Category: Oncology

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Combination of Intracranial Temozolomide With Intracranial Carmustine Improves Survival When Compared With Either Treatment Alone in a Rodent Glioma Model

Neurosurgery:March 2010 – Volume 66 – Issue 3 – p 530–537.doi: 10.1227/01.NEU.0000365263.14725.39

BACKGROUND: Local delivery of temozolomide (TMZ) through polymers is superior to oral administration in a rodent glioma model.

OBJECTIVE: We hypothesized that the observed clinical synergy of orally administered TMZ and carmustine (BCNU) wafers would translate into even greater effectiveness with the local delivery of BCNU and TMZ and the addition of radiotherapy in animal models of malignant glioma.

METHODS: TMZ and BCNU were incorporated into biodegradable polymers that were implanted in F344 rats bearing established intracranial tumors. We used 2 different rodent glioma models: the 9L gliosarcoma and the F98 glioma.

RESULTS: In the 9L rodent glioma model, groups treated with the combination of local TMZ, local BCNU, and radiation therapy (XRT) had 75% long-term survivors (defined as animals alive 120 days after tumor implantation), which was superior to the combination of local TMZ and local BCNU (median survival, 95 days; long-term survival, 25%) and the combination of oral TMZ, local BCNU, and XRT (median survival, 62 days; long-term survival, 12.5%). To simulate the effect of this treatment in chemoresistant gliomas, a second rodent model was used with the F98 glioma, a cell line relatively resistant to alkylating agents. F98 glioma cells express high levels of alkyltransferase, an enzyme that deactivates alkylating agents and is the major mechanism of resistance of gliomas. The triple therapy showed a significant improvement in survival when compared with controls (P = .0004), BCNU (P = .0043), oral TMZ (P = .0026), local TMZ (P = .0105), and the combinations of either BCNU and XRT (P = .0378) or oral TMZ and BCNU (P = .0154).

CONCLUSION: The survival of tumor-bearing animals in the 9L and F98 glioma models was improved with the local delivery of BCNU and TMZ combined with XRT when compared with either treatment alone or oral TMZ, local BCNU, and XRT.

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Awake Surgery for Nonlanguage Mapping

Neurosurgery 66:523-529, 2010 DOI: 10.1227/01.NEU.0000364996.97762.73

During the past decade, numerous reports have supported the contribution  of awake mapping in surgical removal of brain lesions in eloquent areas, with a significant  increase of the extent of resection while minimizing the risk of permanent deficit—and  even improving quality of life.

METHODS: Most of these awake procedures were performed in patients with lesions in  language areas, to avoid postoperative aphasia. Surprisingly, mapping of nonlanguage  functions received less attention, despite the possible consequences of deficits other than  aphasia on daily life. Visuospatial and cognitive deficits are reported after brain surgery,  because of more objective and extensive neuropsychological assessments.

RESULTS AND CONCLUSION: This review provides new insights into the indications of  awake craniotomies for nonlanguage mapping in surgery for lesions in areas not related  to language processing.

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Cellularity and apparent diffusion coefficient in oligodendroglial tumours characterized by genotype

J Neurooncol (2010) 96:385–392. DOI 10.1007/s11060-009-9970-9

Apparent diffusion coefficient (ADC) describes water diffusion within tissues. Previous studies report a negative linear correlation between minimum ADC and tumour cellularity in different types of gliomas, but there are no studies in oligodendroglial tumours. This study evaluated the relationship between ADC and tumour cellularity in oligodendroglial tumours characterized by genotype.

Methods: ADC was assessed in 17 patients with known 1p/19q status: 3 grade II oligodendrogliomas (OII), 9 grade II oligoastrocytomas (OAII), 5 grade III oligoastrocytomas (OAIII). Regions of interest were placed on ADC maps around tumour margins to generate mean tumour ADC, and over minimum and maximum tumour ADC. Histopathology assessment of tumour cellularity determined minimum, maximum and mean cell density in serial stereotactic biopsies.

Results: 1p/19q loss was present in 2/3 OII, 5/9 OAII, 2/5 OAIII. Grade III tumours had higher maximum cell density than grade II tumours (17.2 vs. 10.57%: Mann Whitney U; P = 0.20). Oligoastrocytoma were more likely to have a lower minimum cell density than oligodendrogliomas (Mann Whitney U; P = 0.032). There was no relationship between cell density and genotype. There was no linear correlation between mean ADC and mean cell density (Spearman’s rho; r = 0.486: P = 0.438), minimum ADC and maximum cell density (Spearman’s rho; r = 0.158: P = 0.660), and maximum ADC and minimum cell density (Spearman’s rho; r = 0.039: P = 0.985).

Conclusions: In oligodendroglial tumours there is no relationship between quantitative assessment of cellularity and ADC. This may reflect differences in oligodendroglial tumour biology compared to other gliomas, although the composition of the extracellular matrix may influence ADC more than cellularity.

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High-grade intramedullary astrocytomas: 30 years’ experience at the Neurosurgery Department of the University of Rome “Sapienza”

J Neurosurg Spine 12:144–153, 2010. (DOI: 10.3171/2009.6.SPINE08910)

The goal in this study was to review a series of patients who underwent surgical removal of intramedul- lary high-grade gliomas, focusing on the functional outcome, recurrence rates, and technical problems continually debated in neurosurgical practice.

Methods. Between December 1976 and December 2006, 22 patients underwent removal of intramedullary high- grade gliomas. Lesions were located in the cervical spinal cord in 12 patients, and in the thoracic cord in 10.

Results. Histological examinations showed 10 Grade III astrocytomas and 12 glioblastomas. Only 2 of the 22 high-grade astrocytomas could be completely removed. The clinical postoperative status worsened in 14 patients (63.6%), was unchanged in 7 patients (31.8%), and there was 1 case of intraoperative death (4.5%). None of the 22 patients showed improvement in their neurological status postoperatively. In this series, excluding the 1 intraopera- tive death, all patients died of progression of the malignancy.

Conclusions. Surgical treatment did not ameliorate the postoperative neurological status; instead, in the majority of cases, it prompted a worsening of the deficit. Radiotherapy and chemotherapy have a little influence on the length of survival. In this series, multimodality treatment of intramedullary high-grade astrocytomas has been shown to increase length of survival without improving the neurological status.

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Microsurgical Excision of Colloid Cyst With Favorable Cognitive Outcomes and Short Operative Time and Hospital Stay: Operative Techniques and Analyses of Outcomes With Review of Previous Studies

Neurosurgery: February 2010 – Volume 66 – Issue 2 – p 368–375. doi: 10.1227/01.NEU.0000363858.17782.82

Microsurgical and endoscopic colloid cyst excision differ with regard to operative time, length of hospital stay, and extent of resection.

METHODS: A retrospective review of a single surgeon’s microsurgical colloid cyst resection in 10 consecutive patients was performed. Cyst size, hydrocephalus, symptoms, operative time, postoperative stay, complications, and objective testing of memory, concentration, calculation, and attention (cognition), along with performance at job, were noted.

RESULTS: All 10 patients had complete excision. Mean cyst size, mean operative time, and median postoperative stay were 1.6 cm, 124 minutes, and 3.5 days respectively. The mean operative time from cyst visualization to complete excision was 18 minutes. Follow-up ranged from 6 to 111 months (mean, 49.5 months). There were no recurrences; symptoms (headache, visual and balance problems) improved significantly in 70%. Postoperative cognitive performance, including memory, was the same in 8 patients (5 of whom had preoperative memory problems) and worse in 2 patients who had no preoperative memory problems. The bone flap was removed in 1 patient for wound dehiscence. Hemiparesis in another patient, seen immediately after surgery, completely resolved before discharge. One patient with loculated ventricles and multiple previous shunt revisions had unresolved hydrocephalus after cyst excision.

CONCLUSION: We report the very short operative times and postoperative stay for microsurgery, which are comparable to some endoscopic series. We also report results of objective tests of cognitive performance. With adoption of a callosal incision of 1 cm or less, meticulous dissection around the fornix, and complete excision, acceptable long-term cognitive function and functional performance were achieved. Our results support the microsurgical approach. A larger sample size can more conclusively establish whether it should be chosen over the endoscopic technique.

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Surgical management of World Health Organization Grade II gliomas in eloquent areas: the necessity of preserving a margin around functional structures

Neurosurg Focus 28 (2):E8, 2010. DOI: 10.3171/2009.12.FOCUS09236

Recent surgical studies have demonstrated that the extent of resection is significantly correlated with median survival in WHO Grade II gliomas. Consequently, thanks to advances in intraoperative functional mapping, the authors questioned whether it is actually necessary to leave a “security” margin around eloquent structures.
Methods. The authors first reviewed the classic literature, especially that based on epilepsy surgery and functional neuroimaging techniques, which led them to propose the rule of a security margin. Second, they detailed new developments in the field of intrasurgical electrical mapping, especially with regard to subcortical stimulation of the projection and long-distance association pathways. On the basis of these advances, the removal of gliomas according to functional boundaries has recently been suggested, with no margin around eloquent structures.
Results. Comparative results showed that the rate of permanent deficit was similar with or without a security margin, that is, < 2%. However, a higher rate of transient neurological worsening in the immediate postsurgical period was associated with the absence of a margin, with recovery following adapted rehabilitation. On the other hand, the extent of resection was in essence improved with no margin.
Conclusions. This no-margin technique, based on the subpial dissection, and the repetition of both cortical and subcortical stimulation to preserve eloquent cortex as well as the white matter tracts (U-fibers, projection pathways, and long-distance connectivity) allow optimization of the extent of resection while preserving the quality of life (despite transitory impairment) thanks to mechanisms of brain plasticity.

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Meningiomas in the elderly, the surgical benefit and a new scoring system

Acta Neurochir (2010) 152:87–97 DOI 10.1007/s00701-009-0552-6

Objective The purpose of the study was to define and identify prognostic indicators within an elderly population of patients suffering from intracranial meningiomas. The clinical presentation of the patient with meningioma is diverse, manifesting as a different clinical entity in the elderly patient compared to a similar type of tumor in a young patient.

Methods Two hundred fifty patients aged over 65 years admitted to RAMBAM Medical Center with meningiomas from 1995–2005 were characterized. We report the present- ing symptoms, chronic illnesses, perioperative and long- term follow-up results for a 5-year period.

Results Based on univariate and multivariate analysis, significant prognostic indicators were identified and were implemented into a new geriatric scoring system (GSS) including tumor size and location, peritumoral edema, neurological deficits, Karnofsky score (Clancey J Neurosci Nurs 27:220, 1995; Crooks et al. J Gerontol 46:M139– M144, 1991), and associated diabetes, hypertension or lung disease. Seven outcome parameters were retrospectively tested using the scoring system, namely mortality, Barthel Index score (Mahoney and Barthel Md State Med J 14:61–65, 1965), Karnofsky score and consciousness expressed by the Glasgow Coma Scale score (Jennett and Bond Lancet 1:480–484, 1975) 5 years after surgery, as well as recurrence within and beyond 12 months. Age proved to inversely correlate with outcome. Morbidity and mortality were significantly lower in women. The extent of surgical resection (Simpson J Neurol Neurosurg Psychiatry 20:22–39, 1957) had no influence on function- al outcome, although radical resection was associated with significantly lower mortality. Generally, a GSS score higher than 14 was associated with a significantly more favorable outcome.

Conclusion The present results suggest that common experience-based considerations may be optimized and implemented into a simple scoring system that in turn may allow for outcome prediction and evidence-based decision making.


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Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

Cancer Cell 17, 98–110, January 19, 2010

The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.

This work expands on previous glioblastoma classification studies by associating known subtypes with specific alterations in NF1 and PDGFRA/IDH1 and by identifying two additional subtypes, one of which is characterized by EGFR abnormalities and wild-type p53. In addition, the subtypes have specific differentiation characteristics that, combined with data from recent mouse studies, suggest a link to alternative cells of origin. Together, these data provide a framework for investigation of targeted therapies. Temozolomide and radiation, a common treatment for glioblastoma, has demonstrated a significant increase in survival. Our analysis illustrates that a survival advantage in heavily treated patients varies by subtype, with Classical or Mesenchymal subtypes having significantly delayed mortality that was not observed in the Proneural subtype


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In pursuit of prognostic factors in children with pilocytic astrocytomas

Childs Nerv Syst (2010) 26:19–28 DOI 10.1007/s00381-009-0990-8

This study described a 23-year experience in the treatment of children with pilocytic astrocytomas (piloA) with the aim of identifying putative clinical, histopathological, and/or immunohistochemical features that could be related to the outcome of these patients.

Methods Clinical data of 31 patients under 18 years of age with piloA were obtained from 1984 to 2006.

Results The mean age at the time of surgery was 7.8± 4.2 years (1 to 17 years), and the mean follow-up was 5.7± 5.4 years (1 to 20 years). The most common site of tumor formation was the cerebellum (17), followed by brainstem (4), optic chiasmatic hypothalamic region (4), cerebral hemisphere (3), cervical spinal cord (2), and optic nerve (1). Gross total resection (GTR) was achieved in 23 (74.1%), mainly in those with tumors located in the cerebellum and cerebral hemispheres (P=0.02). The global mortality rate was 6.4%. Nine patients were reoperated. Rosenthal fibers, eosinophilic granular bodies, microvascular proliferation, and lymphocytic infiltration were observed in most cases. The mean Ki-67LI was 4.4 ± 4.5%. In all cases, Gal-3 expression in tumor cells was observed with variable staining pattern.

Conclusions Aside from GTR, no other clinical, histopathological, or immunohistochemical features were found to be related to the prognosis. We postulate that strict follow- up is recommended if piloA is associated with high mitotic activity/Ki67-LI, or if GTR cannot be achieved at surgery. Tumor recurrence or progression of the residual lesion should be strictly observed. In some aspects, childhood piloA remains an enigmatic tumor.


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Meningiomas of the ventral foramen magnum and lower clivus: factors influencing surgical morbidity, the extent of tumour resection, and tumour recurrence

Acta Neurochir (2010) 152:79–86 DOI 10.1007/s00701-009-0511-2

Purpose To identify an appropriate surgical approach for meningiomas of the foramen magnum and lower clivus and determine the factors influencing the surgical outcomes. Method The study involved 23 patients with foramen magnum or lower clival meningiomas (8 men, 15 women; average age, 56 years; range, 26–70 years) treated at Keio University Hospital between 1991 and 2008. Their clinical data were retrospectively reviewed with regard to the surgical approaches and outcomes. The average follow-up duration was 42.8 months, the mean tumour size, 25.9 mm (range, 12.0–50.0 mm).

Findings The tumours most commonly originated in the anterolateral rim of the foramen magnum. In 12 cases with lateral compression of the brain stem, the tumours were resected via the suboccipital approach with C1 laminectomy. The transcondylar approach was adopted in 11 cases where the tumour was located on the anterior rim of the foramen magnum. Four patients required epidural drilling of the jugular tubercle. Gross total resection was achieved in 15 cases (62.5%), the resection rate being lowest in cases of tumour extension to the lower clivus. The transient and permanent morbidity rates were 30.4% and 17.4%, respectively. Logistic regression analysis revealed that extension to the lower clivus (noted in 6 of 23 patients) was a statistically significant, independent factor influencing the permanent morbidity rate (p = 0.005).

Conclusions Selecting an appropriate surgical approach considering the tumour location resulted in a good surgical outcome. However, tumour extension to the lower clivus strongly influenced the morbidity and tumour radicality.

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The natural history of untreated sporadic vestibular schwannomas: a comprehensive review of hearing outcomes

J Neurosurg 112:163–167, 2010.(DOI: 10.3171/2009.4.JNS08895)

Observation is an important consideration when discussing management options for patients with vestibular schwannoma (VS). Most data regarding clinical outcomes after conservative management come from modestsized series performed at individual centers. The authors performed an analysis of the published literature on the natural history of VSs with respect to hearing outcome. Their objective was to provide a comprehensive and unbiased description of outcomes in patients whose disease was managed conservatively. Methods. The authors identified a total of 34 published studies containing hearing outcome data in patients with VSs < 25 mm in largest diameter who underwent observation management. The effects of initial tumor size and tumor growth rate on hearing function at latest follow-up were analyzed. Data from individual and aggregated cases were extracted from each study. Patients with poorer hearing (American Association of Otolaryngology–Head and Neck Surgery Classes C or D, or Gardner-Robertson Classes III, IV, or V) at the time of presentation were excluded.

Results. A total of 982 patients met the inclusion criteria for this analysis, with a mean initial tumor size of 11.3 ± 0.68 mm. The mean growth rate was 2.9 ± 1.2 mm/year. The length of follow-up for these studies ranged from 26 to 52 months. Patients with preserved hearing at latest follow-up had a statistically larger initial tumor size than those whose hearing declined during the observation period (11.5 ± 2.3 mm vs 9.3 ± 2.7 mm, p < 0.0001), but the 2-mm difference of means was at the limit of imaging resolution and observer reliability. In contrast, patients with lower rates of tumor growth (≤ 2.5 mm/year) had markedly higher rates of hearing preservation (75 vs 32%, p < 0.0001) compared with patients with higher tumor growth rates. Interestingly, the authors’ analysis found no difference in the rate of reported intervention for patients in either group (16 vs 18%, p = not significant).

Conclusions. These data suggest that a growth rate of > 2.5 mm/year is a better predictor of hearing loss than the initial tumor size for patients undergoing observation management of VSs < 25 mm in largest diameter.


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Is Preoperative Functional Magnetic Resonance Imaging Reliable for Language Areas Mapping in Brain Tumor Surgery? Review of Language Functional Magnetic Resonance Imaging and Direct Cortical Stimulation Correlation Studies

doi: 10.1227/01.NEU.0000360392.15450.C9

OBJECTIVE: Language functional magnetic resonance imaging (fMRI) has been used extensively in the past decade for both clinical and research purposes. Its integration in the preoperative imaging assessment of brain lesions involving eloquent areas is progressively more diffused in neurosurgical practice. Nevertheless, the reliability of language fMRI is unclear. To understand the reliability of preoperative language fMRI in patients operated on for brain tumors, the surgical studies that compared language fMRI with direct cortical stimulation (DCS) were reviewed.

METHODS: Articles comparing language fMRI with DCS of language areas were reviewed with attention to the lesion pathology, the magnetic field, the language tasks used pre- and intraoperatively, and the validation modalities adopted to establish the reliability of language fMRI. We tried to explore the effectiveness of language fMRI in gliomas.

RESULTS: Nine language brain mapping studies compared the findings of fMRI with those of DCS. The studies are not homogeneous for tumor types, magnetic fields, pre- and intraoperative language tasks, intraoperative matching criteria, and results. Sensitivity and specificity were calculated in 5 studies (respectively ranging from 59% to 100% and from 0% to 97%).

CONCLUSION: The contradictory results of these studies do not allow consideration of language fMRI as an alternative tool to DCS in brain lesions located in language areas, especially in gliomas because of the pattern of growth of these tumors. However, language fMRI conducted with high magnet fields is a promising brain mapping tool that must be validated by DCS in methodological robust studies.

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Non-audiofacial morbidity after Gamma Knife surgery for vestibular schwannoma

Neurosurg Focus 27 (6):E4, 2009. (DOI: 10.3171/2009.9.FOCUS09198)

Object. While many studies have been published outlining morbidity following radiosurgical treatment of ves- tibular schwannomas, significant interpractitioner and institutional variability still exists. For this reason, the authors conducted a systematic review of the literature for non-audiofacial-related morbidity after the treatment of vestibular schwannoma with radiosurgery.

Methods. The authors performed a comprehensive search of the English-language literature to identify studies that published outcome data of patients undergoing radiosurgery treatment for vestibular schwannomas. In total, 254 articles were found that described more than 50,000 patients and were analyzed for satisfying the authors’ inclusion criteria. Patients from these studies were then separated into 2 cohorts based on the marginal dose of radiation: ≤ 13 Gy and > 13 Gy. All tumors included in this study were < 25 mm in their largest diameter.

Results. A total of 63 articles met the criteria of the established search protocol, which combined for a total of 5631 patients. Patients receiving > 13 Gy were significantly more likely to develop trigeminal nerve neuropathy than those receiving < 13 Gy (p < 0.001). While we found no relationship between radiation dose and the rate of developing hydrocephalus (0.6% for both cohorts), patients with hydrocephalus who received doses > 13 Gy appeared to have a higher rate of symptomatic hydrocephalus requiring shunt treatment (96% [> 13 Gy] vs 56% [≤ 13 Gy], p < 0.001). The rates of vertigo or balance disturbance (1.1% [> 13 Gy] vs 1.8% [≤ 13 Gy], p = 0.001) and tinnitus (0.1% [> 13 Gy] vs 0.7% [≤ 13 Gy], p = 0.001) were significantly higher in the lower dose cohort than those in the higher dose cohort.

Conclusions. The results of our review of the literature provide a systematic summary of the published rates of nonaudiofacial morbidity following radiosurgery for vestibular schwannoma.

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Occipital inter-hemispheric approach for lateral ventricular trigone meningioma

Acta Neurochir (2009) 151:1717–1721. DOI 10.1007/s00701-009-0310-9

Objective The optimal surgical approach for a trigone meningioma is still controversial. Here, we report two patients with trigone meningioma treated successfully via an occipital inter-hemispheric and trans-cortical approach in the lateral semi-prone position.

Clinical presentation A 53-year-old woman was admitted to a local hospital with sudden transient dizziness and vomiting. The CT brain scan demonstrated a right intraventricular tumour. She was therefore transferred to our hospital for surgical treatment. The other patient was a 67- year-old woman who was admitted to a local hospital after a traffic accident and a CT brain scan revealed an incidental right intra-ventricular tumour. After referral to our hospital, periodic MRI examinations revealed gradual tumour enlargement within a one-year period. Neither of the patients had any neurological deficits, including in the visual fields.

Intervention The head of each patient was positioned so that the tumour-containing right ventricle was oriented downwards and laterally. An occipital inter-hemispheric approach was performed and using a navigation system, the tumour was identified about 1 cm in depth from the cortical surface. After the medial part of the tumour was debulked, the posterior and then the anterior choroidal blood supplies to the tumour were identified. Occlusion of these vessels achieved tumour haemostasis. The tumours were totally removed via a 1.5-cm cortical incision. Brain retraction was minimal because the right hemisphere was pulled down by gravity. Therefore, the para-splenial cisterns were easily accessed, resulting in early release of cerebrospinal fluid.

Post-operative MRI showed complete removal of the tumour and the patients had no neurological deficits. Antiepileptic medication was withdrawn one week after the operation. Conclusions The occipital inter-hemispheric fissure lacks important bridging veins. The approach used and patient positioning minimized damage to the lateral aspect of the optic radiation and the corpus callosum. Except in patients with very large trigone meningiomas, this approach is useful for decreasing the risk of post-operative hemianopsia or epilepsy, and possibly speech disturbance, even in patients with a tumour in the dominant hemisphere.


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Vestibular Schwannoma: Surgery or Gamma-Knife radiosurgery?. A prospective, non-randomized study

Neurosurgery 64:654–663, 2009 DOI: 10.1227/01.NEU.0000340684.60443.55

OBJECTIVE: To conduct a prospective, open, nonrandomized study of treatment- associated morbidity in patients undergoing microsurgery or gamma knife radiosurgery (GKRS) for vestibular schwannomas.

METHODS: Ninety- one patients with vestibular schwannomas with a maximum tumor diameter of 25 mm in the cerebellopontine angle were treated according to a prospective protocol either by GKRS (63 patients) or open microsurgery (28 patients) using the suboccipital approach. Primary end points included hearing function, according to the Gardner- Robertson scale, and facial nerve function, according to the House- Brackmann scale at 2 years. Clinical data included a balance platform test, score for tinnitus and vertigo using a visual analog scale, and working ability. Patients responded to the qualityof- life questionnaires Short- Form 36 and Glasgow Benefit Inventory.

RESULTS: Three elderly GKRS patients withdrew; all remaining patients were followed for 2 years. Both primary end points were highly significant in favor of GKRS (P<0.001). Evidence of reduced facial nerve function (House- Brackmann grade 2 or poorer) at 2 years was found in 13 of 28 open microsurgery patients and 1 of 60 GKRS patients. Thirteen of 28 patients who underwent surgery had serviceable hearing (Gardner- Robertson grade A or B) preoperatively, but none had serviceable hearing postoperatively. Twentyfive of 60 GKRS patients had serviceable hearing before treatment, and 17 (68%) of them had serviceable hearing 2 years after treatment. The tinnitus and vertigo visual analog scale score, as well as balance platform tests, did not change significantly after treatment, and working status did not differ between the groups at 2 years. Quality of life was significantly better in the GKRS group at 2 years, based on the Glasgow Benefit Inventory questionnaire. One GKRS patient required operative treatment within the 2-year study period.

CONCLUSION: This is the second prospective study to demonstrate better facial nerve and hearing outcomes from GKRS than from open surgery for small- and medium- sized vestibular schwannomas.

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Neurological outcome of long-term glioblastoma survivors

J Neurooncol (2009) 95:301–305 DOI 10.1007/s11060-009-9946-9

Extended survival of 3 or more years is rare in patients with glioblastoma (GBM) but is becoming more common. Clinical outcome has not been well studied. We reviewed GBM patients at Memorial Sloan-Kettering Cancer Center between 2001 and 2003 who were seen for two or more visits. Patient characteristics and long-term clinical outcomes were reviewed for patients who had survived 3 or more years following diagnosis. Thirty-nine (11%) of 352 GBM patients were identified as long-term survivors. Median survival was 9.15 years (range: 3–18 years). Median age was 47 years (range: 16–69); 13% were 65 years or older. Median KPS was 90 (range: 50–100). One long-term survivor underwent biopsy alone; 19 patients each had either complete or subtotal resection. All received focal radiotherapy (RT) with a median dose of 5940 cGy; 18% received concurrent temozolomide. Adjuvant chemotherapy was administered to 35 (90%). Twelve patients (31%) remained in continuous remission. Twenty-seven had tumor progression a median of 29.2 months after diagnosis (range: 1.2–167 months); 18 had multiple relapses. Median KPS at last follow-up was 70 (range: 40–100); 85% of long-term survivors had at least one significant neurologic deficit. Eleven (28%) had clinically significant RT-induced leukoencephalopathy, 9 (23%) developed RT necrosis and 9 (23%) treatment-related strokes. Treatment-related complications occurred a median of 2.7 years from diagnosis (range: 0.9–11.5 years).

Long-term survivors remain rare, but are found across all age groups despite multiple recurrences; clinically significant delayed complications of treatment are common.

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Management of osteoblastoma and osteoid osteoma of the spine in childhood

J Neurosurg Pediatrics 4:434-438, 2009. DOI: 10.3171/2009.6.PEDS08450

Osteoid osteomas and osteoblastoma of the spine are rare lesions in childhood, and management strategies have changed.

The authors reviewed their recent experience with these 2 types of lesions to elucidate current treatment modalities and outcomes.

Methods. Case records and radiographic images from all cases of osteoid osteoma and osteoblastoma diagnosed between 1993 and 2008 were retrospectively reviewed, including those managed nonsurgically.

Results. Thirty cases were identified; 22 were treated surgically and 8 were managed nonsurgically. The patients’mean age at presentation was 13 years (range 3–17 years). Of 30 patients, 29 (97%) presented with pain; 7 (23%) had scoliosis at presentation; 12 (40%) experienced relief with nonsteroidal antiinflammatory medication. Osteoid osteoma was diagnosed in 7 (32%) of the 22 patients who underwent surgery, and osteoblastoma in 15 (68%). Nine (41%) of the 22 surgically treated patients underwent fusion procedures (bone onlay or instrumentation) at the time of surgery. Pain freedom without medication had been achieved in 16 (73%) of the 22 surgically treated patients at a mean follow-up of 28 months (range 2–75 months) and was confirmed in 3 (38%) of the 8 nonsurgically treated patients at a mean follow-up of 33 months (range 24–51 months).

Conclusions. Osteoid osteomas and osteoblastomas can present challenging management problems in pediatric patients. In the majority of cases in which conservative therapy fails or pathological diagnosis is required, surgery using modern intraoperative imaging and spinal instrumentation can provide symptom relief and tumor control.


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ABC Surgical Risk Scale for skull base meningioma

J Neurosurg 111:1053–1061, 2009.DOI: 10.3171/2007.11.17446

Surgery for skull base meningiomas (SBMs) can lead to complications because these lesions are difficult to approach and can involve cranial nerves and arteries. The authors propose a scoring system to evaluate the relative risks and benefits of surgical treatment of SBMs.

Methods. The authors used a 2-step process to construct their scale. First, they derived significant predictive variables from retrospective data on 132 SBM cases treated surgically (primary surgeries only) between May 2000 and December 2005. Next, they validated the predictive accuracy of their scoring system in 60 consecutive cases treated surgically between January 1995 and April 2000, including both primary and repeated surgeries. Finally, they investigated the effect of the surgery on the patients’ preoperative symptoms for consecutive cases treated surgically between January 1995 and December 2005, including both primary surgeries and retreatments.

Results. Five items that predicted surgical risk were identified: 1) tumor attachment size; 2) arterial involvement; 3) brainstem contact; 4) central cavity location; and 5) cranial nerve group involvement. The authors named their scoring system the ABC Surgical Risk Scale, after the initial letters of these items. Each factor was assigned a score of 0–2 points, and an additional point was added for previous surgical treatment or for radiation, giving a possible total score of 12 points. On average, the scoring system allocated 2 points for gross-total resections, 6.1 points for near-total resections, and 9 points for subtotal resections, with significant differences between groups. For cases scoring ≥ 8 points, the percentage of cases showing neurological deterioration postoperatively exceeded the percentage showing improvement.

Conclusions. The authors conclude that this scoring system can be used to predict the extent of tumor removal and that the scores reflect the surgical risk.


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Diagnostic value of proton magnetic resonance spectroscopy in the noninvasive grading of solid gliomas: comparison of maximum and mean choline values

Neurosurgery 65:908–913, 2009 DOI: 10.1227/01.NEU.0000356982.82378.BA

Magnetic resonance spectroscopy is widely used in addition to magnetic resonance imaging in the characterization of brain tumors. Compounds containing choline (Cho) have an important role in the evaluation of tumor malignancy. For this purpose, various ratios of Cho and other metabolites, such as creatine (Cr), have been assessed. The aim of this study was to compare normalized mean and maximum levels of Cho as single parameters in the noninvasive grading of gliomas.

METHODS: Proton spectroscopic imaging data of 63 patients with suspected World Health Organization (WHO) grade II or III gliomas were acquired at 3 T. Cho concentrations of the tumor were analyzed by a frequency domain fit and normalized to the corresponding contralateral healthy brain tissue. Metabolite images were used to determine the maximum and mean Cho as well as Cr concentrations of the tumor. Furthermore, contrast enhancement of the tumor was analyzed on standard magnetic resonance imaging. All patients subsequently underwent tumor resection or stereotactic biopsy to confirm diagnosis of glioma. Statistical analysis using the Kruskal-Wallis test, Mann-Whitney U test, and receiver operating characteristic curve analysis was performed with BiAS software (Epsilon Verlag GmbH, Frankfurt, Germany).

RESULTS: Histopathological examinations revealed WHO grades II (n=27), III (n=26), and IV (n=10). There was a statistically significant difference in both normalized maximum and mean Cho between WHO grade II and non-necrotic WHO grade III/IV gliomas (mean, 1.45 ±0.28 versus 2.16±0.36, P<0.05; maximum, 1.64±0.32 versus 3.32±0.55, P<0.0001). Receiver operating characteristic analyses rendered a 2.02 cutoff value for maximum Cho with a sensitivity and specificity of 86.1% and 77.8%, respectively. For mean Cho, we found a cutoff value of 1.52 (sensitivity, 77.8%; specificity, 63.0%). The diagnostic accuracy of maximum Cho was superior to that of mean Cho and also the ratio of Cho/Cr (82.5% versus 71.4% and 72.1%, respectively), but all 3 parameters were superior to contrast enhancement of the tumor (61.9%).

CONCLUSION: Both maximum and mean Cho differ between low- and high-grade gliomas. Compared with contrast enhancement, mean Cho, and Cho/Cr, maximum Cho of the tumor provides the highest accuracy in discriminating between low- and high-grade tumors, indicating usefulness of this single parameter in the process of therapeutic decision making.

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