Meningioma -

http://emedicine.medscape.com/article/1156552-
overview#showall

Background
Meningioma, the term coined by Harvey Cushing, refers to a set of
tumors that arise contiguously to the meninges.

Pathophysiology
Meningiomas may occur intracranially or within the spinal canal. They
are thought to arise from arachnoidal cap cells, which reside in the
arachnoid layer covering the surface of the brain. See the images
below.

Case 1: MRI of a meningioma on plaque.

Case 1: Bone-window CT reveals calcification of the meningioma.
Meningiomas commonly are found at the surface of the brain, either
over the convexity or at the skull base. In rare cases, meningiomas
occur in an intraventricular or intraosseous location. The problem of
classifying meningioma is that arachnoidal cells may express both
mesenchymal and epithelial characteristics. Other mesodermal
structures also may give rise to similar tumors (eg,
hemangiopericytomas or sarcomas). The classification of all of these
tumors together is controversial. The current trend is to separate
unequivocal meningiomas from other less well-defined neoplasms.
Undoubtedly, advances in molecular biology will allow scientists to
determine the exact genomic aberration responsible for each specific
neoplasm.

Epidemiology
Frequency
United States
The annual incidence of symptomatic meningiomas is approximately 2
cases per 100,000 individuals. Meningiomas account for approximately
20% of all primary intracranial neoplasms. However, the true prevalence
is likely higher than this because autopsy studies reveal that 2.3% of
individuals have undiagnosed asymptomatic meningiomas.
Meningiomas are multiple in 5-40% of cases, particularly when they
associated with neurofibromatosis type 2 (NF2). Familial meningiomas
are rare unless associated with NF2.[1]
International
The frequency of meningiomas in Africa is nearly 30% of all primary
intracranial tumors.[2]
Mortality/Morbidity
Mortality and morbidity rates for meningiomas are difficult to assess.
Some meningiomas are discovered fortuitously when CT or MRI is done
to assess for unrelated diseases or conditions. Therefore, some
patients die with meningioma and not from it. Estimates of the 5-year
survival usually range from 73-94%.
A systematic review of the literature regarding the clinical behavior of
small, untreated meningiomas suggests that most meningiomas 2.5 cm
or less in diameter do not proceed to cause symptoms in the 5 years
following their discovery. Patients with tumors 2.5-3 cm in initial size
went on to develop new or worsened symptoms 17% of the time. Those
that do cause symptoms can usually be predicted with close
radiographic follow-up.[3]
Meningiomas usually grow slowly, and they may produce severe
morbidity before causing death.
Factors that may be predictive of a high postoperative morbidity rate
include patient-related factors (eg, advanced age, comorbid states such
as diabetes or coronary artery disease, preoperative neurological
status), tumor factors (eg, location, size, consistency, vascularity,
vascular or neural involvement), previous surgery, or previous radiation
therapy.
Race
Meningiomas are more prevalent in Africa than in North America or
Europe. In Los Angeles County, meningioma is reported more
commonly in African Americans than in others.
Sex
Meningiomas afflict women more often than men. The male-to-female
ratio ranges from 1:1.4 to 1:2.8.
The female preponderance may be less pronounced in the black
population than in other groups.
Meningiomas are equally distributed between boys and girls.
Age
The incidence increases with age. Ages and corresponding incidence
rates reported from 2002 are as follows:
Age 0-19 years - 0.12
Age 20-34 years - 0.74
Age 35-44 years - 2.62
Age 45-54 years - 4.89
Age 55-64 years - 7.89
Age 65-74 years - 12.79
Age 75-84 years - 17.04
Age 85 years and older - 18.86

History
Meningiomas produce their symptoms by several mechanisms. They
may cause symptoms by irritating the underlying cortex, compressing
the brain or the cranial nerves, producing hyperostosis[4] and/or
invading the overlying soft tissues, or inducing vascular injuries to the
brain.[5] The signs and symptoms secondary to meningiomas may
appear or become exacerbated during pregnancy but usually abate or
improve in the postpartum period.
Irritation: By irritating the underlying cortex, meningiomas can cause
seizures. New-onset seizures in adults justify neuroimaging (eg,
MRI) to exclude the possibility of an intracranial neoplasm.
Compression: Localized or nonspecific headaches are common.
Compression of the underlying brain can give rise to focal or
more generalized cerebral dysfunction, as evinced by focal
weakness, dysphasia, apathy, and/or somnolence.
Stereotypic symptoms: Meningiomas in specific locations may give
rise to the stereotyped symptoms listed in the Table. These
stereotypical symptoms are not pathognomonic of meningiomas
in these locations; they may occur with other conditions or
lesions. Conversely, meningiomas in these locations may remain
asymptomatic or produce other unlisted symptoms.

Table. Symptoms and Signs Associated with Meningiomas in
Specific Locations
Location Symptoms
Parasagittal Monoparesis of the contralateral leg
Subfrontal Change in mentation, apathy or disinhibited
behavior, urinary incontinence
Olfactory
groove
Anosmia with possible ipsilateral optic atrophy and
contralateral papilledema (this triad termed
Kennedy-Foster syndrome)
Cavernous
sinus
Multiple cranial nerve deficits (II, III, IV, V, VI),
leading to decreased vision and diplopia with
associated facial numbness
Occipital
lobe
Contralateral hemianopsia
Cerebellopo
ntine
angle
Decreased hearing with possible facial weakness
and facial numbness
Spinal cord Localized spinal pain, Brown-Sequard (hemispinal
cord) syndrome
Optic nerve Exophthalmos, monocular loss of vision or
blindness, ipsilateral dilated pupil that does not
react to direct light stimulation but might
contract on consensual light stimulation; often,
monocular optic nerve swelling with optociliary
shunt vessels
Sphenoid
wing
Seizures; multiple cranial nerve palsies if the
superior orbital fissure involved
Tentorial May protrude within supratentorial and infratentorial
compartments, producing symptoms by
compressing specific structures within these 2
compartments[6]
Foramen
magnum
Paraparesis, sphincteric troubles, tongue atrophy
associated with fasciculation

Vascular: This presentation, although rare, should be considered.
Meningiomas of the skull base may narrow and even occlude
important cerebral arteries, possibly presenting either as transient
ischemic attack (TIA)like episodes or as stroke.
Miscellaneous
Intraventricular meningiomas may present with obstructive
hydrocephalus.
Meningiomas in the vicinity of the sella turcica may produce
panhypopituitarism.
Meningiomas that compress the visual pathways produce
various visual field defects, depending on their location.
Rarely, chordoid meningiomas can present with hematologic
disturbances, namely Castleman syndrome.[7]

Physical
The physical findings mirror the aforementioned symptoms and include
signs due to raised intracranial pressure, involvement of cranial nerves,
compression of the underlying parenchyma, and involvement of bone
and subcutaneous tissues by the meningioma.
Raised intracranial pressure leads to papilledema, decreased
mentation and, ultimately, to brain herniation.
Involvement of the cranial nerves may lead to anosmia, visual field
defects, optic atrophy, diplopia, decreased facial sensation, facial
paresis, decreased hearing, deviation of the uvula, and
hemiatrophy of the tongue.
Compression of the underlying parenchyma may give rise to
pyramidal signs that are exemplified by pronator drift,
hyperreflexia, positive Hoffman sign, and presence of the
Babinski sign. Parietal-lobe syndrome may occur if the parietal
lobes are compressed.
Compression of the dominant (usually left) parietal lobe may
give rise to Gerstmann syndrome: agraphia, acalculia,
right-left disorientation, and finger agnosia.
Compression of the nondominant (usually right) parietal lobe
leads to tactile and visual extinction and neglect of the
contralateral side.
Compression of the occipital lobes leads to a congruent
homonymous hemianopsia.

Spinal meningiomas may give rise to a Brown-Sequard syndrome (ie,
contralateral decreased pain sensation, ipsilateral weakness,
decrease in position sense), sphincteric weakness and,
ultimately, complete quadriparesis or paraparesis.
Causes
Trauma and viruses have been investigated as possible
causative agents for development of meningiomas. However, no
definitive proof has yet been found.
The role of inflammation (eg, posttraumatic insult) resulting
in the upregulation of COX-2 has been investigated in the
tumorogenesis of meningiomas.[8]
On the other hand, the role of radiation in the genesis of
meningiomas has been shown.
Patients subjected to low-dose irradiation for tinea capitis may
develop multiple meningiomas decades later in the field of
irradiation.
High-dose cranial irradiation may induce meningiomas after a
short latency period.

Genetic causes have been implicated in the development
of meningiomas.
The best-characterized and most common genetic alteration is
the loss of the NF2 gene (NF2) on chromosome 22q[9] .
NF2 encodes a tumor suppressor known as merlin (or
schwannomin).
Of interest, the meningioma locus is close to but probably
different from the gene responsible for NF2.
Up to 60% of sporadic meningiomas were found to harbor NF2
mutations.
Other cytogenetic alterations are chromosomal loss of 1p, 3p,
6q, and 14q.
Loss of chromosome 10 is associated with increased tumor
grade, shortened time to recurrence, and shortened
survival.
Progression to anaplastic meningioma has been associated
with involvement of chromosomal site 17q.
The following events were found to be associated with higher
grades of meningiomas: loss of the tumor suppressor in
lung cancer-1 gene (TSLC-1), loss of progesterone
receptors, increased expression of cyclooxygenase 2 and
ornithine decarboxylase.
Monosomy of chromosome 7 is a rare cytogenetic change.
However, it is frequently reported in radiation-induced
meningiomas.
The invasive potential of meningioma cells seems to be
reflected by a balance between the expression of matrix
metalloproteinases (MMPs) and tissue inhibitors of MMPs
(TIMPs).
The most consistent chromosomal abnormality isolated in
meningiomas is on the long arm of chromosome 22.
Meningiomas can also be associated with different genetic
syndromes, namely Gorlin[10] and Rubinstein-Taybi
syndromes[11] .
IMP3, an oncofetal RNA-binding protein, has been identified as
a potential biomarker in patients who have a high risk of
recurrent meningioma.[12]

Several findings suggest an association between hormones
and the risk for meningiomas, including increased incidence in
women versus men and the presence of estrogen, progesterone,
and androgen receptors on some of these tumors. However, the
exact nature of this relationship and its implication on the
management of meningiomas remain under investigation.
Whether cell phone use increases the risk of meningiomas
(and of brain tumors in general) remains of great interest, especially
with the recent tremendous increase in the use of these devices
worldwide. At present, the available data do not support such an
association; however, all published studies have relatively small sample
sizes and a short period of follow-up.[13]

Differential Diagnoses
Brainstem Gliomas
Cavernous Sinus Syndromes
Complex Partial Seizures
Craniopharyngioma
Frontal Lobe Syndromes
Glioblastoma Multiforme
Low-Grade Astrocytoma
Neurofibromatosis, Type 1
Neurofibromatosis, Type 2
Oligodendroglioma
Persistent Idiopathic Facial Pain
Pituitary Tumors
Primary CNS Lymphoma

Laboratory Studies
No specific laboratory tests are used to screen for meningioma.

Imaging Studies
Imaging studies are the mainstay of diagnosis. See images below for
representative radiologic views of various subtypes.
Plain skull radiograph may reveal hyperostosis and increased vascular
markings of the skull, as well as intracranial calcifications.
On plain head CT scans, meningiomas are usually dural-based tumors
that are isoattenuating to slightly hyperattenuating.
They enhance homogeneously and intensely after the injection of
iodinated contrast material.
Perilesional edema may be extensive. Hyperostosis and intratumoral
calcifications may be present.
The tumor compresses the brain without invading it.
Multiple meningiomas may be difficult to differentiate from metastasis.
On T1- and T2-weighted MRIs, the tumors have variable signal
intensity. If a meningioma is suspected, obtaining an enhanced MRI is
imperative.
Meningiomas enhance intensely and homogeneously after injection of
gadolinium gadopentetate.
The edema may be more apparent on MRI than on CT scanning.
An enhancing tail involving the dura may be apparent on MRI.
Cystic meningiomas may exhibit intratumoral or peritumoral cysts. The
peritumoral cysts may actually represent a gliotic response and may not
necessitate surgical extirpation.
Endovascular angiography allows the surgeon to preoperatively
determine the vascularization of the tumor and its encroachment on vital
vascular structures.
Late venous images are important to determine the patency of the
involved dural sinuses.
Angiographic features of meningiomas include the following:
Supply from the external circulation
Mother-in-law blush (which comes early and leaves late)
Sunburst or radial appearance of the feeding arteries
Although magnetic resonance arteriography (MRA) and magnetic
resonance venography (MRV) have decreased the role of classical
angiography, the latter remains a powerful tool for planning surgery.
Angiography is still indispensable if embolization of the tumor is deemed
necessary.
New research tools such as positron emission tomography (PET),
including octreotide-PET, or magnetic resonance spectroscopy (MRS)
have been used to predict in vivo the aggressiveness of
meningiomas.[14] See the images below.

Case 1: MRI of a meningioma on plaque.

Case 1: Bone-window CT reveals calcification of the meningioma.

Case 2: Gadolinium-enhanced MRI of a meningioma invading the overlying dura and
bone. Compare with appearance in Case 1.

Case 2: Bone-window CT scan reveals the skull involvement. Note the absence of
tumoral calcification.

Case 3: Tentorial meningioma. A, Contrast-enhanced CT scan shows the enhancing
meningioma. Transverse T1-weighted MRIs shows isointensity of the tumor
compared with the surrounding brain (B) and its homogenous enhancement (C).
Coronal (D), coronal enhanced (E), and sagittal enhanced (F) T1-weighted MRIs.
Posterior circulation angiograms show tumoral blush (arrow in G) and the
Bernasconi-Cassinari artery (arrow in H).

Case 3: Tentorial meningioma. Gadolinium-enhanced T1-weighted MRI immediately
(A) and 2 years after surgery (B-D). Transverse images show posterior (arrow in B)
and anterior (arrow in C) recurrence involving the tentorium. Sagittal images show
posterior (D) and anterior (E) recurrence involving the tentorium. Lower vignette
reveals complete excision of the recurrence after a second operation.

Case 3: Tentorial meningioma A, Pathology showed syncytial meningioma. Note
hypercellularity and minimal whorling (hematoxylin-eosin, original magnification
X400). B, MRI performed 4 years after the first operation reveals a recurrence over
the posterior tentorium. C, Two-dimensional planning for stereotactic radiosurgery.
Three recurrences lie in the plane of the tentorium on a single line. D, Three-
dimensional planning for stereotactic radiosurgery. Three arcs were used to irradiate
the largest recurrence.

Case 4: Recurrent subcutaneous meningioma. A, Patient underwent surgery for a
parieto-occipital meningioma in 1978. She was lost to follow-up until 1996, when this
transverse T2-weighted MRI was obtained. Arrow indicates surgical bed of the
resected meningioma. B, Although the initial surgical bed is tumor-free, sagittal T2-
weighted MRI shows a large subcutaneous recurrence. C, Lower transverse section
also shows recurrence. Note variegated appearance of the tumor. D, Transverse
section at a lower level. Postoperative sagittal (E) and transverse (F, G) enhanced
T1-weighted MRI shows gross total removal of the tumor. H and I, Tumoral
recurrence 3 months after surgery, at the same level as in G and F, respectively.
Patient received repeat surgery for subtotal removal of the tumor; a pediculated
subcutaneous flap was used to close the surgical defect. After surgery, patient
received conventional radiotherapy.

Case 5: Bilateral olfactory meningioma invading the facial sinuses. Coronal (A),
transverse (B), and sagittal (C) gadolinium-enhanced T1-weighted MRI shows
bilateral olfactory meningiomas, and the falx dividing the tumor in 2. Arrow indicates
tumor invasion of the sinuses. D, Postoperative enhanced T1-weighted MRI shows
that the tumor was completely removed by means of craniotomy and a transfacial
approach. E, Tumor was first approached intracranially. Enhanced T1-weighted MRI
reveals complete excision of the intracranial component. Arrow indicates residual in
the sinuses. F, Residual was completely excised by means a transfacial approach
performed with the otolaryngology team.

Case 6: Subfrontal meningioma in a patient with abnormal behavior. A, Contrast-
enhanced CT scan clearly shows bilateral subfrontal meningioma. B, Transverse T1-
weighted MRI of same lesion. C, Intense gadolinium enhancement of the tumor.
Coronal (D) and sagittal (E) gadolinium-enhanced T1-weighted MRIs. F, Anterior
circulation angiogram reveals posterior displacement of the anterior cerebral artery
by tumor. G, Postoperative MRI shows complete removal of the tumor. H-I,
Pathology slides (hematoxylin-eosin; original magnification X100 in H, X400 in I)
show syncytial meningioma with well-identified whorls and no psammoma bodies.

Case 7: Parasagittal meningioma invading the superior sagittal sinus (SSS). A,
Sagittal T1-weighted MRI shows a meningioma (arrow). B, T2-weighted MRI. Note
midline shift and tumoral invasion of the skull (arrow). C, Transverse T2-weighted
MRI. D, Angiogram shows invasion of the SSS, which remains patent. Sagittal (E,
G), transverse (F) postoperative T1-weighted MRI. H, Gadolinium-enhanced
postoperative T1-weighted MRI shows residual tumor, which was intentionally left to
preserve patency of the SSS. I, Pathology slide (hematoxylin-eosin, original
magnification X100) shows a highly vascular syncytial meningioma.

This is an extra-axial tumor. Glioblastoma multiforme (GBM) and astrocytoma are
intraparenchymal tumors, and GBM enhances in a variegated fashion. Acoustic
schwannomas are seen in the posterior fossa but not in this location. Fibrous
dysplasia involves the skull but does not cause this amount of compression.
Procedures
Preoperative endovascular embolization of the vascular
feeders from the external circulation may be beneficial in
extremely vascular meningiomas.[15]
If this is the case, resection should be performed shortly
after embolization to decrease the likelihood of tumor
revascularization.
Histologic Findings
Meningiomas are usually globular, well-demarcated neoplasms. They
have a wide dural attachment and become invaginated into the
underlying brain without invading it. Their cut surface is either
translucent pale or homogeneously reddish brown. It may be gritty on
cutting. Some meningiomas occur as a sheetlike extension that covers
the dura but does not invaginate the parenchyma; this variant is called
meningioma en plaque. The last morphologic variant is the cavernous
sinus meningioma that infiltrates the cavernous sinus and becomes
interdigitated with its contents. The 3 most common histologic subtypes
of meningiomas are the meningothelial (syncytial), transitional, and
fibroblastic meningiomas. See images below for representative
pathologic views of various subtypes.

Pathology slides (hematoxylin-eosin; original magnification X400 in A-B, X100 in C-
D). A, Fibroblastic meningioma (arrowheads) abutting the dura (arrow). B,
Psammomatous meningioma (arrow indicates psammoma body). C, Meningothelial
meningioma, tumor in case 4. E, Meningioma with marked vascularity (arrowheads
indicate meningioma cluster; arrow, vessel wall).

Case 4: Pathology slides (hematoxylin-eosin, original magnification X400). A,
Meningioma with malignant features, as evinced by prominent nucleoli (yellow dot)
and mitoses (arrows). B, Intranuclear cytoplasmic intrusion (pseudoinclusion).
Meningothelial meningiomas reveal densely packed cells that are
arranged in sheets with no clearly discernible cytoplasmic borders.
Although not prominent, whorls are present (calcified whorls are termed
psammoma bodies). Nuclei show intranuclear vacuoles.
Fibroblastic (fibrous) meningiomas reveal sheets of interlacing spindle
cells. The intercellular stroma is composed of reticulin and collagen.
The transitional variety reveals features common to both the
meningothelial and fibroblastic varieties; others include angiomatous,
microcystic, secretory,[16] clear cell, choroid, lymphoplasmacyte-rich,
papillary, and metaplastic variants.
Meningiomas may be associated with hyperostosis.[4] The exact nature
of the cause of this hyperostosis is controversial (ie, reactive versus
tumoral infiltration).
Immunohistochemistry
Immunohistochemistry can help diagnose meningiomas, which are
positive for epithelial membrane antigen (EMA) in 80% of cases. They
stain negative for anti-Leu 7 antibodies (positive in schwannomas) and
for glial fibrillary acidic protein (GFAP). Progesterone receptors can be
demonstrated in the cytosol of meningiomas; the presence of other sex
hormone receptors is much less consistent. Somatostatin receptors also
have been demonstrated consistently in meningiomas.[17]
Malignancy
The notion of malignancy in meningiomas is still vague.[18] Some
histologic variants, such as papillary meningioma, undoubtedly carry a
less favorable prognosis than other histologic types.[19] Two features
are considered clear signs of malignancy: cortical invasion by the tumor
and distal metastasis. Of note, in the 2007 WHO grading scheme, brain
invasion is considered a criterion for atypia.
Several stains have been used to help predict the behavior of
meningiomas. These stains quantify the mitotic rate of these tumors.
Bromodeoxyuridine (BudR) labeling requires an intravenous (IV)
injection before tumor removal. On the other hand, immunohistologic
staining for proliferating cell nuclear antigen (PCNA) can be performed
on fixed specimens. Some have attempted to correlate the pathology
and behavior of meningiomas to the loss of specific genetic material.
The World Health Organization classification of meningiomas is
presented in Table 2.
Table. Summary of the 2007 WHO Grading Scheme for Meningiomas
WHO
Grade
Histological Subtype Histological Features
I Meningothelial, fibroblastic,
transitional, angiomatous,
microcystic, secretory,
lymphoplasmacytic metaplastic,
psammomatous
Does not fulfill criteria for grade II or III
II
(Atypical
)
Chordoid, clear cell 4 or more mitotic cells per 10 hpf and/or 3 or more of the
following: increased cellularity, small cells, necrosis,
prominent nucleoli, sheeting, and/or brain invasion in an
otherwise Grade I tumor
III
(Anaplas
tic)
Papillary, rhabdoid[20] 20 or more mitoses per 10 hpf and/or obviously
malignant cytological characteristics such that tumor cell
resembles carcinoma, sarcoma, or melanoma
The expression levels of E- cadherin and beta-catenin were found to be
inversely correlated with peritumoral edema, aggressiveness of
meningiomas, and probability of recurrence.[21]
In a review of 21 pediatric meningiomas operated on over a period of 24
years, 24% were WHO grade II and 24% where associated with a large
cystic component.[22]

Medical Care
Medical care for meningiomas has been disappointing. It is
restricted either to perioperative drugs or to medications that are
used after all other means of treatment have failed.[23]
The use of corticosteroids preoperatively and
postoperatively has significantly decreased the mortality and
morbidity rates associated with surgical resection.
Antiepileptic drugs should be started preoperatively in
supratentorial surgery and continued postoperatively for no less
than 3 months.
The current experience with chemotherapy is
disappointing.
This modality of treatment is reserved for malignant cases after
failure of surgery and radiotherapy to control the disease.
The main drugs studied include temozolomide, which had no
effect against recurrent meningiomas in a phase 2 study[24]
, and hydroxyurea (ribonucleotide reductase inhibitor); RU-
486 (synthetic antiprogestin); and interferon-alpha. The last
3 drugs also showed disappointing results. A recently
published prospective phase 2 study of irinotecan (CPT-11)
also failed to demonstrate any efficacy.
The combination of interferon alpha and 5-fluorouracil
synergistically reduces meningioma cell proliferation in
culture and warrants further investigation.
Some studies have shown a possible role of COX-2 inhibitors in
the treatment of recurrent meningiomas.[8]
The role of targeted chemotherapy to block the tumorogenic
pathways of meningiomas at specific sites is being
extensively investigated.[25]
Molecules to block specific growth factors or enzymes are being
developed. Atypical meningioma (WHO grade II) and
anaplastic meningioma (WHO grade III) showed increased
fatty acid synthase (FAS) expression. FAS inhibitor
(cerulein) decreased meningioma cell survival in vitro.
Thus, increased FAS expression in human meningiomas
represents a novel therapeutic target for the treatment of
unresectable or malignant meningiomas.[26]

Although most meningiomas grow slowly and have a low
mitotic rate, clinical benefit has been reported in many case
series with either tumor regression or stasis after radiotherapy;
however, these results have not been confirmed in randomized
trials. Oya et al reported on the natural history of
meningiomas.[27] The prospect of benign meningioma growth is
an important factor to consider in their proper management.
Approximately 40% of 273 meningiomas (in 244 patients) grew
within a 4-year period. Lack of calcification, hyperintensity in T2
MRI, and peritumoral edema were predictors of growth in follow
up. In addition, age younger than 60 years and tumor size larger
than 25 mm (diameter) were also associated with a greater risk.
Radiotherapy is mainly used as adjuvant therapy for
incompletely resected, high-grade and/or recurrent tumors. It can
also be used as primary treatment in some cases (optic nerve
meningiomas[28] and some unresectable tumors).[29, 30]
In general the ideal treatment of a benign meningioma is
surgical resection if possible. Hasegawa et al treated 46 patients
with gamma knife radiation (GKR) as the initial treatment
modality.[31] The lesions were falcine, convexity, or parasagittal.
The study found GKR to be effective. The main caveat was tumor
size. Large tumors had the possibility of severe postirradiation
edema. This was actually more likely to occur with significant,
baseline peritumoral edema. GKR may be selected over surgery
in patients with significant medical comorbidities.
Stereotactic radiosurgery has been shown to provide
excellent local tumor control with minimal toxicity.[32, 33]
It is mainly used for small (< 3 cm in diameter) residual or
recurrent lesions when surgery is considered to carry a
significantly high risk of morbidity.
It has been advocated as an effective management strategy for
small meningiomas and for meningiomas involving the skull
base or the cavernous sinus.
It is used primarily to prevent tumor progression.
In a recently published series, the long-term follow up after radiosurgery
was reported; a tumor control rate of 94% was found after an average of
103 months.

Surgical Care
The constant principles in meningioma resection are the following: If
possible, all involved or hyperostotic bone should be removed. The dura
involved by the tumor as well as a dural rim that is free from tumor
should be resected (duraplasty is performed). Dural tails that are
apparent on MRI are best removed, even though some may not be
involved with the tumor. Make a provision for harvesting a suitable dural
substitute (pericranium or fascia lata). The surgeon also can use
commercially available dural substitutes. If feasible, always start by
coagulating the arterial feeders to the meningioma. See the images
below.

Case 1: Surgical view of the tumor. The dura is opened, and the meningioma can be
seen extending en plaque over the surface of the brain.

Case 1: Bone flap seen along the removed meningioma in toto.

Case 2: Intraoperative view shows the skull involvement.

Case 2: Bone flap was removed. Note tumoral breach of the dura. The dura and
overlying skull were removed surgically. Duraplasty and cranioplasty were performed

Case 2: Surgical specimen. Complete resection was achieved.
Surgical strategies for managing meningiomas in specific locations
include the following:
Convexity meningioma
Opening the scalp and skull may be bloody because of the
hypertrophy of blood vessels originating from the external
circulation.
The tumor may breach the sanctity of the dura and the bone,
thus appearing subcutaneously.
The dural blood vessels should be coagulated before opening
the dura to decrease tumor vascularity.
Usually the tumor is separated from underlying brain
parenchyma by an arachnoid layer. This layer may not be
complete at the depth of the tumor. In this location,
separating the tumor from the brain may be difficult.
Unless the tumor is small and can be removed in 1 piece, the
best strategy for excising convexity meningiomas is to find
the arachnoidal plane and dissect it gently.
Placing patties circumferentially around the tumor allows quick
identification of this crucial plane at a later time.
Coagulate the surface of the tumor, then core it and invaginate
the outer layer to allow further circumferential dissection.
Perform dural grafting.

Parasagittal meningiomas
These tumors may arise from the convexity and involve the
superior sagittal sinus (SSS) by medial extension, or they
may arise from the falx and involve the SSS by upward
extension. The former subgroup is easier to treat surgically
because of its superficial location.
The foremost consideration in surgically treating parasagittal
meningiomas is to decide what to do with the SSS. MRV is
not yet sensitive enough to confirm unequivocally the
complete occlusion of the SSS.
The diagnostic test of choice is still endovascular angiography
with late venous images to look for a possible delayed
filling of the involved portion of the SSS. If the SSS is
completely obliterated by tumor, it can be ligated safely and
excised. The surgeon should be careful not to injure the
veins that run anteriorly and posteriorly to the tumor. These
veins may provide crucial collateral circulation for the
venous drainage of the cerebrum and should be preserved
at all costs.
If the SSS is only partially involved, the decision of whether to
sacrifice it depends on the involved segment.
The anterior third of the SSS can usually be sacrificed with
impunity; the middle third, sacrificed at times; and the
posterior third, never ligated. In this author's experience,
the SSS is never sacrificed beyond the anterior third.
Some surgeons resect a partially involved sinus and reconstruct
it later (either with a vein or prosthetic graft).
The author's opinion is that explaining to the patient that some
tumor was left behind that may need further resection at a
later date is better than taking undue risk of neurological
deficit by obliterating more of the SSS. If the sinus is
occluded gradually by the tumor, the venous drainage will
be diverted over time through parasagittal veins.

Olfactory groove and tuberculum sellae meningiomas
To avoid undue retraction of the frontal lobes, these tumors are
best approached through a low craniotomy. This is
achieved by removing the supraorbital rim.
A unilateral approach is usually sufficient. The midline burr hole
should be placed just above the frontonasal suture. By
entering the frontal sinus and removing the orbital rim, a
low approach is provided.
To allow adequate visualization, the falx should be sectioned
after ligating the most anterior aspect of the SSS. Every
attempt should be made to preserve at least one of the
olfactory nerves.
These tumors receive their blood supply through various
sources: the ethmoidal branches of the ophthalmic arteries,
branches from the middle meningeal artery, and the carotid
arteries.
These tumors often invade the ethmoid sinuses and, at times,
the sphenoid sinus.
Care should be taken to identify and preserve both optic
nerves. Note that the usual relationship between the optic
nerves and the carotid arteries might not hold true owing to
displacement of these vital structures by tumor.
Tumor arterial supply and perforator arteries to the
hypothalamus must be differentiated because both arise
from the anterior circulation.

Sphenoid-wing meningiomas
Sphenoid-wing meningiomas present either as en plaque
meningiomas or as globular masses.
Removing the zygoma and the orbital rim allows wider
exposure of the sphenoid wing, the middle cranial fossa,
the anterior cranial fossa, and the anterior clinoid.
Medial tumors may extend within the cavernous sinus.

Tentorial and torcular meningiomas
Tentorial meningiomas may be supplied by a multitude of
vessels that arise from the tentorial leaf. These should be
coagulated thoroughly before one attempts to remove the
tumor.
A major supply may be the Bernasconi-Cassinari artery, which
arises from the cavernous portion of the carotid artery and
runs posteriorly to supply the tentorium.
This artery is usually not apparent on normal angiograms but
may be conspicuous in angiograms of tentorial
meningiomas.
A definite attempt should be made at recognizing the
Bernasconi-Cassinari artery during surgery and coagulating
it to decrease tumor vascularity.
Tentorial meningiomas often grow in both the infratentorial and
supratentorial compartments and should be approached
accordingly.
Studying the preoperative angiogram is imperative in cases of
torcular meningiomas to delineate the patency of the
different sinuses and the available collateral circulation.
Removing these tumors completely is often impossible
because of partial involvement of the venous sinuses.

Cerebellopontine angle meningiomas
In acoustic neuromas, the facial nerve usually lies
anterosuperiorly to the tumor and is encountered late in
surgery. This relationship is lost in cerebellopontine angle
meningiomas, because the facial nerve may lie along the
posterior tumor edge and can be injured early in surgery
(unless care is taken to identify it).
Before attempting to remove the tumor, the surgeon should first
diminish its blood supply by coagulating its supplying
arteries from the dura. To do so, the interface of the tumor
and the petrous bone should be followed. A partial
cerebellar resection may be necessary to avoid undue
retraction of the brain.

Meningiomas involving the cavernous sinus
The issue of meningiomas involving the cavernous sinus is
currently an area of intense interest in neurosurgery. No
one doubts that, in experienced hands, such meningiomas
can be treated successfully.
The debate centers on 2 points: when to operate and how
aggressive the resection should be. The following opinion
is a personal reflection on the matter, and diverging views
may be found in the literature.
Asymptomatic cavernous sinus meningiomas should not
be operated but should be monitored carefully by
means of repeated physical examination and serial
MRI.
Symptomatic meningiomas in otherwise healthy patients
should be resected by neurosurgeons who are
trained for such procedures.
Avoid injuring the cranial nerves or the carotid artery. This
author does not believe in the benefit of bypassing and
resecting the cavernous carotid artery in these cases.
The surgeon should remember that a multitude of processes
may affect the cavernous sinus and mimic a meningioma,
including sarcoidosis and infection/inflammation that lead to
the Tolosa-Hunt syndrome.
Gamma knife may be a good treatment option in parasellar
meningiomas.[34] Large tumors can be partially resected
and treated with gamma knife after resection. In a report by
Jensen et al, a good outcome was obtained, with an
impressive 69% local tumor growth control.

Clival and petroclival meningiomas
These tumors represent some of the greatest challenges in
neurosurgery; although partial resection is relatively
straightforward, complete resection remains a daunting
task.
Partial resection usually does not translate into any benefit for
the patient and only renders further surgeries more difficult;
therefore, every attempt should be made to complete the
resection. If surgery has to be interrupted for logistical
reasons, the second operation should be scheduled the
earliest possible opportunity.
A multitude of approaches has been devised for these tumors.
The traditional approaches such as the suboccipital or the
subtemporal are usually insufficient to allow complete
removal. More extensive approaches, such as the petrosal
approach, are needed. This approach consists of combined
supratentorial and infratentorial craniotomies, associated
with a simple mastoidectomy down to the solid angle (ie,
the bone encasing the inner ear). After the tentorium is
split, the petroclival meningioma can be visualized in its
entirety.

Consultations
If the patient has neurofibromatosis, the neurosurgeon may
want to refer the patient for genetic counseling and for
audiometric testing.
If the radiologic diagnosis is not clear cut, a detailed
discussion with the radiologist should attempt to rule out other
pathologic entities, such as neurofibromas or sarcomas.
In specific cases, consulting a radiation oncologist may be
appropriate.
Diet
No dietary restrictions are necessary in patients with meningiomas. If
the patient is on perioperative steroids, a low-salt diet is appropriate.

Activity
Patients with a meningioma who undergo surgery can resume their
normal activities after an adequate period of postoperative rest (1-3
mo).

Medication Summary
The goals of pharmacotherapy are to reduce morbidity and prevent
complications.

Corticosteroids
Class Summary
These agents reduce edema around tumor, frequently leading to
symptomatic and objective improvement in symptoms.
Dexamethasone (Decadron, Dexasone)

Postulated mechanisms of action of corticosteroids in brain tumors
include reduction in vascular permeability, cytotoxic effects on tumors,
inhibition of tumor formation, and decreased CSF production.
Dosing Forms & Strengths
tablet
0.5mg
0.75mg
1mg
1.5mg
2mg
4mg
6mg
injectable suspension
4mg/mL
10mg/mL
elixir/oral solution
0.5mg/5mL
oral concentrate
1mg/1mL
Inflammation
0.75-9 mg/day IV or IM or PO divided q6hr or q12hr
Cerebral Edema
10 mg IV, then 4 mg IM q6hr until clinical improvement is observed;
may be reduced after 2-4 days and gradually discontinued
Adrenal Cortical Hyperfunction Test
After determination of baseline cortisol level, 1 mg PO at bedtime (11:00
PM)
Plasma cortisol level then determined at 8:00 AM on following morning;
level will be decreased in normal individuals but at baseline level in
Cushing syndrome
Shock
1-6 mg/kg IV once or 40 mg IV q2-6hr PRN
Alternative: 20 mg IV, then 3 mg/kg/day by continuous IV infusion
High-dose treatment not to be continued beyond 48-72 hours
Allergic Conditions
Day 1: 4-8 mg IM
Days 2-3: 3 mg/day PO divided q12hr
Day 4: 1.5 mg/day PO divided q12hr
Days 5-6: 0.75 mg/day PO in single daily dose
Dexamethasone Suppression Test
Low-dose test
Screening
Overnight test: 1 mg PO between 11:00 PM and midnight;
cortisol level tested between 8:00 and 9:00 AM on following
morning
Standard 2-day test: 0.5 mg PO q6hr (9:00 AM, 3:00 PM,
9:00 PM, 3:00 AM) for 2 days; cortisol level tested 6 hours after
final dose (9:00 AM)
High-dose test
Confirmed Cushing syndrome in which further workup is
needed to identify etiology
Standard 2-day test: After determination of baseline serum
cortisol or 24-hr urinary free cortisol, 2 mg PO q6hr for 2 days;
urine for free cortisol is collected during test, and serum cortisol is
checked 6 hours after final dose
Overnight test: After determination of baseline serum
cortisol, 8 mg (typically) PO between 11:00 pm and midnight;
cortisol level tested between 8:00 and 9:00 AM on following
morning
IV test: After determination of baseline serum cortisol, 1
mg/hr by continuous IV infusion for 5-7 hours
Chemotherapy-Induced Nausea & Vomiting (Off-label)
8-12 mg PO/IV alone or in combination with other antiemetics before
chemotherapy, then 8 mg PO/IV q24hr for 1-3 days after chemotherapy
(days 2-4)
Altitude Sickness (Off-label)
Prophylaxis
2 mg PO q6hr or 4 mg PO q12hr beginning on day of
ascent; may be discontinued after 2- to 3-day stay at same
elevation or initiation of descent
Treatment
Acute mountain sickness (AMS): 4 mg PO/IV/IM q6hr
High-altitude cerebral edema (HACE): 8 mg once followed
by 4 mg PO/IV/IM q6hr until symptoms resolve
Spinal Cord Compression (Off-label)
10-100 mg IV, then 4-24 mg IV q6hr during radiation therapy, then
tapered
Pharmacology
Mechanism of Action
Potent glucocorticoid with minimal to no mineralocorticoid activity
Decreases inflammation by suppressing migration of
polymorphonuclear leukocytes (PMNs) and reducing capillary
permeability; stabilizes cell and lysosomal membranes, increases
surfactant synthesis, increases serum vitamin A concentration, and
inhibits prostaglandin and proinflammatory cytokines; suppresses
lymphocyte proliferation through direct cytolysis, inhibits mitosis, breaks
down granulocyte aggregates, and improves pulmonary microcirculation
Absorption
Onset: IM, 8-24 hr
Peak plasma time: IM, 8 hr; PO, 1-2 hr
Distribution
Vd: 2 L/kg
Metabolism
Metabolized in liver
Elimination
Half-life: 2-3.5 hr (normal renal function)
Excretion: Urine (mainly), feces (minimally)

Further Inpatient Care
Before or after surgery, patients with skull-base
meningiomas may have numerous disabilities, such as diplopia,
dysphasia, dysphagia, or motor weakness.
These problems should be managed with a
multidisciplinary approach (eg, occupational therapy,
physiotherapy, speech therapy).
Further Outpatient Care
Patients who undergo operation for meningiomas should
receive regular follow-up with enhanced MRI to check for possible
recurrences.[35]
Patients who are discharged home with antiepileptic agents
should be monitored by a neurologist.
Prognosis
Patients whose meningiomas are completely resected
usually have an excellent prognosis.
The following types of meningiomas are most likely to
recur: incompletely excised, malignant, or multiple tumors.


Author
Georges Haddad, MD Clinical Assistant Professor, Department of
Medicine, Division of Vascular Surgery, American University of Beirut,
Lebanon

Ali Turkmani, MD Staff Physician, Department of Neurosurgery,
American University Hospital

Frederick M Vincent Sr, MD Clinical Professor, Department of
Neurology and Ophthalmology, Michigan State University Colleges of
Human and Osteopathic Medicine

Tarakad S Ramachandran, MBBS, FRCP(C), FACP, FRCP Professor
Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine,
Clinical Professor of Family Medicine, Clinical Professor of
Neurosurgery, State University of New York Upstate Medical University;
Neuroscience Director, Department of Neurology, Crouse Irving
Memorial Hospital

Updated May 14, 2013