Heme Biosynthesis Factors and 5-ALA Induced Fluorescence: Analysis of mRNA and Protein Expression in Fluorescing and Non-fluorescing Gliomas.

Objective: The intraoperative visualization of adult-type diffuse gliomas with 5-aminolevulinic acid (5-ALA) induced fluorescence is widely used in the neurosurgical field. While visible 5-ALA induced fluorescence is found in the majority of high-grade gliomas, most low-grade gliomas lack visible fluorescence during surgery. Recently, the heme biosynthesis pathway was identified as crucial influencing factor for presence of visible fluorescence since it metabolizes 5-ALA to fluorescing Protoporphyrin IX (PpIX). However, the exact alterations within the heme biosynthesis pathway resulting in visible 5-ALA induced fluorescence in gliomas are still unclear. The aim of the present study was thus to compare the mRNA and protein expression of promising intramitochondrial heme biosynthesis enzymes/transporters in glioma tissue samples of different fluorescence behavior. Methods: A total of 19 strongly fluorescing and 21 non-fluorescing tissue samples from neurosurgical adult-type diffuse gliomas (WHO grades II-IV) were included in the current analysis. In these samples, we investigated the mRNA expression by quantitative real time PCR and protein expression using immunohistochemistry of the intramitochondrial heme biosynthesis enzymes Coproporphyrinogen Oxidase (CPOX), Protoporphyrinogen Oxidase (PPOX), Ferrochelatase (FECH), and the transporter ATP-binding Cassette Subfamily B Member 2 (ABCG2). Results: Regarding mRNA expression analysis, we found a significantly decreased ABCG2 expression in fluorescing specimens compared to non-fluorescing samples (p = 0.001), whereas no difference in CPOX, PPOX and FECH was present. With respect to protein expression, significantly higher levels of CPOX (p = 0.005), PPOX (p < 0.01) and FECH (p = 0.003) were detected in fluorescing samples. Similar to mRNA expression analysis, the protein expression of ABCG2 (p = 0.001) was significantly lower in fluorescing samples. Conclusion: Distinct alterations of the analyzed heme biosynthesis factors were found primarily on protein level. Our data indicate that heme biosynthesis pathway activity in general is enhanced in fluorescing gliomas with upregulation of PpIX generating enzymes and decreased ABCG2 mediated PpIX efflux outweighing the also increased further metabolization of PpIX to heme. Intramitochondrial heme biosynthesis factors thus constitute promising pharmacological targets to optimize intraoperative 5-ALA fluorescence visualization of usually non-fluorescing tumors such as low-grade gliomas.

The Management of Unresectable Intrathecal Catheter-Tip-Associated Granuloma Using Morphine Therapy Cessation and Spinal Cord Stimulation.

Catheter-tip-associated granulomas (CTG) are a rare but serious complication of intrathecal analgesic delivery pumps (IADP), which interfere with pain modulation and can cause irreversible neurologic deficits. The treatment of symptomatic CTG generally involves surgical resection and catheter removal. We present a case of an unresectable CTG, which we managed using progressive lowering of the intrathecal morphine sulfate (ITMS) dosage as well as spinal cord stimulation (SCS). A 55-year-old female with failed back surgery syndrome (FBSS) presented with new-onset left-sided lumbar radiculopathy after five years of moderately successful ITMS therapy. An MRI study suggested an unknown mass associated with the tip of the catheter. The tumor's adherence to nerve roots of the conus terminalis prevented a complete resection and only allowed for a biopsy. After the SCS implantation, we progressively lowered the ITMS dose. In a follow-up consultation, the patient reported the regression of the radiculopathy as well as satisfactory pain levels without oral opiates. In this case of CTG, cessation of intrathecal morphine prevented the further growth of the granuloma. SCS effectively addressed both the chronic lumbar back pain as well as the new-onset radicular pain caused by the CTG.

[Descriptive epidemiology and frequency variations of astrocytic tumors in the National Institute of Neurology and Neurosurgery of Mexico]. / Epidemiología descriptiva y cambios en la frecuencia de tumores astrocíticos en el Instituto Nacional de Neurología y Neurocirugía de México.

OBJECTIVE: To determine distribution, localization and frequency variations of astrocytic tumors (AT) in a Mexican Institute of neurology. MATERIALS AND METHODS: Institutional registries of AT from five decades were analyzed. AT/ Surgical discharges (SD) and AT/Central Nervous System Tumors (CNST) from 1995 to 2014 were compared. RESULTS: Two thousand two hundred and eighty-seven AT (1 356 men and 931 women) were analyzed. The most common glioma was glioblastoma multiforme (GBM), found in young adults with a higher frequency to that reported in other studies. Relation of AT/SD, as well as, relation of AT/CNST was similar between 1995 and 2014. CONCLUSIONS: In general, the frequency of AT worldwide, being higher in the subgroup of young adults with GBM. There was not significant variation in the frequency of AT during the time studied.

OBJETIVO: Determinar distribución, localización y cambios de la frecuencia de tumores astrocíticos (TA) en un instituto mexicano de neurología. MATERIAL Y MÉTODOS: Se revisaron los registros institucionales de TA de cinco décadas. Se compararon las relaciones TA/egresos quirúrgicos (EQ) y TA/total de tumores del sistema nervioso central (TSNC) de 1995 a 2014. RESULTADOS: Se analizaron 2 287 TA (1 356 en hombres y 931 en mujeres). El glioma más común fue el glioblastoma multiforme (GBM), que estuvo presente en adultos jóvenes con una frecuencia mayor a la reportada en otros estudios. La relación TA/EQ y TA/TNSC fue similar entre 1995 y 2014. CONCLUSIONES: En general, la frecuencia de TA atendidos en el Instituto es similar a la reportada internacionalmente. No obstante, los casos de TA en el subgrupo de adultos jóvenes con GBM son más frecuentes (40%) que las incidencias reportadas en otros estudios (menores al 5%). No se encontró variación significativa en la frecuencia de TA durante las últimas dos décadas.

Epidemiología descriptiva y cambios en la frecuencia de tumores astrocíticos en el Instituto Nacional de Neurología y Neurocirugía de México / Descriptive epidemiology and frequency variations of astrocytic tumors in the National Institute of Neurology and Neurosurgery of Mexico

Resumen: Objetivo: Determinar distribución, localización y cambios de la frecuencia de tumores astrocíticos (TA) en un instituto mexicano de neurología. Material y métodos: Se revisaron los registros institucionales de TA de cinco décadas. Se compararon las relaciones TA/egresos quirúrgicos (EQ) y TA/total de tumores del sistema nervioso central (TSNC) de 1995 a 2014. Resultados: Se analizaron 2 287 TA (1 356 en hombres y 931 en mujeres). El glioma más común fue el glioblastoma multiforme (GBM), que estuvo presente en adultos jóvenes con una frecuencia mayor a la reportada en otros estudios. La relación TA/EQ y TA/TNSC fue similar entre 1995 y 2014. Conclusiones: En general, la frecuencia de TA atendidos en el Instituto es similar a la reportada internacionalmente. No obstante, los casos de TA en el subgrupo de adultos jóvenes con GBM son más frecuentes (40%) que las incidencias reportadas en otros estudios (menores al 5%). No se encontró variación significativa en la frecuencia de TA durante las últimas dos décadas.

Abstract: Objective: To determine distribution, localization and frequency variations of astrocytic tumors (AT) in a Mexican Institute of neurology. Materials and methods: Institutional registries of AT from five decades were analyzed. AT/Surgical discharges (SD) and AT/Central Nervous System Tumors (CNST) from 1995 to 2014 were compared. Results: Two thousand two hundred and eighty-seven AT (1 356 men and 931 women) were analyzed. The most common glioma was glioblastoma multiforme (GBM), found in young adults with a higher frequency to that reported in other studies. Relation of AT/SD, as well as, relation of AT/CNST was similar between 1995 and 2014. Conclusions: In general, the frequency of AT attended at the Institute is similar to that found worldwide, being only higher the number of GBM in younger adults. There was not significant variation in the frequency of AT during the time studied.

Challenging the osseous component of sphenoorbital meningiomas.

BACKGROUND: Intraosseous growth is a unique feature of sphenoorbital meningiomas (SOM). Its close relation to neurovascular structures limits complete surgical resection and possibly contributes to the high recurrence rate. OBJECTIVE: To evaluate the growth behavior of intraosseous remnants and develop a protocol for precise intraoperative visualization of intraosseous SOM. METHODS: We included 31 patients operated for SOM from 2004 to 2017. The growth velocity of the intraosseous tumor component was volumetrically calculated in 20 cases. To improve accuracy of image guidance, we implemented a specialized bone surface-based registration algorithm. For intraoperative bone visualization, we included CT in multimodality continuous image guidance in 23 patients. The extent of resection (EOR) was compared with a standard MR-only navigation group (n = 8). RESULTS: In 11/20 cases (55%), a progressive regrowth of the intraosseous SOM remnant was noted during a mean follow-up of 52 months (range 20-132 months). We observed a mean increase of 6.2 cm3 (range 0.2-23.7 cm3) per patient and side during the follow-up period. Bone surface-based registration was significantly more accurate than skin surface-based registration (mean 0.7 ± 0.4 mm and 1.9 ± 0.7 mm, p < 0.001). The EOR of the intraosseous component was significantly higher using CT + MRI navigation compared with controls (96% vs. 81%, p = 0.044). CONCLUSION: Quantitative assessment of the biological behavior of intraosseous remnants revealed a continuous slow growth rate independent of the soft tumor component of more than half of SOM. According to our data, application of a multimodal image guidance provided high accuracy and significantly increased the resection rate of the intraosseous component of SOM.

Ex-vivo analysis of quantitative 5-ALA fluorescence intensity in diffusely infiltrating gliomas using a handheld spectroscopic probe: Correlation with histopathology, proliferation and microvascular density.

BACKGROUND: Intraoperative semiquantitative classification of different visible 5-aminolevulinic acid (5-ALA) fluorescence levels by the neurosurgeon is subjective. Recently, handheld spectroscopic probes were introduced enabling quantitative analysis of 5-ALA induced fluorescence intensity (FI). The aim of this ex-vivo study was to correlate the FI in gliomas of different grades with histopathology, proliferation and microvasular density (MVD). PATIENTS AND METHODS: Patients with suspected World Health Organization (WHO) grade II-IV gliomas were included and tissue samples from different visible fluorescence levels (strong, vague or none) were intraoperatively collected. After resection, the FI of each sample was investigated ex-vivo by a handheld spectroscopic probe. The FI values were correlated with visible fluorescence, histopathology (WHO grade, quality of tissue, histopathological parameters of anaplasia), proliferation (MIB-1) and MVD. RESULTS: Altogether, 143 tumor samples with strong (n = 61), vague (n = 21) and no fluorescence (n = 61) were collected in 68 patients. We found significantly different median FI values between all three visible fluorescence levels. Moreover, the median FI value was significantly higher in WHO grade III/IV samples and compact tumor tissue compared to WHO grade II samples and infiltrated tumor tissue. Further, significant differences in median FI values were observed in specific histopathological parameters of anaplasia (mitotic rate, cell density, nuclear pleomorphism and microvascular proliferation) in multivariable analysis. Finally, a significant correlation between the proliferation rate and FI, but not between MVD and FI was noted. CONCLUSION: Our data indicate that handheld spectroscopic probes are capable of visualizing intratumoral glioma heterogeneity by objective assessment of fluorescence and may thus optimize future glioma surgery.

Bilateral Simultaneous Temporal Relapses of Medulloblastoma.

Supratentorial relapses are a common component of medulloblastoma after failure of treatment. Craniospinal irradiation (CSI) to cerebrospinal fluid-bearing areas is an essential part of the management of these tumors both in adults and children. Failure of treatment in specific anatomical regions can be attributable to technical inaccuracies in CSI technique leading to radiation underdosing in such areas. We present two cases of patients with bilateral simultaneous metastasis of a primary medulloblastoma treated, in both cases, four years before the recurrence. In both patients the tumors were mirror images, at the right and left temporal pole. Radiotherapeutic plans were analyzed in both cases, and a possible mechanism determining the pattern of relapse is discussed. We consider, in agreement with the literature, that a prone position during treatment, shielding blocks at the cribiform/subfrontal region, and anatomic inadequacies in the CSI fields could have contributed to the presented pattern of relapse.

Systematic histopathological analysis of different 5-aminolevulinic acid-induced fluorescence levels in newly diagnosed glioblastomas.

OBJECTIVE Glioblastoma (GBM) is characterized by distinct intratumoral histopathological heterogeneity with regard to variable tumor morphology, cell proliferation, and microvascularity. Maximum resection of a GBM results in an improved prognosis and thus represents the aim of surgery in the majority of cases. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is currently widely applied for improved intraoperative tumor visualization in patients with a GBM. Three intratumoral fluorescence levels (i.e., strong, vague, or no fluorescence) can usually be distinguished during surgery. So far, however, their exact histopathological correlates and their surgical relevance have not been clarified sufficiently. Thus, the aim of this study was to systematically analyze tissue samples from newly diagnosed GBMs with different fluorescence levels according to relevant histopathological parameters. METHODS This prospective study recruited patients who underwent 5-ALA fluorescence-guided resection of a newly diagnosed radiologically suspected GBM. Each patient received 5-ALA approximately 3 hours before surgery, and a modified neurosurgical microscope was applied for intraoperative visualization of 5-ALA-induced fluorescence. During surgery, tissue samples with strong, vague, or no fluorescence were collected. For each sample, the presence of tumor tissue, quality of tissue (compact, infiltrative, or no tumor), histopathological criteria of malignancy (cell density, nuclear pleomorphism, mitotic activity, and presence of microvascular proliferation/necrosis), proliferation rate (MIB-1 labeling index [LI]), and microvessel density (using CD34 staining) were investigated. RESULTS Altogether, 77 patients with a newly diagnosed, histopathologically confirmed GBM were included, and 131 samples with strong fluorescence, 69 samples with vague fluorescence, and 67 samples with no fluorescence were collected. Tumor tissue was detected in all 131 (100%) of the samples with strong fluorescence and in 65 (94%) of the 69 samples with vague fluorescence. However, mostly infiltrative tumor tissue was still found in 33 (49%) of 67 samples despite their lack of fluorescence. Strong fluorescence corresponded to compact tumors in 109 (83%) of 131 samples, whereas vague fluorescence was consistent with infiltrative tumors in 44 (64%) of 69 samples. In terms of the histopathological criteria of malignancy, a significant positive correlation of all analyzed parameters comprising cell density, nuclear pleomorphism, mitotic activity, microvascular proliferation, and necrosis with the 3 fluorescence levels was observed (p < 0.001). Furthermore, the proliferation rate significantly and positively correlated with strong (MIB-1 LI 28.3%), vague (MIB-1 LI 16.7%), and no (MIB-1 LI 8.8%) fluorescence (p < 0.001). Last, a significantly higher microvessel density was detected in samples with strong fluorescence (CD34 125.5 vessels/0.25 mm2) than in those with vague (CD34 82.8 vessels/0.25 mm2) or no (CD34 68.6 vessels/0.25 mm2) fluorescence (p < 0.001). CONCLUSIONS Strong and vague 5-ALA-induced fluorescence enables visualization of intratumoral areas with specific histopathological features and thus supports neurosurgeons in improving the extent of resection in patients with a newly diagnosed GBM. Despite the lack of fluorescence, tumor tissue was still observed in approximately half of the cases. To overcome this current limitation, the promising approach of complementary spectroscopic measurement of fluorescence should be investigated further.

A novel miniature robotic guidance device for stereotactic neurosurgical interventions: preliminary experience with the iSYS1 robot.

OBJECTIVE Robotic devices have recently been introduced in stereotactic neurosurgery in order to overcome the limitations of frame-based and frameless techniques in terms of accuracy and safety. The aim of this study is to evaluate the feasibility and accuracy of the novel, miniature, iSYS1 robotic guidance device in stereotactic neurosurgery. METHODS A preclinical phantom trial was conducted to compare the accuracy and duration of needle positioning between the robotic and manual technique in 162 cadaver biopsies. Second, 25 consecutive cases of tumor biopsies and intracranial catheter placements were performed with robotic guidance to evaluate the feasibility, accuracy, and duration of system setup and application in a clinical setting. RESULTS The preclinical phantom trial revealed a mean target error of 0.6 mm (range 0.1-0.9 mm) for robotic guidance versus 1.2 mm (range 0.1-2.6 mm) for manual positioning of the biopsy needle (p < 0.001). The mean duration was 2.6 minutes (range 1.3-5.5 minutes) with robotic guidance versus 3.7 minutes (range 2.0-10.5 minutes) with manual positioning (p < 0.001). Clinical application of the iSYS1 robotic guidance device was feasible in all but 1 case. The median real target error was 1.3 mm (range 0.2-2.6 mm) at entry and 0.9 mm (range 0.0-3.1 mm) at the target point. The median setup and instrument positioning times were 11.8 minutes (range 4.2-26.7 minutes) and 4.9 minutes (range 3.1-14.0 minutes), respectively. CONCLUSIONS According to the preclinical data, application of the iSYS1 robot can significantly improve accuracy and reduce instrument positioning time. During clinical application, the robot proved its high accuracy, short setup time, and short instrument positioning time, as well as demonstrating a short learning curve.

Historical distribution of central nervous system tumors in the Mexican National Institute of Neurology and Neurosurgery.

OBJECTIVE: To determine the frequency of central nervous system (CNS) tumors in the first fifty years of the National Institute of Neurology and Neurosurgery of Mexico Manuel Velasco Suárez (Instituto Nacional de Neurología y Neurocirugía de México, INNN) from 1965 to 2014. MATERIALS AND METHODS: A total of 16 116 institutional records of CNS tumors were analyzed. The frequency and distribution of CNS tumors were evaluated by tumor type, patient age and patient gender. The annual relationship between CNS tumors and surgical discharges (SD) over the last 20 years was estimated. RESULTS: The frequencies of most CNS tumors were consistent with those found worldwide, and the most common tumors were neuroepithelial tumors (33%), particularly astrocytic tumors (67%); meningeal tumors (26%); and pituitary tumors (20%). The incidence of pituitary tumors in these data was twice as high as that reported in other regions of the world, and the relationship between CNS tumors and SD was consistent over time (0.22-0.39). CONCLUSION: This study summarizes the largest sample of CNS tumor cases analyzed in Mexico and provides an important reference of the frequency of this tumor type in the country. This work will serve as a basis for conducting studies evaluating factors associated with the presence of CNS tumors and for identifying adequate public health interventions.

Historical distribution of central nervous system tumors in the Mexican National Institute of Neurology and Neurosurgery / Distribución histórica de neoplasias del sistema nervioso central en el Instituto Nacional de Neurología y Neurocirugía de México

Abstract Objective: To determine the frequency of central nervous system (CNS) tumors in the first fifty years of the National Institute of Neurology and Neurosurgery of Mexico Manuel Velasco Suárez (Instituto Nacional de Neurología y Neurocirugía de México, INNN) from 1965 to 2014. Materials and methods: A total of 16 116 institutional records of CNS tumors were analyzed. The frequency and distribution of CNS tumors were evaluated by tumor type, patient age and patient gender. The annual relationship between CNS tumors and surgical discharges (SD) over the last 20 years was estimated. Results: The frequencies of most CNS tumors were consistent with those found worldwide, and the most common tumors were neuroepithelial tumors (33%), particularly astrocytic tumors (67%); meningeal tumors (26%); and pituitary tumors (20%). The incidence of pituitary tumors in these data was twice as high as that reported in other regions of the world, and the relationship between CNS tumors and SD was consistent over time (0.22-0.39). Conclusion: This study summarizes the largest sample of CNS tumor cases analyzed in Mexico and provides an important reference of the frequency of this tumor type in the country. This work will serve as a basis for conducting studies evaluating factors associated with the presence of CNS tumors and for identifying adequate public health interventions.

Resumen Objetivo: Determinar la frecuencia de neoplasias del sistema nervioso central (NSNC) en los primeros 50 años del Instituto Nacional de Neurología y Neurocirugía de México (INNN). Material y métodos: Se analizaron 16 116 registros institucionales de las NSNC, atendidas en el INNN de 1965 a 2014; se estimó su frecuencia y distribución por tipo de neoplasia, edad y género, y se determinó la relación anual de NSNC y egresos quirúrgicos (EQ) en un período de 20 años. Resultados: Las frecuencias de la mayoría de NSNC fueron consistentes con las encontradas a nivel mundial. Las más frecuentes fueron las neuroepiteliales (33%), entre las cuales destacaron las astrocíticas (67%); meníngeas (26%), e hipofisiarias (20%). El número de neoplasias hipofisiarias en esta serie fue dos veces mayor al reportado en otras regiones del mundo y la relación NSNC/EQ fue similar a través del tiempo (0.22-0.39). Conclusión: Ésta es la mayor serie de casos de NSNC analizados en México y proporciona un referente importante sobre la frecuencia de este tipo de neoplasias en el país. Este trabajo servirá de base para llevar a cabo estudios de los factores asociados a la presencia de NSNC e identificar intervenciones de salud pública adecuadas.

Analysis of the surgical benefits of 5-ALA-induced fluorescence in intracranial meningiomas: experience in 204 meningiomas.

OBJECTIVE One of the most important causes for recurrence of intracranial meningiomas is residual tumor tissue that remains despite assumed complete resection. Recently, intraoperative visualization of meningioma tissue by 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence was reported. The aim of this study was to investigate the possible surgical benefits of PpIX fluorescence for detection of meningioma tissue. METHODS 5-ALA was administered preoperatively to 190 patients undergoing resection of 204 intracranial meningiomas. The meningiomas' PpIX fluorescence status, fluorescence quality (strong or vague), and intratumoral fluorescence homogeneity were investigated during surgery. Additionally, specific sites, including the dural tail, tumor-infiltrated bone flap, adjacent cortex, and potential satellite lesions, were analyzed for PpIX fluorescence in selected cases. RESULTS PpIX fluorescence was observed in 185 (91%) of 204 meningiomas. In the subgroup of sphenoorbital meningiomas (12 of 204 cases), the dural part showed visible PpIX fluorescence in 9 cases (75%), whereas the bony part did not show any PpIX fluorescence in 10 cases (83%). Of all fluorescing meningiomas, 168 (91%) showed strong PpIX fluorescence. Typically, most meningiomas demonstrated homogeneous fluorescence (75% of cases). No PpIX fluorescence was observed in any of the investigated 89 dural tails. In contrast, satellite lesions could be identified through PpIX fluorescence in 7 cases. Furthermore, tumor-infiltrated bone flaps could be visualized by PpIX fluorescence in all 13 cases. Notably, PpIX fluorescence was also present in the adjacent cortex in 20 (25%) of 80 analyzed cases. CONCLUSIONS The authors' data from this largest patient cohort to date indicate that PpIX fluorescence enables intraoperatively visualization of most intracranial meningiomas and allows identification of residual tumor tissue at specific sites. Thus, intraoperative detection of residual meningioma tissue by PpIX fluorescence might in future reduce the risk of recurrence.

Primary ectopic frontotemporal craniopharyngioma.

INTRODUCTION: Primary ectopic craniopharyngiomas have only rarely been reported. Craniopharyngiomas involve usually the sellar and suprasellar region, but can be originated from cell remnants of the obliterated craniopharyngeal duct or metaplastic change of andenohypophyseal cells. We present the first case of a primary ectopic frontotemporal craniopharyngioma. PRESENTATION OF CASE: A 35-year old woman presented with a one-year history of headache and diplopia. MRI showed a large frontotemporal cystic lesion. Tumor resection was performed with a keyhole endoscopic frontal lateral approach. The pathological features showed an adamantinomatous craniopharyngioma with a cholesterol granuloma reaction. DISCUSSION: There have been reported different localizations for primary ectopic craniopharyngioma. Our case presented a lobulated frontotemporal cystic mass formed by a dense eosinophilic proteinaceous material dystrophic calcifications and cholesterol crystals, with epithelial remnants. No tumor regrowth was observed in the magnetic resonance image 27 months postoperatively. CONCLUSION: Primary ectopic craniopharyngioma is a rare entity with a pathogenesis that remains uncertain. This is an unusual anatomic location associated with unique clinical findings.

Introduction of a standardized multimodality image protocol for navigation-guided surgery of suspected low-grade gliomas.

OBJECT Surgery of suspected low-grade gliomas (LGGs) poses a special challenge for neurosurgeons due to their diffusely infiltrative growth and histopathological heterogeneity. Consequently, neuronavigation with multimodality imaging data, such as structural and metabolic data, fiber tracking, and 3D brain visualization, has been proposed to optimize surgery. However, currently no standardized protocol has been established for multimodality imaging data in modern glioma surgery. The aim of this study was therefore to define a specific protocol for multimodality imaging and navigation for suspected LGG. METHODS Fifty-one patients who underwent surgery for a diffusely infiltrating glioma with nonsignificant contrast enhancement on MRI and available multimodality imaging data were included. In the first 40 patients with glioma, the authors retrospectively reviewed the imaging data, including structural MRI (contrast-enhanced T1-weighted, T2-weighted, and FLAIR sequences), metabolic images derived from PET, or MR spectroscopy chemical shift imaging, fiber tracking, and 3D brain surface/vessel visualization, to define standardized image settings and specific indications for each imaging modality. The feasibility and surgical relevance of this new protocol was subsequently prospectively investigated during surgery with the assistance of an advanced electromagnetic navigation system in the remaining 11 patients. Furthermore, specific surgical outcome parameters, including the extent of resection, histological analysis of the metabolic hotspot, presence of a new postoperative neurological deficit, and intraoperative accuracy of 3D brain visualization models, were assessed in each of these patients. RESULTS After reviewing these first 40 cases of glioma, the authors defined a specific protocol with standardized image settings and specific indications that allows for optimal and simultaneous visualization of structural and metabolic data, fiber tracking, and 3D brain visualization. This new protocol was feasible and was estimated to be surgically relevant during navigation-guided surgery in all 11 patients. According to the authors' predefined surgical outcome parameters, they observed a complete resection in all resectable gliomas (n = 5) by using contour visualization with T2-weighted or FLAIR images. Additionally, tumor tissue derived from the metabolic hotspot showed the presence of malignant tissue in all WHO Grade III or IV gliomas (n = 5). Moreover, no permanent postoperative neurological deficits occurred in any of these patients, and fiber tracking and/or intraoperative monitoring were applied during surgery in the vast majority of cases (n = 10). Furthermore, the authors found a significant intraoperative topographical correlation of 3D brain surface and vessel models with gyral anatomy and superficial vessels. Finally, real-time navigation with multimodality imaging data using the advanced electromagnetic navigation system was found to be useful for precise guidance to surgical targets, such as the tumor margin or the metabolic hotspot. CONCLUSIONS In this study, the authors defined a specific protocol for multimodality imaging data in suspected LGGs, and they propose the application of this new protocol for advanced navigation-guided procedures optimally in conjunction with continuous electromagnetic instrument tracking to optimize glioma surgery.

A novel protocol of continuous navigation guidance for endoscopic third ventriculostomy.

BACKGROUND: Although considered a standard neurosurgical procedure, endoscopic third ventriculostomy (ETV) is associated with a relatively high complication rate that is predominantly related to malpositioning of the trajectory. OBJECTIVE: To develop an advanced navigation protocol for ETV, assess its possible benefits over commonly used ETV trajectories, and apply this protocol during surgery. METHODS: After development of our advanced protocol, the imaging data of 59 patients who underwent ETV without navigation guidance was transferred to our navigation software. An individualized endoscope trajectory was created according to our protocol in all cases. This trajectory was compared with 2 standard trajectories, especially with regard to the distance to relevant neuronal structures: a trajectory manually measured on preoperative radiological images, as performed in all 59 cases, and a trajectory resulting from a commonly used fixed coronal burr hole. Subsequently, we applied the protocol in 15 ETVs to assess the feasibility and procedural complications. RESULTS: Our individualized trajectory resulted in a significantly greater distance to the margins of the foramen of Monro, and the burr hole was located more posteriorly from the coronal suture in comparison with the standard trajectories. The advanced ETV technique was feasible in all 15 procedures, and no major complications occurred in any procedure. In 1 patient, a fornix contusion without clinical correlation was observed. CONCLUSION: Our data indicate that the proposed navigation protocol for ETV optimizes the distance of the endoscope to important neuronal structures. Continuous endoscope and puncture device guidance may further add to the safety of this procedure.

Analysis of 5-aminolevulinic acid-induced fluorescence in 55 different spinal tumors.

OBJECT: Subtotal resection (STR) of spinal tumors can result in tumor recurrence. Currently, no clinically reliable marker is available for intraoperative visualization of spinal tumor tissue. Protoporphyrin IX (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA) is capable of visualizing malignant gliomas. Fluorescence-guided resections of malignant cerebral gliomas using 5-ALA have resulted in an increased rate of complete tumor removal. Recently, the application of 5-ALA has also been described in the first cases of spinal tumors. Therefore, the aim of this observational study was to systematically investigate 5-ALA-induced fluorescence characteristics in different spinal tumor entities. METHODS: Three hours before the induction of anesthesia, 5-ALA was administered to patients with different intra- and extradural spinal tumors. In all patients a neurosurgical resection or biopsy of the spinal tumor was performed under conventional white-light microscopy. During each surgery, the presence of PpIX fluorescence was additionally assessed using a modified neurosurgical microscope. At the end of an assumed gross-total resection (GTR) under white-light microscopy, a final inspection of the surgical cavity of fluorescing intramedullary tumors was performed to look for any remaining fluorescing foci. Histopathological tumor diagnosis was established according to the current WHO classification. RESULTS: Fifty-two patients with 55 spinal tumors were included in this study. Resection was performed in 50 of 55 cases, whereas 5 of 55 cases underwent biopsy. Gross-total resection was achieved in 37 cases, STR in 5, and partial resection in 8 cases. Protoporphyrin IX fluorescence was visible in 30 (55%) of 55 cases, but not in 25 (45%) of 55 cases. Positive PpIX fluorescence was mainly detected in ependymomas (12 of 12), meningiomas (12 of 12), hemangiopericytomas (3 of 3), and in drop metastases of primary CNS tumors (2 of 2). In contrast, none of the neurinomas (8 of 8), carcinoma metastases (5 of 5), and primary spinal gliomas (3 of 3; 1 pilocytic astrocytoma, 1 WHO Grade II astrocytoma, 1 WHO Grade III anaplastic oligoastrocytoma) revealed PpIX fluorescence. It is notable that residual fluorescing tumor foci were detected and subsequently resected in 4 of 8 intramedullary ependymomas despite assumed GTR under white-light microscopy. CONCLUSIONS: In this study, 5-ALA-PpIX fluorescence was observed in spinal tumors, especially ependymomas, meningiomas, hemangiopericytomas, and drop metastases of primary CNS tumors. In cases of intramedullary tumors, 5-ALA-induced PpIX fluorescence is a useful tool for the detection of potential residual tumor foci.