Neurosurgery Blog


Daily bibliographic review of the Neurosurgery Department. La Fe University Hospital. Valencia, Spain

Navigated 3D–ultrasound versus conventional neuronavigation during awake resections of eloquent low-grade gliomas

Acta Neurochir (2018) 160:331–342

The data showing usefulness of navigated 3D– ultrasound (3DUS) during awake resections of eloquent gliomas are sparse. Results of surgeries performed using 3DUS were never compared to procedures guided by standard neuronavigation. The aim of this work is to assess the effectiveness of 3DUS during awake resections of eloquent low-grade gliomas (LGGs) by comparing surgical results of two series of patients operated on using conventional neuronavigation and using 3DUS. To our knowledge, a similar study is lacking in the literature.

Methods During a 4-year period (September 2006 to August 2010) 21 awake resections of LGGs guided by neuronavigation (series 1, S1) were consecutively performed in Department of Neurosurgery in Bratislava. During another 4-year period (August 2010 to July 2014) 28 awake resections of LGGs guided by 3DUS (series 2, S2) were consecutively conducted. In both patients series, the eloquent cortical and subcortical structures were intraoperatively detected by direct electrical stimulation. Extent of tumor resection (EOR) and functional outcome in both series were compared.

Results EOR was significantly greater (p = 0.022) in S2 (median = 93.25%; mean = 86.79%), as compared to S1 (median 87.1%; mean = 75.85%). One permanent minor deficit in S1 and 2 minor deficits in S2 occurred, the difference was not significant (p = 0.999).

Conclusions Our work represents the first study comparing results of surgeries guided by 3DUS versus conventional navigation. The extent of awake resections of eloquent LGG guided by 3DUS was greater comparing to awake resections guided by standard neuronavigation; use of 3DUS had no impact on the number of new permanent deficits.

The surgical treatment of tumors of the fourth ventricle

J Neurosurg 128:339–351, 2018

Fourth ventricle tumors are rare, and surgical series are typically small, comprising a single pathology, or focused exclusively on pediatric populations. This study investigated surgical outcome and complications following fourth ventricle tumor resection in a diverse patient population. This is the largest cohort of fourth ventricle tumors described in the literature to date.

METHODS This is an 18-year (1993–2010) retrospective review of 55 cases involving patients undergoing surgery for tumors of the fourth ventricle. Data included patient demographic characteristics, pathological and radiographic tumor characteristics, and surgical factors (approach, surgical adjuncts, extent of resection, etc.). The neurological and medical complications following resection were collected and outcomes at 30 days, 90 days, 6 months, and 1 year were reviewed to determine patient recovery. Patient, tumor, and surgical factors were analyzed to determine factors associated with the frequently encountered postoperative neurological complications.

RESULTS There were no postoperative deaths. Gross-total resection was achieved in 75% of cases. Forty-five percent of patients experienced at least 1 major neurological complication, while 31% had minor complications only. New or worsening gait/focal motor disturbance (56%), speech/swallowing deficits (38%), and cranial nerve deficits (31%) were the most common neurological deficits in the immediate postoperative period. Of these, cranial nerve deficits were the least likely to resolve at follow-up. Multivariate analysis showed that patients undergoing a transvermian approach had a higher incidence of postoperative cranial nerve deficits, gait disturbance, and speech/swallowing deficits than those treated with a telovelar approach. The use of surgical adjuncts (intraoperative navigation, neurophysiological monitoring) did not significantly affect neurological outcome. Twenty-two percent of patients required postoperative CSF diversion following tumor resection. Patients who required intraoperative ventriculostomy, those undergoing a transvermian approach, and pediatric patients (< 18 years old) were all more likely to require postoperative CSF diversion. Twenty percent of patients suffered at least 1 medical complication following tumor resection. Most complications were respiratory, with the most common being postoperative respiratory failure (14%), followed by pneumonia (13%).

CONCLUSIONS The occurrence of complications after fourth ventricle tumor surgery is not rare. Postoperative neurological sequelae were frequent, but a substantial number of patients had neurological improvement at long-term followup. Of the neurological complications analyzed, postoperative cranial nerve deficits were the least likely to completely resolve at follow-up. Of all the patient, tumor, and surgical variables included in the analysis, surgical approach had the most significant impact on neurological morbidity, with the telovelar approach being associated with less morbidity.


Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma

J Clin Oncol 36. © 2018

DNX-2401 (Delta-24-RGD; tasadenoturev) is a tumor-selective, replication-competent oncolytic adenovirus. Preclinical studies demonstrated antiglioma efficacy, but the effects and mechanisms of action have not been evaluated in patients.

Methods A phase I, dose-escalation, biologic-end-point clinical trial of DNX-2401 was conducted in 37 patients with recurrent malignant glioma. Patients received a single intratumoral injection of DNX-2401 into biopsy-confirmed recurrent tumor to evaluate safety and response across eight dose levels (group A). To investigate the mechanism of action, a second group of patients (group B) underwent intratumoral injection through a permanently implanted catheter, followed 14 days later by en bloc resection to acquire post-treatment specimens.

Results In group A (n = 25), 20% of patients survived > 3 years from treatment, and three patients had a ≥ 95% reduction in the enhancing tumor (12%), with all three of these dramatic responses resulting in >3 years of progression-free survival from the time of treatment. Analyses of post-treatment surgical specimens (group B, n = 12) showed that DNX-2401 replicates and spreads within the tumor, documenting direct virus-induced oncolysis in patients. In addition to radiographic signs of inflammation, histopathologic examination of immune markers in post-treatment specimens showed tumor infiltration by CD8+ and T-bet+ cells, and transmembrane immunoglobulin mucin-3 downregulation after treatment. Analyses of patient-derived cell lines for damage-associated molecular patterns revealed induction of immunogenic cell death in tumor cells after DNX-2401 administration.

Conclusion Treatment with DNX-2401 resulted in dramatic responses with long-term survival in recurrent highgrade gliomas that are probably due to direct oncolytic effects of the virus followed by elicitation of an immune-mediated antiglioma response.

Adult Pilocytic Astrocytoma: An Institutional Series and Systematic Literature Review for Extent of Resection and Recurrence

World Neurosurg. (2018) 110:276-283

Pilocytic astrocytoma is a classically benign tumor that most often affects pediatric patients. Rarely, it occurs during adulthood. We present a case series and systematic literature review of adult pilocytic astrocytoma (APA) to examine the clinical presentation, extent of resection, and recurrence rate associated with this tumor in this population.

MATERIALS AND METHODS: Our institutional records were retrospectively reviewed for cases of pilocytic astrocytoma in adults. A PubMed search identified English-language studies of pathology-proven APA. A meta-analysis was performed to determine the relationship between extent of tumor resection and recurrence.

RESULTS: Forty-six patients with APA were diagnosed at our institution (mean age 33.6  13.3; 24 [52%] female). Twenty-four patients (52%) underwent gross total resection, 11 (24%) subtotal resection, 4 (9%) near total resection, 4 (9%) observation after biopsy, and 3 (6%) radiotherapy alone. Tumors recurred or progressed in 6 (13%) patients, of whom 4 were treated by STR and 2 were treated by radiotherapy alone. Thirty-nine (95%) patients were still alive at last follow-up. A systematic literature review identified 415 patients with APA in 38 studies. Including our case series, 7 studies reported extent of resection, followup, and recurrence. Of 254 patients with a weighted mean follow-up of 77.7  49.6 (31e250) months, 129 (51%) were treated with gross total resection, and 125 (49%) underwent subtotal resection. Tumor recurred in 79 (31%) patients, 22 (27%) after gross total resection and 57 (73%) after subtotal resection (P < 0.001).

CONCLUSIONS: Pilocytic astrocytoma rarely presents during adulthood. Overall, prognosis is favorable and survival rates are high. APA recurrence is more likely after STR, and the goal of surgery should always be GTR when feasible.

Developing an Algorithm for Optimizing Care of Elderly Patients With Glioblastoma

Neurosurgery 82:64–75, 2018

Elderly patients with glioblastoma have an especially poor prognosis; optimizing their medical and surgical care remains of paramount importance.

OBJECTIVE: To investigate patient and treatment characteristics of elderly vs nonelderly patients and develop an algorithm to predict elderly patients’ survival.

METHODS: Retrospective analysis of 554 patients (mean age=60.8; 42.0% female) undergoing first glioblastoma resection or biopsy at our institution (2005-2011).

RESULTS: Of the 554 patients, 218 (39%) were elderly (≥65 yr). Compared with nonelderly, elderly patients were more likely to receive biopsy only (26% vs 16%), have ≥1 medical comorbidity (40% vs 20%), and develop postresection morbidity (eg, seizure, delirium; 25% vs 14%), and were less likely to receive temozolomide (TMZ) (78% vs 90%) and gross total resection (31% vs 45%). To predict benefit of resection in elderly patients (n = 161), we identified 5 factors known in the preoperative period that predicted survival in a multivariate analysis. We then assigned points to each (1 point: Charlson comorbidity score >0, subtotal resection, tumor >3 cm; 2 points: preoperative weakness, Charlson comorbidity score >1, tumor >5 cm, age >75 yr; 4 points: age >85 yr). Having 3 to 5 points (n = 78, 56%) was associated with decreased survival compared to 0 to 2 points (n = 41, 29%, 8.5 vs 16.9 mo; P = .001) and increased survival compared to 6 to 9 points (n = 20, 14%, 8.5 vs 4.5 mo; P < .001). Patients with 6 to 9 points did not survive significantly longer than elderly patients receiving biopsy only (n = 57, 4.5 vs 2.7 mo; P = .58).

CONCLUSION: Further optimization of the medical and surgical care of elderly glioblastoma patients may be achieved by providing more beneficial therapies while avoiding unnecessary resection in those not likely to receive benefit from this intervention.


Symmetry of the arcuate fasciculus and its impact on language performance of patients with brain tumors in the language-dominant hemisphere

J Neurosurg 127:1407–1416, 2017

Cerebral damage in frontal, parietal, and temporal brain areas and, probably more importantly, their interconnections can lead to deficits in language. However, neural plasticity and repair allow the brain to partly compensate for neural injury, mediated by both functional and structural changes. In this study, the authors sought to systematically investigate the relationship between language performance in brain tumor patients and structural perisylvian pathways (i.e., the arcuate fasciculus [AF]) using probabilistic fiber tracking on diffusion tensor imaging. The authors used a previously proposed model in which the AF is divided into anterior, long, and posterior segments. The authors hypothesized that right-handed patients with gliomas in the language-dominant (left) hemisphere would benefit from a more symmetrical or right-lateralized language pathway in terms of better preservation of language abilities. Furthermore, they investigated to what extent specific tumor characteristics, including proximity to the AF, affect language outcome in such patients.

METHODS Twenty-seven right-handed patients (12 males and 15 females; mean age 52 ± 16 years) with 11 low-grade and 16 high-grade gliomas of the left hemisphere underwent 3-T diffusion-weighted MRI (30 directions) and language assessment as part of presurgical planning. For a systematic quantitative evaluation of the AF, probabilistic fiber tracking with a 2 regions of interest approach was carried out. Volumes of the 3 segments of both hemispheric AFs were evaluated by quantifying normalized and thresholded pathways. Resulting values served to generate the laterality index of the AFs.

RESULTS Patients without language deficits tended to have an AF that was symmetric or lateralized to the right, whereas patients with deficits in language significantly more often demonstrated a left-lateralized posterior segment of the AF. Patients with high-grade gliomas had more severe language deficits than those with low-grade gliomas. Backward logistic regression revealed the laterality index of the posterior AF segment and tumor grade as the only independent statistically significant predictors for language deficits in this cohort.

CONCLUSIONS In addition to the well-known fact that tumor entity influences behavioral outcome, the authors’ findings suggest that the right homologs of structural language-associated pathways could be supportive for language function and facilitate compensation mechanisms after brain damage in functionally eloquent areas. This further indicates that knowledge about preoperative functional redistribution (identified by neurofunctional imaging) increases the chance for total or near-total resections of tumors in eloquent areas. In the future, longitudinal studies with larger groups are mandatory to overcome the methodological limitations of this cross-sectional study and to map neuroplastic changes associated with language performance and rehabilitation in brain tumor patients.


Differentiating brain radionecrosis from tumour recurrence: a role for contrast-enhanced ultrasound?

Acta Neurochir (2017) 159:2405–2408

Differentiating radionecrosis from tumour recurrence is a major issue in neuro-oncology. Conventional imaging is far from being validated as an alternative to histologicalassessment.

We report the case of a patient operated on for suspected recurrence of brain metastasis 9 months after cyberknife radiosurgery. While magnetic resonance imaging showed strong enhancement of the lesion, intraoperative contrast-enhanced ultrasonography (CEUS) surprisingly did
not—different from what is expected for brain metastases.

Histopathological examination documented radionecrosis. For the first time, we describe radionecrosis with CEUS; further investigation is needed; however, the lack of enhancement could represent an important hallmark in differential diagnosis with neoplastic tissue.

Outcomes After Endoscopic Endonasal Resection of Craniopharyngiomas in the Pediatric Population

World Neurosurg. (2017) 108:6-14.

Craniopharyngiomas have traditionally been treated via open transcranial approaches. More recently, endoscopic transsphenoidal approaches have been increasingly used; however, few case series exist in the pediatric population.

METHODS: A retrospective review of patients (aged <18 years) undergoing endoscopic transsphenoidal resection of craniopharyngiomas between 1995 and 2016 was performed. Preoperative data included presenting symptoms, tumor size, location, and components. Postoperative outcomes included symptom resolution, visual outcomes, endocrine outcomes, disease recurrence, and major complications.

RESULTS: Sixteen pediatric patients with mean age of 11.0 years (range, 5-15 years) were included. The median follow-up time was 56.2 months. Mean maximal tumor diameter was 3.98 cm. Most of the tumors had suprasellar (93.8%) and intrasellar (68.8%) components. The gross total resection rate was 93.8%. The most common presenting symptoms were vision changes (81.3%) and increased intracranial pressure (56.3%). Most patients (66.7%) had their presenting symptoms resolved by their first postoperative visit. Vision improved or remained normal in 69.2% of patients. Postoperatively, new incidence of panhypopituitarism or diabetes insipidus developed in 63.6% and 46.7% of patients, respectively. New hypothalamic obesity developed in 28.6% of patients. The postoperative cerebrospinal fluid leak rate was 18.8%. One patient died of intraventricular hemorrhage postoperatively. The major complication rate was 12.5%. Disease recurrence occurred in 1 patient with gross total resection (6.3%).

CONCLUSIONS: Endoscopic transsphenoidal resection for craniopharyngiomas can achieve high rates of total resection with low rates of disease recurrence in larger tumors than previously described. However, hypothalamic-pituitary dysfunction and cerebrospinal fluid leak remain significant postoperative morbidities

A novel weighted scoring system for estimating the risk of rapid growth in untreated intracranial meningiomas

J Neurosurg 127:971–980, 2017

Advances in neuroimaging techniques have led to the increased detection of asymptomatic intracranial meningiomas (IMs). Despite several studies on the natural history of IMs, a comprehensive evaluation method for estimating the growth potential of these tumors, based on the relative weight of each risk factor, has not been developed. The aim of this study was to develop a weighted scoring system that estimates the risk of rapid tumor growth to aid treatment decision making.

METHODS The authors performed a retrospective analysis of 232 patients with presumed IM who had been prospectively followed up in the absence of treatment from 1997 to 2013. Tumor volume was measured by imaging at each follow-up visit, and the growth rate was determined by regression analysis. Predictors of rapid tumor growth (defined as ≥ 2 cm3/year) were identified using a logistic regression model; each factor was awarded a score based on its own coefficient value. The probability (P) of rapid tumor growth was estimated using the following formula:

[Eq. 1]

RESULTS Fifty-nine tumors (25.4%) showed rapid growth. Tumor size (OR per cm3 1.07, p = 0.000), absence of calcification (OR 3.87, p = 0.004), peritumoral edema (OR 2.74, p = 0.025), and hyperintense or isointense signal on T2- weighted MRI (OR 3.76, p = 0.049) were predictors of tumor growth rate. In the Asan Intracranial Meningioma Scoring System (AIMSS), tumor size was categorized into 3 groups of < 2.5 cm, ≥ 2.5 to < 4.0 cm, and ≥ 4.0 cm in diameter and awarded a score of 0, 3, and 6, respectively; the parameters of calcification and peritumoral edema were categorized into 2 groups based on their presence or absence and given a score of 0 or 2 and 1 or 0, respectively; and the signal on T2-weighted MRI was categorized into 2 groups of hypointense and hyperintense/isointense and given a score of 0 or 2, respectively. The risk of rapid tumor growth was estimated to be < 10% when the total score was 0–2, 10%–50% when the total score was 3–6, and ≥ 50% when the total score was 7–11 (Hosmer-Lemeshow goodness-of-fit test, p = 0.9958). The area under the receiver operating characteristic curve was 0.86.

CONCLUSIONS The authors suggest a weighted scoring system (AIMSS) that predicts the specific probability of rapid tumor growth for patients with untreated IM. This scoring system will aid treatment decision making in clinical settings by screening out patients at high risk for rapid tumor growth.

Correlation of volumetric growth and histological grade in 50 meningiomas

Acta Neurochir (2017) 159:2169–2177

Advances in radiological imaging techniques have enabled volumetric measurements of meningiomas to be easily monitored using serial imaging scans. There is limited literature on the relationship between tumour growth rates and the WHO classification of meningiomas despite tumour growth being a major determinant of type and timing of intervention. Volumetric growth has been successfully used to assess growth of low-grade glioma; however, there is limited information on the volumetric growth rate (VGR) of meningiomas. This study aimed to determine the reliability of VGR measurement in patients with meningioma, assess the relationship between VGR and 2016 WHO grading as well as clinical applicability of VGR in monitoring meningioma growth.

Methods All histologically proven intracranial meningiomas that underwent resection in a single centre between April 2009 and April 2014 were reviewed and classified according to the 2016 edition of the Classification of the Tumours of the CNS. Only patients who had two pre-operative scans that were at least 3 months apart were included in the study. Two authors performed the volumetric measurements using the Slicer 3D software independently and the inter-rater reliability was assessed. Multiple regression analyses of factors affecting the VGR and VDE of meningiomas were performed using the R statistical software with p < 0.05 considered to be statistically significant.

Results Of 548 patients who underwent resection of their meningiomas, 66 met the inclusion criteria. Sixteen cases met the exclusion criteria (NF2, spinal location, previous surgical or radiation treatment, significant intra-osseous component and poor quality imaging). Forty-two grade I and 8 grade II meningiomas were included in the analysis. The VGR was significantly higher for grade II meningiomas. Using receiver-operator characteristic (ROC) curve analysis, the optimal threshold that distinguishes between grade I and II meningiomas is 3 cm3/year. Higher histological grade, high initial tumour volume, MRI T2-signal hyperintensity and presence of oedema were found to be significant predictors of higher VGR.

Conclusion Reliable tools now exist to evaluate and monitor volumetric growth of meningiomas. Grade II meningiomas have significantly higher VGR compared with grade I meningiomas and growth of more than 3 cm3/year is strongly suggestive of a higher grade meningioma. A larger, multi-centre prospective study to investigate the applicability of velocity of growth to predict the outcome of patients with meningioma is warranted.


Navigated transcranial magnetic stimulation for glioma removal- prognostic value in motor function recovery from postsurgical neurological deficits

J Neurosurg 127:877–891, 2017

The aim of the present study was to evaluate the usefulness of navigated transcranial magnetic stimulation (nTMS) as a prognostic predictor for upper-extremity motor functional recovery from postsurgical neurological deficits.

METHODS Preoperative and postoperative nTMS studies were prospectively applied in 14 patients (mean age 39 ± 12 years) who had intraparenchymal brain neoplasms located within or adjacent to the motor eloquent area in the cerebral hemisphere. Mapping by nTMS was done 3 times, i.e., before surgery, and 1 week and 3 weeks after surgery. To assess the response induced by nTMS, motor evoked potential (nTMS-MEP) was recorded using a surface electromyography electrode attached to the abductor pollicis brevis (APB). The cortical locations that elicited the largest electromyography response by nTMS were defined as hotspots. Hotspots for APB were confirmed as positive responsive sites by direct electrical stimulation (DES) during awake craniotomy. The distances between hotspots and lesions (DHS-L) were measured. Postoperative neurological deficits were assessed by manual muscle test and dynamometer. To validate the prognostic value of nTMS in recovery from upper-extremity paresis, the following were investigated: 1) the correlation between DHS-L and the serial grip strength change, and 2) the correlation between positive nTMS-MEP at 1 week after surgery and the serial grip strength change.

RESULTS From the presurgical nTMS study, MEPs from targeted muscles were identified in 13 cases from affected hemispheres. In one case, MEP was not evoked due to a huge tumor. Among 9 cases from which intraoperative DES mapping for hand motor area was available, hotspots for APB identified by nTMS were concordant with DES-positive sites. Compared with the adjacent group (DHS-L < 10 mm, n = 6), the nonadjacent group (DHS-L ≥ 10 mm, n = 7) showed significantly better recovery of grip strength at 3 months after surgery (p < 0.01). There were correlations between DHS-L and recovery of grip strength at 1 week, 3 weeks, and 3 months after surgery (r = 0.74, 0.68, and 0.65, respectively). Postsurgical nTMS was accomplished in 13 patients. In 9 of 13 cases, nTMS-MEP from APB muscle was positive at 1 week after surgery. Excluding the case in which nTMS-MEP was negative from the presurgical nTMS study, recoveries in grip strength were compared between 2 groups, in which nTMS-MEP at 1 week after surgery was positive (n = 9) or negative (n = 3). Significant differences were observed between the 2 groups at 1 week, 3 weeks, and 3 months after surgery (p < 0.01). Positive nTMS-MEP at 1 week after surgery correlated well with the motor recovery at 1 week, 3 weeks, and 3 months after surgery (r = 0.87, 0.88, and 0.77, respectively).

CONCLUSIONS Navigated TMS is a useful tool for identifying motor eloquent areas. The results of the present study have demonstrated the predictive value of nTMS in upper-extremity motor function recovery from postsurgical neurological deficits. The longer DHS-L and positive nTMS-MEP at 1 week after surgery have prognostic values of better recovery from postsurgical neurological deficits.


Surgical management of spinal osteoblastomas

J Neurosurg Spine 27:321–327, 2017

Osteoblastoma is a rare primary benign bone tumor with a predilection for the spinal column. Although of benign origin, osteoblastomas tend to behave more aggressively clinically than other benign tumors. Because of the low incidence of osteoblastomas, evidence-based treatment guidelines and high-quality research are lacking, which has resulted in inconsistent treatment. The goal of this study was to determine whether application of the Enneking classification in the management of spinal osteoblastomas influences local recurrence and survival time.

METHODS A multicenter database of patients who underwent surgical intervention for spinal osteoblastoma was developed by the AOSpine Knowledge Forum Tumor. Patient data pertaining to demographics, diagnosis, treatment, crosssectional survival, and local recurrence were collected. Patients in 2 cohorts, based on the Enneking classification of the tumor (Enneking appropriate [EA] and Enneking inappropriate [EI]), were analyzed. If the final pathology margin matched the Enneking-recommended surgical margin, the tumor was classified as EA; if not, it was classified as EI.

RESULTS A total of 102 patients diagnosed with a spinal osteoblastoma were identified between November 1991 and June 2012. Twenty-nine patients were omitted from the analysis because of short follow-up time, incomplete survival data, or invalid staging, which left 73 patients for the final analysis. Thirteen (18%) patients suffered a local recurrence, and 6 (8%) patients died during the study period. Local recurrence was strongly associated with mortality (relative risk 9.2; p = 0.008). When adjusted for Enneking appropriateness, this result was not altered significantly. No significant differences were found between the EA and EI groups in regard to local recurrence and mortality.

CONCLUSIONS In this evaluation of the largest multicenter cohort of spinal osteoblastomas, local recurrence was found to be strongly associated with mortality. Application of the Enneking classification as a treatment guide for preventing local recurrence was not validated.

The Survival Advantage of “Supratotal” Resection of Glioblastoma Using Selective Cortical Mapping and the Subpial Technique

Neurosurgery 81:275–288, 2017

A substantial body of evidence suggests that cytoreductive surgery is a prerequisite to prolonging survival in patients with glioblastoma (GBM).

OBJECTIVE: To evaluate the safety and impact of “supratotal” resections beyond the zone of enhancement seen on magnetic resonance imaging scans, using a subpial technique.

METHODS: We retrospectively evaluated 86 consecutive patients with primary GBM, managed by the senior author, using a subpial resection technique with or without carmustine (BCNU) wafer implantation. Multivariate Cox proportional hazards regression was used to analyze clinical, radiological, and outcome variables. Overall impacts of extent of resection (EOR) and BCNUwafer placementwere compared using Kaplan-Meier survival analysis.

RESULTS: Mean patient age was 56 years. The median OS for the group was 18.1 months. Median OS for patients undergoing gross total, near-total, and subtotal resection were 54, 16.5, and 13.2 months, respectively. Patients undergoing near-total resection (P = .05) or gross total resection (P<.01) experienced statistically significant longer survival time than patients undergoing subtotal resection as well as patients undergoing≥95% EOR (P<.01) when compared to <95% EOR. The addition of BCNU wafers had no survival advantage.

CONCLUSIONS: The subpial technique extends the resection beyond the contrast enhancement and is associated with an overall survival beyond that seen in similar series where resection of the enhancement portion is performed. The effect of supratotal resection on survival exceeded the effects of age, Karnofsky performance score, and tumor volume. A prospective study would help to quantify the impact of the subpial technique on quality of life and survival as compared to a traditional resection limited to the enhancing tumor.


Preserving normal facial nerve function and improving hearing outcome in large vestibular schwannomas with a combined approach

Acta Neurochir (2017) 159:1197–1211

To perform planned subtotal resection followed by gamma knife surgery (GKRS) in a series of patients with large vestibular schwannoma (VS), aiming at an optimal functional outcome for facial and cochlear nerves.

Methods Patient characteristics, surgical and dosimetric features, and outcome were collected prospectively at the time of treatment and during the follow-up.

Results A consecutive series of 32 patients was treated between July 2010 and June 2016. Mean follow-up after surgery was 29 months (median 24, range 4–78). Mean presurgical tumor volume was 12.5 cm3 (range 1.47–34.9). Postoperative status showed normal facial nerve function (House– Brackmann I) in all patients. In a subgroup of 17 patients with serviceable hearing before surgery and in which cochlear nerve preservation was attempted at surgery, 16 (94.1%) retained serviceable hearing. Among them, 13 had normal hearing (Gardner–Robertson class 1) before surgery, and 10 (76.9%) retained normal hearing after surgery. Mean duration between surgery and GKRS was 6.3 months (range 3.8–13.9). Mean tumor volume at GKRS was 3.5 cm3 (range 0.5–12.8), corresponding to mean residual volume of 29.4% (range 6– 46.7) of the preoperative volume. Mean marginal dose was 12 Gy (range 11–12). Mean follow-up after GKRS was 24 months (range 3–60). Following GKRS, there were no new neurological deficits, with facial and hearing functions remaining identical to those after surgery in all patients. Three patients presented with continuous growth after GKRS, were considered failures, and benefited from the same combined approach a second time.

Conclusion Our data suggest that large VS management, with planned subtotal resection followed by GKRS, might yield an excellent clinical outcome, allowing the normal facial nerve and a high level of cochlear nerve functions to be retained. Our functional results with this approach in large VS are comparable with those obtained with GKRS alone in small- and medium-sized VS. Longer term follow-up is necessary to fully evaluate this approach, especially regarding tumor control.


The Cost of Brain Surgery: Awake vs Asleep Craniotomy for Perirolandic Region Tumors

Neurosurgery 81:307–314, 2017

Cost effectiveness has become an important factor in the health care system, requiring surgeons to improve efficacy of procedures while reducing costs. An awake craniotomy (AC) with direct cortical stimulation (DCS) presents one method to resect eloquent region tumors; however, some authors assert that this procedure is an expensive alternative to surgery under general anesthesia (GA) with neuromonitoring.

OBJECTIVE: To evaluate the cost effectiveness and clinical outcomes between AC and GA patients.

METHODS: Retrospective analysis of a cohort of 17 patients with perirolandic gliomas who underwent an AC with DCS were case-control matched with 23 patients with perirolandic gliomas who underwent surgery under GA with neuromonitoring (ie, motor-evoked potentials, somatosensory-evoked potentials, phase reversal). Inpatient costs, qualityadjusted life years (QALY), extent of resection, and neurological outcome were compared between the groups.

RESULTS: Total inpatient expense per patient was $34 804 in the AC group and $46 798 in the GA group (P = .046). QALY score for the AC group was 0.97 and 0.47 for the GA group (P = .041). The incremental cost per QALY for the AC group was $82 720 less than the GA group. Postoperative Karnofsky performance status was 91.8 in the AC group and 81.3 in the GA group (P=.047). Length of hospitalization was 4.12 days in the AC group and 7.61 days in the GA group (P = .049).

CONCLUSION: The total inpatient costs for awake craniotomies were lower than surgery under GA. This study suggests better cost effectiveness and neurological outcome with awake craniotomies for perirolandic gliomas.

A prospective randomized trial of the optimal dose of mannitol for intraoperative brain relaxation in patients undergoing craniotomy for supratentorial brain tumor resection

J Neurosurg 126:1839–1846, 2017

Mannitol is used intraoperatively to induce brain relaxation in patients undergoing supratentorial brain tumor resection. The authors sought to determine the dose of mannitol that provides adequate brain relaxation with the fewest adverse effects.

METHODS A total of 124 patients were randomized to receive mannitol at 0.25 g/kg (Group A), 0.5 g/kg (Group B), 1.0 g/kg (Group C), and 1.5 g/kg (Group D). The degree of brain relaxation was classified according to a 4-point scale (1, bulging; 2, firm; 3, adequate; and 4, perfectly relaxed) by neurosurgeons; Classes 3 and 4 were considered to indicate satisfactory brain relaxation. The osmolality gap (OG) and serum electrolytes were measured before and after mannitol administration.

RESULTS The brain relaxation score showed an increasing trend in patients receiving higher doses of mannitol (p = 0.005). The incidence of satisfactory brain relaxation was higher in Groups C and D than in Group A (67.7% and 64.5% vs 32.2%, p = 0.011 and 0.022, respectively). The incidence of OG greater than 10 mOsm/kg was also higher in Groups C and D than in Group A (100.0% in both groups vs 77.4%, p = 0.011 for both). The incidence of moderate hyponatremia (125 mmol/L ≤ Na+ < 130 mmol/L) was significantly higher in Group D than in other groups (38.7% vs 0.0%, 9.7%, and 12.9% in Groups A, B, and C; p < 0.001, p = 0.008, and p = 0.020, respectively). Hyperkalemia (K+ > 5.0 mmol/L) was observed in 12.9% of patients in Group D only.

CONCLUSIONS The higher doses of mannitol provided better brain relaxation but were associated with more adverse effects. Considering the balance between the benefits and risks of mannitol, the authors suggest the use of 1.0 g/kg of intraoperative mannitol for satisfactory brain relaxation with the fewest adverse effects.

Clinical trial registration no.: NCT02168075 (

Cyst Fluid From Cystic, Malignant Brain Tumors: A Reservoir of Nutrients, Including Growth Factor-Like Nutrients, for Tumor Cells

Neurosurgery 80:917–924, 2017

Brain tumors may have cysts, whose content of nutrients could influence tumor cell microenvironment and growth.

OBJECTIVE: To measure nutrients in cyst fluid from glioblastoma multiforme (GBM) and metastatic brain tumors.

METHODS: Quantification of nutrients in cyst fluid from 12 to 18 GBMs and 4 to 10 metastatic brain tumors.

RESULTS: GBM cysts contained glucose at 2.2 mmol/L (median value; range <0.8-3.5) and glutamine at 1.04 mmol/L (0.17-4.2). Lactate was 7.1 mmol/L (2.4-12.5) and correlated inversely with glucose level (r = –0.77; P < .001). Amino acids, including glutamate, varied greatly, but median values were similar to previously published serum values. Ammonia was 75 μmol/L (11-241). B vitamins were present at previously published serum values, and riboflavin, nicotinamide, pyridoxal 5 -phosphate, and cobalamin were higher in cyst fluid than in cerebrospinal fluid. Inorganic phosphate was 1.25 mmol/L (0.34-3.44), which was >3 times higher than in ventricular cerebrospinal fluid: 0.35 mmol/L (0.22-0.66; P < .001). Tricarboxylic acid cycle intermediates were in the low micromolar range, except for citrate, which was 240 μmol/L (140-590). In cystic metastatic malignant melanomas and lung tumors values were similar to those in GBMs.

CONCLUSION: Tumor cysts may be a nutrient reservoir for brain tumors, securing tumor energy metabolism and synthesis of cell constituents. Serum is one likely source of cyst fluid nutrients. Nutrient levels in tumor cyst fluid are highly variable, which could differentially stimulate tumor growth. Cyst fluid glutamate, lactate, and phosphate may act as tumor growth factors; these compounds have previously been shown to stimulate tumor growth at concentrations found in tumor cyst fluid.


A method for safely resecting anterior butterfly gliomas

J Neurosurg 126:1795–1811, 2017

Gliomas invading the anterior corpus callosum are commonly deemed unresectable due to an unacceptable risk/benefit ratio, including the risk of abulia. In this study, the authors investigated the anatomy of the cingulum and its connectivity within the default mode network (DMN). A technique is described involving awake subcortical mapping with higher attention tasks to preserve the cingulum and reduce the incidence of postoperative abulia for patients with so-called butterfly gliomas.

METHODS The authors reviewed clinical data on all patients undergoing glioma surgery performed by the senior author during a 4-year period at the University of Oklahoma Health Sciences Center. Forty patients were identified who underwent surgery for butterfly gliomas. Each patient was designated as having undergone surgery either with or without the use of awake subcortical mapping and preservation of the cingulum. Data recorded on these patients included the incidence of abulia/akinetic mutism. In the context of the study findings, the authors conducted a detailed anatomical study of the cingulum and its role within the DMN using postmortem fiber tract dissections of 10 cerebral hemispheres and in vivo diffusion tractography of 10 healthy subjects.

RESULTS Forty patients with butterfly gliomas were treated, 25 (62%) with standard surgical methods and 15 (38%) with awake subcortical mapping and preservation of the cingulum. One patient (1/15, 7%) experienced postoperative abulia following surgery with the cingulum-sparing technique. Greater than 90% resection was achieved in 13/15 (87%) of these patients.

CONCLUSIONS This study presents evidence that anterior butterfly gliomas can be safely removed using a novel, attention-task based, awake brain surgery technique that focuses on preserving the anatomical connectivity of the cingulum and relevant aspects of the cingulate gyrus.


Degree of Vascular Encasement in Sphenoid Wing Meningiomas Predicts Postoperative Ischemic Complications

Neurosurgery 80:957–966, 2017

Sphenoid wing meningiomas (SWMs) can encase arteries of the circle of Willis, increasing their susceptibility to intraoperative vascular injury and severe ischemic complications.

OBJECTIVE: To demonstrate the effect of circumferential vascular encasement in SWM on postoperative ischemia.

METHODS: A retrospective review of 75 patients surgically treated for SWM from 2009 to 2015 was undertaken to determine the degree of circumferential vascular encasement (0◦-360◦) as assessed by preoperativemagnetic resonance imaging (MRI). A novel grading system describing “maximum”and “total” arterial encasement scores was created. Postoperative MRIs were reviewed for total ischemia volume measured on sequential diffusionweighted images.

RESULTS: Of the 75 patients, 89.3% had some degree of vascular involvement with a median maximum encasement score of 3.0 (2.0-3.0) in the internal carotid artery (ICA), M1, M2, and A1 segments; 76% of patients had some degree of ischemia with median infarct volume of 3.75 cm3 (0.81-9.3 cm3). Univariate analysis determined risk factors associated with larger infarction volume, which were encasement of the supraclinoid ICA (P < .001), M1 segment (P < .001), A1 segment (P = .015), and diabetes (P = .019). As the maximum encasement score increased from 1 to 5 in each of the significant arterial segments, so did mean and median infarction volume (P < .001). Risk for devastating ischemic injury >62 cm3 was found when the ICA, M1, and A1 vessels all had ≥360◦ involvement (P = .001). Residual tumorwas associated with smaller infarct volumes (P=.022). As infarction volume increased, so did modified Rankin Score at discharge (P = .025).

CONCLUSION: Subtotal resection should be considered in SWM with significant vascular encasement of proximal arteries to limit postoperative ischemic complications.


Putamen involvement and survival outcomes in patients with insular low-grade gliomas

J Neurosurg 126:1788–1794, 2017

Insular glioma has a unique origin and biological behavior; however, the associations between its anatomical features and prognosis have not been well established. The object of this study was to propose a classification system of insular low-grade gliomas based on preoperative MRI findings and to assess the system’s association with survival outcome.

METHODS A total of 211 consecutively collected patients diagnosed with low-grade insular gliomas was analyzed. All patients were classified according to whether tumor involved the putamen on MR images. The prognostic role of this novel putaminal classification, as well as that of Yaşargil’s classification, was examined using multivariate analyses.

RESULTS Ninety-nine cases (46.9%) of insular gliomas involved the putamen. Those tumors involving the putamen, as compared with nonputaminal tumors, were larger (p < 0.001), less likely to be associated with a history of seizures (p = 0.04), more likely to have wild-type IDH1 (p = 0.003), and less likely to be totally removed (p = 0.02). Significant favorable predictors of overall survival on univariate analysis included a high preoperative Karnofsky Performance Scale score (p = 0.02), a history of seizures (p = 0.04), gross-total resection (p = 0.006), nonputaminal tumors (p < 0.001), and an IDH1 mutation (p < 0.001). On multivariate analysis, extent of resection (p = 0.035), putamen classification (p = 0.014), and IDH1 mutation (p = 0.026) were independent predictors of overall survival. No prognostic role was found for Yaşargil’s classification.

CONCLUSIONS The current study’s findings suggest that the putamen classification is an independent predictor of survival outcome in patients with insular low-grade gliomas. This newly proposed classification allows preoperative survival prediction for patients with insular gliomas.

Neurosurgery Department. “La Fe” University Hospital. Valencia, Spain


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