Acoustic neurinoma (vestibular schwannoma)

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NERVE SHEATH TUMORS

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Acoustic neurinoma (vestibular schwannoma) Andrew H. Kaye, Robert J. S. Briggs, and Andrew P. Morokoff

Epidemiology Incidence and prevalence of tumor Acoustic neurinomas (vestibular schwannomas) account for approximately 6–8% of all primary intracranial tumors, and are responsible for about 78% of lesions developing within the cerebellopontine angle (Cushing 1932; Revilla 1947). However, the percentage differs considerably in more recent series, due probably to variations in the referral base. Tumors are bilateral in around 4–5% of cases. With one exception, there have been no large studies to determine the incidence of acoustic neurinoma in a welldefined geographic population. Tos et al (1992a) have estimated an annual detection rate of 9.4 tumors per year per million inhabitants of Denmark. This is much lower than estimates based upon anatomic studies of autopsy material. Hardy & Crowe (1936) found six minute and asymptomatic schwannomas in a study of 250 temporal bones, an incidence of 2.4%. In a similar study, Leonard and Talbot (1970) suggested an incidence of around 1.7%. However, postmortem studies may have overestimated the true incidence of this condition. The fact that audiometry was available in the cadavers studied, and that the specimens were not consecutive, suggests that the material may have been biased to temporal bones with associated pre-existing hearing disorders. In a more recent and unselected post-mortem study of 298 temporal bones, Karjalainen et al (1984) found no occult neurinomas. In a clinical series of 9176 patients investigated for otoneurologic disorders, only 0.76% were found to harbor a cerebellopontine angle tumor, some of which were acoustic neurinomas (Guyot et al 1992). Whatever the true incidence of the condition, the disparity between clinical and pathologic studies does suggest that a substantial number of lesions remain asymptomatic or undiagnosed and that occult neurinomas may follow a benign course (Brackmann & Kwartler 1990a). An increase in the number of tumors treated in the last decade is more likely to represent better awareness of the condition and earlier diagnosis associated with improved imaging modalities, than to suggest a true increase in the prevalence of the disease (Glasscock et al 1987; Tos et al 1992a).

Growth rate The natural history of acoustic neurinomas is variable, and is reflected in marked differences in the duration of 518

symptoms at the time of presentation. Usually such tumors are slow-growing. In some series, around 40% of tumors treated conservatively did not enlarge at all, or even regressed over the period of observation (Luetje et al 1988; Valvassori & Guzman 1989; Thomsen & Tos 1990; Selesnick & Johnson 1998). On average, lesion diameter will increase at a rate of <2 mm per year in around 78% of patients (Nedzelski et al 1992). In other instances, the rate of growth is more rapid, at between 2.5 and 4 mm per year (Wazen et al 1985; Laasonen & Troupp 1986). The rate of expansion may however, be considerably slower in the elderly, where a mean enlargement of 1.4 mm per year has been reported (Sterkers et al 1992). This is in contrast to a study by Valvassori and Guzman (1989), who concluded that there is no correlation between the rate of tumor growth and patient age. Yet there does exist an inverse relationship between age and tumor size at presentation. Large tumors are significantly more common in the younger age groups (Thomsen et al 1992). It has been reported that the future behavior of a tumor can be predicted radiologically within a relatively short period of observation. A pattern of slow or absent growth over a period of 18 months to 3 years makes it unlikely that subsequent enlargement will be significant (Nedzelski et al 1992). Valvassori and Guzman (1989) reached a similar conclusion in a study of 35 patients managed expectantly. Any further growth was evident usually within the first year. On the other hand, Noren and Greitz (1992) studied 98 tumors in 93 patients over a period of 12–183 months and observed that 66% of tumors increased in size over 1–2 years, that 86% enlarged when observed for 3–4 years, but that 100% had expanded if follow-up was continued for >4 years. It appears that some tumors may demonstrate significant growth after an initial period of quiescence. Charabi and co-workers (1998) reported a group of 23 patients with acoustic neurinoma: initially no growth was demonstrated for a mean duration of 1.6 years, followed by a period of tumor growth with a mean growth rate of 0.48 cm per year (Charabi et al 1995). In a more recent report on the follow-up of a series of 123 patients observed in Denmark, by the end of a prolonged observation period (mean 3.8 years) tumor growth was observed in 82%, no growth in 12%, and negative growth in 6% of tumors. Flow cytometric studies have confirmed a variable mitotic rate in acoustic neurinomas, and have shown that this correlates clinically with the speed of tumor growth (Wennerberg & Mercke 1989). DNA cytofluorometric

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Age distribution Acoustic neurinomas occur most frequently in middle age. In a series of 1113 cases reported by the House group, approximately 50% of patients were in either their 5th or 6th decades, and only 15% of tumors developed in people under the age of 30 (Fig. 28.1). Acoustic neurinomas that develop in patients suffering from neurofibromatosis type 2 tend to present earlier, with a peak incidence around the 3rd decade (Revilla 1947; Eldridge 1981; Evans et al 1992a). It is very rare for acoustic neurinomas to develop in children, except in those who have neurofibromatosis type 2 (Allcutt et al 1991). The youngest recorded patient was 12 months of age (Fabiani et al 1975). Presentation often occurs late in children because unilateral deafness may be overlooked (Allcutt et al 1991). An association between acoustic neurinoma, salivary gland tumors, and childhood cranial irradiation has been reported (Shore-Freedman et al 1983).

Sex distribution Cumulative results from large series in the literature show a consistent preponderance of tumors in women; women are affected in around 57%, and men in 43% of cases (Fig. 28.2).

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30

20 % of cases

analysis has been used also to establish the proportion of cells in the S-phase of the cell cycle, but this is not linked to tumor size, or to the duration of symptoms at the time of presentation (Rasmussen et al 1984). These data are supported by the results of clinical studies, which have shown no statistical correlation between tumor size at diagnosis and the rate of subsequent growth (Nedzelski et al 1992). Large tumors do not necessarily grow faster than smaller ones. Factors other than mitotic activity which govern the rate of expansion of these lesions include hemorrhage, cystic degeneration, and peritumoral edema. Any of these may, on occasion, result in precipitate enlargement of the tumor (Nager 1969; Lee & Wang 1989). A hormone closely related closely to bovine pituitary growth factor may play a role in Schwann cell proliferation in acoustic neurinoma (Brockes et al 1986). Other hormone receptors have also been identified in a varying proportion of tumors. Estrogen and progesterone receptors are among them, although neither of these is thought to govern growth behavior, despite a female preponderance of tumors (Markwalder et al 1986; Whittle et al 1987). Estrogen binding receptors are present in 45% of male and 48% of female neurinomas (Martuza et al 1981). There are, however, reports of an increase in size and vascularity of tumors in women, particularly during pregnancy (Allen et al 1974). Recent evidence suggests that a variety of tumors may secrete their own (‘autocrine’) growth factors, which bind to specific receptors on the cell membrane and stimulate it to traverse the cell cycle more quickly (for review, see Rutka et al 1990). The growth rate of bilateral tumors is also very variable, but is on average considerably faster than for unilateral lesions (Kasantikul et al 1980a). However, it is uncertain whether this reflects a different biology for these neoplasms, or the fact that they occur in a younger patient population – a sub-group already known to exhibit a more rapid rate of growth (Graham & Sataloff 1984).

Acoustic neurinoma (vestibular schwannoma)

10

0

<20

21–30

31–40

41–50 51–60 Age (years)

61–70

>70

Figure 28.1  Age distribution of a cumulative series of 1113 cases of acoustic neurinoma.

Female 56.8% Male 43.2%

Figure 28.2  Distribution of tumors by sex.

This is not true of tumors in childhood, however, where an equal sex distribution is seen (Hermanz-Schulman et al 1986). A difference in the age distribution of tumors between the sexes was noted by Borcck and Zülch (1951). Men had an earlier peak prevalence (36–42 years) than women (42– 56 years), although this finding has not been confirmed by later work.

Racial, national, and geographic considerations There have, to date, been no large multinational studies to determine demographic factors relating to acoustic neurinoma. However, the proportion which these tumors contribute to the total number of primary intracranial neoplasms varies considerably in different populations. Unfortunately, this does not provide a complete profile of the condition because it depends also on the prevalence of other primary tumors. The incidence of acoustic neurinoma appears to be greatest in the Far East, where they account for 10.6% of primary intracranial neoplasms in India (Dastur et al 1968) and 10.2% of those occurring in China (Huang et al 1982). In the Middle East, a 9% incidence is found in Egypt (Sorour et al 1973). Rates of 4.9% and 4% are reported in England (Barker et al 1976) and the USA, respectively (Kurland et al 1982). The lowest incidence is found in African negroes, figures of 2.6% being recorded in Kenya (Ruberti & Poppi 1971), 0.9% in Nigeria (Adeloye 1979), and 0.5% in what 519



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was formerly Rhodesia. The latter can be contrasted with a 3.7% incidence in the white population of the same country (Levy & Auchterlonie 1975). Misdiagnosis may, however, play some part in the low incidence rates reported in Africans. With the use of immunohistochemical markers, Simpson et al (1990) established that some acoustic neurinomas had been misdiagnosed as meningiomas and they concluded that the true incidence in black South Africans was 3.7%. In our experience acoustic neurinomas are very uncommon in negroes, and few if any such families have ever been documented to develop bilateral forms of the disease. Although we are not aware of any studies on social factors, the condition appears to be more common in middle than lower social classes. This may be because the latter are less likely to seek medical attention for relatively minor symptoms.

Genetic factors Acoustic neurinomas occur in both sporadic and hereditary forms. The vast majority (96%) of tumors are sporadic and unilateral. Hereditary acoustic neurinomas are associated with the condition known as NF-2 (bilateral acoustic neurinomas; central neurofibromatosis). NF-2 was first described in 1822 by the Scottish surgeon Wishart, but bilateral acoustic neurinoma was for a long time regarded as a central form of von Recklinghausen’s disease (NF-1). Cushing considered them part of the same disease, however, the two conditions are now known to be distinct in all aspects, clinically and genetically (Kanter et al 1980). NF-1 is much more common than NF-2, and has an incidence of 1/4000 population (Korf 1990). It is characterized by widespread neurofibromas occurring both intra- and extracranially as well as gliomas and other lesions and the NF-1 gene has been localized to chromosome 17 (Barker et al 1987). It is now recognized that there is no increased incidence of schwannomas in NF-1 (Holt 1978; Huson et al 1988) and bilateral tumors are exceptionally rare (Rubenstein 1986). NF-2 is much more uncommon than NF-1 and has an incidence of about 1 in 33 000–50 000 individuals (Evans et al 2000). The disease is transmitted in an autosomal dominant fashion with high penetrance. The spontaneous mutation rate of the NF-2 gene is high, at around 50% and the hereditary picture is complicated by the high incidence of mosaicism. Bilateral acoustic neurinomas are pathognomonic of this condition, but are not fully penetrant. Other cranial and spinal tumors may also develop. The mean age at onset of symptoms is 22 years, and at diagnosis 28 years. The age at onset of symptoms is significantly younger in maternally than paternally affected cases (18.2 vs 24.5 years). The natural history of NF-2 is variable, and males may sometimes have a milder form of the disease than that which is seen in females. Café-au-lait patches are found in 41% of patients, and presenile lens opacity or subcapsular cataract in 38%. As well as bilateral acoustic neurinomas, the definition of NF-2 also encompasses individuals who have a 1st degree relative suffering from the condition and who have either a unilateral acoustic neurinoma or two of the following: a neurofibroma or schwannoma, meningioma, glioma, or juvenile posterior subcapsular lenticular opacity. 520

The acoustic neurinomas do not always develop simultaneously, although this is usual. A span of a few months or several years may at times separate them.

The NF-2 gene and Merlin protein By examining tissue from sporadic tumors, loss of parts of chromosome 22 was recognized early on as a common cytogenetic marker for schwannoma (Seizinger et al 1986) and this was subsequently confirmed by genetic linkage analysis in bilateral acoustic schwannoma patients (Rouleau et al 1987). The chromosome 22 region had previously been found to be abnormal in meningiomas as well (Zang, 1982) and appeared to be commonly mutated in schwannomas, neurofibromas and meningiomas (Seizinger et al 1987b; Jacoby et al 1990; Fontaine et al 1991; Twist et al 1994). Thus, NF-2 associated tumors occur throughout the classic Knudsen ‘two-hit’ mechanism, whereby a mutation in the second NF-2 allele, on a background of inherited NF-2 gene mutation, leads to abnormalities of both copies of NF-2. The human NF-2 gene located at chromosome 22q12.2 was cloned in 1993 (Rouleau et al 1993; Trofatter et al 1993) and found to have 17 exons encoding a 595 amino acid protein with homology to the Ezrin, Radixin, and Moesin (ERM) superfamily of proteins. The NF-2 gene product was therefore named Merlin (Moesin Ezrin Radixin-like protein) or alternatively, Schwannomin. Alternate splicing of exon 16 which codes for the C-terminus gives rise to two isoforms of Merlin. Isoform 1 is 595 amino acids long, whereas isoform 2 is 590 amino acids long (Bianchi et al 1995). Isoform 1 appears to be the active tumor-suppressing variant and is able to adopt a closed conformation (Sherman et al 1997). Proteins within the ERM family have a highly conserved amino-terminal region known as the FERM domain (F for 4.1 protein, E for Ezrin, R for Radixin, and M for Moesin) (Chishti et al 1998). The FERM domain forms a 3-part cloverleaf structure that is able to coordinate multiple protein binding partners (McClatchey et al 2009). The second part of the protein consists of a long alpha helical region, followed by a C-terminus, which is less highly conserved (Fig. 28.3). A common feature of proteins having a FERM domain appears to be their involvement in linking the cytoskeleton to the plasma membrane and this appears to be true for Merlin as well. Even although it can be well expected that many regulatory mechanisms applicable to ERM proteins will overlap with those acting on Merlin, in fact none of the ERM proteins, unlike Merlin, have been implicated in a tumor suppressor syndrome and that ERM protein levels are often normal in NF-2 related tumors (Stemmer-Rachamimov et al 1997). Merlin and cell proliferation Because it was frequently lost in tumors, the NF-2 gene was suspected early of being a tumor suppressor gene and its protein product, Merlin, was confirmed initially to have a negative effect on cell proliferation, possibly by an anti-Ras action (Tikoo et al 1994; Lutchman et al 1995; Pelton et al 1998). Loss of Merlin has also been linked to cell transformation (Kissil et al 2002). It has been difficult to develop robust cell models for Merlin for a number of reasons, especially because its anti-proliferative action means that establishing



Acoustic neurinoma (vestibular schwannoma) FERM domain

alpha helical domain

c-homology box 831

1

Protein 4.1 1

1115 4.1B/dal1

1

575 Moesin

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P

585 Ezrin

1

583 Radixin

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595 isoform 1 Merlin/NF-2 590 isoform 2

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CD44, CD43 ICAM-1, ICAM-2 Membrane

C

N

Merlin

B

C ERM

N

Merlin

N N ERM

Rho

C

C Actin

β2-spectrin

Figure 28.3  (A) Schematic of the protein band 4.1 superfamily. The structural domains of six members of the family are depicted. Each has a common, conserved N-terminal FERM domain (yellow) and a more centrally located alpha helical domain of unknown function (orange). Merlin, ezrin, and radixin have a proline-rich segment (blue) which may possibly interact with SH3 domain proteins. The C-termini of protein 4.1 and 4.1B/dal 1 are conserved (pink), as are the C-termini of moesin, ezrin, and radixin (green). The two isoforms of Merlin are depicted. (B) A putative interaction model of Merlin associations. The isoform 1 of Merlin is thought to be able to switch between an open and closed state, which is in turn thought to enable its association with other cellular proteins. Stimulated, perhaps, by input from the Rho kinase and secondary messenger pathways, Merlin ‘flips’ to the open conformation similar to the ERM proteins and thence interacts with the ERM proteins and components of the cytoskeleton and integral membrane receptors.

cell lines with stable Merlin expression is problematic. However, in recent years a number of lines of evidence have slowly built up a coherent picture of the normal function of Merlin, and why loss of function leads to deregulated cell growth and tumorigenesis. For example, Merlin has been shown to downregulate Ras and Rac (Jin et al 2006), inhibit the PI3 kinase pathway by binding to PI3 kinase enhancer long (PIKE-L) (Rong et al 2004b) and decrease STAT function via binding to hepatocyte-growth factor receptor tyrosine kinase substrate (HRS), a molecule which also traffics

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growth factor receptors to the degradation pathway (Scoles et al 2002). Merlin also appears to downregulate NF-kappaB activity and to have an anti-apoptotic effect (Utermark et al 2005; Kim et al 2002). The epithelial growth factor receptor family are an important group of membrane growth factors that includes EGFR (ErbB1), ErbB2 and ErbB3. ErbB2 and ErbB3 and their growth factor ligand neuregulin (NRG), are critical in the proliferation of Schwann cells during development and myelinogenesis where the receptors are activated in response to NRG production by axons (Simons et al 2007). Recently, Merlin has been shown to downregulate ErbB2/3 function and thereby decrease activation of the MAPK pathway, probably by limiting the availability of these receptors at the cell membrane (Lallemand et al 2009). Neuregulin, ErbB2 and ErbB3 expression levels and phosphorylation status have been reported to be increased in schwannomas (Hansen et al 2004) and may confer radio-resistance (Hansen et al 2008). Furthermore, ErbB inhibitors are capable of reducing schwannoma cell proliferation in vitro (Hansen et al 2006; Clark et al 2008) prompting some groups to point to this pathway as a potential target for molecular therapy in schwannomas (Stonecypher et al 2006; Doherty et al 2008). Merlin also downregulates EGFR (Curto et al 2007) as well as other growth factors such insulin-like growth factor-1 receptor (IGF1R) and platelet-derived growth factor receptor (PDGFR) (Lallemand et al 2009). In addition, the degradation of PDGFR is increased by Merlin (Fraenzer et al 2003). Merlin: role in cytoskeletal organization An important realization in the last few years has been that, although it is a moderate suppressor of cell proliferation, the more important tumor-suppressor function of Merlin is its role in membrane organization and cell contact inhibition. In fact, this property makes it unique among tumor suppressor genes. Contact inhibition of growth is a feature of cells that grow to confluence and is mediated by cell-cell protein complexes known as adherens junctions that contain cadherins, and function to limit proliferation once a solid cell sheet has been formed. Cells grown on ECM under subconfluent conditions on the other hand, as well as tumor cells, form multiple focal contacts that help the cell to migrate. The migration is achieved by the cell making actin-rich protrusions at its leading edge called lamellipodia. Focal contacts involve the proteins β-integrins, focal adhesion kinase (FAK) and paxillin. Multiple lines of evidence implicate Merlin in the adhesive cytoskeleton organization of the Schwann cell. Merlin is found is the actin-rich cell protrusions such as lamellipodia and membrane ruffles (GonzalezAgosti et al 1996; Schmucker et al 1997) as well as in cell-cell and cell-matrix contacts which are formed by focal adhesion and focal contact proteins respectively (Fernandez-Valle et al 2002; Lallemand et al 2003). Loss of Merlin can result in loss of contact inhibition, a more spread out shape and more adhesion and motility along the extracellular matrix – all features which can be reversed upon re-expression of the protein (Gutmann et al 1999; Bashour et al 2002). Schwannoma cells are known to have increased adhesion via activation of integrins α6, β1 and β4 and Schwann cells that lack Merlin have increased numbers of focal contacts, allowing them to adhere more strongly to extracellular 521



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matrix and presumably migrate abnormally (Utermark et al 2003). The FERM domain of Merlin can also bind the membrane glycoproteins CD43 and CD44. During growth arrest and when cells become confluent, Merlin exists in a complex with CD44 and the other ERM proteins (Morrison et al 2001) and is able to negatively regulate CD44 binding to hyaluronan, thus reducing ECM adhesion (Bai et al 2007). Merlin is also able to bind other proteins involved in cell adhesion such as Na+/H+ exchanger regulatory factor-1 and 2 (NHERF1/2), FAK, paxillin and β1-integrin (StemmerRachamimov et al 2001; Poulikakos et al 2006; Obremski et al 1998; Fernandez-Valle et al 2002). Additionally, Merlin coordinates the downregulation of EGFR with contact inhibition by sequestering EGFR into a non-signaling membrane compartment (Curto et al 2007). The adaptor PDZ domain containing protein Erbin, has been found to be a possible link between Merlin, the adherens junction and MAPK activation as well (Rangwala et al 2005). Unlike the other ERM proteins which contain an actinbinding site in their C-terminus, the N-terminus of Merlin is able to directly bind F-actin, the key component of the cytoskeleton, albeit somewhat more weakly than the other members of the ERM family (James et al 2001). Merlin also binds and thereby inhibits N-WASP (Wiskott–Aldrich Syndrome Protein), which polymerizes actin via Arp2/3 (Manchanda et al 2005).Thus, Merlin is probably involved in stabilization of the cytoskeleton, but it is not entirely clear what role it plays. The C-terminus of Merlin can fold back on itself (selfassociate) and block both the N-terminal (FERM) and C-terminal binding sites. In ERM proteins, this selfassociation appears to switch off the function of the protein, whereas current evidence suggests that the tumor-suppressor function of Merlin is active in the closed conformation, although this is somewhat controversial (McClatchey et al 2005). It is notable that most NF-2 missense mutations affect exon 2, causing protein substitution in the FERM domain, which is likely to disrupt this self-association (Okada et al 2007). Merlin has a tyrosine phosphorylation site (T230) as well as a serine phosphorylation site (S518) in its C-terminus, the latter of which plays a critical role in its function. Phosphorylation of Merlin appears to keep the protein in an open (growth permissive) state, whereas when dephosphorylated it can self-associate and become closed (Rong et al 2004a). In this respect, Merlin is the opposite of the other ERM proteins. The Rho family of GTPases (Rho, Rac and cdc42) which are critical membrane-cytoskeletal regulatory molecules that promote focal contact formation upon integrin binding, appear to be prominently involved in the function and activation of Merlin. Merlin is phosphorylated at S518 by p21activated kinase (PAK1) which is a downstream effector of Rac and cdc42 (Sherman et al 1997; Xiao et al 2002; Kissil et al 2003; Alfthan et al 2004). Furthermore, Merlin participates in a negative feedback loop with Rac, PAK1 and PI3K (Shaw et al 2001; Kaempchen et al 2003; Kissil et al 2003; Hirokawa et al 2004; Okada et al 2007) and thus when Merlin is lost or phosphorylated, Rac is activated at the cell membrane, promoting increased membrane ruffling and immature adherens junctions (Flaiz et al 2007; Lallemand 522

et al 2003). In addition, Merlin can be phosphorylated by protein kinase A (PKA) in response to NRG binding to ErbB2/ ErbB3 (Alfthan et al 2004; Thaxton et al 2008) and by PI3Kinase (Ye, 2007; Okada et al 2009). On the other hand, increase in dephosphorylated Merlin is necessary for cells undergoing growth arrest and contact inhibition (Shaw et al 1998b). Merlin is dephosphorylated by myosin phosphatase (MYPT-1-PP1δ). For example, hyaluronan binding by CD44 and adherens junction formation can both activate MYPT1 which dephosphorylates Merlin leading to an accumulation of the growth-suppressing closed form (Okada et al 2007). The MYPT inhibitor protein CPI-17, has also been shown to participate in tumorigenesis by promoting phosphorylation of Merlin (Jin et al 2006). Overall, Merlin appears to be a key regulator of contactmediated inhibition of cell proliferation, as well as ECM adhesion. This may explain why schwannoma cells that lack functional Merlin continue to grow despite confluent cell density and form a ‘pseudomesaxon’ in which the cells wrap around the perineural extracellular matrix rather than properly myelinate the axon (Dickersin 1987). Overall Merlin is known to bind over 30 different proteins (Scoles 2008), not all of which are fully understood in terms of its cellular function, but these are slowly being elucidated. A better understanding of these pathways might highlight areas for targeted molecular drug therapy for schwannomas in the future.

Mouse models of NF-2 Insights into the cell-specific function, and possible role in tumorigenesis of the NF-2 gene have been obtained from knockout mouse models developed in recent years. These models have shown that NF-2/Merlin is essential for normal embryonic development. Mice that are NF-2 −/− die prior to gastrulation due to lack of development of extra-embryonic structures that are required for mesoderm formation (McClatchey et al 2005) During development, NF-2 expression appears to be upregulated during the final stages of tissue fusion after cell-cell adhesion has been established, at the time of neural tube closure and in migratory neural crest cells (Akhmametyeva et al 2006). Merlin seems to play an essential role in tissue adherence and fusion, especially in the nervous system, which is consistent with its role in stabilizing cell-cell adherens junctions (Lallemand et al 2003). In contrast to the narrow spectrum of benign tumors in NF-2 patients, NF-2 heterozygous mice (NF2 +/–) develop a variety of malignant tumors, mainly osteosarcomas, fibrosarcomas and liver carcinomas, that display additional loss of the wild type allele (McClatchey et al 1998). There is a lower incidence of other tumors in these heterozygous mice, as well as increased sensitivity to asbestos, but they do not develop the classical features of NF-2. However, when both alleles of NF-2 are conditionally knocked-out in Schwann cells and neural crest cells using the flox-cre system in mice, schwannomas, Schwann cell hyperplasia, cataracts and cerebral calcifications do occur (Giovannini et al 2000) suggesting that there is an insufficient rate of second NF-2 allele mutation in the heterozygous mouse models compared to that in human NF-2 patients. Similarly, when NF-2 is knocked out in arachnoid cells in mice, different subtypes of meningiomas develop (Kalamarides et al 2002).



An important distinction, however, is that the schwannomas in these mouse models of NF-2 do not have a predilection for the vestibular nerve. The schwannomas also tend to behave more aggressively in mice (Stemmer-Rachamimov et al 2004). Two possible explanations as to why mouse models differ from human schwannomas include differences in the background expression of Merlin binding partners between mouse and human tissues, and differences in the timing of Merlin mutations. The fact that mice in the animal models develop tumors later in life suggest another mutant ‘hit’ is occurring in addition to the wild type NF-2 allele, however no additional genetic or epigenetic events have been found in tumors in NF-2 patients. A recent report demonstrated that NF-2 −/− glial cells result in upregulated Src, FAK and paxillin activity and that ErbB2 inhibition can reduce the effects of Merlin loss on proliferation (Houshmandi et al 2009). Although these models are instructive, further work needs to be done to understand and develop models more accurately representing acoustic schwannomas and NF-2.

Molecular alterations in schwannomas Most sporadically occurring schwannomas have bi-allelic loss of NF-2 (Stemmer-Rachamimov et al 1997) as well as many meningiomas and also sporadic mesotheliomas of the lung associated with asbestos exposure (Bianchi et al 1995), thyroid carcinoma, hepatocellular carcinoma cell lines and perineural tumors, suggesting a common role in tumorigenesis. Missense mutations in the NF-2 gene occur at an extremely low frequency, with nearly all the mutations being nonsense, frameshift, or splice site mutations that would all lead to the production of N-terminally truncated Merlin. Strikingly, truncated Merlin species are rarely detected in primary tumor samples, suggesting that mutant Merlin proteins are unstable and actively degraded. In one study mutation of both NF-2 alleles occurred in 65% of sporadic schwannomas with a relatively high frequency of mosaicism within the tumors themselves (Mohyuddin et al 2002). It has now become apparent that attempts to correlate NF-2-gene mutation frequency with NF-2-associated tumor types only provides an incomplete picture of Merlin involvement in these tumors. Even although genetic loss of NF-2 material is not found in all schwannomas, loss of expression of Merlin has been reported in 100% of tumors (Stemmer-Rachamimov et al 1997). Similarly, Merlin protein is also reduced or absent in most sporadically occurring meningiomas, schwannomas, and ependymomas (Kimura et al 1998; Gutmann 1997; Lee 1997). This suggests that there are frequent posttranslational mechanisms downregulating Merlin expression in these tumors. As discussed above, phosphorylation of Merlin at its S518 site is an important physiological mechanism to switch off the growth suppression activity of the protein and lending support to this, increased levels of phosphorylated Merlin have been found in schwannomas (Cai et al 2008; Wang et al 2009). Cleavage by calpain has been proposed as another possibly important mechanism of Merlin downregulation (Kimura et al 1998; Kaneko 2001). It is likely that other gene or protein alterations are involved in schwannoma formation besides NF-2/Merlin

Acoustic neurinoma (vestibular schwannoma)

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alone. Micro-array cDNA analysis has been used to screen the differential expression of genes in schwannomas and cultured Schwann cells and found altered regulation of 41 genes, 13 of which were confirmed after real-time PCR analysis (Hanemann et al 2006). Some of these genes play a role in other types of tumors and warrant further investigation in schwannoma molecular pathogenesis. Vestibular schwannomas are also a component of the Carney complex – a unique multiple endocrine neoplasia syndrome comprising myxomas, spotty pigmentation, and endocrine overactivity (Carney et al 1985, 1986; Mansell et al 1991). This syndrome is usually sporadic, although autosomal dominant inheritance has been reported (Carney et al 1986). Interestingly, mutations in the protein kinase A1α regulatory sub-unit (PRKAR1A) gene have been found in these tumors (Boikos et al 2006) and Protein Kinase A is one of the major proteins interacting with Merlin (phosphorylating it at the C-terminus), suggesting that mutations in other parts of the molecular signalling pathway that involves Merlin could lead to the development of schwannomas. Much work still needs to be done to elucidate fully the function of Merlin and how it promotes schwannoma formation, but a clearer picture of this fascinating tumor-suppressor molecule has been slowly emerging in recent years. Better understanding may lead to the development of novel targeted therapies for schwannoma and NF-2, directed at one or more of the molecules described.

Sites of predilection Acoustic neurinomas are thought to arise at the point where glial (central) nerve sheaths are replaced by those of Schwann (peripheral) cells and fibroblasts. This transition (the Obersteiner–Redlich zone) is located usually within the internal auditory canal. The variability of this demarcation, however, means that some tumors arise laterally within the internal auditory meatus, while others lie entirely within the cerebellopontine angle (Neely & Hough 1986). It was at one time believed that tumors arose primarily from the superior vestibular nerve, but evidence now suggests an almost equal incidence of superior and inferior vestibular nerve lesions (Clemis et al 1986). Only rarely is the cochlear division involved (Bebin 1979). Clemis et al (1986) concluded that 50–60% of tumors arose from the superior vestibular nerve, 40–50% from the inferior vestibular nerve, and <10% from the cochlear nerve. Neurinomas can arise from other nerves within the temporal bone, and at times it may be impossible to determine their nerve of origin (Best 1968). The reason why this neoplasm should arise so frequently from the vestibular nerve is unknown, but it does contain an excess of the embryonic precursors of Schwann cells (SC) (Bebin 1979). It has been suggested that schwannomas express key markers of immature Schwann cells (Hung et al 2002) whereas other studies have observed dedifferentiation (Harrisingh et al 2004). SC precursors originate from the neural crest and migrate along peripheral and cranial nerves. During embryogenesis a genetically distinct, transient population of neral-crest derived cells known as boundary cap cells is formed that are thought to give rise to SC precursors and immature SC which go on to migrate along and myelinate nerve roots (Coulpier et al 2009; Maro et al 523



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2004). These boundary cap cells are situated at the margin between the CNS and PNS, where neurinomas are thought to arise (Feltri et al 2008). The question of whether schwannomas, like gliomas, may actually arise from a type of stem cell such as the boundary cap cells is, however, yet to be answered.

Presenting features Unilateral sensorineural hearing loss, tinnitus, and disequilibrium are the most common presenting symptoms, although only about 10% of patients with such features will be found on investigation to harbor an acoustic neurinoma (Valvassori & Potter 1982). The mode of presentation is dependent on tumor size, and whether or not early symptoms are overlooked. In the past four decades, there has been a steady increase in the proportion of small tumors detected and, therefore, a shift in the pattern of symptoms away from those due to mass effect (Symon et al 1989). The most common symptoms of acoustic neurinoma are unilateral sensorineural hearing loss (96%), unsteadiness (77%), tinnitus (71%), mastoid pain or otalgia (28%), headache (29%), facial numbness (7%), and diplopia (7%) (Hardy et al 1989a). Only around one-third of patients first seek medical attention for non-audiologic complaints (Hart et al 1983) and, at the time of presentation, only around 50% of patients will have objective neurologic findings other than from the 8th nerve. Unilateral or asymmetric sensorineural hearing loss is almost always the initial symptom, and has been present usually for a median of 1–3 years at the time of diagnosis (Johnson 1977). If hearing loss is neglected, however, there follows a ‘silent’ interval, usually of 1–4 years, although it may be much longer, while the tumor expands into the cerebellopontine angle cistern. Symptoms then ensue from compression of the cerebellum, adjacent cranial nerves, or brain stem. With lesions >4 cm, 58% of patients will exhibit cerebellar dysfunction, and 53% will have corneal or facial hypoesthesia (Thomsen et al 1983).

Hearing loss Patients with unilateral or bilateral asymmetric sensorineural deafness or with unexplained unilateral tinnitus should be investigated to exclude an acoustic neurinoma. Speech discrimination is typically affected more than the pure tone loss, and can cause difficulty when using the telephone. Loudness recruitment is uncommon. Although hearing loss is most often progressive, it can on occasion be sudden, due perhaps to compromise of the inner ear vasculature. The incidence of sudden hearing loss varies between series, but is around 10–20% (Sataloff et al 1985). Yet, of patients who present with sudden hearing loss, in only around 1% will the cause be found to be an acoustic neurinoma (Shaia & Sheehy 1976). More recent reports suggest that magnetic resonance imaging will detect acoustic neuromas in a greater number of patients who present with sudden hearing loss (Chaimoff et al 1999). Rarely, hearing loss fluctuates (Pensak et al 1985; Berg et al 1986). Only about 5% of patients with acoustic neurinoma will have normal hearing. This is more likely to occur if the tumor is very small, or if it is confined 524

to the cerebellopontine angle cistern and there is no significant intracanalicular component (Beck et al 1986). These tumors have been shown to present with balance disturbance or trigeminal or facial nerve dysfunction, headache, or unilateral subjective hearing difficulty (Lustig et al 1998). Delayed or missed diagnosis is more likely if the presentation is atypical, or if hearing loss is attributed by the patient to a specific event. It is particularly likely if the patient suffers already from a longstanding ear disorder such as Ménière’s disease. The other group likely to be missed is those with normal results in investigations which are almost always abnormal in cases of acoustic neurinoma (pure tone audiometry and auditory evoked brain stem responses, see below). Rarely, a cochlear rather than a retrocochlear pattern of hearing loss develops (Flood & Brightwell 1984).

Disequilibrium Disequilibrium and vertigo are common because the tumor origin is nearly always from the vestibular nerve. True paroxysmal vertigo is rare (6.3%) (Morrison 1975), and is only occasionally accompanied by nausea. The onset is not usually abrupt, as it is in Ménière’s disease, although 5% of acoustic neurinoma patients will give a history that would be accepted as typical of that condition. While mild chronic disequilibrium has often been present for some years before diagnosis, it is unusual for either ataxia or vertigo to be the presenting complaint. The reason why destruction of the vestibular nerve is not often disabling lies with the brain stem and contralateral vestibular apparatus, which compensate for the loss. The elderly, however, appear less well able to adapt to this change. Clinically, mild abnormalities of balance may be detected by Unterberger’s stepping test (Moffat et al 1989a). The patient is asked to stand upright with eyes closed, with the arms outstretched at 90° to the trunk, and then to mark time on the spot (i.e. to raise the legs alternately, bringing the thigh to a horizontal position). The result is positive if the patient deviates >50 cm from the spot, or rotates by >30° within 50 steps. The presence of severe ataxia more likely suggests that the patient has developed compression of the cerebellum, or has obstructive hydrocephalus secondary to distortion of the brain stem. Involvement of the cerebellum causes incoordination, primarily of the lower limbs, and a tendency for the patient to deviate to the side of the tumor. Brain stem compression may also involve the sensory and motor tracts, usually of the contralateral side.

Tinnitus Tinnitus is the presenting symptom in around 3% of patients (Wiegand & Fickel 1989), and is occasionally the sole manifestation of acoustic neurinoma. Preoperative tinnitus affects 57–83% of patients, but is troublesome in only 13–38% (Brow 1979; Wiegand & Fickel 1989). Symptoms are usually low-grade, constant, and confined to the affected ear. There is great variation in the type of sounds experienced.

Raised intracranial pressure Papilledema is almost exclusive to lesions >3 cm in diameter, and is present in around 7–15% of patients (Hardy et al



1989a; Boesen et al 1992). Large tumors displace the cerebellum and deform the brain stem, compressing the fourth ventricle or aqueduct. Associated features of spontaneous nystagmus, opticokinetic nystagmus, and trigeminal nerve dysfunction are significantly more common in patients with papilledema than in cases in which the tumor is of a comparable size but where swelling of the optic discs is absent (Boesen et al 1992). Very large tumors may result in herniation of the cerebellar tonsils.

Nystagmus Nystagmus may be spontaneous, positional (when the neck is hyperextended and the head turned to right or left), or opticokinetic (driven in response to an image slip on the retina from a rotating target). The latter may be evident if there is significant compression of the gaze center in the pons (Thomsen et al 1983). The most common type is unilateral labyrinthine nystagmus, which is evident as fine horizontal beats directed away from the side of the lesion. It is of peripheral vestibular origin, and is enhanced by abolition of ocular fixation using Frenzel’s glasses. In about 16% of patients, nystagmus will be of Bruns type, which is indicative of a large tumor producing significant brain stem distortion. It comprises bidirectional nystagmus with a coarse gazeevoked nystagmus on looking to the ipsilateral side and a high frequency small amplitude vestibular nystagmus on looking to the contralateral side (Croxson et al 1988). Electronystagmography will demonstrate impaired vestibular function in over 80% of cases, but this is a non-specific finding and, therefore, of limited diagnostic value.

Cranial nerve palsy Trigeminal nerve involvement manifests usually as corneal or lower facial hypoesthesia. Only rarely is the whole face affected, and the motor division is spared. Facial weakness is uncommon, and is almost exclusive to large tumors (Portmann & Sterkers 1975). Minor degrees of facial weakness can be detected by delay or absence of the blink reflex (Pulec & House 1964) and may be preceded by subtle facial twitching, particularly involving the orbicularis oculi muscle (Jackler & Pitts 1990). Hemifacial spasm is another rare presentation, affecting only 1% of patients. Epidermoid tumor, aneurysm, and facial neurinoma should, in particular, be considered in the differential diagnosis when hemifacial spasm is evident. Altered sensation over the posterior aspect of the external auditory canal, which is innervated by the nervus intermedius, is said to occur in 95% of patients (Hitselberger 1966). Alteration in taste is reported rarely. Facial nerve dysfunction in the presence of a small tumor is much more likely to suggest that the lesion is a facial neurinoma or a meningioma rather than an acoustic neurinoma. Several classifications have been devised to grade preand postoperative facial nerve function. The system of House and Brackmann (1985) has gained wide support, and is shown in Table 28.1. On occasions, very large tumors will compress the nerves in the jugular foramen causing dysphagia, dysphonia and, in late cases, complete bulbar palsy. However, loss of the pharyngeal reflex or the presence of vocal cord palsy

Acoustic neurinoma (vestibular schwannoma)

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Table 28.1  Facial nerve grading system (House & Brackmann 1985) Grade

Description

Characteristics

I

Normal

Normal facial function in all areas

II

Mild dysfunction

Gross: slight weakness noticeable on close inspection; may have very slight synkinesis At rest: normal symmetry and tone Motion:   Forehead: moderate to good function   Eye: complete closure with minimum effort   Mouth: slight asymmetry

III

Moderate dysfunction

Gross: obvious but not disfiguring difference between two sides; noticeable but not severe synkinesis, contracture, and/or hemifacial spasm At rest: normal symmetry and tone Motion:   Forehead: slight to moderate movement   Eye: complete closure with effort   Mouth: slightly weak with maximum effort

IV

Moderately severe dysfunction

Gross: obvious weakness and/or disfiguring asymmetry At rest: normal symmetry and tone Motion:   Forehead: none   Eye: incomplete closure   Mouth: asymmetric with maximum effort

V

Severe dysfunction

Gross: only barely perceptible motion At rest: asymmetry Motion:   Forehead: none   Eye: incomplete closure   Mouth: slight movement

VI

Total paralysis

No movement

From House J W & Brackmann D E (1985) Facial nerve grading system. Otolaryngol Head Neck Surg 93: 146–147.

may indicate a second neurinoma in the jugular foramen if the patient suffers from neurofibromatosis. Rarely is the abducent nerve involved directly, except by the largest of lesions. Occasionally an increase in intracranial pressure may displace the brain stem caudally, and thereby cause distortion of the 6th nerve by the anterior cerebellar artery, which overlies it (Bebin 1979).

Other presenting features Several case reports have documented exceptional presentations, including subarachnoid hemorrhage (Gleeson et al 1978; Yonemitsu et al 1983), and tumor within the external auditory canal (Tran Ba Huy et al 1987) or middle ear (Amoils et al 1992). Intralabyrinthine schwannomas have also been reported. These may arise from either the cochlear or vestibular nerves. Here, tumor is present in the inner ear but is absent from either the internal auditory canal or the cerebellopontine angle (for review, see Amoils et al 1992). Very occasionally, brain stem compression may produce symptoms contralateral to the side of the tumor. This may manifest as contralateral trigeminal nerve dysfunction (Koenig et al 1984), facial pain, or hemifacial spasm (Nishi et al 1987; Snow & Fraser 1987), although such features are much more common with meningiomas than acoustic neurinoma. Although they are usually slow-growing, acoustic neurinomas can present with acute neurologic deterioration due 525



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Figure 28.5  Plain tomograms of the internal auditory meatus showing enlargement of the porus acousticus (arrow) and an alteration in canal shape.

A

imag­ing modalities have evolved through plain films, poly-tomography, air contrast and oil-based contrast cisternography, angiography, computed tomography (CT) with and without cisternal air contrast or intravenous contrast, and, currently, magnetic resonance imaging (MRI) with and without paramagnetic contrast agents. The increased sensitivity for detecting acoustic neurinomas is undoubtedly affecting the pattern of presentation and will influence management strategies and outcomes. Magnetic resonance imaging is currently the investigation of choice for both diagnosis and follow-up of acoustic neurinomas.

Radiology

B Figure 28.4  (A) Contrast enhanced CT scan of a large, partially cystic acoustic neurinoma. (B) Repeat CT scan following acute deterioration while awaiting surgery, showing hemorrhage within the tumor.

either to hemorrhage within the tumor (Fig. 28.4) or to rapid expansion of a cyst. Intratumoral hemorrhage is generally confined to lesions >2 cm (Goetting & Swanson 1987). Rapid expansion of a cyst is said to occur in around 2% of patients (Lanser et al 1992). Acute enlargement of a lesion in the cerebellopontine angle may cause multiple cranial nerve palsies, cerebellar dysfunction, and brain stem compromise – symptoms that could be misinterpreted as a vascular event within the posterior fossa (Lanser et al 1992).

Imaging diagnosis There has been a dramatic improvement in the sensitiv­ ity of diagnostic imaging over recent decades. Available 526

Plain tomographs of the internal auditory canals will demonstrate enlargement of the porus acousticus in 80–90% of cases. Pressure from the tumor causes enlargement of the canal by stimulating osteoclastic activity, although it does not cause necrosis of the dural lining (Pulec & House 1964). A disparity of >1–2 mm between the two sides is significant, particularly if it is accompanied by a difference in canal shape or by the presence of bone erosion, or if there is shortening of the posterior canal wall (Fig. 28.5) (Valvassori 1984). However, a normal tomograph does not exclude the diagnosis. Pulec et al (1971) found that approximately 10% of tomographs were normal, and Ojemann et al (1972) reported this in 18% of their patients. Positive contrast cisternography has in the past been used as an adjunct for the diagnosis of small tumors, but has now been superseded by CT and MRI.

Computed tomography Prior to the introduction of MRI, CT was the primary radiologic method for diagnosis (Curtin 1984). Contrast enhanced CT, with 5 mm axial slices through the skull base, will detect all but the smallest soft tissue masses within the cerebellopontine angle. In one series of 131 cases there were no false negative scans (Harner & Reese 1984), but others have reported a false positive rate of 0.6% (Charabi et al 1992). The center of each internal auditory meatus should be included if a small intrameatal tumor is not to be missed as a result of the partial volume effect. The characteristic CT appearance is that of an isoor hypodense lesion centered upon the internal auditory



Figure 28.6  Contrast enhanced CT scan showing a uniformly enhancing tumor centered on the porus acousticus.

meatus, with homogeneous enhancement after intravenous contrast (Fig. 28.6). Cerebellopontine angle meningiomas may have similar appearances but are usually hyperdense prior to contrast injection and commonly are placed asymmetrically in relation to the porus acousticus. Erosion of the porus is rare in meningioma, but may be seen on the posterior surface of the petrous pyramid – a very uncommon occurrence in all except the largest of acoustic neurinomas. A further feature for differentiating an acoustic neurinoma from a meningioma is the configuration seen at the boundary between tumor and dura. Meningiomas generally have a flat, broad-based attachment to the petrous bone, whereas the angle between the tumor and the petrous bone should be acute in cases of acoustic neurinoma (Wu et al 1986). Enhancement of the dural edge adjacent to the main tumor bulk is also highly suggestive of meningioma (Aoki et al 1990), as is the presence of calcification, which will be evident in 25% of cases (Moller et al 1978). Macroscopic calcification is exceptionally rare in acoustic neurinoma (Thomsen et al 1984). Of the imaging modalities currently available, CT is the most suitable for delineation of the bony anatomy. Bone detail is important for several reasons. First, it may establish the diagnosis. This is true particularly for small tumors which may enhance little, but where expansion of the internal auditory meatus is an early feature (Fig. 28.7). Only on rare occasions is the meatus enlarged by a meningioma, but erosion of the temporal bone by cholesteatoma, facial neurinoma, or carcinoma may be evident and assist in the differential diagnosis. Second, delineation of the anatomy of the temporal bone provides useful information to assist the surgeon. The size of the inferior permeatal and perilabyrinthine air cells should be noted. A high jugular bulb can be anticipated if the temporal bone is poorly pneumatized

Acoustic neurinoma (vestibular schwannoma)

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Figure 28.7  High resolution CT scan of the petrous bones. There is expansion of the internal auditory meatus by an intracanalicular acoustic neurinoma. The mastoid bone is well pneumatized, and the relationship of the posterior, semicircular canal (arrows) to the fundus of the internal meatus is evident.

(Graham 1975) whereas, if the mastoid is well pneumatized, air cells may extend medially almost to the porus. This increases the likelihood of postoperative CSF leakage when the posterior wall of the internal auditory meatus is removed and alerts the surgeon to pay particular attention to seal these air cells. High resolution CT may be used also to identify the relationship between the semicircular canals, the vestibule, and the internal auditory meatus (Fig. 28.7). This is important when hearing conservation procedures are contemplated via a suboccipital approach. If the posterior semicircular canal or crus commune lie medial to an imaginary line drawn between the medial aspect of the sigmoid sinus and fundus of the internal auditory canal, they are at risk of injury when the intracanalicular portion of the tumor is exposed (Tatagiba et al 1992). Erosion of bone by tumor in the region of the jugular bulb should also be noted. A major limiting factor of CT in the posterior fossa is the streak-like beam-hardening (Hounsfield) artifact that originates from the petrous bones and tends to interfere with definition in the adjacent soft tissues. The CT detection rate of small lesions can be improved by the introduction of a small amount of air into the cerebellopontine angle cistern (air contrast cisternography, Fig. 28.8), although several authors have warned of the risk of false positive scans. This may arise as a result of a meniscus effect at the gas–CSF interface, an intracanalicular loop of the anterior inferior cerebellar artery, or subdural injection of air (Khangure & Moijtahedi 1983; Barrs et al 1984a; Larsson & Holtas 1986).

MRI MRI is now the imaging modality of choice, particularly for the detection of intracanalicular tumors (Valvassori 1984; 527



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Figure 28.8  CT air contrast cisternogram demonstrating a small acoustic neurinoma.

House et al 1986; Stack et al 1988). Most acoustic neurinomas are visible on non-contrasted T1-weighted images (Fig. 28.9), but not on T2-weighted images, where the tumor may be isointense with CSF. Intravenous contrast enhancement with gadolinium-DTPA improves the detection rate of small neurinomas, which may otherwise have a signal intensity similar to that of brain parenchyma (Glasscock et al 1988; Brackmann & Kwartler 1990a). Tumors enhance markedly after gadolinium (Fig. 28.10), with which it becomes possible to detect lesions as small as 2–3 mm (Welling et al 1990). The major advantages of MRI over CT are superior contrast resolution, lack of beam-hardening artifact, the facility to image the tumor in multiple planes, and the ability to identify vascular structures and therefore assess vessel displacement or encasement. However, because cortical bone emits no signal, MRI is inferior to CT for delineation of the anatomy of the petrous temporal bone. Newer MRI techniques such as T2 fast spin echo (FSE) and three dimensional Fourier transformation-constructive interference in steady state sequence (3DFT-CISS) allow high resolution imaging of labyrinthine and cerebrospinal fluid interface with bone and soft tissue (Casselman et al 1993; Phelps 1994). These techniques outline acoustic tumors, nerves, and vessels in the cerebellopontine angle and internal auditory canal without paramagnetic contrast (Fig. 28.11). The relationship of the tumor to the lateral end of the internal auditory canal (IAC) can be assessed, as can the relationship of the posterior semicircular canal to the fundus of the IAC. The remaining advantage of CT over MR imaging is the accurate preoperative assessment of petrous apex and perilabyrinthine pneumatization and jugular bulb position. False positive MRI has 528

Figure 28.9  T1-weighted axial MR scan showing bilateral acoustic neurinomas (arrows).

A

B Figure 28.10  (A) Gadolinium enhanced MR scan of a small acoustic neurinoma. (B) Cystic acoustic neurinoma, note peripheral enhancement.



Acoustic neurinoma (vestibular schwannoma)

28

imaging, tumor volume rather than maximum diameter will become ultimately the measurement upon which these lesions are graded.

Laboratory diagnosis Audiometry

Figure 28.11  Magnetic resonance T2-weighted ‘CISS’ sequences demonstrating the acoustic neurinoma as a filling defect in the right internal auditory canal.

been reported occasionally as a consequence of arachnoiditis or adhesions (Haberman & Kramer 1989; Von Glass et al 1991).

Arteriography The indications for arteriography have diminished considerably with the advent of CT and MRI, but it is necessary if an aneurysm or AVM is suspected in the differential diagnosis (Dalley et al 1986). Some surgeons still advocate angiography to define the vascular anatomy in relation to very large lesions. On occasions, it may aid in differentiating a large acoustic neurinoma from a meningioma, particularly if a dilated tentorial artery of Bernasconi is demonstrated in the case of the latter. Angiography has been advocated also for childhood tumors, which may be extremely vascular, and where preoperative embolization is said to be beneficial (Allcutt et al 1991).

Assessment of tumor size CT and MRI are used routinely to measure tumor size. Unfortunately there are many different classifications in current usage, none of which is universally accepted. Tumors have been classified by Pulec et al (1971) into three groups: small (intracanalicular), medium-sized (extending beyond the internal meatus but by <2.5 cm), and large (>2.5 cm). This, and the Koos (1988) classification, are probably used more widely than most. At the First International Conference on Acoustic Neuroma, however, Tos & Thomsen (1992) made a plea that the following classification be adopted universally, so that reporting of results could be standardized. They have proposed that the intrameatal component (usually about 1–1.5 cm) not be included in the measurement. Size instead is measured as the largest extrameatal diameter. Tumors are classified as intrameatal, small (1–10 mm), medium (11–25 mm), large (26–40 mm), and extra large (>40 mm). It remains to be seen whether this becomes the accepted scheme or just one more to add to the bewildering myriad already in existence. It appears likely that, with the advent of computerized three-dimensional reconstruction

Air, bone, and speech hearing tests are the mainstay screening procedures for acoustic neurinoma. High frequency hearing loss is the most common abnormality seen on pure tone audiometry (PTA) (Johnson 1977). Only 5% of patients will have normal hearing with good speech discrimination (Beck et al 1986), making PTA an important and reliable test in routine neuro-otologic investigation. The pattern of hearing loss is variable. In several large series hearing loss was reported variously as being primarily of a high frequency in 35–66% of patients and low frequency in 4–9%, while the audiogram was flat in 13–18% (pure tone pattern differing by not >10 dB throughout the speech range) and trough-shaped in 4–12%, and in 16–27% of patients the ear was dead (Johnson 1977; Bebin 1979; Hardy et al 1989a). The likelihood of abnormal audiometry correlates with tumor size (Johnson 1977). However, even when the pure tone audiogram is normal, speech discrimination is often impaired, and almost all such patients will exhibit abnormalities also on auditory evoked brain stem response testing (Musiek et al 1986). Tone, decay, and the absence of recruitment are also characteristic audiologic findings (Johnson 1977). Other audiometric parameters include Bekesey audiometry, the SISI test, alternate bilateral loudness balance (ABLB) tests, and the acoustic reflex test. A full account can be found in Johnson (1979), although these ‘site of lesion’ tests are applied only rarely in modern practice.

Speech discrimination Speech discrimination is not related simply to the degree of pure tone hearing loss. Some patients may have exceptionally poor speech discrimination despite near normal pure tone audiometry. Speech discrimination scores in a series of 425 cases of acoustic neurinoma were 0% in 35% of patients, very poor (2–30% discrimination score) in 21%, moderate to poor (32–60% discrimination) in 16%, and moderate to good (62–100%) in the remaining 28% of cases (Johnson 1977). In total, only 20% of patients with acoustic neurinoma had good speech discrimination. The speech discrimination score is an important consideration when contemplating hearing preservation procedures. When hearing is normal in the contralateral ear, residual hearing on the operated side is useful socially only if speech discrimination is good and the pure tone audiogram is within 30 dB of the normal side.

Caloric testing Over the years, much time and effort has been invested in examination of the vestibular system of patients suspected of harboring an acoustic neurinoma. The object was to find a simple and inexpensive screening test for the condition. Caloric testing was pioneered by Barany, for which he was awarded the Nobel Prize in 1914. In the era before modern 529



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neurosurgical imaging, the differentiation of labyrinthine from cerebellar ataxia was of considerable importance. Vestibular assessment by caloric testing often reveals an ipsilateral canal paresis in acoustic neurinoma, but this is a non-specific finding which is often absent in small tumors (Dix 1974). The detection rate for lesions larger than 4.5 cm is considerably better. In this group, Hallpike’s caloric test will be normal in <4%, diminished in 33%, and absent in the remaining 70% (Boesen et al 1992). Electronystagmography has now superseded bithermal caloric testing in many centers (Linthicum & Churchill 1968). In a prospective study of 409 patients with asymmetric hearing loss or tinnitus, caloric testing had a sensitivity of 80% for the detection of acoustic neurinoma, but achieved a specificity of only 50% (Swan & Gatehouse 1992). This makes it inappropriate as a screening test, both on the grounds of an unacceptable number of missed tumors and because of the high false positive rate. Other conditions that may produce abnormal caloric results include vestibular neuronitis and Ménière’s disease. One of the reasons for the poor sensitivity of this investigation is that it stimulates the lateral semicircular canal and, therefore, only the superior vestibular nerve.

Auditory brain stem evoked responses Auditory brain stem evoked responses (ABRs) are the most sensitive indicator of a retrocochlear lesion, and have both a higher detection rate and a lower false positive rate than other non-radiologic screening tests (Selters & Brackmann 1977). Unlike lesions of the cochlea, compression or stretching of the cochlear nerve produces a delay in the response latency which may be detected even when hearing is normal. The stimulus applied is a click from an earphone, and this elicits an electrical response which is recorded from scalp electrodes sited over the mastoids and vertex. The non-test ear is masked with white noise, and an averaging computer extracts the auditory response from the random signal. Generally, ABR testing is applicable only if hearing is better than 70 dB. Patients with retrocochlear hearing loss show a consistent interaural difference in the latency of wave V during ABRs (Selters & Brackmann 1977). The upper limit of normal is 0.2 ms. Other algorithms used to detect a retrocochlear lesion include the absolute latency of wave V, and the intervals between waves I and V (upper limit of normal = 4.5 ms). ABRs are reported to be abnormal in 95% of patients with acoustic neurinoma (Josey et al 1980), and the false positive rate is said to be about 10% (Brackmann & Kwartler 1990a). Other series, however, have found that ABRs are considerably less specific than this. Weiss et al (1990) reported that the probability of finding a cerebellopontine angle tumor in the presence of an abnormal result was only around 15%. This is perhaps not surprising because ABRs test the function of the auditory system as a whole. Despite this shortcoming, the ABR is still used widely as a screening procedure, even though a negative result does not exclude the diagnosis. A recent study reports the sensitivity of ABR for detection of extracanalicular tumors to be 94% but only 77% for intra­ canalicular tumors (Godey et al 1998). Tumor size cannot be predicted from the degree of latency delay. However, 530

large lesions may cause sufficient brain stem compression to affect contralateral latencies as well (Selters & Brackmann 1977). It is of interest that ABRs are abnormal in more than 30% of patients with NF-1, even though acoustic neurinomas are rare in this group of patients (Schorry et al 1989).

Stapedial reflex testing Stapedial reflex testing is a further test of retrocochlear pathology, but is less sensitive than ABR. Abnormalities are found in around 80% of patients.

Electrocochleography Transtympanic electrocochleography (EcoG) is usually nonspecific, although the presence of an action potential complex in the absence of subjective hearing is said to be pathognomonic (Morrison et al 1976). EcoG and ABR may be combined, particularly as the former is more sensitive for the detection of wave I. This increases the number of instances when the wave I–V interval can be measured (Prasher & Gibson 1983).

Electroneuronography Electroneuronography (EnoG) has been used preoperatively to assess facial nerve involvement in temporal bone tumors. A compound action potential is measured in response to supramaximal bipolar stimulation of the main trunk of the facial nerve, and its amplitude compared with that of the contralateral side. Amplitude reduction is said to relate to tumor size, but cannot predict postoperative facial nerve function (Kartush et al 1987).

Screening tests Moffat & Hardy (1989) have justified the early diagnosis and treatment of acoustic neurinomas on both economic and humanitarian grounds. Unfortunately MRI, and even CT, are too expensive in most countries to use as a routine screening test for patients with asymmetric hearing loss or other features which may represent a cerebellopontine angle tumor. Over the years many different test results have been proposed as being almost pathognomonic of retrocochlear hearing loss, only to be found wanting on closer examination. Examples include the phenomenon of loudness recruitment, abnormally rapid tone decay, disproportionately poor speech discrimination, and the stapedial reflex threshold. In order to reduce the financial burden from radiologic imaging of large numbers of patients and yet avoid missing a significant number of tumors, several non-diagnostic investigations have been combined to provide a screening battery. The necessary trade-off in every case is between sensitivity and specificity. Of patients with an acoustic neurinoma, over 98% will manifest an abnormality in at least two out of three of the following: caloric testing, ABR, and plain radiology of the internal auditory meatus (Moffat et al 1989b). Other workers have proposed combining pure tone audiometry, ABR, caloric testing, and the stapedial reflex test (Thomsen et al 1992). If the results are abnormal or equivocal, radiologic assessment is then undertaken. In a study of 82 cerebellopontine angle tumor suspects, Barrs & Olsson (1987) found that the interaural wave V (IT5) latency



difference on ABR testing had a sensitivity of 100% and a specificity of 80%. One tumor was diagnosed for every three abnormal IT5 results. Although the sensitivity from nonradiologic screening is high, it is inevitable that a few tumors will be missed using such algorithms. This may have medicolegal implications. It is clear that the sensitivity of auditory brain stem response testing has fallen as the ability to image smaller acoustic neurinomas has improved. The cost of screening with MRI can be reduced substantially if the fast spin echo magnetic resonance imaging techniques without gadolinium enhancement are used. A limited non-enhanced fast spin echo MRI can be used to image the internal auditory canal and cerebellopontine angle. This technique currently provides maximal sensitivity for acoustic neurinoma detection with minimal cost (Daniels et al 1998).

Gross morphologic features

Acoustic neurinoma (vestibular schwannoma)

28

Microscopically, the tumor consists of two distinct patterns of architecture which, in any individual lesion, are intermingled but well demarcated. These are known as Antoni types A and B, and are fundamental to the diagnosis (Antoni 1920). Antoni type A tissue predominates, and consists of groups of spindle-shaped cells with elongated hyperchromatic nuclei. The cytoplasm is pale and has a stringy appearance due to numerous hairlike argyrophilic fibers which lie parallel to the long axis of the cell (Fig. 28.12) (Russell & Rubinstein 1989). Characteristic of schwannomas in general, although frequently absent in acoustic neurinomas, is the presence of palisading. The cells are grouped together in bundles (Verocay bodies). Within each bundle the cells lie roughly parallel with their nuclei aligned in rows, separated by clear hyaline bands. The fibers interlace with those of other bundles, which are orientated at different angles. Antoni type B tissue has a less compact structure. The cells are pleomorphic, vacuolated, and separated by a loose eosinophilic matrix (Fig. 28.13). Microcystic change is

Acoustic neurinomas typically are firm, well circumscribed, and encapsulated. They distort and compress rather than invade brain. The tumor, which is invested in a sheet of arachnoid, is of a yellowish white appearance and has a rubbery consistency. These lesions are relatively avascular except in childhood, or when very large (Kasantikul et al 1980a). The presence of areas of red or brown discoloration indicates old or recent hemorrhage. The surface of large tumors in particular is often irregular and lobulated. Usually the neoplasm is solid, although small thin-walled cysts may be evident. On occasion the greater part of the lesion will be found to be cystic (Fig. 28.10B). Large tumors compress and deform the cerebellum and the lateral aspect of the pons, the upper medulla, and the brachium pontis. Very large lesions may displace the cerebellum inferiorly, causing tonsillar herniation.

Histopathology In 1842, Cruveilhier (1842) produced a detailed report of the clinical and pathologic features of a 26-year-old patient who died from an acoustic neurinoma. Intracranial schwannomas have a marked preponderance for sensory nerves, particularly the eighth cranial nerve. Although the tumor is usually confined to the vestibular division, invasion of the cochlear (Neely 1981; Marquet et al 1990) and facial nerves has been described (Luetje et al 1983). Tumors arise at the neurilemmal–glial junction, or anywhere between this and the origin of the nerves within the labyrinth (Stewart et al 1975). There have been no reports of primary tumors occurring in the neuroglial portion of the nerve. It was Virchow who called these tumors ‘neuromas’, based upon their macroscopic appearance. Microscopy revealed many parallel fibers, which were mistaken for axons, hence the later term ‘neurinoma’. However, Murray & Stout (1940) identified the cell of origin correctly as the Schwann cell, using in vitro tissue culture techniques. Despite this, some controversy still remains as to whether the Schwann cell or the related perineural fibroblast is indeed the true source of this neoplasm.

Figure 28.12  Acoustic neurinoma containing bundles of spindle-shaped cells forming Antoni type A tissue. A Verocay body is present. (H&E ×380.)

Figure 28.13  Microscopic appearance of Antoni type B tissue in an acoustic neurinoma. The cells are more pleomorphic than Antoni A, and are separated by a loose eosinophilic matrix. (H&E ×380.)

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frequent, although Antoni type B tissue does not represent degeneration of type A (Murray & Stout 1940). Confluence of these areas is responsible for the cysts which are sometimes a feature of these tumors. Type B tissue may also become xanthomatous, due to lipid accumulation; this gives rise to a yellowish naked eye appearance. The degree of tumor cellularity may be quite variable. Secondary changes occur in some schwannomas. Areas of infarction or hemorrhage may be seen, particularly in tumors with excessive vascularization. On occasion, angiomas may be combined with neurinomas, particularly in women (Kasantikul et al 1980b). Hemosiderin-filled macrophages may be evident within foci of degeneration, and areas of necrosis may be present. Other tumors may contain foci of calcification. The term ‘ancient schwannoma’ has been given to lesions where the nuclei are atypical, hyperchromatic, and enlarged, and the tumor is associated with a dense fibrous stroma. Mitotic activity is not increased in ancient schwannomas, however, and neither this appearance, nor the presence of pleomorphism, by itself signifies malignant change. Other neoplasms have been reported occasionally to metastasize to an acoustic neurinoma (le Blanc 1974) and melanotic acoustic neurinomas have been described on very rare occasions (Russell & Rubinstein 1989). Benign schwannomas rarely present a diagnostic challenge histologically, although meningiomas may on occasion have similar features, including the presence of Verocay bodies (Sobel & Michaud 1985). Immunohistochemical markers are therefore generally of rather limited value. Acoustic neurinomas stain strongly positive for the S-100 protein (Fig. 28.14). This is a cytoplasmic protein but it is not specific to this condition. Its uses primarily are for the identification of nerve sheath tumors, amelanotic melanoma, and myoepithelial cells. Meningiomas by contrast, stain positively only weakly with S-100, but can be differentiated further by their reaction to HMFG (epithelial membrane antigen) (Schnitt & Vogel, 1986; Simpson et al 1990). A proportion of acoustic neurinomas stain positively for glial fibrillary acidic protein (GFAP) (Stanton et al 1987).

Figure 28.14  Positivity of an acoustic neurinoma for the S-100 protein. (H&E ×620.)

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The bilateral acoustic neurinomas of NF-2 do not differ microscopically from those that occur sporadically. They do, however, show a tendency to be more adherent to adjacent structures (Linthicum & Brackmann 1980). Rarely, meningioma has been observed to be intermixed microscopically with schwannoma (Gruskin & Carberry 1979). Under the electron microscope, Antoni type A tissue has a lamellar pattern composed of thin elongated cell processes covered by a basal lamina, which are separated by intercellular basement membrane material. Antoni B tissue contains large numbers of organelles and vacuoles, consistent with high metabolic activity (Russell & Rubinstein 1989). Other typical electron microscopic features include long-spaced collagen fibrils and the development of whorls and lamellae composed of stacks of double membranes grouped tightly together.

Malignancy Malignancy is far more common in peripheral than in cranial neurinomas. The vast majority present de novo rather than as malignant change in a pre-existing benign lesion (Yousem et al 1985). Around 50–70% are associated with von Recklinghausen’s disease, and the age at presentation in these cases is considerably younger than for those that occur sporadically (for review, see Russell & Rubinstein 1989). Malignant acoustic neurinomas are exceptionally rare, and only a handful have been reported in the world literature. Russell & Rubinstein (1989) collected a series of only six, in patients ranging from 26 to 72 years of age. In one there was considerable bony erosion by tumor, while three manifested themselves as recurrence after previous surgical excision. Histologically, the features were similar to neuro­ fibrosarcoma, with increased cellularity and numerous mitoses. Initially the tumors were encapsulated, but later they became locally invasive. Recurrence is common after surgery and these tumors may become progressively more anaplastic with the passage of time. The risk of recurrence entails a poor long-term prognosis, although the rarity of malignant change means that precise details of tumor behavior are lacking. Studies of large numbers of malignant peripheral schwannomas indicate that metastases are uncommon and occur late. The degree of mitotic activity and anaplasia is said not to predict survival (Ducatman et al 1986). Nager (1969) was unable to find any report of malignant degeneration within a pre-existing acoustic neurinoma. Such a case was documented by McLean et al (1990) although, in retrospect, the original specimen did exhibit some atypical features. A malignant schwannoma with rhabdomyoblastic differentiation is otherwise known as a malignant triton tumor. This very rare soft tissue sarcoma arises almost exclusively from peripheral nerves, usually in patients with von Recklinghausen’s disease. Few cases of acoustic nerve triton tumors have been reported (Best 1987; Han et al 1992; Comey et al 1998). Total excision with adjuvant chemotherapy and radiotherapy has been advocated, however the prognosis in all cases was poor. Concerns have been raised that radiation therapy for acoustic neuromas may induce malignant transformation. The 5-year survival for this tumor in peripheral nerves is 12% (Brooks et al 1985).



General management plan Differential diagnosis Acoustic neurinomas are by far the most common tumors occurring within the cerebellopontine angle. In a review of 205 tumors, Revilla (1948) found that 78% were neurinomas (mostly acoustic), 6% meningioma, 6% cholesteatoma, 6% gliomas, and the remaining 4% miscellaneous. The presenting features of meningioma can be similar to acoustic neurinoma but, because the tumor arises frequently from the anterior or superior lip of the internal auditory meatus, there may be early involvement of the facial and trigeminal nerves with relative sparing of hearing (Sekhar & Jannetta 1984). Similarly, inferior extension may involve the cranial nerves in the jugular foramen. The relationship between the cranial nerves and the tumor is much less predictable than with acoustic neurinoma, but the success of hearing preservation is greater, particularly for larger lesions (Maurer & Okawara 1988). Schwannomas of adjacent cranial nerves, in particular of the trigeminal, facial, glossopharyngeal, or vagus nerves, can also involve the cerebellopontine angle. Facial neurinomas, which account for about 1% of cerebellopontine angle tumors, may be difficult to differentiate from an acoustic neurinoma preoperatively. However, facial neurinomas sometimes arise from the region of the geniculate ganglion and may extend into the middle cranial fossa via erosion of the petrous temporal bone (King & Morrison 1990). Very large acoustic neurinomas, by contrast, are more likely to extend into the middle cranial fossa via the tentorial hiatus, although this is uncommon. The presence of contrast enhancement in the region of the genicular ganglion, despite features otherwise typical of an acoustic neurinoma, can also aid in the differential diagnosis. Facial neurinomas may also evolve from the tympanic or mastoid segments of the nerve. Other schwannomas of the temporal bone include those arising from the chorda tympani nerve, the auricular branch of the glossopharyngeal (Jacobson’s) nerve, and the auricular branch of the vagus (Arnold’s) nerve (Amoils et al 1992). At times it may not be possible to ascertain from which nerve a neurinoma of the petrous temporal bone has arisen (Best 1968). As well as meningioma and neurinoma of adjacent cranial nerves, the differential diagnosis of acoustic neurinoma includes epidermoid, aneurysm, arteriovenous malformation, glomus jugulare tumor, choroid plexus papilloma, hemangioma, lipoma, lymphoma, medulloblastoma, enterogenous cyst, and metastatic tumor within the temporal bone (Schisano & Olivecrona 1960; Brackmann & Bartels 1980; Robinson & Rudge 1983; Wakabayashi et al 1983; Yoshi et al 1989; Umezu et al 1991; Yamada et al 1993). Differentiation of these lesions is not usually difficult on radiologic grounds.

Conservative treatment and the timing of surgery The question of the timing of acoustic neurinoma surgery remains unresolved and, in many respects, has become less clear with the passage of time. Age by itself is not a contra­ indication to successful surgery (Samii et al 1992), although an expectant policy with careful follow-up may be

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28

a reasonable alternative to surgery when the tumor is small and the patient is infirm or perhaps reluctant to contemplate excision for other reasons. The difficulty in assessing tumor growth rates in the pre-CT era, and the dramatic reduction in mortality and morbidity from surgery in the 1960s to 1980s suggested that all tumors, with a few notable exceptions, should be removed at diagnosis. This view was strengthened by the knowledge that larger tumor size is associated undoubtedly with an increase in morbidity and, in particular, poorer prospects for facial nerve recovery, preservation of residual hearing, and good quality of life. Yet despite this, the decision to offer immediate treatment is not always clear cut. Better awareness among clinicians, coupled with improvements in diagnostic screening, has resulted in greater numbers of tumors being diagnosed at an early or even asymptomatic stage. Although the surgical results for facial nerve function and overall morbidity are likely to be excellent under these circumstances, unfortunately this is not yet true for preservation of hearing. With the advent of MRI, and subsequent reports which suggest that up to 50% of untreated patients with small lesions will display no further tumor growth, expectant treatment has become a viable alternative to surgery in some cases. It can be argued that small tumors should be managed conservatively in the first instance, excision not being contemplated until it has been established that the lesion is actually expanding. In a study of 35 patients, Valvassori & Guzman (1989) determined that any further tumor growth was evident usually within the first 12 months of follow-up. A relatively short observation period may therefore allow patients with indolent forms of the disease to be selected out. Lifelong follow-up will be necessary, as demonstrated by Charabi et  al (1995, 1998). This is not to suggest that delayed treatment is applicable for any but a minority of patients. Conservative management is probably unwise in the younger age groups because the rate of tumor growth is possibly more rapid. Similarly, an expectant policy is unsuitable for lesions larger than 2.0 cm because any further expansion is liable to have a significant influence upon surgical morbidity. In our experience, the great majority of patients are far more concerned about their facial nerve function and prospects for a good outcome in general than they are about preservation of hearing in the affected ear. We believe that early surgery remains the treatment of choice for most patients because outcome relates so strongly to tumor size. If patients are to be managed conservatively in the first instance, repeat MRI at 8 months, 18 months, and subsequently at 2-yearly intervals has been recommended (Valvassori & Guzman 1989).

Neurofibromatosis type 2 NF-2 is particularly challenging to manage satisfactorily. As well as bilateral acoustic neurinomas other tumors may occur, notably cranial and spinal neurinomas, meningiomas, and ependymomas. Any patient under the age of 30 years who presents with an acoustic neurinoma or meningioma should be suspected of suffering from NF-2. MRI with gadolinium enhancement should be performed to screen both for 533



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a small contralateral lesion and for the presence of other intracranial tumors. The major objective of treatment is to preserve functional hearing for as long as possible. Unfortunately, auditory symptoms often occur late in the disease (Linthicum & Brackmann 1980; Bess et  al 1984). Furthermore, deterioration of hearing in a series of nine patients with bilateral tumors treated conservatively was rapid in every case, and ranged from 11 to 16  dB per year (Kitamura et  al 1992). However, as with sporadic tumors, the speed of progression does appear to be highly variable (Baldwin et  al 1991). The combination of rapid tumor growth and poorer prognosis as the tumor enlarges argues for these lesions being treated promptly. However, examination of the temporal bone in NF-2 patients shows that minor infiltration of the cochlear nerve and inner ear is more common than with sporadic tumors (Linthicum & Brackmann 1980). The prognosis for hearing preservation is likely therefore to be correspondingly less favorable (Brackmann 1979). The dilemma is whether to offer early treatment, which provides the only hope of preserving long-term hearing, albeit a small one, or to delay surgery until useful hearing has been lost or tumor size mandates surgery, and to train the patient to cope with impending deafness in the interim. Hearing loss is not the only difficulty when treating this patient subgroup. Involvement of the facial nerve is more common (Martuza & Ojemann 1982; Baldwin et  al 1991), and facial nerve preservation rates are correspondingly less good. A large symptomatic tumor will require treatment, regardless of the risk of total deafness. In every case surgery should aim to conserve residual hearing, unless the tumor is very large. If the tumors are small and hearing is good, the National Institutes of Health consensus document (1988) proposes that an attempt should be made to excise one tumor. The authors’ preference is to remove first the tumor on the side of poorer hearing (usually, but not invariably, the larger of the two). In the fortunate circumstance where useful hearing remains intact, the contralateral lesion may be explored later. However, if hearing is lost at the first operation, there are four options. Treatment of the contralateral neurinoma can be delayed until useful hearing is lost, since hearing at even very low levels may assist the patient with lip reading. Alternatively, the remaining tumor can be excised macroscopically or the patient offered stereotactic radiosurgery. The fourth option is to undertake sub-total tumor removal with decompression of the internal auditory canal, which may delay the progression of hearing loss (Miyamoto et  al 1991). However, even elective sub-total tumor removal can result in total deafness (Wigand et  al 1988; Baldwin et  al 1991), and total excision with hearing preservation is very unlikely if the lesion is >2  cm in diameter (Hughes et  al 1982). Sub-total excision that fails to preserve hearing should be followed shortly by total removal. In a report of 19 patients with bilateral tumors, 65% retained facial function after surgery, but the outlook for hearing in both the operated and unoperated groups was dismal (Baldwin et  al 1991). In a recent report of hearing preservation in patients with NF-2, using the middle fossa approach, 23 procedures were performed on 18 patients 534

and measurable hearing was preserved in 65% (Slattery et  al 1998). The mean tumor size in this group was 1.1  cm; this reinforces the importance of early diagnosis and family screening in NF-2 patients. Since the results for hearing preservation by both surgery and stereotactic radiosurgery are poor, and the course of untreated disease is variable, we do not believe that operation is justified at present on a solitary hearing ear with a small tumor. If bilateral excision is contemplated, the second operation should, where possible, be delayed until there has been recovery of facial nerve function. Although the likelihood is very small, it should be remembered that surgery carries with it the risk of bilateral rather than just unilateral deafness (Linthicum & Brackmann 1980; Miyamoto et al 1990). Sometimes removal of tumor on one side will result in some improvement in residual hearing in the contralateral ear. Stereotactic radiosurgery is an alternative to surgery in NF-2 patients. However, this technique also may result in both delayed hearing loss and facial palsy. Progressive hearing deterioration or deafness will ensue in 64% of such patients (Hirsch & Noren 1988). More recent reports claim better hearing preservation rates when the mean tumor margin radiation dosage is reduced and studies in non-NF-2 related tumors have shown adequate long-term control rates. Similarly, high rates of hearing preservation have been claimed with the use of fractionated stereotactic radiation therapy rather than single fraction stereotactic radiation (Lederman et al 1997). If long-term tumor growth control rates are demonstrated then fractionated stereotactic radiation therapy may have a significant role in the management of NF-2 patients. On rare occasions a cerebellopontine angle tumor in neurofibromatosis will be a facial rather than an acoustic tumor, and theoretically may permit total tumor removal with preservation of hearing (Piffko & Pasztor 1981). King & Morrison (1990) found that 21% of their cases of facial neurinoma developed in patients with NF-2. Unfortunately the translabyrinthine operation, involving destruction of hearing, is often more favorable than a retrosigmoid approach to these tumors because of improved access to the petrous segment of the lesion, and to normal facial nerve beyond it.

Tumor in a solitary hearing ear Such a patient presents a challenge similar to that faced when dealing with NF-2. Whether or not to operate at the time of diagnosis remains controversial, and is a matter of personal judgment. Some authors advocate early surgery, arguing that the success of hearing preservation will only diminish as the tumor enlarges (Pensak et al 1991). Yet hearing preservation is successful currently in around only one-third of patients. We think that the risk of deafness is too high, particularly when the natural history of the condition is uncertain. Initially we favor conservative treatment, unless the tumor is large and exerting mass effect. Large tumors we treat by radical subcapsular excision. The results of hearing preservation with stereotactic radiosurgery have improved with lower tumor margin doses and this form of treatment is now a first-line option in many centers.



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Surgical management

Surgical anatomy

Historical perspective

A detailed account of the surgical anatomy can be found in Rhoton (1986) and Rhoton & Tedeschi (1992). In brief, the cerebellopontine angle cistern is bounded laterally by the petrous face, medially by the pons, and superiorly by the tentorium cerebelli. It contains the trigeminal, facial, and vestibulocochlear nerves, together with the anterior inferior cerebellar artery (AICA), and superior petrosal vein. Although the facial and vestibulocochlear nerves may at first sight appear to pass as a single bundle from the pontomedullary junction to the internal auditory meatus, they are separate. The superior and inferior vestibular nerves lie posteriorly and superiorly, and the cochlear nerve posteriorly and inferiorly. A shallow groove marks the boundary between them. The facial nerve lies anteriorly and slightly superiorly, with the nervus intermedius lying between the facial and vestibular nerves. The labyrinthine artery (and occasionally the main trunk of the anterior inferior cerebellar artery) lies usually between the facial and vestibular nerves. However, in all except the smallest lesions, the neural relationships will be distorted as the tumor enlarges; because of its position, the facial nerve is usually displaced anteriorly and superiorly, although in around 5% of cases the nerve will lie over the posterior tumor capsule. The constant landmarks for identification of the neural structures during tumor excision are their medial and lateral extents. Within the internal auditory meatus each of the nerves is separated from the others by two bony septa, the transverse crest and the vertical crest (Bill’s bar, named after William House). Within the porus acousticus the superior and inferior vestibular nerves lie posteriorly, the facial nerve anterosuperiorly, and the cochlear nerve anteroinferiorly. Identification of Bill’s bar will therefore allow the nerves anterior to it (the facial and cochlear) to be delineated with confidence from those posterior to it (the superior and inferior vestibular). At the brain stem, the facial, cochlear, and vestibular nerves are more widely separated. The most important structures to identify here are the flocculus and the tuft of choroid plexus which emerges from the foramen of Luschka at the lateral margin of the pontomedullary sulcus. The foramen of Luschka is situated just dorsal to the glossopharyngeal root entry zone (Rhoton 1986). Immediately anterosuperior to the choroid plexus lies the entry of the vestibulocochlear nerve. The facial nerve arises in the pontomedullary sulcus a further 1–2 mm anterior to the vestibulocochlear nerve. The anterior inferior cerebellar artery may pass around the brain stem either anterior to, ventral to (the most common finding), or between the facial and vestibulocochlear nerves; in only 23% of 132 subjects was the AICA not related significantly to the nerves (Sunderland 1945). The degree to which it loops laterally toward the internal auditory meatus is variable. On occasion the artery may actually enter the meatus (around 14%) and it is particularly vulnerable to injury in this instance. In the majority of cases the artery loops laterally almost to the internal meatus (50%), while in 16% of patients there is no loop, and the AICA lies close to the brain stem. After passing the nerves, the artery loops back consistently to the surface of the middle cerebellar peduncle above the flocculus (Rhoton 1986).

The first successful operation to remove a cerebellopontine angle tumor is credited to Sir Charles Ballance in 1894. Unfortunately the patient required enucleation of the eye subsequently as a consequence of complications secondary to trigeminal and facial nerve palsy. Krause described the retrosigmoid suboccipital approach in 1903, but mortality at the time was very high, ranging from 67% to 84% (Dandy 1925). Tumor removal was achieved usually by extraction with a finger inserted into the posterior fossa, a practice which carried with it a high risk of injury to branches of the basilar artery as well as to the cranial nerves and brain stem. As a consequence of the poor results, Cushing proposed sub-total tumor removal. This he achieved by scooping out the center of the lesion, and by the application of Zinker’s solution to the cavity for hemostasis. This technique, which was combined with a generous decompressive suboccipital craniectomy and uncapping of the cerebellum, reduced mortality to about 25% by 1917, and 4% by 1931 (Cushing 1917, 1931). However, 40% of patients died within 5 years from tumor recurrence (Cushing 1931). An excellent account summarizing Cushing’s techniques and surgical results can be found in German (1961). The first successful attempt at total tumor excision with preservation of the facial nerve was reported by Sir Hugh Cairns in 1932. Recognition that the anterior inferior cerebellar artery was often adherent to the tumor capsule, that changes in vital signs were often related to brain stem ischemia, and that preservation of the arteries within the cerebellopontine angle was essential to a good outcome were further milestones in the surgery of this disease (Adams 1943; Atkinson 1949). Elliott & McKissock (1954) were perhaps the first to report successful preservation of hearing. In 1961, McKissock (1961) reported a remarkable series of patients with small tumors undergoing surgery, without the aid of magnification. In each case the facial and cochlear nerves remained intact, and residual hearing was present in some cases. The translabyrinthine operation was proposed by Panse (1904). A radical mastoidectomy was performed, which included removal of the labyrinth, the cochlea, and the facial nerve. The procedure quickly fell into disrepute because of limited access, sub-total tumor excision, destruction of the facial nerve, hemorrhage from the venous sinuses, cerebrospinal fluid leakage, and the resultant high mortality (Dandy 1925). Later the translabyrinthine and suboccipital approaches were combined, but mortality remained high, mainly because of meningitis secondary to cerebrospinal fluid fistula. The operation was reintroduced by House (1964a), using modern microsurgical techniques. In his monograph, which was to become a landmark in the surgery of acoustic neurinoma, a series of 41 cases was reported in which there were no deaths, and almost all patients achieved some return of facial function. The results from House’s group stimulated a great striving for better and better technical excellence. Mortality is now very low, and attention has turned to the preservation of hearing and of normal facial function.

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Occasionally, the AICA may be substituted by a branch of the posterior inferior cerebellar artery. Penetrating branches of the AICA enter the pons and upper medulla to supply the facial and vestibular nuclei, the spinal tract of the trigeminal nucleus, part of the medial lemniscus, and much of the middle and inferior cerebellar peduncles. The superior petrosal vein (vein of Dandy) drains the upper aspect of the cerebellum into the superior petrosal sinus. The vein (or group of veins) may be divided to improve exposure if necessary, or if there is a risk of avulsion during retraction of the cerebellum. It has been suggested, however, that this may, on occasion, exacerbate postoperative cerebellar swelling, particularly if the suboccipital route has been employed for tumor excision. Knowledge of the arachnoid is important because it provides the key to dissection of the tumor from the surrounding structures. Within the internal meatus the nerves and internal auditory artery are covered in a sleeve of arachnoid. A tumor arising from the vestibular nerve, therefore, will also be invested in arachnoid. As the lesion grows from the porus acousticus into the cerebellopontine angle, the arachnoid which covers it comes into contact with the arachnoid which overlies the cerebellum and the adjacent nerves and vessels of the angle cistern (Tos et al 1988). The only structures not separated from the tumor by arachnoid are the facial and cochlear nerves, and the brain stem end of the vestibulocochlear complex. As a result, when the tumor encroaches on the medially placed structures there is a double layer of arachnoid separating it from the brain stem and cerebellum. This arachnoidal cap provides an important cleavage plane during tumor dissection. The tumor obtains its blood supply from two sources. The principal supply is via the dura of the petrous pyramid at the margins of the internal auditory meatus. Bleeding in this region may be tedious and troublesome during tumor removal. Medially the tumor is supplied by the labyrinthine artery and by the other branches of the anterior inferior cerebellar artery. As well as encroaching upon the cerebellum and brain stem, large tumors may be related to the abducent nerve and basilar artery. The superior pole of large tumors will involve the trigeminal nerve, and may abut on the undersurface of the tentorium cerebelli. It is exceptional for the trochlear nerve to be involved at the incisural notch. Inferiorly, large tumors may become adherent to structures in the region of the jugular foramen. The height of the jugular bulb is variable, and may on occasion lie above the level of the lower border of the internal auditory canal (Shao et al 1993). This has important consequences during surgery because it limits exposure in the translabyrinthine operation, and there is a risk of injury when the posterior wall of the internal auditory meatus is removed via a suboccipital approach. The relationship between the jugular bulb and the internal meatus should be determined preoperatively by high resolution CT scan of the temporal bones.

Intraoperative monitoring The use of constant electromyographic (EMG) facial nerve monitoring is now accepted as essential during acoustic 536

neurinoma surgery. Electrodes are placed in the ipsilateral orbicularis oculi and orbicularis oris for the detection of muscle action potentials in response to surgical manipulation or monopolar or bipolar electrical stimulation of the facial nerve. Although objections that the current may harm the nerve have been raised, this is not borne out in clinical practice. For optimal benefit from the facial nerve EMG monitoring it is preferable that a non-muscle relaxant anesthetic technique is used. In a study of 108 patients, Dickins & Graham (1991) concluded that facial nerve monitoring does improve functional results. The stimulator is used to identify the anatomic configuration of the facial nerve, to warn the surgeon if the nerve is being traumatized by manipulation or by traction, and to confirm physiologic as well as anatomic integrity at the completion of the procedure. The early postoperative facial nerve function after tumor removal can be predicted by measurement of the stimulation threshold and the response amplitude to proximal facial nerve stimulation (Mandpe et al 1998). During tumor dissection, the stimulus intensity should be reduced as much as possible, particularly when a unipolar device is in use (~0.25 m/A), or current may leak to the facial nerve when adjacent non-neural tissue is stimulated and produce a false positive response. Care must be taken also not to confuse a masseter contraction from stimulation of the trigeminal nerve with movement of the facial musculature. Dissection of the nerve in a medial to lateral direction is likely to maximize the usefulness of monitoring. Clearly, if physiologic function is lost at any stage, the stimulator is of no further use to aid dissection proximal to that point. Dealing with the region just medial to the porus is usually the most difficult part of the procedure. However, the manner in which the tumor is dissected from the nerve must be tempered by the clinical situation, because a lateral to medial dissection is often easier technically, particularly when the translabyrinthine operation is used. Intraoperative audiometric monitoring has been employed during hearing preservation procedures (Ojemann et al 1984). The methods available currently are monitoring of the electrocochleogram (EcoG) via a transtympanic electrode placed through the inferior part of the tympanic membrane to rest on the promontory of the medial wall of the middle ear, or extratympanic electrode, recording of brain stem auditory evoked potentials (BAEPs) using scalp electrodes, direct monitoring of the cochlear nerve, or measurement of oto-acoustic emissions. EcoG has a larger signal to noise ratio than BAEP, making it more sensitive. A significant reduction in wave V amplitude on BAEP, or a shift in latency, warns the surgeon to moderate dissection, retraction, or the use of bipolar cautery. When wave V is unchanged at the end of surgery useful hearing will be preserved, even if it was lost transiently at some stage (Nadol et al 1992). However, the value of such monitoring remains uncertain. In many instances changes are abrupt, dramatic, and irreversible, and reflect compromise to inner ear vascularity or damage to the labyrinth (Ojemann et al 1984). Unlike monitoring of the facial nerve, there is a delay in response because the measurements require averaging. This is reduced with the use of direct 8th nerve monitoring where changes are closer to real time. In only a few cases does a change in operative technique, such as modification of cerebellar



retraction (Sekiya & Moller 1987) lead to a recovery of monitored potentials. However, identification of the event that caused hearing loss may still be of benefit if it allows the surgeon to modify operative technique in future cases. In a series of 28 patients, Kveton & Book (1992) found no advantage for intraoperative BAEP monitoring in terms of final outcome, although this has not been the experience of other groups (Ebersold et al 1992; Fischer et al 1992).

Instrumentation In addition to the usual array of microsurgical instruments, a fenestrated sucker of the Brackmann type is a useful aid to dissection and minimizes risk of injury to the nerves and vessels. It has been suggested that sucker-induced trauma contributes significantly to postoperative facial neurapraxia (Tos et al 1992c). The Cavitron ultrasonic surgical aspirator (CUSA) or House–Urban rotary dissector may be used to debulk large tumors. We have no experience with either the CO2 or NdYAG lasers, which are reported by some authors to be more advantageous still (Takeuchi et al 1982; Cerullo & Mardichian 1987). The major benefit is said to be rapid tumor debulking with minimal manipulation of the tumor or neurovascular structures (Gardner et al 1983). Use of lasers has not become popular because of the lack of precision associated with uncontrolled heating of adjacent tissue and potential for neural injury.

Surgical approach There are three basic approaches to the cerebellopontine angle: by excision of the labyrinth (translabyrinthine); through a posterior fossa craniectomy (suboccipital/ retrosigmoid); or via the middle cranial fossa. On occasion, more than one approach may be combined at the same or separate operations. No clear consensus has emerged from the literature as to which is the procedure of choice. There are definite advantages and disadvantages associated with each surgical approach. The route chosen is governed by tumor size, the degree of hearing loss, the hearing level in the contralateral ear, and the surgical preference and expertise of the operator. There have, in particular, been many publications recently that compare and contrast the suboccipital and translabyrinthine operations (Di Tullio et al 1978; Tos & Thomsen 1982; Glasscock et al 1986; Mangham 1988; Hardy et al 1989a). Good results are reported with each method and a surgeon can expect progressive improvement in results with experience. It has been proposed that a surgeon should perform the operation at least 10 times a year to remain proficient. The major advantage of the translabyrinthine operation is that the facial nerve can be identified lateral to the tumor at an early stage in the dissection, and access to the fundus of the internal auditory meatus is excellent. Furthermore, retraction of the cerebellum is minimal and the risk of postoperative edema is consequently less. The major disadvantage of this route is that residual hearing is irrevocably destroyed. The approach is unfamiliar to neurosurgeons, and requires the close cooperation of a neurootologist experienced in dissection of the temporal bone. Access is confined,

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but even the largest of tumors can be removed safely via this approach (Briggs et al 1994; Lanman et al 1999). As a consequence of progressive improvements in operative results, particularly in mortality and facial nerve outcome, attention has turned more recently to the ability to preserve useful hearing. The suboccipital operation provides good access to the cerebellopontine angle but, if hearing is to be conserved, tumor at the fundus of the internal auditory meatus may be difficult to expose under direct vision. This is true particularly when the posterior semicircular canal is medially placed. Theoretically, this may increase the risk of sub-total tumor excision when compared with the translabyrinthine operation. This limitation can be reduced by use of the middle fossa exposure which unroofs the internal auditory canal from above, although the falciform crest still obscures the inferior half of the IAC fundus (Haberkamp et al 1998). Recently there has been renewed interest in the middle fossa approach for removal of intracanalicular tumors or those with a small cerebellopontine angle component, particularly where the IAC portion extends to the fundus. Higher rates of hearing preservation have been reported without any compromise of facial nerve function (Brackmann et al 1994; Weber & Gantz 1996). However, this route provides more limited access to the cerebellopontine angle, and is therefore restricted to the treatment of small lesions. The question of hearing conservation deserves careful consideration when selecting the surgical approach. Anatomic preservation of the inner ear and cochlear nerve does not guarantee function, and it is exceptional for hearing to improve on its preoperative level (Telian et al 1988). Whether such hearing is useful depends upon the level of hearing in the contralateral ear. Hearing loss need not be profound before it is socially useless when the other ear is normal. For hearing to be useful socially there must be both good speech discrimination, and a pure tone audiogram within 20–40 dB of the contralateral ear (House & Nelson 1979). Anything less is the equivalent of deafness because there is no balance between the good and impaired ears, directional hearing becomes difficult, and there are problems in coping with noisy environments. In one unselected series, only 16% of patients with an intact cochlear nerve were able to use a telephone with the operated side – 4.4% of the entire group who had undergone suboccipital tumor excision (Bentivoglio et al 1988a). As well as the poor success rate for hearing preservation, there is also the issue of whether such attempts compromise the likelihood of complete tumor removal. Neely (1981, 1984) has shown that the cochlear nerve may be involved with tumor, and that attempts to preserve hearing may not be consistent with one of the major goals of surgery, namely macroscopic tumor excision. We favor the translabyrinthine operation for large tumors, regardless of hearing level, and for medium-sized lesions with poor hearing. It provides a more direct approach to the cerebellopontine angle, and retraction of the cerebellum is negligible. In our hands the morbidity is lower and hospital stay generally a little shorter than after a suboccipital approach. For hearing preservation removal, two of the authors (AK and RB) prefer the retrosigmoid approach for tumors with up to 2 cm CPA extension, particularly where cerebrospinal fluid can be seen lateral to the tumors within the IAC. The middle fossa approach is preferred for 537



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intracanalicular tumors and those with up to 1 cm CPA extension where tumor completely fills the IAC. The merits of the different approaches will be considered further in the section dealing with results. Staged resection Excision of large lesions is difficult and time-consuming. Although planned two-stage resection was described by Ojemann et al (1972), Ojemann and Crowell (1978), and Sheptak and Jannetta (1979), for dealing with very large tumors (>4 cm), one-stage removal is now the norm. Hitselberger and House (1979) observed that when surgery was abandoned because of persistent vital sign changes, a second operation was often tolerated better than the first. They have proposed that the tumor may disengage itself from the brain stem and major vessels in the interim, and thereby reduce vascular compression. In contrast, Mangham (1988) found that the morbidity of planned two-stage operations was significantly higher than for one-stage resection, particularly in relation to facial nerve function. However, if technical difficulties do force abandonment of the procedure short of total removal, a second operation should be undertaken unless there are strong reasons for not doing so. A second operation is best performed within 2–4 days of the initial exploration, before adhesions start to form and the operative site becomes hyperemic. Sub-total excision Elective sub-total removal may be indicated in the elderly, or the infirm, where the aim is to achieve safe brain stem decompression with preservation of facial nerve function, or in patients with bilateral tumors in whom the aim is to preserve residual hearing for as long as possible. More contentious is the issue of achieving the twin aims of total tumor excision and hearing preservation, particularly in the light of the histologic study by Neely (1984), in which he showed that microscopic invasion of the cochlear nerve by tumor was common. However, his work has not been confirmed by Perre et al (1990), who found no infiltration of the cochlear nerve by acoustic neurinoma, except in NF-2 patients. Yet recurrence is not an inevitable sequel, even if tumor is left behind at operation. Capsule remnant may be of no clinical significance, and indeed can atrophy. We will return to this issue later. Suboccipital/retrosigmoid operation Although many neurosurgeons utilize solely the suboccipital approach for excision of vestibular schwannoma our preference is that this is used only for those in which hearing preservation is attempted. The suboccipital approach does provide a wide visualization and the ability to save hearing. Good results have been reported by many groups. (Ojemann et al 1972; Ojemann 1978, 1979, 1980, 1990, 1992, 1993, 1996; Ojemann & Crowell 1978; Ojemann et al 1984; Nadol et al 1987; Ojemann & Black 1988; Ojemann & Martuza 1990; Nadol et al 1992; Rhoton 1986; Symon et al 1989; Klemink et al 1990; Ebersold et al 1992; Samii et al 1992; Gormley et al 1997; Samii & Matthies 1997a,b; Koos et al 1998) The operative approach and techniques have been reported and illustrated in detail in other publications (Ojemann et al 1984; Ojemann & Martuza 1990; Ojemann 538

1992, 1993, 1996, 2001). The operation is done in collaboration with an otologic surgeon, who exposes the internal auditory canal and dissects the tumor within that region. Preoperative medical therapy Steroids are usually commenced prior to the operation if the tumor is large and there is edema of the cerebellum. The steroid dose is continued postoperatively and tapered over 3–7 days, depending on the size of the tumor and facial nerve function. We do not use steroid therapy for smaller tumors. Antibiotics are given intravenously and continue for 24 h postoperatively. Management of preoperative hydrocephalus Symptomatic hydrocephalus is now uncommon in patients presenting with vestibular schwannoma, but if present will usually improve with steroid therapy. A ventricular drain may occasionally be needed at surgery, and for a few days postoperatively. Only rarely does a patient need a ventricular peritoneal shunt as a preliminary procedure. Patients with acoustic neuroma may have enlarged ventricles with no symptoms, and no special treatment is needed. Occasionally an elderly patient with a tumor and large ventricles has symptoms suggestive of normal pressure hydrocephalus. If the only symptom is hearing loss, a ventricular peritoneal shunt may be the only treatment needed. If there are also symptoms of brain stem or cerebellar compression, treatment of the tumor will also be necessary. Positioning Numerous positions have been utilized for this operation, including semi-sitting, prone, supine/oblique, lateral or park bench and a lateral oblique position. In general, we have utilized the lateral or park bench position, preserving the semi-sitting position for very large patients with short necks. The patient is placed on the table with the operative side superiorly with a pad and axillary roll under the torso. Both legs are flexed and two pillows placed between them. The hips are taped for stability and an armrest and back support are placed. The head is held in a three-pin head holder, and flexed and rotated 10–15° towards the floor. The ipsilateral shoulder is taped to hold it away from the surgeon’s access to the craniotomy. The Frameless Stereotactic System may be used to help guide the approach, particularly to mark out the position of the transverse and sigmoid sinus. Continuous electrophysiological monitoring for facial nerve function during the operation is essential and some surgeons use auditory evoked responses in an attempt to help preserve hearing. Incision and exposure A linear or slightly sigmoid shaped incision is made one figure breadth posterior to the transverse-sigmoid sinus junction. The inferior end of the incision is curved medially. The muscles are divided longitudinally and dissected off the bone using monopolar cautery until the root of the digastric groove is visible. Care must be taken to avoid diathermy injury to the extracranial facial nerve which exits the stylomastoid foramen anteriorly in the groove. Pericranium may be harvested at this stage for use in closure of the dura at the end of the procedure. Special care is taken to include the arterial vessels as they are encountered in the muscle. The occipital nerve may be divided during the opening. An



emissary vein is usually exposed in the region of the medial mastoid area, and is usually controlled with bone wax. The bone over the lateral half of the cerebellar hemisphere is exposed. The initial burr hole is made near the asterion to expose the ‘corner’ of the transverse-sigmoid sinus junction and the bone flap is elevated using the high speed drill. A large emissary vein frequently arises from the sigmoid sinus and should be skeletonized with the drill, dissected free of the bone flap and coagulated before division. Small tears in the venous sinus should be covered with a patch of Gelfoam and cottonoid patties. Further bone can be removed anteriorly over the edge of the sigmoid sinus to improve exposure, but this often necessitates opening the mastoid air cells, which must be waxed thoroughly. We have generally utilized a craniotomy, with three burr holes being inserted, the first being in the region of the asterion anteriorly and superiorly, the second being approximately 2 cm posteriorly along the border of the transverse sinus and the third being through the very thin bone inferiorly. However, in elderly patients with very adherent dura it may be more prudent to perform a craniectomy, as it is essential to preserve the dura to enable a watertight closure at the end of the procedure. It is essential to remove the bone laterally and superiorly to expose the edges of the transverse and sigmoid sinuses, as this will allow them to be retracted with sutures to hold the dural flaps and allow a direct line of site down the posterior surface of the petrous temporal bone. The dura is opened in an asymmetrical Y-shaped fashion, with the larger flap hinged anteriorly on the sigmoid sinus, and the smaller flap hinged superiorly on the transverse sinus edge. A critical next step is to open the arachnoid membrane over the infero-lateral cerebellar cisterns and drain CSF to allow the cerebellum to relax. This process is made easier by the preoperative institution of a lumbar drain, and it is essential in larger tumors. A Greenberg retractor system is attached and the retractor blade is used to gently retract the cerebellum. At this stage the operating microscope is brought in, the cerebellopontine angle exposed and the tumor is identified. It is essential to identify the arachnoid plane around the tumor; this greatly facilitates dissection of the surrounding neurovascular structures, which must be preserved. The petrosal vein, which s usually coming off the cerebellum or middle cerebellar peduncle to the petrosal sinus just above the tumor, is preserved if possible, but it may be necessary to take the vein to improve access. It is far better to coagulate and divide this vein rather than inadvertently avulse it from the superior petrosal sinus. The posterior capsule of the tumor is stimulated to locate the facial nerve. In the majority of patients the facial nerve will be on the anterior surface of the tumor and there will be no response on this first stimulation. However, in some patients the nerve is displaced more superiorly, particularly in its lateral course just before it enters the internal auditory canal. In this situation a response may be seen on the initial stimulation. The facial nerve can also be displaced antero-medially along the brain stem and over the anterior superior aspect of the tumor and in this circumstance the facial nerve may be displaced against the 5th nerve. On rare

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occasions, the facial nerve is on the inferior or posterior surface of the tumor capsule (Ojemann 2001). The 9th, 10th and 11th cranial nerves must be identified and the arachnoid adjacent to the cerebellum is carefully dissected to aid exposure of the inferior medial capsule. The arachnoid in this area may need to be opened over these nerves to aid the exposure and prevent traction on the nerves. There is frequently an arterial loop in this region, arising from the anterior inferior cerebellar artery. With large tumors the 9th and 10th nerves are carefully reflected off the tumor and arterial branches going to the capsule are diathermied and divided. It is essential to protect the lower cranial nerves during the remainder of the operation. Except in the largest tumors, it is usually possible to continue the dissection between the tumor capsule and cerebellum down to the brain stem before opening the tumor capsule. This aids in the careful identification and preservation of the plane between the tumor capsule and the adjacent neural structures. Following dissection of the tumor capsule away from the cerebellum, and identification of the lower cranial nerves the posterior capsule is then opened through a linear incision and internal decompression of the tumor is performed utilizing a combination of sharp dissection, bipolar coagulation and the ultrasonic aspirator. It is essential to realize that heat transmission from the bipolar can damage the cranial nerves, therefore the lowest effective voltage must be used. Irrigating or non-stick ‘cool’ bipolars are helpful. Further debulking of the tumor will allow identification and dissection of the tumor- arachnoid plane. It is then possible to retract the tumor capsule laterally, away from the cerebellum and in medium size tumors the 8th nerve complex can usually be defined with minimal dissection. In larger tumors these nerves will usually not be seen initially, and only become apparent after removal of more tumor. Internal decompression of the tumor superiorly will allow the tumor to be reflected laterally away from the cerebellum and inferiorly from the tentorium above, displaying the 5th nerve which may be splayed superiorly and anteriorly across the brainstem. Generally, it is best to continue the dissection on a ‘broad’ front along the whole line of the tumor, rather than just restricted the resection to one section. If hearing preservation is not an aim of the surgery, the vestibular and cochlear fibres entering the tumor can be divided using bipolar coagulation and sharp dissection. The surgeon must carefully look for a branch of the anterior inferior cerebellar artery which may loop behind or between these nerves. The facial nerve is located just under the 8th nerve complex, or may be a few millimeters away. It is usually recognized by its ‘whitish’ color, which is different to the adjacent brain stem. Intermittent stimulation with the facial nerve monitor may help localize the nerve. A further aid to identification of the facial nerve is to follow the 9th nerve to the root entry zone, with the facial nerve arising just adjacent to this region. Following further debulking, the tumor capsule is then gently dissected away from the brain stem and cranial nerves, including the 7th nerve. There is usually a good plane between the brain stem and the tumor capsule, but at 539



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times the tumor may be adherent within the brain stem and the dissection must proceed with meticulous care. The edge of the 7th nerve is carefully identified, with the arachnoid between the tumor and the capsule being dissected with a sharp arachnoid knife or microscissors. It is usually best to dissect the tumor capsule from the 7th nerve ‘side to side’, rather than along the length of the nerve in order to prevent stretching and damage to the nerve. For those tumors in which hearing preservation is an aim of the surgery it is essential to identify the vestibular and cochlear nerves and the relationship to the capsule prior to significant debulking of the tumor. This will help to preserve the plane between the nerves and the tumor capsule. The arachnoid between the nerves and the tumor is opened with sharp dissection, a plane identified and then the tumor can be internally decompressed to allow further dissection of the capsule away from the nerves. Following resection of the tumor from within the cerebellopontine angle the next step is to expose the tumor in the internal auditory canal. Gelatine sponge (Gelfoam) is placed in the subarachnoid space so as to prevent dissemination of bone dust in the cerebrospinal fluid A dural flap, with the base lying along the posterior lip of the internal auditory canal, is lifted from the posterior aspect of the petrous temporal bone over the region of the internal auditory canal and the bone is then carefully removed using the high speed air drill with constant suction irrigation for cooling. Occasionally, a high jugular bulb will be exposed during the bone removal. The surgeon must avoid entering the labyrinth, as this would cause loss of hearing. After the internal auditory canal is exposed the dura is opened and an internal decompression may be performed using sharp dissection so that the capsule can be mobilized with minimal pressure. Dissection then depends on assessment of the relationship of the tumor to the vestibular and cochlear nerves and the facial nerve. In some patients the vestibular nerves entering the medial edge of the tumor are divided and the cochlear and facial nerves are identified and the dissection proceeds from medial to lateral. In other patients it may be difficult to define the cochlear nerve medially. In those cases the tumor is carefully rotated near the lateral end of the canal, looking for the 7th nerve anterosuperiorly and the cochlear nerve anteroinferiorly. Again, it is important to avoid stretching or putting tension on the cochlear or facial nerves so that the fibres are not avulsed. The position of the 7th nerve can be confirmed with stimulation. An internal decompression of the tumor may be performed with sharp dissection to facilitate the exposure. Dissection along the facial and cochlear nerves is undertaken with micro dissectors and a sharp arachnoid knife. The dissection is alternated from different directions, depending on what seems to give the best exposure, the easiest plane of dissection and the least traction on the nerves. In some patients, the lateral end of the tumor may not be exposed because of the limitations in the bone canal. In these patients, and routinely at the end of all procedures we are now using the 70° endoscope to either confirm the complete excision of tumor within the canal, or to aid in resection of the last fragments of the tumor lying laterally within the canal. 540

Closure Following resection of the tumor the dural flap over the posterior petrous temporal bone is then laid back over the exposed bone, which has previously been carefully waxed to prevent CSF leakage. The dural flap is held in place with oxycellulose. Meticulous hemostasis is essential at the end of the procedure. The aim to achieve a watertight dural closure in all cases; in most cases this requires sewing in a dural patch either pericranium or artificial material. The bone flap is replaced, being held in place by small titanium plates and any bone defects repaired using bone substitute. A complete bone repair may reduce the incidence of postoperative headache. The wound is closed in layers. Postoperative care The patient is nursed in the high dependency neurosurgery care unit for the first 24–48 h postoperatively. Intravenous antibiotics are given for 24 h. Particular attention is given to control of postoperative hypertension. We aim to minimize the use of postoperative steroids unless there is brain stem or cerebellar edema. The patient is mobilized early and anti-thromboembolism management is instituted. A non contrast CT scan is performed routinely on day 1 postoperatively to exclude hematoma and hydrocephalus. Delayed facial palsy can occur after 14 days postoperatively. This is usually managed with a short course of oral steroids and frequently resolves. Translabyrinthine operation The translabyrinthine operation was reintroduced to neurosurgery by William House (1964a). The posterior fossa dura is opened in Trautmann’s triangle, bounded by the sigmoid sinus, jugular bulb, and superior petrosal sinus. This exposure provides a more direct route to the cerebellopontine angle than does suboccipital craniectomy, and access is at the expense of bone rather than cerebellar retraction. The surgical field is confined, particularly in the region of the inferior pole of large tumors, but the apex of the cerebellopontine angle is more readily exposed than via the suboccipital route. The presence of an anteriorly placed sigmoid sinus or a high jugular bulb may render access slightly more difficult, but rarely does this cause undue problems. A high jugular bulb occurs in around 9–18% of temporal bones and can be anticipated in petrous bones that are poorly pneumatized (Turgut & Tos 1992; Shao et al 1993). Translabyrinthine exposure can, however, be increased in three ways: (1) superiorly, by opening the middle fossa dura and dividing the tentorium; (2) posteriorly, with or without division of the sigmoid sinus (venous phase angiography should be undertaken to establish the dominance of the sinus and to assess the size of the torcular herophili if ligation is contemplated); or (3) anteriorly, via a transotic approach. The transotic approach was proposed by Jenkins and Fisch (1980) as a modification of House and Hitselberger’s transcochlear operation (1976). This is essentially a sub-total petrosectomy, but with skeletonization rather than translocation of the facial nerve. Access is thus provided circumferentially around the internal auditory meatus. We have never found this extension to the translabyrinthine approach necessary when dealing with primary tumors. Sacrifice of residual hearing is the major disadvantage of the translabyrinthine operation. However, only 1% of affected



ears will have normal hearing after suboccipital surgery (Harner et al 1984), and it is rare for hearing to improve on preoperative levels (Telian et al 1988). The question of hearing preservation will be discussed later. Translabyrinthine surgery is contraindicated in the presence of chronic perforation of the tympanic membrane or acute infection of the middle ear or mastoid, because of the risk of meningitis. The operation requires close cooperation between neurosurgeon and neurootologist. House (1979) suggests that both should be thoroughly proficient in all phases of the procedure and be able to act interchangeably. We think that this is unnecessary, and that each specialist should utilize the skill in which (s)he has the greater expertise. Occasionally, the preoperative diagnosis of acoustic neurinoma is found at surgery to be incorrect. Although access is more confined via the labyrinth, King and Morrison (1980) removed three jugular neurinomas successfully via this route. Meningiomas with an origin anterior to the porus may however prove more problematic because the angle of approach to the petrous face is less acute than with suboccipital surgery, although access to the petrous apex is unquestionably better. In these cases exposure can be extended by opening the dura over the temporal lobe and dividing the superior petrosal sinus and tentorium. This exposure is best planned in advance, a small temporal craniectomy being used in addition to the usual translabyrinthine exposure. However, it can be done as an ad hoc procedure by extending the mastoid incision upwards onto the temporal squamosa. Technique The patient is anesthetized, prepared, and placed in the supine position. The operation is conducted under general anesthesia with endotracheal intubation and continuous facial nerve EMG monitoring. Although spontaneous ventilation was at one time popular to identify potential brain stem compromise, mechanical ventilation is now the norm because of the ability to lower intracranial tension. Continuous monitoring of arterial blood pressure, electrocardiogram, and central venous pressure is established, together with adequate venous access. Changes in blood pressure (hypertension) or heart rate (bradycardia or arrhythmia) during tumor dissection warn the surgeon of pressure or traction effects to the brain stem, or impairment of its blood supply. The bladder is drained via a urethral catheter. The head is rotated around 45°, avoiding obstruction to the great veins of the neck. Dissection of the petrous bone adds a further 1.5–2 h to the duration of the procedure, so that attempts to avoid pressure sores and to keep the patient warm are essential. Fat and fascia lata are taken from the lateral aspect of the right thigh and are soaked in antibiotic solution until required. Mannitol may be useful if the tumor is large. An inverted hockey stick incision commences just below the mastoid tip, runs about 2 cm behind and parallel to the root of the pinna, and curves anteriorly to end about 1 cm above the external auditory meatus. The exposure from this incision is larger than necessary, but keeps the hemostats away from the operative field. In addition, it allows access to the middle cranial fossa with division of the superior petrosal sinus and tentorium should it be required. This is not necessary for acoustic neurinoma surgery, but may be appropriate when dealing with other lesions of the cerebellopontine angle.

Acoustic neurinoma (vestibular schwannoma)

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The scalp flap is reflected anteriorly. Using cutting diathermy, a pericranial flap is raised in a similar fashion, and turned anteriorly to expose the posterior bony rim of the external meatus. Two of the authors (AK and RB), prefer to secure the patient’s head using a three-pin fixation. This allows use of the Greenberg retractor for subsequent sigmoid sinus compression and dural retraction during the temporal bone dissection. Abdominal fat is harvested immediately prior to use at completion of the procedure rather than tissue from the thigh. We also prefer a more generous C-shaped incision which is placed well behind the mastoid and sigmoid sinus. After the scalp flap is elevated, fibro­periosteal flaps are created with a T-shaped incision which can be securely closed over the fat packing (Fig. 28.15).

Scalp flap A

T-shaped fibro periosteal incision

B Figure 28.15  (A) Skin incision for the translabyrinthine operation. (B) Fibroperiosteal incisions to expose mastoid cortex.

541



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Next the neurootologist performs an extensive cortical mastoidectomy using an air drill with a cutting burr. The bone dust is collected for use later. The initial dissection is conducted under direct vision, resorting to the operating microscope as the exposure deepens. The opening is roughly the shape of a large keyhole. The external opening should be as large as possible, to permit extradural retraction of the cerebellum and temporal lobe if necessary, particularly if the sigmoid sinus is anteriorly placed or the middle fossa dura low. Anteriorly, the posterior wall of the external meatus is thinned. Superiorly, the dissection should expose the edge of the middle fossa dura and superior petrosal sinus. The dissection is carried anteriorly above the external meatus as far as possible. The sigmoid sinus is exposed posteriorly, and approximately 1 cm of dura exposed behind the sinus, but a small island of bone may be left over the sinus, allowing it to be depressed without risk of injury (Bill’s island) (Fig. 28.16). Inferiorly, the mastoid process is hollowed out. It is particularly important to remove sufficient bone posteriorly and superiorly to improve access by retraction of the dura. The margins of the bony defect should be smoothed and beveled to avoid overhanging edges, and perhaps to lessen the risk of postoperative chronic wound pain. The dissection is deepened in the space between the middle fossa dura and superior margin of the meatus, to open the mastoid antrum and aditus. The incus and head of the malleus are exposed, and the incus is removed. The lateral semicircular canal is identified on the medial wall of the epitympanic recess. This is the key landmark for the horizontal portion of the facial nerve, which lies below and parallel to the anterior part. Once the position of the facial nerve has been established, its descending portion can be skeletonized and this marks the anterior limit of the exposure inferiorly (Fig. 28.17A). Even when covered with a thin plate of bone, the stimulator may still be used to identify the location of the intrapetrous portion of the facial nerve,

although the stimulus current will have to be increased temporarily. Dense bone marks the otic capsule surrounding the semicircular canals. The lateral canal is removed first, and its anterior limb leads into the vestibule. The posterior and superior canals are followed to the crus commune, but the ampullated end of the posterior canal is not removed because it lies deep to the second genu of the facial nerve. The labyrinthine vein traverses the arc of the superior semicircular canal, and is a useful landmark (Fig. 28.17B). The posterior fossa dura is skeletonized and the vestibular aqueduct and endolymphatic sac removed. The jugular bulb is identified. Exposure here must be adequate to allow mobilization of the lower pole of the tumor later. Removal of bone in the angle between the jugular bulb and dura is particularly useful in this regard. The position of the jugular bulb is variable. It

Descending facial nerve Digastric ridge

Sigmoid sinus A

Incus

Vestibular labyrinth Middle fossa dura

Presigmoid dura Endolymphatic sac Vestibule opened Superior semicircular canal Common crus Vestibular aqueduct Endolymphatic duct Endolymphatic sac

B Figure 28.16  Postoperative CT demonstrating the left temporal bone defect following translabyrinthine removal of a large acoustic neurinoma. Exposure of the cerebellopontine angle and internal auditory meatus is more direct than via a suboccipital approach.

542

Figure 28.17  (A) Extended mastoidectomy completed with skeletonization of the semicircular canals and descending facial nerve.   (B) Labyrinthectomy completed.



Acoustic neurinoma (vestibular schwannoma)

may be quite high, on occasion almost reaching the ampulla of the posterior semicircular canal (House 1979). Bleeding from injury to the jugular bulb can be controlled by hemostatic gauze or with a muscle pack. After completion of the labyrinthectomy the descending and horizontal segments of the facial nerve should be skeletonized on the medial aspect to allow maximal access to the vestibule and internal auditory canal. The internal auditory meatus lies immediately deep to the vestibule. The most satisfactory way of entering the internal meatus is to remove the utricle and saccule, to identify the stump of the superior vestibular nerve, and to follow it through the thin bone into the internal auditory meatus. Once exposed, the entire posterior wall, and as much of the superior and inferior walls as possible, are removed. A diamond burr is used at this stage. Initially bone removal is performed inferiorly between the jugular bulb and internal auditory canal. The cochlear aqueduct is opened and followed medially to the posterior fossa dura. This forms the most inferior aspect of the bony dissection to prevent injury to the lower cranial nerves. Further bone is removed anteriorly above the cochlear aqueduct at least until the anterior wall of the internal auditory canal can be palpated. Great care is needed when drilling away the anterior aspect of the superior margin of the meatus, as the facial nerve lies directly beneath the dura. A burr should be selected to fit between the middle fossa dura and the dura of the IAC, where if possible the direction of rotation of the drill should be changed such that, should the drill tip run off, it will be directed away from the nerve. The bone dissection is completed by removing the lateral lip of the porus acousticus. If necessary, the intrapetrous portion of the facial nerve lying between the internal meatus and geniculate ganglion can

28

also be exposed with a diamond burr. In the lateral end of the meatus the facial and superior vestibular nerves are separated by a vertical crest (Bill’s bar), which provides a constant landmark for the identification of the facial nerve lateral to the tumor (Fig. 28.18). The resultant cavity in the temporal bone is roughly pyramidal, bounded posteriorly by the sigmoid sinus and posterior fossa dura, superiorly by the middle fossa dura and superior petrosal sinus, and anteriorly by the petrous bone, middle ear cavity and facial nerve, and with the internal auditory meatus as its apex. The otologic dissection is completed using an elevator to remove the remaining bone flakes left behind on the dura. The neurosurgeon starts the next phase of the procedure by opening the dura, first of the posterior fossa, and then of the meatus. The extent of the dural incision in the posterior fossa is dependent upon the tumor size. For large lesions the incision runs posteriorly from the meatus and divides into upper and lower limbs. The superior limb extends to the junction of the sigmoid and superior petrosal sinuses, and the inferior limb down toward the jugular bulb. Retraction sutures are placed on each of the dural flaps (Fig. 28.19). The incision is then extended into the porus. Here the dura forms a rough fibrous ring, which is often quite vascular. Once divided, the dura is freed from the vestibular nerves using a blunt hook or dissector, and the thin dura of the internal meatus is divided up to the fundus of the canal. The tumor and superior vestibular nerve are gently displaced inferiorly until the facial nerve is identified anterior to it and Bill’s bar, and confirmed with the nerve stimulator. The superior and inferior vestibular nerves are then divided lateral to the tumor. A blunt hook can be passed behind them to assist with division, if required. The apex of the

Facial nerve (labyrinthian segment) Cochlear aqueduct

Vertical crest (Bill’s bar)

Facial nerve

Transverse crest

Tumour

Dural incision Figure 28.18  Temporal bone and internal auditory canal dissection complete: lines for dural incision shown.

Figure 28.19  Initial tumor exposure following dural incision and retraction.

543



II

Specific brain tumors

intracanalicular component of the tumor is then displaced posteriorly, and the plane between tumor and facial nerve is developed by sharp dissection. It is necessary to divide the arachnoid lying either side of the facial nerve. Care should be taken not to apply traction to the nerve. The tumor is freed progressively from its attachment to the arachnoid and dura. If the tumor is very small this plane can be continued and the tumor freed from the attachment at the porus, at which point it is always densely adherent to the dura. However, this is not the best strategy for large tumors, for two reasons. First, the facial nerve usually deviates acutely just medial to the porus (almost always either anteriorly or upward), and it is very easy to lose the correct plane and become subcapsular. Second, if the attachment of the tumor to the porus is divided completely, the weight of the tumor is suspended from the facial nerve and may cause a traction neurapraxia. For these reasons, large tumors occupying the cerebellopontine angle should be mobilized and debulked before the dissection is completed at the porus. Particular care should be taken when dissecting along the inferior margin of the porus, as it is here that the anterior inferior cerebellar artery is most likely to be encountered. The dissection begins in the cerebellopontine angle by incision of the arachnoidal cap between the cerebellum and the posterior tumor capsule. The medullary CSF cistern is opened in the region of the jugular foramen and the 9th to 11th nerves are freed from the mass. The anterior inferior cerebellar and vertebral arteries may at times be visible at this point. The plane between tumor and cerebellum is then developed progressively. Only vessels actually entering the lesion can be coagulated. Gentle retraction using a sucker tip held against a pattie will prevent the capsule of more friable tumors from breaking up. Once the limit of mobilization is reached, or when any of the major landmarks are identified, a pattie or small silastic sheet is placed to mark their position, and the point of attack is then shifted to another direction. However, it is a mistake to line the dissection with too much material, and a conscious effort should be made to keep it to a minimum. Larger neurinomas must be debulked to continue the dissection; the Cavitron ultrasonic aspirator (CUSA) is ideal for this purpose. Care must be taken not to breach the tumor capsule or apply excessive movement to it, which might injure the nerves or induce spasm in adjacent arteries. Progressively more of the arachnoidal plane can be developed as the tumor is debulked until, ultimately, the brain stem is exposed. Rarely, induced hypotension may be useful if the tumor is excessively vascular, or a small piece of wool soaked in saline, thrombin, or hydrogen peroxide can be left temporarily within the tumor cavity. A systolic blood pressure of 80–100 mmHg can be sustained for long periods without adverse consequences. The white surface of the brain stem is readily distinguishable from the more yellowish appearance of the cerebellum. The flocculus and the choroid plexus emerging from the foramen of Luschka should be identified, and are important landmarks for the adjacent cranial nerves. With larger tumors, exposure of the facial nerve entry zone is difficult until nearly all of the tumor has been debulked. Adhesions between tumor and brain stem are rarely dense, but a number of veins are usually encountered here, and bleeding may be troublesome. It is absolutely essential that all arteries 544

are preserved because they may supply not only the tumor but the brain stem. Any arterial bleeding should be treated by patient, gentle pressure on a piece of appropriately placed hemostatic gauze. If the anesthetist reports changes in vital signs during this or at any other point in the dissection, traction on the tumor should be discontinued. It may be necessary also to remove some of the packing in order to reduce compression of the adjacent vessels. The vestibular and cochlear nerves are divided once they have been differentiated from the facial nerve, remembering that the anterior inferior cerebellar and/or labyrinthine arteries may on occasion lie directly anterior to the vestibular nerve. The upper and lower poles of the tumor can be mobilized only when the position of the facial nerve has been established. Usually it is displaced anterior to the tumor mass or, less commonly, over the superior surface. During dissection of the upper pole, the trigeminal nerve is encountered deep down as a white band passing across the subarachnoid space to enter Meckel’s cave. The nerve is often adherent to the tumor capsule near the pons, and the basilar artery and abducent nerve may be visible deep to them. The dissection is completed by working from lateral to, medial to, or above the facial nerve. Sharp dissection is less traumatic to the nerve than blunt, and traction must be avoided. Throughout the dissection the nerve should be irrigated with saline, both to wash away any bleeding which will otherwise obscure the field, and to keep it moist. It is often easier to dissect the facial nerve from the tumor in a lateral to medial direction. However, if the plane has been lost medial to the porus, the facial nerve can usually be identified by displacing the tumor inferiorly with the sucker. The nerve is exposed deep to and slightly above the porus, and is separated from it by sharp dissection. The facial nerve is most vulnerable to injury if it lies on the superior pole or, much more rarely, posteriorly. In either case, the tumor must be dissected deep to the nerve. Constant EMG monitoring during tumor debulking and facial nerve dissection is essential to reduce injury to the nerve. Proximal stimulation can be used to assess functional integrity both during dissection and at the completion of the tumor removal. Once the tumor has been removed (Fig. 28.20), the facial nerve and porus acousticus should be inspected carefully for capsular remnants or residual neurinoma. If it is necessary to leave tumor fragments behind, bipolar coagulation of the remnants may make regrowth less likely (Lye et al 1992), although care must be taken to avoid heat injury to the structure to which they are adherent. In general, neural integrity should not be jeopardized in an attempt to excise every last vestige of tumor capsule. This occasions some agonizing at operation, and the alternative is resection and nerve grafting. However, the likelihood of symptomatic recurrence from small capsular remnants appears to be slight (Lye et al 1992), The least satisfactory outcome is to leave tumor attached to the nerve, having already damaged it irrevocably in an attempt at total tumor excision. The physiologic integrity of the facial nerve is tested at the conclusion of the procedure. Although non-function does not preclude a good final outcome, success almost guarantees it (Mandpe et al 1998). The technique for dealing with a divided facial nerve is given below. All cottonoids and



Acoustic neurinoma (vestibular schwannoma)

Vertebral artery Lower cranial nerves

Facial nerve N.VIII stump

Figure 28.20  The tumor bed at completion of the resection. The facial nerve is shown in its most usual position displaced medially and upwards.

silastic sheeting are then removed from the wound, and any small clots are evacuated. Meticulous hemostasis must be obtained, and the blood pressure should be restored to preoperative levels before the wound is closed. Some surgeons may choose to line the cerebellum and brain stem with hemostatic gauze. This, however, should not be used to excess because it swells over a period of hours by absorption of fluid into the cellulose, and can itself induce pressure effects. Careful attention is required during wound closure if cerebrospinal fluid leakage, the most common complication of acoustic neurinoma surgery, is to be avoided. The bone dust collected during labyrinthectomy is made into a thick paste (bone pate) by mixing it with a small amount of autologous blood. During excision of the labyrinth the incus is removed, and a posterior tympanotomy slot is cut to expose the middle ear cavity and the mesotympanic end of the eustachian tube. Small pieces of fat, each about the size of a grain of wheat, are packed into the eustachian tube and middle ear cavity. Particular attention is paid to the region of the aditus, the head of the malleus, and the stapes footplate. The drilled surface of the petrous bone, posterior canal wall, aditus, and any exposed mastoid air cells are then covered with bone pate. A patch of fascia late (~2.5 cm × 2 cm), or abdominal fascial flap, is then applied to the area and sealed with fibrin glue. No attempt is made to close the dural defect. The temporal bone is filled with two or three finger-sized fat strips, which are positioned through the dural defect, just into the cerebellopontine angle. These are sealed laterally with the remaining fibrin glue. The remainder of the wound closure technique is the same as that used for a retrosigmoid approach. If the skin has been elevated from the posterior wall of the external auditory canal, a BIPP pack should be

28

placed in the ear for 7 days. The authors (AK and RB) repair the dural defect with interrupted proline sutures and if necessary place a patch graft of fascia or dermis sutured into position if the dura is very fragmented. This does not provide a watertight seal as no attempt is made to close the defect at the porus, but rather a secure bed for the abdominal fat graft is created. For extensively pneumatized temporal bones the incus is removed and the eustachian tube occluded in the protympanum as described above. For less pneumatized temporal bones the incus is not removed. Muscle is packed around the incus in the aditus and then the translabyrinthine defect is obliterated with longitudinal strips of fat. The fibroperiosteal flaps are then securely closed to hold the fat packing in position. Middle cranial fossa approach The middle cranial fossa approach was described by House in 1961. It is unique in allowing access to the labyrinthine segment of the facial nerve without sacrifice of hearing. On its own it has been used for hearing preservation operations on tumors confined to the internal auditory canal or extending less than 5 mm into the cerebellopontine angle (Glasscock et al 1986). In addition, it may be combined with either the translabyrinthine or suboccipital approaches for the removal of larger lesions (Glasscock et al 1986). It has been criticized on the grounds of its restricted exposure, and because of potential complications which include temporal lobe epilepsy, dysphasia, intracerebral hematoma, and a greater risk to the facial nerve (Gantz et al 1986). Access to the posterior fossa is very limited, and this may give rise to problems in securing adequate hemostasis. With this approach the facial nerve lies superior to the tumor, requiring the surgeon to work around it. Manipulation of the nerve is therefore likely to be greater than with either the suboccipital or translabyrinthine approaches and is reflected in slightly poorer early facial nerve results. Despite these potential limitations the middle fossa approach is now favored in a number of centers for tumor removal where hearing preservation is attempted, particularly where preoperative imaging demonstrates that tumor extends to the fundus of the IAC (Brackmann et al 1994; Weber & Gantz 1996). Technique The technique described here is that currently used by the authors RB and AK. The patient is positioned supine with the head rotated into a full lateral position and secured with three-pin fixation. A lumbar spinal drain is initially inserted to facilitate subsequent dural and temporal lobe elevation. An area of abdomen is prepared for harvesting of a fat graft. The surgeon sits at the head of the table. A variety of incisions have been described, such as a vertical preauricular muscle splitting or an inverted U-shaped flap. We prefer a curved incision with an inferior vertical limb placed just anterior to the helix to allow elevation of an anteriorly based scalp flap. Temporalis muscle is then elevated separately as an anteroinferiorly based flap. A generous rectangular craniotomy measuring approximately 5 × 4 cm is then made in the squamous portion of the temporal bone (Fig. 28.21). The base of the craniotomy should be level with the middle fossa floor as identified by the temporal root of the zygomatic arch, and the opening is placed two-thirds 545



II

Specific brain tumors

Ossicles

Labyrinth

Geniculate ganglion

Bill’s bar

Greater petrosal nerve Middle meningeal artery

Superior vestibular nerve

Cochlea Cochlear nerve Facial nerve

Figure 28.22  Middle fossa craniotomy with dural elevation and outline of intratemporal structures.

Figure 28.21  Skin incision and site of craniotomy for middle fossa operation.

anterior and one-third posterior to the external auditory meatus. The lumbar spinal drain is opened while the craniotomy is being performed. The dura is initially separated from both the lateral and inferior borders of the craniotomy. Inferiorly, further bone may be removed using a rongeur or burr to the level of the surface of the temporal bone. Any mastoid cells which are opened posteriorly should be occluded with bone wax. Dural elevation should commence posteriorly with progressive exposure of the tegmen mastoideum, tegmen tympani, and arcuate eminence. Elevation in an anterior direction will avoid elevation of the greater superficial petrosal nerve and therefore inadvertent traction to the facial nerve. In approximately 5% of cases the bony covering of the greater superficial petrosal nerve and geniculate ganglion is dehiscent at the facial hiatus (Rhoton et al 1968; Buchheit & Rosenwasser, 1988). Dura is elevated forward until the foramen spinosum and middle meningeal artery are exposed (Fig. 28.22). Medially the superior petrosal sinus is identified and carefully elevated from its groove to identify the true posterior surface of the temporal bone. Dural retraction can be achieved using the specifically designed House–Urban middle fossa retractor, which is secured to the craniotomy margins. We prefer to use the Greenberg retractor with a 1 cm wide metal blade. The blade is bent to avoid the projection that occurs with the self-retaining device. The blade of the retractor is inserted to the apex of dural elevation and is progressively advanced as elevation proceeds. If at any stage the dura is torn the defect should be repaired immediately to prevent herniation of the temporal lobe. Anteromedial to the arcuate eminence the surface of the temporal bone is somewhat flattened and this has been termed the ‘meatal plane’ as it lies above the 546

region of the internal auditory canal. The line of the IAC bisects the angle between the superior semicircular canal (SSC) arcuate eminence and the greater superficial petrosal nerve (GSPN). Bleeding may be troublesome during dural elevation. Bleeding of small dural vessels is easily controlled by bipolar cautery and venous bleeding from the bone surface by bone wax. Venous sinus bleeding, e.g., around the foramen spinosum, is controlled by Surgicel packing. A variety of techniques have been described for identification of the internal auditory canal (IAC). The early techniques used the GSPN and SSC as landmarks to define the internal canal. The GSPN was identified as it exited the facial hiatus and then bone was removed posteriorly along the course of the nerve until the geniculate ganglion was uncovered. The labyrinthine portion of the facial nerve was then identified medial to the ganglion and hence the IAC exposed further medially. The superior semicircular canal was bluelined by removal of bone over the arcuate eminence to provide a further posterior landmark. These methods required meticulous technique with little margin for error as the ampullated end of the SSC and the cochlea lie within millimeters of the labyrinthine segment of the facial nerve. We prefer the method of identifying and dissecting the IAC that is described by Garcia-Ibanez and Garcia-Ibanez (1980) and more recently by Brackmann et al (1994). Bone removal is commenced at the medial aspect of the meatal plane where both the SSC and cochlea are at greatest distance. Drilling begins directly over the bisection of the angle between GSPN and SSC until the dura of the IAC is exposed beneath the petrous bridge. To facilitate safe tumor removal, wide bone removal is required and so dissection extends anteriorly into the petrous apex medial to the otic capsule of the cochlea and posteriorly to the level of the SSC. Bone is progressively removed around the medial IAC until the posterior fossa dura and IAC dura is exposed over 270°. After medial exposure of the internal canal, bone is gradually removed in a lateral direction. The semicircular canal is skeletonized and the labyrinthine segment of the facial nerve identified. Bill’s bar is identified laterally, however care is



Acoustic neurinoma (vestibular schwannoma)

28

Dura of internal auditory canal incised

Tumor

Medial bone drilled away

Tumor exposed in internal auditory canal

Figure 28.23  Internal auditory canal bony dissection.

Figure 28.24  Tumor exposure within the internal auditory canal following dural incisions.

taken not to remove bone >120° at the lateral IAC to avoid entering the cochlea or SSC ampulla. As the dura of the IAC is exposed, the exact extent of the canal can be assessed by extradural palpation with a small hook or elevator. Continuous facial nerve EMG monitoring is essential to ensure atraumatic bony dissection as the dura and fallopian canal is exposed. Separation of the IAC dura from the bony canal also helps to prevent accidental injury to the dura and underlying facial nerve. Bill’s bar, the vertical crest of bone at the fundus, marks the lateral extent of the IAC and also the clear anatomic division between the superior vestibular nerve and the facial nerve (Fig. 28.23). At the completion of bone removal, the cerebellopontine angle is initially opened by incising the posterior fossa dura between the posterior aspect of the porus acousticus and the superior petrosal sinus. Cerebrospinal fluid is released by dividing the arachnoid, and the dural incision is continued laterally along the posterior aspect of the IAC. The dura is elevated and reflected anteriorly to expose the facial nerve overlying the anterior aspect of the tumor (Fig. 28.24). Great care must be taken where the dura is adherent to the tumor and the nerves at the porus acousticus. At the fundus of the IAC the dura is carefully divided posterior to Bill’s bar and then over the facial nerve until the separation of superior vestibular nerve and facial nerve is clearly displayed. The electrode for continuous 8th nerve monitoring can now be placed beneath the reflected dural flap anteriorly or on the cochlear nerve medially within the cerebellopontine angle. Tumor removal with successful facial nerve preservation is accomplished by initial separation of the facial nerve from the superior vestibular nerve (SVN) and from the tumor. If the tumor has arisen from the superior vestibular nerve the lateral fibers of the nerve blend into the tumor and the posterior border of the facial nerve must be sharply dissected

from tumor capsule. The line of anatomic dissection is easily identified laterally. With inferior vestibular nerve tumors the facial nerve must be separated from the SVN along its length and then separated from the tumor capsule beneath. A normal preoperative caloric response may provide indirect evidence that the tumor arises from the inferior vestibular nerve, and this may be considered as a relative contraindication to this approach (House & Luetje 1979). The principles of tumor dissection are the same as those outlined above. The superior vestibular nerve is divided laterally and, unless the tumor is small and only involving the superior vestibular nerve, the inferior vestibular nerve is likewise divided. After initial separation of the facial nerve from the tumor, debulking is performed unless the tumor is very small. Debulking allows subsequent manipulation within the IAC without stretching of the facial or cochlear nerves. The previous anterior bone removal medial to the cochlea allows displacement of the facial nerve towards the petrous apex, thereby facilitating dissection of the tumor from the cochlear nerve. The facial nerve will be most densely adherent to the tumor at the level of the porus, and the exact direction of the course of the nerve must be established as sharp dissection proceeds. For successful hearing preservation, the arterial supply to the cochlea must be preserved and so bipolar cautery is only used when absolutely necessary. The arterial supply to the cochlea consists of vessels which run between the facial and cochlear nerves in the anterior half of the canal so the utmost care must be taken to preserve vessels anteriorly within the IAC. Similarly, during medial dissection of the tumor, care must be taken to identify and preserve the anterior inferior cerebellar artery, which may loop between the facial and vestibulocochlear nerves at the porus. After initial debulking of the tumor progressive dissection from the cochlear nerve should be performed in a medial to lateral dissection direction. This avoids traction on the fragile 547



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Specific brain tumors

cerebellopontine angle hematoma are masked. The patient should be nursed 15° head-up to reduce venous pressure. Peri­operative antibiotics should be administered, and dexa­ methasone may be of limited benefit, not only to reduce postoperative edema in the cerebellum, but to reduce swelling of the facial nerve and resultant delayed facial weakness. When large tumors have been excised, the patient should be assessed for bulbar palsy before oral fluids are commenced. The consequences of facial palsy are dealt with below. Vestibular sedatives may be required if dizziness and vomiting are troublesome, but their use should be restricted to a minimum. Scalp sutures and the BIPP ear pack are removed on the 7th day.

Superior vestibular nerve remnant

Inferior vestibular nerve

Facial nerve

Figure 28.25  Tumor removal complete. Superior vestibular nerve divided. Cochlear nerve beneath facial nerve.

nerve fibers entering the cochlea laterally at the spiral foramina and is important in preserving hearing (Fig. 28.25). After total tumor removal is achieved and hemostasis is noted to be secure, the anterior dural flap is replaced to protect the facial nerve. A watertight dural repair is not possible, however a single suture may be used to re-approximate the posterior fossa dura. This provides support for a piece of abdominal fat which is used to occlude the bony IAC defect. Any air cells opened on the temporal bone surface are occluded with bone wax and if necessary reinforced with a sheet of temporalis fascia. The dura is secured to the margins of the craniotomy, the bone flap is replaced and secured with rigid fixation, and the wound is then closed in layers in the usual fashion. The spinal drain is removed at the completion of the procedure. Combined approaches Should exposure prove to be inadequate, the translabyrinthine approach may be combined with the transtentorial or suboccipital routes, as may be suboccipital and middle fossa operations. Although we have undertaken combined approaches in the past, and still do so on occasion for other tumors of the cerebellopontine angle, particularly meningiomas, we no longer find them necessary for excision of acoustic neurinomas. Postoperative care Patients are extubated at completion of the procedure and after perioperative recovery are nursed in a neurosurgical intensive care unit for 24  h. A brief period of postoperative ventilation may be appropriate after long procedures, particularly if the patient has become hypothermic during surgery. Although this has the advantage that intracranial pressure is kept low, one major disadvantage is that early signs of neurologic deterioration from an impending 548

Results Most of the complications that may befall a patient after surgery are common to all three approaches. The exceptions are epilepsy and dysphasia, which are confined to the middle fossa operation, or in the exceptional case when it has been necessary to divide the tentorium. In unselected series mortality figures for the different surgical approaches are almost identical and range from 0 to 2% in the hands of experienced surgeons in specialist centers. Almost all fatalities occur in patients with very large tumors. The major causes of death are brain stem infarction and hematoma in the cerebellopontine angle. Most other deaths follow cardiovascular or respiratory complications. Tumor size is by far the most important single determinant of outcome, in terms of mortality, facial nerve outcome, and the prospect for a good general recovery (Olivecrona 1967; House & Luetje 1979). Several large series have documented surgical results as they relate to tumor size. Outcome is regarded as excellent if patients are able to resume their previous employment, fair if they remain independent but unable to work, and poor if their independence has been lost. This classification excludes facial nerve function. The results of five series are summarized in Table 28.2. There has been much discussion in the literature comparing and contrasting the merits and disadvantages of the suboccipital, translabyrinthine, and middle fossa approaches to the cerebellopontine angle. Good results are reported with each method, which indicates that experience, operative microsurgical technique, and postoperative management are more important determinants of outcome than the surgical approach per se. Direct comparisons between large series employing different surgical techniques are often misleading for two reasons. First, tumor size is the most important predictor of outcome, yet there is no single accepted classification to enable standardization of reporting of results. Second, the suboccipital and middle fossa approaches are often selected for hearing preservation procedures. Inevitably such patients have a higher proportion of small tumors and therefore a better prognosis than with the translabyrinthine operation, which is more appropriate for larger lesions with poor residual hearing. Patients with small or mediumsized tumors also have a significantly shorter mean hospital stay than those with larger lesions (Mangham 1988). When considering the approach of choice for any one lesion, we agree with Chen & Fisch (1992) that ‘most patients are far more concerned about the complete removal of their



Acoustic neurinoma (vestibular schwannoma)

28

Table 28.2  Surgical results by tumor size Author Yasargil & Fox 1974

Cases (n)

Operation

Tumor size

(%)a

Mortality (%)

100

SO

Small Medium Large

4 19 77

0 0 4

Facial nerve result (%)b 85

Outcome in survivors Excellent (%) Fair (%) Poor (%) 95 82 56

5 13 37

0 5 7

100 100 91

0 0 7

0 0 2

Ojemann et al 1984

123

SO

Small Medium Large

15 30 55

0 0 1

King & Morrison 1980

150

TLc

Small Medium Large

11 42 47

0 2 3

100 80 20

94 100 93

6 0 5

0 0 2

Bentivoglio et al 1988a

94

SO

Small Medium Large

14 28 58

0 0 4

100 85 45

100 92 66

0 4 28

0 4 8

100

TL

Small Medium Large

4 30 66

0 0 4

82

100 83 66

0 17 29

0 0 5

Hardy et al 1989a

SO, suboccipital; TL, translabyrinthine. a The results of the different series are not strictly comparable as the definitions of tumor size varied. Small, medium, and large approximate to the Pulec classification. b Facial nerve figures in some series are anatomic preservation rates, while others relate to functional outcome. c Denotes primary surgical approach, although series mixed.

tumor and their facial function postoperatively than about hearing’. It is primarily for this reason that we favor the translabyrinthine operation for the majority of patients. Postoperative morbidity and hospital stay are generally shorter after translabyrinthine surgery (Tos & Thomsen 1982; Gardner et al 1983; Tator & Nedzelski 1985), although the incidence of postoperative meningitis may be slightly higher because of a more direct route for contamination of the CSF by nasopharyngeal organisms (Mangham 1988). Sterkers et al (1984) initially favored the translabyrinthine operation but used the suboccipital approach subsequently for hearing preservation. They have since reverted to the translabyrinthine operation as a result of higher morbidity and an increased incidence of facial nerve palsy. Although the results reported in the literature are excellent with each of the approaches, it should be remembered that they represent the best in the field. For the less experienced surgeon the translabyrinthine approach is probably more likely to produce a good result because of improved access to the fundus of the tumor and the ability to identify the facial nerve lateral to it at an early stage of the dissection, but it is unfamiliar to most neurosurgeons, who may be uncomfortable with it, at least to start with.

Facial nerve function In unselected series, anatomic preservation rates for the facial nerve are generally around 71–90% using the suboccipital route (Yasargil et al 1977; Sugita & Kobayashi 1982; Harner & Ebersold 1985; Bentivoglio et al 1988a) and 80– 96% for the translabyrinthine group (House & Luetje 1979; Whittaker & Luetje 1985; Hardy et al 1989a). In neither group was anatomic preservation of the nerve achieved at the expense of sub-total tumor excision, as previously suggested by Di Tullio et al (1978). Success at preservation is highly dependent on tumor size (Table 28.2). In a series of 444 patients, House & Luetje (1979) reported complete facial

paralysis in 0% of patients with small tumors, in 10.4% of those with medium-sized lesions, and in 21.4% of those with large tumors. In a report of 43 patients with small tumors operated on through the middle fossa, Gantz et al (1986) were able to preserve the facial nerve in all but one case. However, 60% had some facial nerve dysfunction immediately after surgery and 38% experienced complete paralysis. Ultimately, 86% achieved near normal function. Improved results, both in terms of hearing preservation and facial nerve function, have been reported in a subsequent series of patients from the same institution (Weber & Gantz 1996). Shelton et al (1989a) reported their experience of 106 cases operated via the middle fossa, with near normal facial nerve function in 89% of patients, and with some residual hearing in 59%. The increased trauma to the facial nerve via the middle fossa approach is probably the reason for the higher incidence of early facial weakness. Anatomic integrity of the facial nerve does not guarantee facial function, either in the short or long term. If the nerve is intact anatomically but facial paralysis is complete postoperatively, then some return of function can be anticipated in 90% of cases (Hitselberger 1979), although it is unlikely to be complete. The rate at which the nerve recovers also predicts the final outcome. While recovery may continue for up to 3 years, Hitselberger (1979) found that it was always less than perfect if >4 months had elapsed from the time of surgery. Return of facial function may be heralded by transient facial pain. Facial nerve dysfunction does not usually affect all regions of the face to the same degree. Adequate movement of the oral commissure is more than twice as likely to occur than complete eye closure, and asymmetry of the forehead is particularly common (Wiegand & Fickel 1989). The presence of preoperative facial weakness increases the probability of facial nerve injury at surgery, but does not predict the final outcome if the nerve is spared anatomically (Lye et al 1982). These authors were able to 549



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Specific brain tumors

preserve the nerve in 91% of cases with normal preoperative facial nerve function, but in only 67% of patients with preoperative weakness. However, it is not clear whether some of the disparity between the two groups is the result of differences in tumor size. The degree of facial nerve weakness in the early postoperative period may be predicted at surgery from a comparison of the amplitude of the compound muscle action potential obtained by facial nerve stimulation proximal and distal to the site of tumor excision. If the percentage amplitude is >90% then very good early facial function may be anticipated. If the amplitude lies between 50% and 90% then temporary weakness may occur, but the final outcome is likely to be good. An amplitude of <50% suggests that a temporary lateral tarsorrhaphy may be advisable under the same anesthetic, and that some degree of permanent facial weakness is probable (Ebersold et al 1992). We prefer to assess facial nerve function postoperatively in order to determine the most effective and cosmetic measures appropriate for eye protection. Hearing preservation In only around 30–50% of hearing preservation operations will functional hearing remain, despite anatomic preservation of the auditory apparatus (Tatagiba et al 1992). This figure may be significantly higher for selected small tumors, particularly when a middle fossa approach is used. In an analysis of the English language literature from 1954 to 1986, the overall success with hearing preservation was 33% in series with a preponderance of small tumors (Gardner & Robertson 1988). The causes of such high failure rates are thought to be multifactorial. Possible factors include nerve manipulation with disruption of the myelin sheath (Sekiya & Moller 1987), impairment to the vasculature of the inner ear or cochlear nerve (Ebersold et al 1992), heat or vibration injury to the nerve and cochlea during removal of the posterior wall of the internal auditory canal, and damage to the labyrinth (Tatagiba et al 1992). From their experience with intraoperative monitoring, Ojemann et al (1984) observed that one of the critical stages in terms of hearing preservation was removal of tumor from the lateral aspect of the internal auditory canal. They proposed that dissection avulses some of the cochlear nerve fibers at the cribriform area, where they enter the modiolus. The most frequently injured labyrinthine structures are the crus commune of the posterior and superior semicircular canals, and the posterior semicircular canal (Tatagiba et al 1992). Hearing loss after labyrinthine injury is ascribed to loss of perilymph from the inner ear, although total deafness is not an inevitable sequel to it, particularly if the opening into the labyrinth is occluded quickly (Tatagiba et al 1992). It is generally accepted that hearing preservation is deemed successful only if that which remains is of serviceable quality. The 50/50 rule is often applied: that there is less than a 50 dB hearing loss in the pure tone range, and that speech discrimination is >50%. Yet this is not sufficient to be useful socially if contralateral hearing is normal. A pure tone average (PTA) of 30 dB and a speech discrimination score (SDS) of >70% is required. As with tumor size and facial nerve function, there is no single accepted classification for the reporting of hearing 550

Table 28.3  Classification for hearing for the evaluation of hearing preservation in acoustic neurinoma Classification

Pure tone threshold

Speech discrimination (%)

A B C D

<30 dB >30 dB and <50 dB >50 dB Any level

>70 dB >50 dB >50 dB <50 dB

American Academy of Otolaryngology Head and Neck Surgery, (Committee on Hearing and Equilibrium (1995).

results. The Shelton–Brackmann classification (Shelton et al 1989b) is, however, gaining support. Hearing is classified as good (PTA <30 dB, SDS >70%), serviceable (PTA <50 dB, SDS >50%), measurable (any residual hearing), or anacusis. More recently, the American Academy of Otolaryngology Head and Neck Surgery Committee on Hearing and Equilibrium have proposed a classification for hearing for the evaluation of hearing preservation in acoustic neuroma (Committee on Hearing and Equilibrium 1995). Hearing threshold should be reported as the average of the pure tone hearing thresholds by air conduction at 0.5, 1.0, 2.0, and 3.0 kHz. The best word recognition (speech discrimination) scores at presentation levels of up to 40 dB sensation level should be recorded before and after treatment. Hearing is classified according to the classes in Table 28.3. Formal testing is necessary. Great caution must be exercised in believing the patient’s evaluation of his/her residual hearing. Some patients have claimed that hearing in the operated ear was unchanged after translabyrinthine surgery. Clearly this is not the case, and the contralateral ear is responding to the auditory stimulus. For this reason, evaluation must insure adequate masking of the unoperated ear. Success at preservation varies considerably between series, but Wigand et al (1991) reported a success rate of 51% in a series which included tumors as large as 3 cm. Using the middle fossa approach, Brackmann et al (1994) retained hearing at or near the preoperative level in 71% of a series of 24 consecutive patients with small tumors. Nadol et al (1992) were able to retain useful hearing in 50% of cases in which the tumor extended <5 mm into the cerebellopontine angle, but in only 12% of tumors >25 mm. It is exceptional for hearing to improve upon the preoperative level. Nadol et al (1992) reported this in only 5% of patients, and Gardner & Robertson (1988) in 6%. This is probably because atrophy of the organ of Corti occurs secondary to denervation, because the elevated protein concentration in the perilymph damages the outer hair cells, and because of inner ear ischemia caused by compression of the labyrinthine artery within the porus acousticus. Perlman & Kimura (1955) demonstrated that temporary vascular occlusion of only 30 min was sufficient to produce permanent impairment of hearing as a consequence of severe hair cell and spiral ganglion cell loss. Finally, the cochlear nerve itself may be invaded by tumor (Neely 1981). Kveton (1990) hypothesized that improvement in hearing was the result of reversal of conduction block. Small tumor size, good preoperative speech discrimination, and male sex correlate significantly with a good hearing outcome (Nadol et al 1992). Similarly, the topical application of papaverine to the



cochlear nerve after tumor removal has been recommended (Brackmann et al 1994). Hearing may worsen or fluctuate months or even years after surgery. The formation of scar tissue around the cochlear nerve as a consequence of packing the drilled surface of the porus may be a contributory factor (Shelton et al 1990). However, because the tumor may on occasion invade the cochlear nerve, delayed hearing loss can represent tumor recurrence (Neely 1984). Delayed edema is a further etiologic factor in early hearing loss, and may respond to corticosteroids (Goel et al 1992). Prophylactic nimodipine administration has been suggested in order to prevent vasospasm of the internal auditory artery and also because of its neural protective effects (Nadol et al 1987). In >50% of patients in whom hearing preservation has been successful there will be a significant decline in function as follow-up lengthens, even in the absence of recurrent disease (Shelton et al 1990). In an 8-year follow-up study of 25 patients the unoperated side remained the better hearing ear in all patients over the entire period (Shelton et al 1992). This argues that the philosophy of preserving any measurable hearing in order to safeguard against the possibility of deafness developing in the contralateral ear is unjustified. Taking into account late deterioration, it has been estimated that only 7–9% of the total group who undergo hearing preservation procedures will have useful hearing in the long term (Whittaker & Luetje 1992). It may be anticipated that medially placed tumors, that is those which do not occupy the fundus of the internal auditory meatus, might have a better prognosis for both facial nerve function and for hearing preservation than tumors which fill the porus. Although it is much easier to identify the nerves lateral to the tumor, the surgical results are no better in this subgroup of patients, either in terms of facial nerve recovery or hearing preservation. This is because these lesions often present late, and when the tumor is correspondingly of a greater size (Tos et al 1992b). Complications of surgery Hematoma in the operative cavity Hematoma is a rare but potentially fatal consequence of surgery. If hemostasis has been meticulous, this complication should occur in <2% of cases. Profound unconsciousness, respiratory failure, and pulmonary edema can develop very rapidly and temperature elevation may be evident. Prompt action is required if the diagnosis is suspected. The patient should be ventilated to protect the airway and, if a frontal burr hole has been placed, intracranial pressure should be lowered by tapping the lateral ventricles. The patient should be transferred with the greatest speed to the operating room. If the patient’s state is perilous, the wound can be opened in the ward; however, this should be avoided if at all possible as the hematoma may lie deep in the cavity, adherent to the pons. Optimal conditions are required if the clot is to be evacuated without risk to the cranial nerves and brain stem vasculature, and this is unlikely to be achieved without proper illumination, magnification, and instrumentation. Copious irrigation and a fine sucker will help to evacuate the hematoma and lessen the risk of nerve injury. A period of postoperative ventilation is recommended if re-exploration has been necessary.

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Brain stem infarction Devastating neurologic sequelae may follow injury to the anterior inferior cerebellar artery. It is a fundamental principle of this type of surgery that arteries of any size within the cerebellopontine angle are preserved, even if they are firmly adherent to the tumor capsule. Only small branches actually entering the substance of the tumor may be cauterized and divided. Larger vessels must be mobilized from the capsule or, if this proves impossible, capsular remnants should be left attached to the vessel. For the same reason, some surgeons have found it necessary on very rare occasions to leave capsular remnants adherent to the brain stem, since subpial dissection in this region may be equally catastrophic. Bleeding from a brain stem vessel should be controlled by gentle pressure on a piece of crushed muscle or hemostatic gauze. Cerebrospinal fluid leakage With the exception of facial nerve palsy, cerebrospinal fluid leakage from the wound or middle ear cavity (rhinorrhea) is the most common postoperative complication of acoustic neurinoma surgery (House et al 1982; Tos & Thomsen 1985; Gordon & Kerr 1986; Brackmann & Kwartler 1990a). An incidence of around 10–15% is reported in most major series (Di Tullio et al 1978; King & Morrison 1980; Glasscock et al 1986; Hardy et al 1989a; Ebersold et al 1992). The major contributing factors are poor wound healing, hydrocephalus, and failure to obliterate air cells opened in the porus acousticus or mastoid. After translabyrinthine or suboccipital surgery CSF may leak into the permeatal or retrofacial air cells, or via the dural defect into the mastoid air cells, and thence gain access to the middle ear cavity and eustachian tube. In addition to CSF leakage, symptomatic aerocele may develop. Meticulous attention to the technique of wound closure can dramatically diminish the incidence of this complication. Using the method described in the operative section above, Hardy et al (1993) reduced their CSF leakage rate to 1.6% in a recent series of 230 patients. Some authors have argued that fat should not be used in wound closure because it may make subsequent MRI studies difficult to interpret (Ebersold et al 1992), but their CSF leakage rate using bone wax alone is unacceptably high. Current MRI techniques using fat suppression sequences in combination with gadolinium enhancement allow very sensitive identification of residual or recurrent tumor. We have no experience with synthetic bone replacement materials pioneered recently; ionomeric cement has the ability to adhere even to moist surfaces, and is reported to be a significant advance over other synthetic cements such as polymethyl methacrylate (Ramsden et al 1992). Apparently there is concern, however, about toxicity when ionomeric cement is in contact with CSF. Hydroxyapatite cement has been used successfully to repair the bone defect after suboccipital craniotomy, however it can only be applied in a relatively dry site. If CSF leakage does occur, conservative measures such as lumbar drain insertion or the placement of additional sutures in the wound are successful in around 25% of patients (Hardy et al 1989a), but the remainder will require re-exploration. In general, CSF leakage from the wound is much more likely to settle with conservative treatment than 551



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is rhinorrhea. The value of prophylactic antibiotics is questionable. The technique used to seal the defect should be the same as described above. Bone pate is used to fill the exposed air cells, and is reinforced with a fascia lata patch sealed in place with fibrin glue. Fat is used to fill the bony defect, and this too is sealed with fibrin glue. A persistent CSF fistula after the translabyrinthine approach may be managed by permanent closure of the external auditory meatus, removal of the bony external auditory canal and middle ear cleft, and direct closure of the eustachian tube in the protympanum. This achieves very secure closure; however, the removal of squamous epithelium from the external canal and tympanic membrane must be meticulous. A lumbar drain may be placed for a few days to maintain a low CSF pressure until the wound has had the opportunity to heal. Meningitis The risk of postoperative meningitis relates not only to the development of CSF leakage. The protracted nature of the operation and the communication of the operative site with the eustachian tube are other important factors. Infection rates in the literature are generally around 3–6% (Di Tullio et al 1978; King & Morrison 1980; Bentivoglio et al 1988b; Hardy et al 1989a). Diplopia Postoperative unilateral abducent nerve paresis must be differentiated from a gaze palsy secondary to involvement of the lateral gaze center in the pons. The latter usually resolves within a few days of surgery, whereas injury to the abducent nerve may take considerably longer. Diplopia can be treated by an eye patch although, if the patient has a concomitant facial palsy, a more than adequate tarsorrhaphy will achieve the same result. Meningitis should be considered in the differential diagnosis of a delayed 6th nerve palsy. Hearing loss It is quite common for hearing to be decreased transiently after any surgery to the posterior fossa. The current hypothesis is that the low CSF pressure is transmitted via the cochlear aqueduct to the perilymph, producing perilymphatic hypotonia (Walstead et al 1991). Hearing loss in the contralateral ear after acoustic neurinoma removal has also been attributed to an autoimmune response (Harris et al 1985). Clemis et al (1982) reported three such patients, all of whom recovered spontaneously. Special considerations Tumors

in the

Elderly

and Infirm

In view of the slow growth rate in the majority of tumors, a conservative approach to management may be appropriate for very elderly or infirm patients, particularly if the tumor is small. However, the value of an expectant policy in aged but otherwise fit patients is less clear. Nedzelski et al (1986) studied the growth behavior of 50 untreated acoustic neurinomas in elderly patients followed up for between 12 and 144 months. They reported that around 20% of such patients required surgery within a third of their life expectancy. Yet even quite old patients will tolerate surgical excision of tumors. Two recent series, one suboccipital, the other translabyrinthine, have emphasized that age is not a contraindication to successful surgery. House et al (1987) reported a series of 116 patients over the age of 65 years 552

with only one death, and functional preservation of the facial nerve in 91% of cases. Samii et al (1992) recorded 61 patients operated on without mortality, with anatomic preservation of the facial nerve in 95%, and with residual hearing in 41%. In both series the majority of excisions were macroscopic (91% and 97%, respectively). As well as tumor size and evidence of mass effect, the presence of disabling symptoms such as vertigo is an indication for early intervention. Predictive factors for a poor outcome are ASA (American Society of Anesthesiologists) grading of physical status >3, a Karnofsky score <80, and tumor size >3 cm (Samii et al 1992). In the case of surgery for a symptomatic tumor in a frail patient, it may be appropriate to reduce the duration of the operation, either by elective sub-total excision or, rarely, by macroscopic removal with no attempt at preservation of the facial nerve. Sub-total excision Sub-total excision may be a planned procedure in, for example, a patient with a large tumor in a solitary hearing ear, or if facial weakness would be completely unacceptable. On other occasions it may be necessary to leave a rim of capsule adherent to the brain stem or adjacent vessels. Olivecrona (1967) observed that half of his 83 patients remained asymptomatic after partial tumor removal. This was also the experience of Wazen et al (1985): 11 of 13 elderly patients who had residual tumor after surgery showed no significant expansion over an average period of 6 years. In a series of 12 patients who underwent radical intracapsular removal of large tumors, and who were followed for up to 22 years, Lownie and Drake (1991) reported recurrence in only two cases, both within 3 years of surgery. However, Hitselberger and House (1979) found that the late recurrence rate necessitating re-exploration in their series was high, and that surgery on the second occasion was more hazardous. Ransohoff et al (1961) noted ultimately that 60% of patients treated in the 1930s by sub-total excision either died from recurrent disease or required a second operation. In Cushing’s series of 182 patients, those who underwent sub-total excision but died eventually from tumor recurrence lived for an average of 5 years after the initial operation (German 1961). With the exception of NF-2 patients, elective sub-total excision is unsatisfactory and illogical for small or mediumsized tumors. If a cure is not to be effected when the tumor is of a favorable size, then treatment should be delayed until symptoms become more serious. A more vexing issue is whether it is preferable to excise every last remnant of tumor at the risk of compromise to neural integrity, or to minimize the possibility of nerve or brain stem injury by leaving capsular or tumor remnants behind. Recent studies suggest that it is very reasonable to leave a small volume of tumor capsule along the course of the facial nerve in order to preserve anatomic and functional continuity of the nerve. Ohta and co-workers (1998) demonstrated tumor regrowth in only one of 8 patients with residual tumor along the facial nerve and suggested that removal of tumor in the internal auditory meatus may make regrowth unlikely. This issue is particularly relevant to attempts at hearing preservation. The success rate is generally poor, and any residual hearing may not be socially useful. In order to answer this question fully



Acoustic neurinoma (vestibular schwannoma)

28

it is clear that longitudinal MRI studies are required, given that the growth potential of residual tumor appears at present to be unpredictable. Lye et al (1992) reported recently the results of a follow-up MRI study of 14 patients with capsular remnants left attached to vital structures at the time of otherwise total tumor removal. Over a mean period of 70 months, half the patients had radiologic evidence of persistent neurinomas. Four of these showed signs of progressive enlargement, although none was symptomatic and CT was normal in each. Persistence of tumor was more common if the residual fragment had not been cauterized at the time of operation (Lye et al 1992).

delivered as a single fraction over 10–20  min. The dose gradient of the radiation is extremely steep at the edge of the target tissue. The mechanism by which tumor growth is inhibited remains uncertain. In vitro studies suggest that Schwann cells suffer irreversible damage after single fraction doses of 30 Gy (Anniko et al 1981). Histopathology reveals interstitial fibrosis, tumor necrosis, vascular hyperplasia, and hyalinization (Lunsford et al 1992a). Apoptosis has been reported in the tumor cells (Fukuoka et al 1998).

Facial nerve neurinoma Facial nerve neurinomas account for <2% of lesions thought preoperatively to be acoustic neurinomas (House & Luetje 1979). The radiologic differential diagnosis has been discussed. At operation the facial nerve fibers are found to enter the tumor, and cannot be separated from it. The lateral extent of the tumor is often considerably greater than that of tumors of vestibular origin, and may involve the entire intratemporal course of the facial nerve. The basic principles of excision are the same as for removal of an acoustic neurinoma, although the facial nerve will be divided. Direct end-to-end anastomosis may be possible, or a primary graft may be fashioned from the greater auricular or sural nerves.

Following initial experience with poor hearing preservation and high rates of trigeminal and facial nerve dysfunction, it was recognized that the incidence of cranial neuropathy is directly related to the radiation dose at the tumor margin. Between 1987 and 1992, the marginal tumor dose was therefore reduced from around 16 Gy to 12–13 Gy (Flickinger et al 1996; Miller et al 1999). A number of centers have now published series with follow-up of ≥5 years (Table 28.4). In most large series, the tumor control rate, usually defined as absence from further treatment) was between 90% and 100% at the end of the follow-up period. The Pittsburgh group has reported on 252 patients who received 12–13 Gy margin dose Gamma Knife radiosurgery between 1991 and 2001 and who had at least 10 years of follow-up (Lunsford et al 2005; Chopra et al 2007). The tumor control rate (absence of any further intervention) was 98%. A 99% tumor control rate at 5 years was reported by the Gainesville, Florida center (Friedman 2008; Friedman et al 2006). The first report to include very long-term follow-up (317 patients receiving a median margin dose of 13.2 Gy with a mean follow up of 7.8 years at the Komaki City Gamma Knife Center in Japan showed a 10-year actuarial control rate of only 92% (Hasegawa et al 2005). Despite this, the results displayed little or no difference between the 5- and 10-year PFS; the authors point of that most failures occurred within the first 3 years. It may be that further very long-term follow-up data may not reveal an increasing late recurrence rate compared to what we know already. There is still debate about the exact dose that achieves control. In the Komaki City series, there was a difference between those treated with >13 Gy and those with ≤13 Gy margin dose, with 97% and 89% PFS, respectively (Hasegawa et al 2005). In another series, however, there

Indications for and results of radiotherapy Conventional external beam radiotherapy has been used as an adjuvant therapy for patients with sub-total tumor resection, or in cases of advanced disease (Cushing 1921). In a series of 31 patients receiving postoperative irradiation, Wallner et al (1987) reported that a dose of 50–55 Gy was well tolerated, and reduced the probability of recurrence from 46% to 6%. Treatment was administered in 1.8 Gy fractions, 5 days per week. However, irradiation did not influence recurrence rates if >90% of the tumor had been excised, and radiation therapy for tumor recurrence after a previous surgical resection was associated with a poor prognosis. Irradiation is reported also to reduce tumor vascularity (Wallner et al 1987) and has been used in the preoperative management of highly vascular tumors (Ikeda et al 1988). Sequelae of radiation therapy include multiple cranial nerve palsies, brain stem edema, and brain stem ischemia (Brackmann & Kwartler 1990a).

Stereotactic radiosurgery Since the first treatment of a vestibular schwannoma in 1967 by Lars Leksell using a 201 source Co60 Gamma Knife for stereotactic delivery of radiation, a large experience has been obtained in treating acoustic neurinomas in a number of centers (Leksell 1971). Generally, only lesions <3  cm are suitable for this form of treatment. The principle of the technique is that multiple converging gamma beams are collimated to a focus, targeted on the lesion via a stereo­ tactic frame applied to the skull. A dose of 10–15  Gy is delivered to the tumor periphery and a maximum of 15– 25  Gy to the center (Noren et  al 1992). The entire dose is

Tumor control

Table 28.4  Recent published series of radiosurgical treatment of small to moderate sized VS with lower margin doses Author

Year

Flickinger et al Chung et al Wowra et al Hasegawa et al Hasegawa et al Chopra et al Friedman et al Pollock et al

2004 2005 2005 2005a 2005b 2007 2008 2009

Patients

Margin dose (Gy)

Median f/up (years)

Tumor control rate (%) (at time)

313 195 111 317 73 216 450 293

12–13 12–13 13 13.2 14.6 12–13 12.5 13

2 3 7 7.8 11 5.7 5 5

98 (6 years) 95 (7 years) 95 92 (10 years) 87 98 99 94 (7 years)

553



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was no difference between 12 Gy and 13 Gy; only doses <12 Gy led to an increased rate of treatment failure (Chung et al 2005). The control rate for NF2-associated tumors is recognized to be worse, but this must be understood in the context that lower doses are often applied in order to preserve hearing in an unaffected ear (Wowra et al 2005). Finally, it is clear that the tumor control for large tumors is much worse (Hasegawa et al 2005), emphasizing the fact that surgery should be the treatment of choice for those tumors of >3 cm diameter. In the larger radiosurgery series, the rate of later surgical resection ranged from 1% to 4%, occurring at an average time of 25–30 months post-treatment (Chopra et al 2007; Pollock et al 2006; Pollock et al 1998b; Friedman, 2008). There have been concerns about the increased risk of operating after radiosurgery, due to fibrosis. Histopathologically, variable rates of fibrosis both in the recurrent tumor and around the CP angle have been observed, suggesting that the radiation effect is not as uniform as supposed (Lee et al 2003). In the older Mayo Clinic series, it was reported that surgery was more difficult than usual in about two thirds of the cases, but this was not a statistically significant finding (Pollock et al 1998a). Surgical difficulties may have been more pronounced in the earlier series of patients treated before 1992 in whom higher radiation doses were used but more modern series have noted problems also. A retrospective analysis of 38 patients with surgery post SRS vs a comparable cohort of primary surgical patients found an increased incidence of moderate to severe adhesion in the post SRS group and a higher rate of facial palsy (Friedman et al 2005). The Marseille group reported that about 50% of cases were sub-optimally resected following radiosurgery at an average of 39 months (Roche et al 2008b). Our experience is that surgery is much more difficult and hazardous following SRS due to dense adhesions between the tumor and adjacent vascular and neural structures. Although tumor growth is well recognized, the radiological pattern of failure has not been clearly defined. Tumor swelling is also known to occur in the first few months postSRS. Delsanti et al (2008) followed 332 tumors post-SRS and found that 53% had significant growth at 6 months and 22% of tumors were still larger, but stable, at 3 years. Other groups have reported only a 6% incidence of continued enlargement in the first 6–12 months (Lunsford et al 2005). Most centers report around a 50–60% shrinkage rate and a 40–50% stabilization rate in the long term. Continual MRI monitoring post-SRS is recommended but there are currently no guidelines as to how long to continue screening; long-term failures out to 15 years have been recognized (Friedman et al 2005). It has been pointed out that schwannomas are late responders to radiotherapy, and that therefore the decision to perform ‘salvage’ surgery should be delayed until continued progressive growth on follow-up imaging is definitively demonstrated, unless increasing symptoms of mass effect warrant immediate intervention. Repeat SRS at the time of recurrence with a second marginal dose of 12 Gy has recently been reported, with poor rates of hearing preservation but good facial nerve function (Yomo et al 2009; Dewan & Norén 2008); this option remains to be further explored. 554

Hearing preservation A number of studies have looked at hearing preservation rates with stereotactic radiosurgery. In the Pittsburgh series of 121 patients with good hearing after 3 years follow-up, 71% kept the same Gardner-Robertson hearing level, 74% preserved ‘serviceable’ hearing and 95% had some testable hearing present (Chopra et  al 2007). The rates of hearing preservation in small intracanalicular tumors were considerably better still. In one of the largest series of 184 patients with functional hearing (GardnerRobertson grade I or II) prior to SRS, the Marseille group reported a 77.8% functional hearing preservation rate for patients initially G-R grade 1 (Regis et  al 2008). All patients were followed for at least 3 years. Other groups have reported similar outcomes (Kano et  al 2009). A marginal dose of <12.5  Gy, presence of pre-treatment tinnitus, younger age (<60), a pretreatment pure tone average of <20 dB and small tumor size have been reported as positive predictive factors for good hearing outcome (Regis et  al 2008; Kano et  al 2009) although one recent systematic review found no difference between those patients under and over 65 years of age (Yang et  al 2009). Linskey et  al (2008) have suggested that limiting the maximal dose to <12  Gy, carefully ensuring 3-D tumor conformality, limiting dose to the ventral cochlear nucleus to <9  Gy and limiting dose to the cochlear to <4  Gy are critical factors in maximizing hearing preservation after SRS. Facial and cranial nerve outcomes Pollock et al (2006) published an evidence-based review of studies comparing SRS and microsurgical resection and found only five case-control series (level III evidence), one prospective cohort study (level II) and no randomized control trials (level I) comparing SRS with microsurgical resection (Pollock 2008). These five studies showed improved cranial nerve outcome, better cost-effectiveness and better quality of life (QoL) scores for patients having radiosurgery. A prospective cohort of 82 patients (46 SRS vs 36 surgery) with a median follow-up of 3.5 years showed better facial nerve and hearing preservation, better short-term QoL outcomes at 3 months for the SRS cohort, and comparable (96% SRS vs 100% surgery) tumor control. A recent updated prospective non-randomized Norwegian study of 91 patients comparing gamma knife SRS (12 Gy tumor margin dose) with retrosigmoid surgery found a better facial nerve and hearing outcome after SRS, in tumors of ≤25 mm (Myrseth et al 2009). However, in this study, there was no significant difference in vertigo, balance and QoL outcomes at 2 years. One patient out of a total of 60 in the SRS group had an increase in tumor diameter at 18 months and underwent surgery, which resulted in a facial nerve palsy. The incidence of trigeminal nerve dysfunction after SRS is about 2% (Pollock et al 2006). The incidence of lacrimal dysfunction and dry eye symptoms appears to be significantly higher after microsurgery (Tamura et al 2004). Although SRS has shown better short-term QoL scores, it probably does not offer much advantage in long-term outcome at 2 years or more, once the patient has fully recovered from surgery. SRS does appear, however, to have comparable or better facial, hearing and trigeminal nerve



preservation at least for selected smaller tumors. Long-term data, that is 10 years plus, on tumor control is yet to be published but some centers favor a recommendation of radiosurgery for those tumors under 3 cm, in the older or medically unfit population. Concerns have been raised about the long-term risk of neoplasia following radiosurgery but best estimates at the present time suggest that this is probably very low, of the order of <0.1%. Nevertheless, this needs to be considered in discussing the treatment options with patients. Communicating hydrocephalus has been recorded as a complication of stereotactic radiosurgery (Thomsen et al 1990; Noren et al 1992), even in the absence of further tumor enlargement. The incidence appears to be between 1% and 9% but the need for shunting is somewhat less (Pollock et al 2006; Hasegawa et al 2005; Roche et al 2008a; Rogg et al 2005). Time to shunt requirement was generally 12–18 months. This phenomenon is thought to be related to elevation of the CSF protein content but the exact mechanisms are controversial. Older patients, larger tumors, bilateral tumors and NF2 are risk factors for the development of de-novo hydrocephalus after SRS (Roche et al 2008a). Other radiosurgery techniques As well as the cobalt 60 Gamma Knife unit, stereotactic radiation can also be delivered using a linear accelerator (LINAC). Rather than the multiple simultaneous radiation beams generated by the Gamma Knife unit, the linear accelerator uses a single source that is rotated in multiple non co-planar arcs (Mendenhall et al 1994). Results from centers using linear accelerator appear to be comparable to those using Gamma Knife (Friedman et al 2005). The CyberKnife (Accuray, Sunnyvale, CA) robotic stereotactic SRS platform has also been used and facilitates fractionating the dose into two or more fractions at different treatment episodes (Ishihara et al 2004; Sakamoto et al 2009). To avoid potential neurologic deficits associated with single dose stereotactic radiation, many centers now advocate fractionated stereotactic radiation therapy (Lederman et al 1997). As opposed to single dose SRS, fractionated dosing regimes utilizing either 2–5 or 20–30 doses have been advocated (Koh et al 2007). Early reports demonstrated an advantage over observation alone (Shirato et al 1999) however, to date, there is no long-term follow-up data available to help determine the advantages of these approaches over single-dose radiosurgery, which has now improved technically, particularly in terms of accuracy of tumor isodose targeting. In fact, it has been suggested that the biology of vestibular schwannomas, as late responding tissues with a low proliferative index, is more suitable to single high dose radiosurgery and not fractionated schedules (Linskey 2008). While current evidence does suggest that hearing preservation may be better with fractionated techniques, especially with 2–5 dose schedules, the long-term tumor control is still under question and concerns that tumor control, which is the primary goal of therapy, may be sacrificed for short-term functional gain have been expressed. This concern has been supported by the literature on meningiomas, which has found a long-term control rate of only 76–81% with fractionated regimens, compared with 93% with single dose SRS (Kondziolka et al 2008).

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Treatment decisions For tumors of 3 cm diameter and over, or those with mass effect or with a large cystic component, surgical resection is the preferred treatment modality. Surgery provides excellent extremely long-term tumor control or cure and in experienced centers is associated with good facial and hearing outcomes. For tumors ≤3 cm in diameter, radiosurgery is now preferred in many centers. Because it is unlikely that a randomized control trial will ever be done comparing radiosurgery and resection for acoustic neuroma, due both to patient and physician biases for one form of treatment and availability of local expertise, decision-making must be based on available evidence, which for the most part are case series. Although results of radiosurgery in terms of tumor control, hearing preservation and facial nerve outcomes are very good and improving, the current data with respect to at least 10 years follow-up with modern dose prescriptions, only includes a small number of patients. The next few years should clarify whether the 95% and better tumor control rates are continuing in the long term. A number of other issues still need to be clarified. The decision as to when and by what method to treated ‘failed’ progressive tumors after SRS is still controversial and dependent on individual biases at each treating center. It is recognized that a small proportion of tumors will continue to grow for 6–12 months before stabilizing so this should be taken into account. The increased risks associated with operating on a previously SRS-treated tumor and for younger patients, the low but documented risk of malignancy are particularly relevant because of a life expectancy of 40 years or more, which is well beyond current follow-up times in SRS series. The risk of inducing more aggressive tumor behavior at late recurrence, as has been seen in meningiomas (Couldwell et al 2007), may be less likely in schwannomas but is still a concern. Ultimately, the availability of expertise locally, whether microsurgical or radiation, the patient’s own preferences and biases regarding surgery and the tolerability of complications, as well as the experience of the local treating team in regards to the different treatment modalities, should all be taken into consideration.

Indications for and results of chemotherapy Chemotherapy has little place in the management of this condition, but has been proposed as an alternative treatment for bilateral acoustic neurinomas (Jahrsdoerfer & Benjamin 1988). A course of six treatments of cyclophosphamide, doxorubicin, and dacarbazine over a period of 6 months resulted in cessation of tumor growth and stabilization of hearing in two patients. Follow-up was for only 15 months, however, and long-term data are lacking.

Management of associated phenomena Management of the eye Incomplete eye closure and reduced lacrimation make the postoperative patient vulnerable to infection and exposure keratitis, particularly when corneal sensation is also diminished. Poor lid closure, ectropion, inadequate Bell’s 555



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phenomenon, and/or incomplete blinking may cause drying of the cornea and conjunctiva, leading to corneal epithelial damage. Not only does reduced corneal sensation exacerbate the likelihood of injury, but corneal healing is impaired, and neurotropic keratitis may ensue. The cornea can be protected with artificial tears such as methyl cellulose, but this has the disadvantage of requiring frequent applications. Ointments (e.g., Lacrilube) last much longer, and are useful at night when blurring of vision is not important. Antimicrobial pre­parations such as chloramphenicol are used if infection develops, while corneal injury may require judicious use of topical steroids and cycloplegics. Although the eye may be protected with a patch at night there is still the risk of desiccation and, for this reason, we prefer an eye bubble to retain moisture and prevent contact with the cornea. Protective spectacles may be worn by day. If eye closure is deficient and Bell’s phenomenon is inadequate to provide corneal cover, a lateral tarsorrhaphy may be necessary but should be avoided where possible because of poor cosmesis. It is preferable to try accurately to assess the likelihood of long-term facial nerve recovery by a combination of intraoperative and postoperative electrical testing (see below). If early recovery is likely then eye closure with botulinum toxin or temporary tarsorrhaphy is reasonable. If recovery is likely to be delayed or permanent weakness persists, then early intervention with plastic surgical procedures such as upper lid gold weight insertion combined with medial canthoplasty and lower lid shortening is appropriate. The gold weight can always be removed if good recovery occurs. The technique of palpebral spring implantation provides the most effective active eye closure (Levine 1994). Although excellent results are achieved in some centers with wire spring implantation, extrusion has been a significant problem elsewhere and hence gold weight implantation is more commonly used.

Management of the facial nerve Even when the facial nerve has been preserved in anatomic continuity, the inevitable manipulation required to dissect it from the tumor capsule may result in neurapraxias. The lack of protective epithelium in the cerebellopontine angle segment increases the risk of injury (Sunderland 1978). The success with which the nerve can be preserved anatomically, and its ultimate functional outcome, are dependent on tumor size. Of patients with complete clinical paralysis despite anatomic preservation, some improve rapidly within weeks of surgery and the end result is functionally acceptable (Morgon et al 1985). However, 9–18% never recover facial tone or active movement (House & Luetje 1979; Moffat et al 1989c). Patients with wallerian degeneration have a worse prognosis than those with neurapraxia (Gantz et al 1984). Croxson et al (1989) and Hardy et al (1989b) have reported that postoperative electroneuronography one week after surgery is a good predictor of final outcome in patients with clinically complete paresis. A percentage degeneration is calculated by comparing the amplitude of the ipsilateral compound action potential with that of the normal side. In these two studies, all patients with incomplete degeneration attained House grade I–II, while those with complete degeneration had a protracted and incomplete recovery in every case. 556

Spontaneous regeneration of an anatomically intact nerve is more likely to provide a good cosmetic result than secondary grafting. If the nerve remains in continuity, facial reanimation should therefore be delayed for around 12 months before any secondary procedures are contemplated. However, if the final outcome is House grade III or worse, there is no significant difference in the cosmetic appearance between regeneration of an intact nerve, primary facial nerve repair, or facial hypoglossal nerve anastomosis (King et al 1993). Primary facial nerve repair If the facial nerve is divided at operation, primary repair is likely to provide the most satisfactory outcome. Although the functional result is probably little different from donor nerve grafting techniques (Stennert 1979), the major advantages are that function in a normal nerve is not sacrificed and a second surgical procedure is not required. A good outcome may be anticipated in around 65% of patients (Barrs et al 1984b), although the final result is unlikely to be known for one year after grafting. The results are considerably poorer in NF-2 patients, possibly because of a more invasive growth pattern (Jääskeläinen et al 1990). As the nerve has been stretched by the tumor, direct end-to-end facial nerve anastomosis may be possible. Direct anastomosis without a cable graft was possible in 37% of cases in one suboccipital series (Ebersold et al 1992). If the translabyrinthine approach has been used, an additional 1 cm of length may be gained by mobilization of the nerve from the fallopian canal with detachment of the greater superficial petrosal nerve from the geniculate ganglion (Whittaker & Luetje 1985), although rarely is this of value in practice. If there is insufficient length to allow direct anastomosis of the divided ends, a sural or great auricular nerve interposition graft may be used. The anastomosis is either sutured or wrapped in a tube of fascia lata and sealed with fibrin glue. Fisch et al (1987) have proposed the use of a fenestrated collagen splint for nerve anastomosis. Primary repair is not always possible, particularly if the nerve has been divided at the brain stem, or if the remnants are severely attenuated. In this instance there are several alternatives. The first involves anastomosis of the distal facial nerve to either the hypoglossal, spinal accessory (Migliavacca 1967), glossopharyngeal (Duel 1934), or phrenic nerves (Conley & Baker 1979), or the performance of a crossfacial anastomosis (Smith 1979). Of these options, the phrenic and glossopharyngeal nerves are unsuitable donors because of the unacceptable consequences of denervation. The spinal accessory nerve, with or without preservation of the branch to trapezius, has been reported by some to give good results (Migliavacca 1967; Ebersold & Quast 1992), but others have found greater success with hypoglossal–facial anastomosis (Mingrino & Zuccarello 1981). This may be because the cortical representation of the tongue is larger and more closely related to the face than is the shoulder. Cross-facial anastomosis is technically more demanding and involves sural nerve interposition grafts between the two facial nerves. Results are generally poorer than with hypoglossal–facial anastomosis, perhaps because of decreased axonal input for reinnervation (Tran Ba Huy et al 1985; Zini et al 1985). For all of these reasons we prefer



facial–hypoglossal anastomosis, except if the patient also has a bulbar palsy. If there has been some return of facial function but the cosmetic result remains unsatisfactory, plastic surgical procedures may be beneficial. An upper lid gold weight can improve eye closure. Facial asymmetry at rest may be restored by a fascia lata sling. If necessary, this can be supplemented by a face lift, brow lift, or canthoplasty. These procedures are, however, static and do not provide active movements. The latter may be achieved to a limited degree by temporalis muscle transfer. Hypoglossal–facial nerve anastomosis The first attempt at facial reanimation by hypoglossal–facial anastomosis is attributed to Korte in 1901 (Pitty & Tator 1992). Many series have been published in the literature, and their results range from poor to good (for review, see Pitty & Tator 1992). Results are better in younger patients, and when the interval between nerve division and anastomosis is short, although this latter point has been contested by Hitselberger (1979). In a recent series of 22 cases, good or fair results occurred in 77% of patients. Evidence of reinnervation was seen between 3 and 6 months after surgery in 59% and in the remainder within 8 months (Pitty & Tator 1992). The result often improves with time, possibly because of the plasticity within the nervous system. Technique The operation is conducted with the patient supine, and the head in a neutral position. Rotation of the neck should be avoided as this makes dissection of the hypoglossal nerve more difficult. A facial nerve stimulator is of benefit only if the operation is performed before wallerian degeneration has occurred in the distal fibers. The skin incision starts anterior to the tragus, curves posteriorly below the pinna, and then is carried forward down into the neck, a fingerbreadth below the angle of the mandible. Where possible, the greater auricular nerve should be preserved. The facial nerve emerges from the skull through the stylomastoid foramen, anterior and deep to the mastoid tip. Two muscular branches pass posteriorly to supply the occipital belly of occipitofrontalis and the posterior belly of digastric. The main trunk passes forward horizontally to enter the posteromedial surface of the parotid gland. Here it divides into two branches, the temporozygomatic and the cervicofacial. The facial nerve can be identified at surgery in one of three ways. The plane anterior to the sternomastoid muscle can be developed by sharp dissection, and the posterior belly of digastric exposed near its origin from the digastric notch on the medial aspect of the mastoid tip. The nerve to digastric is then identified and traced proximally to the main trunk of the facial nerve. The styloid process lies just anterior and slightly deep to the facial nerve and is a useful landmark. The second option is to use the technique described by Hitselberger (1979). Via a cortical mastoidectomy the descending portion of the facial nerve is identified in the fallopian canal within the mastoid bone. The facial nerve is skeletonized from the mid-portion of the horizontal segment to the stylomastoid foramen, is divided proximally, and is then delivered down into the neck. The third technique, which we favor, is to expose the tragal cartilage. The facial nerve can

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be found 1 cm inferior, and 1 cm deep, to the inferior margin of the cartilage (the tragal point) (Mattox 1992). The hypoglossal nerve is readily identified in the anterior triangle of the neck, where it lies above the greater cornu of the hyoid – a useful reference point. The common facial vein is divided between ligatures. The hypoglossal nerve lies on the carotid sheath deep to the internal jugular vein and posterior belly of digastric. It passes in front of the lower branches of the external carotid artery, and divides into several branches shortly before entering the tongue. If the main trunk of the nerve cannot be identified, the descendens hypoglossi (innervation to the infrahyoid muscles) can be exposed on the front of the internal jugular vein and traced proximally. The entire trunk of the hypoglossal nerve is divided just as it starts to divide at the tongue. It is very important to divide the nerve as distally as possible or there may be insufficient length to reach the facial nerve. An end-to-end anastomosis is fashioned under magnification and without tension between the hypoglossal and distal facial nerves using interrupted 8–0 epineural sutures. The suture line is then coated with fibrin glue. In an attempt to minimize atrophy of the tongue, the descendens hypoglossi nerve may be divided and sutured to the distal hypoglossal nerve stump. Hammerschlag et al (1992) have reported the results of a technique for facial–hypoglossal anastomosis which both avoids wasting of the tongue and reduces facial hypertonus. The hypoglossal nerve is hemisectioned obliquely, just distal to the descendens hypoglossi, and a sural or greater auricular nerve graft is interposed between the partially divided nerve and the distal facial nerve. Results Pitty & Tator (1992) have summarized the literature on hypoglossal–facial nerve anastomosis over the past 37 years, and summated the results of 562 cases. Good results were achieved in 65% of cases, fair results in 22%, and poor or no recovery in the remaining 13%. Despite reinnervation, incomplete eye closure and mass facial movement may be evident and require additional cosmetic procedures (see above). Hemiatrophy of the tongue produced only minimal dysfunction (impaired intraoral food manipulation), and anastomosis of the descendens hypoglossi to the distal stump did not influence hemiatrophy (Pitty & Tator 1992). Although results were better if the anastomosis was performed early, it is reported that surgery many years after nerve section may still on occasion produce a satisfactory outcome (McKenzie & Alexander 1950; Hitselberger 1979).

Deafness and auditory brain stem implantation Patients with unilateral hearing loss after surgery may benefit from a CROS (contralateral routing of signals) hearing aid. Total deafness may face a patient with bilateral acoustic neurinoma, or tumor in a solitary hearing ear. There are two potential surgical options for hearing restoration if hearing is lost postoperatively and bilateral deafness results. If the cochlear nerve is physiologically preserved but there is no residual hearing due to impairment of inner ear vasculature or injury to the labyrinth, a response to stimulation 557



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of the round window or promontory is predictive for likely success with a cochlear implant (Waltzman et al 1990; Friedman et al 1998). This is an electronic device placed in the inner ear to stimulate the cochlear nerve. If the cochlear nerve is lost, however, or if the hair cells and spiral ganglion cells have been destroyed, the only other option is direct electrical stimulation of the cochlear nucleus with an auditory brain stem implant (Hitselberger et al 1984). A fully implantable multi-electrode prosthesis has been developed based on the nucleus 22 channel cochlear implant. Experience in Europe has been with a 21 electrode array and in the USA and Australia with an 8 electrode array. The electrode array is placed over the surface of the cochlear nucleus within the lateral recess of the fourth ventricle, usually at the time of translabyrinthine acoustic neurinoma removal. The translabyrinthine approach provides the most direct lateral access with visualization of the foramen of Luschka, although a retrosigmoid approach has been successfully used in some centers for electrode placement. Stimulation is via a transcutaneous coil system with a variety of processing strategies available, depending on the results of electrode mapping. In most cases, multiple channels have been available for stimulation (Brackmann et al 1993; Laszig et al 1999). The multichannel auditory brain stem implant is still in experimental use; it appears that the majority of subjects achieve a significant aid to lipreading and useful perception of environmental sounds. Only a very occasional patient (1%) has achieved open set speech understanding. Patients may get non-auditory sensation with stimulation of some electrodes, but in the majority this can be avoided when using the device by selective programming of electrodes (Shannon et al 1993). Auditory brain stem implantation should now be considered in all patients with neurofibromatosis type 2 when non-hearing preservation surgical removal of an acoustic neurinoma is performed. Suitable candidates are those patients with non-aidable hearing and any size tumor, or patients with serviceable hearing where hearing preservation is unlikely due to tumor size. Implantation at the time of first side tumor removal is a reasonable option if there is a bilateral profound hearing loss, but can also be considered in a patient with serviceable hearing in the contralateral ear, particularly if the contralateral tumor is large and further hearing loss is likely in the near future.

Bulbar palsy Transient bulbar palsy may develop after removal of large tumors. Provided that the nerves are intact, the prognosis for recovery appears good (Hardy et al 1989a). To reduce the risk of aspiration, patients should undergo formal assessment of swallowing to ensure bulbar competence before oral fluids are commenced postoperatively.

Patterns of failure House (1968) noted that, when tumor regrowth does occur, it does so within 4 years of the initial resection. Incomplete tumor resection may be a conscious decision at the time of surgery; the most common indications are adherence of the 558

capsule to the brain stem or other vital structures (e.g., AICA), and preservation of good facial nerve function. The behavior of the tumor remnant is unpredictable. Recurrence is not an inevitable sequel, and spontaneous involution of the remnant is well documented (Shea et al 1985). However, in a study of 33 patients with residual tumor followed up for a mean of 5.5 years, 36.5% required surgery for symptomatic recurrent tumor, and 9% died (Shea et al 1985). After ‘total’ tumor excision, recurrence rates in most large series are less than 1–2%. Inadvertent sub-total excision has been discussed in the preceding sections, but is most likely if visualization of the fundus of the internal auditory canal has been inadequate. Recurrence rates as high as 15% have been reported for retrosigmoid tumor removal where hearing preservation is attempted (Cerullo et al 1998). Continued tumor expansion can be expected in 5–15% of patients treated with stereotactic radiosurgery.

Management of recurrent disease The growth rate of recurrent tumors is said to be more rapid than that of de novo lesions (Sterkers et al 1992). The rarity of recurrence means that there are no large series to quantify accurately the risks of reoperation. Many large series include a few recurrent tumors, and the risks of reexploration and tumor removal may not differ substantially from those of the treatment of primary tumors (Ebersold et al 1992). Shea et al (1985), however, did note that morbidity for second operations is substantially higher than for primary tumors; they reported a 25% mortality. Arachnoidal adhesions resulting from previous exploration hinder identification of the nerves, and may make the lesion more difficult to free from the brain stem and adjacent vessels. Yet this is not the experience of Hitselberger & House (1979), who have commented that surgical planes are not obscured after a previous translabyrinthine operation. Tos et al (1988) reoperated on four patients through the labyrinth between 1 and 6 months after previous translabyrinthine surgery, without apparent difficulty. The interval between operations is likely to have a significant bearing on the density of adhesions. The treatment options for recurrent disease are similar to those for a primary tumor. If the facial nerve is nonfunctional as a consequence of the first operation, further surgery may be considerably less difficult. The translabyrinthine approach is ideal if the previous exploration was via a retrosigmoid or middle fossa route. The facial nerve can then be identified lateral to the tumor before any scar tissue is encountered. After translabyrinthine surgery a second operation may be via a retrosigmoid or transcochlear approach, so that at least some of the important landmarks may be identified before approaching the area of the tumor, where normal anatomic planes will be obscured by the previous surgery. Hearing preservation is very unlikely in this group, and the results of facial nerve preservation are also likely to be correspondingly less good than for primary tumors.

Management outcome The results of surgery as they relate to death, facial nerve function, and hearing are discussed in the section dealing with the results of surgery.



Headache It is our experience, and that of others (Schessel et al 1992), that postoperative headache is much more common with the suboccipital than translabyrinthine operation. Symptoms may last for years after surgery. The etiology remains unclear, but may be related to dissection of the nuchal musculature, scarring around the greater and lesser occipital nerves, or traction on the dura by adherence of the musculature. Replacement of the posterior fossa bone flap and reduction of muscle dissection to a minimum may help to reduce the incidence of this complication. A further factor which merits consideration is that, during the translabyrinthine operation, drilling of the temporal bone is completed before the dura is opened. In contrast during suboccipital surgery bone dust enters the basal cisterns when the posterior wall of the internal auditory canal is removed and thereby may precipitate chemical meningitis.

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Animal studies have shown that early visual and somatosensory stimulation determines both the speed and ultimate recovery after vestibular injury (Igarashi et al 1979). For this reason, vestibular exercises are important in the early postoperative period, and patients with bilateral vestibular nerve loss, impaired vision, or altered proprioception are less likely to make a good recovery. Healthy patients with unilateral vestibular loss should have a structured program of exercise, with emphasis on head movement. Initially the patient will experience feelings of instability, but labyrinthine sedatives should be avoided if possible, as these are likely to delay the compensatory process. An exercise strategy for rehabilitation following vestibular injury can be found in Goebel (1992). However, despite good compensation, all patients will have some chronic disturbance of postural equilibrium after labyrinthectomy, albeit insignificant clinically (House & Nelson 1979).

Quality of life Tinnitus Tinnitus is thought to be generated by the cochlea (Moller 1984), the cochlear nerve (Shea et al 1981), or the brain stem (Pulec et al 1978). Tinnitus may not be able to be abolished even by section of the cochlear nerve. After tumor removal there is only a 40–60% chance that tinnitus will improve, and a 6–40% likelihood that it will worsen (Silverstein et al 1986; Goel et al 1992). The probability of this is determined in part by the severity of preoperative symptoms. Baguley et al (1992) reported recently the effect of translabyrinthine surgery on tinnitus in a series of 129 patients. If tinnitus was not present preoperatively there was a 27% chance that it would develop after surgery, but it was very unlikely to be troublesome. If mild or moderate tinnitus was present before surgery there was a 25% chance that it would be abolished and a 37% chance that it would worsen. However, the risk that it would be severe under such circumstances was only around 2.5%. Severe tinnitus was very likely to improve after surgery, and was abolished entirely in one-fifth of patients.

Vestibular rehabilitation Initially, after labyrinthectomy or vestibular nerve section there is ataxia, with the patient veering to the operated side. Horizontal nystagmus, with the slow phase toward the ablated side, may also be evident. Although it may be anticipated that symptoms and signs are likely to be greatest in patients with small tumors and normal preoperative vestibular function, this is not in fact the case. Jenkins (1985) found that age, sex, tumor size, or the presence of brain stem compression did not alter significantly the rate of postoperative vestibular compensation. In most patients symptoms will be short-lived and, within a few weeks, nystagmus will be abolished and ataxia minimal (Fisch 1973). A recent study found that 31% of patients had disequilibrium lasting longer than 3 months after surgical removal of an acoustic neurinoma. Age >55.5 years, female gender, constant preoperative disequilibrium present for >3.5 months and central findings on electronystagmography were associated with a worse outcome (Driscoll et al 1998).

Figures for quality of life as they relate to tumor size are given in Table 28.2. Although it is customary to exclude facial nerve outcome from this analysis, a poor functional result in this regard may have profound social implications for the patient, because of the disfiguring appearance. In particular, the combination of hearing loss and cosmetic deformity may lead to a reluctance to resume social contacts (Wiegand & Fickel 1989). For others, the psychological impact of surgery is less but the physical aspects are more debilitating, particularly loss of balance. A detailed account of the patient’s perspective of his or her illness and recovery can be found in Wiegand and Fickel (1989). Recently, more objective studies of quality of life following acoustic neurinoma surgery have been performed and have demonstrated that the surgery can have a significant impact on patients’ overall quality of life (Nickolopoulos et al 1998). Key points

results of treatment have improved dramatically since the • The pioneering days of surgery in the early 1900s, and House’s landmark monograph of 1964. During that time mortality has fallen from 80% to <5%, primarily as a result of the introduction of modern anesthesia and the operating microscope.

of morbidity is now the major goal, particularly the • Reduction preservation of good facial function and the salvage of residual hearing.

modifications of operative technique, the introduction of • Incremental new technology such as stereotactic radiosurgery, and understanding of molecular genetics provide the prospect for further improvements in outcome during the coming decade.

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