Functional connectivity reveals different brain networks underlying the idiopathic foreign accent syndrome.

Foreign accent syndrome (FAS) is characterized by new onset speech that is perceived as foreign. Available data from acquired cases suggests focal brain damage in language and sensorimotor brain networks, but little remains known about abnormal functional connectivity in idiopathic cases of FAS without structural damage. Here, connectomic analyses were completed on three patients with idiopathic FAS to investigate unique functional connectivity abnormalities underlying accent change for the first time. Machine learning (ML)-based algorithms generated personalized brain connectomes based on a validated parcellation scheme from the Human Connectome Project (HCP). Diffusion tractography was performed on each patient to rule out structural fiber damage to the language system. Resting-state-fMRI was assessed with ML-based software to examine functional connectivity between individual parcellations within language and sensorimotor networks and subcortical structures. Functional connectivity matrices were created and compared against a dataset of 200 healthy subjects to identify abnormally connected parcellations. Three female patients (28-42 years) who presented with accent changes from Australian English to Irish (n = 2) or American English to British English (n = 1) demonstrated fully intact language system structural connectivity. All patients demonstrated functional connectivity anomalies within language and sensorimotor networks in numerous left frontal regions and between subcortical structures in one patient. Few commonalities in functional connectivity anomalies were identified between all three patients, specifically 3 internal-network parcellation pairs. No common inter-network functional connectivity anomalies were identified between all patients. The current study demonstrates specific language, and sensorimotor functional connectivity abnormalities can exist and be quantitatively shown in the absence of structural damage for future study.

Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of cytoreductive surgery in the management of progressive glioblastoma in adults.

QUESTION: In patients with previously diagnosed glioblastoma who are suspected of experiencing progression, does repeat cytoreductive surgery improve progression free survival or overall survival compared to alternative interventions? TARGET POPULATION: These recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process and are amenable to surgical resection. RECOMMENDATION: Level II: Repeat cytoreductive surgery is recommended in progressive glioblastoma patients to improve overall survival.

A consensus definition of supratotal resection for anatomically distinct primary glioblastoma: an AANS/CNS Section on Tumors survey of neurosurgical oncologists.

INTRODUCTION: Supratotal resection (SpTR) of glioblastoma may be associated with improved survival, but published results have varied in part from lack of consensus on the definition and appropriate use of SpTR. A previous small survey of neurosurgical oncologists with expertise performing SpTR found resection 1-2 cm beyond contrast enhancement was an acceptable definition and glioblastoma involving the right frontal and bilateral anterior temporal lobes were considered most amenable to SpTR. The general neurosurgical oncology community has not yet confirmed the practicality of this definition. METHODS: Seventy-six neurosurgical oncology members of the AANS/CNS Tumor Section were surveyed, representing 34.0% of the 223 members who were administered the survey. Participants were presented with 11 definitions of SpTR and rated each definition's appropriateness. Participants additionally reviewed magnetic resonance imaging for 10 anatomically distinct glioblastomas and assessed the tumor location's eloquence, perceived equipoise of enrolling patients in a randomized trial comparing gross total to SpTR, and their personal treatment plans. RESULTS: Most neurosurgeons surveyed agree that gross total plus resection of some non-contrast enhancement (n = 57, 80.3%) or resection 1-2 cm beyond contrast enhancement (n = 52, 73.2%) are appropriate definitions for SpTR. Cases were divided into three anatomically distinct groups by perceived equipoise between gross total and SpTR. The best clinical trial candidates were thought to be right anterior temporal (n = 58, 76.3%) and right frontal (n = 55, 73.3%) glioblastomas. CONCLUSION: Support exists among neurosurgical oncologists with varying familiarity performing SpTR to adopt the proposed consensus definition of SpTR of glioblastoma and to potentially investigate the utility of SpTR to treat right anterior temporal and right frontal glioblastomas in a clinical trial. A smaller proportion of general neurosurgical oncologists than SpTR experts would personally treat a left anterior temporal glioblastoma with SpTR.

Beyond guidelines: analysis of current practice patterns of AANS/CNS tumor neurosurgeons.

INTRODUCTION: Evidence-based medicine guidelines are increasingly published and sanctioned by organized neurosurgery. However, implementation, interpretation, and use of clinical guidelines may vary substantially on a regional, national and international basis. Survey research can help bridge the gap by providing a snapshot of neurosurgeon attitudes, knowledge, and practices. The American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS) Section on Tumors formed a Survey Committee to formalize the process by which surveys are submitted and reviewed before distribution to our membership. The goal of this committee is to provide peer-review so that collected information will be scientifically robust and useful to the neurosurgical community. METHODS: Surveys submitted to the AANS/CNS tumor section between 2015 and 2019 were reviewed and metrics such as response rate and publication status assessed. RESULTS: Six surveys were submitted to the Survey Committee of the AANS/CNS section on tumors between 2015 and 2019. Four have been circulated to section members, of which three have been published. Response rate has averaged 19% (range 16-23%), a majority of respondents (mean 70%) practice in academic settings. CONCLUSIONS: The AANS/CNS Section on Tumors Survey Committee has and continues to help promote and improve the practice of surveying our community to answer important questions that can advance future training, research, and practice. There remains significant room for improvement in response rates, but ongoing tumor section efforts to increase member engagement will likely improve these numbers.

Use of MRI in diabetic lumbosacral radiculoplexus neuropathy: case report and review of the literature.

Diabetic lumbosacral radiculoplexus neuropathy is often confused with radiculopathy in the context of spinal degenerative disc disease including spinal stenosis. Accuracy in diagnosis may prevent unnecessary interventional procedures including selective nerve root blocks or epidural steroid injections or even surgery in selected cases. Our patient with known diabetes and lumbar disc disease presented with acute onset of pain in L5-S1 distribution of the left lower extremity. Initial MR imaging of the lumbar spine did not show sufficient structural changes to explain her symptomatology. An MR neurogram of the lumbosacral plexus revealed inflammation within the bilateral sciatic and femoral nerves; subsequent EMG demonstrated a generalized sensorimotor neuropathy but no evidence of plexopathy. To our knowledge, this is the first case report that utilized MR imaging of the pelvis to assist in the diagnosis of diabetic lumbosacral radiculoplexus neuropathy (DLRPN).

Orbital malignant meningioma: a unique presentation of a rare entity.

An elderly female with progressive proptosis was found to have an aggressive retrobulbar solid orbital mass. The mass was distinct from the optic nerve sheath and intracranial meninges, and produced concave erosion of the sphenoid wing. Operative findings demonstrated an orbital mass adherent to the dura of the superior orbital fissure. The mass did not demonstrate meningeal violation, infiltrate the superior orbital fissure, or display intracranial spread. The dura remained intact after gross total resection. Histopathology revealed a malignant meningioma with papillary and focal rhabdoid morphology and bony invasion (WHO grade III). The patient received 2500cGy of stereotactic radiotherapy in addition to gross total resection. Postoperatively, the signs and symptoms of orbital mass effect resolved (proptosis, relative afferent papillary defect, and periorbital edema) and the vision improved. There was no orbital recurrence or intracranial extension. The follow-up time was limited to eight months secondary to the patient succumbing to metastatic lung adenocarcinoma, which was demonstrated to be a separate process from the orbital meningioma. We propose the etiology of this tumor to be most consistent with an orbital malignant primary extradural meningioma - the first case reported in the literature.

Foxd4 is essential for establishing neural cell fate and for neuronal differentiation.

Many molecular factors required for later stages of neuronal differentiation have been identified; however, much less is known about the early events that regulate the initial establishment of the neuroectoderm. We have used an in vitro embryonic stem cell (ESC) differentiation model to investigate early events of neuronal differentiation and to define the role of mouse Foxd4, an ortholog of a forkhead-family transcription factor central to Xenopus neural plate/neuroectodermal precursor development. We found that Foxd4 is a necessary regulator of the transition from pluripotent ESC to neuroectodermal stem cell, and its expression is necessary for neuronal differentiation. Mouse Foxd4 expression is not only limited to the neural plate but it is also expressed and apparently functions to regulate neurogenesis in the olfactory placode. These in vitro results suggest that mouse Foxd4 has a similar function to its Xenopus ortholog; this was confirmed by successfully substituting murine Foxd4 for its amphibian counterpart in overexpression experiments. Thus, Foxd4 appears to regulate the initial steps in establishing neuroectodermal precursors during initial development of the nervous system.

Enhancing cold atmospheric plasma treatment of cancer cells by static magnetic field.

It has been reported since late 1970 that magnetic field interacts strongly with biological systems. Cold atmospheric plasma (CAP) has also been widely studied over the past few decades in physics, biology, and medicine. In this study, we propose a novel idea to combine static magnetic field (SMF) with CAP as a tool for cancer therapy. Breast cancer cells and wild type fibroblasts were cultured in 96-well plates and treated by CAP with or without SMF. Breast cancer cells MDA-MB-231 showed a significant decrease in viability after direct plasma treatment with SMF (compared to only plasma treatment). In addition, cancer cells treated by the CAP-SMF-activated medium (indirect treatment) also showed viability decrease but was slightly weaker than the direct plasma-SMF treatment. By integrating the use of SMF and CAP, we were able to discover their advantages that have yet to be utilized. Bioelectromagnetics. 38:53-62, 2017. © 2016 Wiley Periodicals, Inc.

Does Extended Reality Simulation Improve Surgical/Procedural Learning and Patient Outcomes When Compared With Standard Training Methods?: A Systematic Review.

INTRODUCTION: The use of extended reality (XR) technologies, including virtual, augmented, and mixed reality, has increased within surgical and procedural training programs. Few studies have assessed experiential learning- and patient-based outcomes using XR compared with standard training methods. METHODS: As a working group for the Society for Simulation in Healthcare, we used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and a PICO strategy to perform a systematic review of 4238 articles to assess the effectiveness of XR technologies compared with standard training methods. Outcomes were grouped into knowledge, time-to-completion, technical proficiency, reactions, and patient outcomes. Because of study heterogeneity, a meta-analysis was not feasible. RESULTS: Thirty-two studies met eligibility criteria: 18 randomized controlled trials, 7 comparative studies, and 7 systematic reviews. Outcomes of most studies included Kirkpatrick levels of evidence I-III (reactions, knowledge, and behavior), while few reported level IV outcomes (patient). The overall risk of bias was low. With few exceptions, included studies showed XR technology to be more effective than standard training methods in improving objective skills and performance, shortening procedure time, and receiving more positive learner ratings. However, XR use did not show significant differences in gained knowledge. CONCLUSIONS: Surgical or procedural XR training may improve technical skill development among trainees and is generally favored over standard training methods. However, there should be an additional focus on how skill development translates to clinically relevant outcomes. We recommend longitudinal studies to examine retention and transfer of training to clinical settings, methods to improve timely, adaptive feedback for deliberate practice, and cost analyses.

The role of stereotactic radiosurgery for multiple brain metastases in stable systemic disease: a review of the literature.

BACKGROUND: Cancer patients with brain metastases display a median survival of only 1 to 2 months if left untreated. Although whole-brain radiation therapy (WBRT) has lengthened median patient survival, the long-term neurotoxic effects of WBRT have become a deterrent to its use in the context of stable systemic disease. Therefore, it is important to identify patients who might benefit from stereotactic radiosurgery (SRS) in order to delay or avoid WBRT. Here we present a review of the literature to elucidate the role of SRS in patients with multiple brain metastases. METHODS: MEDLINE search for English-language articles from 1998 to 2012 describing survival or neurocognitive functioning of patients with multiple brain metastases treated with SRS, WBRT, or a combination. RESULTS: SRS monotherapy yields an equivalent survival with low risk of long-term neurotoxicity, but higher rate of recurrence, compared to WBRT or combined radiotherapy. Patients with ≤4 brain metastases or KPS ≥ 80 are expected to survive significantly longer than the onset time of prominent WBRT-induced neurocognitive decline. CONCLUSIONS: SRS, administered alone or adjuvant to surgical resection of symptomatic metastases, is preferred for patients with ≤4 brain metastases or KPS ≥ 80 to delay or avoid WBRT. WBRT can then be employed in the event of recurrence. WBRT with or without resection is preferred for patients with ≥5 brain metastases and KPS < 80, due to these patients' shorter survival and increased recurrence risk. SRS boost treatments can then be used in the event of poor tumor response or progression.

Impact of metabolic syndrome on morbidity and mortality following transforaminal interbody fusion (TLIF).

Study design: Retrospective Multi-Institutional Database Study. Objective: Investigate the effect of metabolic syndrome (MetS) on the outcomes of Transforaminal Lumbar Interbody Fusion (TLIF). Summary of background data: TLIF procedures in lumbar spine pathology are common. MetS is a combination of conditions, including medication required hypertension, diabetes mellitus (DM), and body mass index (BMI) of 30 kg/m2s or more. The prevalence of MetS has increased drastically over the past two decades. Our study aimed to understand the effect of MetS on morbidity and mortality of TLIF postoperatively. Methods: Our study used American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) data from 2006 to 2019 to find all patients who underwent TLIF. Patients with MetS were compared to those without MetS. Fisher's test identified univariate relationships between MetS and preoperative/postoperative variables. Multivariable logistic regression models were utilized to analyze the association between MetS and postoperative morbidity and mortality. Results: 54,980 patients were identified who received TLIF. 10.7 % had MetS preoperatively. Patients with and without MetS showed statistically significant univariate differences in most preoperative and postoperative variables. After adjusting for preoperative comorbidities, patients with MetS had greater multivariate-adjusted odds of wound infections (aOR = 1.5889, CI 1.1952-2.112, p = 0.00144), pulmonary events (aOR = 1.5517, CI 1.1207-2.1485, p = 0.00813), renal events (aOR = 2.8685, CI 1.5511-5.3045, p = 0.00078), sepsis (aOR = 1.6773, CI 1.1647-2.4155, p = 5.44E-03), and return to OR (aOR = 1.4764, CI 1.2201-1.7866, p = 6.19E-05). Conclusions: Patients with MetS are at elevated risk for various morbidity and mortality markers after TLIF. Surgeons performing TLIFs on these patients should be aware of the increased potential for postoperative events that may complicate the patient's recovery. Level of evidence: Level III.

Postoperative Morbidity and Mortality in Lumbar Spine Surgery Patients With Chronic Kidney Disease and Chronic Steroid Use.

BACKGROUND: Perioperative steroids have traditionally been administered during lumbar spine surgery in order to decrease local inflammation and prevent scar tissue formation, which can otherwise contribute to significant, long-lasting postoperative pain due to the formation of epidural fibrosis around lumbar nerve roots. However, the use of steroids in lumbar spine patients has raised concerns of postoperative wound complications caused by corticosteroid-induced immunomodulatory effects and changes in collagen synthesis. Patients with chronic kidney disease (CKD) undergoing spine surgery are at a particularly elevated risk of various complications due to chronic CKD-related systemic inflammation and endothelial dysfunction. It is currently uncertain whether chronic steroid use in CKD patients exerts a protective effect postoperatively due to decreased systemic inflammation or instead is correlated with increased rates of wound complications. RESULTS: Using adjusted odds ratios to control for CKD-related comorbidities, our study of lumbar spine fusion patients who were chronic steroid users vs nonusers found no significant differences in rates of postoperative wound infections in later stage CKD patients. However, we also did not observe statistically significant reductions in hospital length of stay or rates of 30-day mortality, sepsis, or cardiac, pulmonary, and renal events. CONCLUSIONS: Our results indicate chronic steroid use neither contributes significantly to rates of wound infections nor exerts a protective effect against postoperative inflammatory complications in lumbar spine patients with CKD. CLINICAL RELEVANCE: Our findings do not support the practice of holding steroids in chronic users prior to lumbar spine surgery. Perioperative steroids do not appear to increase the risk of postoperative complications, but neither do they improve lumbar spine patient outcomes.

Impact of Obesity on Anterior Cervical Discectomy and Fusion (ACDF): Postoperative Morbidity and Mortality.

AIM: To investigate the impact of obesity on postoperative morbidity and mortality in patients who underwent anterior cervical discectomy and fusion (ACDF). MATERIAL AND METHODS: The American College of Surgeons' National Surgical Quality Improvement Project (NSQIP) files from 2006 to 2019 were queried for all patients who underwent an ACDF. Fisher exact tests were used in analyzing univariate differences in preoperative comorbidities and postoperative morbidity and mortality between patients with and without obesity (BMI ?30 kg/ m < sup > 2 < /sup > ). Results with a p value < 0.05 were considered statistically significant. Multivariable logistic regression models were used in determining the independent impact of obesity on ACDF postoperative morbidity and mortality. A p value < 0.017 was required for multivariate statistical significance. RESULTS: There were 96,882 patients who underwent an ACDF from 2006 to 2019 found. 53.77% had non-obese BMI. Patients had statistically significant differences in most perioperative comorbidities and postoperative outcomes on univariate analysis. On multivariate analysis, patients with obesity has decreased adjusted odds of wound infections (aOR=0.7208, CI 0.574-0.9075, p=0.0053), pulmonary events (aOR=0.7939, CI 0.6903-0.9129, p=0.0012), sepsis (aOR=0.5670, CI 0.4359-0.7374, p=2.32E-05), transfusion requirements (aOR=0.5396, CI 0.4498-0.6473, p=3.04E-11), return to operating room (aOR=0.7537, CI 0.6727-0.8447, p=1.17E-06), and length of stay > 10 days (aOR=0.7061, CI 0.6438-0.7744, p=1.49E-13). CONCLUSION: Obesity is a protective factor toward ACDF postoperative complications. Obesity as a marker of patient selection criteria for ACDF procedures should not be used by spine surgeons.

Impact of Cochlear Dose on Hearing Preservation Following Stereotactic Radiosurgery in Treatment of Vestibular Schwannomas: A Multi-Center Study.

OBJECTIVE: Stereotactic radiosurgery (SRS) is a well-established treatment for vestibular schwannomas (VS). Hearing loss remains a main morbidity of VS and its treatments, including SRS. The effects of radiation parameters of SRS on hearing remain unknown. The goal of this study is to determine the effect of tumor volume, patient demographics, pretreatment hearing status, cochlear radiation dose, total tumor radiation dose, fractionation, and other radiotherapy parameters on hearing deterioration. METHODS: Multicenter retrospective analysis of 611 patients who underwent SRS for VS from 1990-2020 and had pre- and post-treatment audiograms. RESULTS: Pure tone averages (PTAs) increased and word recognition scores (WRSs) decreased in treated ears at 12-60 months while remaining stable in untreated ears. Higher baseline PTA, higher tumor radiation dose, higher maximum cochlear dose, and usage of single fraction resulted in higher post radiation PTA; WRS was only predicted by baseline WRS and age. Higher baseline PTA, single fraction treatment, higher tumor radiation dose, and higher maximum cochlear dose resulted in a faster deterioration in PTA. Below a maximum cochlear dose of 3 Gy, there were no statistically significant changes in PTA or WRS. CONCLUSIONS: Decline of hearing at one year in VS patients after SRS is directly related to maximum cochlear dose, single versus 3-fraction treatment, total tumor radiation dose, and baseline hearing level. The maximum safe cochlear dose for hearingtbrowd preservation at one year is 3 Gy, and the use of 3 fractions instead of one fraction was better at preserving hearing.

Radiation necrosis following treatment of high grade glioma--a review of the literature and current understanding.

Radiation therapy is an integral part of the standard treatment paradigm for malignant gliomas, with proven efficacy in randomized control trials. Radiation treatment is not without risk however, and radiation injury occurs in a certain proportion of patients. Difficulties in differentiating recurrence from radiation injury complicate the treatment course and can compromise care. These complexities are compounded by the recent distinction of two types of radiation injury: pseudoprogression and radiation necrosis, which are likely the result of radiation injury to the tumor and normal tissue, respectively. A thorough understanding of radiation-induced injury offers insights to guide further therapies. We detail the current knowledge of the mechanisms of radiation injury, along with potential targets for therapeutic intervention. Various diagnostic modalities are also described, in addition to the multiple options for treatment within the context of their pathophysiology and clinical efficacy. Radiation therapy is an integral part of the multidisciplinary management of gliomas, and the optimal diagnosis and management of radiation injury is paramount to improving patient outcomes.

Theranostic Potential of Adaptive Cold Atmospheric Plasma with Temozolomide to Checkmate Glioblastoma: An In Vitro Study.

Cold atmospheric plasma (CAP) has been used for the treatment of various cancers. The anti-cancer properties of CAP are mainly due to the reactive species generated from it. Here, we analyze the efficacy of CAP in combination with temozolomide (TMZ) in two different human glioblastoma cell lines, T98G and A172, in vitro using various conditions. We also establish an optimized dose of the co-treatment to study potential sensitization in TMZ-resistant cells. The removal of cell culture media after CAP treatment did not affect the sensitivity of CAP to cancer cells. However, keeping the CAP-treated media for a shorter time helped in the slight proliferation of T98G cells, while keeping the same media for longer durations resulted in a decrease in its survivability. This could be a potential reason for the sensitization of the cells in combination treatment. Co-treatment effectively increased the lactate dehydrogenase (LDH) activity, indicating cytotoxicity. Furthermore, apoptosis and caspase-3 activity also significantly increased in both cell lines, implying the anticancer nature of the combination. The microscopic analysis of the cells post-treatment indicated nuclear fragmentation, and caspase activity demonstrated apoptosis. Therefore, a combination treatment of CAP and TMZ may be a potent therapeutic modality to treat glioblastoma. This could also indicate that a pre-treatment with CAP causes the cells to be more sensitive to chemotherapy treatment.

Cold Plasma Discharge Tube Enhances Antitumoral Efficacy of Temozolomide.

Glioblastoma (GBM) is a fatal human brain tumor with a low survival rate. Temozolomide (TMZ) has been widely used in GBM therapy with noticeable side effects. Cold plasma is an ionized gas that is generated near room temperature. Here, we demonstrated the enhancement therapeutic efficacy of TMZ via using a cold plasma source based on nonequilibrium plasma in a sealed glass tube, named a radial cold plasma discharge tube (PDT). The PDT affected glioblastoma cells' function just by its electromagnetic (EM) emission rather than any chemical factors in the plasma. The PDT selectively increased the cytotoxicity of TMZ on two typical glioblastoma cell lines, U87MG and A172, compared with normal astrocyte cell line hTERT/E6/E7 to some extent. Furthermore, on the basis of a patient-derived xenograft model, our preliminary in vivo studies demonstrated the drastically improved mean survival days of the tumor-barrier mice by more than 100% compared to control. The PDT is not only independent of continuous helium supply but is also capable of resisting the interference of environmental changes. Thus, the PDT was a stable and low-cost cold atmospheric plasma source. In short, this study is the first to demonstrate the promising application of PDTs in GBM therapy as a noninvasive and portable modality.

Malignant Pineal Parenchymal Tumors in Adults: A National Cancer Database Analysis.

BACKGROUND: Limited retrospective data exist on malignant pineal parenchymal tumors (PPTs) in adults, and there are no large previous studies that review clinical outcomes across the 3 treatment arms of surgery, radiotherapy, and chemotherapy. As a result, optimal disease management has yet to be defined. OBJECTIVE: To evaluate treatment trends and perform survival analysis in adult PPT. METHODS: The National Cancer Database was queried for histologically confirmed PPT diagnosed from 2007 to 2016. Univariate and multivariate Cox regressions were used to evaluate the prognostic impact of covariates. Kaplan-Meier survival curves were generated for comparative subanalyses. RESULTS: Of the 251 patients who met inclusion criteria, 172 had PPTs of intermediate differentiation (PPTID) and 79 had pineoblastoma. A plurality of patients with pineoblastoma were treated with trimodal therapy (39.1%), whereas patients with PPTID were commonly treated with either surgery alone or surgery and radiation (33.7% each). Factors independently associated with improved overall survival include younger patient age, female sex, lower comorbidity score, lower tumor grade, and treatment with surgery or radiation (each P < .05). Subanalyses confirm the effect of radiation on survival in patients with grade III PPTID with subtotal resection; however, no survival benefit of adjuvant radiation is demonstrated in patients with grade II PPTID with subtotal resection. CONCLUSION: Although radiotherapy and surgery were found to increase survival in all patients with PPT, there was no demonstrable survival benefit of adjuvant radiation in surgically treated patients with grade II PPTID. This suggests that adjuvant radiotherapy may not add significant survival benefit in many adult patients with grade II PPTID.

5-Aminolevulinic acid for enhanced surgical visualization of high-grade gliomas: a prospective, multicenter study.

OBJECTIVE: Greater extent of resection (EOR) is associated with longer overall survival in patients with high-grade gliomas (HGGs). 5-Aminolevulinic acid (5-ALA) can increase EOR by improving intraoperative visualization of contrast-enhancing tumor during fluorescence-guided surgery (FGS). When administered orally, 5-ALA is converted by glioma cells into protoporphyrin IX (PPIX), which fluoresces under blue 400-nm light. 5-ALA has been available for use in Europe since 2010, but only recently gained FDA approval as an intraoperative imaging agent for HGG tissue. In this first-ever, to the authors' knowledge, multicenter 5-ALA FGS study conducted in the United States, the primary objectives were the following: 1) assess the diagnostic accuracy of 5-ALA-induced PPIX fluorescence for HGG histopathology across diverse centers and surgeons; and 2) assess the safety profile of 5-ALA FGS, with particular attention to neurological morbidity. METHODS: This single-arm, multicenter, prospective study included adults aged 18-80 years with Karnofsky Performance Status (KPS) score > 60 and an MRI diagnosis of suspected new or recurrent resectable HGG. Intraoperatively, 3-5 samples per tumor were taken and their fluorescence status was recorded by the surgeon. Specimens were submitted for histopathological analysis. Patients were followed for 6 weeks postoperatively for adverse events, changes in the neurological exam, and KPS score. Multivariate analyses were performed of the outcomes of KPS decline, EOR, and residual enhancing tumor volume to identify predictive patient and intraoperative variables. RESULTS: Sixty-nine patients underwent 5-ALA FGS, providing 275 tumor samples for analysis. PPIX fluorescence had a sensitivity of 96.5%, specificity of 29.4%, positive predictive value (PPV) for HGG histopathology of 95.4%, and diagnostic accuracy of 92.4%. Drug-related adverse events occurred at a rate of 22%. Serious adverse events due to intraoperative neurological injury, which may have resulted from FGS, occurred at a rate of 4.3%. There were 2 deaths unrelated to FGS. Compared to preoperative KPS scores, postoperative KPS scores were significantly lower at 48 hours and 2 weeks but were not different at 6 weeks postoperatively. Complete resection of enhancing tumor occurred in 51.9% of patients. Smaller preoperative tumor volume and use of intraoperative MRI predicted lower residual tumor volume. CONCLUSIONS: PPIX fluorescence, as judged by the surgeon, has a high sensitivity and PPV for HGG. 5-ALA was well tolerated in terms of drug-related adverse events, and its application by trained surgeons in FGS for HGGs was not associated with any excess neurological morbidity.

Neurosurgery for brain tumors: update on recent technical advances.

Advances in diagnostic imaging modalities and improved access to specialty care have led directly to an increased diagnosis of both metastatic and primary brain tumors. As technology has improved, so has the ability to treat this larger patient population. Diffusion tensor imaging (DTI) has recently shown the potential to aid in histologic diagnosis as well as to identify local brain invasion outside of that readily identifiable by conventional MRI. Similar to DTI, functional MRI provides a noninvasive means of delineating tumor margin from eloquent cortex and aids in preoperative surgical planning. As the literature shows increasing support for the advantages of extensive resection in glioma patients, modalities that aid in this regard are displaying increased importance. Surgeons have recently demonstrated the utility of intraoperative MRI in increasing extent of resection in both low- and high-grade glioma patients. Intraoperative tumor fluorescence provided by the chemical compound 5-aminolevulinic acid assists surgeons in identifying the true tumor margin during resection of glial neoplasms consequently increasing extent of resection. Finally, laser interstitial thermal therapy is an emerging treatment modality allowing surgeons to treat small intracranial lesions with potentially decreased morbidity via this minimally invasive approach. The following review analyzes the recent literature in an effort to describe how these modalities can and should be used in the treatment of patients with intracranial pathology.