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Attrition rates in neurosurgery residency

surgeons

J Neurosurg 122:240–249, 2015

The objective of this study is to determine neurosurgery residency attrition rates by sex of matched applicant and by type and rank of medical school attended.

Methods The study follows a cohort of 1361 individuals who matched into a neurosurgery residency program through the SF Match Fellowship and Residency Matching Service from 1990 to 1999. The main outcome measure was achievement of board certification as documented in the American Board of Neurological Surgery Directory of Diplomats. A secondary outcome measure was documentation of practicing medicine as verified by the American Medical Association DoctorFinder and National Provider Identifier websites. Overall, 10.7% (n = 146) of these individuals were women. Twenty percent (n = 266) graduated from a top 10 medical school (24% of women [35/146] and 19% of men [232/1215], p = 0.19). Forty-five percent (n = 618) were graduates of a public medical school, 50% (n = 680) of a private medical school, and 5% (n = 63) of an international medical school. At the end of the study, 0.2% of subjects (n = 3) were deceased and 0.3% (n = 4) were lost to follow-up.

Results The total residency completion rate was 86.0% (n = 1171) overall, with 76.0% (n = 111/146) of women and 87.2% (n = 1059/1215) of men completing residency. Board certification was obtained by 79.4% (n = 1081) of all individuals matching into residency between 1990 and 1999. Overall, 63.0% (92/146) of women and 81.3% (989/1215) of men were board certified. Women were found to be significantly more at risk (p < 0.005) of not completing residency or becoming board certified than men. Public medical school alumni had significantly higher board certification rates than private and international alumni (82.2% for public [508/618]; 77.1% for private [524/680]; 77.8% for international [49/63]; p < 0.05). There was no significant difference in attrition for graduates of top 10–ranked institutions versus other institutions. There was no difference in number of years to achieve neurosurgical board certification for men versus women.

Conclusions Overall, neurosurgery training attrition rates are low. Women have had greater attrition than men during and after neurosurgery residency training. International and private medical school alumni had higher attrition than public medical school alumni.

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Brain surface reformatted imaging (BSRI) for intraoperative neuronavigation in brain tumor surgery

Brain surface reformatted imaging (BSRI) for intraoperative neuronavigation in brain tumor surgery

Acta Neurochir (2015) 157:265–274

For safe resection of lesions situated in or near eloquent brain regions, determination of their spatial and functional relationship is crucial. Since functional magnetic resonance imaging and intraoperative neurophysiological mapping are not available in all neurosurgical departments, we aimed to evaluate brain surface reformatted imaging (BSRI) as an additional display mode for neuronavigation.

Methods Eight patients suffering from perirolandic tumors were preoperatively studied withMRI and navigated transcranial magnetic stimulation (nTMS). Afterwards, the MRI was automatically transformed into BSR images in neuronavigation software (Brainlab, Brainlab AG, Feldkirchen, Germany). One experienced neuroradiologist, one experienced neurosurgeon, and two residents determined hand representation areas ipsilateral to each tumor on two-dimensional (2D) MR images and on BSR images. All results were compared to results from intraoperative direct cortical mapping of the hand motor cortex and to preoperative nTMS results.

Results Findings from nTMS and intraoperative direct cortical mapping of the hand motor cortex were congruent in all cases. Hand representation areas were correctly determined on BSR images in 81.3%and on 2D-MR images in 93.75%(p= 0.26). In a subgroup analysis, experienced observers showed more familiarity with BSRI than residents (96.9 vs. 84.4 % correct results, p=0.19), with an equal error rate for 2D-MRI. The time required to define hand representation areas was significantly shorter using BSRI than using standard MRI (mean 27.4 vs. 40.4 s, p=0.04).

Conclusions With BSRI, a new method for neuronavigation is now available, allowing fast and easy intraoperative localization of distinct brain regions.

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A treatment paradigm for high-grade brain arteriovenous malformations: volume-staged radiosurgical downgrading followed by microsurgical resection

A treatment paradigm for high-grade brain arteriovenous malformations- volume-staged radiosurgical downgrading followed by microsurgical resection

J Neurosurg 122:419–432, 2015

The surgical treatment of many large arteriovenous malformations (AVMs) is associated with substantial risks, and many are considered inoperable. Furthermore, AVMs larger than 3 cm in diameter are not usually treated with conventional single-session radiosurgery encompassing the entire AVM volume. Volume-staged stereotactic radiosurgery (VS-SRS) is an option for large AVMs, but it has mixed results. The authors report on a series of patients with highgrade AVMs who underwent multiple VS-SRS sessions with resultant downgrading of the AVMs, followed by resection.

Methods. A cohort of patients was retrieved from a single-institution AVM patient registry consisting of prospectively collected data. VS-SRS was performed as a planned intentional treatment. Surgery was considered as salvage therapy in select patients.

Results Sixteen AVMs underwent VS-SRS followed by surgery. Four AVMs presented with rupture. The mean patient age was 25.3 years (range 13–54 years). The average initial Spetzler-Martin grade before any treatment was 4, while the average supplemented Spetzler-Martin grade (Spetzler-Martin plus Lawton-Young) was 7.1. The average AVM size in maximum dimension was 5.9 cm (range 3.3–10 cm). All AVMs were supratentorial in location and all except one were in eloquent areas of the brain, with 7 involving primary motor cortex. The mean number of VS-SRS sessions was 2.7 (range 2–5 sessions). The mean interval between first VS-SRS session and resection was 5.7 years. There were 4 hemorrhages that occurred after VS-SRS. The average Spetzler-Martin grade was reduced to 2.5 (downgrade, -1.5) and the average supplemented Spetzler-Martin grade was reduced to 5.6 (downgrade, -1.5). The maximum AVM size was reduced to an average of 3.0 cm (downsize = -2.9 cm). The mean modified Rankin Scale (mRS) scores were 1.2, 2.3, and 2.2 before VS-SRS, before surgery, and at last follow-up, respectively (mean follow-up, 6.9 years). Fifteen AVMs were cured after surgery. Ten patients had good outcomes at last follow-up (7 with mRS Score 0 or 1, and 3 with mRS Score 2). There were 2 deaths (both mRS Score 1 before treatment) and 4 patients with mRS Score 3 outcome (from mRS Scores 0, 1, and 2 [n = 2]).

Conclusions Volume-staged SRS can downgrade AVMs, transforming high-grade AVMs (initially considered inoperable) into operable AVMs with acceptable surgical risks. This treatment paradigm offers an alternative to conservative observation for young patients with unruptured AVMs and long life expectancy, where the risk of hemorrhage is substantial. Difficult AVMs were cured in 15 patients. Surgical morbidity associated with downgraded AVMs is reduced to that of postradiosurgical/preoperative supplemented Spetzler-Martin grades, not their initial AVM grades.

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Linear array ultrasound in low-grade glioma surgery: histology-based assessment of accuracy in comparison to conventional intraoperative ultrasound and intraoperative MRI

Linear array ultrasound in low-grade glioma surgery

Acta Neurochir (2015) 157:195–206

In low-grade glioma (LGG) surgery, intraoperative differentiation between tumor and most likely tumor-free brain tissue can be challenging. Intraoperative ultrasound can facilitate tumor resection. The aim of this study is to evaluate the accuracy of linear array ultrasound in comparison to conventional intraoperative ultrasound (cioUS) and intraoperative high-field MRI (iMRI).

Methods We prospectively enrolled 13 patients harboring a LGG of WHO Grade II. After assumed near total removal, a resection control was performed using navigated cioUS, navigated lioUS, and iMRI. We harvested 30 navigated biopsies from the resection cavity and compared the histopathological findings with the respective imaging results. Spearman’s rho was calculated to test for significant correlations. Sensitivity and specificity as well as receiver operating characteristics (ROC) were calculated to assess test performance of each imaging modality.

Results Imaging results of lioUS correlated significantly (p<0.009) with iMRI. Both iMRI and lioUS correlated significantly with final histopathological diagnosis (p<0.006, p<0.014). cioUS did not correlate with other imaging findings or with final diagnosis. The highest sensitivity for residual tumor detection was found in iMRI (83 %), followed by lioUS (79 %). The sensitivity of cioUS was only 21 %. Specificity was highest in cioUS (100 %), whereas iMRI and lioUS both achieved 67 %. ROC curves showed fair results for iMRI and lioUS and a poor result for cioUS.

Conclusions Intraoperative resection control in LGGs using lioUS reaches a degree of accuracy close to iMRI. Test results of lioUS are superior to cioUS. cioUS often fails to discriminate solid tumors from “normal” brain tissue during resection control. Only in lesions <10 cc cioUS does show good accuracy.

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Volumetric CT analysis as a predictor of seizure outcome following temporal lobectomy

Volumetric brain analysis in neurosurgery- Part 3

J Neurosurg Pediatr 15:133–143, 2015

The incidence of temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (MTS) can be high in developing countries. Current diagnosis of MTS relies on structural MRI, which is generally unavailable in developing world settings. Given widespread effects on temporal lobe structure beyond hippocampal atrophy in TLE, the authors propose that CT volumetric analysis can be used in patient selection to help predict outcomes following resection.

METHODS Ten pediatric patients received preoperative CT scans and temporal resections at the CURE Children’s Hospital of Uganda. Engel classification of seizure control was determined 12 months postoperatively. Temporal lobe volumes were measured from CT and from normative MR images using the Cavalieri method. Whole brain and fluid volumes were measured using particle filter segmentation. Linear discrimination analysis (LDA) was used to classify seizure outcome by temporal lobe volumes and normalized brain volume.

RESULTS Epilepsy patients showed normal to small brain volumes and small temporal lobes bilaterally. A multivariate measure of the volume of each temporal lobe separated patients who were seizure free (Engel Class IA) from those with incomplete seizure control (Engel Class IB/IIB) with LDA (p < 0.01). Temporal lobe volumes also separate normal subjects, patients with Engel Class IA outcomes, and patients with Class IB/IIB outcomes (p < 0.01). Additionally, the authors demonstrated that age-normalized whole brain volume, in combination with temporal lobe volumes, may further improve outcome prediction (p < 0.01).

CONCLUSIONS This study shows strong evidence that temporal lobe and brain volume can be predictive of seizure outcome following temporal lobe resection, and that volumetric CT analysis of the temporal lobe may be feasible in lieu of structural MRI when the latter is unavailable. Furthermore, since the authors’ methods are modality independent, these findings suggest that temporal lobe and normative brain volumes may further be useful in the selection of patients for temporal lobe resection when structural MRI is available.

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Effects of Hematoma Reduction by Stereotactic Aspiration for Patients With Spontaneous Intracerebral Hemorrhage

Effects of Hematoma Reduction by Stereotactic Aspiration for Patients With Spontaneous Intracerebral Hemorrhage

Neurosurg Q 2015;25:17–23

Spontaneous intracerebral hemorrhage (ICH) is a devastating medical condition associated with significant morbidity and mortality. Whether the hematoma should be surgically removed remains controversial. This study was a retrospective analysis of patients with spontaneous ICH who were treated with computed tomography (CT)-guided stereotactic aspiration. The aim of this study was to investigate whether hematoma volume reduction in deep-seated ICH utilizing this minimally invasive surgical procedure improves clinical outcome.

Methods: Ninety-nine patients who suffered spontaneous ICH provided informed consent and were included in the study. Patients were divided into an operated group that underwent CT-guided stereotactic aspiration, and a nonoperated group that received only medical treatment. CT-guided stereotactic aspiration was performed at least 8 hours after onset of ICH. Using the Leksell stereotactic frame for guidance, a 4-mm-diameter catheter was inserted into the body of the hematoma through a frontal burr hole. Glasgow Coma Scale, motor function, and length of hospital stay were used to assess differences in outcomes between the 2 groups. The correlation between clinical outcome and stereotactic aspiration was evaluated using multivariate regression analysis.

Results: Ninety-nine consecutive patients were entered into this study. Patients in the operated group (n=41) were treated with CT-guided stereotactic hematoma aspiration. The 3-month Glasgow Outcome Scale score in the nonoperated group (n=58) was significantly lower than that in the operated group (2.32±1.26 vs. 3.15±1.33, P<0.001). Patients in the operated group experienced greater motor function recovery than those in the nonoperated group. The average length of hospital stay of the operated group was significantly shorter than that of the nonoperated group (31.2±14.6 vs. 41.7±17.2 d, P=0.002).

Conclusions: Stereotactic aspiration may improve the functional outcome and shorten the hospital stay of patients who have suffered spontaneous ICH. This procedure is minimally invasive and shows promise as a safe and effective treatment method for these patients.

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Is atlantoaxial instability the cause of Chiari malformation? Outcome analysis of 65 patients treated by atlantoaxial fixation

Is atlantoaxial instability the cause of Chiari malformation?

J Neurosurg Spine 22:116–127, 2015

Understanding that atlantoaxial instability is the cause of Chiari malformation (CM), the author treated 65 patients using atlantoaxial stabilization. The results are analyzed.

Methods Cases of CM treated using atlantoaxial fixation during the period from January 2010 to November 2013 were reviewed and analyzed. Surgery was aimed at segmental arthrodesis.

Results The author treated 65 patients with CM in the defined study period. Fifty-five patients had associated syringomyelia. Forty-six patients had associated basilar invagination. Thirty-seven patients had both basilar invagination and syringomyelia. Three patients had been treated earlier using foramen magnum decompression and duraplasty. According to the extent of their functional capabilities, patients were divided into 5 clinical grades. On the basis of the type of facetal alignment and atlantoaxial instability, the patients were divided into 3 groups. Type I dislocation (17 patients) was anterior atlantoaxial instability wherein the facet of the atlas was dislocated anterior to the facet of the axis. Type II dislocation (31 patients) was posterior atlantoaxial instability wherein the facet of the atlas was dislocated posterior to the facet of the axis. Type III dislocation (17 patients) was the absence of demonstrable facetal malalignment and was labeled as “central” atlantoaxial dislocation. In 18 patients, dynamic images showed vertical, mobile and at-least partially reducible atlantoaxial dislocation. All patients were treated with atlantoaxial plate and screw fixation using techniques described in 1994 and 2004. Foramen magnum decompression or syrinx manipulation was not performed in any patient. Occipital bone and subaxial spinal elements were not included in the fixation construct. One patient died, and death occurred in the immediate postoperative phase and was related to a vertebral artery injury incurred during the operation. One patient had persistent symptoms. In the rest of the patients there was gratifying clinical improvement. More remarkably, in 7 patients, the symptoms of lower cranial nerve paresis improved. No patient worsened in their neurological function after surgery. Reductions in the size of the syrinx and regression of the CM were observed in 6 of 11 cases in which postoperative MRI was possible. During the follow-up period, there was no delayed worsening of neurological function or symptoms in any patient. Sixty-three patients improved after surgery, and the improvement was sustained during the average follow-up period of 18 months.

Conclusions On the basis of outcomes in this study, it appears that the pathogenesis of CM with or without associated basilar invagination and/or syringomyelia is primarily related to atlantoaxial instability. The data suggest that the surgical treatment in these cases should be directed toward atlantoaxial stabilization and segmental arthrodesis. Except in cases in which there is assimilation of the atlas, inclusion of the occipital bone is neither indicated nor provides optimum stability. Foramen magnum decompression is not necessary and may be counter-effective in the long run.

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Microvascular decompression under neuroendoscopic view in hemifacial spasm

Microvascular decompression under neuroendoscopic view in hemifacial spasm

Acta Neurochir (2015) 157:329–332

We report microvascular decompression (MVD) under neuroendoscopic view in hemifacial spasm (HFS) patients with rostral- and perforator-type compression of the root exit zone (REZ) of the facial nerve.

Using either a wireless iPad Mini as a monitor on the microscope or a high-resolution monitor, microscopic and endoscopic views enabled MVD for complete cure of HFS with rostral-type compression (the offender compressing the REZ on the opposite rostral side to the operative approach) or perforator-type compression (the offender tethered to the REZ by the perforator).

MVD under neuroendoscopic view may offer more accurate MVD and complete resolution of HFS.

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Anatomic features of glioblastoma and their potential impact on survival

Anatomic features of glioblastoma and their potential impact on survival

Acta Neurochir (2015) 157:179–186

Many reports on glioblastoma multiforme discuss the prognostic impact of anatomical features such as cysts, necrotic changes, extent of edema or subependymal spread of tumor cells. In the present study, we examined different growth patterns and their possible relations to patient survival.

Methods To analyze whether anatomical characteristics are related to prognosis, we reviewed the prospectively collected pre- and postoperative MRIs of 83 patients in the 5-ALA study, provided by the 5-ALA Glioma Study Group. Following a standardized analytic work flow, the tumor volume and site, presence of necrosis or cysts, and perifocal edema were assessed preoperatively. In the same way, postoperative MRI and the MRI at first recurrence were analyzed. In addition, survival time of the patients was documented.

Results Median survival time of all 83 patients was 15.1 months (range 1.5 to 70.1, mean 18). The site or volume of glioblastoma, as well as the presence of intratumoral necrosis or cysts, did not exert a significant effect on survival time; 96.4 % of recurrences occurred within the former resection margin. Tumors with initial contact with the subependymal zone had multifocal or ventricular recurrences significantly more often. In patients with residual tumor on early postoperative MRI, the follow-up images displayed enlargement of the remnants in 91.9 % of these cases.

Conclusions A merely anatomical analysis of the glioblastoma growth pattern cannot reliably provide prognostic information. The occurrence of most recurrences next to the resection margin and the high percentage of growing residual tumors underline the importance of complete resections.

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Incidence and Clinical Implications of Carotid Branch Occlusion Following Treatment of Internal Carotid Artery Aneurysms With the Pipeline Embolization Device

Incidence and Clinical Implications of Carotid Branch Occlusion Following Treatment of Internal Carotid Artery Aneurysms With the Pipeline Embolization Device

Neurosurgery 76:173–178, 2015

The use of flow diverters such as the pipeline embolization device (PED) for treatment of intracranial aneurysms carries the risk of side branch occlusion.

OBJECTIVE: To determine the incidence and clinical outcomes associated with supraclinoid internal carotid artery (ICA) branch occlusion after deployment of PEDs for ICA aneurysms.

METHODS: We reviewed patients who underwent endovascular treatment with PEDs for ICA aneurysms between June 2011 and March 2013. Forty-nine patients (43 women, mean age 56.36 1.8 years, 68 aneurysms) in whom PEDs traversed the origin of supraclinoid ICA branches (ophthalmic [OA], posterior communicating [PcommA], and anterior choroidal artery [AChA]) were selected for this study. Follow-up angiograms (mean follow-up, 12.8 6 0.8 months) were studied to determine the location of PEDs and the patency of ICA branches.

RESULTS: PEDs were placed across the ostia of 49 OAs, 14 PcommAs, and 11 AChAs. Multiple PEDs were deployed in 16 patients. Rate of branch occlusion was 4% (2/49) for the OA, 7.1% (1/14) for the PcommA, and 0% for the AChA. Patients with branch occlusion did not endure new neurological deficits. ICA branch occlusion was not associated with the number of PEDs covering the ostia (P = .76) or the origin of ICA branches from the aneurysm (P = .24).

CONCLUSION: The incidence of major supraclinoid ICA branch occlusion after treatment with PEDs was low. These events were not associated with new neurological deficits nor were they related to the number of PEDs deployed or the origin of ICA branches from the aneurysm.

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Intraoperative 3D imaging control during subthalamic Deep Brain Stimulation procedures using O-arm® technology

Intraoperative 3D imaging control during subthalamic Deep Brain Stimulation procedures using O-arm® technology- Experience in 15 patients

Neurochirurgie 60(2014)276–282

O-arm® now gives us the opportunity not only to perform 2D but also 3D scans during deep brain stimulation (DBS) procedures. We present our experience with the intraoperative use of this device. Our objective was to measure the geometrical accuracy of electrode placement during surgical procedures driven under O-arm® control.

Methods. Fifteen patients underwent STN-DBS.  For  the first 4 patients, 3D  scans were performed at the end of the procedure. We  calculated the accuracy of electrode positioning, i.e. the distance between final electrode positioning and the planned trajectory. For  the next 11  patients, who underwent both intraoperative and final 3D scan, we also calculated the accuracy of the microelectrode positioning.

Results. Average stimulation-induced improvement of UPDRS-III  score was 52.5 ± 15%. For  the first 4 patients, the mean electrode positioning accuracy was 1.46 ± 0.56 mm. For the 11  patients who underwent intraoperative 3D scan, the mean microelectrodes positioning accuracy was 1.59 ± 1.1 mm. Aberrant positioning was detected in two cases, and was analyzed by fusing 3D scan with preoperative MR images. The definite electrodes positioning accuracy was 1.05 ± 0.54 mm.

Conclusion. Intraoperative 3D scan is feasible, and can help us detect and correct early aberrant trajectories.

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Frameless robotic stereotactic biopsies: a consecutive series of 100 cases

Frameless robotic stereotactic biopsies- a consecutive series of 100 cases

J Neurosurg 122:342–352, 2015

Stereotactic biopsy procedures are an everyday part of neurosurgery. The procedure provides an accurate histological diagnosis with the least possible morbidity. Robotic stereotactic biopsy needs to be an accurate, safe, frameless, and rapid technique. This article reports the clinical results of a series of 100 frameless robotic biopsies using a Medtech ROSA device.

Methods The authors retrospectively analyzed their first 100 frameless stereotactic biopsies performed with the robotic ROSA device: 84 biopsies were performed by frameless robotic surface registration, 7 were performed by robotic bone fiducial marker registration, and 9 were performed by scalp fiducial marker registration. Intraoperative flat-panel CT scanning was performed concomitantly in 25 cases. The operative details of the robotic biopsies, the diagnostic yield, and mortality and morbidity data observed in this series are reported.

Results A histological diagnosis was established in 97 patients. No deaths or permanent morbidity related to surgery were observed. Six patients experienced transient neurological worsening. Six cases of bleeding within the lesion or along the biopsy trajectory were observed on postoperative CT scans but were associated with transient clinical symptoms in only 2 cases. Stereotactic surgery was performed with patients in the supine position in 93 cases and in the prone position in 7 cases. The use of fiducial markers was reserved for posterior fossa biopsy via a transcerebellar approach, via an occipital approach, or for pediatric biopsy.

Conclusions ROSA frameless stereotactic biopsies appear to be accurate and safe robotized frameless procedures.

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Combined use of 18 F-FDG PET and corticosteroid for diagnosis of deep-seated primary central nervous system lymphoma without histopathological confirmation

Combined use of 18 F-FDG PET and corticosteroid for diagnosis of deep-seated primary central nervous system lymphoma without histopathological confirmation

Acta Neurochir (2015) 157:187–194

Although histological diagnosis is indispensable in treating primary central nervous system lymphoma (PCNSL), we sometimes face an intractable situation in which tissue can be obtained only from a deep-seated brain lesion. In place of a histological diagnosis, the diagnostic adequacy of the combined use of 18 F-FDG PET and corticosteroid administration for PCNSL located in a deep-seated brain structure is reported.

Methods Patients with a deep-seated tumor were treated as having PCNSL without histological confirmation, based on the following criteria: (1) there was no evidence of systemic malignancy; (2) the tumor showed an extremely high FDG uptake relative to normal gray matter on pretreatment 18 FFDG PET;

(3) the tumor decreased in size 1 week after diagnostic therapy by corticosteroid administration on contrast-enhanced T1-weighted magnetic resonance imaging (MRI). FDG uptake of the lesion was evaluated by the maximum of standardized uptake values (SUVmax) and tumor-tonormal ratio of the SUV (T/N ratio). The extent of the tumor reduction was calculated by volumetric analysis for the treatment response to corticosteroid administration.

Results Ten patients (4 males and 6 females) matched these criteria. On pretreatment 18 F-FDG PET, mean SUVmax in the tumor was 24.8 (8.75–60.75), and mean T/N ratio was 3.24 (2.17–5.12). The extent of tumor volume reduction was shown to be 21 to 68 % 1 week after diagnostic therapy by corticosteroids. Mean total dose and duration of corticosteroids were 719 mg as prednisolone and 6.5 days, respectively. Nine patients achieved complete response and one patient achieved partial response on MRI after standard treatment for PCNSL with high-dose methotrexate and/or whole-brain irradiation.

Conclusion Although the value of biopsy is universal, combining 18 F-FDG PET and corticosteroid administration is an important alternative method that may lead to the diagnosis of deep-seated PCNSLs in cases with intractable histopathological confirmations.

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Fluorescent Cancer-Selective Alkylphosphocholine Analogs for Intraoperative Glioma Detection

Fluorescent_Cancer_Selective_Alkylphosphocholine

Neurosurgery 76:115–124, 2015

5-Aminolevulinic acid (5-ALA)-induced tumor fluorescence aids brain tumor resections but is not approved for routine use in the United States. We developed and describe testing of 2 novel fluorescent, cancer-selective alkylphosphocholine analogs, CLR1501 (green) and CLR1502 (near infrared), in a proof-of-principle study for fluorescence-guided glioma surgery.

OBJECTIVE: To demonstrate that CLR1501 and CLR1502 are cancer cell-selective fluorescence agents in glioblastoma models and to compare tumor-to-normal brain (T:N) fluorescence ratios with 5-ALA.

METHODS: CLR1501, CLR1502, and 5-ALA were administered to mice with magnetic resonance imaging-verified orthotopic U251 glioblastoma multiforme- and glioblastoma stem cell-derived xenografts. Harvested brains were imaged with confocal microscopy (CLR1501), the IVIS Spectrum imaging system (CLR1501, CLR1502, and 5-ALA), or the Fluobeam near-infrared fluorescence imaging system (CLR1502). Imaging and quantitative analysis of T:N fluorescence ratios were performed.

RESULTS: Excitation/emission peaks are 500/517 nm for CLR1501 and 760/778 nm for CLR1502. The observed T:N ratio for CLR1502 (9.28 6 1.08) was significantly higher (P , .01) than for CLR1501 (3.51 6 0.44 on confocal imaging; 7.23 6 1.63 on IVIS imaging) and 5-ALA (4.81 6 0.92). Near-infrared Fluobeam CLR1502 imaging in a mouse xenograft model demonstrated high- contrast tumor visualization compatible with surgical applications.

CONCLUSION: CLR1501 (green) and CLR1502 (near infrared) are novel tumor-selective fluorescent agents for discriminating tumor from normal brain. CLR1501 exhibits a tumor-to-brain fluorescence ratio similar to that of 5-ALA, whereas CLR1502 has a superior tumor-to-brain fluorescence ratio. This study demonstrates the potential use of CLR1501 and CLR1502 in fluorescence-guided tumor surgery.

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Vago-glossopharyngeal neuralgia

Vago-glossopharyngeal neuralgiaActa Neurochir (2015) 157:311–321

Glossopharyngeal neuralgia (GPN), or better named vago-glossopharyngeal neuralgia (VGPN), is a rare disorder amounting to 1 % of the incidence of trigeminal neuralgia (TN). Pain is paroxysmal, of the electrical shooting type, and mainly provoked by stimulation of the pharynx or deep throat, especially during swallowing. Due to its rarity, VGPN is often misdiagnosed. The front line of medical treatment is based on anticonvulsants. Surgery should be considered when the pain is refractory to medications. In most patients, the cause is neurovascular conflict on root entry zone (REZ) or midcistern portion, of the IXth and/or Xth cranial nerves. Compressive vessels can be evidenced by means of a high sensibility and a high specificity resolution MR imaging in most centers.

Present consensus is that the first option of neurosurgical treatment be microvascular decompression. In patients with precarious general conditions, stereotactic radiosurgery may be considered. Also, thermo-rhizotomy at the pars nervosa of foramen jugularis or tractotomy-nucleotomy at brainstem may be alternatives, but these methods entail a significant risk of deficits.

In this article, the authors reviewed the main literature series on neurosurgical treatments of this disease.

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Atlantoaxial Instability of Inflammatory Origin in Adults

Atlantoaxial Instability of Inflammatory Origin in Adults

Neurosurgery 76:E226–E232, 2015

Acquired atlantoaxial instability of inflammatory origin (Grisel syndrome) is a rare condition. It usually occurs in children with benign upper airway problems and responds well to immobilization, rarely requiring C1-2 arthrodesis. Our recent experience with 2 adult cases suggests this may not be true in an older subpopulation.

CLINICAL PRESENTATION: A 71-year-old man developed C1-2 instability in the setting of culture-negative endocarditis. Initial immobilization was attempted for 8 weeks but new imaging revealed progressive destruction of the odontoid and worsening instability. Symptoms resolved after C1-4 arthrodesis. A 35-year-old woman developed C1-2 instability after a molar extraction and otitis media. Despite 12 weeks of immobilization and antibiotics, symptoms persisted and the atlantodental interval increased. She was successfully treated with a C1-2 arthrodesis.

CONCLUSION: A literature review revealed 13 reports (14 cases) of inflammatory atlantoaxial instability in patients aged 18 and older since 1830. Including the 2 cases reported here, 11 cases underwent initial nonoperative treatment with durable satisfactory results in only 2 of them (18.2%). Aspiration of the C1-2 phlegmon was diagnostic in only 4 of these 16 cases. Destruction of the odontoid was seen in a minority of cases (5/16, 31.3%). In this first review of the topic since the introduction of screwbased C1-2 fixation, it is suggested that nonoperative treatment is futile for inflammatory atlantoaxial instability in adults and strong consideration should be given to C1-2 arthrodesis. This procedure can reliably produce good outcomes with minimal morbidity.

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True aqueductal tumors: a unique entity

True aqueductal tumors-a unique entity

Acta Neurochir (2015) 157:169–177

Pure aqueductal tumors (ATs) differ from pineal region and tectal/tegmental tumors in that they are epicentered within the aqueduct. Nevertheless, these tumors are rarely described as a separate type of tumor, and are often grouped with other lesions located in the same vicinity. The present multicenter study focuses on our experience treating patients with pure ATs.

Methods Data from three large tertiary centers was collected retrospectively, including presenting symptoms, treatment paradigm, surgical approaches, pathology, and outcome.

Results Between 1999 and 2013, 16 patients with AT were diagnosed and treated at the three tertiary centers. Ages at presentation ranged from 5.5 to 57 years. Thirteen patients presented with hydrocephalus-related symptoms, and two were identified incidentally. Thirteen patients underwent an endoscopic third ventriculostomy, and two of these underwent a simultaneous endoscopic biopsy (one grade II ependymoma, one non-specified low-grade glioma). Two others underwent shunt placement. Three patients underwent resection due to tumor progression. Pathologies included glioblastoma multiforme, glioneural tumor, and ependymoma grade II. All non-resected tumors remained stable or grew only minimally.

Conclusions ATs are a rare entities that usually present with obstructive hydrocephalus. Treatment includes primarily cerebrospinal fluid drainage (preferably via an endoscopic third ventriculostomy). Simultaneous endoscopic biopsy may be done in selected cases. Tumor resection should be reserved for growing tumors; the trans-fourth ventricular or transchoroidal approaches are probably safer than other approaches used to reach the tectal region.

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Factors Predicting Recurrence After Resection of Clival Chordoma

Clivus chordomas

Neurosurgery 76:179–186, 2015

Clival chordomas frequently recur because of their location and invasiveness.

OBJECTIVE: To investigate clinical, operative, and anatomic factors associated with clival chordoma recurrence.

METHODS: Retrospective review of clival chordomas treated at our center from 1993 to 2013.

RESULTS: Fifty patients (56% male) with median age of 59 years (range, 8-76) were newly diagnosed with clival chordoma of mean diameter 3.3 cm (range, 1.5-6.7). Symptoms included headaches (38%), diplopia (36%), and dysphagia (14%). Procedures included transsphenoidal (n = 34), transoral (n = 4), craniotomy (n = 5), and staged approaches (n = 7). Gross total resection (GTR) rate was 52%, with 83%mean volumetric reduction, values that improved over time.While the lower third of the clivus was the least likely superoinferior zone to contain tumor (upper third = 72%/middle third = 82%/lower third = 42%), it most frequently contained residual tumor (upper third = 33%/middle third = 38%/lower third = 63%; P , .05). Symptom improvement rates were 61% (diplopia) and 53% (headache). Postoperative radiation included proton beam (n = 19), cyberknife (n = 7), intensity-modulated radiation therapy (n = 6), external beam (n = 10), and none (n = 4). At last follow-up of 47 patients, 23 (49%) remain disease-free or have stable residual tumor. Lower third of clivus progressed most after GTR (upper/mid/lower third = 32%/ 41%/75%). In a multivariate Cox proportional hazards model, male gender (hazard ratio [HR] = 1.2/P = .03), subtotal resection (HR = 5.0/P = .02), and the preoperative presence of tumor in the middle third (HR = 1.2/P = .02) and lower third (HR = 1.8/P = .02) of the clivus increased further growth or regrowth, while radiation modality did not.

CONCLUSION: Our findings underscore long-standing support for GTR as reducing chordoma recurrence. The lower third of the clivus frequently harbored residual or recurrent tumor, despite staged approaches providing mediolateral (transcranial 1 endonasal) or superoinferior (endonasal 1 transoral) breadth. There was no benefit of proton-based over photonbased radiation, contradicting conventional presumptions.

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Utility of postmortem imaging system for anatomical education in skull base surgery

Utility of postmortem imaging system for anatomical education in skull base surgery

Neurosurg Rev (2015) 38:165–170

Although cadaver dissections are important for skull base surgeons to acquire anatomical knowledge and techniques, their opportunities are limited in Japan. The Autopsy Imaging Center of the University of Fukui Hospital has both a CT scanner and an MR unit solely for deceased patients.

The authors applied the postmortemimaging to cadaver dissections and evaluated its usefulness in surgical education. Ten sides of five formalin-fixed cadaver heads were dissected by ten neurosurgeons. Five neurosurgeons were young, three were moderately experienced, and two were experts in skull base surgery. They performed orbitozygomatic, anterior transpetrosal, posterior transpetrosal, and transcondylar approaches. CT bone images were taken before and after dissections, and MR images were taken before dissection to merge with the CT bone images. The usefulness of the images for each neurosurgeon and for each skull base approach was evaluated.

The postmortem imaging system was useful for all neurosurgeons, especially in anterior transpetrosal, posterior transpetrosal, and transcondylar approaches. They could find the insufficiency or excessiveness of their drilling of specific bony structures with the images. Even the experts in skull base surgery could identify regions in which they could add drilling safely to widen the surgical field more.

The postmortem imaging system was useful for skull base cadaver dissections. This system is expected to be utilized for education and research on surgical anatomy.

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Mapping p53 Mutations in Low-Grade Glioma: A Voxel-Based Neuroimaging Analysis

Mapping p53 Mutations in Low-Grade Glioma

AJNR Am J Neuroradiol 36:70–76

Brain tumor location has proved to be a prognostic factor that may be associated with features of neoplastic origin. Mutation of p53 is an atypical genetic change that occurs during tumorigenesis. Thus, a potential correlation may exist between tumor location and p53 status. The purpose of the current study was to identify anatomic characteristics of mutant p53 expression by using quantitative neuroimaging analyses.

MATERIALS AND METHODS: Preoperative MR images from 182 patients with histologically confirmed low-grade gliomas were retrospectively analyzed. All tumors were manually marked and registered to the standard space. Using a voxel-based lesion-symptom mapping analysis, we located brain regions associated with a high occurrence of p53 mutation and corrected them by using a permutation test. The acquired clusters were further included as a factor in survival analyses.

RESULTS: Statistical analysis demonstrated that the left medial temporal lobe and right anterior temporal lobe were specifically associated with high expression of mutant p53. Kaplan-Meier curves showed that tumors located in these regions were associated with significantly worse progression-free survival compared with tumors occurring elsewhere.

CONCLUSIONS: Our voxel-level imaging analysis provides new evidence that genetic changes during cancer may have anatomic specificity. Additionally, the current study suggests that tumor location identified on structural MR images could potentially be used for customized presurgical outcome prediction.

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