Update in Cushing disease: What the neurosurgeon has to KNOW, on behalf of the EANS skull base section.

Introduction: Cushing's disease is a state of chronic and excessive cortisol levels caused by a pituitary adenoma. Research question: CD is a complex entity and often entails difficulties in its diagnosis and management. For that reason, there are still controversial points to that respect. The aim of this consensus paper of the skull base section of the EANS is to review the main aspects of the disease a neurosurgeon has to know and also to offer updated recommendations on the controversial aspects of its management. Material and methods: PUBMED database was used to search the most pertinent articles published on the last 5 years related with the management of CD. A summary of literature evidence was proposed for discussion within the EANS skull base section and other international experts. Results: This article represents the consensual opinion of the task force regarding optimal management and surgical strategy in CD. Discussion and conclusion: After discussion in the group several recommendations and suggestions were elaborated. Patients should be treated by an experienced multidisciplinary team. Accurate clinical, biochemical and radiological diagnosis is mandatory. The goal of treatment is the complete adenoma resection to achieve permanent remission. If this is not possible, the treatment aims to achieving eucortisolism. Radiation therapy is recommended to patients with CD when surgical options have been exhausted. All patients in remission should be tested all life-long.

Cerebrospinal Fluid Leak after Transsphenoidal Surgery: A Systematic Review and Meta-analysis.

Background Cerebrospinal fluid (CSF) leak is widely recognized as a challenging and commonly occurring postoperative complication of transsphenoidal surgery (TSS). The primary objective of this study is to benchmark the current prevalence of CSF leak after TSS in the adult population. Methods The authors followed the PRISMA guidelines. The PubMed, Embase, and Cochrane Library databases were searched for articles reporting CSF leak after TSS in the adult population. Meta-analysis was performed using the Untransformed Proportion metric in OpenMetaAnalyst. For two between-group comparisons a generalized linear mixed model was applied. Results We identified 2,408 articles through the database search, of which 70, published since 2015, were included in this systematic review. These studies yielded 24,979 patients who underwent a total of 25,034 transsphenoidal surgeries. The overall prevalence of postoperative CSF leak was 3.4% (95% confidence interval or CI 2.8-4.0%). The prevalence of CSF leak found in patients undergoing pituitary adenoma resection was 3.2% (95% CI 2.5-4.2%), whereas patients who underwent TSS for another indication had a CSF leak prevalence rate of 7.1% (95% CI 3.0-15.7%) (odds ratio [OR] 2.3, 95% CI 0.9-5.7). Patients with cavernous sinus invasion (OR 3.0, 95% CI 1.1-8.7) and intraoperative CSF leak (OR 5.9, 95% CI 3.8-9.0) have increased risk of postoperative CSF leak. Previous TSS and microscopic surgery are not significantly associated with postoperative CSF leak. Conclusion The overall recent prevalence of CSF leak after TSS in adults is 3.4%. Intraoperative CSF leak and cavernous sinus invasion appear to be significant risk factors for postoperative CSF leak.

Intracranial Meningiomas Decrease in Volume on Magnetic Resonance Imaging After Discontinuing Progestin.

BACKGROUND: The behavior of meningiomas under influence of progestin therapy remains unclear. OBJECTIVE: To investigate the relationship between growth kinetics of intracranial meningiomas and usage of the progestin cyproterone acetate (PCA). METHODS: This study prospectively followed 108 women with 262 intracranial meningiomas and documented PCA use. A per-meningioma analysis was conducted. Changes in meningioma volumes over time, and meningioma growth velocities, were measured on magnetic resonance imaging (MRI) after stopping PCA treatment. RESULTS: Mean follow-up time was 30 (standard deviation [SD] 29) mo. Ten (4%) meningiomas were treated surgically at presentation. The other 252 meningiomas were followed after stopping PCA treatment. Overall, followed meningiomas decreased their volumes by 33% on average (SD 28%). A total of 188 (72%) meningiomas decreased, 51 (20%) meningiomas remained stable, and 13 (4%) increased in volume of which 3 (1%) were surgically treated because of radiological progression during follow-up after PCA withdrawal. In total, 239 of 262 (91%) meningiomas regressed or stabilized during follow-up. Subgroup analysis in 7 women with 19 meningiomas with follow-up before and after PCA withdrawal demonstrated that meningioma growth velocity changed statistically significantly (P = .02). Meningiomas grew (average velocity of 0.25 mm3/day) while patients were using PCA and shrank (average velocity of -0.54 mm3/day) after discontinuation of PCA. CONCLUSION: Ninety-one percent of intracranial meningiomas in female patients with long-term PCA use decrease or stabilize on MRI after stopping PCA treatment. Meningioma growth kinetics change significantly from growth during PCA usage to shrinkage after PCA withdrawal.

Postoperative headache after surgical treatment of cerebellopontine angle tumors: a systematic review.

PURPOSE: Postoperative headache (POH) is a complication that occurs after surgical resection of cerebellopontine angle (CPA) tumors. The two most common surgical approaches are the translabyrinthine (TL), and retrosigmoid (RS) approach. The objective of this systematic review was to investigate whether POH occurs more frequently after RS compared to TL approaches. METHODS: A systematic search was conducted in Cochrane, Pubmed and Embase. Studies were included if POH after CPA tumor removal was reported and both surgical approaches were compared. The methodological quality of the studies was assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. RESULTS: In total, 3,942 unique articles were screened by title and abstract. After the initial screening process 63 articles were screened for relevance to the inquiry, of which seven studies were included. Three studies found no significant difference between both surgical approaches (p = 0.871, p = 0.120, p = 0.592). Three other studies found a lower rate of POH in the TL group compared to the RS group (p = 0.019, p < 0.001, p < 0.001). Another study showed a significantly lower POH rate in the TL group after one and six months (p = 0.006), but not after 1 year (p = 0.6). CONCLUSION: The results of this systematic review show some evidence of a lower rate of POH in favor of the TL approach versus the RS approach for CPA tumor resection. Prospective research studies are needed to further investigate this finding.

Delayed Instrumentation Following Removal of Cranio-Vertebral Junction Chordomas: A Technical Note.

Objective To investigate on the feasibility and safety of a new approach which consists of delaying instrumentation after destabilizing craniovertebral junction (CVJ) chordoma surgery, allowing proton beam radiotherapy to be performed in a metal-free tumoral cavity. Design This is a retrospective series of a prospectively maintained database. Participants Five consecutive patients operated on for a CVJ chordomas for which instrumentation after tumor resection was deferred to after radiotherapy treatment. Main Outcome Measures The main outcome consisted of measurements of the following parameters: C0-C2 angle, atlanto-dens interval (ADI), condylar gap, and the position of the dens relative to McGregor's line and coronal inclination, performed at 3 different times for all patients: before tumor surgery (baseline), before instrumentation surgery, and after instrumentation surgery. Results For all patients, CVJ parameters deteriorated during the delay period, but stayed within normal limits for most. Because of radiological instability, one patient necessitated instrumentation before receiving radiotherapy. All parameters except condylar gap were partially corrected after instrumentation. No new neurological symptom or evolving neck pain occurred during the delay period. Conclusion Delayed instrumentation of CVJ chordomas can be a safe alternative that might lead to improved subsequent radiotherapeutical treatment. Patient's selection and close clinical and radiological follow-up are mandatory for the success of this approach.

The orbitopterygoid corridor as a deep keyhole for endoscopic access to the paranasal sinuses and clivus.

OBJECTIVE: The anteromedial triangle (AMT) is the triangle formed by the ophthalmic (V1) and maxillary (V2) nerves. Opening of this bony space offers a limited access to the sphenoid sinus (SphS). This study aims to demonstrate the utility of the orbitopterygopalatine corridor (OPC), obtained by enlarging the AMT and transposing the contents of the pterygopalatine fossa (PPF) and V2, as an entrance to the SphS, maxillary sinus (MaxS), and nasal cavity. METHODS: Five formalin-injected cadaveric specimens were used for this study (10 approaches). A classic pterional approach was performed. An OPC was created through the inferior orbital fissure, between the orbit and the PPF, by transposing the PPF inferiorly. The extent of the OPC was measured using neuronavigation and manual measurements. Two illustrative cases using the OPC to access skull base tumors are presented in the body of the article. RESULTS: Via the OPC, the SphS, MaxS, ethmoid sinus (EthS), and nasal cavity could be accessed. The use of endoscopic assistance through the OPC achieved better visualization of the EthS, SphS, MaxS, clivus, and nasal cavity. A significant gain in the area of exposure could be achieved using the OPC compared to the AMT (22.4 mm2 vs 504.1 mm2). CONCLUSIONS: Opening of the AMT and transposition of V2 and the contents of the PPF creates the OPC, a potentially useful deep keyhole to access the paranasal sinuses and clival region through a middle fossa approach. It is a valuable alternative approach to reach deep-seated skull base lesions infiltrating the cavernous sinus and middle cranial fossa and extending into the paranasal sinus.

Petroclival meningiomas: the risk of post-operative cranial nerve deficits among different surgical approaches-a systematic review and meta-analysis.

BACKGROUND: The surgical resection of petroclival meningiomas (PCMs) remains a challenge. Both the relationship with neurovascular structures and the deep location of the tumor can affect the extent of resection and the rate of post-operative morbidity. METHODS: The authors performed a systematic review and meta-analysis of the literature examining the rate of new cranial nerve (CN) deficits after resection of PCM. A systematic search of two databases was performed for studies published between 1990 and 2018. Random-effect meta-analysis was used to pool the rate of post-operative CN deficits, mortality rate, and rate of radical resection. RESULTS: We included twelve studies and 334 patients harboring PCM. The overall rate of complete resection was 68% (95% CI 57.9-78.2%; p < 0.01; I2 = 83%). The rate of early and late post-operative CN deficits was the following: 3.8 and 2.7% (III CN), 6.6 and 3% (IV), 7.3 and 5.5% (V CN), 8 and 3.6% (VI CN), 8.9 and 8.9%% (VIII), and 4 and 2.7% (IX-XI CNs) (I2 = 0%, and p < 0.01 for all analyses). The risk of post-operative deficit of the IV CN was higher among the petrosal group (7.6%; I2 = 0% vs 2.1%; I2 = 0%), whereas the impairment of VII CN function was higher among retrosigmoid group (16.6%; I2 = 64.6% vs 11.4%; I2 = 52.8%), but it was transient in the majority of cases. CONCLUSIONS: This systematic review and meta-analysis provides a detailed overview of post-operative CN deficits ensuing surgical resection of PCMs. These findings should be acknowledged when counseling patients with PCMs regarding the more appropriate approach for their tumor.

Vertebrobasilar Artery Encasement by Skull Base Chordomas: Surgical Outcome and Management Strategies.

BACKGROUND: Vascular encasement by skull base chordomas can increase surgical risk and hinder completeness of resection. However, the evidence behind this remains anecdotic. OBJECTIVE: To give a better portrayal of chordomas encasing vertebrobasilar arteries mainly in regard of surgical vascular risk and its impact on extent of resection. METHODS: A retrospective cohort study comparing skull base chordomas with encasement (≥180o encirclement) of the vertebrobasilar arteries to a control group of skull base chordomas with intradural extension. Data gathered involved pre- and postoperative volumetric analysis of the tumor, degree of encasement of involved vessel, occurrence of complication, and survival data including progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 24 patients with vertebrobasilar encasement were included in the study and an equal number of control cases were randomly selected from the same time period, totalizing 48 patients. Lower clival tumors with condyle involvement were more likely to have encasement. Gross total resection (GTR) rate was significantly lower in the encasement group (13% vs 42%, P = .023). Rates of postoperative new neurological deficit, CFS leak and 30 d postoperative mortality were not statistically different between groups. There was no statistically significant difference in mean PFS (P = .608) and OS (P = .958). CONCLUSION: Skull base chordomas encasing vertebrobasilar arteries are highly challenging tumors. This study demonstrates that although safe resection is possible, GTR is hindered by the presence of encasement. We advocate letting the tumor's adherence to vessels lead the resection, leaving a small piece of tumor behind if adherent to the vessels.

Distance Control and Virtual Drilling Improves Anatomical Orientation During Anterior Petrosectomy.

BACKGROUND: A combined drill distance control and virtual drilling image guidance feedback method was developed. OBJECTIVE: To investigate whether first-time usage of the proposed method, during anterior petrosectomy (AP), improves surgical orientation and surgical performance. The accuracy of virtual drilling and the clinical practicability of the method were also investigated. METHODS: In a simulated surgical setting using human cadavers, a trial was conducted with 5 expert skull base surgeons from 3 different hospitals. They performed 10 AP approaches, using either the feedback method or standard image guidance. Damage to critical structures was assessed. Operating time, drill cavity sizes, and proximity of postoperative drill cavities to the cochlea and the acoustic meatus, were measured. Questionnaires were obtained postoperatively. Errors in the virtual drill cavities as compared with actual postoperative cavities were calculated. In a clinical setup, the method was used during AP. RESULTS: Surgeons rated their intraoperative orientation significantly better with the feedback method compared with standard image guidance. During the cadaver trial, the cochlea was harmed on 1 occasion in the control group, while surgeons drilled closer to the cochlea and meatus without injuring them in the group using feedback. Virtual drilling under- and overestimation errors were 2.2 ± 0.2 and -3.0 ± 0.6 mm on average. The method functioned properly during the clinical setup. CONCLUSION: The proposed feedback method improves orientation and surgical performance in an experimental setting. Errors in virtual drilling reflect spatial errors of the image guidance system. The feedback method is clinically practicable during AP.

Chordoma of the Craniocervical Junction: Endoscopic Endonasal Approach.

Objective This study was aimed to achieve gross-total removal of a chordoma of the craniocervical junction via an endonasal approach ( Fig. 1 ). Fig. 1 Pre- and postoperative images of the craniocervical junction chordoma. ( A ) It shows a preoperative sagittal T2-weighted MRI image. ( B ) It shows a preoperative axial T2-weighted MRI image. Note that a T2-hyperintense lesion is located in the lower clivus and the odontoid. ( C ) It shows the postoperative sagittal T1-weighted gadolinium enhanced MRI image. ( D ) shows a postoperative axial T2-weighted MRI image. These images show the fat graft used for closure, but no evident tumor remnant. MRI, magnetic resonance imaging Design The present study is a case report. Setting The study was conducted at neurosurgical clinic of university hospital. Participant A 40-year-old male, with normal neurologic exam and no prior medical history, presented with a 2-year history of cervicalgia. On preoperative imaging, a midline lesion, with image characteristics of chordoma, was seen in the lower clivus and odontoid. It had limited lateral extension. Main Outcome Measures This study measures postoperative neurological deficits and postoperative tumor volume on magnetic resonance imaging (MRI). Results A binostril approach to the upper nasopharynx was performed using endoscope at 30- and 45-degree angles. Subsequently, a heart-shaped mucosal flap was made and the clivus was drilled to expose the lesion ( Fig. 2 ). After initial debulking, the ring of C1 was slightly drilled to reach the tumor in and around the odontoid. Postoperative MRI showed that a gross-total resection was achieved. The patient had no neurologic deficits postoperatively. Pathologic examination revealed a chordoma of the classical type. Fig. 2 Illustration of the endoscopic endonasal surgical technique. ( A ) It shows the surgical route (blue arrow), and location of the heart-shaped mucosal flap that was made in the upper nasopharynx (blue crescent). This figure highlights that angled endoscopes are needed to visualize the relevant operative field (yellow translucent triangle). ( B ) shows the axial view, ( C ) shows an intraoperative endoscopic view of the incision performed to achieve a heart-shaped mucosal flap, as was utilized during this case, and ( D ) shows the coronal view. ( B and D ) They show the results of postoperative image analysis, during which we segmented the drill cavity (in blue) and projected it on the preoperative CT scan of the patient. Note that besides the inferior clivus, the superior part of the ring of C1 was also drilled slightly to reach the tumor in the odontoid. CT, computed tomography. Conclusion An endoscopic endonasal approach, utilizing the heart-shaped flap and angled endoscopes and instruments, can be considered for resection of select cases of craniocervical junction chordoma with limited lateral expansion. The link to the video can be found at: https://youtu.be/rwVoZJRBIEo .

Anterolateral Approach with Endoscopic Assistance for Resection of a Craniovertebral Junction Chordoma.

Craniovertebral junction chordomas can represent a surgical challenge, especially when intradural extension and contact with neurovascular structures is involved. To date, there is still controversy on the choice of optimal surgical corridor for such lesions, with endoscopic endonasal, far lateral and anterolateral corridors being those most commonly used. In this operative video, we present a case of craniovertebral junction chordoma with significant bone destruction and intradural extension ( Fig. 1 ). The tumor was safely removed using an anterolateral approach with transposition of the vertebral artery to gain access to the lateral craniovertebral junction. The endoscope is demonstrated to help with intradural tumor removal, providing a wide angle of view through a relatively narrow dural opening ( Fig. 2 ). In this video, nuances of the anterolateral approach, chordoma removal strategies and closure technique are presented in detail. A gross total resection was achieved, and the postoperative course was uneventful. In summary, the anterolateral approach with endoscopic assistance can offer a safe and effective corridor for the surgical management of craniovertebral junction chordomas. The link to the video can be found at: https://youtu.be/pC0YxKgNoMY .

Cognitive functioning in patients with nonfunctioning pituitary adenoma before and after endoscopic endonasal transsphenoidal surgery.

OBJECTIVE: Patients with nonfunctioning pituitary adenomas (NFPAs) can suffer from cognitive dysfunction. However, the literature on longitudinal cognitive follow-up of patients undergoing endoscopic endonasal transsphenoidal surgery (EETS) is limited. This study was performed to investigate perioperative cognitive status and course in patients with NFPAs. METHODS: Patients underwent computerized neuropsychological assessment 1 day before (n = 45) and 3 months after (n = 36) EETS. Performance in 7 domains was measured with a computerized test battery (CNS Vital Signs) and standardized using data from a healthy control group. The authors conducted analyses of cognitive performance at both time points and changes pre- to post-ETSS on a group and an individual level. Linear multiple regression analyses were employed to investigate predictors of cognitive performance. RESULTS: On average, patients scored significantly lower in 6 of 7 cognitive domains before and after surgery than controls. Impairment proportions were significantly higher among patients (56% before surgery, 63% after surgery) than among controls. Patients showed no change over time in group-level (mean) performance, but 28% of individual patients exhibited cognitive improvement and 28% exhibited cognitive decline after surgery. Hormonal deficiency showed a positive correlation with verbal memory before surgery. Postoperative performances in all cognitive domains were predicted by preoperative performances. CONCLUSIONS: Cognitive impairment was present before and after EETS in over half of NFPA patients. Individual patients showed diverse postoperative cognitive courses. Monitoring of cognitive functioning in clinical trajectories and further identification of disease-related and psychological predictors of cognition are warranted.

Implications of Extracranial Distortion in Ultra-High-Field Magnetic Resonance Imaging for Image-Guided Cranial Neurosurgery.

BACKGROUND: Ultra-high-field magnetic resonance imaging (MRI) of the brain is attractive for image guidance during neurosurgery because of its high tissue contrast and detailed vessel visualization. However, high-field MRI is prone to distortion artifacts, which may compromise image guidance. Here we investigate intra- and extracranial distortions in 7-T MRI scans. METHODS: Five patients with and 5 patients without skin-adhesive fiducials received magnetization-prepared T1-weighted 7-T MRI and standard 3-T MRI scans. The 7- and 3-T images were rigidly coregistered and compared. Intracranial distortions were evaluated qualitatively, whereas shifts at the skin surface and shifts of the center positions of skin-adhesive fiducials were measured quantitatively. Moreover, we present an illustrative case of an ultra-high-field image-guided skull base meningioma resection. RESULTS: We found excellent intracranial correspondence between 3- and 7-T MRI scans. However, the average maximum skin shift was 6.8 ± 2.0 mm in group A and 5.2 ± 0.9 mm in group B. The average maximum difference between the skin-adhesive fiducial positions was 5.6 ± 3.1 mm in group B. In our tumor resection case, the meningioma blood supply could be targeted early thanks to 7-T image guidance, which made subsequent tumor removal straightforward. CONCLUSIONS: There are no visible intracranial distortions in magnetization-prepared T1-weighted 7-T MRI cranial images. However, we found considerable extracranial shifts. These shifts render 7-T images unreliable for patient-to-image registration. We recommend performing patient-to-image registration on a routine (computed tomography scan or 3-T magnetic resonance) image and subsequently fusing the 7-T magnetic resonance image with the routine image on the image guidance machine, until this issue is resolved.

Benchmarking Distance Control and Virtual Drilling for Lateral Skull Base Surgery.

BACKGROUND: Novel audiovisual feedback methods were developed to improve image guidance during skull base surgery by providing audiovisual warnings when the drill tip enters a protective perimeter set at a distance around anatomic structures ("distance control") and visualizing bone drilling ("virtual drilling"). OBJECTIVE: To benchmark the drill damage risk reduction provided by distance control, to quantify the accuracy of virtual drilling, and to investigate whether the proposed feedback methods are clinically feasible. METHODS: In a simulated surgical scenario using human cadavers, 12 unexperienced users (medical students) drilled 12 mastoidectomies. Users were divided into a control group using standard image guidance and 3 groups using distance control with protective perimeters of 1, 2, or 3 mm. Damage to critical structures (sigmoid sinus, semicircular canals, facial nerve) was assessed. Neurosurgeons performed another 6 mastoidectomy/trans-labyrinthine and retro-labyrinthine approaches. Virtual errors as compared with real postoperative drill cavities were calculated. In a clinical setting, 3 patients received lateral skull base surgery with the proposed feedback methods. RESULTS: Users drilling with distance control protective perimeters of 3 mm did not damage structures, whereas the groups using smaller protective perimeters and the control group injured structures. Virtual drilling maximum cavity underestimations and overestimations were 2.8 ± 0.1 and 3.3 ± 0.4 mm, respectively. Feedback methods functioned properly in the clinical setting. CONCLUSION: Distance control reduced the risks of drill damage proportional to the protective perimeter distance. Errors in virtual drilling reflect spatial errors of the image guidance system. These feedback methods are clinically feasible.

Amide proton transfer (APT) imaging of brain tumors at 7 T: The role of tissue water T1 -Relaxation properties.

PURPOSE: To provide insight into the effect of water T1 relaxation (T1wat ) on amide proton transfer (APT) contrast in tumors. Three different metrics of APT contrast-magnetization transfer ratio (MTRRex ), relaxation-compensated MTRRex (AREX), and traditional asymmetry (MTRasym )-were compared in normal and tumor tissues in a variety of intracranial tumors at 7 Tesla (T). METHODS: Six consented intracranial tumor patients were scanned using a low-power, three-dimensional (3D) APT imaging sequence. MTRRex and MTRasym were calculated in the region of 3 to 4 ppm. AREX was calculated by T1wat correction of MTRRex . Tumor tissue masks, which classify different tumor tissues, were drawn by an experienced neuroradiologist. ROI-averaged tumor tissue analysis was done for MTRRex , AREX, and MTRasym . RESULTS: MTRRex and MTRasym were slightly elevated in tumor-associated structures. Both metrics were positively correlated to T1wat . The correlation coefficient (R) was determined to be 0.88 (P < 0.05) and 0.92 (P << 0.05) for MTRRex and MTRasym , respectively. After T1wat correction (R = -0.21, P = 0.69), no difference between normal and tumor tissues was found for AREX. CONCLUSIONS: The strong correlation of MTRRex and MTRasym with T1wat and the absence thereof in AREX suggests that much of APT contrast in tumors for the low-power, 3D-acquisition scheme at 7 T originates from the inherent tissue water T1 -relaxation properties. Magn Reson Med 77:1525-1532, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Surgical instrument tracking optimizes trans-sphenoidal endoscopic treatment of petrous apex cholesterol granuloma.

During endoscopic trans-sphenoidal treatment of petrous apex cholesterol granuloma, the challenge for the surgeon is to drill the posterior wall of the sphenoid sinus to reach the lesion while attempting to avoid the internal carotid artery (ICA). A refined neuronavigation technique is presented that diminishes bonework needed for exposure and marsupialization, and simultaneously minimizes risks of accidental harm to the ICA. The technique utilizes real-time intraoperative instrument tracking of a drill, enabling safe creation of a direct canal toward the cyst just medial to the paraclival ICA and of a curette for entirely image-guided marsupialization of the cyst's deep areas through the canal.

Validation of exposure visualization and audible distance emission for navigated temporal bone drilling in phantoms.

BACKGROUND: A neuronavigation interface with extended function as compared with current systems was developed to aid during temporal bone surgery. The interface, named EVADE, updates the prior anatomical image and visualizes the bone drilling process virtually in real-time without need for intra-operative imaging. Furthermore, EVADE continuously calculates the distance from the drill tip to segmented temporal bone critical structures (e.g. the sigmoid sinus and facial nerve) and produces audiovisual warnings if the surgeon drills in too close vicinity. The aim of this study was to evaluate the accuracy and surgical utility of EVADE in physical phantoms. METHODOLOGY/PRINCIPAL FINDINGS: We performed 228 measurements assessing the position accuracy of tracking a navigated drill in the operating theatre. A mean target registration error of 1.33±0.61 mm with a maximum error of 3.04 mm was found. Five neurosurgeons each drilled two temporal bone phantoms, once using EVADE, and once using a standard neuronavigation interface. While using standard neuronavigation the surgeons damaged three modeled temporal bone critical structures. No structure was hit by surgeons utilizing EVADE. Surgeons felt better orientated and thought they had improved tumor exposure with EVADE. Furthermore, we compared the distances between surface meshes of the virtual drill cavities created by EVADE to actual drill cavities: average maximum errors of 2.54±0.49 mm and -2.70±0.48 mm were found. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that EVADE gives accurate feedback which reduces risks of harming modeled critical structures compared to a standard neuronavigation interface during temporal bone phantom drilling.

Determination of a facial nerve safety zone for navigated temporal bone surgery.

BACKGROUND: Transtemporal approaches require surgeons to drill the temporal bone to expose target lesions while avoiding the critical structures within it, such as the facial nerve and other neurovascular structures. We envision a novel protective neuronavigation system that continuously calculates the drill tip-to-facial nerve distance intraoperatively and produces audiovisual warnings if the surgeon drills too close to the facial nerve. Two major problems need to be solved before such a system can be realized. OBJECTIVE: To solve the problems of (1) facial nerve segmentation and (2) calculating a safety zone around the facial nerve in relation to drill-tip tracking inaccuracies. METHODS: We developed a new algorithm called NerveClick for semiautomatic segmentation of the intratemporal facial nerve centerline from temporal bone computed tomography images. We evaluated NerveClick's accuracy in an experimental setting of neuro-otologic and neurosurgical patients. Three neurosurgeons used it to segment 126 facial nerves, which were compared with the gold standard: manually segmented facial nerve centerlines. The centerlines are used as a central axis around which a tubular safety zone is built. The zone's thickness incorporates the drill tip tracking errors. The system will warn when the tracked tip crosses the safety zone. RESULTS: Neurosurgeons using NerveClick could segment facial nerve centerlines with a maximum error of 0.44 ± 0.23 mm (mean ± standard deviation) on average compared with manual segmentations. CONCLUSION: Neurosurgeons using our new NerveClick algorithm can robustly segment facial nerve centerlines to construct a facial nerve safety zone, which potentially allows timely audiovisual warnings during navigated temporal bone drilling despite tracking inaccuracies.

Association of schizophrenia in 22q11.2 deletion syndrome and gray matter volumetric deficits in the superior temporal gyrus.

OBJECTIVE: Individuals with 22q11.2 deletion syndrome are known to be at high risk of developing schizophrenia. Previous imaging studies have provided limited data on the relation of schizophrenia expression in 22q11.2 deletion syndrome to specific regional brain volumetric changes. The authors hypothesized that the main structural brain finding associated with schizophrenia expression in 22q11.2 deletion syndrome, as for schizophrenia in the general population, would be gray matter volumetric deficits, especially in the temporal lobes. METHOD: MR brain images from 29 patients with 22q11.2 deletion syndrome and schizophrenia and 34 comparison subjects with 22q11.2 deletion syndrome and no history of psychosis were analyzed using a voxel-based morphometry method that also yielded volumes for related region-of-interest analyses. The authors compared data from the two groups using an analysis of covariance model correcting for total intracranial volume, age, sex, IQ, and history of congenital cardiac defects. The false discovery rate threshold was set at 0.05 to account for multiple comparisons. RESULTS: Voxel-based morphometry analyses identified significant gray matter reductions in the left superior temporal gyrus (Brodmann's area 22) in the schizophrenia group. There were no significant between-group differences in white matter or CSF volumes. Region-of-interest analyses showed significant bilateral gray matter volume reductions in the temporal lobes and superior temporal gyri in the schizophrenia group. CONCLUSIONS: The structural brain expression of schizophrenia associated with the highly penetrant 22q11.2 deletion involves lower gray matter volumes in temporal lobe regions. These structural MRI findings in a 22q11.2 deletion syndrome form of schizophrenia are consistent with those from studies involving schizophrenia samples from the general population. The results provide further support for 22q11.2 deletion syndrome as a genetic subtype and as a useful neurodevelopmental model of schizophrenia.

Skull base tumor model.

OBJECT: Resident duty-hours restrictions have now been instituted in many countries worldwide. Shortened training times and increased public scrutiny of surgical competency have led to a move away from the traditional apprenticeship model of training. The development of educational models for brain anatomy is a fascinating innovation allowing neurosurgeons to train without the need to practice on real patients and it may be a solution to achieve competency within a shortened training period. The authors describe the use of Stratathane resin ST-504 polymer (SRSP), which is inserted at different intracranial locations to closely mimic meningiomas and other pathological entities of the skull base, in a cadaveric model, for use in neurosurgical training. METHODS: Silicone-injected and pressurized cadaveric heads were used for studying the SRSP model. The SRSP presents unique intrinsic metamorphic characteristics: liquid at first, it expands and foams when injected into the desired area of the brain, forming a solid tumorlike structure. The authors injected SRSP via different passages that did not influence routes used for the surgical approach for resection of the simulated lesion. For example, SRSP injection routes included endonasal transsphenoidal or transoral approaches if lesions were to be removed through standard skull base approach, or, alternatively, SRSP was injected via a cranial approach if the removal was planned to be via the transsphenoidal or transoral route. The model was set in place in 3 countries (US, Italy, and The Netherlands), and a pool of 13 physicians from 4 different institutions (all surgeons and surgeons in training) participated in evaluating it and provided feedback. RESULTS: All 13 evaluating physicians had overall positive impressions of the model. The overall score on 9 components evaluated--including comparison between the tumor model and real tumor cases, perioperative requirements, general impression, and applicability--was 88% (100% being the best possible achievable score where the evaluator strongly agreed with the proposed factor). Individual components had scores at or above 80% (except for 1). The only score that was below 80% was related to radiographic visibility of the model for adequate surgical planning (score of 74%). The highest score was given to usefulness in neurosurgical training (98%). CONCLUSIONS: The skull base tumor model is an effective tool to provide more practice in preoperative planning and technical skills.