Meningioma

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.

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.

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 withneurofibromatosis 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.

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.² 

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

Clinical

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 hyperostosis³ and/or invading the overlying soft tissues, or inducing vascular injuries to the brain. 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 1. Symptoms and Signs Associated with Meningiomas in Specific Locations
  
  Open table in new window

  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 4
  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.⁵

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.⁶
• 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 22q⁷ . 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 Gorlin⁸ and Rubinstein-Taybi syndromes⁹ .
• 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