Neurosurgery Blog

J Neurosurg 116:390–398, 2012.DOI: 10.3171/2011.10.JNS11783

The cavernous sinus and surrounding regions—specifically the Meckel cave, posterior sector of the cavernous sinus itself, and the upper part of the petroclival region—are the location of a large variety of lesions that require individual consideration regarding treatment strategy. These regions may be reached for biopsy by a percutaneous needle inserted through the foramen ovale. The aim of this retrospective study was to evaluate the diagnostic accuracy of percutaneous biopsy in a consecutive series of 50 patients referred for surgery between 1991 and 2010.

Methods. Seven biopsies (14%) were unproductive and 43 (86%) were productive, among which 28 lesions subsequently underwent histopathological examination during a second (open) surgery. To evaluate the diagnostic accuracy of the procedure, results from surgery were compared with those from the biopsy.

Results. Sensitivity of the percutaneous biopsy was 0.83 (95% CI 0.52–0.98), specificity was 1 (95% CI 0.79–1), and k coefficient was 0.81.

Conclusions. Because of its valuable diagnostic accuracy, percutaneous biopsy of the cavernous sinus and surrounding regions should be performed in patients with parasellar masses when neuroimaging does not provide sufficient information of a histopathological nature. This procedure would enable patients to obtain the most appropriate therapy, such as resective surgery, corticosteroids, chemotherapy, radiotherapy, or radiosurgery.

J Neurosurg 116:341–345, 2012.DOI: 10.3171/2011.9.JNS11656

The presence of angiogenesis is a hallmark of glioblastoma (GBM). Vascular endothelial growth factor (VEGF), which drives angiogenesis, provides an additional target for conventional therapy. The authors conducted a prospective clinical trial to test the effectiveness of bevacizumab, an inhibitor of VEGF, in newly diagnosed GBM.

Methods. From 2006 through 2010, 51 eligible patients with newly diagnosed GBM were treated with involvedfield radiation therapy and concomitant temozolomide (75 mg/m2 daily for 42 days) along with bevacizumab (10 mg/ kg every 2 weeks), starting 29 days after surgery. This was followed by 6 cycles of adjuvant temozolomide therapy (150 mg/m2 on Days 1–7 of a 28-day cycle) with bevacizumab administered at 10 mg/kg on Days 8 and 22 of each 28-day cycle.

Results. The 6- and 12-month progression-free survival (PFS) rates were 85.1% and 51%, respectively. The 12- and 24-month overall survival (OS) rates were 85.1% and 42.5%, respectively. Grade III/IV toxicities were noted in 10 patients (19.6%). No treatment-related deaths were observed. Asymptomatic intracranial bleeding was noted in 5 patients.

Conclusions. The addition of bevacizumab to conventional therapy in newly diagnosed GBM appears to improve both PFS and OS in patients with newly diagnosed GBM, with acceptable morbidity. A shift toward diffuse relapse was noted in a significant number of patients. Ongoing Phase III clinical trials will show the true benefit of this antiangiogenic approach.

Neurosurgery 70:283–294, 2012 DOI: 10.1227/NEU.0b013e31823020e6

Diffusion tensor (DT) imaging-based fiber tracking is a noninvasive magnetic resonance technique that can delineate the course of white matter fibers.

OBJECTIVE: To evaluate the accuracy and usefulness of this DT imaging-based fiber tracking for surgery in patients with gliomas near the pyramidal tract (PT).

METHODS: Subjects comprised 32 patients with gliomas near the PT. DT imagingbased fiber tracks of the PT were generated before and within 3 days after surgery in all patients. A tractography-integrated navigation system was used during the operation. Cortical and subcortical motor-evoked potentials (MEPs) were also monitored during resection to maximize the preservation of motor function. The threshold intensity for subcortical MEPs was examined by searching the stimulus points and changing the stimulus intensity. Minimum distance between the resection border and the illustrated PT was measured on postoperative tractography.

RESULTS: In all subjects, DT imaging-based tractography of the PT was successfully performed, preoperatively demonstrating the relationship between tumors and the PT. With the use of the tractography-integrated navigation system and intraoperative MEPs, motor function was preserved postoperatively in all patients. A significant correlation was seen between threshold intensity for subcortical MEPs and the distance between the resection border and PT on postoperative DT imaging.

CONCLUSION: DT imaging-based fiber tracking is a reliable and accurate method for mapping the course of subcortical PTs. Fiber tracking and intraoperative MEPs were useful for preserving motor function in patients with gliomas near the PT.

Acta Neurochir (2012) 154:223–228. DOI 10.1007/s00701-011-1200-5

Microsurgical, circumferential stripping of intracerebral metastases often proves to be insufficient to prevent local tumor recurrence.

Objective We were interested in the potential impact of 5- aminolevulinic acid (5-ALA)-induced-fluorescence (5-AIF) as a diagnostic tool for the resection of intracerebral metastases.

Methods A retrospective analysis was performed for 52 patients who underwent 5-AIF-guided resection for intracerebral mass lesions that histologically corresponded to metastases from tumors outside the central nervous system. The presence of ALA fluorescence in the tumor was determined in each patient. In 42 patients, fluorescence of the resection cavity after tumor removal was additionally recorded. Data were correlated with neuropathological findings in tissue specimens.

Results A total of 32 of the 52 metastases (62%) exhibited 5-AIF in tumor parts. All 5-AIF-positive metastases exhibited an inhomogeneous fluorescence pattern. 5-AIF was neither associated with the histological type nor with the site of origin of the metastases. Residual fluorescence of the resection cavity was detected after macroscopically complete white light resection in 24 patients with 5-AIF positive metastases. Residual tumor tissue was histologically confirmed in 6 of 18 patients with available tissue specimens from such 5-AIF positive areas (33%).

Conclusions The majority of metastases (62%) were 5-AIF positive, suggesting a potential impact of 5-AIF for improved visualization of metastatic tumor tissue within the brain. However, residual 5-AIF after macroscopically complete resection of a metastasis needs to be interpreted with caution because of the limited specificity for detection of residual tumor tissue.

Neurosurg Rev (2012) 35:95–110. DOI 10.1007/s10143-011-0336-3

We hereby report our initial clinical experience of a dual-room intraoperative magnetic resonance imaging (iMRI) suite with a movable 1.5-T magnet for both neurosurgical and independent diagnostic uses. The findings from the first 45 patients who underwent scheduled neurosurgical procedures with iMRI in this suite (mean age, 41.3±12.0 years; intracranial tumors, 39 patients; cerebral vascular lesions, 5 patients; epilepsy surgery, 1 patient) were reported. The extent of resection depicted at intraoperative imaging, the surgical consequences of iMRI, and the clinical practicability of the suite were analyzed.

Fourteen resections with a trans-sphenoidal/transoral approach and 31 craniotomies were performed. Eighty-two iMRI examinations were performed in the operating room, while during the same period of time, 430 diagnostic scans were finished in the diagnostic room. In 22 (48.9%) of 45 patients, iMRI revealed accessible residual tumors leading to further resection. No iMRI-related adverse event occurred. Complete lesion removal was achieved in 36 (80%) of all 45 cases.

It is concluded that the dual-room 1.5-T iMRI suite can be successfully integrated into standard neurosurgical workflow. The layout of the dual-room suite can enable the maximum use of the system and save costs by sharing use of the 1.5-T magnet between neurosurgical and diagnostic use. Intraoperative MR imaging may provide valuable information that allows intraoperative modification of the surgical strategy.

Neurosurgery 70:56–65, 2012 DOI: 10.1227/NEU.0b013e31822cb882

To reduce the risk of disabling postoperative functional deficit in patients with lesions in the dominant hemisphere, information about the localization of eloquent language areas is mandatory.

OBJECTIVE: To demonstrate the feasibility of arcuate fascicle (AF) tractography for proper localization of eloquent language areas in the superior temporal (STG) and inferior frontal gyrus (IFG).

METHODS: Between January and June 2010, we performed surgery in 13 patients with highly eloquent lesions with close spatial relationship to the primary language areas. All of them received preoperative diffusion tensor imaging for AF tractography. The STG and IFG were delineated at the ends of the AF. Five patients underwent functional magnetic resonance imaging of the primary language areas. The results were compared with tractography.

RESULTS: Tractography of the AF without prior knowledge of the localization of the STG and IFG was feasible in all cases. In the cases with functional magnetic resonance imaging, the activation maps matched the tractography results. In all but 1 patient, preservation of the primary language areas was possible, proven by the good neurological outcome. One patient suffered from a language dysfunction caused by a lesion in the medial and inferior temporal gyrus along the surgical pathway.

CONCLUSION: Tractography of the AF is a useful tool for identification of parts of the main primary language areas. Using tractography as a localization procedure to determine the primary language areas aids in the delineation of the STG and IFG and thus may help reduce the risk of postoperative permanent neurological deficit.

Neurosurg Rev (2012) 35:53–66. DOI 10.1007/s10143-011-0333-6

Meningiomas of the posterior fossa represent a heterogeneous group of tumors regarding difficulty of resection and functional outcome.

The aim of this review was to focus on tumors located mainly on the posterior surface of the petrous bone and threatening hearing and facial functions.

An anatomical classification was used to evaluate surgical outcome depending on the relationship of the tumor to the internal auditory meatus. The authors performed a retrospective chart review of 53 consecutive patients operated on for a posterior petrous bone meningioma in a tertiary referral center and a literature review. Tumors were classified in four groups according to the modified Desgeorges and Sterkers classification: posterior petrous (P; 17 tumors), meatus and internal auditory canal (M; 12 tumors), petrous apex without invasion of the internal auditory canal (A; 9 tumors), and cerebellopontine angle with invasion of the internal auditory canal (AMP; 15 tumors).

The facial function was preserved in 100% of P and A tumors, 75% of group M tumors, and 53% of AMP tumors. Hearing preservation was attempted only in P, A, and M groups where rates of serviceable hearing preservation were 82%, 80%, and 66%, respectively. The cumulative rate of hearing preservation for AMP tumors was 45% in our literature review. The increased facial morbidity associated with AMP tumors compared with other groups was also confirmed by the review of the literature.

In conclusion, this study shows that among posterior petrous bone meningiomas, tumors invading the internal auditory canal present with increased postoperative functional morbidity in spite of a tailored approach regarding dural insertion.

Neurosurgery 70:211–219, 2012 DOI: 10.1227/NEU.0b013e31822d5f17

This second part of a comprehensive review of primary vertebral tumors focuses on locally aggressive and malignant tumors. As discussed in the earlier part of the review, both benign and malignant types of these tumors affect the adult and the pediatric population, and an understanding of their subtleties may increase their effective resection. In this review, we discuss the epidemiologic, histological, and imaging features of the most common locally aggressive primary vertebral tumors (chordoma and giantcell tumor) and malignant tumors (chondrosarcoma, Ewing sarcoma, multiple myeloma or plasmacytoma, and osteosarcoma). The figures used for illustration are from operative patients of the senior authors (Z.L.G. and J.H.C.). Taken together, parts 1 and 2 of this article provide a thorough and illustrative review of primary vertebral tumors.

Neurosurgery 70:234–244, 2012 DOI: 10.1227/NEU.0b013e318223f5

The Response Assessment in Neuro-Oncology (RANO) Working Group is an international, multidisciplinary effort to develop new standardized response criteria for clinical trials in brain tumors. The RANO group identified knowledge gaps relating to the definitions of tumor response and progression after the use of surgical or surgically based treatments.

OBJECTIVE: To outline a proposal for new response and progression criteria for the assessment of the effects of surgery and surgically delivered therapies for patients with gliomas.

METHODS: The Surgery Working Group of RANO identified surgically related end-point evaluation problems that were not addressed in the original Macdonald criteria, performed an extensive literature review, and used a consensus-building process to develop recommendations for how to address these issues in the setting of clinical trials.

RESULTS: Recommendations were formulated for surgically related issues, including imaging changes associated with surgical resection or surgically mediated adjuvant local therapies, the determination of progression in the setting where all enhancing tumor has been removed, and how new enhancement should be interpreted in the setting where local therapies that are known to produce nonspecific enhancement have been used. Additionally, the terminology used to describe the completeness of surgical resections has been recognized to be inconsistently applied to enhancing vs nonenhancing tumors, and a new set of descriptors is proposed.

CONCLUSION: The RANO process is intended to produce end-point criteria for clinical trials that take into account the effects of prior and ongoing therapies. The RANO criteria will continue to evolve as new therapies and technologies are introduced into clinical trial and/or practice.

Neurosurgery 70:40–48, 2012 DOI: 10.1227/NEU.0b013e31822ff0ed

The long-term prognosis of cerebellar astrocytomas needs to be reviewed.

OBJECTIVE: To elucidate the factors influencing tumor recurrence or progression and to determine how long these patient with cerebellar astrocytomas require surveillance with neuroimaging.

METHODS: A retrospective review of 101 children surgically treated for a cerebellar astrocytoma and followed up for >10 years was performed.

RESULTS: Mean follow-up was 18.4 years. Total resection confirmed by postoperative imaging was performed in 51 patients (50.5%; group A). Twenty-three patients (22.8%) had surgical total resection; however, equivocal residual tumor was found on postoperative imaging (group B). Subtotal resection leaving a portion of brainstem or cerebellar peduncle was performed in 27 patients (26.7; group C). Of these 50 residual tumors, 16 (32%) showed spontaneous regression and 8 (16%) showed arrested growth. Radiographic recurrence or progression was noted in 29 patients (28.7%). Only 3 of 51 patients (5.9%) of group A with total resection had recurrence, whereas 26 of 50 residual tumors (52%; groups B and C) progressed. The only factor affecting recurrence or progression by multivariate analysis was the extent of surgical resection. All tumor recurrence or progression except for 1 (96.6%) occurred within 8 years from the original surgery (range, 2-132 months).

CONCLUSIONS: Overall prognosis of cerebellar astrocytomas is good; the 10-year survival rate was 100% and recurrence- or progression-free rate was 71.3% in our cohort. Almost half of residual tumors showed spontaneous regression or arrested growth in the long term. Eight to 10 years is considered to be a reasonable follow-up period by neuroimaging.

J Neurosurg 115:1115–1125, 2011. DOI: 10.3171/2011.8.JNS11488

Insular gliomas can be resected with acceptable rates of neurological morbidity, but little is known with regard to impairment of higher-order neurocognitive functions. The frequency and functional impact of neurocognitive deficits in patients with gliomas has until recently been underappreciated. The authors therefore examined neurocognitive function in patients with insular gliomas and compared the findings in this group to those in a matched control group of patients with gliomas in nearby brain regions.

Methods. Thirty-three patients with WHO Grade II or III insular gliomas participated in neuropsychological evaluations before and after resection. To establish whether the pattern of neurocognitive performance was different from that of other patients with tumors in neighboring areas, patients with insular tumors were matched with control patients for age, educational level, preoperative Karnofsky Performance Scale score, tumor side, grade, and volume. The control group comprised patients in whom gliomas had been resected from frontal, temporal, and parietal areas near the insula. Baseline pre- and postoperative neurocognitive test results were compared between and within groups.

Results. Preoperative neurocognitive impairment was common in both insular and control groups. Patients with insular tumors had significantly worse preoperative performance on naming tests. In both groups, postoperative decline occurred in most neurocognitive domains. There were no statistically significant differences between patients in the insular and control groups with regard to rates of postoperative decline on any test. However, there were trends suggesting differential cognitive performance postoperatively, because patients with insular tumors were more likely to experience greater decline in learning and memory. Neurological morbidity was similar to prior rates reported in the literature.

Conclusions. Few statistically significant differences in cognitive function were observed between patients in the insular and control groups at either the pre- or postoperative evaluation, although there was a trend for patients with insular tumors to exhibit greater postoperative decline in learning and memory. Although technically more challenging, surgery for insular region glioma appears feasible without profound neurological or cognitive morbidity for many patients.

Acta Neurochir (2011) 153:2403–2426. DOI 10.1007/s00701-011-1149-4

This study investigates retrospectively the clinical, neuroradiological, pathological and surgical evidence verifying the infundibulo-tuberal topography for craniopharyngiomas (CPs). Infundibulo-tuberal CPs represent a surgical challenge due to their close anatomical relationships with the hypothalamus. An accurate definition of this topographical category is essential in order to prevent any undue injury to vital diencephalic centres.

Methods A systematic review of all scientific reports involving pathological, neuroradiological or surgical descriptions of either well-described individual cases or large series of CPs published in official journals and text books from 1892 to 2011 was carried out. A total of 1,232 documents providing pathological, surgical and/or neuroradiological evidence for the infundibulo-tuberal or hypothalamic location of CPs were finally analysed in this study.

Findings For a total of 3,571 CPs included in 67 pathological, surgical or neuroradiological series, 1,494 CPs (42%) were classified as infundibulo-tuberal lesions. This topography was proved in the autopsy of 122 nonoperated cases. The crucial morphological finding characterizing the tubero-infundibular topography was the replacement of the third ventricle floor by a lesion with a predominant intraventricular growth. This type of CP usually presents a circumferential band of tight adherence to the third ventricle floor remnants, formed by a functionless layer of rective gliosis of a variable thickness. After complete surgical removal of an infundibulo-tuberal CP, a wide defect or breach at the floor of the third ventricle is regularly observed both in the surgical field and on postoperative magnetic resonance imaging studies.

Conclusions Infundibulo-tuberal CPs represent a major topographical category of lesions with a primary subpial development at the floor of the third ventricle. These lesions expand within the hypothalamus itself and subsequently occupy the third ventricle; consequently, they can be classified as not strictly intraventricular CPs. A tight attachment to the hypothalamus and remnants of the third ventricle floor is the pathological landmark of infundibulotuberal CPs.

Neurosurgery 69:1272–1280, 2011 DOI: 10.1227/NEU.0b013e3182233e24

Convection-enhanced delivery of chemotherapeutics for the treatment of malignant glioma is a technique that delivers drugs directly into a tumor and the surrounding interstitium through continuous, low-grade positive-pressure infusion. This allows high local concentrations of drug while overcoming the limitations imposed by toxicity and the blood-brain barrier in systemic therapies that prevent the use of many potentially effective drugs.

OBJECTIVE: To examine the safety profile of a conventional chemotherapeutic agent, topotecan, via convection-enhanced delivery in the treatment of recurrent malignant gliomas and secondarily to assess radiographic response and survival.

METHODS: We performed a prospective, dose-escalation phase Ib study of the topoisomerase- I inhibitor topotecan given by convection-enhanced delivery in patients with recurrent malignant gliomas.

RESULTS: Significant antitumor activity as described by radiographic changes and prolonged overall survival with minimal drug-associated toxicity was demonstrated. A maximum tolerated dose was established for future phase II studies.

CONCLUSION: Topotecan by convection-enhanced delivery has significant antitumor activity at concentrations that are nontoxic to normal brain. The potential for use of this therapy as a generally effective treatment option for malignant gliomas will be tested in subsequent phase II and III trials

J Neurosurg 115:1087–1093, 2011. DOI: 10.3171/2011.7.JNS11495

The reliable preoperative visualization of facial nerve location in relation to vestibular schwannoma (VS) would allow surgeons to plan tumor removal accordingly and may increase the safety of surgery. In this prospective study, the authors attempted to validate the reliability of facial nerve diffusion tensor (DT) imaging–based fiber tracking in a series of patients with large VSs. Furthermore, the authors evaluated the potential of this visualization technique to predict the morphological shape of the facial nerve (tumor compression–related flattening of the nerve).

Methods. Diffusion tensor imaging and anatomical images (constructive interference in steady state) were acquired in a series of 22 consecutive patients with large VSs and postprocessed with navigational software to obtain facial nerve fiber tracking. The location of the cerebellopontine angle (CPA) part of the nerve in relation to the tumor was recorded during surgery by the surgeon, who was blinded to the results of the fiber tracking. A correlative analysis was performed of the imaging-based location of the nerve compared with its in situ position in relation to the VS.

Results. Fibers corresponding to the anatomical location and course of the facial nerve from the brainstem to the internal auditory meatus were identified with the DT imaging–based fiber tracking technique in all 22 cases. The location of the CPA segment of the facial nerve in relation to the VS determined during surgery corresponded to the location of the fibers, predicted by the DT imaging–based fiber tracking, in 20 (90.9%) of the 22 patients. No DT imaging–based fiber tracking correlates were found with the 2 morphological types of the nerve (compact or flat).

Conclusions. The current study of patients with large VSs has shown that the position of the facial nerve in relation to the tumor can be predicted reliably (in 91%) using DT imaging–based fiber tracking. These are preliminary results that need further verification in a larger series.

Neurosurgery 69:1171–1180, 2011 DOI: 10.1227/NEU.0b013e31822b8107

Primary vertebral tumors, although less common than metastases to the spine, make up a heterogeneous group of neoplasms that can pose diagnostic and treatment challenges. They affect both the adult and the pediatric population and may be benign, locally aggressive, or malignant.

An understanding of typical imaging findings will aid in accurate diagnosis and help neurosurgeons appreciate anatomic subtleties that may increase their effective resection. An understanding of the histological similarities and differences between these tumors is imperative for all members of the clinical team caring for these patients. In this first review of 2 parts, we discuss the epidemiological, histological, and imaging features of the most common benign primary vertebral tumors— aneurysmal bone cyst, chondroma and enchondroma, hemangioma, osteoid osteoma, and osteoblastoma—and lesions related to eosinophilic granuloma and fibrous dysplasia.

In addition, we discuss the basic management paradigms for each of these diagnoses. In combination with part II of the review, which focuses on locally aggressive and malignant tumors, this article provides a comprehensive review of primary vertebral tumors

Neurosurgery 69[ONS Suppl 2]:ons121–ons140, 2011. DOI: 10.1227/NEU.0b013e31822a547b

Schwannomas originating from the hypoglossal nerve are extremely rare. Microsurgical resection with the goal for cure has traditionally been associated with a high risk of postoperative deficits.

OBJECTIVE: To summarize our clinical experience using tailored cranial base approaches for these formidable lesions.

METHODS: The clinical records of 13 patients were retrospectively reviewed. In addition, all reported patients in the literature were reviewed. The extreme lateral infrajugular transcondylar-transtubercular exposure approach was used in all of our patients. Based on our experience and literature analysis, we propose the following modified grading scale to facilitate surgical planning: type A, intradural tumors; type B, dumbbell-shaped tumors; type C, extracranial tumors; and type D, peripheral tumors.

RESULTS: All 13 patients underwent total, near-total, or subtotal tumor resection. Eight patients were men, 5 were women (mean age, 41.7 years). Sural nerve graft reconstruction for the hypoglossal nerve was performed in 4 patients. Three of the 4 patients in whom nerve reconstruction was performed regained satisfactory movement of their tongue. In the review of the literature, the mean patient age was 45.8 years. Patients presented with tongue atrophy (91.6%), headache (60.9%), and dysphagia (31.8%). The tumors were categorized as type A in 31.7% of these patients, type B in 38.6%, type C in 6.2%, and type D in 23.4%.

CONCLUSION: The extreme lateral infrajugular transcondylar-transtubercular exposure approach, which is a modification of the extreme lateral suboccipital approach, provides sufficient exposure for most intracranial dumbbell-shaped hypoglossal schwannomas. Hypoglossal nerve reconstruction using a sural nerve graft improves tongue atrophy and movement for patients with resected nerves.

Neurosurgery 69:1116–1123, 2011 DOI: 10.1227/NEU.0b013e31822932fe
Traditional treatment options for optic nerve sheath meningiomas (ONSMs) include observation, surgery, and radiotherapy, but to date none of these has become the clear treatment of choice.
OBJECTIVE: To evaluate the effectiveness and safety of multisession radiosurgery for ONSMs.
METHODS: From May 2004 to June 2008, 21 patients with ONSMs were treated by radiosurgery using the frameless CyberKnife system. Patient age ranged from 36 to 73 years (mean, 54 years). All patients were treated using multisession radiosurgery, with 5 fractions of 5 Gy each to a total dose of 25 Gy prescribed to the 75% to 85% isodose line. Patients were evaluated for tumor growth control and visual function.
RESULTS: The median pretreatment tumor volume was 2.8 mL (range, 0.3-23 mL). The mean follow-up was 30 months (range, 11-68 months). All patients tolerated treatment well, with only 1 patient in whom a mild optic neuropathy developed (which remitted after systemic steroid therapy). No other acute or late radiation-induced toxicities were observed. No patients showed ONSM progression on follow-up magnetic resonance imaging. Two patients (10%) had a partial response. No patients had worsening of visual function; visual function was stable in 65% and improved in 35% of patients.
CONCLUSION: Multisession radiosurgery for ONSMs was found to be safe and effective. The preliminary results from this study, in terms of growth control, visual function improvement, and toxicity, are quite promising. Further investigations are warranted.

J Neurosurg 115:906–914, 2011. DOI: 10.3171/2011.6.JNS11131

Vestibular schwannomas are histopathologically benign tumors arising from the Schwann cell sheath surrounding the vestibular branch of cranial nerve VIII and are related to the NF2 gene and its product merlin.

Merlin acts as a tumor suppressor and as a mediator of contact inhibition. Thus, deficiencies in both NF2 genes lead to vestibular schwannoma development.

Recently, there have been major advances in our knowledge of the molecular biology of vestibular schwannomas as well as the development of novel therapies for its treatment.

In this article the authors comprehensively review the recent advances in the molecular biology and characterization of vestibular schwannomas as well as the development of modern treatments for vestibular schwannoma. For instance, merlin is involved with a number of receptors including the CD44 receptor, EGFR, and signaling pathways, such as the Ras/raf pathway and the canonical Wnt pathway. Recently, merlin was also shown to interact in the nucleus with E3 ubiquitin ligase CRL4DCAF1.

A greater understanding of the molecular mechanisms behind vestibular schwannoma tumorigenesis has begun to yield novel therapies. Some authors have shown that Avastin induces regression of progressive schwannomas by over 40% and improves hearing. An inhibitor of VEGF synthesis, PTC299, is currently in Phase II trials as a potential agent to treat vestibular schwannoma.

Furthermore, in vitro studies have shown that trastuzumab (an ERBB2 inhibitor) reduces vestibular schwannoma cell proliferation.

With further research it may be possible to significantly reduce morbidity and mortality rates by decreasing tumor burden, tumor volume, hearing loss, and cranial nerve deficits seen in vestibular schwannomas.

Neuroradiology (2011) 53:1017–1024. DOI 10.1007/s00234-011-0898-3

Recurrent gliomas are usually histologically high grade; either due to recurrence of a de novo high-grade primary or anaplastic transformation in case of low-grade tumors. Survival in these patients is variable. The objective of the present study is to evaluate the role of FDG PET-CT for predicting survival in a large group of patients with suspected recurrent glioma.

Methods A total of 81 previously treated histopathologically proven glioma patients; with clinical and conventional imaging findings suspicious of recurrence were included in this study. All patients underwent FDG PET-CT study. Based on tumor to white matter (T/W) and tumor to grey matter (T/G) ratios, all lesions were scored on PET-CT (PET scores 0, 1 and 2). Patients were followed up clinically and by repeated imaging. Data was censored, if the patient died of disease or at the end of the study. Survival analysis was done for each variable employing univariate analysis followed by multivariate analysis, using variables found significant on univariate analysis.

Results PET score was found to be the most significant predictor of survival in univariate and multivariate analysis (p 0.003). Patients having PET score 2 had poorer survival compared to both PET score 0 (p 0.001) and PET score 1 (p 0.004). Other covariates found to have significant correlation with survival were primary treatment modality and clinical symptoms at the time of recurrence.

Conclusion FDG uptake on PET-CT is a strong predictor of survival in patients with suspected recurrent glioma.

J Neurosurg 115:885–893, 2011.DOI: 10.3171/2011.6.JNS101963

In large vestibular schwannomas (VSs), microsurgery is the main treatment option. A wait-and-scan policy or radiosurgery are generally not recommended given concerns of further lesion growth or increased mass effect due to transient swelling. Note, however, that some patients do not present with symptomatic mass effect or may still have serviceable hearing. Moreover, others may be old, suffer from severe comorbidity, or refuse any surgery. In this study the authors report the results in patients with large, growing VSs primarily treated with Gamma Knife surgery (GKS), with special attention to volumetric growth, control rate, and symptoms.

Methods. The authors retrospectively analyzed 33 consecutive patients who underwent GKS for large, growing VSs, which were defined as > 6 cm3 and at least indenting the brainstem. Patients with neurofibromatosis Type 2 were excluded from analysis, as were patients who had undergone previous treatment. Volume measurements were performed on contrast-enhanced T1-weighted MR images at the time of GKS and during follow-up. Medical charts were analyzed for clinical symptoms.

Results. Radiological growth control was achieved in 88% of cases, clinical control (that is, no need for further treatment) in 79% of cases. The median follow-up was 30 months, and the mean VS volume was 8.8 cm3 (range 6.1–17.7 cm3). No major complications occurred, although ventriculoperitoneal shunts were placed in 2 patients. The preservation of serviceable hearing and facial and trigeminal nerve function was achieved in 58%, 91%, and 86% of patients, respectively, with any facial and trigeminal neuropathy being transient. In 92% of the patients presenting with trigeminal hypesthesia before GKS, the condition resolved during follow-up. No patient- or VS-related feature was correlated with growth.

Conclusions. Primary GKS for large VSs leads to acceptable radiological growth rates and clinical control rates, with the chance of hearing preservation. Although a higher incidence of clinical control failure and postradiosurgical morbidity is noted, as compared with that for smaller VSs, primary radiosurgery is suitable for a selected group of patients. The absence of symptomatology due to mass effect on the brainstem or cerebellum is essential, as are close clinical and radiological follow-ups, because there is little reserve for growth or swelling.