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

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

PathophysiologyMeningiomas 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.

EpidemiologyFrequency

United StatesThe 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]

InternationalThe 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 - 17.04Age 85 years and older - 18.86

HistoryMeningiomas 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

• Cerebellopontine 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.

• MiscellaneousIntraventricular 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]•

PhysicalThe 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.

CausesTrauma 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 TumorsPrimary CNS Lymphoma

Laboratory StudiesNo specific laboratory tests are used to screen for meningioma.

Imaging StudiesImaging 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 circulationMother-in-law blush (which comes early and leaves late)Sunburst or radial appearance of the feeding arteriesAlthough 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.

ProceduresPreoperative 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 FindingsMeningiomas 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 (Anaplastic)

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 CareThe 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 meningiomaOpening 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.

DietNo dietary restrictions are necessary in patients with meningiomas. If the patient is on perioperative steroids, a low-salt diet is appropriate.

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

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

CorticosteroidsClass 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 & Strengthstablet

• 0.5mg• 0.75mg• 1mg• 1.5mg• 2mg• 4mg

• 6mginjectable suspension

• 4mg/mL• 10mg/mLelixir/oral solution

0.5mg/5mLoral concentrate

1mg/1mLInflammation

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

ScreeningOvernight test: 1 mg PO between 11:00 PM and midnight; cortisol level tested between 8:00 and 9:00 AM on following morningStandard 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 etiologyStandard 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 doseOvernight 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 morningIV 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 q6hrHigh-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

PharmacologyMechanism 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.

PrognosisPatients 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.

AuthorGeorges 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