Decision Making in Meningiomas

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CHAPTER 18 Decision Making in Meningiomas

M. Necmettin Pamir, Peter M. Black, Rudolf Fahlbusch

INTRODUCTION

The goal of management strategy in meningiomas is to keep the patient fully functional and provide long-term relief or prevent intracranial tumor growth associated problems. The clinical picture at presentation is very variable, and very little is known regarding the natural history of these tumors; therefore the management strategy is not universal. The initial dilemma that the surgeon faces starts with the decision to treat or not to treat. Only then is this followed by the decision of how to treat. Both decisions are taken together with the patient and the surgeon plays the role of an advisor, rather than directly deciding for the patient. Treatment choice in patients who present to medical attention for the first time with a symptomatic meningioma or in those with neural compression is mostly straightforward. The goal is well defined and the possible gains most commonly far outweigh the risks. However; decision making is not so easy in non- or marginally symptomatic patients, for whom the risks of treatment should be weighed against the risk of iatrogenic injury. The mortality and morbidity of surgical treatment decreased significantly and continuously in the last century, mainly as a result of the application of microsurgery, bipolar coagulation, and other new technologies. A better appreciation of microsurgical anatomy and increasing use of skull-base surgery have further improved results. The advent and popularization of alternative treatment modalities such as radiation treatment and radiosurgery have also made significant contributions. Finally, with accumulating experience and scientific data much more is known today about the biology of meningiomas. Even with all these advances, today’s neurosurgeon still has very little clinical evidence on which to base his or her clinical decisions. This chapter aims to summarize the controversies, discussing different management paradigms and thus providing a general guideline for treatment (or nontreatment) of meningiomas.

Five factors influence the treatment decision in meningiomas: operative gains, operative risks, tumor biology, mass effect/symptomatology, and the preference of the patient. In short, the balance between the risks and benefits of surgery is evaluated in light of the tumor’s biology, mass effect/symptomatology, and preference of the patient (Fig. 18-1).

FIGURE 18-1 In many situations the physician will guide the meningioma patient during the management of the disease. The decision to treat or not to treat relies on a fine balance between the risks and benefits of surgery, which in turn should be evaluated in the light of the tumor’s biology, presence of mass effect/symptomatology and very importantly, the preference of the patient.

MASS EFFECT AND SYMPTOMATOLOGY

For well circumscribed benign intracranial tumors, such as meningiomas, total surgical excision provides immediate symptom relief and long-term control of tumor growth and tumor-associated problems. Therefore, for a symptomatic meningioma surgery remains the treatment of choice, provided that it can be performed with acceptable morbidity and mortality. The presence of a mass effect in the form of (present or imminent) neural compression and increased intracranial pressure are also direct indications for surgery, independent of whether the patient is symptomatic or asymptomatic. In asymptomatic cases with radiologically documented neural compression, surgery is performed with the intent of altering the natural history. The treatment decision in asymptomatic, incidental meningiomas is much more difficult. With advances in noninvasive diagnostic technologies and an aging population, incidental meningiomas are more commonly diagnosed than ever before. Close radiologic follow-up in such an incidental, asymptomatic meningioma that does not cause neural compression is an acceptable strategy, and a large proportion of these cases remain asymptomatic during follow-up.

The incidence of asymptomatic meningiomas in the general population ranges from 1% to 1.4% both in noninvasive imaging studies in the general population ^1,² and in autopsy series.³^–⁵ The prevalence of meningiomas steadily increases with age;^1,^2,⁶^–⁹ in patients older than 60 years of age it is 3%.⁴ Similarly, the incidence of patients with meningiomas who come to clinical attention is reported to be 3.5 times higher over the age of 70.¹⁰ This observation is in line with the hypothesis that oncogenesis in meningiomas is a slow process, which occurs over decades. Most meningiomas remain asymptomatic throughout life, and in fact; half of all meningiomas are discovered only at autopsy.⁵ Studies that have analyzed the clinical behavior in asymptomatic meningiomas have reported growth rates ranging from 0 to 37.3%,¹¹^–¹⁷ which indicates that in the short term at least 2/3 of meningiomas do not grow. There are, however, no long-term studies that have evaluated the incidence of growth in asymptomatic meningiomas. Yano and colleagues¹⁶ reported their experience with 351 conservatively treated incidental meningiomas. Over a period of 5 years tumor growth was detected in 37.3%, and 16.4% had tumor growth and became symptomatic. Several authors have analyzed factors that may indicate growth potential in meningiomas. A summary of these studies is provided in Table 18-1. As can be seen in the table, there is no general consensus on this issue. The presence of calcifications and a low T2 signal was associated with nongrowth in all studies. In four of six studies age correlated significantly with nongrowth. Many other studies also indicate that, disproportionally with their increasing incidence, the likelihood of a meningioma becoming symptomatic decreases with age. Most meningiomas in the elderly, detected at autopsy, are less than 1 cm in diameter.⁴ However, the incidence of growth in incidental meningiomas in the elderly is comparable to that in the younger population. Niiro and colleagues¹⁴ have reported on the natural history of 40 incidental meningiomas in patients older than the age of 70. During a mean follow-up of 38.4 months, 35% of the tumors showed radiologically documented growth and 12.5% became symptomatic. In contrast, meningiomas in the pediatric population have greater risk of aggressive behavior.¹⁰ Several authors have looked for an association between the initial tumor size and the annual growth rate. A higher growth rate was reported in larger tumors by some authors.^14,¹⁸ Still others have reported very high tumor growth rates in very small tumors.¹¹ A summary of reported growth rates is also presented in Table 18-1.

TABLE 18-1 Studies on growth of incidental meningiomas

TUMOR BIOLOGY

The natural history of the tumor and its behavior after treatment depend on its intrinsic biology. Many biologic and clinical parameters were found to provide clues on the biology of a meningioma. None of these is exclusively predictive of the clinical behavior, but when considered together these parameters strongly influence treatment strategy.

Histology

Most meningiomas are slow growing benign tumors that histologically correspond to World Health Organization (WHO) grade I. Rare histologic variants such as clear cell, chordoid, papillary, and rhabdoid meningiomas, as well as atypical (WHO grade II) and anaplastic (WHO grade III) meningiomas can present with more aggressive behavior and relentless growth despite multimodal treatment, and have a high incidence of recurrences and a less favorable prognosis.¹⁰

Molecular Biology and Genetics

Molecular genetic analysis of meningiomas has revealed that they carry a wide variety of chromosomal aberrations. In general the complexity of these aberrations correlates with increasing histologic grade.¹⁹ Partial loss or monosomy of chromosomes 1, 10, and 14 is associated with aggressive behavior and higher histologic grades.²⁰^–²³

Angiogenesis

Meningiomas are highly vascular tumors and their angiogenic potential plays an important role in their growth. Studies have shown that an increased expression of vascular endothelial growth factor (VEGF) was correlated with an increased risk of recurrence and higher incidence of peritumoral edema.²⁴^–²⁶ Extracellular matrix associated structural proteins and growth factors such as tenascin and matrix metalloprotease MMP-9 were also shown to have a correlation with tumor recurrence.^27,²⁸

Hormonal Influences

Hormonal dependence of meningiomas has been suggested by clinical observations such as predominance of female patients, growth during pregnancy, and the luteal phase of pregnancy. Further, the presence of progesterone receptors was associated with benign histology and lower likelihood of recurrences.²⁹^–³¹

Growth Rate of Meningiomas

As is the case for most other parameters on meningiomas, very little is known concerning the growth kinetics of meningiomas. Most meningiomas are slow growing tumors. But there is significant variation between the growth rates of individual meningiomas. Current classification schemes, such as histologic grading, fall short of predicting this growth rate. Jaaskelainen and colleagues ³² have shown that the histologic appearance correlated only grossly with the growth rate but did not exactly predict the tumor doubling time. When typical, atypical, and malignant meningiomas were considered there was significant variation within and significant overlap between histologic subgroups.³²

In addition to the variability in growth rate between individual tumors, it is also likely that there are temporal changes in the growth rate of individual meningiomas. The assumption that a meningioma will grow at a constant rate is most likely an oversimplification, and most meningiomas do not exhibit a constant growth rate but change in their growth characteristics during their clinical course. Clinical analyses have indicated that they do have variations in the growth characteristics of meningiomas during their growth.³³ This is certainly not unexpected. Current evidence indicates that meningiomas, like most other malignancies, develop and progress as a result of accumulating genetic and epigenetic changes; therefore one can easily conclude that the growth rate will change with increasing malignancy.¹⁰ As expected, studies have concluded that the growth rate increased with successive recurrences.^32,³⁴ This finding was also supported by the demonstration of a decreasing time interval between recurrences.^35,³⁶

It is also not known whether tumor growth rate changes during pregnancy or in women receiving postmenopausal hormone treatment.

The tumor doubling time in recurrent benign meningiomas was estimated to be 317 days using computed tomography (CT) volumetrics and bromodeoxyuridine labeling and 415 days using CT planimetry.^32,³⁷ Much variation is reported in the tumor doubling times, but it ranged from 138 to 1045 days (mean 415 days) in WHO grade I, 34 to 551 days (mean 178 days) in WHO grade II and 30 to 472 (mean 205 days) in grade III meningiomas.³² The clinical implication of this is that recurrences should be expected late in the course in most meningiomas. Ninety-five percent of meningiomas are either adherent or invasive to the surrounding neurovascular structures, which will preclude a “true” oncologic resection of meningiomas and residual tumor cells will be the source of a recurrence. Jaaskelainen and colleagues have calculated the estimated time to a recurrence detectable by CT, after a seemingly gross total surgical resection to be approximately 8.5 years. This hypothesis is supported by Simpson’s elegant demonstration that up to 10% of meningiomas recurred 10 years after a seemingly complete resection.³⁸ The incidence of detected recurrences increased over time, reaching 20% at the end of the second decade after surgery.^36,^38,³⁹ This and other studies have shown that up to 50% of all recurrences occurred after 5 years.^36,^38,³⁹

Quantification of the proliferative potential is important for predicting future recurrences and planning an optimal management strategy. Several studies have looked for histopathologic findings to evaluate the growth potential of meningiomas. Tumor growth is a function of cell proliferation and death. Cell death has not been systematically studied in meningiomas. Proliferative indices, however, are commonly used. Demonstration of proliferating cell nuclear antigen (PCNA), silver staining for nucleolar organizer regions (AgNOR), immunohistochemistry for MIB-1 (Ki-67), and bromodeoxyuridine (BrdU) labeling are the most common methods for demonstrating the proportion of proliferating cell fraction.^10,^40,⁴¹ There is a well demonstrated correlation between high proliferative indices and recurrences. However, this correlation is not exclusive. Low MIB-1 indices were demonstrated in many recurrent tumors and very high proliferative indices are sometimes demonstrated in typical meningiomas.⁴²

Anatomic Localization

Natural history, symptomatology, and the surgical outcome vary significantly among meningiomas in different intracranial localizations.⁴³ To present a striking example, a small meningioma in the optic canal will come to clinical attention much earlier than a large convexity meningioma. Therefore, clinical correlates of localization should be taken into consideration when planning surgery for meningiomas. Eighty to ninety-six percent of tuberculum sella meningiomas present to clinical attention with progressive visual impairment. Despite wide availability of magnetic resonance imaging (MRI), most anterior fossa meningiomas are quite large at presentation. Seventy-three percent of anterior fossa meningiomas present when larger than 4 cm.⁴⁴ The same holds true for olfactory groove meningiomas, 65% of which have a diameter larger than 3 cm at presentation.⁴⁵ Optic nerve sheath meningiomas are associated also with a progressive decrease in vision. Kennerdell and colleagues⁴⁶ observed 18 patients without treatment, and none of the patients who had normal visual acuity retained it for more than 5 years. Similarly, Keane and colleagues⁴⁷ and Sarkies⁴⁸ reported progressive decrease in vision in 20 of 22 patients. Petroclival meningiomas have variable and unpredictable growth patterns. Radiologic growth was reported in 76% of patients at a median follow-up of 85 months, and in 63% this growth was associated with functional deterioration.⁴⁹

Peritumoral Edema

A significant proportion of meningiomas present with varying degrees of edema in the surrounding brain parenchyma. Different studies have reported incidences ranging from 46% to 92%.^31,⁵⁰ The presence and extent of edema are highly variable and the underlying pathogenesis is not entirely clear. Tumor compression, parasitization of pial vasculature, convexity/middle fossa/anterior fossa localization, irregular tumor–brain interface, hyperintensity on T2-weighted images, brain invasion, high grade, secretory, microcystic and/or angiomatous variants, and high VEGF expression have all been suggested as the cause of edema but none has been proven to date.³¹ A minor amount of edema may be negligible but significant peritumoral edema may interfere with normal brain function and may be the patient’s presenting symptom.⁵⁰ Peritumoral edema is also reported to complicate surgery and to be a source of perioperative morbidity.⁵⁰ Therefore surgical resection is favored in cases with peritumoral edema.⁵⁰

Invasion of Surrounding Structures

Meningiomas are mesenchymal tumors and have a tendency to invade the surrounding structures including dura, bone, muscle, and brain parenchyma.³¹ Bone invasion is common in meningiomas, particularly those at the skull base, and presents as hyperostosis and less commonly as bone destruction.⁵¹ Hyperostosis is almost invariably associated with tumor invasion. Invaded bone is a source of recurrence and should be removed along with the tumor. The need for bone removal creates a significant challenge in the skull base. Neurovascular invasion is also a significant problem in meningiomas. Such invasion of neighboring brain parenchyma, cranial nerves, and blood vessels is observed in only a minority of meningiomas but in those cases it precludes a gross total resection and is a source of relapse.¹⁰ Yasargil⁵² has reported that 5% of meningiomas were nonadherent, 85% were adherent, and 10% were adhesive so that dissection is impossible without damaging vital structures. Neurovascular invasion may be observed in benign, atypical, and anaplastic meningiomas; however, it signifies a more aggressive biologic behavior so that benign meningiomas with brain invasion have a prognosis similar to that of atypical meningiomas.¹⁰ Borovich and colleagues^53,⁵⁴ have demonstrated isolated tumor cell nests detectable at a distance from the main tumor bulk. Preoperative radiologic diagnosis of neural or vascular invasion is not reliable.⁵²

Multiplicity

Multiplicity is observed in 0.9% to 8.9% of meningiomas in clinical series. In 50% of these cases, multiple meningiomas are diagnosed at the initial presentation, excluding the possibility of recurrence, seeding, or metastasis. Autopsy series report a higher incidence of multiplicity.⁴ Most of these cases are associated with neurofibromatosis type II. Sixty to ninety percent of multiple meningiomas are observed in women. No difference in clinical tumor behavior or outcome has been reported for multiple meningiomas, and the treatment decision does not differ from that for solitary meningioma cases.

Special Conditions

Meningiomas are the second most commonly encountered intracranial tumor in neurofibromatosis type 2 (NF-2) and are seen in approximately 50% of the cases.¹⁰ The incidence of this association is clearer in pediatric meningiomas, 25% to 40% of which are seen in association with NF-2. The clinical behavior (their anatomic localization, growth rate, and recurrence rates) of meningiomas associated with NF-2 is not significantly different from sporadic cases. Multiplicity is more commonly observed in meningiomas associated with NF-2.

Meningiomas in children are rare, comprising 1% to 7.7% of all pediatric brain tumors and 2% of all meningiomas.^10,^55,⁵⁶ Very little is known regarding the characteristics of meningiomas in children, and the number of reports add up to only a few hundred cases. Studies to date have concluded that pediatric meningioma patients have a poorer prognosis that their adult counterparts due to higher incidence of malignant or aggressive forms of meningioma, increased relative size of the tumors, and their unusual and complicated anatomic localizations.^10,⁵⁵^–⁵⁷ Cases occurring in association with NF-2 (25%–40% of cases) or secondary to radiation are more common than in the adult population and the predominance of female cases documented in adults is not observed.^55,⁵⁶ The incidence of unusual anatomic localizations such as the orbit and the ventricular system, the incidence of cases in the posterior fossa, and the incidence of meningiomas without a dural attachment are higher in the pediatric population.^55,⁵⁶ Pediatric cases almost invariably are symptomatic and present with increased head size in infants, focal neurologic deficits, seizures, and increased intracranial pressure and this justifies a surgical intervention. Drake and Hoffman⁵⁵ analyzed 207 patients from 11 available series published between 1972 and 1987 and calculated the overall 5-year survival to be 76%. When meningeal sarcomas were excluded, the overall survival increased to 84%. Malignant meningiomas and meningeal sarcomas made up 15% of all childhood meningiomas. A 5-year survival rate of 94% was reported in cases without recurrence and 64% in cases with recurrences.⁵⁵ The mean operative mortality was 3%.⁵⁵ In summary, children with typical meningiomas and a gross total surgical resection benefited from surgery. However, those with a papillary histologic subtype, meningeal sarcomas, or subtotally resected tumors and those with recurrences had a poorer prognosis.

OPERATIVE GAINS

The two goals of meningioma surgery are symptom palliation and alteration of the tumor’s natural history. Resection of the tumor results in decompression of the nearby neural structures and also of their vascular supply.

Surgical Outcome in Different Anatomic Localizations

As is the case for their natural history, anatomic localization of the meningioma also strongly influences the surgical outcome. A summary of the surgical outcome in meningiomas at different anatomic localizations is provided in Table 18-2.

TABLE 18-2 Surgical results in selected meningiomas in relation to localization

Anterior fossa meningiomas are notorious for remaining asymptomatic for long periods, presenting with large sizes and having a high incidence of recurrence.¹⁰⁵ Mathiesen and colleagues¹⁰⁶ showed that 10% of these cases recur at 10 years and that 20% of the patients die as a result of these recurrences. Surgical resection of olfactory groove meningiomas is complicated by the fact that they may invade the anterior skull base and the paranasal sinuses.¹⁰⁷ Radical resection of the tumor, involved dura, and bone in the anterior fossa or the paranasal sinuses is technically difficult and is associated with a high risk of complications. More conservative resections, in contrast, may result in recurrences as high as 41% at 10 years.³⁶ Bakay¹⁰⁸ reported subtotal resection in 17% of his patients, which was associated with blindness in half of these patients due to recurrence. The likelihood of preserving smell after resection of olfactory groove meningiomas is possible in tumors smaller than 3 cm in diameter, whereas ipsilateral smell is lost in all cases.¹⁰⁹ In tuberculum sella meningiomas, surgery provides objective, quantifiable, and significant improvement in vision.^62,⁶⁶ The reported likelihood of visual improvement after surgery ranges from 42.4% to 80% in a recent series.⁶²^–⁶⁷ In contrast, some studies reported 10% to 20% incidence of iatrogenic worsening in vision.⁶²^–⁶⁷ The visual outcome in young patients after surgical resection is significantly better than in the elderly^62,^66,⁶⁷ Severity and duration of visual symptoms were also shown as predictors of a poor visual outcome.^62,^65–67,^110,¹¹¹ Size of the tumor,^66,¹¹² shape of the tumor,⁶⁶ extent of tumor removal,^62,⁶⁶ absence of an arachnoid plane,⁶⁶ binocular involvement,⁶² optic disc pallor,¹¹⁰ and presence of significant peritumoral edema⁶⁶ were associated with a worse outcome as reported by some authors and contradicted or not supported by others. Large tumors may involve distal branches of the anterior cerebral artery which will preclude total resection and increase recurrences. Another source of recurrences is small tumor extensions in the optic canals, which can easily be missed when not inspected during surgery. Several authors also have shown that a simple pterional craniotomy is sufficient to achieve high total resection rates with very little morbidity.^62,⁶⁶ Low morbidity rates and good chance of benefit to the patient favor a surgical treatment in tuberculum sella meningiomas. Sphenoid wing meningiomas are classified into pterional, alar, clinoidal, and en plaque subtypes according to their epicenter along the sphenoid ridge.¹¹³ The elegant report by Al-Mefty and colleagues⁶⁸ established clinoidal meningiomas as a new meningioma subtype, distinct from sphenoid wing meningiomas. Clinoidal meningiomas can be differentiated from sphenoid wing meningiomas radiologically, unless the tumor has reached a giant size.⁷¹ Visual symptomatology is reported in 45.5% to 91.6% of patients with clinoidal meningiomas.⁶⁸^–⁷³ The most important factor that determines the surgical outcome in clinoidal meningiomas is the anatomic relationship of the tumor to the internal carotid artery and surrounding arachnoid cisterns.⁶⁸ Large tumor size⁷¹ and cavernous sinus invasion⁶⁸^–⁷³ are other factors that have a negative impact on surgical outcome.

Meningiomas of the optic nerve and orbit fall into different categories. Surgery is clearly the treatment of choice in meningiomas invading the optic canal and compressing the optic nerve. This also holds true for ectopic meningiomas within the orbit. However, the results of surgical excision in tumors that arise from the optic sheath and completely surround the optic nerve are dismal and most cases result in blindness. Surgical resection may be performed in patients with intracranial extension, disfiguring proptosis, and in patients with rapid visual deterioration.¹¹⁴ Radiosurgery or fractionated stereotactic radiotherapy is the option in all other cases.

True cavernous sinus meningiomas are among the most difficult meningiomas to resect. Although very conflicting reports can be found in the early literature, it is well established now that gross total resection is possible but is very rarely achieved in meningiomas that involve the cavernous sinus proper.^115,¹¹⁶ Meningiomas can invade the cranial nerves inside the cavernous sinus.⁷⁷ Radical strategies are associated with significant permanent cranial nerve morbidity, which can reach 59%.¹¹⁵ Owing to the disappointing results and high morbidity of radical surgical strategies, most authors to date advocate resection of the extracavernous portion with or without postoperative radiosurgery.^80,^115,¹¹⁶ A recent study by Sindou and colleagues⁸⁰ at progression was observed in 13.3% of subtotally resected cases. Small but symptomatic cavernous sinus meningiomas can be successfully treated with radiosurgery alone with adequate short-term tumor growth control and minimal morbidity.¹¹⁶^–¹¹⁸ Secondary cavernous sinus involvement may be invaded by tuberculum sella, clinoidal, medial sphenoid wing, and sphenopetroclival meningiomas. Tumors that are localized to the lateral wall (Hirsch grades 0 and 1) can be surgically excised without excess cranial nerve morbidity.¹¹⁹ Less radical treatment strategies paralleling those for cavernous sinus meningiomas are planned for more invasive cases.

Convexity meningiomas are the most easily resected type of meningiomas and therefore have the greatest potential for a “curative” resection. Epilepsy may complicate surgery of convexity meningiomas. Chan and Thompson ⁶⁰ have shown a strong correlation with sacrifice of the surrounding venous structures and postoperative epilepsy. Parasagittal meningiomas are located along the superior sagittal sinus (SSS) in the anterior, middle, or posterior third. Both the surgical treatment and the surgical results are influenced by the extent and localization of sinus invasion. The aim of the surgery is total surgical resection along with the involved dura, bone, and the involved venous sinus. This can be easily accomplished anterior to the Rolandic veins. However, two thirds of parasagittal meningiomas are located posterior to the coronal suture. Resection of a partially occluded sinus caries a high risk of mortality and morbidity. Contrary to general belief, the resection of a totally occluded sinus is not universally safe.^120,¹²¹ Venous reconstruction has been proposed as a management strategy but even in the hands of the most experienced surgeons, radical surgical resection of meningiomas of the middle third involving venous reconstruction carries substantial risk of morbidity.¹²⁰ The reported mortality ranged from 0 to 2.7% and surgical morbidity rates ranged from 8.3% to 29%.¹²⁰^–¹²² An alternative strategy in cases that do not or partially occlude the sinus is to treat the portion that invades the SSS with a gamma-knife after removal of the tumor outside the sinus.¹²³^–¹²⁵ This paradigm has yielded tumor growth control rates of 89% and a reduction in tumor size in approximately 50% of the tumors during follow-up. Surgical series with follow-up in the range of 5 to 10 years have reported recurrence in 7.2% to 24% of parasagittal meningiomas. Bonnal and Brotchi¹²⁰ have reported a 63% incidence of recurrence even after radical total resection of the tumor and the involved sinus. Meningiomas of the falx are less commonly observed. Involvement of the SSS is far less common in falx meningiomas and surgical removal is less complicated.

Tentorial meningiomas comprise one third of all posterior fossa meningiomas.^52,¹²⁶ Several surgical classification schemes were provided but the one by Yaşargil⁵² is the most clinically relevant one and differentiates between meningiomas of the free tentorial edge (T1,T2, T3), intermediate tentorial surface (T4), torcular (T5), lateral tentorial (T6, T7), and falcotentorial meningiomas (T8). Difficulty in the management of falcotentorial meningiomas results from their proximity to the brain stem and involvement of the deep venous system and major venous sinuses. Adherence to the vein of Galen is the most common cause for a subtotal resection. Some authors have reported that resection of involved parts of the vein of Galen and the straight sinuses can be performed, but reports have indicated that such a radical resection is associated with significant mortality and morbidity and not necessarily with a decreased recurrence rate.⁸⁹^–⁹² Meningiomas that arise from the posterior surface of the temporal bone are classified according to their relation to the fifth cranial nerve and fall into two distinct subgroups: cerebellopontine angle (CPA) and petroclival meningiomas. Those that arise laterally are CPA (posterior pyramis) meningiomas, and these tumors can be resected with conventional approaches and have a favorable surgical outcome. Hearing can be preserved in 5% to 8% of vestibular schwannomas, but because meningiomas do not invade, but rather compress the 7th to 8th nerve complex, preoperative nerve function is better preserved in CPA meningiomas and the postoperative cranial nerve outcome is better in meningiomas. Although they are invariably abnormal in vestibular schwannomas, a normal speech audiometry is found in 50% and a normal pure tone audiometry is found in 20% of patients with CPA meningiomas.¹²⁷ Preservation and even improvement in cranial nerve function can be expected in CPA meningiomas.¹²⁸ Anatomic preservation of the 7th and 8th cranial nerves was reported in 94% and functional preservation of the 7th and 8th cranial nerves was reported in 86% and 77% of CPA meningiomas, respectively.^129,¹³⁰ The reported outcome was worse in cases that arose in or at the internal auditory canal.¹³¹ A report on elderly patients with CPA meningiomas indicated similar good surgical results.¹³¹ At 85.7%, the total resection rate was not any different from that of the younger population.¹³¹ Elderly patients had higher incidences of cerebrospinal fluid (CSF) fistula and pneumonia but the incidence of other postoperative morbidity was not significantly different.¹³¹ In contrast to cerebellopontine angle meningiomas, petroclival meningiomas arise medial to the trigeminal nerve, at the petroclival junction and the upper two thirds of the clivus, and are associated with a progressive natural history and poor surgical outcomes. Sphenopetroclival lesions with involvement of the cavernous sinus and the orbit are the most difficult ones to manage. The treatment strategy for petroclival meningiomas is still evolving. The initial belief that they were “unresectable” was challenged after the introduction of skull-base surgery,⁸⁴^–⁸⁸ but during the following decades these extensive approaches fell out of favor due to their unacceptably high surgical morbidity and mortality⁸⁸ and have given way to simpler, more conservative presigmoid¹³² or retrosigmoid¹³³ approaches. Fibrous tumors with hard consistency; adherence to the brain stem, cranial nerves, and perforating arteries; encasement of major vessels; and cavernous sinus invasion are the most common causes of failure in total resection. The most common morbidity in petroclival meningioma surgery results from iatrogenic cranial nerve palsies, which is reported in 22% to 76% of petroclival meningioma surgeries. Cranial nerve palsies result in a very significant decrease in functionality and quality of life of patients, which is more pronounced in the elderly.¹³¹ Therefore most authors favor preservation of function to a more “impressive” postoperative MRI.^88,¹³⁴ With current surgical techniques, petroclival meningiomas can be resected with minimal mortality, and the morbidity is in the range of 30% with radical surgery and less with more conservative approaches.⁸⁴^–⁸⁸ Tumor progression has been reported in 42% of petroclival meningiomas with a mean time to progression of 36 months and in such cases radiosurgery or radiotherapy provides adequate tumor growth control.⁸⁶ According to their localization on the axial plane, foramen magnum meningiomas can be classified into ventral, ventrolateral, posterolateral, and posterior groups. Posterior and posterolateral cases can be resected with conventional approaches (or their slight modifications) with low morbidity and good surgical outcome. However, a small percentage of ventral foramen magnum meningiomas are located strictly ventral to the neuraxis or have extradural extensions. These cases present a formidable surgical challenge, require an extreme lateral transcondylar approach, and are associated with high surgical morbidity and poor surgical results. Gross total resection rates of 72% to 96% have been reported.⁹⁵^–¹⁰⁴ The surgical outcome of ventral foramen magnum meningiomas is among the poorest of all meningiomas with 4% to 16.6% surgical mortality, and permanent morbidity in up to one fifth of all cases. Use of radiosurgery as an adjunct or adjuvant treatment in case of recurrence or documented growth in residual tumors or in patients with multiple meningiomas has also been reported.¹³⁵

Tumor Recurrence After Surgery

An oncologic resection is seldom possible for meningiomas, and it is well known that most meningiomas do recur. The risk of this recurrence is dictated by the intrinsic biology of the tumor. However; meningiomas are slow growing tumors and even a subtotal resection can prevent neural compression, and the results may be durable for decades. More complete resections are associated with a lower risk of recurrences. Simpson ³⁸ was the first author to report that the risk of recurrence was lower after more complete resections. In his original report Simpson underlined the necessity to address the invasive nature of the tumor and recommended resection of the involved bone and dura and provided a surgical prognostication scheme that has withstood the test of time. His analysis proved that gross total resections, with resection of the involved bone and dura, yielded the most durable long-term results and underlined the fact that a subtotal resection is nothing but a glorified biopsy. In the original report Simpson grade 4 resections had a 39.2% regrowth rate. Others have also supported these findings, reporting recurrence/progression rates of 81% to 85% in 15 to 18 years after subtotal surgery (Simpson grade 4).^36,³⁹ A gross total resection is reported in 64% to 97% of operated patients.^36,^60,^81,^136,¹³⁷ However, despite such good surgical results recurrence is observed in 20% to 32% of the patients.^36,^105,^137,¹³⁸ Borovich and colleagues^53,⁵⁴ have demonstrated isolated meningioma nests around and at a distance from the tumor bulk. In addition, meningiomas also have a propensity to invade the surrounding dura, bone, and even the brain parenchyma, soft tissue and the skin. Borovich and colleagues⁵³ and Al-Mefty and colleagues¹³⁹ developed a concept of “grade zero removal” for convexity meningiomas, which denoted resection of a dural margin of 2 cm around the tumor in convexity meningiomas. The authors demonstrated a recurrence-free short-term survival; however, their mean follow-up duration was a modest 5.6 years. In addition, such a radical resection is possible only for some convexity meningiomas. The anatomic location of meningioma influences the recurrence risk. Meningiomas that are difficult to resect totally are more likely to recur. However; the lack of prospect for a total resection is not a contraindication for surgery. A gross-total surgical resection is difficult or impossible in certain locations, and a mere subtotal resection or its combination with adjuvant therapies such as radiosurgery may also be an acceptable treatment strategy. As an example meningiomas of the cavernous sinus can rarely be resected totally.⁷⁴^–⁸⁰ However, the resection of the extracavernous portion of the tumor significantly alters the natural history of the tumor.^80,¹¹⁵ Symptomatic regrowth is observed in 10% of patients after gross total resection in 13.3% to 15% of the patients after resection of the intracavernous part.^74,^80,¹¹⁵

Alternative Strategies in Treatment

Poor surgical results, unacceptably high surgical morbidity in certain meningiomas, or high recurrence rate in others have induced a search for alternative treatment strategies. With current technology, radiosurgery has arisen as an effective, reliable, and safe treatment modality for meningiomas.^124,¹⁴⁰ The major limiting factors for radiosurgery are the size of the tumor and the radiation damage to neural structures in very close vicinity. The efficiency of gamma-knife radiosurgery is significantly worse for lesions larger than 3 cm in diameter, which results in a limitation. In current practice radiosurgery finds four indications: (1) Primary treatment option for small meningiomas; (2) as a part of combination treatment with surgery in localizations that pose high surgical risks, (3) to prevent or stop growth in residual meningiomas; and last but not least (4) treatment of recurrent meningiomas. Radiosurgery does not result in immediate shrinkage of meningiomas; therefore, favorable outcome is expressed in “tumor growth control rates.” Very high tumor growth control rates are reported in the literature. In a large recent study by Kondziolka and colleagues,¹²⁴ which involved 972 patients with intracranial meningiomas, an overall growth control rate of 93% was reported for intracranial WHO grade I meningiomas at a median follow-up of 4 years. The outcomes in WHO grade II and III meningiomas are worse, with 50% and 17% tumor growth control rates, respectively.¹²⁴ The results of gamma-knife surgery are certainly very promising; however, even the largest studies are plagued by small cohorts and short follow-up durations to draw definitive conclusions on efficiency and safety. But we must express again that gamma-knife radiosurgery has provided one of the most significant advancements in the treatment of intracranial meningiomas.

Treatment of cavernous sinus meningiomas is a striking example to the change in treatment protocols. Popularization of skull-base surgery in the 1990s made surgery of cavernous sinus meningiomas possible. Initial reports in the CT era indicated very high total resection rates, however, at the expense of very significant cranial nerve morbidity even in the hands of master surgeons. Use of MRI for postoperative evaluation made it clear that the surgical results were in fact not so brilliant. Again, in the second half of the 1990s, encouraging reports of successful use of gamma-knife radiosurgery in small cavernous sinus meningiomas appeared in the neurosurgical literature.¹¹⁷ However, the efficacy of the gamma-knife was limited by the size of the tumor. These observations led our clinic to an alternative approach of resecting the extracavernous portion of cavernous sinus meningiomas and treating the intracavernous portion with the gamma-knife.¹¹⁶

Conventional radiotherapy and chemotherapy are still used in meningioma treatment, especially in recurrent or inoperable meningiomas.¹⁴¹ In certain cases, such as optic nerve sheath meningiomas, conventional radiotherapy or radiosurgery is the first-line treatment.¹¹⁴ Radiosurgery is also an effective and safe primary treatment option in small meningiomas that have a high morbidity risk, such as small cavernous sinus meningiomas.^116,¹²⁴ In the majority of cases, however, the high complication rate and the seriousness of the side effects of radiation treatment and the low efficiency of chemotherapy exclude them as first-line treatment for meningiomas.

OPERATIVE RISKS

Surgical treatment of meningiomas is associated with a risk mortality and morbidity. With the advent of microsurgery the mortality and morbidity have decreased significantly. In certain cases, the risk of neurologic or medical complications is higher than in the general population. This risk is pronounced in elderly patients and in patients with recurrent tumors.

Age and Medical Condition of the Patient

Surgical decision making in meningiomas is far more difficult in the elderly than in the younger population. There are several factors that blend into this problem: The prevalence, size, and multiplicity of meningiomas increase with age. The incidence of intracranial tumors steadily increases with age and reaches its peak in the 8th decade. This is especially true for meningiomas. The likelihood of a meningioma remaining asymptomatic also increases with age.⁷ To complicate the matters even more, the world population is aging, which results in a steady increase in the elderly population. The decision to treat cannot be made as easily as in a young and symptomatic patient.

Although old age is not a contraindication for surgery, the outcome of meningioma surgery in the elderly is less satisfactory and the complication rate is higher than in younger patients. Yano and colleagues ¹⁶ reported their experience with a large cohort of meningioma patients consisting of 603 asymptomatic and 831 symptomatic meningiomas. When 213 surgically treated asymptomatic meningiomas were considered, a perioperative morbidity of 4.4% was observed in patients younger than 70 years and 9.1% in patients older than 70 years. Bateman and colleagues¹⁴² reported surgical results of meningioma resection in 8861 patients, and 26% of their cases were 70 years or older. These authors indicated a five times higher mortality (1.4% vs. 7%) in patients older than 80 years when compared to those between 50 and 59 years and also a five times higher morbidity in patients who were older than 70 years.¹⁴² A summary of articles on the outcome of surgery for meningiomas in the elderly is provided in Table 18-3. Well over a thousand cases have been reported in the literature, and most studies concluded that poor preoperative general health and severe neurologic findings, large tumor size, critical locations, and marked peritumoral edema were indicators of poor outcome.^142–150,¹⁵²^–¹⁵⁹ Preoperative health was assessed with the American Society of Anesthesiology (ASA) classification scheme and functionality with the Karnofsky performance scoring. ASA classes of 3 and 4 and KPS of 60 or less were associated with higher mortality and morbidity. Interestingly, female sex was also associated with poor outcome in several studies.¹⁵⁸ In patients with good functional status and no associated systemic morbidity surgery is a safe and effective treatment.

TABLE 18-3 Operative mortality and morbidity in elderly meningioma patients

Recurrent Tumors

The surgical outcome in a recurrent meningioma is worse than at the initial presentation. Meningiomas grow epi-arachnoidally, which creates a plane of safe dissection between the tumor and the surrounding neurovascular structures at surgery. These planes are disrupted during initial surgery and this increases the risk of adherence or infiltration of surrounding neurovascular structures. Therefore the risk of surgical complications is higher and the probability of a gross total resection is lower in recurrent cases. Nevertheless, in benign tumors such as meningiomas, surgery provides an option of tumor debulking and can prolong and increase the quality of life of the patient. Radiosurgery and radiotherapy are more deliberately and preferentially used at the time of recurrence than at initial presentation.

PREFERENCE OF THE PATIENT

As noted in the preceding text, the management strategy in meningiomas focuses on the patient and is aimed at keeping the patient fully functional and providing long-term relief from or preventing intracranial tumor growth–associated problems. In an age where the technology overshadows the humanitarian side of medicine, the surgeon can easily be tempted by the ideal of treating the MRI rather than the disease. A quick tour of the existing literature on meningiomas will reveal that there is very little written on natural history or the outcome. Owing to the lack of systematically collected, objective evidence much of our practice is based on the available dogma and expert opinions. Therefore it is a significant challenge for the treating physician to decide on the treatment option that he or she will offer to the patient.

The diagnosis of an intracranial tumor is a significant psychological burden for the patient.¹⁶⁰ Immediately after diagnosis the patient will go through questions as: What is this thing in my head? What is the risk that it will grow? How fast will it grow? What will it cause? Will I die or become crippled? Is there any treatment? What are the treatment options? Can it be operated on? Will the surgery get rid of the tumor? Will it grow again? If it does so, how fast will it grow again? Will I have any options then? What are the risks of surgery? What if I don’t want to be operated? Often, the experienced surgeon does not have all the answers either. Therefore, when possible, the treatment decision must be taken together with the patient. The discussion with the patient related to informed consent should include a brief description of the natural history of the condition and its presumed course without treatment and the treatment alternatives, with their possible complications and benefits. Every patient has a different potential of understanding the proposed treatment and its risks, but it is he or she who will live through the treatment and afterwards; therefore the surgeon should make every attempt to empathetically share his or her thoughts with the patient.