Neurosurgery Blog


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

The Fluoropen: a simple low-cost device to detect intraoperative fluorescein fluorescence in stereotactic needle biopsy of brain tumors

Acta Neurochir (2017) 159:371–375

The use of fluorescein fluorescence-guided stereotactic needle biopsy has been shown to improve diagnostic accuracy and to expedite operative procedure in the stereotactic needle biopsy of high-grade gliomas. We developed a device (Fluoropen) for detecting fluorescence in brain tumor tissues obtained by fluorescein fluorescence-guided stereotactic needle biopsy.

Methods: The Fluoropen is a device consisting of a light source fitted with color filters to create the required emission and visualization wavelengths. The proof-of-concept study consisted of four consecutive patients who underwent fluorescein fluorescence-guided frameless stereotactic biopsy of brain tumor. Each sample was examined for the presence of fluorescence using the Fluoropen and compared with a microscope with fluorescence visualization capability.

Results: A total of six samples were obtained from four stereotactic needle biopsy procedures. Four out of five samples (80%) taken from the contrast-enhancing part of the tumors were shown to be fluorescent under the microscope fitted with fluorescence module and the Fluoropen. One non-contrast enhancing lesion was non-fluorescent using both the microscope fitted with fluorescence module and the Fluoropen. The Fluoropen was shown to have 100% concordance with the microscope fitted with fluorescence module.

Conclusions: The Fluoropen is a low-cost and simple standalone device for the detection of fluorescein fluorescence that can expedite stereotactic needle biopsy by providing instant confirmation of the diagnostic sample and therefore avoid the need for an intraoperative frozen section. In patients with non-contrast enhancing tumors and those who were pre-treated with dexamethasone prior to surgery, fluorescein fluorescence-guided stereotactic needle biopsy will need to be used with caution.

Fluorescein sodium-guided resection of cerebral metastases

Acta Neurochir (2017) 159:363–367

Cerebral metastasis (CM) is the most common malignancy affecting the brain. In patients eligible for surgery, complete tumor removal is the most important predictor of overall survival and neurological outcome. The emergence of surgical microscopes fitted with a fluorescein-specific filter have facilitated fluorescein-guided microsurgery and identifi- cation of tumor tissue. In 2012, we started evaluating fluores- cein (FL) with the dedicated microscope filter in cerebral me- tastases (CM). After describing the treatment results of our first 30 patients, we now retrospectively report on 95 patients.

Methods: Ninety-five patients with CM of different primary cancers were included (47 women, 48 men, mean age, 60 years, range, 25–85 years); 5 mg/kg bodyweight of FL was intrave- nously injected at induction of anesthesia. A YELLOW 560-nm filter (Pentero 900, ZEISS Meditec, Germany) was used for microsurgical tumor resection and resection control. The extent of resection (EOR) was assessed by means of early postoperative contrast-enhanced MRI and the grade of fluorescent staining as described in the surgical reports. Furthermore, we evaluated information on neurological outcome and surgical complications as well as any adverse events.

Results: Ninety patients (95%) showed bright fluorescent staining that markedly enhanced tumor visibility. Five patients (5%); three with adenocarcinoma of the lung, one with melanoma of the skin, and one with renal cell carcinoma) showed insufficient FL stain- ing. Thirteen patients (14%) showed residual tumor tissue on the postoperative MRI. Additionally, the MRI of three patients did not confirm complete resection beyond doubt. Thus, gross-total resection had been achieved in 83% (n = 79) of patients. No adverse events were registered during the postoperative course.

Conclusions: FL and the YELLOW 560-nm filter are safe and feasible tools for increasing the EOR in patients with CM. Further prospective evaluation of the FL-guided technique in CM-surgery is in planning.

Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery

Neurosurgery 79:856–871, 2016

Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense.

OBJECTIVE: To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease.

METHODS: Fifteen patients were identified and administered a Food and Drug Administration-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) before surgical resection. An NIR camera was utilized to localize the tumor before resection and to visualize surgical margins following resection. Neuropathology and magnetic resonance imaging data were used to assess the accuracy and precision of NIR fluorescence in identifying tumor tissue.

RESULTS: NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low-grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12 of 15 tumors were visualized with the NIR camera. The mean signal-tobackground ratio was 9.5 6 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with signal-to-background ratio (P = .03). Nonenhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71).

CONCLUSION: With the use of Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity.

Intraoperative Probe-Based Confocal Laser Endomicroscopy in Surgery and Stereotactic Biopsy of Low-Grade and High-Grade Gliomas


Neurosurgery 79:604–612, 2016

The management of gliomas is based on precise histologic diagnosis. The tumor tissue can be obtained during open surgery or via stereotactic biopsy. Intraoperative tissue imaging could substantially improve biopsy precision and, ultimately, the extent of resection.

OBJECTIVE: To show the feasibility of intraoperative in vivo probe-based confocal laser endomicroscopy (pCLE) in surgery and biopsy of gliomas.

METHODS: In our prospective observational study, 9 adult patients were enrolled between September 2014 and January 2015. Two contrast agents were used: 5-aminolevulinic acid (3 cases) or intravenous fluorescein (6 cases). Intraoperative imaging was performed with the Cellvizio system (Mauna Kea Technologies, Paris). A 0.85-mm probe was used for stereotactic procedures, with the biopsy needle modified to have a distal opening. During open brain surgery, a 2.36-mm probe was used. Each series corresponds to a separate histologic fragment.

RESULTS: The diagnoses of the lesions were glioblastoma (4 cases), low-grade glioma (2), grade III oligoastrocytoma (2), and lymphoma (1). Autofluorescence of neurons in cortex was observed. Cellvizio images enabled differentiation of healthy “normal” tissue from pathological tissue in open surgery and stereotactic biopsy using fluorescein. 5-Aminolevulinic acid confocal patterns were difficult to establish. No intraoperative complications related to pCLE or to use of either contrast agent were observed.

CONCLUSION: We report the initial feasibility and safety of intraoperative pCLE during primary brain tumor resection and stereotactic biopsy procedures. Pending further investigation, pCLE of brain tissue could be utilized for intraoperative surgical guidance, improvement in brain biopsy yield, and optimization of glioma resection via analysis of tumor margins.

In vivo visualization of the facial nerve in patients with acoustic neuroma using diffusion tensor imaging–based fiber tracking


J Neurosurg 125:787–794, 2016

Preoperative determination of the facial nerve (FN) course is essential to preserving its function. Neither regular preoperative imaging examination nor intraoperative electrophysiological monitoring is able to determine the exact position of the FN. The diffusion tensor imaging–based fiber tracking (DTI-FT) technique has been widely used for the preoperative noninvasive visualization of the neural fasciculus in the white matter of brain. However, further studies are required to establish its role in the preoperative visualization of the FN in acoustic neuroma surgery. The object of this study is to evaluate the feasibility of using DTI-FT to visualize the FN.

Methods: Data from 15 patients with acoustic neuromas were collected using 3-T MRI. The visualized FN course and its position relative to the tumors were determined using DTI-FT with 3D Slicer software. The preoperative visualization results of FN tracking were verified using microscopic observation and electrophysiological monitoring during microsurgery.

Results: Preoperative visualization of the FN using DTI-FT was observed in 93.3% of the patients. However, in 92.9% of the patients, the FN visualization results were consistent with the actual surgery.

Conclusions: DTI-FT, in combination with intraoperative FN electrophysiological monitoring, demonstrated improved FN preservation in patients with acoustic neuroma. FN visualization mainly included the facial-vestibular nerve complex of the FN and vestibular nerve.

Resting-state functional MRI in an intraoperative MRI setting

Resting-state functional MRI in an intraoperative MRI setting-1

J Neurosurg 125:401–409, 2016

The authors’ aim in this paper is to prove the feasibility of resting-state (RS) functional MRI (fMRI) in an intraoperative setting (iRS-fMRI) and to correlate findings with the clinical condition of patients pre- and postoperatively.

Methods: Twelve patients underwent intraoperative MRI-guided resection of lesions in or directly adjacent to the central region and/or pyramidal tract. Intraoperative RS (iRS)–fMRI was performed pre- and intraoperatively and was correlated with patients’ postoperative clinical condition, as well as with intraoperative monitoring results. Independent component analysis (ICA) was used to postprocess the RS-fMRI data concerning the sensorimotor networks, and the mean z-scores were statistically analyzed.

Results: iRS-fMRI in anesthetized patients proved to be feasible and analysis revealed no significant differences in preoperative z-scores between the sensorimotor areas ipsi- and contralateral to the tumor. A significant decrease in z-score (p < 0.01) was seen in patients with new neurological deficits postoperatively. The intraoperative z-score in the hemisphere ipsilateral to the tumor had a significant negative correlation with the degree of paresis immediately after the operation (r = -0.67, p < 0.001) and on the day of discharge from the hospital (r = -0.65, p < 0.001). Receiver operating characteristic curve analysis demonstrated moderate prognostic value of the intraoperative z-score (area under the curve 0.84) for the paresis score at patient discharge.

Conclusions: The use of iRS-fMRI with ICA-based postprocessing and functional activity mapping is feasible and the results may correlate with clinical parameters, demonstrating a significant negative correlation between the intensity of the iRS-fMRI signal and the postoperative neurological changes.

Semi-quantitative assessment of flow dynamics during indocyanine green video-angiography in the treatment of intracranial dural arteriovenous fistulas

Semi-quantitative assessment of flow dynamics during indocyanine green video-angiography in the treatment of intracranial dural arteriovenous fistulas

Acta Neurochir (2016) 158:1387–1391

Indocyanine green video-angiography (IG-VA) is applied for intraoperative localisation and verification of surgical disconnection of intracranial dural arteriovenous fistulas (iDAVFs).

Method We describe the technique of semiquantitative flow analysis using Flow800 software that implements conventional IG-VA. Our method relies on simple comparison of the fluorescence curves of the exposed vessels, allowing precise localisation of the DAVF draining vein and verification of its surgical disconnection.

Conclusions Semi-quantitative flow analysis with Flow800 software during IG-VA is a reproducible technique that may overcome the limitations of conventional IG-VA in the surgical treatment of DAVFs.

Three-dimensional MRS–guided glioma resection

Metabolic approach

J Neurosurg 124:1585–1593, 2016

The extent of resection is one of the most essential factors that influence the outcomes of glioma resection. However, conventional structural imaging has failed to accurately delineate glioma margins because of tumor cell infiltration. Three-dimensional proton MR spectroscopy (1H-MRS) can provide metabolic information and has been used in preoperative tumor differentiation, grading, and radiotherapy planning. Resection based on glioma metabolism information may provide for a more extensive resection and yield better outcomes for glioma patients. In this study, the authors attempt to integrate 3D 1H-MRS into neuronavigation and assess the feasibility and validity of metabolically based glioma resection.

Methods: Choline (Cho)–N-acetylaspartate (NAA) index (CNI) maps were calculated and integrated into neuronavigation. The CNI thresholds were quantitatively analyzed and compared with structural MRI studies. Glioma resections were performed under 3D 1H-MRS guidance. Volumetric analyses were performed for metabolic and structural images from a low-grade glioma (LGG) group and high-grade glioma (HGG) group. Magnetic resonance imaging and neurological assessments were performed immediately after surgery and 1 year after tumor resection.

Results: Fifteen eligible patients with primary cerebral gliomas were included in this study. Three-dimensional 1HMRS maps were successfully coregistered with structural images and integrated into navigational system. Volumetric analyses showed that the differences between the metabolic volumes with different CNI thresholds were statistically significant (p < 0.05). For the LGG group, the differences between the structural and the metabolic volumes with CNI thresholds of 0.5 and 1.5 were statistically significant (p = 0.0005 and 0.0129, respectively). For the HGG group, the differences between the structural and metabolic volumes with CNI thresholds of 0.5 and 1.0 were statistically significant (p = 0.0027 and 0.0497, respectively). All patients showed no tumor progression at the 1-year follow-up.

Conclusions: This study integrated 3D MRS maps and intraoperative navigation for glioma margin delineation. Optimum CNI thresholds were applied for both LGGs and HGGs to achieve resection. The results indicated that 3D 1H-MRS can be integrated with structural imaging to provide better outcomes for glioma resection.

Endo ICG videoangiography: localizing the carotid artery in skull-base endonasal approaches

Endo ICG videoangiography- localizing the carotid artery in skull-base endonasal approaches

Acta Neurochir (2016) 158:1351–1353

In this work, the applicability of ICG-VA to skull base endoscopic surgery and its capacity to locate the internal carotid artery are shown.

Methods: An adapted optical module to perform ICG-VA was used to perform endoscopic procedures. There were two intraoperative phases of interest that were used to evaluate the ICA: upon exposure of the skull base and during the intradural exploration.

This new tool for obtaining ICA images in real time (as opposed to with navigation), and it is demonstrated that this tool provides a superior ability to detect the margins of the ICA compared with the Doppler technique. On the other hand, the present technique also provides enhancement of the artery through the bone of the skull base without the need for drilling.

Conclusions: ICG-VA is a safe and effective technique for locating the ICA in skull-base expanded endonasal surgery. Furthermore, this technique can provide real-time guidance for the surgeon and increase safety for the patient.

A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas

Combining 5-Aminolevulinic Acid Fluorescence and Intraoperative Magnetic Resonance Imaging in Glioblastoma Surgery

J Neurosurg 124:1300–1309, 2016

There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity.

Methods A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated.

Results A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating with cellularity Grade 3 ranged from 95% to 100% and 86% to 100%, respectively. In biopsies without tumor (cellularity Grade 0), 35.4% still demonstrated ALA fluorescence. Of those biopsies, 90.9% contained abnormal brain tissue, characterized by reactive astrocytes, scattered atypical cells, or inflammation, and 8.1% had normal brain. In nonfluorescent (ALA intensity 0) biopsies, 62.3% had tumor cells present. The ALA-associated complication rate among the study cohort was 3.4%.

Conclusions The PPV of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the NPV of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence.

Intraoperative 3D contrast-enhanced ultrasound (CEUS)

Intraoperative 3D contrast-enhanced ultrasound (CEUS)

Acta Neurochir (2016) 158:685–694

Reliable intraoperative resection control during surgery of malignant brain tumours is associated with the longer overall survival of patients. B-mode ultrasound (BUS) is a familiar intraoperative imaging application in neurosurgical procedures and supplies excellent image quality. However, due to resection-induced artefacts, its ability to distinguish between tumour borders, oedema, surrounding tissue and tumour remnants is sometimes limited. In experienced hands, this Bbright rim effect^ could be reduced. However, it should be determined, if contrast-enhanced ultrasound can improve this situation by providing high-quality imaging during the resection. The aim of this clinical study was to examine contrast-enhanced and three-dimensional reconstructed ultrasound (3D CEUS) in brain tumour surgery regarding the uptake of contrast agent pre- and post-tumour resection, imaging quality and in comparison with postoperative magnetic resonance imaging in different tumour entities.

Methods Fifty patients, suffering from various brain tumours intra-axial and extra-axial, who had all undergone surgery with the support of neuronavigation in our neurosurgical department, were included in the study. Their median age was 56 years (range, 28–79). Ultrasound imaging was performed before the Dura was opened and for resection control at the end of tumour resection as defined by the neurosurgeon. A high-end ultrasound (US) device (Toshiba Aplio XG®) with linear and sector probes for B-mode and CEUS was used. Navigation and 3D reconstruction were performed with a LOCALITE SonoNavigator® and the images were transferred digitally (DVI) to the navigation system. The contrast agent consists of echoic micro-bubbles showing tumour vascularisation. The ultrasound images were compared with the corresponding postoperative MR data in order to determine the accuracy and imaging quality of the tumours and tumour remnants after resection.

Results Different types of tumours were investigated. High, dynamic contrast agent uptake was observed in 19 of 21 patients (90 %) suffering from glioblastoma, while in 2 patients uptake was low and insufficient. In 52.4 % of glioblastoma and grade III astrocytoma patients CEUS led to an improved delineation in comparison to BUS and showed a highresolution imaging quality of the tumour margins and tumour boarders. Grade II and grade III astrocytoma (n=6) as well as metastasis (n = 18) also showed high contrast agent uptake, which led in 50 % to an improved imaging quality. In 5 of these 17 patients, intraoperative CEUS for resection control showed tumour remnants, leading to further tumour resection. Patients treated with CEUS showed no increased neurological deficits after tumour resection. No pharmacological sideeffects occurred.

Conclusions Three-dimensional CEUS is a reliable intraoperative imaging modality and could improve imaging quality. Ninety percent of the high-grade gliomas (HGG, glioblastoma and astrocytoma grade III) showed high contrast uptake with an improved imaging quality in more than 50 %. Gross total resection and incomplete resection of glioblastoma were adequately highlighted by 3D CEUS intraoperatively. The application of US contrast agent could be a helpful imaging tool, especially for resection control in glioblastoma surgery.

Parkinson’s disease outcomes after intraoperative CT-guided “asleep” deep brain stimulation in the globus pallidus internus

Parkinson’s disease outcomes after intraoperative CT-guided “asleep” deep brain stimulation in the globus pallidus internus

J Neurosurg 124:902–907, 2016

Recent studies show that deep brain stimulation can be performed safely and accurately without microelectrode recording or test stimulation but with the patient under general anesthesia. The procedure couples techniques for direct anatomical targeting on MRI with intraoperative imaging to verify stereotactic accuracy. However, few authors have examined the clinical outcomes of Parkinson’s disease (PD) patients after this procedure. The purpose of this study was to evaluate PD outcomes following “asleep” deep brain stimulation in the globus pallidus internus (GPi).

Methods The authors prospectively examined all consecutive patients with advanced PD who underwent bilateral GPi electrode placement while under general anesthesia. Intraoperative CT was used to assess lead placement accuracy. The primary outcome measure was the change in the off-medication Unified Parkinson’s Disease Rating Scale motor score 6 months after surgery. Secondary outcomes included effects on the 39-Item Parkinson’s Disease Questionnaire (PDQ-39) scores, on-medication motor scores, and levodopa equivalent daily dose. Lead locations, active contact sites, stimulation parameters, and adverse events were documented.

Results Thirty-five patients (24 males, 11 females) had a mean age of 61 years at lead implantation. The mean radial error off plan was 0.8 mm. Mean coordinates for the active contact were 21.4 mm lateral, 4.7 mm anterior, and 0.4 mm superior to the midcommissural point. The mean off-medication motor score improved from 48.4 at baseline to 28.9 (40.3% improvement) at 6 months (p < 0.001). The PDQ-39 scores improved (50.3 vs 42.0; p = 0.03), and the levodopa equivalent daily dose was reduced (1207 vs 1035 mg; p = 0.004). There were no significant adverse events.

Conclusions Globus pallidus internus leads placed with the patient under general anesthesia by using direct anatomical targeting resulted in significantly improved outcomes as measured by the improvement in the off-medication motor score at 6 months after surgery.

Combining 5-Aminolevulinic Acid Fluorescence and Intraoperative Magnetic Resonance Imaging in Glioblastoma Surgery

Combining 5-Aminolevulinic Acid Fluorescence and Intraoperative Magnetic Resonance Imaging in Glioblastoma Surgery

Neurosurgery 78:475–483, 2016

Glioblastoma resection guided by 5-aminolevulinic acid (5-ALA) fluorescence and intraoperative magnetic resonance imaging (iMRI) may improve surgical results and prolong survival.

OBJECTIVE: To evaluate 5-ALA fluorescence combined with subsequent low-field iMRI for resection control in glioblastoma surgery.

METHODS: Fourteen patients with suspected glioblastoma suitable for complete resection of contrast-enhancing portions were enrolled. The surgery was carried out using 5-ALA–induced fluorescence and frameless navigation. Areas suspicious for tumor underwent biopsy. After complete resection of fluorescent tissue, low-field iMRI was performed. Areas suspicious for tumor remnant underwent biopsy under navigation guidance and were resected. The histological analysis was blinded.

RESULTS: In 13 of 14 cases, the diagnosis was glioblastoma multiforme. One lymphoma and 1 case without fluorescence were excluded. In 11 of 12 operations, residual contrast enhancement on iMRI was found after complete resection of 5-ALA fluorescent tissue. In 1 case, the iMRI enhancement was in an eloquent area and did not undergo a biopsy. The 28 biopsies of areas suspicious for tumor on iMRI in the remaining 10 cases showed tumor in 39.3%, infiltration zone in 25%, reactive central nervous system tissue in 32.1%, and normal brain in 3.6%. Ninety-three fluorescent and 24 non-fluorescent tissue samples collected before iMRI contained tumor in 95.7% and 87.5%, respectively.

CONCLUSION: 5-ALA fluorescence–guided resection may leave some glioblastoma tissue undetected. MRI might detect areas suspicious for tumor even after complete resection of all fluorescent tissue; however, due to the limited accuracy of iMRI in predicting tumor remnant (64.3%), resection of this tissue has to be considered with caution in eloquent regions.

The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features

The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features

Neurosurgery 78:401–411, 2016

Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade.

OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics.

METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operatingcharacteristic curves were generated for defining predictors.

RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio .1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P , .001) and Ki-67/MIB-1 index (P , .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted.

CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.

Tissue Ablation Dynamics During Magnetic Resonance–Guided, Laser-Induced Thermal Therapy

Use of High-Field Intraoperative Magnetic Resonance Imaging to Enhance the Extent of Resection of Enhancing and Nonenhancing Gliomas

Neurosurgery 77:51–58, 2015

Magnetic resonance–guided, laser-induced thermal therapy is a real- time magnetic resonance thermometry–guided, minimally invasive procedure used in the treatment of intracranial tumors, epilepsy, and pain. Little is known about its dynamics and the effects of various pathologies on overall ablation.

OBJECTIVE: To determine the relationship between thermal energy delivery and the time to maximal estimares thermal damage and whether differences exist between various intracranial pathologies.

METHODS: We used real-time ablation data from 28 patients across 5 unique intra- cranial pathologies. All ablations were performed using the Visualase Thermal Therapy System (Medtronic, Inc, Minneapolis, Minnesota), which uses a 980-nm diffusing tip diode laser. The thermal damage area was plotted against time for each ablation. We then estimated the duration of time required to reach 50% (t 50 ) and 97% (t 97 ) of maximal damage. Comparisons were then made between different intracranial pathologies.

RESULTS: The duration required to reach maximal thermal damage estimate (TDE) among all ablations was 159+-2 seconds, and the t 50 and t 97 were 43  21 and 136+-57 seconds, respectively, where t 97 was reached at an average of 23 seconds before the maximal TDE. The t 97 was shorter in the recurrent metastasis/radiation necrosis and epilepsy groups compared with the previously untreated glioblastoma multiforme group.

CONCLUSION: The optimal duration can be estimated by the t 97 , which can be achieved in less than 3 minutes and differs across ablation targets. TDE expansion decelerates with prolonged ablation. Future studies are needed to examine the radiographic and clinical outcomes as well as the effects of ablation power, irrigation speed, and the effect of previous therapies on ablation dynamics.

Combination of Intraoperative Magnetic Resonance Imaging and Intraoperative Fluorescence to Enhance the Resection of Contrast Enhancing Gliomas

Combination of Intraoperative Magnetic Resonance Imaging and Intraoperative Fluorescence to Enhance the Resection of Contrast Enhancing Gliomaspdf

Neurosurgery 77:16–22, 2015

Evidence suggests that extent of resection (EOR) is a prognostic factor for patients harboring gliomas. Recent studies have displayed the importance of intraoperative magnetic resonance imaging (iMRI) with 5-aminolevulinic acid (5-ALA) fluorescence-guidance in order to maximize EOR.

OBJECTIVE: To compare iMRI and 5-ALA fluorescence-guidance and the impact on patient survival.

METHODS: Thirty-two patients with contrast-enhancing gliomas undergoing intended gross total resection (GTR) were included in a prospective study. Surgeries were started under white-light conditions. When GTR was thought to be achieved, an iMRI scan was performed and a blue light turned on to search for unintentionally remaining tumor tissue. iMRI findings were compared with intraoperative fluorescence findings. Histological examination of tumor bulk and any additionally resected tissue was performed. All patients underwent early postoperative high-field MRI to determine EOR.

RESULTS: In 13 patients (40.6%), iMRI and fluorescence unequivocally did not show residual tumor intraoperatively. In 19 patients (59.4%), resection was continued due to iMRI or fluorescence findings. In 9 of these (47.4%), iMRI and fluorescence findings were inconsistent regarding residual tumor. GTR according to postoperative MRI was achieved in all but 1 patient. Histological examination ruled out false positive findings in all additionally resected specimens. Sensitivity and specificity to detect residual tumor tissue were 75% and 100%, respectively, for iMRI and 70% and 100% for 5-ALA fluorescence.

CONCLUSION: Use of iMRI as well as fluorescence-guidance are appropriate methods to improve the extent of resection in surgery of contrast-enhancing gliomas. Best results can be achieved by complementary use of both modalities.

Fluorescein sodium-guided resection of cerebral metastases — experience with the first 30 patients

Fluorescein sodium-guided resection of cerebral metastases — experience with the first 30 patients

Acta Neurochir (2015) 157:899–904

Surgical resection is a key element of the multidisciplinary treatment of cerebral metastases (CMs). Recent studies have highlighted the importance of complete resection of CMs for improving recurrence-free and overall survival rates. This study presents the first data on the use of fluorescein sodium (FL) under the dedicated surgical microscope filter YELLOW560 nm (ZeissMeditec, Germany) in patients with CM.

Methods Thirty patients with CMs of different primary cancers were included (15 females, 15 males; mean age 61.1 years); 200 mg of FL was intravenously injected directly before CM resection. A YELLOW560 nm filter was used for microsurgical tumor resection and resection control. Surgical reports were evaluated regarding the degree of fluorescent staining, postoperative MRIs regarding the extent of resection [gadolinium (Gd)-enhanced T1-weighted sequence] and the postoperative courses regarding any adverse effects.

Results Most patients (90.0 %, n=27) showed bright fluorescent staining, which markedly enhanced tumor visibility. Three patients (10.0 %) (two with adenocarcinoma of the lung and one with melanoma of the skin) showed no or only insufficient FL staining. Another three patients (10.0 %) showed residual tumor tissue in the postoperative MRI examination. In two other patients, radiographic examination could not exclude the possibility of very small areas of residual tumor tissue. Thus, gross-total resection was achieved in 83.3 % (n=25) of patients. No adverse effects were registered over the postoperative course.

Conclusions FL and the YELLOW560 nm filter are safe and practical tools for the resection of CM, but further prospective research is needed to confirm that this advanced technique will improve the quality of CM resection.

Does Navigated Transcranial Stimulation Increase the Accuracy of Tractography?

Does Navigated Transcranial Stimulation Increase the Accuracy of Tractography?

Neurosurgery 0:1–10, 2015

Tractography based on diffusion tensor imaging has become a popular tool for delineating white matter tracts for neurosurgical procedures.

OBJECTIVE: To explore whether navigated transcranial magnetic stimulation (nTMS) might increase the accuracy of fiber tracking.

METHODS: Tractography was performed according to both anatomic delineation of the motor cortex (n = 14) and nTMS results (n = 9). After implantation of the definitive electrode, stimulation via the electrode was performed, defining a stimulation threshold for eliciting motor evoked potentials recorded during deep brain stimulation surgery. Others have shown that of arm and leg muscles. This threshold was correlated with the shortest distance between the active electrode contact and both fiber tracks. Results were evaluated by correlation to motor evoked potential monitoring during deep brain stimulation, a surgical procedure causing hardly any brain shift.

RESULTS: Distances to fiber tracks clearly correlated with motor evoked potential thresholds. Tracks based on nTMS had a higher predictive value than tracks based on anatomic motor cortex definition (P < .001 and P = .005, respectively). However, target site, hemisphere, and active electrode contact did not influence this correlation.

CONCLUSION: The implementation of tractography based on nTMS increases the accuracy of fiber tracking. Moreover, this combination of methods has the potential to become a supplemental tool for guiding electrode implantation.

Comparison of language cortex reorganization patterns between cerebral arteriovenous malformations and gliomas: a functional MRI study

Comparison of language cortex reorganization patterns between cerebral arteriovenous malformations and gliomas- a functional MRI study

J Neurosurg 122:996–1003, 2015

Cerebral arteriovenous malformations (AVMs) are congenital malformations that may grow in the language cortex but usually do not lead to aphasia. In contrast, language dysfunction is a common presentation for patients with a glioma that involves language areas. The authors attempted to demonstrate the difference in patterns of language cortex reorganization between cerebral AVMs and gliomas by blood oxygen level–dependent (BOLD) functional MRI (fMRI) evaluation.

Methods The authors retrospectively reviewed clinical and imaging data of 63 patients with an unruptured cerebral AVM (AVM group) and 38 patients with a glioma (glioma group) who underwent fMRI. All the patients were right handed, and all their lesions were located in the left cerebral hemisphere. Patients were further categorized into 1 of the 2 following subgroups according to their lesion location: the BA subgroup (overlying or adjacent to the inferior frontal or the middle frontal gyri [the Broca area]) and the WA subgroup (overlying or adjacent to the supramarginal, angular, or superior temporal gyri [the Wernicke area]). Lateralization indices of BOLD signal activations were calculated separately for the Broca and Wernicke areas. Statistical analysis was performed to identify the difference in patterns of language cortex reorganization between the 2 groups.

Results In the AVM group, right-sided lateralization of BOLD signal activations was observed in 23 patients (36.5%), including 6 with right-sided lateralization in the Broca area alone, 12 in the Wernicke area alone, and 5 in both areas. More specifically, in the 34 patients in the AVM-BA subgroup, right-sided lateralization of the Broca area was detected in 9 patients (26.5%), and right-sided lateralization of the Wernicke area was detected in 4 (11.8%); in the 29 patients in the AVM-WA subgroup, 2 (6.9%) had right-sided lateralization of the Broca area, and 13 (44.8%) had right-sided lateralization of the Wernicke area. In the glioma group, 6 patients (15.8%) showed right-sided lateralization of the Wernicke area, including 2 patients in the glioma-BA subgroup and 4 patients in the glioma-WA subgroup. No patient showed right-sided lateralization of the Broca area. Moreover, although the incidence of right-sided lateralization was higher in cases of low-grade gliomas (5 in 26 [19.2%]) than in high-grade gliomas (1 in 12 [8.3%]), no significant difference was detected between them (p = 0.643). Compared with the AVM group, the incidence of aphasia was significantly higher (p < 0.001), and right-sided lateralization of language areas was significantly rarer (p = 0.026) in the glioma group.

Conclusions Right-sided lateralization of BOLD signal activations was observed in patients with a cerebral AVM and in those with a glioma, suggesting that language cortex reorganization may occur with both diseases. However, the potential of reorganization in patients with gliomas seems to be insufficient compared with patients AVMs, which is suggested by clinical manifestations and the fMRI findings. Moreover, this study seems to indicate that in patients with an AVM, a nidus near the Broca area mainly leads to right-sided lateralization of the Broca area, and a nidus near the Wernicke area mainly leads to right-sided lateralization of the Wernicke area.

A Pilot Cost-Effectiveness Analysis of Treatments in Newly Diagnosed High-Grade Gliomas: The Example of 5-Aminolevulinic Acid Compared With White-Light Surgery

5-ALA-induced fluorescence behavior of reactive tissue changes following glioblastoma treatment with radiation and chemotherapy

Neurosurgery 76:552–562, 2015

High-grade gliomas are aggressive, incurable tumors characterized by extensive diffuse invasion of the normal brain parenchyma. Novel therapies at best prolong survival; their costs are formidable and benefit is marginal. Economic restrictions thus require knowledge of the cost-effectiveness of treatments. Here, we show the cost-effectiveness of enhanced resections in malignant glioma surgery using a well-characterized tool for intraoperative tumor visualization, 5-aminolevulinic acid (5-ALA).

OBJECTIVE: To evaluate the cost-effectiveness of 5-ALA fluorescence-guided neurosurgery compared with white-light surgery in adult patients with newly diagnosed high-grade glioma, adopting the perspective of the Portuguese National Health Service.

METHODS: We used a Markov model (cohort simulation). Transition probabilities were estimated with the use of data from 1 randomized clinical trial and 1 noninterventional prospective study. Utility values and resource use were obtained from published literature and expert opinion. Unit costs were taken from official Portuguese reimbursement lists (2012 values). The health outcomes considered were quality-adjusted life-years, lifeyears, and progression-free life-years. Extensive 1-way and probabilistic sensitivity analyses were performed.

RESULTS: The incremental cost-effectiveness ratios are below €10 000 in all evaluated outcomes, being around €9100 per quality-adjusted life-year gained, €6700 per life-year gained, and €8800 per progression-free life-year gained. The probability of 5-ALA fluorescence-guided surgery cost-effectiveness at a threshold of €20000 is 96.0% for quality-adjusted life-year, 99.6% for life-year, and 98.8% for progression-free life-year.

CONCLUSION: 5-ALA fluorescence-guided surgery appears to be cost-effective in newly diagnosed high-grade gliomas compared with white-light surgery. This example demonstrates cost-effectiveness analyses for malignant glioma surgery to be feasible on the basis of existing data.

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


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