
MRI and CT. MRI and CT are essential
procedures in the diagnostic evalua-
tion of brain tumors. An MRI should
be performed when the CT is negative
despite a high degree of clinical sus-
picion (e.g., of an infiltrative, low-
grade astrocytoma), or when the clin-
ical findings suggest a lesion in the
posterior fossa. It should never be for-
gotten that a negative CT does not
rule out a brain tumor, particularly an
infiltrative, low-grade glioma. Thus, it
may be necessary to repeat an ini-
tially negative study, particularly
when the symptoms and signs are
progressive.
Arteriography. This technique has
vastly declined in importance since
the introduction of CT and MRI, but
may still be required as a comple-
mentary preoperative study in some
cases. In yet other cases, a decision to
remove the tumor surgically or to ad-
minister radiation therapy can only
be made after a diagnostic stereotac-
tic biopsy.
EEG. EEG no longer plays a role in the
diagnostic evaluation of brain tu-
mors.
Cerebrospinal fluid examination. The
cerebrospinal fluid is normal or else
Mumenthaler, Neurology 2004 Thieme
All rights reserved. Usage subject to terms and conditions of license.
shows an elevation of protein and cell
count, particularly when the tumor
abuts the ependymal or pial surface.
Acoustic neuromas are characteristi-
cally accompanied by an elevation of
cerebrospinal fluid protein. Tumor
cells are sometimes noted on cytolog-
ical examination of the cellular sedi-
ment.
Plain skull roentgenogram. Plain
skull roentgenograms may reveal evi-
dence of intracranial hypertension:
increase of the digitate markings, en-
larged sella turcica, demineralized
dorsum sellae (note the distinction
between this finding and that of an
intrasellar tumor!), diastasis of the
sutures in young children, or, in pos-
terior fossa tumors, an increased ver-
tical height of the posterior fossa
with thinning of the occipital bone.
The pineal calcification or falcine cal-
cification (if present) may be dis-
placed to the side opposite the tumor.
The skull may be locally sclerotic
(meningioma) or destroyed (metasta-
sis). Meningiomas may also be associ-
ated with abnormally deep vascular
grooves, reflecting the meningeal
blood supply to the tumor. Some tu-
mors may be calcified (meningioma,
oligodendroglioma, craniopharyngi-
oma, choroid plexus papilloma, li-
poma of the corpus callosum), but
this finding is not pathognomonic for
tumor, as various kinds of inflamma-
tion may also be calcified (e.g., tuber-
culoma). Large intracranial aneu-
rysms may display sickle-shaped cal-
cifications.
ECG. Potentially misleading ECG ab-
normalities (QT prolongation, sinus
tachy- or bradycardia, pathological U
wave, and ST elevation or depression)
are found in association with 40 %
 Intracranial Hypertension and Brain Tumors 61

of tumors involving the temporal lobe tumor suppressor genes primarily af-
(529). fect protein phosphorylation and
phosphatase activity.
| Individual Types of Brain
Tumor Grade IV astrocytoma (glioblastoma
The most important types of brain tu- multiforme). Grade IV astrocytomas
mor and their frequency in a neuro- grow very rapidly and are highly ma-
surgical patient base are listed in lignant. Histologically, they are char-
Table 2.14. acterized by necrosis and vascular
proliferation. They are the most com-
| Astrocytic Tumors (Gliomas) mon primary brain tumor, appearing
The loss of tumor suppressor genes is mainly in the fifth and sixth decades
a contributing factor in the genera- of life, and they grow by infiltrating
tion of astrocytic tumors (e.g., LOH 10 into the brain substance. They usually
in glioblastoma). Mutations of the arise in a cerebral hemisphere but
may cross the corpus callosum to in-
Table 2.14 Frequency of different types
volve both sides (butterfly glioma)
of brain tumors in a group of neurosurgical
patients or grow downward into the basal
ganglia (Fig. 2.9). They account for
Tumor Percent approximately 90 % of all cerebral gli-
omas in adults. The patients generally
Gliomas:
come to medical attention because of
> Glioblastoma multiforme 20 neurologic deficits within weeks or,
(= astrocytoma, grade IV) at most, a few months of their first
> Astrocytoma, grades IIII 10 symptom. Apart from general tumor
symptoms and signs, focal deficits
> Ependymoma 6 such as hemiparesis and dysphasia
> Medulloblastoma 4 are usually present. Even after gross
total neurosurgical resection of the
> Oligodendroglioma 5 tumor, patients generally die of tu-
Meningioma 15 mor recurrence within a few months
to, at most, 2 years. A combination of
Pituitary adenoma 7 surgery, radiotherapy, and chemo-
Schwannoma (= neurinoma) 7 therapy improves the prognosis only
slightly. Wafers containing the cyto-
Metastasis 6 static agent BCNU bound to a poly-
Craniopharyngioma, dermoid, 4 mer are sometimes surgically im-
epidermoid, teratoma planted in the tumor cavity when a
recurrent tumor is resected, although
Angioma 4 this has been found to prolong sur-
Sarcoma 4 vival by no more than a few weeks
(136). Temozolomide has also been
Unclassifiable 5 recommended recently for chemo-
Other, rarer tumors (pinealoma, 3 therapy of recurrent tumors. The only
chondroma, granuloma, etc.) beneficial prognostic factor for a
grade IV astrocytoma is a younger age
Total 100
of onset of the disease.

Mumenthaler, Neurology 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.
 62 2 Diseases Mainly Affecting the Brain and its Coverings

a b
Fig. 2.9a, b Grade IV astrocytoma (glioblastoma multiforme). The T1- and T2-
weighted spin-echo images (a and b, respectively) reveal a polycystic tumor surrounded by
marked edema. The peripheral portion of the tumor is strongly contrast-enhancing (a).

Grade IIII astrocytoma (972a). These circumscribed fibrillary astrocytomas

astrocytomas of the cerebrum arise
most commonly in the fourth decade
of life. They generally grow slowly
and are sometimes well circum-
scribed, but often infiltrate into the
white matter of the frontal and tem-
poral lobes. Pilocytic astrocytoma is a
subtype of grade I astrocytoma, while
astrocytomas of grades I and II are
sometimes termed low-grade astro-
cytomas; grade II tumors differ from
grade I tumors in the degree of cellu-
lar abnormality. An increased mitotic
rate is found in grade III tumors (so-
called anaplastic astrocytoma). Well-
differentiated tumors may reside in
the cerebral white matter for years
while they slowly grow and produce
progressive clinical manifestations.
The most common of these are cogni-
tive changes, slowly progressive
hemiparesis, ataxia, papilledema,
headache, and epileptic seizures. The
tumor is often initially detectable
only on MRI, and not on CT. Well-
that have been macroscopically to-
tally resected may not recur till years
afterward (792a), and permanent sur-
gical cures are occasionally seen. In
many cases, however, the tumor
eventually transforms itself into a
glioblastoma. Sometimes the tumor
appears to be multifocal, with a
highly heterogeneous degree of ma-
lignity; in such cases, one may speak
of gliomatosis of the brain.
Cerebellar astrocytoma (pilocytic as-
trocytoma of the cerebellum). These
tumors have a much better prognosis
than supratentorial astrocytomas.
They usually arise between the ages
of 5 and 15 and account for
25 % of all brain tumors of childhood
and adolescence. They are well-
circumscribed, often cystic tumors
that usually reside in the cerebellar
hemispheres but may also be found
in the vermis or pons. They give rise
to slowly progressive cerebellar signs

Mumenthaler, Neurology 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.
 Intracranial Hypertension and Brain Tumors
such as ataxia, dysequilibrium, nys-
tagmus, and sometimes intracranial
hypertension as an early manifesta-
tion. Neurosurgical resection may be
difficult because of the location of the
tumor, but a total resection, if
achieved, can be curative.
Ependymoma. These tumors, too,
generally affect children and adoles-
cents, and only rarely adults. They
arise from ependymal cells that lie
abnormally deep within the tissue
substance, rather than at the ependy-
mal surface. The arrangement of tu-
mor cells into perivascular pseudoro-
settes is the histologic hallmark of
this tumor. It is found in the vicinity
of the ventricular system, more often
below the tentorium than above it;
the commonest site is the area
around the fourth ventricle. Intrame-
dullary ependymomas are most com-
monly found in the conus medullaris
of the spinal cord (cf. Fig. 3.4e, f).
Ependymomas of the posterior fossa
produce focal cerebellar signs as well
as obstructive hydrocephalus, which
often dominates the clinical picture.
Unusual (persistent) headache in a
child should arouse suspicion of an
ependymoma. Such tumors also
manifest themselves on occasion by
focal signs of the pons or medulla,
e.g., hemifacial spasm (p. 678) (780a).
They are relatively benign, and the
patient may survive many years after
the initial resection; the older the
child at first manifestation of the tu-
mor, the better the prognosis. Radical
resection may be impossible if the tu-
mor involves the floor of the fourth
ventricle. Surgery should always be
followed by radiation therapy, which
should encompass not only the brain,
but also the entire spinal cord. The
combination of surgery and radiation
Mumenthaler, Neurology 2004 Thieme
All rights reserved. Usage subject to terms and conditions of license.
63
yields a 10-year survival rate of nearly
70 %.
Medulloblastoma. This malignant tu-
mor of childhood and adolescence ac-
counts for 20 % of brain tumors in this
age group. It is found in the inferior
portion of the vermis in nine out of 10
cases but may also arise in the cere-
bellar hemispheres or the pons. It
grows by infiltration and often fills
the fourth ventricle, thereby ob-
structing cerebrospinal fluid flow and
sending drop metastases caudally
along the cerebrospinal fluid pathway
into the spine. These may lead to clin-
ical findings relating to the spinal
cord or cauda equina. In general, me-
dulloblastomas cause symptoms and
signs similar to those of cerebellar as-
trocytoma (see above). Much less
commonly, a medulloblastoma may
appear in adulthood, practically al-
ways in the posterior fossa. Even after
appropriate treatment, these tumors
usually recur and go on to metasta-
size to other locations in the central
nervous system and other organs
(756). Macroscopically radical resec-
tion combined with radiation ther-
apy, to which this tumor has a high
rate of response, still cannot prevent
recurrences, which frequently appear
within months or years, in both older
and younger patients. In one study,
58 patients with a mean age of
17 years underwent surgical resection
followed by radiation therapy (331).
The rates of survival and of
recurrence-free survival were 50 %/
46 % at 5 years, and 32 %/32 % at
10 years. Positive prognostic factors
included radical resection, radiation
dose above 50 Gy, and radiation of the
entire neuraxis. Further chemother-
apy for the treatment of recurrence
yielded a 2-year survival rate of 46 %,
64 2 Diseases Mainly Affecting the Brain and its Coverings
while the survival rate after tumor re-
currence without further chemother-
apy was zero.
Oligodendroglioma. These tumors
most commonly appear between the
ages of 35 and 45. They grow by dis-
placement or infiltration of brain tis-
sue in the cerebral hemispheres or
basal ganglia or, particularly in youn-
ger patients, in the thalamus. More
than half of all oligodendrogliomas
are located in the frontal lobes. They
grow very slowly, and, in the pre-CT
era, there was usually an interval of
several years between the appear-
ance of the first symptom and the di-
agnosis. Epileptic seizures occur in
70 % of patients and are the initial
manifestation in 50 %. Focal neuro-
logic deficits develop over the ensu-
ing months or years. Gross total re-
section is almost invariably followed
by recurrence, but sometimes at a la-
tency of 35 years, so that the median
postoperative survival time of 5 years
Table 2.15 Signs and symptoms of a
brainstem tumor
Nuclear cranial nerve palsies with:
> Dysphagia
> Trigeminal sensory and motor defi-
cits
> Peripheral facial nerve palsy
Hemifacial spasm
Oculomotor disturbances
Long tract manifestations:
> Pyramidal tract signs
> Hemiparesis
> Ataxia
> (possibly) dissociated sensory deficit
> All of the above may be bilateral
Intracranial hypertension, if the
aqueduct is occluded
Mumenthaler, Neurology 2004 Thieme
All rights reserved. Usage subject to terms and conditions of license.
is comparable to that of supratento-
rial astrocytomas of grades IIII. Oli-
godendrogliomas are responsive to
PCV chemotherapy, which is recom-
mended as an adjuvant treatment.
A study of 81 patients revealed a me-
dian survival time of 7.9 years for
those who were treated with a com-
bination of surgery and local radia-
tion therapy at a dose of at least 50
Gy. 31 % of these patients survived
10 years or more (867).
Brainstem glioma. The different his-
tological types of glioma occurring in
the brainstem may be considered to-
gether because of the typical clinical
features associated with this location.
They generally arise in the first two
decades of life and cause progressive
symptoms and signs through involve-
ment of the pons and medulla ob-
longata, as summarized in Table
2.15.
These tumors are often difficult to
distinguish from other brainstem tu-
mors and vascular malformations,
brainstem encephalitis, or the initial
manifestations of multiple sclerosis.
Surgical resection is only rarely pos-
sible and usually incomplete. The
benefit of chemotherapy is uncertain.
Ventricular shunting may be neces-
sary if hydrocephalus develops. The
median survival time is 1 year.
Optic and chiasmatic glioma. These
tumors are found nearly exclusively
in children and adolescents, and are
twice as common in girls. Fourteen
percent of cases are associated with
neurofibromatosis. Their clinical
manifestations are listed in Ta-
ble 2.16. The diagnosis is made by CT
or MRI, by means of which these tu-
mors can be distinguished from pitui-
tary tumors, intraorbital meningi-
 Intracranial Hypertension and Brain Tumors
oma, medial sphenoid wing meningi-
oma, and the lesions of Hand-
Schller-Christian disease. The com-
bination of surgery and radiation
therapy yields a long-term survival
rate of 85 % for anterior tumors and
50 % for posterior tumors.
Hypothalamic tumors. Astrocytoma is
the most common histological type.
These tumors lie in the rostral portion
of the floor of the third ventricle and
usually arise in the first 2 years of life.
Their clinical hallmark is a progres-
sive emaciation that leads to ca-
chexia, despite normal food intake
and otherwise normal behavior (Rus-
sell syndrome). This picture is to be
distinguished from anorexia nervosa,
which generally strikes older girls.
Colloid cysts are also found in the
third ventricle and may lead to an ob-
struction of cerebrospinal fluid flow
in one or both foramina of Monro,
and thereby to uni- or bilateral hy-
drocephalus of the lateral ventricles.
They are treated neurosurgically.
| Meningioma
This is a benign tumor that arises
from the dura mater and grows
slowly over the years, compressing
the adjacent brain tissue. Malignant
transformation is rare, but there is a
statistical association with other, ma-
lignant tumors, especially breast can-
cer. Meningioma is the most common
intracranial tumor of mesodermal or-
igin and most often becomes clini-
cally evident between the ages of 40
and 50. It may also be encountered as
an incidental finding at autopsy or on
CT or MRI studies of the brain. In such
cases, follow-up studies have shown
highly variable annual growth rates,
ranging from 1 % to 21 %; thus, slowly
growing, asymptomatic meningio-
Mumenthaler, Neurology 2004 Thieme
All rights reserved. Usage subject to terms and conditions of license.
65
Table 2.16 Symptoms of optic and chias-
matic glioma
Almost exclusively in children and ad-
olescents
Visual disturbances
Visual field defects
Exophthalmos
Late diencephalic manifestations:
> Polyuria
> Obesity
> Infantilism
> Arousal disturbances
mas can be treated by observation
(301), particularly in elderly patients
(709b). Larger tumors and those
displaying hyperintensity on T2-
weighted images are more likely to
progress (709b). In general, meningi-
omas should be neurosurgically re-
sected.
Although meningiomas may, in prin-
ciple, arise from the dura mater at
any site, they are preferentially found
at a number of classic sites, which are
listed in Table 2.17, together with
some of the particularities associated
with tumors at each site.
Figure 2.10 shows an MR image of a
meningioma.
The adjacent bony structures are
thickened and demonstrate radially
arranged bony spicules. Exostoses
may also be present. Flat en plaque
meningiomas may develop largely
within the bone of the skull and give
rise to a picture resembling fibrous
dysplasia (287). Supratentorial me-
ningiomas in any location are fre-
quently associated with epileptic sei-
zures, which may be their initial
symptom.
All rights reserved. Usage subject to terms and conditions of license.
Mumenthaler, Neurology 2004 Thieme

Table 2.17 Preferential locations of meningioma, and associated clinical features

66
Site Most common initial Course Special features
manifestations

2
Olfactory groove Anosmia Seizures, headache, personality The frontal branch of the

Diseases Mainly Affecting the Brain and its Coverings

change with frontal features, temporal artery may be en-
possible involvement of optic larged
nerve
Convexity Seizures Hemiparesis
Parasagittal and falx Lower extremity paresis, Seizures Rarely causes paraparesis
(sometimes) bilateral Babinski
sign
Sphenoid wing Visual disturbances Exophthalmos, hemiparesis Lateral tumors may be externally
(when medially located, adjacent evident as temporal hyperostosis
to optic nerve)
Tuberculum sellae Visual disturbances, pale optic Progressive visual field defect
disks
Cerebellopontine angle Deafness, vertigo Facial and trigeminal nerve Differential diagnosis:
deficits, brainstem compression acoustic neuroma
Foramen magnum Spastic quadriparesis, dysphagia, Lower cranial nerve deficits Diagnosis difficult, clinical find-
dysarthria ings may be misleading
Intraventricular Intermittent headaches and Progressive hydrocephalus Often found in trigone
vomiting
Intraspinal Progressive paraparesis Paraplegia
 Intracranial Hypertension and Brain Tumors 67

a b

Fig. 2.10ac Meningioma. An 85-year-

old man who had had a slowly progressive
right hemiparesis for 2 years.
a, b The T1- and T2-weighted spin-echo
images (a and b, respectively) reveal a
large left frontal convexity meningi-
oma compressing the underlying brain
tissue. Abnormal signal in compressed
cortex (arrowhead); brain edema (T1-
hypointensity and T2-hyperintensity).
c Marked contrast enhancement, typical
for meningioma.

Mumenthaler, Neurology 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.
68 2 Diseases Mainly Affecting the Brain and its Coverings
| Pituitary Adenoma
Only about 10 % of these tumors are
associated with sellar enlargement
and other signs of an intracranial
space-occupying lesion. Adenomas
mainly occur in patients between the
ages of 30 and 50. Practically all cases
exhibit endocrine disturbances:
> The rare growth-hormone secreting
tumors (in older nomenclature, eo-
sinophilic adenomas) cause acro-
megaly.
> Nonsecreting tumors (chromophobe
adenomas) cause panhypopituita-
rism, with thin, wrinkled skin and
secondary thyroid and sex hor-
mone deficiencies.
> Prolactinomas (serum prolactin
G 100 ng/mL) cause galactorrhea
and secondary amenorrhea in
women, and impotence in men.
Larger pituitary adenomas cause vi-
sual field defects (usually bitemporal
hemianopsia or bitemporal upper
quadrantanopsia) and sellar enlarge-
ment, which may be balloon-like or
plate-like in radiological views. The
degree of improvement of visual acu-
ity and visual fields after surgical re-
section is highest in patients with
milder impairment preoperatively,
shorter duration of visual symptoms,
and slower tumor progression.
ACTH-secreting tumors (basophil ade-
nomas) are the responsible lesion in
Cushings disease. They cause symp-
toms not through mass effect, but
rather through secondary adrenocor-
tical hypersecretion of cortisol, which
leads to truncal obesity, hyperten-
sion, osteoporosis, and hyperglyce-
mia as well as abdominal striae, hir-
sutism, and (in women) secondary
amenorrhea. Craniopharyngiomas
may arise in the pituitary fossa and
are described below on p. 69.
Mumenthaler, Neurology 2004 Thieme
All rights reserved. Usage subject to terms and conditions of license.
| Schwannoma (Neurinoma)
Schwannomas are benign neoplasms
arising from the Schwann cells. They
most commonly affect the eighth cra-
nial nerve, where they are familiarly
but inaccurately known as acoustic
neuromas. These usually appear in
the fourth and fifth decades of life
and give rise to the clinical syndrome
of the tumor of the cerebellopontine
angle, including progressive unilat-
eral deafness, tinnitus, dysequilib-
rium, (later) trigeminal nerve deficits,
facial palsy, and possibly (in ad-
vanced stages) cerebellar deficits, py-
ramidal tract signs, and signs of intra-
cranial hypertension.
Acoustic neuroma is sometimes a
manifestation of von Recklinghau-
sens neurofibromatosis (p. 86) and is
then often bilateral.
The syndrome of the tumor of the ce-
rebellopontine angle is more rarely
produced by other processes, e.g.,
meningioma or epidermoid.
Acoustic neuroma is always associ-
ated with an elevation of the cerebro-
spinal fluid protein concentration.
The diagnosis is established by CT or
MRI (Fig. 2.11). Small, intracanalicular
tumors are well seen on MRI but only
with difficulty on CT; they may be
seen more easily on CT after the in-
troduction of positive or negative
contrast (air) into the subarachnoid
space, which outlines the tumor in
the internal auditory canal. Microsur-
gical resection can usually be per-
formed without injury to the facial
and trigeminal nerves. Stereotactic
radiosurgery (Gamma Knife) is rap-
idly becoming the treatment of
choice for smaller tumors.
| Brain Metastases
Some 1015 % of cancer patients
eventually develop clinically evident
 Intracranial Hypertension and Brain Tumors
Fig. 2.11 Acoustic neuroma.
T1-weighted spin-echo MR image after the
administration of intravenous contrast. Ob-
serve the marked displacement of the pons
to the opposite side and the compression
of the fourth ventricle (small arrow). The
beak-like projection of the tumor into the
internal auditory canal (arrowhead) and
the marked contrast enhancement are typ-
ical features of acoustic neuroma.
brain metastases. The commonest
brain metastases arise from carci-
noma of the lung (in men) and breast
(in women), followed by melanoma
and renal cell carcinoma. In at least
three-quarters of cases, brain metas-
tases are already multiple by the time
of clinical presentation; this fraction
is even higher for melanoma, while
metastatic renal cell carcinoma is
more often solitary. Sometimes, a
cancer outside the central nervous
system may initially present as a
brain metastasis; this occurs most
commonly in lung cancer. According
to the literature, brain metastases ac-
count for 420 % of all brain tumors.
The mean life expectancy after diag-
nosis of one or more brain metastases
is only 12 months. Positive prognos-
tic factors for survival include supra-
Mumenthaler, Neurology 2004 Thieme
All rights reserved. Usage subject to terms and conditions of license.
69
tentorial location, gross total resec-
tion, and advanced age. Only about
30 % of cases are suitable for surgical
treatment (71a). In one study, of 122
patients from whom apparently soli-
tary brain metastases were removed,
only 5 % were alive 4 years later. In the
overall group of 122 patients with ap-
parently solitary brain metastases,
the longest survival was attained by
those who underwent gross total re-
section of the metastasis followed by
whole-brain radiation therapy in the
absence of other systemic evidence of
disease. The median survival time in
this group was 1.3 years; 41 % were
alive at 2 years, and 21 % at 5 years
(888). Whole-brain radiation therapy
led to an improvement of symptoms
in 80 % of patients (71a).
For carcinomatous meningitis, see p.
410; for paraneoplastic encephalopa-
thy, see p. 321.
| Tumors of Maldevelopmental
Origin
Craniopharyngioma. This tumor en-
ters into the differential diagnosis of a
pituitary tumor. It is diagnosed most
commonly in children and adoles-
cents, with peak incidence in the sec-
ond decade of life, but older patients
may also present with initial symp-
toms of craniopharyngioma, particu-
larly visual disturbances. Endocrine
disturbances are almost always pre-
sent except in the less common cases
of purely suprasellar tumor. Cranio-
pharyngioma is far more likely than
pituitary adenoma to extend into the
diencephalon and third ventricle and
produce the corresponding clinical
signs (hydrocephalus, behavioral dis-
turbances, diabetes insipidus, etc.).
Craniopharyngiomas are often calci-
fied and contain cholesterol. Al-
though they are histologically benign,
 70 2 Diseases Mainly Affecting the Brain and its Coverings

Fig. 2.12ac Cavernoma (cavernous an-

gioma).
A 59-year-old woman with temporal lobe
epilepsy of increasing severity, despite anti-
convulsant treatment. A neuroradiological
evaluation after the first seizure (10 years
previously) was normal. This follow-up
study reveals a cavernoma combined with
anomalous venous drainage. This finding
suggests the possibility of treatment by
neurosurgical resection of the cavernoma.
a The coronal, T2-weighted spin-echo im-
age reveals a cavernoma in the left supe-
rior temporal gyrus. The hemosiderin
ring around the lesion, seen as loss of
a signal, is typical.
b The hemosiderin ring is even more
clearly seen in this axial gradient-echo
image, because of signal loss due to a
susceptibility effect.
c Venous phase angiogram. An anoma-
lous venous drainage with caput medu-
sae is seen (arrow). Anomalous venous
drainage is frequently associated with
cavernoma. The neurosurgeon need
only resect the cavernoma.

their clinical management can be

problematic, because they are often
not radically resectable for technical
reasons.

Other tumors of maldevelopmental

origin. Epidermoid and dermoid tu-
mors are derived from tissues not
normally found within the central
nervous system. Epidermoid tumors
generally present between the ages of
25 and 45 and are most often located
at the skull base and in the cerebello-
pontine angle. Dermoid tumors, on
c the other hand, are tumors of child-

Mumenthaler, Neurology 2004 Thieme

All rights reserved. Usage subject to terms and conditions of license.
 Intracranial Hypertension and Brain Tumors
hood and are most often located in
the parapituitary, parapontine, and
orbitomaxillary regions. They often
present with visual disturbances
(from involvement of the optic chi-
asm), lower cranial nerve palsies,
brainstem compression, seizures, and
(occasionally) behavioral abnormali-
ties and signs of intracranial hyper-
tension. Both of these types of tumor
grow very slowly and compress,
rather than invade, the adjacent ner-
vous tissue. They are only rarely
found in the spinal canal. Radical re-
moval is associated with a good prog-
nosis.
Cavernomas (cavernous angiomas)
(564, 792, 879, 905) are a variety of
hamartoma composed of abnormal
blood vessels (Fig. 2.12). Pathological
examination reveals a well-
circumscribed mass of blood vessels
without intervening nervous tissue,
containing foci of calcification. Caver-
nomas may be found anywhere in the
brain, brainstem, or spinal cord, but
are most commonly found subcorti-
cally in the cerebral hemispheres.
They are multiple in nearly one-
fourth of all cases (674a) and may oc-
cur in families (679c). Approximately
two-thirds cause epileptic seizures
(188c), and 16 % cause clinically ap-
parent hemorrhage (674a). A caver-
noma gene is found at the CCM 1 lo-
cus on chromosome 7 (367b). The
commonest presenting manifesta-
tions are seizures, headache, and in-
tracranial hemorrhage. In CT images,
they appear as hyperdense regions
with contrast enhancement; calcifi-
cation may also be seen. MRI com-
monly reveals hemosiderin deposits
reflecting previous, often clinically si-
lent hemorrhage. The treatment con-
sists of microsurgical removal and is
advisable because these lesions tend
Mumenthaler, Neurology 2004 Thieme
All rights reserved. Usage subject to terms and conditions of license.
71
to bleed with a frequency estimated
at 0.7 % per year, and somewhat
higher in women (674a, 792). The risk
of a symptomatic hemorrhage is par-
ticularly high when there has been a
previous hemorrhage, but substan-
tially lower when seizures are the
only presenting feature or when the
lesion is an incidental radiological
finding (16).
Tumors of the pineal region are rarely
derived from cells intrinsic to the pi-
neal gland (pineocytoma, pineoblas-
toma), and belong somewhat more
commonly to the glioma series (as-
trocytoma, ependymoma), but are
most often of maldevelopmental ori-
gin (germinoma, teratoma, choriocar-
cinoma, embryonal cell carcinoma,
endodermal sinus tumor). Any of
these tumors may compress the aq-
ueduct and cause obstructive hydro-
cephalus. Physical findings include
paresis of upward gaze (sometimes a
late sign) and wide pupils that con-
tract on convergence, but not in re-
sponse to light (all of these findings
together constitute the Parinaud syn-
drome). Germ cell tumors of the pi-
neal region occur predominantly in
young men.
| Other Brain Tumors
The following tumors are rare and
will be mentioned only briefly.
Malignant lymphoma. Malignant
lymphoma may occur as a solitary or
multiple lesion anywhere in the cere-
brum or cerebellum. These tumors
grow rapidly and infiltrate the sur-
rounding tissue. They are seen more
commonly, but by no means exclu-
sively, in immunocompromised per-
sons, including AIDS patients. Their
prevalence is approximately five per
10 million population, and they ac-
72 2 Diseases Mainly Affecting the Brain and its Coverings
count for only about 1 % of all brain
tumors. They are clinically mani-
fested by general signs of intracranial
hypertension, seizures, and/or focal
neurological and neuropsychological
abnormalities. Simultaneous involve-
ment of the cranial nerves and eyes is
not uncommon. CT reveals one or
more foci of tumor in the vicinity of
the cerebral ventricles; these are ini-
tially hyperdense and enhance
strongly on the administration of
contrast. They are solitary in only
one-third of cases (135). The treat-
ment consists of whole-brain radia-
tion therapy at a dose of 50 Gy and
sometimes chemotherapy as well
(448). Treatment is effective, but not
curative (135). Brain lymphoma only
rarely represents metastasis of extra-
cerebral disease.
Intraventricular tumors. These tu-
mors may intermittently obstruct the
flow of cerebrospinal fluid. See the
above discussion of intraventricular
meningioma (p. 65) and colloid cyst of
the third ventricle (p. 819).
Choroid plexus papilloma. These tu-
mors are most common in the first
decade of life, particularly in the first
2 years. They are most commonly lo-
cated in the fourth ventricle, grow by
compression rather than invasion,
may become calcified, give rise to
drop metastases, and are accessible to
radical surgical resection (706).
Syphilitic gummata and tuberculo-
mas. These intracranial masses are
uncommon in Europe and North
America. Suspicion of either should
prompt a search for other manifesta-
tions of the underlying disease.
Hydatid cysts and cysticercosis. Hy-
datid cysts are quite rare lesions, but
Mumenthaler, Neurology 2004 Thieme
All rights reserved. Usage subject to terms and conditions of license.
cysticercosis of the nervous system
affects up to 4 % of persons harboring
the pork tapeworm Taenia solium in
regions in which this infection is en-
demic. Neurocysticercosis evokes
symptoms by mass effect in approxi-
mately half of affected individuals.
Differential Diagnosis of Brain
Tumors
Other intracranial processes may pro-
duce clinical manifestations resem-
bling those of brain tumor, either by
mass effect or by other mechanisms.
Table 2.18 provides an overview of
the differential diagnosis of brain tu-
mors.
Treatment of Intracranial
Hypertension and Cerebral
Edema
The available means of treating in-
tracranial hypertension and cere-
bral edema are most effective
when these are due to brain tumor,
but can also be used in cases of
pseudotumor cerebri (p. 58), intra-
cranial hemorrhage, and traumatic
brain injury. Dexamethasone (De-
cadron) is given at an initial dose of
4 mg every 6 hours intravenously,
later by mouth. 50150 mg of solu-
ble prednisone may be given in-
stead. A 20 % solution of mannitol
can be given in an initial dose of
100 mL over 3060 minutes, and
thereafter up to eight times daily,
as needed. Furosemide (Lasix) can
be given as a diuretic in a dose of
40 mg intravenously up to three
times a day. If either of the latter
two medications are given to som-
nolent or comatose patients, a uri-
nary catheter should be inserted.
All rights reserved. Usage subject to terms and conditions of license.
Mumenthaler, Neurology 2004 Thieme

Table 2.18 General differential diagnosis of brain tumors

Category Example Specific features Important for differential diagnosis

Space-occupying lesion Chronic subdural Headache (always), fluctuating mental Prior head trauma (almost always)
other than tumor hematoma changes, few neurological deficits
Brain abscess Fever, high erythrocyte sedimentation Febrile, acutely ill
rate, rapid progression
Arachnoid cyst Most common in young males, on the Skull asymmetry (common); often
left side, fronto-temporal complicated by subdural hematoma
after traumatic brain injury
Encephalitis Herpes encephalitis Involves temporal lobe Fever, CSF pleocytosis and xantho-
chromia, positive CT or MRI

Intracranial Hypertension and Brain Tumors

Brainstem encephalitis Brainstem signs, bilateral long tract
signs
Multiple sclerosis Progressive hemiparesis over a few days
Vascular processes Stroke in progress Rapidly progressive hemiparesis without
signs of intracranial hypertension
Intracerebral hemorrhage Headache (always), rapid progression,
decline in level of consciousness
Positive MRI
Absence of general signs of intra-
cranial hypertension; positive MRI
Vascular risk factors, possible demon-
stration of carotid stenosis by Doppler
ultrasound
CT, MRI

73
All rights reserved. Usage subject to terms and conditions of license.
Mumenthaler, Neurology 2004 Thieme

Table 2.18 General differential diagnosis of brain tumors (Cont.)

74
Category Example Specific features Important for differential diagnosis

2
Arteriovenous malforma- Seizures, (possibly) progressive focal CT, MRI

Diseases Mainly Affecting the Brain and its Coverings

tion manifestations, may bleed acutely
(Giant) aneurysm Cranial nerve deficits, (rarely) hemi- CT, MRI may show sickle-shaped
paresis calcification in wall of aneurysm
Other Mills paralysis Hemiparesis slowly ascending from CT, MRI (diagnosis of exclusion)
leg to arm (years)
Alzheimers disease and In rare cases, there may only be a focal CT, MRI
Picks disease progressive deficit (e.g., dysphasia) for
several years
Pseudotumor cerebri, Manifestations of intracranial hyper- Young, obese women; CT shows
benign intracranial tension without focal deficit but possibly symmetrical narrowing of the lateral
hypertension with papilledema ventricles