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Svetlana Pravdenkova, Ossama Al-Mefty, Jeffrey Sawyer and Muhammad Husain

Object

The preponderance of progesterone receptors (PRs) and the scarcity of estrogen receptors (ERs) in meningiomas are well known. The expression of PRs may relate to tumor grade and recurrence. Cytogenetic abnormalities are associated with aggressive behavior, recurrence, and progression. In this study, the authors focus on the prognostic implications of hormone receptors in meningiomas to help determine the clinical and biological aggressiveness of tumors and their correlations with cytogenetic abnormalities.

Methods

Two hundred thirty-nine patients with meningiomas were separated into three groups. Group 1 (PR-positive group) comprised patients whose meningiomas displayed expression of PRs alone. Group 2 (receptor-negative group) included patients whose lesions did not have receptors for either progesterone or estrogen. Group 3 (ER-positive group) included patients whose tumors displayed expression of ERs. Clinical and histological findings, proliferative indices, tumor recurrence, and cytogenetic findings were analyzed by performing the Fisher exact test.

Compared with the receptor-negative (Group 2) and ER-positive (Group 3) groups, the PR-positive group (Group 1) had a statistically significant lower proliferative index and a smaller number of patients in whom there were aggressive histopathological findings or changes in karyotype. In Groups 1, 2, and 3, the percentages of cases with aggressive histopathological findings were 10, 31, and 33%, respectively; the percentages of cases with chromosomal abnormalities were 50, 84, and 86%, respectively; and the percentages of cases in which there initially was no residual tumor but recurrence was documented were 5, 30, and 27%, respectively. A statistically significant increase in the involvement of chromosomes 14 and 22 was identified in receptor-negative and ER-positive de novo meningiomas, when compared with the PR-positive group. Abnormalities on chromosome 19 were statistically significantly higher in receptor-negative meningiomas than in PR-positive tumors.

Conclusions

The expression of the PR alone in meningiomas signals a favorable clinical and biological outcome. A lack of receptors or the presence of ERs in meningiomas correlates with an accumulation of qualitative and quantitative karyotype abnormalities, a higher proportional involvement of chromosomes 14 and 22 in de novo tumors, and an increasing potential for aggressive clinical behavior, progression, and recurrence of these lesions. Sex hormone receptor status should routinely be studied for its prognostic value, especially in female patients, and should be taken into account in tumor grading. The initial receptor status of a tumor may change in progression or recurrence of tumor.

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Kadir Erkmen, Svetlana Pravdenkova and Ossama Al-Mefty

Petroclival meningiomas remain one of the most challenging intracranial tumors to treat surgically. This is attributable to their location deep within the skull base and their association with multiple critical neural and vascular structures. Over the years, many skull base approaches have been described that are meant to improve resection and decrease patient morbidity. Appropriate selection of the surgical approach requires a thorough preoperative evaluation of clinical and radiological factors. In this paper the authors retrospectively reviewed 97 patients treated surgically for petroclival meningiomas by the senior author (O.A.M.) between 1995 and 2005 to assess the factors used to determine the choice of surgical approach, and to assess complication rates based on the approach selected. The skull base approaches used in these patients included the middle fossa anterior petrosal, posterior petrosal, and combined petrosal approaches, and complete petrosectomy. Factors found to be important in determining the selection of approach included the size, location, and extension of the tumor, preoperative hearing evaluation, and venous sinus anatomy.

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Ossama Al-Mefty

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Ossama Al-Mefty and Aramis Teixeira

Object

Tumors of the glomus jugulare are benign, slow-growing paragangliomas. Their natural history, surgical treatment, and outcome have been well addressed in the recent literature; however, there remains a subgroup of complex tumors—multiple, giant, malignant, neuropeptide-secreting lesions, and those treated previously by an intervention with an adverse outcome—that is high risk, presents surgical challenges, and is associated with treatment controversy. In this article the authors report on a series of patients with complex glomus jugulare tumors and focus on treatment decisions, avoidance of complications, surgical refinements, and patient outcomes.

Methods

In this retrospective study, the patient population was composed of 11 male and 32 female patients (mean age 47 years) with complex tumors of the glomus jugulare who were treated by the senior author within the past 20 years. These include 38 patients with giant tumors, 11 with multiple paragangliomas (seven bilateral and four ipsilateral), two with tumors that hypersecreted catecholamine, and one with a malignant tumor. Six patients had associated lesions: one dural arteriovenous malformation, one carotid artery (CA) aneurysm, two adrenal tumors, and two other cranial tumors.

All but one patient presented with neurological deficits. Cranial nerve deficits, particularly those associated with the lower cranial nerves, were the prominent feature. Twenty-eight patients underwent resection in an attempt at total removal, and gross-total resection was achieved in 24 patients. Particularly challenging were cases in which the patient had undergone prior embolization or CA occlusion, after which new feeding vessels from the internal CA and vertebrobasilar artery circulation developed.

The surgical technique was tailored to each patient and each tumor. It was modified to preserve facial nerve function, particularly in patients with bilateral tumors. Intrabulbar dissection was performed to increase the likelihood that the lower cranial nerves would be preserved. Each tumor was isolated to improve its resectability and prevent blood loss. No operative mortality occurred. In one patient hemiplegia developed postoperatively due to CA thrombosis, but the patient recovered after an endovascular injection of urokinase. In four patients a cerebrospinal fluid leak was treated through spinal drainage, and in five patients infection developed in the external ear canal. Two of these infections progressed to osteomyelitis of the temporal bone. There were two recurrences, one in a patient with a malignant tumor who eventually died of the disease.

Conclusions

Despite the challenges encountered in treating complex glomus jugulare tumors, resection is indicated and successful. Multiple tumors mandate a treatment plan that addresses the risk of bilateral cranial nerve deficits. The intra-bulbar dissection technique can be used with any tumor, as long as the tumor itself has not penetrated the wall of the jugular bulb or infiltrated the cranial nerves. Tumors that hypersecrete catecholamine require perioperative management and malignant tumors carry a poor prognosis.

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Ossama Al-Mefty, Paulo A. S. Kadri, Svetlana Pravdenkova, Jeffrey R. Sawyer, Colin Stangeby and Muhammad Husain

Object. The malignant progression of benign tumors is well documented in gliomas and other systemic lesions. It is also well known that some meningiomas become progressively aggressive despite their original benign status. The theory of clonal evolution is widely believed to explain malignant progression in meningioma; however, the data used to explain stepwise progression have typically been derived from the cytogenetic analysis of different types of tumors of different grades and in different patients. In this study, the authors examined the data obtained in a group of patients with meningiomas that showed clear histopathological progression toward a higher grade of malignancy and then analyzed the underlying cytogenetic findings.

Methods. Among 175 patients with recurrent meningiomas, 11 tumors showed a histopathological progression toward a higher grade that was associated with an aggressive clinical course. Six tumors progressed to malignancy and five to the atypical category over a period averaging 112 months. Tests for MIB-1 and p53 and cytogenetic studies with the fluorescence in situ hybridization (FISH) method were performed in successive specimens obtained in four patients.

The MIB-1 value increased in subsequent samples of tumors. Cytogenetic analysis with FISH showed deletions of 22, 1p, and 14q. In all but one case, these aberrations were also present in the previous specimen despite its lower hispathological grade.

Conclusions. The authors documented the progression of meningiomas from benign to a higher histological grade. These tumors were associated with a complex karyotype that was present ab initio in a histologically lower-grade tumor, contradicting the stepwise clonal evolution model. Although it was limited to the tested probes, the FISH method appears to be more accurate than the standard cytogenetic one in detecting these alterations. Tumors that present with complex genetic alterations, even those with a benign histological grade, are potentially aggressive and require closer follow up.

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Paulo A. S. Kadri and Ossama Al-Mefty

Object

Schwannomas of the jugular foramen are rare, comprising between 2 and 4% of intracranial schwannomas. The authors retrospectively analyzed their surgical experience with schwannomas of the lower cranial nerves that presented with intra- and extracranial extensions through an enlarged jugular foramen. The transcondylar suprajugular approach was used without sacrificing the labyrinth or the integrity of the jugular bulb. In this report the clinical and radiological features are discussed and complications are analyzed.

Methods

This retrospective study includes six patients (three women and three men, mean age 31.6 years) with dumbbell-shaped jugular foramen schwannomas that were surgically treated by the senior author during a 5.5-year period. One patient had undergone previous surgery elsewhere. Glossopharyngeal and vagal nerve deficits were the most common signs (appearing in all patients), followed by hypoglossal and accessory nerve deficits (66.6%). Two or more signs or symptoms were present in every patient. Three tumors presented with cystic degeneration. In four patients the jugular bulb was not patent on neuroimaging studies. The suprajugular approach was used in five patients; the origin of the tumor from the 10th cranial nerve could be defined in three of them. All lesions were completely resected. No death or additional postoperative cranial nerve deficits occurred in this series. Aspiration pneumonia developed in one patient. Preoperative deficits of the ninth and 10th cranial nerves improved in one third of the patients and half recovered mobility of the tongue. No recurrence was discovered during the mean follow-up period of 32.8 months.

Conclusions

With careful, extensive preoperative evaluation and appropriate planning of the surgical approach, dumbbell-shaped jugular foramen schwannomas can be radically and safely resected without creating additional neurological deficits. Furthermore, recovery of function in the affected cranial nerves can be expected.

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Ossama Al-Mefty, Cahide Topsakal, Svetlana Pravdenkova, Jeffrey R. Sawyer and Michael J. Harrison

Object. Radiation-induced meningiomas are known to occur after high- and low-dose cranial radiation therapy. The goal of this study was to discern the distinguishing findings and characteristics of radiation-induced meningiomas.

Methods. The records of 16 patients (seven men and nine women) who fulfilled the criteria for radiation-induced meningiomas were retrospectively reviewed. Clinical, histopathological, cytokinetic, and cytogenetic findings as well as the patients' outcome were analyzed.

The mean age of the patients was 38.8 years and the mean tumor latency was 26.5 years. Five patients had multiple meningiomas in the irradiated field. The recurrence rate was 100% after the initial resection; 62% of patients had a second recurrence and 17% had a third recurrence. Thirty-eight percent of patients had atypical or malignant histopathological findings. The presence of progesterone receptors and low proliferation indices in these patients did not correlate with benign tumor behavior. Cytogenetic analysis showed multiple clonal aberrations in all tumors studied. The most frequent aberrations were found on chromosomes 1p, 6q, and 22. Derivative, lost, or additional chromosome 1p was found in 89% of cases and loss or deletion on chromosome 6 was found in 67%.

Conclusions. The age of patients at presentation with meningioma and the latency period of radiation-induced meningiomas are dose related. These tumors are more aggressive and are certain to recur, have a higher histopathological grade, and are associated with complex cytogenetic aberrations particularly involving 1p and 6q.

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Paulo A. S. Kadri and Ossama Al-Mefty

Object. Mobilizing the temporal muscle is a common neurosurgical maneuver. Unfortunately, the cosmetic and functional complications that arise from postoperative muscular atrophy can be severe. Proper function of the muscle depends on proper innervation, vascularization, muscle tension, and the integrity of muscle fibers. In this study the authors describe the anatomy of the temporal muscle and report technical nuances that can be used to prevent its postoperative atrophy.

Methods. This study was designed to determine the susceptibility of the temporal muscle to injury during common surgical dissection. The authors studied the anatomy of the muscle and its vascularization and innervation in seven cadavers. A zygomatic osteotomy was performed followed by downward mobilization of the temporal muscle by using subperiosteal dissection, which preserved the muscle and allowed a study of its arterial and neural components.

The temporal muscle is composed of a main portion and three muscle bundles. The muscle is innervated by the deep temporal nerves, which branch from the anterior division of the mandibular nerve. Blood is supplied through a rich anastomotic connection between the deep temporal arteries (anterior and posterior) on the medial side and the middle temporal artery (a branch of the superficial temporal artery [STA]) on the lateral side.

Conclusions. Based on these anatomical findings, the authors recommend the following steps to preserve the temporal muscle: 1) preserve the STA; 2) prevent injury to the facial branches by using subfascial dissection; 3) use a zygomatic osteotomy to avoid compressing the muscle, arteries, and nerves, and for greater exposure when retracting the muscle; 4) dissect the muscle in subperiosteal retrograde fashion to preserve the deep vessels and nerves; 5) deinsert the muscle to the superior temporal line without cutting the fascia; and 6) reattach the muscle directly to the bone.

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Jason A. Heth and Ossama Al-Mefty

Cavernous sinus meningiomas were once considered unresectable. The development of microsurgical and skull base techniques as well as advances in anesthesia and neuroradiology have allowed safe and systematic treatment of these lesions. Proper evaluation and patient counseling are required. A thorough understanding of the anatomy and surgical approaches are crucial to success, as is knowledge of the possible adverse outcomes including cranial neuropathy and stroke. The authors discuss these issues in the treatment of cavernous sinus meningiomas.

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Ossama Al-Mefty and Aramis Teixeira

Object. Tumors of the glomus jugulare are benign, slow-growing paragangliomas. Their natural history, surgical treatment, and outcome have been well addressed in the recent literature; however, there remains a subgroup of complex tumors—multiple, giant, malignant, neuropeptide-secreting lesions, and those treated previously by an intervention with an adverse outcome—that is high risk, presents surgical challenges, and is associated with treatment controversy. In this article the authors report on a series of patients with complex glomus jugulare tumors and focus on treatment decisions, avoidance of complications, surgical refinements, and patient outcomes.

Methods. In this retrospective study, the patient population was composed of 11 male and 32 female patients (mean age 47 years) with complex tumors of the glomus jugulare who were treated by the senior author within the past 20 years. These include 38 patients with giant tumors, 11 with multiple paragangliomas (seven bilateral and four ipsilateral), two with tumors that hypersecreted catecholamine, and one with a malignant tumor. Six patients had associated lesions: one dural arteriovenous malformation, one carotid artery (CA) aneurysm, two adrenal tumors, and two other cranial tumors.

All but one patient presented with neurological deficits. Cranial nerve deficits, particularly those associated with the lower cranial nerves, were the prominent feature. Twenty-eight patients underwent resection in an attempt at total removal, and gross-total resection was achieved in 24 patients. Particularly challenging were cases in which the patient had undergone prior embolization or CA occlusion, after which new feeding vessels from the internal CA and vertebrobasilar artery circulation developed.

The surgical technique was tailored to each patient and each tumor. It was modified to preserve facial nerve function, particularly in patients with bilateral tumors. Intrabulbar dissection was performed to increase the likelihood that the lower cranial nerves would be preserved. Each tumor was isolated to improve its resectability and prevent blood loss. No operative mortality occurred. In one patient hemiplegia developed postoperatively due to CA thrombosis, but the patient recovered after an endovascular injection of urokinase. In four patients a cerebrospinal fluid leak was treated through spinal drainage, and in five patients infection developed in the external ear canal. Two of these infections progressed to osteomyelitis of the temporal bone. There were two recurrences, one in a patient with a malignant tumor who eventually died of the disease.

Conclusions. Despite the challenges encountered in treating complex glomus jugulare tumors, resection is indicated and successful. Multiple tumors mandate a treatment plan that addresses the risk of bilateral cranial nerve deficits. The intrabulbar dissection technique can be used with any tumor, as long as the tumor itself has not penetrated the wall of the jugular bulb or infiltrated the cranial nerves. Tumors that hypersecrete catecholamine require perioperative management and malignant tumors carry a poor prognosis.