High-fidelity, simulation-based microsurgical training for neurosurgical residents.

OBJECTIVE: Simulation is increasingly recognized as an important supplement to operative training. The live rat femoral artery model is a well-established model for microsurgical skills simulation. In this study, the authors present an 11-year experience incorporating a comprehensive, longitudinal microsurgical training curriculum into a Canadian neurosurgery program. The first goal was to evaluate training effectiveness, using a well-studied rating scale with strong validity. The second goal was to assess the impact of the curriculum on objective measures of subsequent operating room performance during postgraduate year (PGY)-5 and PGY-6 training. METHODS: PGY-2 neurosurgery residents completed a 1-year curriculum spanning 17 training sessions divided into 5 modules of increasing fidelity. Both perfused duck wing and live rat vessel training models were used. Three modules comprised live microvascular anastomosis. Trainee performance was video recorded and blindly graded using the Objective Structured Assessment of Technical Skills Global Rating Scale. Eleven participants who completed the training curriculum and 3 subjects who had not participated had their subsequent operative performances evaluated when they were at the PGY-5 and PGY-6 levels. RESULTS: Eighteen participants completed 106 microvascular anastomoses during the study. There was significant improvement in 6 measurable skills during the curriculum. The mean overall score was significantly higher on the fifth attempt compared with the first attempt for all 3 live anastomotic modules (p < 0.001). Each module had a different improvement profile across the skills assessed. Those who completed the microvascular skills curriculum demonstrated a greater number of independent evaluations during superficial surgical exposure, deep exposure, and primary maneuvers at the PGY-5 and PGY-6 levels. CONCLUSIONS: High-fidelity microsurgical simulation training leads to significant improvement in microneurosurgical skills. Transfer of acquired skills to the operative environment and durability for at least 3 to 4 years show encouraging preliminary results and are subject to ongoing investigation.

Combination laser interstitial thermal therapy plus stereotactic radiotherapy increases time to progression for biopsy-proven recurrent brain metastases.

Background: Improved survival for patients with brain metastases has been accompanied by a rise in tumor recurrence after stereotactic radiotherapy (SRT). Laser interstitial thermal therapy (LITT) has emerged as an effective treatment for SRT failures as an alternative to open resection or repeat SRT. We aimed to evaluate the efficacy of LITT followed by SRT (LITT+SRT) in recurrent brain metastases. Methods: A multicenter, retrospective study was performed of patients who underwent treatment for biopsy-proven brain metastasis recurrence after SRT at an academic medical center. Patients were stratified by "planned LITT+SRT" versus "LITT alone" versus "repeat SRT alone." Index lesion progression was determined by modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Results: Fifty-five patients met inclusion criteria, with a median follow-up of 7.3 months (range: 1.0-30.5), age of 60 years (range: 37-86), Karnofsky Performance Status (KPS) of 80 (range: 60-100), and pre-LITT/biopsy contrast-enhancing volume of 5.7 cc (range: 0.7-19.4). Thirty-eight percent of patients underwent LITT+SRT, 45% LITT alone, and 16% SRT alone. Median time to index lesion progression (29.8, 7.5, and 3.7 months [P = .022]) was significantly improved with LITT+SRT. When controlling for age in a multivariate analysis, patients treated with LITT+SRT remained significantly less likely to have index lesion progression (P = .004). Conclusions: These data suggest that LITT+SRT is superior to LITT or repeat SRT alone for treatment of biopsy-proven brain metastasis recurrence after SRT failure. Prospective trials are warranted to validate the efficacy of using combination LITT+SRT for treatment of recurrent brain metastases.

History of Women in Neurosurgery (WINS).

In 2020, the Women in Neurosurgery (WINS) organization, a joint section of the AANS and Congress of Neurological Surgeons, celebrated 30 years since its inception. In this paper, the authors explore the history of WINS from its beginnings through its evolution over the past three decades. The achievements of the group are highlighted, as well as the broader achievements of the women in the neurosurgical community over this time period.

Impact of Multi-modality Monitoring Using Direct Electrical Stimulation to Determine Corticospinal Tract Shift and Integrity in Tumors using the Intraoperative MRI.

INTRODUCTION: Preserving the integrity of the corticospinal tract (CST) while maximizing the extent of tumor resection is one of the key principles of brain tumor surgery to prevent new neurologic deficits. Our goal was to determine the impact of the use of perioperative diffusion tensor imaging (DTI) fiber-tracking protocols for location of the CSTs, in conjunction with intraoperative direct electrical stimulation (DES) on patient neurologic outcomes. The role of combining DES and CST shift in intraoperative magnetic resonance imaging (iMRI) to enhance extent of resection (EOR) has not been studied previously. METHODS: A total of 53 patients underwent resection of tumors adjacent to the motor gyrus and the underlying CST between June 5, 2009, and April 16, 2013. All cases were performed in the iMRI (BrainSuite 1.5 T). Preoperative DTI mapping and intraoperative cortical and subcortical DES including postoperative DTI mapping were performed in all patients. There were 32 men and 21 women with 40 high-grade gliomas (76%), 4 low-grade gliomas (8%), and 9 (17%) metastases. Thirty-four patients (64%) were newly diagnosed, and 19 (36%) had a previous resection. There were 31 (59%) right-sided and 22 (42%) left-sided tumors. Eighteen patients (34%) had a re-resection after the first intraoperative scan. Most patients had motor-only mapping, and one patient had both speech and motor mapping. Relative to the resection margin, the CST after the first iMRI was designated as having an outward shift (OS), inward shift (IS), or no shift (NS). RESULTS: A gross total resection (GTR) was achieved in 41 patients (77%), subtotal resection in 4 (7.5%), and a partial resection in 8 (15%). Eighteen patients had a re-resection, and the mean EOR increased from 84% to 95% (p = 0.002). Of the 18 patients, 7 had an IS, 8 an OS, and in 3 NS was noted. More patients in the OS group had a GTR compared with the IS or NS groups (p = 0.004). Patients were divided into four groups based on the proximity of the tumor to the CST as measured from the preoperative scan. Group 1 (32%) included patients whose tumors were 0 to 5 mm from the CST based on preoperative scans; group 2 (28%), 6 to 10 mm; group 3 (13%), 11 to 15 mm; and group 4 (26%), 16 to 20 mm, respectively. Patients in group 4 had fewer neurologic complications compared with other groups at 1 and 3 months postoperatively (p = 0.001 and p = 0.007, respectively) despite achieving a similar degree of resection (p = 0.61). Furthermore, the current of intraoperative DES was correlated to the distance of the tumor to the CST, and the regression equation showed a close linear relationship between the two parameters. CONCLUSIONS: Combining information about intraoperative CST and DES in the iMRI can enhance resection in brain tumors (77% had a GTR). The relative relationship between the positions of the CST to the resection cavity can be a dynamic process that could further influence the surgeon's decision about the stimulation parameters and EOR. Also, the patients with an OS of the CST relative to the resection cavity had a GTR comparable with the other groups.

Phase 0 and window of opportunity clinical trial design in neuro-oncology: a RANO review.

Glioblastoma is a devastating disease with poor prognosis. Few effective chemotherapeutics are currently available, and much effort has been expended to identify new drugs capable of slowing tumor progression. The phase 0 trial design was developed to facilitate early identification of promising agents for cancer that should undergo accelerated approval. This design features an early in-human study that enrolls a small number of patients who receive subtherapeutic doses of medication with the goals of describing pharmacokinetics through drug blood level measurements and determining intratumoral concentrations of the investigational compound as well as pharmacodynamics by studying the biochemical and physiological effects of drugs. In neuro-oncology, however, the presence of the blood-brain barrier and difficulty in obtaining brain tumor tissue warrant a separate set of considerations. In this paper, we critically reviewed the protocols used in all brain tumor related in-human phase 0 and phase 0-like ("window of opportunity") studies between 1993 and 2018, as well as ongoing clinical trials, and identified major challenges in trial design as applied to central nervous system tumors that include surgical specimen collection and storage, brain tumor drug level analysis, and confirmation of drug action. We therefore propose that phase 0 trials in neuro-oncology should include (i) only patients in whom a resection of the tumor is planned, (ii) use of clinical doses of an investigational agent, (iii) tissue sampling from enhancing and non-enhancing portions of the tumor, and (iv) assessment of drug-specific target effects. Standardization of clinical protocols for phase 0/window of opportunity studies can help accelerate the development of effective treatments for glioblastoma.

Pathologic Correlation of Cellular Imaging Using Apparent Diffusion Coefficient Quantification in Patients with Brain Metastases After Gamma Knife Radiosurgery.

OBJECTIVE: To evaluate the role of apparent diffusion coefficient (ADC) in differentiating radiation necrosis (RN) from recurrent tumor after Gamma Knife radiosurgery (GKRS) for brain metastases (BMs). METHODS: Forty-one patients with BM who underwent surgical intervention after GKRS at Cleveland Clinic (2006-2017) were included in this retrospective study. The ADC values of the growing lesions and the contralateral hemisphere were calculated using picture archiving and communication system. These values were correlated to the percentage of RN identified on pathologic evaluation of the surgical specimen. RESULTS: The median age of the patients was 59 years (range, 25-86 years), and lung cancer (63.4%) was the most common malignancy. Median initial (pre-GKRS) target volume of the lesions was 5.4 cc (range, 0.135-45.6 cc), and median GKRS dose was 18.0 Gy. Surgical resection or biopsy was performed at a median of 176 days after GKRS. Two variables were statistically significant predictors of predominate RN (75%-100%) in the surgical specimen: 1) ADC of the lesion on the preresection magnetic resonance imaging (MRI) and 2) initial pre-GKRS target volume. ADC >1.5 × 10-3 mm2/s within the lesion on MRI predicted significant RN on pathologic evaluation of the lesion (P < 0.05). Similarly, when the target volume before GKRS was large (>10 cc), the risk of identifying significant necrosis in the pathologic specimen was elevated (P < 0.05). CONCLUSIONS: Our data suggest that the combination of lesion ADC on MRI prior to surgical intervention and the initial target volume can predict RN with reasonable accuracy.

Laser Interstitial Thermal Therapy for Posterior Fossa Lesions: An Initial Experience.

BACKGROUND: The application of laser interstitial thermal therapy (LITT) for intracranial lesions in the posterior fossa tumors remains challenging due to the smaller size of this compartment as well as the thickness and angle of the occipital bone. In this study, we reviewed our experience with this treatment modality for posterior fossa lesions. METHODS: We retrospectively reviewed our series of 8 patients with posterior fossa tumors treated with LITT from an Institutional Review Board-approved brain tumor database (2012-2017) of more than 200 cases at our institution. RESULTS: The 8 patients underwent LITT targeting 3 metastases, 2 pilocytic astrocytomas, 2 zones of radiation necrosis after radiosurgery, and 1 glioblastoma (GBM). The mean preoperative lesion volume was 4.35 cm3. A 6 months postsurgery, the mean lesion volume had decreased from 9.64 cm3 to 5.72 cm3. Two of the tumors (the GBM and a metastatic adenocarcinoma) progressed after 8.5 and 7.5 months, respectively, with mortality after 1.1 and 1.6 years, respectively. Surgical resection was performed in a patient with metastatic adenocarcinoma tumor at 7.7 months after LITT. All other lesions remained stable or were diminished at a median follow-up of 14.8 months (range, 0.4-37.5 months). Magnetic resonance imaging (MRI) on the first postoperative day, showed an increase in mean tumor-related edema volume from 9.45 cm3 to 14.10 cm3. After a postoperative follow-up of at least 1 month, this mean decreased to 8.70 cm3. One case each of transient partial unilateral sixth cranial nerve palsy, superficial wound infection, and a late obstructive hydrocephalus were noted postoperatively. No mortality was associated with the procedure. CONCLUSIONS: LITT is a safe and feasible treatment modality even in challenging locations like the posterior fossa. However, surgical indications should be tailored for each individual patient based on the size and location of tumor.

Laser interstitial thermal therapy for an eloquent region supratentorial brain lesion.

Laser interstitial thermal therapy (LITT) is a minimally invasive stereotactic technique that causes tumor ablation using thermal energy. LITT has shown to be efficacious for the treatment of deep-seated brain lesions, including those near eloquent areas. In this video, the authors present the case of a 62-year-old man with a history of metastatic melanoma who presented with worsening right-sided hemiparesis. MRI revealed a contrast-enhancing lesion in left centrum semiovale in close proximity to corticospinal tracts, consistent with radiation necrosis. The authors review their stepwise technique of LITT with special attention to details for a lesion located near eloquent area. The video can be found here: https://youtu.be/ndrTgi6MXqE .

Combining Functional Studies with Intraoperative MRI in Glioma Surgery.

Maximal safe resection is the cornerstone of treatment for low-grade and high-grade gliomas. In addition to high-resolution anatomic MRI studies that highlight tumor architecture, it is important to determine the relationship of the tumor to the eloquent cortical and subcortical areas to avoid introducing or exacerbating a neurologic deficit. The goal of this review was to highlight imaging modalities that provide functional information and can be integrated with intraoperative MRI navigation to maximize the extent of resection while preserving a patient's neurologic function.

Technical principles in glioma surgery and preoperative considerations.

The goal of glioma surgery is maximal safe resection. These intrinsic brain neoplasms, however, lack a clear margin and frequently infiltrate eloquent areas of the brain thus making their surgical resection challenging. This review first focuses on discussion of preoperative investigations that aid in anatomical and functional tumor characterization that help define tumor extent and determine the feasibility of complete resection. The second part of this review outlines intraoperative adjuncts that help identify tumor infiltrated tissues during surgery to maximize the extent of resection. In addition, we discuss the principles of intraoperative functional cortical and subcortical mapping and monitoring that enable maximal tumor resection while minimizing the risk of postoperative neurological deficit. Combined use of different modalities before and during surgery is encouraged to meet surgical goals and to ensure best patient outcome.

Cerebellar liponeurocytoma: a rare intracranial tumor with possible familial predisposition. Case report.

The biological origin of cerebellar liponeurocytomas is unknown, and hereditary forms of this disease have not been described. Here, the authors present clinical and histopathological findings of a young patient with a cerebellar liponeurocytoma who had multiple immediate family members who harbored similar intracranial tumors. A 37-year-old otherwise healthy woman presented with a history of progressive headaches. Lipomatous medulloblastoma had been diagnosed previously in her mother and maternal grandfather, and her maternal uncle had a supratentorial liponeurocytoma. MRI revealed a large, poorly enhancing, lipomatous mass emanating from the superior vermis that produced marked compression of posterior fossa structures. An uncomplicated supracerebellar infratentorial approach was used to resect the lesion. Genetic and histopathological analyses of the lesion revealed neuronal, glial, and lipomatous differentiation and confirmed the diagnosis of cerebellar liponeurocytoma. A comparison of the tumors resected from the patient and, 22 years previously, her mother revealed similar features. Cerebellar liponeurocytoma is a poorly understood entity. This report provides novel evidence of an inheritable predisposition for tumor development. Accurate diagnosis and reporting of clinical outcomes and associated genetic and histopathological changes are necessary for guiding prognosis and developing recommendations for patient care.

ErbB4-neuregulin signaling modulates synapse development and dendritic arborization through distinct mechanisms.

Perturbations in neuregulin-1 (NRG1)/ErbB4 function have been associated with schizophrenia. Affected patients exhibit altered levels of these proteins and display hypofunction of glutamatergic synapses as well as altered neuronal circuitry. However, the role of NRG1/ErbB4 in regulating synapse maturation and neuronal process formation has not been extensively examined. Here we demonstrate that ErbB4 is expressed in inhibitory interneurons at both excitatory and inhibitory postsynaptic sites. Overexpression of ErbB4 postsynaptically enhances size but not number of presynaptic inputs. Conversely, knockdown of ErbB4 using shRNA decreases the size of presynaptic inputs, demonstrating a specific role for endogenous ErbB4 in synapse maturation. Using ErbB4 mutant constructs, we demonstrate that ErbB4-mediated synapse maturation requires its extracellular domain, whereas its tyrosine kinase activity is dispensable for this process. We also demonstrate that depletion of ErbB4 decreases the number of primary neurites and that stimulation of ErbB4 using a soluble form of NRG1 results in exuberant dendritic arborization through activation of the tyrosine kinase domain of ErbB4 and the phosphoinositide 3-kinase pathway. These findings demonstrate that NRG1/ErbB4 signaling differentially regulates synapse maturation and dendritic morphology via two distinct mechanisms involving trans-synaptic signaling and tyrosine kinase activity, respectively.