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Idiopathic intracranial hypertension (IIH) can cause debilitating symptoms and optic nerve ischemia if untreated. Cerebrospinal fluid diversion is often necessary to reduce intracranial pressure; however, current ventriculoperitoneal and lumboperitoneal shunting techniques have high failure rates in patients with IIH.To describe our experience treating IIH with a novel stereotactic-guided transcerebellar cisternoperitoneal shunt (SGTC-CPS) technique that places the proximal shunt catheter in the posterior cisterna magnum.Retrospective perioperative and postoperative data from all patients who underwent SGTC-CPS placement for IIH from March 1, 2015, to December 31, 2020, were analyzed. Patients were positioned as for ventriculoperitoneal shunt placement but with the head turned farther laterally to adequately expose the retrosigmoid space. Using neuronavigation, an opening was made near the transverse-sigmoid junction, and the proximal catheter was inserted transcerebellarly into the posterior foramen magnum.Thirty-two patients underwent SGTC-CPS placement (29 female; mean body mass index, 36.0 ± 7.5; 14 with prior shunt failures). The mean procedure time for shunt placement was 145 minutes. No intraoperative complications occurred, and all patients were discharged uneventfully. At the 6-month follow-up, 81% of patients (21 of 26) had relief of their presenting symptoms. Shunt survival without revision was 86% (25 of 29) at 1 year and 67% (10 of 15) at 3 years, with no infections.The SGTC-CPS offers an alternative solution for cerebrospinal fluid diversion in patients with IIH and demonstrates a lower failure rate and more durable symptom relief compared with ventriculoperitoneal or lumboperitoneal shunt placement. Using proper techniques and equipment promotes safe and facile placement of the proximal catheter.

Objective Surgical techniques to achieve complete resection of mesial–basal temporal tumors should be pursued by neurosurgical oncologists. We describe the anatomical subpial amygdalohippocampectomy (SpAH) technique for tumor resection. Methods The key anatomical landmarks and critical steps of the SpAH technique were outlined and emphasized with medical illustrations and intraoperative photographs. The senior author's 90-day surgical outcomes with this approach were reviewed. Results Twenty-five patients (men, 17 [68%]; women, 8 [32%]; median [range] age, 59 [23–80] years) with temporal tumors involving the amygdalohippocampal region were included. SpAH was performed selectively in 8 [32%] patients, whereas 17 [68%] patients underwent SpAH in conjunction with an anterior temporal lobectomy due to tumor involvement of the anterolateral temporal cortex. The subpial resection of the amygdala protected the critical structures of the suprasellar cistern and sylvian fissure. Identifying the choroidal fissure as the superior-most aspect of hippocampal resection protected the optic tract and the thalamus. Subpial resection of the parahippocampal gyrus inferiorly protected the brainstem and critical structures of the ambient cistern. Tumors in the amygdalohippocampal region were anatomically and completely resected in all 25 patients. Of the 15 patients who presented with seizures, 13 (87%) were seizure-free at the 90-day postsurgical follow-up. Permanent neurologic deficits occurred in 3 patients (12%). Conclusions The SpAH technique permits complete resection of mesial–basal temporal tumors with an acceptable morbidity profile. An in-depth understanding of temporal lobe anatomy combined with a refined microsurgical technique allows for reproducible resection of tumor in the amygdalohippocampal region while protecting critical neurovascular structures.

Objective Epilepsy with periventricular nodular heterotopia (PVNH) lacks a conclusive surgical treatment strategy as eloquent cortex and important white matter tracts frequently overlay the deep periventricular nodules. Our goal was to evaluate the safety and efficacy of laser interstitial thermal therapy (LITT) for the treatment of epilepsy in PVNH. Methods Data on demographic characteristics, complications, visual outcomes, Engel classification at last follow-up, antiepileptic drug use, morbidity, and mortality among patients who underwent this procedure were retrospectively reviewed. Results Between May 2015 and January 2019, 5 patients underwent 6 LITT procedures for epilepsy with PVNH. One patient had residual nodules after their first procedure and underwent a second ablation. The average follow-up time was 12 months. Three patients were Engel class Ia, 1 patient was Engel class II, and 1 patient was Engel class III at last follow-up. Two patients were able to reduce their antiepileptic drugs postoperatively. Three patients had no changes in vision, 1 patient experienced a quadrantanopsia, and 1 patient had subjective blurry vision after their procedures. No patients experienced motor deficits, dysphasia, infection, or mortality. Conclusions LITT appears to be a safe and promising option to provide seizure relief for patients with refractory epilepsy and PVNH that otherwise may not be surgical candidates. Some appropriately determined patients with refractory epilepsy may benefit from LITT before proceeding with an invasive intracranial evaluation. A larger sample size and long-term follow-up is necessary to further elucidate safety and efficacy.

BACKGROUND Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate System (LAANTERN) is an ongoing multicenter prospective NeuroBlate (Monteris Medical) LITT (laser interstitial thermal therapy) registry collecting real-world outcomes and quality-of-life (QoL) data. OBJECTIVE To compare 12-mo outcomes from all subjects undergoing LITT for intracranial tumors/neoplasms. METHODS Demographics, intraprocedural data, adverse events, QoL, hospitalizations, health economics, and survival data are collected; standard data management and monitoring occur. RESULTS A total of 14 centers enrolled 223 subjects; the median follow-up was 223 d. There were 119 (53.4%) females and 104 (46.6%) males. The median age was 54.3 yr (range 3-86) and 72.6% had at least 1 baseline comorbidity. The median baseline Karnofsky Performance Score (KPS) was 90. Of the ablated tumors, 131 were primary and 92 were metastatic. Most patients with primary tumors had high-grade gliomas (80.9%). Patients with metastatic cancer had recurrence (50.6%) or radiation necrosis (40%). The median postprocedure hospital stay was 33.4 h (12.7-733.4). The 1-yr estimated survival rate was 73%, and this was not impacted by disease etiology. Patient-reported QoL as assessed by the Functional Assessment of Cancer Therapy-Brain was stabilized postprocedure. KPS declined by an average of 5.7 to 10.5 points postprocedure; however, 50.5% had stabilized/improved KPS at 6 mo. There were no significant differences in KPS or QoL between patients with metastatic vs primary tumors. CONCLUSION Results from the ongoing LAANTERN registry demonstrate that LITT stabilizes and improves QoL from baseline levels in a malignant brain tumor patient population with high rates of comorbidities. Overall survival was better than anticipated for a real-world registry and comparative to published literature., Graphical Abstract Graphical Abstract

BACKGROUND AND PURPOSE: Perfusion MR imaging measures of relative CBV can distinguish recurrent tumor from posttreatment radiation effects in high-grade gliomas. Currently, relative CBV measurement requires normalization based on user-defined reference tissues. A recently proposed method of relative CBV standardization eliminates the need for user input. This study compares the predictive performance of relative CBV standardization against relative CBV normalization for quantifying recurrent tumor burden in high-grade gliomas relative to posttreatment radiation effects. MATERIALS AND METHODS: We recruited 38 previously treated patients with high-grade gliomas (World Health Organization grades III or IV) undergoing surgical re-resection for new contrast-enhancing lesions concerning for recurrent tumor versus posttreatment radiation effects. We recovered 112 image-localized biopsies and quantified the percentage of histologic tumor content versus posttreatment radiation effects for each sample. We measured spatially matched normalized and standardized relative CBV metrics (mean, median) and fractional tumor burden for each biopsy. We compared relative CBV performance to predict tumor content, including the Pearson correlation (r), against histologic tumor content (0%–100%) and the receiver operating characteristic area under the curve for predicting high-versus-low tumor content using binary histologic cutoffs (≥50%; ≥80% tumor). RESULTS: Across relative CBV metrics, fractional tumor burden showed the highest correlations with tumor content (0%–100%) for normalized (r = 0.63, P

Background Stereoelectroencephalography (SEEG) is a commonly used technique for mapping the epileptogenic zone before epilepsy surgery. Many SEEG depth electrode implantation techniques involve the use of extensive technological equipment and shaving of the patient's entire head before electrode implantation. Our goal was to evaluate an SEEG depth electrode implantation technique that used readily available cost-effective neurosurgical equipment, was minimally invasive in nature, and required negligible hair shaving. Methods Data on demographic characteristics, operative time, hemorrhagic complications, implantation complications, infection, morbidity, and mortality among patients who underwent this procedure were reviewed retrospectively. Results Between April 2016 and March 2018, 23 patients underwent implantation of 213 depth electrodes with use of this technique. Mean (SD) operative time was 123 (32) minutes (range, 66–181 minutes). A mean (SD) of 9.3 (1.4) electrodes were placed for each patient (range, 8–13 electrodes). Two of the 213 electrodes (0.9%) were associated with postimplantation asymptomatic hemorrhage. One of the 213 electrodes (0.5%) was placed extradurally or incorrectly. None of the 213 electrodes was associated with symptomatic complications. No patients experienced infectious complications at any point in the preoperative, perioperative, or postoperative stages. Conclusions This minimally invasive, cost-effective technique for SEEG depth electrode implantation is a safe, efficient method that uses readily available basic neurosurgical equipment. This technique may be useful in neurosurgery centers with more limited resources. This study suggests that leaving the patient's hair largely intact throughout the procedure does not pose an additional infection risk.

OBJECTIVE Communication between neurosurgeons and pathologists is mandatory for intraoperative decision-making and optimization of resection, especially for invasive masses. Handheld confocal laser endomicroscopy (CLE) technology provides in vivo intraoperative visualization of tissue histoarchitecture at cellular resolution. The authors evaluated the feasibility of using an innovative surgical telepathology software platform (TSP) to establish real-time, on-the-fly remote communication between the neurosurgeon using CLE and the pathologist. METHODS CLE and a TSP were integrated into the surgical workflow for 11 patients with brain masses (6 patients with gliomas, 3 with other primary tumors, 1 with metastasis, and 1 with reactive brain tissue). Neurosurgeons used CLE to generate video-flow images of the operative field that were displayed on monitors in the operating room. The pathologist simultaneously viewed video-flow CLE imaging using a digital tablet and communicated with the surgeon while physically located outside the operating room (1 pathologist was in another state, 4 were at home, and 6 were elsewhere in the hospital). Interpretations of the still CLE images and video-flow CLE imaging were compared with the findings on the corresponding frozen and permanent H&E histology sections. RESULTS Overall, 24 optical biopsies were acquired with mean ± SD 2 ± 1 optical biopsies per case. The mean duration of CLE system use was 1 ± 0.3 minutes/case and 0.25 ± 0.23 seconds/optical biopsy. The first image with identifiable histopathological features was acquired within 6 ± 0.1 seconds. Frozen sections were processed within 23 ± 2.8 minutes, which was significantly longer than CLE usage (p < 0.001). Video-flow CLE was used to correctly interpret tissue histoarchitecture in 96% of optical biopsies, which was substantially higher than the accuracy of using still CLE images (63%) (p = 0.005). CONCLUSIONS When CLE is employed in tandem with a TSP, neurosurgeons and pathologists can view and interpret CLE images remotely and in real time without the need to biopsy tissue. A TSP allowed neurosurgeons to receive real-time feedback on the optically interrogated tissue microstructure, thereby improving cross-functional communication and intraoperative decision-making and resulting in significant workflow advantages over the use of frozen section analysis.

OBJECTIVEEffective treatments for recurrent, previously irradiated intracranial meningiomas are limited, and resection alone is not usually curative. Thus, the authors studied the combination of maximum safe resection and adjuvant radiation using permanent intracranial brachytherapy (R+BT) in patients with recurrent, previously irradiated aggressive meningiomas.METHODSPatients with recurrent, previously irradiated meningiomas were treated between June 2013 and October 2016 in a prospective single-arm trial of R+BT. Cesium-131 (Cs-131) radiation sources were embedded in modular collagen carriers positioned in the operative bed on completion of resection. The Cox proportional hazards model with this treatment as a predictive term was used to model its effect on time to local tumor progression.RESULTSNineteen patients (median age 64.5 years, range 50–78 years) with 20 recurrent, previously irradiated tumors were treated. The WHO grade at R+BT was I in 4 (20%), II in 14 (70%), and III in 2 (10%) cases. The median number of prior same-site radiation courses and same-site surgeries were 1 (range 1–3) and 2 (range 1–4), respectively; the median preoperative tumor volume was 11.3 cm3 (range 0.9–92.0 cm3). The median radiation dose from BT was 63 Gy (range 54–80 Gy). At a median radiographic follow-up of 15.4 months (range 0.03–47.5 months), local failure (within 1.5 cm of the implant bed) occurred in 2 cases (10%). The median treatment-site time to progression after R+BT has not been reached; that after the most recent prior therapy was 18.3 months (range 3.9–321.9 months; HR 0.17, p = 0.02, log-rank test). The median overall survival after R+BT was 26 months, with 9 patient deaths (47% of patients). Treatment was well tolerated; 2 patients required surgery for complications, and 2 experienced radiation necrosis, which was managed medically.CONCLUSIONSR+BT utilizing Cs-131 sources in modular carriers represents a potentially safe and effective treatment option for recurrent, previously irradiated aggressive meningiomas.

Precise communication between neurosurgeons and pathologists is crucial for optimizing patient care, especially for intraoperative diagnoses. Confocal laser endomicroscopy (CLE) combined with a telepathology software platform (TSP) provides a novel venue for neurosurgeons and pathologists to review CLE images and converse intraoperatively in real-time.To describe the feasibility of integrating CLE and a TSP in the surgical workflow for real-time review of in vivo digital fluorescence tissue imaging in 3 patients with intracranial tumors.Although the neurosurgeon used the CLE probe to generate fluorescence images of histoarchitecture within the operative field that were displayed on monitors in the operating room, the pathologist simultaneously remotely viewed the CLE images. The neurosurgeon and pathologist discussed in real-time the histological structures of intraoperative imaging locations.The neurosurgeon placed the CLE probe at various locations on and around the tumor, in the surgical resection bed, and on surrounding brain tissue with communication through the TSP. The neurosurgeon oriented the pathologist to the location of the CLE, and the pathologist and neurosurgeon discussed the CLE images in real-time. The TSP and CLE were integrated successfully and rapidly in the operating room in all 3 cases. No patient had perioperative complications.Two novel digital neurosurgical cellular imaging technologies were combined with intraoperative neurosurgeon-pathologist communication to guide the identification of abnormal histoarchitectural tissue features in real-time. CLE with the TSP may allow rapid decision-making during tumor resection that may hold significant advantages over the frozen section process and surgical workflow in general.

Glioblastomas (GBMs) are the most aggressive primary brain tumours and have no known cure. Each individual tumour comprises multiple sub-populations of genetically-distinct cells that may respond differently to targeted therapies and may contribute to disappointing clinical trial results. Image-localized biopsy techniques allow multiple biopsies to be taken during surgery and provide information that identifies regions where particular sub-populations occur within an individual GBM, thus providing insight into their regional genetic variability. These sub-populations may also interact with one another through a competitive or cooperative nature; it is important to ascertain the nature of these interactions, as they may have implications for responses to targeted therapies. We combine genetic information from biopsies with a mechanistic model of interacting GBM sub-populations to characterise the nature of interactions between two commonly occurring GBM sub-populations, those with EGFR and PDGFRA genes amplified. We study population levels found across image-localized biopsy data from a cohort of 25 patients and compare this to model outputs under competitive, cooperative and neutral interaction assumptions. We explore other factors affecting the observed simulated sub-populations, such as selection advantages and phylogenetic ordering of mutations, which may also contribute to the levels of EGFR and PDGFRA amplified populations observed in biopsy data.

Objective The Barrow Innovation Center consists of an educational program that promotes interdisciplinary collaboration among neurosurgery, legal, and engineering professionals to foster the development of new medical devices. This report describes a common issue faced during the placement of ventricular shunts for the treatment of hydrocephalus and the solution to this problem that was developed through the Barrow Innovation Center. Methods Neurosurgery residents involved in the Barrow Innovation Center presented the problem of ferromagnetic retractors interfering with pinless image-guidance systems at a monthly meeting. Potential solutions were openly discussed by an interdisciplinary committee of neurosurgeons, patent lawyers, and biomedical engineers. The committee decided to pursue development of a novel self-retaining retractor made of nonferromagnetic material as a solution to the problem. Results Each retractor design was tested in the cadaver laboratory for size and functionality. A final design was chosen and used in a surgical case requiring ventriculoperitoneal shunt placement. The new retractor successfully retracted the scalp without interfering with the electromagnetic image-guidance system. Conclusions Through the interdisciplinary Barrow Innovation Center program, a newly designed, 3-dimensional–printed skin and soft-tissue retractor was created, along with an innovative universal shunt retainer. Through this integrated program dedicated to surgical innovation (i.e., the Barrow Innovation Center), the process of developing and implementing new technology at our institution has been streamlined, creating a culture of innovation within the neurosurgery training program.

Background The diagnosis and management of patients with idiopathic intracranial hypertension (IIH) frequently relies on lumbar puncture to ascertain intracranial pressure (ICP). However, ICP values derived this way may be spurious owing to patient body habitus and behavior. We recently incorporated direct continuous ICP monitoring into the work-up for IIH. Methods Through billing records, we identified all patients during a 3-year period who had a diagnosis of IIH and who underwent ICP monitoring before shunt placement or revision. Patient demographics and clinical data were reviewed. Results Of 30 patients who underwent ICP monitoring with an intraparenchymal wire, 17 had undergone lumbar puncture within the previous 6 months. Results from lumbar punctures showed an elevated opening pressure in all 17 patients, whereas only 2 patients (12%) were found to have consistently elevated ICP with direct ICP monitoring. Of 15 patients being evaluated for shunting, 4 (27%) were found to have elevated ICP. Of the 15 patients with existing shunts, 2 patients (13%) were found to have malfunctioning shunts after pressure monitoring, and 3 patients (20%) had shunts that were found to be unnecessary and were removed. No patient experienced any complication from invasive monitoring. Conclusions Direct ICP monitoring is the gold standard for determining ICP and can be safely and effectively applied to the work-up and treatment of patients with IIH to reduce the occurrence of misdiagnosis and unnecessary surgery.

OBJECTIVE Cerebral venous pressure gradient (CVPG) from dural venous sinus stenosis is implicated in headache syndromes such as idiopathic intracranial hypertension (IIH). The incidence of CVPG in headache patients has not been reported. METHODS The authors reviewed all cerebral venograms with manometry performed for headache between January 2008 and May 2015. Patient demographics, headache etiology, intracranial pressure (ICP) measurements, and radiographic and manometric results were recorded. CVPG was defined as a difference ≥ 8 mm Hg by venographic manometry. RESULTS One hundred sixty-four venograms were performed in 155 patients. There were no procedural complications. Ninety-six procedures (58.5%) were for patients with IIH. The overall incidence of CVPG was 25.6% (42 of 164 procedures): 35.4% (34 of 96 procedures) in IIH patients and 11.8% (8 of 68 procedures) in non-IIH patients. Sixty procedures (36.6%) were performed in patients with preexisting shunts. Seventy-seven patients (49.7%) had procedures preceded by an ICP measurement within 4 weeks of venography, and in 66 (85.7%) of these patients, the ICP had been found to be elevated. CVPG was seen in 8.3% (n = 5) of the procedures in the 60 patients with a preexisting shunt and in 0% (n = 0) of the 11 procedures in the 77 patients with normal ICP (p < 0.001 for both). Noninvasive imaging (MR venography, CT venography) was assessed prior to venography in 112 (68.3%) of 164 cases, and dural venous sinus abnormalities were demonstrated in 73 (65.2%) of these cases; there was a trend toward CVPG (p = 0.07). Multivariate analysis demonstrated an increased likelihood of CVPG in patients with IIH (OR 4.97, 95% CI 1.71–14.47) and a decreased likelihood in patients with a preexisting shunt (OR 0.09, 95% CI 0.02–0.44). CONCLUSIONS CVPG is uncommon in IIH patients, rare in those with preexisting shunts, and absent in those with normal ICP.

OBJECTIVE Debate continues over proper surgical treatment for mesial temporal lobe epilepsy (MTLE). Few large comprehensive studies exist that have examined outcomes for the subtemporal selective amygdalohippocampectomy (sSAH) approach. This study describes a minimally invasive technique for sSAH and examines seizure and neuropsychological outcomes in a large series of patients who underwent sSAH for MTLE. METHODS Data for 152 patients (94 women, 61.8%; 58 men, 38.2%) who underwent sSAH performed by a single surgeon were retrospectively reviewed. The sSAH technique involves a small, minimally invasive opening and preserves the anterolateral temporal lobe and the temporal stem. RESULTS All patients in the study had at least 1 year of follow-up (mean [SD] 4.52 [2.57] years), of whom 57.9% (88/152) had Engel class I seizure outcomes. Of the patients with at least 2 years of follow-up (mean [SD] 5.2 [2.36] years), 56.5% (70/124) had Engel class I seizure outcomes. Preoperative and postoperative neuropsychological test results indicated no significant change in intelligence, verbal comprehension, perceptual reasoning, attention and processing, cognitive flexibility, visuospatial memory, or mood. There was a significant change in word retrieval regardless of the side of surgery and a significant change in verbal memory in patients who underwent dominant-side resection (p < 0.05). Complication rates were low, with a 1.3% (2/152) permanent morbidity rate and 0.0% mortality rate. CONCLUSIONS This study reports a large series of patients who have undergone sSAH, with a comprehensive presentation of a minimally invasive technique. The sSAH approach described in this study appears to be a safe, effective, minimally invasive technique for the treatment of MTLE.

Glioblastoma (GBM) is a heterogeneous and lethal brain cancer. These tumors are followed using magnetic resonance imaging (MRI), which is unable to precisely identify tumor cell invasion, impairing effective surgery and radiation planning. We present a novel hybrid model, based on multiparametric intensities, which combines machine learning (ML) with a mechanistic model of tumor growth to provide spatially resolved tumor cell density predictions. The ML component is an imaging data-driven graph-based semi-supervised learning model and we use the Proliferation-Invasion (PI) mechanistic tumor growth model. We thus refer to the hybrid model as the ML-PI model. The hybrid model was trained using 82 image-localized biopsies from 18 primary GBM patients with pre-operative MRI using a leave-one-patient-out cross validation framework. A Relief algorithm was developed to quantify relative contributions from the data sources. The ML-PI model statistically significantly outperformed (p

Background Choroid plexus papillomas (CPPs) are benign World Health Organization grade I tumors that comprise 2%–4% of all brain tumors among children and less than 1% of brain tumors in adults. Most adult cases occur in the fourth ventricle, with only 1 previous report describing an adult patient with a temporal horn CPP. Case Description We report a rare case of a temporal horn CPP presenting in an adult with seizures. We performed a minimally invasive subtemporal approach for gross total resection of the lesion. Conclusions CPP presenting in the temporal horn is rare among adults. We discuss the surgical nuances of the subtemporal approach for resection and review the literature regarding adult presentation of CPP and the treatment strategies for adult CPP.

BackgroundThe selective posterior cerebral artery (PCA) amobarbital test, or PCA Wada test, is used to predict memory impairment after epilepsy surgery in patients who have previously had a failed internal carotid artery (ICA) amobarbital test.MethodsMedical records from 2012 to 2018 were retrospectively reviewed for all patients with seizures who underwent a selective PCA Wada test at our institution following a failed or inconclusive ICA Wada test. Standardized neuropsychological testing was performed before and during the Wada procedure and postoperatively in patients who underwent resection.ResultsThirty-three patients underwent a selective PCA Wada test, with no complications. Twenty-six patients with medically refractory epilepsy had a seizure focus amenable to selective amygdalohippocampectomy (AHE). Six patients (23%, n=26) had a failed PCA Wada test and did not undergo selective AHE, seven (27%) declined surgical resection, leaving 13 patients who underwent subtemporal selective AHE. Hippocampal sclerosis was found in all 13 patients (100%). Twelve patients (92%) subsequently underwent formal neuropsychological testing and all were found to have stable memory. Ten patients (77%) were seizure-free (Engel Class I), with average follow-up of 13 months.ConclusionThe selective PCA Wada test is predictive of memory outcomes after subtemporal selective AHE in patients with a failed or inconclusive ICA Wada test. Furthermore, given the low risk of complications and potential benefit of seizure freedom, a selective PCA Wada test may be warranted in patients with medically intractable epilepsy who are candidates for a selective AHE and who have a prior failed or inconclusive ICA Wada test.

BACKGROUND: MRI-based modeling of tumor cell density (TCD) can significantly improve targeted treatment of Glioblastoma (GBM). Unfortunately, interpatient variability limits the predictive ability of many modeling approaches. We present a Transfer Learning (TL) method that generates individualized patient models, grounded in the wealth of population data, while also detecting and adjusting for interpatient variabilities based on each patient’s own histologic data. METHODS: We recruited primary GBM patients undergoing image-guided biopsies and preoperative imaging including contrast-enhanced MRI (CE-MRI), Dynamic-Susceptibility-Contrast (DSC)-MRI, and Diffusion Tensor Imaging (DTI). We calculated relative cerebral blood volume (rCBV) from DSC-MRI and mean diffusivity (MD) and fractional anisotropy (FA) from DTI. Following image coregistration, we assessed TCD for each biopsy and identified corresponding localized MRI measurements. We then explored a range of univariate and multivariate predictive models of TCD based on MRI measurements in a generalized one-model-fits-all (OMFA) approach. We then implemented both univariate and multivariate individualized TL predictive models, which harness the available population level data but allow for individual variability in their predictions. Finally, we compared Pearson correlation coefficients and mean absolute error between the individualized TL versus generalized OMFA models. RESULTS: TCD significantly correlated with rCBV (r=0.33,p

Background Glioblastoma (GBM) exhibits profound intratumoral genetic heterogeneity. Each tumor comprises multiple genetically distinct clonal populations with different therapeutic sensitivities. This has implications for targeted therapy and genetically informed paradigms. Contrast-enhanced (CE)-MRI and conventional sampling techniques have failed to resolve this heterogeneity, particularly for nonenhancing tumor populations. This study explores the feasibility of using multiparametric MRI and texture analysis to characterize regional genetic heterogeneity throughout MRI-enhancing and nonenhancing tumor segments. Methods We collected multiple image-guided biopsies from primary GBM patients throughout regions of enhancement (ENH) and nonenhancing parenchyma (so called brain-around-tumor, [BAT]). For each biopsy, we analyzed DNA copy number variants for core GBM driver genes reported by The Cancer Genome Atlas. We co-registered biopsy locations with MRI and texture maps to correlate regional genetic status with spatially matched imaging measurements. We also built multivariate predictive decision-tree models for each GBM driver gene and validated accuracies using leave-one-out-cross-validation (LOOCV). Results We collected 48 biopsies (13 tumors) and identified significant imaging correlations (univariate analysis) for 6 driver genes: EGFR, PDGFRA, PTEN, CDKN2A, RB1, and TP53. Predictive model accuracies (on LOOCV) varied by driver gene of interest. Highest accuracies were observed for PDGFRA (77.1%), EGFR (75%), CDKN2A (87.5%), and RB1 (87.5%), while lowest accuracy was observed in TP53 (37.5%). Models for 4 driver genes (EGFR, RB1, CDKN2A, and PTEN) showed higher accuracy in BAT samples (n = 16) compared with those from ENH segments (n = 32). Conclusion MRI and texture analysis can help characterize regional genetic heterogeneity, which offers potential diagnostic value under the paradigm of individualized oncology.

Mesial temporal lobe epilepsy is a common condition that is frequently drug resistant. Anterior temporal lobectomy has been shown to be effective in controlling seizures but entails resecting anterior and lateral temporal lobe regions that are not necessarily included in the epileptogenic zone. Selective amygdalohippocampectomy spares uninvolved structures while providing the same benefit as anterior temporal lobectomy. This article describes the 3 most common surgical approaches for performing selective amygdalohippocampectomy and discusses their relative merits and risks.

Neurocomputational models have long posited that episodic memories in the human hippocampus are represented by sparse, stimulus-specific neural codes. A concomitant proposal is that when sparse-distributed neural assemblies become active, they suppress the activity of competing neurons (neural sharpening). We investigated episodic memory coding in the hippocampus and amygdala by measuring single-neuron responses from 20 epilepsy patients (12 female) undergoing intracranial monitoring while they completed a continuous recognition memory task. In the left hippocampus, the distribution of single-neuron activity indicated that only a small fraction of neurons exhibited strong responding to a given repeated word and that each repeated word elicited strong responding in a different small fraction of neurons. This finding reflects sparse distributed coding. The remaining large fraction of neurons exhibited a concurrent reduction in firing rates relative to novel words. The observed pattern accords with longstanding predictions that have previously received scant support from single-cell recordings from human hippocampus.

It remains unclear how single neurons in the human brain represent whole-object visual stimuli. While recordings in both human and nonhuman primates have shown distributed representations of objects (many neurons encoding multiple objects), recordings of single neurons in the human medial temporal lobe, taken as subjects' discriminated objects during multiple presentations, have shown gnostic representations (single neurons encoding one object). Because some studies suggest that repeated viewing may enhance neural selectivity for objects, we had human subjects discriminate objects in a single, more naturalistic viewing session. We found that, across 432 well isolated neurons recorded in the hippocampus and amygdala, the average fraction of objects encoded was 26%. We also found that more neurons encoded several objects versus only one object in the hippocampus (28 vs 18%,p< 0.001) and in the amygdala (30 vs 19%,p< 0.001). Thus, during realistic viewing experiences, typical neurons in the human medial temporal lobe code for a considerable range of objects, across multiple semantic categories.

OBJECTIVEHemispherectomy is a surgical technique that is established as a standard treatment in appropriately selected patients with drug-resistant epilepsy. It has proven to be successful in pediatric patients with unilateral hemispheric lesions but is underutilized in adults. This study retrospectively evaluated the clinical outcomes after hemispherectomy in adult patients with refractory epilepsy.METHODSThis study examined 6 cases of hemispherectomy in adult patients at Barrow Neurological Institute. In addition, all case series of hemispherectomy in adult patients were identified through a literature review using MEDLINE and PubMed. Case series of patients older than 18 years were included; reports of patients without clear follow-up duration or method of validated seizure outcome quantification were excluded. Seizure outcome was based on the Engel classification.RESULTSA total of 90 cases of adult hemispherectomy were identified, including 6 newly added by Barrow Neurological Institute. Sixty-five patients underwent functional hemispherectomy; 25 patients had anatomical hemispherectomy. Length of follow-up ranged from 9 to 456 months. Seizure freedom was achieved in 80% of patients. The overall morbidity rate was low, with 9 patients (10%) having new or additional postoperative speech or language dysfunction, and 19 patients (21%) reporting some worsening of hemiparesis. No patients lost ambulatory or significant functional ability, and 2 patients had objective ambulatory improvement. Among the 41 patients who underwent additional formal neuropsychological testing postoperatively, overall stability or improvement was seen.CONCLUSIONSHemispherectomy is a valuable surgical tool for properly selected adult patients with pre-existing hemiparesis and intractable epilepsy. In published cases, as well as in this series, the procedure has overall been well tolerated without significant morbidity, and the majority of patients have been rendered free of seizures.

Background Hypothalamic hamartomas (HH) are rare lesions associated with treatment-resistant epilepsy. Open surgery results in modest seizure control (about 50%) but has a significant associated morbidity. Radiosurgery is limited to a subset of patients due to latent therapeutic effects. Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) offers a novel minimally invasive option. Objective To evaluate a single center's outcomes for the LITT treatment of HH. Methods We retrospectively reviewed our experience with LITT for the treatment of HH using our institution's prospectively maintained patient database. Results Eighteen patients (mean age, 21.1 yr; median age, 11 yr) underwent 21 total LITT treatments for HH. Mean follow-up was 17.4 mo. The length of stay was 1 night for 16 (89%) patients. At the end of follow-up, 11 of 18 patients (61%) had full disconnection of the HH, and 12 of 15 (80%) patients with gelastic seizures and 5 (56%) of 9 patients with nongelastic seizures were seizure free (International League Against Epilepsy Class 1). Immediate complications included a 39% (7/18) incidence of neurological deficits, including 1 case of hemiparesis. At the end of follow-up, 22% of patients (4/18) had persistent deficits. The hypothyroidism that occurred was delayed in 11% of patients (2/18), as was short-term memory loss (22%, 4/18) and weight gain (22%, 4/18). Conclusion LITT therapy for HH can achieve excellent rates of seizure control with low morbidity and a short postoperative stay in a majority of patients. Additional research is needed to assess the durability of results and the full spectrum of cognitive outcomes.

Although the epilepsy refractory to medical therapy can potentially be cured by the resection of epileptogenic tissue, many patients do not qualify for surgery, because epileptogenic tissue can arise from eloquent areas of the brain, where surgical resection would result in severe neurological deficits. Palliative surgical treatments currently used in these situations include deep brain stimulation, responsive neurostimulation, and vagal nerve stimulation.1 A previously developed technique, multiple subpial transections (MSTs), although used infrequently, is another effective tool.2 Our patient, a 34-yr-old man, had epilepsy that was refractory to medical management. His preoperative work-up demonstrated a potential seizure focus in the left pars opercularis and left superior temporal gyrus, which was verified using invasive stereoelectroencephalography. Functional magnetic resonance imaging demonstrated a significant verbal and motor function in this region. After informed consent was obtained, the patient underwent a left-sided craniotomy. The central portion of the seizure focus was resected using the subpial technique. The surrounding presumed epileptogenic cortex, which was considered functionally eloquent, was then horizontally disconnected with MSTs. For each transection, a small puncture incision was made in the pia, and a vertical cut was completed using Morrell dissectors.2 MSTs were performed circumferentially around the entire resection cavity in 5-mm increments. All hemostasis was achieved with irrigation instead of electrocautery, although noncauterizing hemostatic agents are also acceptable. The patient was neurologically intact after the operation and was discharged home on postoperative day 2. He was free of seizures at 11-month follow-up. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.

Background Magnetic resonance-guided laser-induced thermal therapy (MRgLITT) is a minimally invasive surgical treatment for progressive neoplasms and post-radiation treatment effect (PRTE). Objective To evaluate the radiographic response and efficacy of MRgLITT for biopsy-confirmed PRTE and the quality-of-life outcomes of patients following MRgLITT. Methods We conducted a single-center retrospective study of radiographic responses and clinical outcomes of 25 patients with previously treated primary or secondary brain neoplasms (World Health Organization grades 4 [n = 8], 3 [n = 5], 2 [n = 5]) and metastatic brain tumors (n = 7). MRgLITT was applied directly following stereotactic needle biopsy confirming PRTE without any evidence of tumor presence. Results Mean overall survival times (months) for grades 4 and 3 and for metastatic brain tumors were 39.2 (standard error [SE], 7.6; 95% confidence interval [CI], 24.3-54.1), 29.1 (SE, 7.7; 95% CI, 14.0-44.2), and 55.9 (SE, 10.0; 95% CI, 36.3-75.4), respectively. Mean progression-free survival times after MRgLITT were 9.1 (SE, 3.6; 95% CI, 2.1-16.1), 8.5 (SE, 2.4; 95% CI, 3.9-13.2), and 11.4 (SE, 3.9; 95% CI, 3.8-19.0), respectively. Mean survival times after MRgLITT were 13.1 (SE, 2.3; 95% CI, 8.5-17.6), 12.2 (SE, 4.0; 95% CI, 4.4-20.0), and 19.2 (SE, 5.3; 95% CI, 8.9-29.6), respectively. The SF-36 indicated significant overall effects on mental health (P = .029) and vitality (P = .005). Conclusion MRgLITT may be a viable option for patients with symptomatic advancing PRTE and is less invasive than open craniotomy. Although our results suggest a positive effect for MRgLITT on PRTE, prospective randomized trials with larger numbers of patients are needed to validate the study results. Abbreviations cRBV, relative cerebral blood volumeHIF1a, hypoxia-inducible factor 1aIMRT, intensity-modulated radiation therapyKPS, Karnofsky Performance StatusLITT, laser-induced thermal therapyMBT, metastatic brain tumorMRgLITT, magnetic resonance-guided laser-induced thermal therapyPRTE, post-radiation treatment effectSRS, stereotactic radiosurgeryVEGF, vascular endothelial growth factorWBXRT, whole brain radiation therapy.

OBJECTIVE Therapeutic options for brain metastases (BMs) that recur after stereotactic radiosurgery (SRS) remain limited. METHODS The authors provide the collective experience of 4 institutions where treatment of BMs that recurred after SRS was performed with stereotactic laser ablation (SLA). RESULTS Twenty-six BMs (in 23 patients) that recurred after SRS were treated with SLA (2 patients each underwent 2 SLAs for separate lesions, and a third underwent 2 serial SLAs for discrete BMs). Histological findings in the BMs treated included the following: breast (n = 6); lung (n = 6); melanoma (n = 5); colon (n = 2); ovarian (n = 1); bladder (n = 1); esophageal (n = 1); and sarcoma (n = 1). With a median follow-up duration of 141 days (range 64–794 days), 9 of the SLA-treated BMs progressed despite treatment (35%). All cases of progression occurred in BMs in which < 80% ablation was achieved, whereas no disease progression was observed in BMs in which ≥ 80% ablation was achieved. Five BMs were treated with SLA, followed 1 month later by adjuvant SRS (5 Gy daily × 5 days). No disease progression was observed in these patients despite ablation efficiency of < 80%, suggesting that adjuvant hypofractionated SRS enhances the efficacy of SLA. Of the 23 SLA-treated patients, 3 suffered transient hemiparesis (13%), 1 developed hydrocephalus requiring temporary ventricular drainage (4%), and 1 patient who underwent SLA of a 28.9-cm3 lesion suffered a neurological deficit requiring an emergency hemicraniectomy (4%). Although there is significant heterogeneity in corticosteroid treatment post-SLA, most patients underwent a 2-week taper. CONCLUSIONS Stereotactic laser ablation is an effective treatment option for BMs in which SRS fails. Ablation of ≥ 80% of BMs is associated with decreased risk of disease progression. The efficacy of SLA in this setting may be augmented by adjuvant hypofractionated SRS.

Since 2003, only two chemotherapeutic agents, evaluated in phase III trials, have been approved by the US Food and Drug Administration for treatment of newly diagnosed high-grade glioma (HGG): Gliadel wafers (intracranially implanted local chemotherapy) and temozolomide (TMZ) (systemic chemotherapy). Neither agent is curative, but each has been shown to improve median overall survival (OS) compared to radiotherapy (RT) alone. To date, no phase III trial has tested these agents when used in sequential combination; however, a number of smaller trials have reported favorable results. We performed a systematic literature review to evaluate the combination of Gliadel wafers with standard RT (60 Gy) plus concurrent and adjuvant TMZ (RT/TMZ) for newly diagnosed HGG. A literature search was conducted for the period of January 1995 to September 2015. Data were extracted and categorized, and means and ranges were determined. A total of 11 publications met criteria, three prospective trials and eight retrospective studies, representing 411 patients who received Gliadel plus standard RT/TMZ. Patients were similar in age, gender, and performance status. The weighted mean of median OS was 18.2 months (ten trials, n = 379, range 12.7 to 21.3 months), and the weighted mean of median progression-free survival was 9.7 months (seven trials, n = 287, range 7 to 12.9 months). The most commonly reported grade 3 and 4 adverse events were myelosuppression (10.22 %), neurologic deficit (7.8 %), and healing abnormalities (4.3 %). Adverse events reflected the distinct independent safety profiles of Gliadel wafers and RT/TMZ, with little evidence of enhanced toxicity from their use in sequential combination. In the 11 identified trials, an increased benefit from sequentially combining Gliadel wafers with RT/TMZ was strongly suggested. Median OS tended to be improved by 3 to 4 months beyond that observed for Gliadel wafers or TMZ when used alone in the respective phase III trials. Larger prospective trials of Gliadel plus RT/TMZ are warranted.

Purpose The present study provides a detailed account of neurocognitive outcome following minimal access subtemporal selective amygdalohippocampectomy (SAH) and establishes rates of neurocognitive decline in the largest sample to date. Use of a subtemporal surgical approach to SAH has been proposed to possibly reduce the risk for postoperative neurocognitive decline since lateral neocortical tissues is not resected and the temporal stem is preserved. The current study extends prior research with subtemporal SAH patients to include not only group level analyses but also analyses based on reliable change data. Methods Neurocognitive comparisons are made between 47 patients that underwent subtemporal SAH. Statistical comparisons were made between neurocognitive performance at the group level and with use of reliable change scores. Results Approximately 75% of patients were seizure free postoperatively. At the group level, there were no significant postoperative changes. For the left SAH patients, reliable change scores demonstrated a decline in approximately one third of patients for memory, verbal intellect, and naming. Right SAH patients showed decline primarily in memory. Conclusions These results indicated good seizure control following subtemporal SAH with greatest risk for neurocognitive decline following dominant SAH and best cognitive outcome following non-dominant SAH. Findings demonstrated the importance of reliable change analyses that make individual based comparisons and take into account measurement error. Despite preservation of the lateral neocortical tissue and the temporal stem, subtemporal SAH presents a risk for cognitive decline in a notable portion of patients.

As drug discovery programs search for new treatment strategies to improve the survival of patients with glioblastoma multiforme (GBM), the need for a timely and accurate end point to judge treatment efficacy has never been greater.1 Overall survival (OS) represents the benchmark measure of outcome but has clear disadvantages for clinical trial assessment. Clinical trials that use OS are lengthened because of the time needed to observe mortality,1,2 and correlations between OS and initial treatment are modified by subsequent salvage therapies.2,3 These limitations have led to the use of progression-free survival (PFS) as a surrogate marker for OS. However, PFS requires accurate estimates of tumor growth based on MRI, and such estimates are not always readily made, nor does PFS correlate well with OS.2,3 Contrast-enhanced MRI (CE-MRI) represents the best available method for measuring treatment response and predicting survival after standard first-line therapy and is used to define PFS.2–4 Currently, decisions about treatment are guided by criteria (Macdonald, RANO) that equate increasing size of CE-MRI enhancement with progressive tumor burden, treatment failure, and poor prognosis.5,6 Despite its widespread use, this approach has distinct limitations. First, CE-MRI cannot distinguish tumor growth from treatment-induced parenchymal injury, so called post-treatment radiation effect (PTRE), which exactly mimics tumor on CE-MRI. Two well documented forms of PTRE are pseudoprogression (pP) and radiation necrosis (RN). Unlike tumor, PTRE represents a positive response to treatment and, therefore, a good prognosis; however, PTRE-related enhancement underlies erroneous declaration of treatment failure in up to half of cases.7–10 In addition, tumor often coexists and variably admixes with PTRE in most patients.11 The histologic tumor fraction (i.e., tumor burden) therefore comprises a subcomponent of the total CE-MRI enhancement and represents a potentially useful predictor of survival in patients with recurrent brain tumor.12–14 In fact, studies suggest that histologically quantifying tumor burden provides more meaningful prognostic information than simply reporting the presence of tumor.12–15 Because CE-MRI cannot reliably distinguish the coexistence of PTRE and tumor burden, surgical biopsy and histologic evaluation remain the current benchmark.13 Unfortunately, surgery is not without medical risk, morbidity, and cost. These issues underscore a clear need to develop a noninvasive method to accurately estimate tumor burden as a potential alternative or adjunct to surgical biopsy. Perfusion MRI (pMRI) noninvasively detects GBM and PTRE microvascular characteristics, most commonly with the dynamic susceptibility-weighted contrast-enhanced (DSC) method. With use of pMRI, relative cerebral blood volume (rCBV) is measured on a voxel-wise basis across CE-MRI lesions, providing regionally specific estimates of tissue microvasculature and histologic identity.16–24 To date, several pMRI-based analytic methods have been proposed to estimate histologic tumor fraction, each with potential advantages and limitations. First, calculating mean rCBV across all CE-MRI lesion voxels is the easiest method but does not assess intervoxel variations that may reflect histologic heterogeneity.16,17 Second, histogram analysis contributes additional metrics, including mode, maximum, and histogram width, although these may be biased by spatial statistics.18,19 Finally, the voxel-based thresholding method applies predetermined rCBV criteria to classify individual voxels based on histologic identity, but requires that the accuracy of the threshold be prospectively validated.20,21 To date, no published studies support consensus regarding which pMRI-based analytic method best estimates histologic tumor fraction as a predictor of survival in recurrent GBM. Our hypothesis is that tumor burden and OS will correlate more strongly with those pMRI-based methods that use a voxel-based approach to assess histologic heterogeneity. We here report a study in a cohort of patients with recurrent GBM with CE-MRI evidence of tumor progression. Our goals were to (1) determine the strengths of correlation between histologic tumor fraction and previously published pMRI-based metrics (rCBV mean, mode, maximum, and histogram width) and a new voxel-based thresholding metric, called pMRI fractional tumor burden (pMRI-FTB), and (2) identify which pMRI-based metric best correlates with OS.

A large number of studies have demonstrated that structures within the medial temporal lobe, such as the hippocampus, are intimately involved in declarative memory for objects and people. Although these items are abstractions of the visual scene, specific visual details can change the speed and accuracy of their recall. By recording from 415 neurons in the hippocampus and amygdala of human epilepsy patients as they viewed images drawn from 10 image categories, we showed that the firing rates of 8% of these neurons encode image illuminance and contrast, low-level properties not directly pertinent to task performance, whereas in 7% of the neurons, firing rates encode the category of the item depicted in the image, a high-level property pertinent to the task. This simultaneous representation of high- and low-level image properties within the same brain areas may serve to bind separate aspects of visual objects into a coherent percept and allow episodic details of objects to influence mnemonic performance.

INTRODUCTION: Recent developments in optical science and image processing have miniaturized the components required for confocal microscopy. Clinical confocal imaging applications have emerged, including assessment of colonic mucosal dysplasia during colonoscopy. We present our initial experience with handheld, miniaturized confocal imaging in a murine brain tumor model. METHODS: Twelve C57/BL6 mice were implanted intracranially with 10 5 GL261 glioblastoma cells. The brains of 6 anesthetized mice each at 14 and 21 days after implantation were exposed surgically, and the brain surface was imaged using a handheld confocal probe affixed to a stereotactic frame. The probe was moved systematically over regions of normal and tumor-containing tissue. Intravenous fluorescein and topical acriflavine contrast agents were used. Biopsies were obtained at each imaging site beneath the probe and assessed histologically. Mice were killed after imaging. RESULTS: Handheld confocal imaging produced exquisite images, well-correlated with corresponding histologic sections, of cellular shape and tissue architecture in murine brain infiltrated by glial neoplasm. Reproducible patterns of cortical vasculature, as well as normal gray and white matter, were identified. Imaging effectively distinguished between tumor and nontumor tissue, including infiltrative tumor margins. Margins were easily identified by observers without prior neuropathology training after minimum experience with the technology. CONCLUSION: Miniaturized handheld confocal imaging may assist neurosurgeons in detecting infiltrative brain tumor margins during surgery. It may help to avoid sampling error during biopsy of heterogeneous glial neoplasms, with the potential to supplement conventional intraoperative frozen section pathology. Clinical trials are warranted on the basis of these promising initial results.

BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) accuracy can vary substantially depending on the dynamic susceptibility-weighted contrast-enhanced (DSC) acquisition and postprocessing methods, due to blood-brain barrier disruption and resulting T1-weighted leakage and T2- and/or T2*-weighted imaging (T2/T2*WI) residual effects. We set out to determine optimal DSC conditions that address these errors and maximize rCBV accuracy in differentiating posttreatment radiation effect (PTRE) and tumor. MATERIALS AND METHODS: We recruited patients with previously treated high-grade gliomas undergoing image-guided re-resection of recurrent contrast-enhancing MR imaging lesions. Thirty-six surgical tissue samples were collected from 11 subjects. Preoperative 3T DSC used 6 sequential evenly timed acquisitions, each by using a 0.05-mmol/kg gadodiamide bolus. Preload dosing (PLD) and baseline subtraction (BLS) techniques corrected T1-weighted leakage and T2/T2*WI residual effects, respectively. PLD amount and incubation time increased with each sequential acquisition. Corresponding tissue specimen stereotactic locations were coregistered to DSC to measure localized rCBV under varying PLD amounts, incubation times, and the presence of BLS. rCBV thresholds were determined to maximize test accuracy (average of sensitivity and specificity) in distinguishing tumor ( n = 21) and PTRE ( n = 15) samples under the varying conditions. Receiver operator characteristic (ROC) areas under the curve (AUCs) were statistically compared. RESULTS: The protocol that combined PLD (0.1-mmol/kg amount, 6-minute incubation time) and BLS correction methods maximized test AUC (0.99) and accuracy (95.2%) compared with uncorrected rCBV AUC (0.85) and accuracy (81.0%) measured without PLD and BLS ( P = .01). CONCLUSIONS: Combining PLD and BLS correction methods for T1-weighted and T2/T2*WI errors, respectively, enables highly accurate differentiation of PTRE and tumor growth.

Object The purpose of this study was to determine whether increased local control and improved survival can be achieved in patients with glioblastoma multiformes (GBMs) who undergo aggressive resection, Gliadel wafer implantation, Gamma Knife radiosurgery (GKS), and fractionated radiotherapy (RT) as the initial treatment. Methods Thirty patients with radiographically suspected GBMs were screened for enrollment in a Phase I/II prospective clinical trial. Twenty-seven patients were eligible and underwent gross-total resection and Gliadel wafer implantation. Gamma Knife radiosurgery (12 Gy at 50%) was administered to the resection cavity within 2 weeks of surgery. Patients then received standard fractionated RT (total dose 60 Gy over 6 weeks). Temozolomide was prescribed for patients at the time of recurrence. Surveillance MR imaging, neurological examination, and quality-of-life evaluations were performed at 2-month intervals. To estimate the potential effects on the DNA repair mechanism, tumor tissue was analyzed with methylation-specific polymerase chain reaction analysis and immunohistochemical assays for MGMT gene promoter methylation and protein expression. Results The median survival for all patients was 50 weeks and the 2-year survival rate was 22%. When stratified into standard and high-risk patient groups, the median survivals were 76 and 33 weeks, respectively. Two patients remain alive at the time of this report with no clinical or radiographic evidence of disease at > 189 and 239 weeks posttreatment and excellent performance status. Local tumor control was achieved in 53% of patients, and local failure occurred in 47%. No acute early toxicity was noted; however, delayed symptomatic radionecrosis occurred in 47% of patients, which required repeated operations 9–24 months after the initial treatment. Delayed hydrocephalus requiring ventriculoperitoneal shunt placement occurred in 47% of patients. There was a significant difference in survival between patients whose tumors contained the methylated and unmethylated MGMT promoter, 103 versus 45 weeks, respectively (p = 0.0009, log-rank test). Conclusions The combination of aggressive resection, Gliadel wafer implantation, and GKS in addition to standard fractionated RT in selected patients resulted in increased local control and increased survival compared with a historical control group treated with surgery and involved-field RT alone. Delayed focal radionecrosis was increased to 47% in this series and was managed with steroids and repeated resection. Aggressive local tumor control with these multimodal therapies should be approached judiciously for a select group of high performance patients and the probability of developing symptomatic radionecrosis requiring surgery should be anticipated and fully disclosed to patients who undergo this treatment.

Objective For frameless stereotaxy, users can choose between anatomic landmarks (ALs) or surface fiducial markers (FMs) for their match points during registration to define an alignment of the head in the physical and radiographic image space. In this study, we sought to determine the concordance among a point-merged FM registration, a point-merged AL registration, and a combined point-merged anatomic/surface-merged (SM) registration, i.e., to determine the accuracy of registration techniques with and without FMs by examining the extent of agreement between the system-generated predicted value and physical measured values. Methods We examined 30 volunteers treated with gamma knife surgery. The frameless stereotactic image-guidance system called the StealthStation (Medtronic Surgical Navigation Technologies, Louisville, CO) was used. Nine FMs were placed on the patient's head and four were placed on a Leksell frame rod-box, which acted as a rigid set to determine the difference in error. For each registration form, we recorded the generated measurement (GM) and the physical measurement (PM) to each of the four checkpoint FMs. Bland and Altman plot difference analyses were used to compare measurement techniques. Correlations and descriptive analyses were completed. Results The mean of values for GMs were 1.14 mm for FM, 2.3 mm for AL, and 0.96 mm for SM registrations. The mean errors of the checkpoints were 3.49 mm for FM, 3.96 mm for AL, and 3.33 mm for SM registrations. The correlation between GMs and PMs indicated a linear relationship for all three methods. AL registration demonstrated the greatest mean difference, followed by FM registration; SM registration had the smallest difference between GMs and PMs. Differences in the anatomic registration methods, including SM registration, compared with FM registration were within a mean +/- 1.96 (standard deviation) according to the Bland and Altman analysis. Conclusion For our sample of 30 patients, all three registration methods provided comparable distances to the target tissue for surgical procedures. Users may safely choose anatomic registration as a less costly and more time-efficient registration method for frameless stereotaxy.

Background Genetic profiling represents the future of neuro-oncology but suffers from inadequate biopsies in heterogeneous tumors like Glioblastoma (GBM). Contrast-enhanced MRI (CE-MRI) targets enhancing core (ENH) but yields adequate tumor in only ~60% of cases. Further, CE-MRI poorly localizes infiltrative tumor within surrounding non-enhancing parenchyma, or brain-around-tumor (BAT), despite the importance of characterizing this tumor segment, which universally recurs. In this study, we use multiple texture analysis and machine learning (ML) algorithms to analyze multi-parametric MRI, and produce new images indicating tumor-rich targets in GBM. Methods We recruited primary GBM patients undergoing image-guided biopsies and acquired pre-operative MRI: CE-MRI, Dynamic-Susceptibility-weighted-Contrast-enhanced-MRI, and Diffusion Tensor Imaging. Following image coregistration and region of interest placement at biopsy locations, we compared MRI metrics and regional texture with histologic diagnoses of high- vs low-tumor content (≥80% vs

Background and purposeRelative cerebral blood volume, as measured by T2*-weighted dynamic susceptibility-weighted contrast-enhanced MRI, represents the most robust and widely used perfusion MR imaging metric in neuro-oncology. Our aim was to determine whether differences in modeling implementation will impact the correction of leakage effects (from blood-brain barrier disruption) and the accuracy of relative CBV calculations as measured on T2*-weighted dynamic susceptibility-weighted contrast-enhanced MR imaging at 3T field strength.Materials and methodsThis study included 52 patients with glioma undergoing DSC MR imaging. Thirty-six patients underwent both non-preload dose- and preload dose-corrected DSC acquisitions, with 16 patients undergoing preload dose-corrected acquisitions only. For each acquisition, we generated 2 sets of relative CBV metrics by using 2 separate, widely published, FDA-approved commercial software packages: IB Neuro and nordicICE. We calculated 4 relative CBV metrics within tumor volumes: mean relative CBV, mode relative CBV, percentage of voxels with relative CBV > 1.75, and percentage of voxels with relative CBV > 1.0 (fractional tumor burden). We determined Pearson (r) and Spearman (ρ) correlations between non-preload dose- and preload dose-corrected metrics. In a subset of patients with recurrent glioblastoma (n = 25), we determined receiver operating characteristic area under the curve for fractional tumor burden accuracy to predict the tissue diagnosis of tumor recurrence versus posttreatment effect. We also determined correlations between rCBV and microvessel area from stereotactic biopsies (n = 29) in 12 patients.ResultsWith IB Neuro, relative CBV metrics correlated highly between non-preload dose- and preload dose-corrected conditions for fractional tumor burden (r = 0.96, ρ = 0.94), percentage > 1.75 (r = 0.93, ρ = 0.91), mean (r = 0.87, ρ = 0.86), and mode (r = 0.78, ρ = 0.76). These correlations dropped substantially with nordicICE. With fractional tumor burden, IB Neuro was more accurate than nordicICE in diagnosing tumor versus posttreatment effect (area under the curve = 0.85 versus 0.67) (P < .01). The highest relative CBV-microvessel area correlations required preload dose and IB Neuro (r = 0.64, ρ = 0.58, P = .001).ConclusionsDifferent implementations of perfusion MR imaging software modeling can impact the accuracy of leakage correction, relative CBV calculation, and correlations with histologic benchmarks.

We report the results of a bilingual continuous recognition memory task during which single- and multi-neuron activity was recorded in human subjects with intracranial microwire implants. Subjects (n = 5) were right-handed Spanish-English bilinguals who were undergoing evaluation prior to surgery for severe epilepsy. Subjects were presented with Spanish and English words and the task was to determine whether any given word had been seen earlier in the testing session, irrespective of the language in which it had appeared. Recordings in the left and right hippocampus revealed notable laterality, whereby both Spanish and English items that had been seen previously in the other language (switch trials) triggered increased neural firing in the left hippocampus. Items that had been seen previously in the same language (repeat trials) triggered increased neural firings in the right hippocampus. These results are consistent with theories that propose roles of both the left- and right-hemisphere in real-time linguistic processing. Importantly, this experiment presents the first instance of intracranial recordings in bilinguals performing a task with switching demands.

We report a 23-year-old man with intractable epilepsy and an incidental posterior communicating artery aneurysm who was treated simultaneously for both pathologies. He was counseled regarding the potential to treat both pathologies with one procedure. He elected to undergo a simultaneous approach. The patient was doing well at his 5-month follow-up examination with no residual seizures or neurologic deficits. We conclude that access to aneurysms within the basal cisterns is viable with transchoroidal approaches through the temporal horn of the lateral ventricle. Anterior extension through portions of the amygdala further increases access. In our patient, selective amygdalohippocampectomy and posterior communicating artery aneurysm clipping were performed during the same surgical setting/approach. This directly lateral corridor allowed our young patient with an incidental aneurysm to undergo a less invasive combined operation rather than two separate procedures.

Neurocomputational models hold that sparse distributed coding is the most efficient way for hippocampal neurons to encode episodic memories rapidly. We investigated the representation of episodic memory in hippocampal neurons of nine epilepsy patients undergoing intracranial monitoring as they discriminated between recently studied words (targets) and new words (foils) on a recognition test. On average, single units and multiunits exhibited higher spike counts in response to targets relative to foils, and the size of this effect correlated with behavioral performance. Further analyses of the spike-count distributions revealed that (i) a small percentage of recorded neurons responded to any one target and (ii) a small percentage of targets elicited a strong response in any one neuron. These findings are consistent with the idea that in the human hippocampus episodic memory is supported by a sparse distributed neural code.

Despite improvements in the medical and surgical management of patients with glioblastoma, tumor recurrence remains inevitable. For recurrent glioblastoma, however, the clinical value of a second resection remains uncertain. Specifically, what proportion of contrast-enhancing recurrent glioblastoma tissue must be removed to improve overall survival and what is the neurological cost of incremental resection beyond this threshold?The authors identified 170 consecutive patients with recurrent supratentorial glioblastomas treated at the Barrow Neurological Institute from 2001 to 2011. All patients previously had a de novo glioblastoma and following their initial resection received standard temozolomide and fractionated radiotherapy.The mean clinical follow-up was 22.6 months and no patient was lost to follow-up. At the time of recurrence, the median preoperative tumor volume was 26.1 cm(3). Following re-resection, median postoperative tumor volume was 3.1 cm(3), equating to an 87.4% extent of resection (EOR). The median overall survival was 19.0 months, with a median progression-free survival following re-resection of 5.2 months. Using Cox proportional hazards analysis, the variables of age, Karnofsky Performance Scale (KPS) score, and EOR were predictive of survival following repeat resection (p = 0.0001). Interestingly, a significant survival advantage was noted with as little as 80% EOR. Recursive partitioning analysis validated these findings and provided additional risk stratification at the highest levels of EOR. Overall, at 7 days after surgery, a deterioration in the NIH stroke scale score by 1 point or more was observed in 39.1% of patients with EOR ≥ 80% as compared with 16.7% for those with EOR80% (p = 0.0049). This disparity in neurological morbidity, however, did not endure beyond 30 days postoperatively (p = 0.1279).For recurrent glioblastomas, an improvement in overall survival can be attained beyond an 80% EOR. This survival benefit must be balanced against the risk of neurological morbidity, which does increase with more aggressive cytoreduction, but only in the early postoperative period. Interestingly, this putative EOR threshold closely approximates that reported for newly diagnosed glioblastomas, suggesting that for a subset of patients, the survival benefit of microsurgical resection does not diminish despite biological progression.

Purpose: To assess the efficacy and complications of Gamma Knife radiosurgery for trigeminal neuralgia. Methods and Materials: The Barrow Neurological Institute (BNI) Gamma Knife facility has been operational since March 17, 1997. A total of 557 patients have been treated, 89 for trigeminal neuralgia (TN). This report includes the first 54 TN patients with follow-up exceeding 3 months. Patients were treated with Gamma Knife stereotactic radiosurgery (RS) in uniform fashion according to two sequential protocols. The first 41 patients received 35 Gy prescribed to the 50% isodose via a single 4-mm isocenter targeting the ipsilateral trigeminal nerve adjacent to the pons. The dose was increased to 40 Gy for the remaining 13 patients; however, the other parameters were unvaried. Outcome was evaluated by each patient using a standardized questionnaire. Pain before and after RS was scored as level I–IV per our newly-developed BNI pain intensity scoring criteria (I: no pain; II: occasional pain, not requiring medication; III: some pain, controlled with medication; IV: some pain, not controlled with medication; V: severe pain/no pain relief). Complications, limited to mild facial numbness, were similarly graded by a BNI scoring system. Results: Among our 54 TN patients, 52 experienced pain relief, BNI score I in 19 (35%), II in 3 (6%), III in 26 (48%), and IV in 4 (7%). Two patients (4%) reported no relief (BNI score V). Median follow-up was 12 months (range 3–28). Median time to onset of pain relief was 15 days (range 0–192), and to maximal relief 63 days (range 0–253). Seventeen (31%) noted immediate improvement (≤ 24 h). Prior to RS, all patients were on pharmacologic therapy felt to be optimal or maximal. Twenty-two (41%) were able to stop medications entirely (BNI score I or II). Another 16 (30%), with BNI Score III relief, decreased medication intake by at least 50%. Patients with classical TN pain symptoms were more likely to stop medications than those with atypical features, 49% (21 of 43) versus 9% (1 of 11). This difference was significant at p = 0.040. Statistically, the finding most predictive for pain relief was new facial numbness following RS. Each of the 5 patients with new numbness after RS developed BNI score I relief, contrasting with 35% for the 49 patients with no new numbness ( p = 0.019). Complications have been limited to delayed, mild facial sensory loss. Before RS, 17 patients had numbness from prior invasive procedures, none of whom reported a worse numbness score after treatment. Thirty-seven patients had no facial numbness at the time of RS, of whom 5 developed facial hypesthesia. Each rated this as "mild, not bothersome." There have been no other sequellae. Conclusion: RS is an effective treatment, and is the least invasive nonpharmacologic therapy for TN. It carries a small risk of mild facial hypesthesia, a side effect which, somewhat ironically, may be desirable, because it appears to correlate favorably with an excellent pain response. We currently include radiosurgery among the appropriate options for TN patients who have failed optimal medical management, with or without prior invasive neurosurgical procedures. We present here BNI scoring systems for pain intensity and facial numbness. These have proved simple and reliable, have facilitated data collection, rendered analysis more objective, and improved our ability to discuss results with patients and colleagues.

UNLABELLED OBJECTIVES AND IMPORTANCE: Although controversial, revascularization of the distal posterior cerebral artery (PCA) may become necessary in treating complex PCA aneurysms before proximal parent vessel sacrifice. The revascularization of the distal PCA territories of two patients with peripheral PCA aneurysms is presented. CLINICAL PRESENTATIONS One patient had an aneurysm of the P2-P3 segment and failed a selective P2 balloon occlusion test by developing homonymous hemianopia before planned parent vessel sacrifice. The other patient with a giant P2 segment aneurysm presented with visual field deficits. TECHNIQUE The distal segment of PCA was revascularized before the aneurysms were trapped by surgical clipping or coil occlusion of the distal P2 segment, proximal to the aneurysms. In both cases, the occipital artery was used as the "donor" vessel. Temporary occlusion times were 22 and 20 minutes, respectively. Both grafts were patent on postoperative angiography, and both patients had full visual fields at the time of their follow-up examinations. CONCLUSION De novo distal P2 sacrifice, advocated for treating peripheral PCA aneurysms, leads to visual field deficits in some patients. Revascularization of the distal segment of the PCA, less technically demanding than bypass to other PCA segments, preserves blood flow, thus sparing vision in this subset of patients.

Patients with atypical meningioma often undergo gross-total resection (GTR) at initial presentation, but the role of adjuvant radiation therapy remains unclear. The increasing prevalence of stereotactic radiosurgery (SRS) in the modern neurosurgical era has led to the use of routine postoperative radiation therapy in the absence of evidence-based guidelines. This study sought to define the long-term recurrence rate of atypical meningiomas and identify the value of SRS in affecting outcome.The authors identified 228 patients with microsurgically treated atypical meningiomas who underwent a total of 257 resections at the Barrow Neurological Institute over the last 20 years. Atypical meningiomas were diagnosed according to current WHO criteria. Clinical and radiographic data were collected retrospectively.Median clinical and radiographic follow-up was 52 months. Gross-total resection, defined as Simpson Grade I or II resection, was achieved in 149 patients (58%). The median proliferative index was 6.9% (range 0.4%-20.6%). Overall 51 patients (22%) demonstrated tumor recurrence at a median of 20.2 months postoperatively. Seventy-one patients (31%) underwent adjuvant radiation postoperatively, with 32 patients (14%) receiving adjuvant SRS and 39 patients (17%) receiving adjuvant intensity modulated radiation therapy (IMRT). The recurrence rate for patients receiving SRS was 25% (8/32) and for IMRT was 18% (7/39), which was not significantly different from the overall group. Gross-total resection was predictive of progression-free survival (PFS; relative risk 0.255, p0.0001), but postoperative SRS was not associated with improved PFS in all patients or in only those with subtotal resections.Atypical meningiomas are increasingly irradiated, even after complete or near-complete microsurgical resection. This analysis of the largest patient series to date suggests that close observation remains reasonable in the setting of aggressive microsurgical resection. Although postoperative adjuvant SRS did not significantly affect tumor recurrence rates in this experience, a larger cohort study with longer follow-up may reveal a therapeutic benefit in the future.

✓ The use of the supratentorial—infraoccipital approach is reported in seven patients with posteromedial temporal lobe lesions. No patient had permanent morbidity. Gross total resection of three low-grade gliomas and two gangliogliomas was achieved in five patients; one patient had subtotal resection of a low-grade glioma with adjacent gliosis, and one was initially thought to have a glioma but proved to have encephalomalacia on final pathological analysis. The patients ranged in age from 5 to 34 years. All seven patients presented with seizures, and four had uncontrolled seizures preoperatively. Six have been seizure-free since surgery (mean follow-up period 15 months), and one is well controlled on anticonvulsant medication. An anatomical study was performed to delineate the microsurgical anatomy relevant to operating on the medial temporal lobe through this posterior approach. A viewing wand intraoperative navigational system was utilized with this approach and proved helpful in gaining access as far anterior as the uncus through this occipital craniotomy. This approach is favorable in selected patients with posterior, medial, temporal lobe tumors because resection of otherwise difficult lesions may be accomplished without sacrificing lateral temporal lobe cortex or transecting the optic radiations.

Intradural spinal teratomas are rare tumors of the spinal cord that are infrequently encountered in children. Although the mechanistic basis for the formation of these tumors is unclear, several lines of evidence suggest that a dysembryogenic process in the embryo results in their formation. The authors present a case of spinal intradural teratoma in an 18-year-old, previously healthy man and review the literature linking the development of these tumors to defects in neurulation and embryogenesis.

The optimal management of pineocytomas remains controversial. Although the value of complete microsurgical removal is well accepted, gross-total resection is not always feasible. Data regarding the role of postoperative adjuvant stereotactic radiosurgery (SRS) for residual disease is limited and conflicting. Here, the authors review the largest single-institution experience with multimodal pineocytoma management in an effort to quantify the utility of adjuvant radiosurgical treatment of residual disease.The medical records and radiographic studies for all patients with histologically confirmed pineocytoma at the Barrow Neurological Institute between 1999 and 2011 were retrospectively reviewed. Clinical and radiographic data, including the volumetric extent of resection, were collected retrospectively, and Kaplan-Meier analysis was used to identify progression-free survival.Fourteen adults with newly diagnosed pineocytomas were surgically treated in the period from 1999 to 2011. The median clinical and radiographic follow-ups were 44 and 53 months, respectively. Twelve patients (86%) underwent microsurgical removal and 2 (14%) underwent endoscopic biopsy. Five patients (36%) had complete resections and 9 (64%) demonstrated residual disease. Three patients (21%) presented with radiographic recurrence at a median interval of 43 months after initial treatment (range 13-83 months). At the time of recurrence, the median preoperative tumor volume was 2.6 cm(3). Adjuvant SRS was used to treat 3 subtotally resected tumors (33%) following initial presentation and 2 (66%) at the time of recurrence. Among patients with subtotally resected tumors, progression-free survival was significantly longer (p0.05) for those who did as compared with those who did not undergo adjuvant radiosurgery. To date, no patient who underwent adjuvant radiosurgery has demonstrated radiographic or clinical evidence of disease progression.Microsurgical removal remains the definitive treatment for pineocytomas, yet residual disease can be effectively controlled using adjuvant SRS.

Oligodendrogliomas that enhance on MR images are associated with poor prognosis. However, the importance of the volume of enhancing tumor tissue, and the extent of its resection, is uncertain. The authors examined the prognostic significance of preoperative and residual postoperative enhancing tissue volumes in a large single-center series of patients with oligodendroglioma. They also examined the relationship between enhancement and characteristic genetic signatures in oligodendroglial tumors, specifically deletion of 1p and 19q (del 1p/19q).The authors retrospectively analyzed 100 consecutive cases of oligodendroglioma involving patients who had undergone T1-weighted gadolinium-enhanced MRI at diagnosis and immediately after initial surgical intervention. The presence of preoperative enhancement was determined by consensus. Preoperative and residual postoperative volumes were measured using a quantitative, semiautomated method by a single blinded observer. Intrarater reliability for preoperative volumes was confirmed by remeasurement in a subset of patients 3 months later. Intrarater and interrater reliability for residual postoperative volumes was confirmed by remeasurement of these volumes by both the original and a second blinded observer. Multivariate analysis was used to assess the influence of contrast enhancement at diagnosis and the volume of pre- and postoperative contrast-enhancing tumor tissue on time to relapse (TTR) and overall survival (OS), while controlling for confounding clinical, pathological, and genetic factors.Sixty-three of 100 patients had enhancing tumors at initial presentation. Presence of contrast enhancement at diagnosis was related to reduced TTR and OS on univariate analysis but was not significantly related on multivariate analysis. In enhancing tumors, however, greater initial volume of enhancing tissue correlated with shortened TTR (p = 0.00070). Reduced postoperative residual enhancing volume and a relatively greater resection of enhancing tissue correlated with longer OS (p = 0.0012 and 0.0041, respectively). Interestingly, patients in whom 100% of enhancing tumor was resected had significantly longer TTR (174 vs 64 weeks) and OS (392 vs 135 weeks) than those with any residual enhancing tumor postoperatively. This prognostic benefit was not consistently maintained with greater than 90% or even greater than 95% resection of enhancing tissue. There was no relationship between presence or volume of enhancement and del 1p/19q.In enhancing oligodendrogliomas, completely resecting enhancing tissue independently improves outcome, irrespective of histological grade or genetic status. This finding supports aggressive resection and may impact treatment planning for patients with these tumors.