Neurosurgery Blog

J Neurosurg 118:801–808, 2013

The aim of surgical treatment of glioma is the complete resection of tumor tissue with preservation of neurological function. Inclusion of diffusion-weighted imaging (DWI) in the postoperative MRI protocol could improve the delineation of ischemia-associated postoperative neurological deficits. The present study aims to assess the incidence of infarctions following resection of newly diagnosed gliomas in comparison with recurrent gliomas and the influence on neurological function.

Methods. Patients who underwent glioma resection for newly diagnosed or recurrent gliomas had early postoperative MRI, including DWI and apparent diffusion coefficient (ADC) maps. Postoperative areas of restricted diffusion were classified as arterial territorial infarctions, terminal branch infarctions, or venous infarctions. Tumor entity, location, and neurological function were recorded.

Results. New postoperative ischemic lesions were identified in 26 (31%) of 84 patients with newly diagnosed gliomas and 20 (80%) of 25 patients with recurrent gliomas (p < 0.01). New permanent and transient neurological deficits were more frequent in patients with recurrent gliomas than in patients with newly diagnosed tumors. Patients with neurological deficits had a significantly higher rate of ischemic lesions.

Conclusions. Postoperative infarctions occur frequently in patients with newly diagnosed and recurrent gliomas and do have an impact on postoperative neurological function. In this patient cohort there was a higher risk for ischemic lesions and for deterioration of neurological function after resection of recurrent tumors. Radiogenic and postoperative tissue changes could contribute to the higher risk of an ischemic infarction in patients with recurrent tumors.

J Neurosurg 118:812–820, 2013

Glioblastoma is the most common and aggressive type of primary brain tumor in adults. These tumors recur regardless of intervention. This propensity to recur despite aggressive therapies has made many perceive that repeated resections have little utility. The goal of this study was to evaluate if patients who underwent repeat resections experienced improved survival as compared with patients with fewer numbers of resections, and whether the number of resections was an independent predictor of prolonged survival.

Methods. The records of adult patients who underwent surgery for an intracranial primary glioblastoma at an academic tertiary-care institution between 1997 and 2007 were retrospectively reviewed. Multivariate proportionalhazards regression analysis was used to identify an association between glioblastoma resection number and survival after controlling for factors known to be associated with survival, such as age, functional status, periventricular location, extent of resection, and adjuvant therapy. Survival as a function of time was plotted using the Kaplan-Meier method, and survival rates were compared using log-rank analysis.

Results. Five hundred seventy-eight patients with primary glioblastoma met the inclusion/exclusion criteria. At last follow-up, 354, 168, 41, and 15 patients underwent 1, 2, 3, or 4 resections, respectively. The median survival for patients who underwent 1, 2, 3, and 4 resections was 6.8, 15.5, 22.4, and 26.6 months (p < 0.05), respectively. In multivariate analysis, patients who underwent only 1 resection experienced shortened survival (relative risk [RR] 3.400, 95% CI 2.423–4.774; p < 0.0001) as compared with patients who underwent 2 (RR 0.688, 95% CI 0.525–0.898; p = 0.0006), 3 (RR 0.614, 95% CI 0.388–0.929; p = 0.02), or 4 (RR 0.600, 95% CI 0.238–0.853; p = 0.01) resections. These results were verified in a case-control evaluation, controlling for age, neurological function, periventricular tumor location, extent of resection, and adjuvant therapy. Patients who underwent 1, 2, or 3 resections had a median survival of 4.5, 16.2, and 24.4 months, respectively (p < 0.05). Additionally, the risk of infections or iatrogenic deficits did not increase with repeated resections in this patient population (p > 0.05).

Conclusions. Patients with glioblastoma will inevitably experience tumor recurrence. The present study shows that patients with recurrent glioblastoma can have improved survival with repeated resections. The findings of this study, however, may be limited by an intrinsic bias associated with patient selection. The authors attempted to minimize these biases by using strict inclusion criteria, multivariate analyses, and case-control evaluation.

J Neurooncol (2013) 112:141–152

Differentiating post radiation necrosis from progression of glioma and pseudoprogression poses a diagnostic conundrum for many clinicians. As radiation therapy and temozolomide chemotherapy have become the mainstay of treatment for higher-grade gliomas, radiation necrosis and post treatment changes such as pseudoprogression have become a more relevant clinical problem for neurosurgeons and neurooncologists. Due to their radiological similarity to tumor progression, accurate recognition of these findings remains paramount given their vastly different treatment regimens and prognoses. However, no consensus has been reached on the optimal technique to discriminate between these two lesions.

In order to clarify the types of imaging modalities for recurrent enhancing lesions, we conducted a systematic review of case reports, case series, and prospective studies to increase our current understanding of the imaging options for these common lesions and their efficacy. In particular, we were interested in distinguishing radiation necrosis from true tumor progression. A PubMed search was performed to include all relevant studies where the imaging was used to differentiate between radiation necrosis and recurrent gliomas with post-radiation enhancing lesions.

After screening for certain parameters in our study, seventeen articles with 435 patients were included in our analysis including 10 retrospective and 7 prospective studies. The average time from the end of radiation therapy to the onset of a recurrent enhancing lesion was 13.2 months. The most sensitive and specific imaging modality was SPECT with a sensitivity of 87.6 % and specificity of 97.8 %.

Based on our review, we conclude that certain imaging modalities may be preferred over other less sensitive/specific techniques. Overall, tests such as SPECT may be preferable in differentiating TP (tumor progression) from RN (radiation necrosis) due to its high specificity, while nonspecific imaging such as conventional MRI is not ideal.

Neurosurgery 72:555–565, 2013

Functional magnetic resonance imaging (fMRI) has become part of routine brain mapping in patients with epilepsy or tumor undergoing resective surgery. However, robust localization of crucial functional areas is required.

OBJECTIVE: To establish a simple, short fMRI task that reliably localizes crucial language areas in individual patients who undergo respective surgery.

METHODS: fMRI was measured during an 8-minute auditory semantic decision task in 28 healthy controls and 35 consecutive patients who had focal epilepsy or a brain tumor. Nineteen underwent resective surgery. Group and individual analyses were performed. Results in patients were compared with postsurgical language outcome and electrocortical stimulation when available.

RESULTS: fMRI activations concordant with the anterior and posterior language areas were found in 96% and 89% of the controls, respectively. The anterior and posterior language areas were both activated in 93% of the patients. These results were concordant with electrocortical stimulation results in 5 patients. Transient postsurgical language deficits were found in 2 patients in whom surgery was performed in the vicinity of the fMRI activations or who had postsurgical complications implicating areas of fMRI activations.

CONCLUSION: The proposed fast fMRI language protocol reliably localized the most relevant language areas in individual subjects. It appears to be a valuable complementary tool for surgical planning of epileptogenic foci and of brain tumors.

J Neurosurg 118:884–888, 2013

The authors retrospectively analyzed data on brainstem gangliogliomas treated in their department and reviewed the pertinent literature to foster understanding of the preoperative characteristics, management, and clinical outcomes of this disease.

Methods. In 2006, the authors established a database of treated lesions of the posterior fossa. The epidemiology findings, clinical presentations, radiological investigations, pathological diagnoses, management, and prognosis for brainstem gangliogliomas were retrospectively analyzed.

Results. Between 2006 and 2012, 7 patients suffering from brainstem ganglioglioma were treated at the West China Hospital of Sichuan University. The mean age of the patients, mean duration of symptoms prior to diagnosis, and mean duration of follow-up were 28.6 years, 19.4 months, and 38.1 months, respectively. The main presentations were progressive cranial nerve deficits and cerebellar signs. Subtotal resection was achieved in 2 patients, and partial resection in 5. All tumors were pathologically diagnosed as WHO Grade I or II ganglioglioma. Radiotherapy and adjuvant chemotherapy were not administered. After 21–69 months of follow-up, patient symptoms were resolved or stable without aggravation, and MRI showed that the size of residual lesions was unchanged without progression or recurrence.

Conclusions. The diagnosis of brainstem ganglioglioma is of great importance given its favorable prognosis. The authors recommend the maximal safe resection followed by close observation without adjuvant therapy as the optimal treatment for this disease.

Neurosurg Rev (2013) 36:205–214

Historically, brain tumour resection has relied upon standardised anatomical atlases and classical mapping techniques for successful resection. While these have provided adequate results in the past, the emergence of new technologies has heralded a wave of less invasive, patient-specific techniques for the mapping of brain function.

Functional magnetic resonance imaging (fMRI) and, more recently, diffusion tensor imaging (DTI) are two such techniques. While fMRI is able to highlight localisation of function within the cortex, DTI represents the only technique able to elucidate white matter structures in vivo. Used in conjunction, both of these techniques provide important presurgical information for thorough preoperative planning, as well as intraoperatively via integration into frameless stereotactic neuronavigational systems.

Together, these techniques show great promise for improved neurosurgical outcomes. While further research is required for more widespread clinical validity and acceptance, results from the literature provide a clear road map for future research and development to cement these techniques into the clinical setup of neurosurgical departments globally.

Acta Neurochir Volume 155, Issue 4, April 2013, 685-692

Glioma patients often complain about problems in daily conversation. A detailed spontaneous speech analysis could provide more insight in these communicative problems; no previous studies are reported.
Objective
To select sensitive parameters in spontaneous speech pre- and post-operatively in patients with gliomas in eloquent areas.
Methods
We included 27 patients and 21 healthy controls. In addition to a naming and category fluency test, spontaneous speech was collected 1 month pre-operatively and 3 months post-operatively, and analysed with the variables: Self-corrections, Repetitions, Lexical Diversity, Incomplete Sentences and Mean Length of Utterance (MLUw). A correlation analysis was performed between the linguistic variables and tumour characteristics (grade, localisation and volume), treatment related factors, and between the linguistic variables and the language tasks.
Results
Pre-operatively, patients produced more Incomplete Sentences than the controls (p < 0.001). Post-operatively, patients’ utterance length (MLUw) (p < 0.05) was also deviant. The quality of the spontaneous speech was influenced by tumour grade and localisation. There was no influence of tumour volume or treatment-related factors. Pre- and post-operatively, patients’ performance on the naming and the fluency task deviated from normal (p < 0.001). The majority of the linguistic variables did not correlate with the language tasks, pointing to a measurement of distinct linguistic aspects.
Conclusion
Pre- and post-operatively there was a disorder in naming, category fluency and spontaneous speech, partly influenced by tumour characteristics. A spontaneous speech analysis appeared to be a valuable addition to standardised language tasks. Both measurements are important tools to obtain a complete linguistic profile.
Keywords

J Neurosurg Spine 18:207–214, 2013

Decompression surgery followed by adjuvant radiotherapy is an effective therapy for preservation or recovery of neurological function and achieving durable local disease control in patients suffering from metastatic epidural spinal cord compression (ESCC). The authors examine the outcomes of postoperative image-guided intensity-modulated radiation therapy delivered as single-fraction or hypofractionated stereotactic radiosurgery (SRS) for achieving long-term local tumor control.

Methods. A retrospective chart review identified 186 patients with ESCC from spinal metastases who were treated with surgical decompression, instrumentation, and postoperative radiation delivered as either single-fraction SRS (24 Gy) in 40 patients (21.5%), high-dose hypofractionated SRS (24–30 Gy in 3 fractions) in 37 patients (19.9%), or low-dose hypofractionated SRS (18–36 Gy in 5 or 6 fractions) in 109 patients (58.6%). The relationships between postoperative adjuvant SRS dosing and fractionation, patient characteristics, tumor histology–specific radiosensitivity, grade of ESCC, extent of surgical decompression, response to preoperative radiotherapy, and local tumor control were evaluated by competing risks analysis.

Results. The total cumulative incidence of local progression was 16.4% 1 year after SRS. Multivariate Gray competing risks analysis revealed a significant improvement in local control with high-dose hypofractionated SRS (4.1% cumulative incidence of local progression at 1 year, HR 0.12, p = 0.04) as compared with low-dose hypofractionated SRS (22.6% local progression at 1 year, HR 1). Although univariate analysis demonstrated a trend toward greater risk of local progression for patients in whom preoperative conventional external beam radiation therapy failed (22.2% local progression at 1 year, HR 1.96, p = 0.07) compared with patients who did not receive any preoperative radiotherapy (11.2% local progression at 1 year, HR 1), this association was not confirmed with multivariate analysis. No other variable significantly correlated with progression-free survival, including radiation sensitivity of tumor histology, grade of ESCC, extent of surgical decompression, or patient sex.

Conclusions. Postoperative adjuvant SRS following epidural spinal cord decompression and instrumentation is a safe and effective strategy for establishing durable local tumor control regardless of tumor histology–specific radiosensitivity. Patients who received high-dose hypofractionated SRS demonstrated 1-year local progression rates of less than 5% (95% CI 0%–12.2%), which were superior to the results of low-dose hypofractionated SRS. The local progression rate after singlefraction SRS was less than 10% (95% CI 0%–19.0%).

A low triiodothyronine (T3) state is highly prevalent and is associated with a poor prognosis in critically ill patients. The authors investigated, in patients undergoing brain tumor surgery, the direct association of a perioperative low T3 syndrome with clinical outcomes and also with symptoms of depression and anxiety.

Methods. Ninety consecutive patients (71% women, median age 55 years), on admission for brain tumor surgery, were evaluated for sociodemographic and clinical characteristics. Their thyroid function profile was assessed on the morning of brain tumor surgery and on the morning after brain tumor surgery. Patients with free T3 concentrations of 3.1 pmol/L or less were considered to have low T3 syndrome. The patients were evaluated for symptoms of depression and anxiety using the Hospital Anxiety and Depression Scale (HADS) before and after surgery and for clinical outcomes using the Glasgow Outcome Scale (GOS) at discharge.

Results. After brain tumor surgery, free T3 concentrations decreased (p < 0.001) and the proportion of patients with low T3 levels increased from 38% to 54% (p = 0.02). Lower preoperative (rho = 0.30, p = 0.004) and postoperative (rho = 0.33, p = 0.002) free T3 concentrations correlated with low GOS scores at discharge. Preoperative low T3 syndrome (OR 5.49, 95% CI 1.27–23.69, p = 0.02) and postoperative low T3 syndrome (OR 8.73, 95% CI 1.49–51.21, p = 0.02) both increased risk for unfavorable clinical outcomes (GOS scores < 5) at discharge, after adjusting for age, sex, histological diagnosis of brain tumor, preoperative functional impairment, previous treatment for brain tumor, and depressive symptoms. Preoperative low T3 syndrome increased the risk for preoperative (HADS-depression subscale score ≥ 11; OR 4.12, 95% CI 1.16–14.58, p = 0.03) but not postoperative depressive symptoms independently from sociodemographic and clinical factors.

Conclusions. Low T3 syndrome is a strong independent predictor of unfavorable clinical outcomes and depressive symptoms, and its diagnosis and preoperative management should be considered in patients undergoing neurosurgery for the treatment of brain tumors.

Acta Neurochir (2013) 155:415–420

Maximal safe resection is the goal of correct surgical treatment of parasagittal meningiomas, and it is intimately related to the venous anatomy both near and directly involved by the tumor. Indocyanine green videoangiography (ICGV) has already been advocated as an intra-operative resourceful technique in brain tumor surgery for the identification of vessels. The aim of this study was to investigate the role of ICGV in surgery of parasagittal meningiomas occluding the superior sagittal sinus (SSS).

Method In this study, we prospectively analyzed clinical, radiological and intra-operative findings of patients affected by parasagittal meningioma occluding the SSS, who underwent ICGVassisted-surgery. Radiological diagnosis of complete SSS occlusion was pre-operatively established in all cases. ICGV was performed before dural opening, before and during tumor resection, at the end of the procedure.

Results Five patients were included in our study. In all cases, ICGV guided dural opening, tumor resection, and venous management. The venous collateral pathway was easily identified and preserved in all cases. Radical resection was achieved in four cases. Surgery was uneventful in all cases.

Conclusions Despite the small number of patients, our study shows that ICG videoangiography could play a crucial role in guiding surgery of parasagittal meningioma occluding the SSS. Further studies are needed to define the role of this technique on functional and oncological outcome of these patients.

Clinical Neurology and Neurosurgery 115 (2013) 146– 153

Magnetic resonance spectroscopy (MRS) is an imaging diagnostic method based that allows non-invasive measurement of metabolites in tissues. There are a number of metabolites that can be identified by standard brain proton MRS but only a few of them has a clinical significance in diagnosis of gliomas including N-acetylaspartate, choline, creatine, myo-inositol, lactate, and lipids.

Methods: In this review, we describe potential of MRS for grading of gliomas.

Results: Low-grade gliomas are generally characterized by a relatively high concentration of Nacetylaspartate, low level of choline and absence of lactate and lipids. The increase in creatine concentration indicates low-grade gliomas with earlier progression and malignant transformation. Progression in grade of a glioma is reflected in the progressive decrease in the N-acetylaspartate and myo-inositol levels on the one hand and elevation in choline level up to grade III on the other. Malignant transformation of the glial tumors is also accompanied by the presence of lactate and lipids in MR spectra of grade III but mainly grade IV gliomas. It follows that MRS is a helpful method for detection of glioma regions with aggressive growth or upgrading due to favorable correlation of the choline and N-acetylaspartate levels with histopathological proliferation index Ki-67. Thus, magnetic resonance spectroscopy is also a suitable method for the targeting of brain biopsies.

Conclusions: Gliomas of each grade have some specific MRS features that can be used for improvement of the diagnostic value of conventional magnetic resonance imaging in non-invasive assessment of glioma grade.

J Neurosurg Pediatrics 11:107–114, 2013

Intracranial germ cell tumors (GCTs) frequently present with bifocal lesions in both the suprasellar and pineal areas. The pathogenesis of these bifocal GCTs has been the subject of controversy. Bifocal GCTs may be caused by synchronous tumors or by metastatic spread of tumor cells from one site to the other. The prognosis associated with bifocal GCTs has also been a cause of concern.

Methods. The authors constructed a single-institution patient cohort comprising 181 patients with intracranial GCTs. The clinical characteristics of bifocal GCTs were compared with those of suprasellar and pineal GCTs.

Results. Bifocal GCTs were observed in 23 patients (12.8%). Eighteen patients presented with bifocal GCTs that were diagnosed as germinomas, but 5 patients exhibited mixed GCTs. Analyses of age distributions and comparisons of tumor sizes were compatible with a model of a metastatic origin of bifocal GCTs. Eleven patients (47.8%) presenting with bifocal GCTs exhibited tumor seeding at presentation. Tumor seeding was significantly associated with bifocal lesions (p < 0.001). Patients with bifocal germinomas showed significantly shorter event-free survival and overall survival than did those presenting with germinomas from a single site of origin.

Conclusions. Bifocal GCTs are not restricted to germinomas, as had been previously reported, but do include mixed GCTs. The authors hypothesize that bifocal GCTs may result from the metastatic spread of suprasellar or pineal GCTs. The bifocal presentation of germinomas may be a poor prognostic sign and should alert clinicians to the possibility of a disseminated disease.

Neurosurgical Focus Feb 2013 / Vol. 34 / No. 2 / Page E6

Insular gliomas were traditionally considered a nonsurgical entity due to the high morbidity associated with resection. For the past 20 years, advances in microsurgical and brain mapping techniques have allowed neurosurgeons to resect insular gliomas with acceptable morbidity rates. Maximizing the extent of resection is nowadays the goal of surgery since this has proven to be an independent factor contributing to longer survival. Despite much progress, insular tumors remain a challenge for the neurosurgeon due to the complex anatomy of the region and technical expertise required to minimize morbidity during surgery.

Herein, the authors describe the current surgical nuances, based on their experience and a literature review, that will allow the surgeon to achieve a thorough resection while ensuring patient safety. The key factors for successful surgery in the insular region include detailed knowledge of the surgical anatomy, mastery of the nuances of cortical and subcortical mapping methods, and meticulous microsurgical technique.

Neurosurgery 72:160–169, 2013

Tailored craniotomies for awake procedures limit cortical exposure. Recently we demonstrated that the identification of eloquent areas increased the risk of postoperative deficits. However, it was not clear whether the observed neurological deficits were caused by proximity of functional cortex to the tumor [cortical injury] or subcortical injury.

OBJECTIVE: We hypothesize that subcortical injury during tumor resection is an important predictor of postoperative neurological deficits compared to cortical injury.

METHODS: A retrospective review of 214 patients undergoing awake craniotomy was carried out in whom preoperative functional magnetic resonance imaging (fMRI) and cortical mapping (CM) were performed. A radiologist blinded to the clinical data reviewed and graded the postoperative changes on diffusion-weighted MR-imaging (DWI).

RESULTS: Of the 40 cases who developed new intraoperative neurological deficit, 36 (90%) occurred during subcortical dissection, 3 (7.5%) during both subcortical and cortical dissection, and 1 (2.5%) during cortical dissection. Neurological dysfunction acquired during subcortical dissection was an independent predictor of postoperative deficits both in the immediate postoperative period (P< .001) and at the 3-month follow-up (P < .001). Significant DWI restriction in the subcortical white matter was predictive of neurological deficits both immediately and at 3 months, P = .011 and P < .001, respectively. New or worsening deficits were seen in 38% of patients; however, at 3 months 13% had a mild persistent neurological deficit.

CONCLUSION: Subcortical injury with significant DWI changes result in postoperative neurological decline despite our efforts to preserve cortical areas of function. This underscores the importance of preserving subcortical fiber tracts during awake craniotomy procedures.

Neuro-Oncology 15(1):91–96, 2013

The subventricular zone (SVZ) lines the lateral ventricles and represents the origin of neural and some cancer stem cells. Tumors contacting the SVZ may be more invasive with higher potential to recruit migratory progenitor cells.

Our specific aim was to determine whether SVZ involvement in glioblastoma multiforme (GBM) is associated with a higher recurrence rate and shorter overall survival.

MR imaging and clinical data from 91 patients with GBM treated at our institution were retrospectively reviewed. Tumors were classified as type I if the contrast- enhancing lesion contacted both the SVZ and cortex on pre-operative MRI, type II if only the SVZ was involved, type III if only cortex was involved, and type IV if the lesion did not contact either the SVZ or cortex. Progression-free survival (PFS) and overall survival were estimated based on Kaplan-Meier calculations.

When comparing type I tumors with types II-IV, only 39% of patients with type I tumors were free of recurrence and alive at 6 months, significantly fewer than for all other types combined (67%; P = .01). PFS at 6 months was also less, at only 47% among patients with SVZ-positive tumors, compared with 69% in the SVZ-negative group (P = .002). Patients with SVZ involvement also demonstrated a more rapid time to progression, compared with those not involving the SVZ (P = .003). Patients with GBM involving the SVZ have decreased overall survival and PFS, which may have prognostic and therapeutic implications.

Neurosurgery 72:77–91, 2013

Glioblastoma multiforme (GBM), a high-grade glioma, is characterized by being diffuse, invasive, and highly angiogenic and has a very poor prognosis. Identification of new biomarkers could help in the further diagnosis of GBM.

OBJECTIVE: To identify ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1) as a putative gliomaassociated marker via a bioinformatic method.

METHODS: We used advanced data mining and a novel bioinformatics method to predict ELTD1 as a potential novel biomarker that is associated with gliomas. Validation was done with immunohistochemistry, which was used to detect levels of ELTD1 in human high-grade gliomas and rat F98 glioma tumors. In vivo levels of ELTD1 in rat F98 gliomas were assessed using molecular magnetic resonance imaging.

RESULTS: ELTD1 was found to be significantly higher (P = .03) in high-grade gliomas (50 patients) compared with low-grade gliomas (21 patients) and compared well with traditional immunohistochemistry markers including vascular endothelial growth factor, glucose transporter 1, carbonic anhydrase IX, and hypoxia-inducible factor 1a. ELTD1 gene expression indicates an association with grade, survival across grade, and an increase in the mesenchymal subtype. Significantly high (P , .001) in vivo levels of ELTD1 were additionally found in F98 tumors compared with normal brain tissue.

CONCLUSION: Results of this study strongly suggests that associative analysis was able to accurately identify ELTD1 as a putative glioma-associated biomarker. The detection of ELTD1 was also validated in both rodent and human gliomas and may serve as an additional biomarker for gliomas in preclinical and clinical diagnosis of gliomas.

Acta Neurochir (2013) 155:25–31

Tuberculum sellae meningiomas present a special challenge because of their proximity to major arteries, visual pathways, and the hypothalamus. The aim of this study was to determine the prognostic determinants of clinical and visual outcomes of these tumors, focusing on the functional reversibility of an unserviceable eye after surgery.

Methods We retrospectively reviewed 86 patients on the basis of clinical and radiological factors that appeared to affect outcome. The visual acuity and visual fields were analyzed according to the visual impairment score (VIS). Unserviceable visual acuity included no perception of light (NPL), hand movement (HM), and counting fingers (CF). Ophthalmological functioning was tested in the preoperative period, the postoperative short-term period (≤2 weeks after surgery), and the postoperative long-term period (>6 months after surgery). Our own clinical outcome criteria including tumor control, visual improvement, and complications were used for evaluation.

Results Seventy-four of 86 patients (86 %) underwent total removal of the tumor. In three of these cases (3.4 %), recurrence developed. Thirty patients were classified into the “Excellent” group, 21 into the “Good” group, 20 into the “Fair” group, and 15 into the “Poor” group. In multivariate analysis, adhesion to optic nerve was an independent and significant predictor of clinical outcome. Favorable visual outcomes in both short- and long-term postoperative periods were achieved in 80.8%of cases. Preoperative and short-term visual outcomes were closely related to long-term visual outcome. Six of eight patients with preoperative CF status showed reversibility to a serviceable status after surgery. However, there was no conversion to serviceable status from NPL or HM.

Conclusions For patients with unilateral unserviceable visual function, maintenance of serviceable visual function on the opposite side might be more important. Of the patients with unserviceable visual function, careful surgery might be able to improve the visual function in CF eyes.

Acta Neurochir (2013) 155:33–40

Advances in comprehension of molecular biology of glioblastoma (GBM) have led to the development of targeted therapies. The aim of the present study was to evaluate the efficacy and safety of a targeted therapeutic approach in which administration of bevacizumab and erlotinib was tailored on the molecular profile of recurrent GBM.

Methods We prospectively enrolled ten adult patients suffering from recurrent GBM who had undergone surgical resection and standard chemo-radiotherapy. Tumor tissue was assessed for the expression of EGFRvIII and MGMT promoter methylation by RT-PCR, and for PTEN and VEGF expression by immunohistochemistry. Normal PTEN status was required for inclusion. Patients with VEGF overexpressing tumors (10/10) were treated with bevacizumab (10 mg/kg iv every 2 weeks in 6-weekcycles); patients whose tumor expressed EGFRvIII (4/ 10) added erlotinib (150 mg/day orally; 300 mg/day if on enzyme-inducing antiepileptic drugs). Therapy was continued until disease progression or unacceptable toxicity. Primary endpoints of the study were response rate (RR), 6-month progression-free survival (PFS-6), and safety profile.

Results The RR and PFS-6 were 100 % (4/4) and 50 % (3/6) in patients treated with bevacizumab+erlotinib (n=4) and bevacizumab (n=6), respectively. In the whole cohort (n= 10), RR and PFS-6 were both 70 % (7/10); median PFS and overall survival (OS) were 8.0 (3.0–31.0) and 9.5 (5.0–31.0) months, respectively. No grade 3/4 adverse events were observed; three patients treated with bevacizumab+erlotinib displayed grade 1/2 rash not requiring dose reduction; one patient treated with bevacizumab developed intratumoral hemorrhage requiring treatment discontinuation.

Conclusion To our knowledge, this is the first study on recurrent GBM in which administration of bevacizumab and erlotinib was tailored on the molecular profile of the patient’s tumor. Although we treated a limited number of patients, we obtained significantly higher RR and PFS-6 than those reported in a previous trial lacking molecular tumor analysis.

J Neurooncol (2013) 111:49–57

Various degrees of peritumoral brain edema (PTBE) are observed in patients with intracranial meningiomas. Factors affecting the occurrence of PTBE in intracranial meningioma were investigated.

PTBE was investigated retrospectively for 110 patients with primary intracranial meningiomas. Predictive factors related to PTBE were analyzed, for example patient age, sex, magnetic resonance imaging features (contrast enhancement, tumor shape, tumor location, tumor volume), angiographical features (tumor stain, pial–cortical arterial supply, venous obstruction), and histopathological features (histological subtypes, mindbomb homolog 1 labeling index (MIB1-LI)). Histological subtypes were classified into World Health Organization (WHO) grade I common type (meningothelial, transitional, fibrous), grade I uncommon type, and grade II and III types. The extent of PTBE was assessed by calculation of the edema index (EI).

PTBE was present in 53 cases (48 %). Male sex, heterogeneous enhancement, superficial location, tumor volume (≥10 cm3), remarkable tumor stain, pial supply, venous obstruction, malignant pathology, and MIB1-LI ≥4 % were correlated with PTBE in univariate analysis. Pial supply and remarkable tumor stain were correlated with PTBE in multivariate analysis. WHO grade I uncommon type had obviously higher EI than WHO grade I common type, and WHO grade II and III types (P<0.001). Seven cases with prominently high EI (EI ≥10) were all WHO grade I uncommon type, including angiomatous, microcystic, secretory, and lymphoplasmacyte-rich meningioma. Prominently extensive PTBE might indicate the presence of WHO grade I uncommon type meningioma.