Survival implications of postoperative restricted diffusion in high-grade glioma and limitations of intraoperative MRI detection.

PURPOSE: Here we assess whether the volume of cerebral ischemia induced during glioma surgery may negatively impact survival independently of neurological function. We also evaluate the sensitivity of intraoperative MRI (iMRI) in detecting cerebral ischemia during surgery. METHODS: We retrospectively reviewed 361 cranial surgeries that used a 3 Tesla iMRI. 165 patients met all inclusion criteria and were included in the final analysis. Diffusion weighted imaging (DWI) obtained during iMRI was compared to postoperative DWI obtained within 7 days of the operation in cases where no further resection occurred after the iMRI. RESULTS: 42 of 165 patients (25%) showed at least some evidence of restricted diffusion on postoperative (poMRI). 37 of these 42 (88%) cases lacked evidence of restricted diffusion on iMRI, meaning iMRI had a false-negative rate of 88% and a sensitivity of 12% in assessing the extent of ischemic brain after surgery. In high-grade gliomas, the volume of restricted diffusion on poMRI was predictive of overall survival, independent of new functional deficits acquired during surgery (p = 0.011). CONCLUSION: This study presents the largest case series to date analyzing the sensitivity of iMRI in detecting surgical ischemia. In high-grade gliomas, increased volume of ischemia correlated with worsening median overall survival (OS) irrespective of postoperative neurologic deficits. Future work will focus on improving intraoperative detection of ischemia during the hyperacute phase when interventions such as blood pressure modulation or direct application of vasodilator agents may be effective.

Radio-pathomic maps of glioblastoma identify phenotypes of non-enhancing tumor infiltration associated with bevacizumab treatment response.

BACKGROUND: Autopsy-based radio-pathomic maps of glioma pathology have shown substantial promise inidentifying areas of non-enhancing tumor presence, which may be able to differentiate subsets of patients that respond favorably to treatments such as bevacizumab that have shown mixed efficacy evidence. We tested the hypthesis that phenotypes of non-enhancing tumor fronts can distinguish between glioblastoma patients that will respond favorably to bevacizumab and will visually capture treatment response. METHODS: T1, T1C, FLAIR, and ADC images were used to generate radio-pathomic maps of tumor characteristics for 79 pre-treatment patients with a primary GBM or high-grade IDH1-mutant astrocytoma for this study. Novel phenotyping (hypercellular, hypocellular, hybrid, or well-circumscribed front) of the non-enhancing tumor front was performed on each case. Kaplan Meier analyses were then used to assess differences in survival and bevacizumab efficacy between phenotypes. Phenotype compartment segmentations generated longitudinally for a subset of 26 patients over the course of bevacizumab treatment, where a mixed effect model was used to detect longitudinal changes. RESULTS: Well-Circumscribed patients showed significant/trending increases in survival compared to Hypercellular Front (HR = 2.0, p = 0.05), Hypocellular Front (HR = 2.02, p = 0.03), and Hybrid Front tumors (HR = 1.75, p = 0.09). Only patients with hypocellular or hybrid fronts showed significant survival benefits from bevacizumab treatment (HR = 2.35, p = 0.02; and HR = 2.45, p = 0.03, respectively). Hypocellular volumes decreased by an average 50.52 mm3 per day of bevacizumab treatment (p = 0.002). CONCLUSION: Patients with a hypocellular tumor front identified by radio-pathomic maps showed improved treatment efficacy when treated with bevacizumab, and reducing hypocellular volumes over the course of treatment may indicate treatment response.

Quantitative assessments of finger individuation with an instrumented glove.

BACKGROUND: In clinical and research settings, hand dexterity is often assessed as finger individuation, or the ability to move one finger at a time. Despite its clinical importance, there is currently no standardized, sufficiently sensitive, or fully objective platform for these evaluations. METHODS: Here we developed two novel individuation scores and tested them against a previously developed score using a commercially available instrumented glove and data collected from 20 healthy adults. Participants performed individuation for each finger of each hand as well as whole hand open-close at two study visits separated by several weeks. Using the three individuation scores, intra-class correlation coefficients (ICC) and minimal detectable changes (MDC) were calculated. Individuation scores were further correlated with subjective assessments to assess validity. RESULTS: We found that each score emphasized different aspects of individuation performance while generating scores on the same scale (0 [poor] to 1 [ideal]). These scores were repeatable, but the quality of the metrics varied by both equation and finger of interest. For example, index finger intra-class correlation coefficients (ICC's) were 0.90 (< 0.0001), 0.77 (< 0.001), and 0.83 (p < 0.0001), while pinky finger ICC's were 0.96 (p < 0.0001), 0.88 (p < 0.0001), and 0.81 (p < 0.001) for each score. Similarly, MDCs also varied by both finger and equation. In particular, thumb MDCs were 0.068, 0.14, and 0.045, while index MDCs were 0.041, 0.066, and 0.078. Furthermore, objective measurements correlated with subjective assessments of finger individuation quality for all three equations (ρ = - 0.45, p < 0.0001; ρ = - 0.53, p < 0.0001; ρ = - 0.40, p < 0.0001). CONCLUSIONS: Here we provide a set of normative values for three separate finger individuation scores in healthy adults with a commercially available instrumented glove. Each score emphasizes a different aspect of finger individuation performance and may be more uniquely applicable to certain clinical scenarios. We hope for this platform to be used within and across centers wishing to share objective data in the physiological study of hand dexterity. In sum, this work represents the first healthy participant data set for this platform and may inform future translational applications into motor physiology and rehabilitation labs, orthopedic hand and neurosurgery clinics, and even operating rooms.

Quantifying Hand Strength and Isometric Pinch Individuation Using a Flexible Pressure Sensor Grid.

Modulating force between the thumb and another digit, or isometric pinch individuation, is critical for daily tasks and can be impaired due to central or peripheral nervous system injury. Because surgical and rehabilitative efforts often focus on regaining this dexterous ability, we need to be able to consistently quantify pinch individuation across time and facilities. Currently, a standardized metric for such an assessment does not exist. Therefore, we tested whether we could use a commercially available flexible pressure sensor grid (Tekscan F-Socket [Tekscan Inc., Norwood, MA, USA]) to repeatedly measure isometric pinch individuation and maximum voluntary contraction (MVC) in twenty right-handed healthy volunteers at two visits. We developed a novel equation informed by the prior literature to calculate isometric individuation scores that quantified percentage of force on the grid generated by the indicated digit. MVC intra-class correlation coefficients (ICCs) for the left and right hands were 0.86 (p < 0.0001) and 0.88 (p < 0.0001), respectively, suggesting MVC measurements were consistent over time. However, individuation score ICCs, were poorer (left index ICC 0.41, p = 0.28; right index ICC -0.02, p = 0.51), indicating that this protocol did not provide a sufficiently repeatable individuation assessment. These data support the need to develop novel platforms specifically for repeatable and objective isometric hand dexterity assessments.

Freezing of Gait in Parkinson's Disease: Invasive and Noninvasive Neuromodulation.

INTRODUCTION: Freezing of gait (FoG) is one of the most disabling yet poorly understood symptoms of Parkinson's disease (PD). FoG is an episodic gait pattern characterized by the inability to step that occurs on initiation or turning while walking, particularly with perception of tight surroundings. This phenomenon impairs balance, increases falls, and reduces the quality of life. MATERIALS AND METHODS: Clinical-anatomical correlations, electrophysiology, and functional imaging have generated several mechanistic hypotheses, ranging from the most distal (abnormal central pattern generators of the spinal cord) to the most proximal (frontal executive dysfunction). Here, we review the neuroanatomy and pathophysiology of gait initiation in the context of FoG, and we discuss targets of central nervous system neuromodulation and their outcomes so far. The PubMed database was searched using these key words: neuromodulation, freezing of gait, Parkinson's disease, and gait disorders. CONCLUSION: Despite these investigations, the pathogenesis of this process remains poorly understood. The evidence presented in this review suggests FoG to be a heterogenous phenomenon without a single unifying pathologic target. Future studies rigorously assessing targets as well as multimodal approaches will be essential to define the next generation of therapeutic treatments.

Characterization of Perinatal Risk Factors and Complications Associated With Nonsyndromic Craniosynostosis.

BACKGROUND: Certain intrauterine risk factors are known to increase the risk of premature cranial suture fusion and may cause complications during birth. Some of these risk factors may be modifiable. Therefore, the authors sought to characterize the institutional patterns of prenatal risk factors and perinatal complications in nonsyndromic craniosynostosis patients compared to normal births from the surrounding area to identify areas for possible intervention or prevention. METHODS: The medical records of all infants with nonsyndromic craniosynostosis and full birth records born at Duke University Health System from 2006 to 2017 were retrospectively reviewed. Maternal comorbidities, prenatal risk factors, and perinatal complications were collected. The North Carolina State Center for Health Statistics was queried for perinatal statistics from Durham county and the Northeastern Perinatal Care Region to represent a control cohort of normal births from the same time period and region. The primary outcome investigated was the incidence of prenatal risk factors and complications at birth associated with premature fusion of cranial sutures. RESULTS: Eighty births with nonsyndromic craniosynostosis were included in this study. The majority of these patients were males (61.7%) and born via cesarean section (55.0%). Intrauterine growth restriction occurred in 10.0% and head trauma during delivery occurred in 2.5%. Twinning (14.8% vs 3.6%, P < 0.0001), cesarean births (55.5% vs 30.0%, P < 0.0001), and breech presentation (17.3% vs 3.2%, P < 0.0001) were significantly more common in craniosynostosis patients. Prenatally, mothers of craniosynostosis infants had higher incidence of gestational diabetes (13.5% vs 5.0%, P < 0.0001) and oligohydramnios (6.1% vs 1.3%, P < 0.0001) compared to regional controls. CONCLUSION: This study demonstrates that premature suture fusion is associated with prenatal risk factors such as gestational diabetes and oligohydramnios. Continued research into potentially modifiable prenatal risk factors and more refined prenatal diagnostic tools has the potential to reduce both the incidence of premature suture fusion and the sequelae of birth complications in this population.

Socioeconomic Factors, Perioperative Complications, and 30-Day Readmission Rates Associated With Delayed Cranial Vault Reconstruction for Craniosynostosis.

BACKGROUND: Premature fusion of the cranial sutures can lead to significant neurocognitive, developmental, and esthetic consequences, especially if not corrected within the first year of life. This study aimed to identify the drivers of delayed cranial vault reconstruction (CVR) and its impact on complication and 30-day readmission rates among craniosynostosis patients. METHODS: The medical records of all children who underwent CVR for craniosynostosis between 2005 and 2017 at an academic institution were retrospectively reviewed. A delay in operation was defined by surgery performed >12 months of age. Patient demographics, comorbidities, perioperative complication rates, and 30-day readmission rates were collected. RESULTS: A total of 96 patients underwent primary CVR, with 79 (82.3%) patients undergoing nondelayed surgery and 17 (17.7%) patients undergoing surgery >12 months of age. Children undergoing delayed surgery were significantly more likely to be non-White (P < 0.0001), have Medicaid insurance (P = 0.023), and have a non-English primary language (P < 0.005). There was increased incidence of developmental disability identified at first consult (no-delay: 3.9% vs delay: 41.2%, P < 0.0001) and increased intracranial pressure (no-delay: 6.3% vs delay: 29.4%, P < 0.005) among children undergoing delayed surgery. The delayed cohort had a significantly higher unplanned 30-day readmission rate (no-delay: 0.0% vs delay: 5.9%, P = 0.03). CONCLUSION: Our study suggests that craniosynostosis patients who are non-White, have a non-English primary language, and have Medicaid insurance are at risk for delayed primary surgery, which may lead to increased 30-day readmission. Interventions are necessary to reduce craniosynostosis patients' barriers to care to minimize the sequelae associated with delayed surgery.

A novel paraplegia model in awake behaving macaques.

Lower limb paralysis from spinal cord injury (SCI) or neurological disease carries a poor prognosis for recovery and remains a large societal burden. Neurophysiological and neuroprosthetic research have the potential to improve quality of life for these patients; however, the lack of an ethical and sustainable nonhuman primate model for paraplegia hinders their advancement. Therefore, our multidisciplinary team developed a way to induce temporary paralysis in awake behaving macaques by creating a fully implantable lumbar epidural catheter-subcutaneous port system that enables easy and reliable targeted drug delivery for sensorimotor blockade. During treadmill walking, aliquots of 1.5% lidocaine with 1:200,000 epinephrine were percutaneously injected into the ports of three rhesus macaques while surface electromyography (EMG) recorded muscle activity from their quadriceps and gastrocnemii. Diminution of EMG amplitude, loss of voluntary leg movement, and inability to bear weight were achieved for 60-90 min in each animal, followed by a complete recovery of function. The monkeys remained alert and cooperative during the paralysis trials and continued to take food rewards, and the ports remained functional after several months. This technique will enable recording from the cortex and/or spinal cord in awake behaving nonhuman primates during the onset, maintenance, and resolution of paraplegia for the first time, thus opening the door to answering basic neurophysiological questions about the acute neurological response to spinal cord injury and recovery. It will also negate the need to permanently injure otherwise high-value research animals for certain experimental paradigms aimed at developing and testing neural interface decoding algorithms for patients with lower extremity dysfunction.NEW & NOTEWORTHY A novel implantable lumbar epidural catheter-subcutaneous port system enables targeted drug delivery and induction of temporary paraplegia in awake, behaving nonhuman primates. Three macaques displayed loss of voluntary leg movement for 60-90 min after injection of lidocaine with epinephrine, followed by a full recovery. This technique for the first time will enable ethical live recording from the proximal central nervous system during the acute onset, maintenance, and resolution of paraplegia.

Rates and predictors of success and failure in repeat epilepsy surgery: A meta-analysis and systematic review.

OBJECTIVE: Medically refractory epilepsy is a debilitating disorder that is particularly challenging to treat in patients who have already failed a surgical resection. Evidence regarding outcomes of further epilepsy surgery is limited to small case series and reviews. Therefore, our group performed the first quantitative meta-analysis of the literature from the past 30 years to assess for rates and predictors of successful reoperations. METHODS: A PubMed search was conducted for studies reporting outcomes of repeat epilepsy surgery. Studies were excluded if they reported fewer than five eligible patients or had average follow-ups < 1 year, and patients were excluded from analysis if they received a nonresective intervention. Outcomes were stratified by each variable of interest, and quantitative meta-analysis was performed to generate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Seven hundred eighty-two patients who received repeat resective epilepsy surgery from 36 studies were included. Engel I outcome was observed in 47% (n = 369) of patients. Significant predictors of seizure freedom included congruent over noncongruent electrophysiology data (OR = 3.6, 95% CI = 1.6-8.2), lesional over nonlesional epilepsy (OR = 3.2, 95% CI = 1.9-5.3), and surgical limitations over disease-related factors associated with failure of the first surgery (OR = 2.6, 95% CI = 1.3-5.3). Among patients with at least one of these predictors, seizure freedom was achieved in 58%. Conversely, the use of invasive monitoring was associated with worse outcome (OR = 0.4, 95% CI = 0.2-0.9). Temporal lobe over extratemporal/multilobe resection (OR = 1.5, 95% CI = 0.8-3.0) and abnormal over normal preoperative magnetic resonance imaging (OR = 1.9, 95% CI = 0.6-5.4) showed nonsignificant trends toward seizure freedom. SIGNIFICANCE: This analysis supports considering further resection in patients with intractable epilepsy who continue to have debilitating seizures after an initial surgery, especially in the context of factors predictive of a favorable outcome.

Extracting kinetic information from human motor cortical signals.

Brain machine interfaces (BMIs) have the potential to provide intuitive control of neuroprostheses to restore grasp to patients with paralyzed or amputated upper limbs. For these neuroprostheses to function, the ability to accurately control grasp force is critical. Grasp force can be decoded from neuronal spikes in monkeys, and hand kinematics can be decoded using electrocorticogram (ECoG) signals recorded from the surface of the human motor cortex. We hypothesized that kinetic information about grasping could also be extracted from ECoG, and sought to decode continuously-graded grasp force. In this study, we decoded isometric pinch force with high accuracy from ECoG in 10 human subjects. The predicted signals explained from 22% to 88% (60 ± 6%, mean ± SE) of the variance in the actual force generated. We also decoded muscle activity in the finger flexors, with similar accuracy to force decoding. We found that high gamma band and time domain features of the ECoG signal were most informative about kinetics, similar to our previous findings with intracortical LFPs. In addition, we found that peak cortical representations of force applied by the index and little fingers were separated by only about 4mm. Thus, ECoG can be used to decode not only kinematics, but also kinetics of movement. This is an important step toward restoring intuitively-controlled grasp to impaired patients.

Non-hemorrhagic cerebellar contrast enhancement on intraoperative MRI during a supratentorial glioma resection: Concerning finding of no significance.

Intraoperative magnetic resonance imaging (iMRI) is a powerful tool used to verify maximal safe resection of gliomas. However, unsuspected new or incidental findings can present difficult clinical scenarios. Here we present a case of a large supratentorial glioma resection where new, incidental bilateral cerebellar hemispheric enhancement was noted on iMRI. A 52-year-old male with a large intra-axial mass spanning the right temporal and parietal lobes underwent a craniotomy for tumor resection utilizing iMRI. Imaging displayed new, remote, bilateral cerebellar enhancement. Upon completion of surgery, the patient was extubated and was at his neurological baseline. An immediate CT scan showed no abnormalities in the cerebellum, and the duration of his hospital stay was unaffected by this finding. An MRI 24 hours after the procedure demonstrated complete resolution of the enhancement. New, remote contrast enhancement in the cerebellum raises concerns for the potentially emergent, well-defined pathology known as remote cerebellar hemorrhage (RCH). However, here we describe a case where these findings turned out to be clinically insignificant, CT-negative, and self-limiting. Therefore, here we call this finding remote non-hemorrhagic cerebellar contrast enhancement (RNHCCE) to differentiate it from RCE, and we discuss nuances and management considerations for differentiating the two.

Application of Delta T1 maps for quantitative and objective assessment of extent of resection and survival prediction in glioblastoma.

Background and Objectives: Gross-total resection (GTR) and low residual tumor volume (RTV) have been associated with increased survival in glioblastoma. Largely due to the subjectivity involved, the determination of GTR and RTV remains difficult in the postoperative setting. In response, the objective of this study is to evaluate the clinical efficacy of an easy-to-use MRI metric, called delta T1 (dT1), to quantify extent of resection (EOR) and RTV, in comparison to radiologist impression, to predict overall survival (OS) in glioblastoma patients. Methods: 59 patients who underwent resection of glioblastoma were retrospectively identified. Delta T1 (dT1) images, automatically created from the difference between calibrated post- and pre-contrast T1-weighted images, were used to quantify EOR and RTV. Kaplan-Meier survival estimates were determined for EOR categories, an RTV cutoff of 5cm3 and radiologist interpretation of EOR. Multivariate Cox proportional hazard regression analysis was used to evaluate RTV and EOR along with effects related to sex, KPS, MGMT, and age on OS. Results: Kaplan-Meier analysis revealed a statistically significant difference in median OS for a dT1-determined RTV cutoff of 5 cm3 (P=.0024, HR=2.18 (1.232-3.856)), but not for radiological impression (P=0.666) or dT1-determined EOR (P=0.0803), which was limited to a comparison between partial and subtotal resections. Furthermore, when covariates were accounted for in multivariate Cox regression, significant differences in OS were retained for dT1-determined RTV. Additionally, a significantly strong yet short-term effect of MGMT methylation status on OS was revealed for each RTV and EOR model. Conclusion: The utility of dT1 maps to quantify EOR and RTV in glioblastoma and predict survival, suggests an emerging role for dT1s with relevance for intraoperative MRI, neuro-navigation and postoperative disease surveillance.

Radio-pathomic maps of glioblastoma identify phenotypes of non-enhancing tumor infiltration associated with bevacizumab treatment response.

Background: Autopsy-based radio-pathomic maps of glioma pathology have shown substantial promise inidentifying areas of non-enhancing tumor presence, which may be able to differentiate subsets of patients that respond favorably to treatments such as bevacizumab that have shown mixed efficacy evidence. We tested the hypthesis that phenotypes of non-enhancing tumor fronts can distinguish between glioblastoma patients that will respond favorably to bevacizumab and will visually capture treatment response. Methods: T1, T1C, FLAIR, and ADC images were used to generate radio-pathomic maps of tumor characteristics for 79 pre-treatment patients with a primary GBM or high-grade IDH1-mutant astrocytoma for this study. Novel phenotyping (hypercellular, hypocellular, hybrid, or well-circumscribed front) of the non-enhancing tumor front was performed on each case. Kaplan Meier analyses were then used to assess differences in survival and bevacizumab efficacy between phenotypes. Phenotype compartment segmentations generated longitudinally for a subset of 26 patients over the course of bevacizumab treatment, where a mixed effect model was used to detect longitudinal changes. Results: Well-Circumscribed patients showed significant/trending increases in survival compared to Hypercellular Front (HR = 2.0, p = 0.05), Hypocellular Front (HR = 2.02, p = 0.03), and Hybrid Front tumors (HR = 1.75, p = 0.09). Only patients with hypocellular or hybrid fronts showed significant survival benefits from bevacizumab treatment (HR = 2.35, p = 0.02; and HR = 2.45, p = 0.03, respectively). Hypocellular volumes decreased by an average 50.52 mm3 per day of bevacizumab treatment (p = 0.002). Conclusion: Patients with a hypocellular tumor front identified by radio-pathomic maps showed improved treatment efficacy when treated with bevacizumab, and reducing hypocellular volumes over the course of treatment may indicate treatment response.

Noninvasive Autopsy-Validated Tumor Probability Maps Identify Glioma Invasion Beyond Contrast Enhancement.

BACKGROUND AND OBJECTIVES: This study identified a clinically significant subset of patients with glioma with tumor outside of contrast enhancement present at autopsy and subsequently developed a method for detecting nonenhancing tumor using radio-pathomic mapping. We tested the hypothesis that autopsy-based radio-pathomic tumor probability maps would be able to noninvasively identify areas of infiltrative tumor beyond traditional imaging signatures. METHODS: A total of 159 tissue samples from 65 subjects were aligned to MRI acquired nearest to death for this retrospective study. Demographic and survival characteristics for patients with and without tumor beyond the contrast-enhancing margin were computed. An ensemble algorithm was used to predict pixelwise tumor presence from pathological annotations using segmented cellularity (Cell), extracellular fluid, and cytoplasm density as input (6 train/3 test subjects). A second level of ensemble algorithms was used to predict voxelwise Cell, extracellular fluid, and cytoplasm on the full data set (43 train/22 test subjects) using 5-by-5 voxel tiles from T1, T1 + C, fluid-attenuated inversion recovery, and apparent diffusion coefficient as input. The models were then combined to generate noninvasive whole brain maps of tumor probability. RESULTS: Tumor outside of contrast was identified in 41.5% of patients, who showed worse survival outcomes (hazard ratio = 3.90, P < .001). Tumor probability maps reliably tracked nonenhancing tumor on a range of local and external unseen data, identifying tumor outside of contrast in 69% of presurgical cases that also showed reduced survival outcomes (hazard ratio = 1.67, P = .027). CONCLUSION: This study developed a multistage model for mapping gliomas using autopsy tissue samples as ground truth, which was able to identify regions of tumor beyond traditional imaging signatures.

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.

Large-scale brain networks and intra-axial tumor surgery: a narrative review of functional mapping techniques, critical needs, and scientific opportunities.

In recent years, a paradigm shift in neuroscience has been occurring from "localizationism," or the idea that the brain is organized into separately functioning modules, toward "connectomics," or the idea that interconnected nodes form networks as the underlying substrates of behavior and thought. Accordingly, our understanding of mechanisms of neurological function, dysfunction, and recovery has evolved to include connections, disconnections, and reconnections. Brain tumors provide a unique opportunity to probe large-scale neural networks with focal and sometimes reversible lesions, allowing neuroscientists the unique opportunity to directly test newly formed hypotheses about underlying brain structural-functional relationships and network properties. Moreover, if a more complete model of neurological dysfunction is to be defined as a "disconnectome," potential avenues for recovery might be mapped through a "reconnectome." Such insight may open the door to novel therapeutic approaches where previous attempts have failed. In this review, we briefly delve into the most clinically relevant neural networks and brain mapping techniques, and we examine how they are being applied to modern neurosurgical brain tumor practices. We then explore how brain tumors might teach us more about mechanisms of global brain dysfunction and recovery through pre- and postoperative longitudinal connectomic and behavioral analyses.

Pinless Electromagnetic Neuronavigation During Awake Craniotomies: Technical Pearls, Pitfalls, and Nuances.

BACKGROUND: Awake craniotomies are often performed with rigid pin fixation to support optical neuronavigation. Newer electromagnetic (EM) neuronavigation technology now enables unpinned cranial neurosurgery while maintaining robust intraoperative image guidance. Here, we share technical nuances, operative pearls, and lessons learned from our institutional experience using Curve EM neuronavigation during awake, unpinned craniotomies. METHODS: We describe our process for patient positioning, instrumentation setup, system registration, intraoperative navigation, and surgical adjunct use (e.g., intraoperative neuromonitoring and intraoperative magnetic resonance imaging) in detail. At each step, we provide pearls for success and tips for pitfall avoidance based on our experience. RESULTS: Ten patients underwent awake pinless intra-axial tumor resection using Curve EM neuronavigation from May 2021 to August 2022 with a single surgeon. Postoperative transient neurological deficits were seen in 8 of 10 cases (80.0%), as all resections were taken to functional margins. Of the 9 patients with a 3-month follow-up visit at the time of publication, all 9 (100%) had improved or stable preoperative symptoms. No surgical complications, clinically appreciable inaccuracies, intraoperative losses of registration, unexpected postoperative magnetic resonance imaging findings, or errors related to the use of EM neuronavigation occurred. CONCLUSIONS: The technical pearls outlined here will help interested neurosurgeons integrate EM neuronavigation into awake craniotomies. In our experience, using unpinned neuronavigation during awake cases provides many advantages to the patient, surgeon, and entire operative team. It has thus become the standard practice at our institution.

Symptomatic radionecrosis after postoperative but not preoperative stereotactic radiosurgery in a single patient: illustrative case.

BACKGROUND: Standard of care for brain metastases involves stereotactic radiosurgery (SRS). For cases that also require surgery because of lesion size, edema, or neurological symptoms, whether to provide pre- or postoperative SRS has become a prevalent debate. OBSERVATIONS: Herein, the unique case of a patient with brain metastases of the same pathology and similar size in two different brain locations at two different times is described. The patient underwent surgery with preoperative SRS for the first lesion and surgery with postoperative SRS for the second lesion. Although both treatments resulted in successful local control, the location that received postoperative SRS developed symptomatic and rapidly progressive radiation necrosis (RN) requiring a third craniotomy. LESSONS: Large randomized controlled trials are ongoing to compare pre- versus postoperative SRS for the treatment of symptomatic brain metastases (e.g., study NRG-BN012). Recent interest in preoperative SRS has emerged from its theoretical potential to decrease rates of postoperative RN and leptomeningeal disease. This valuable case in which both therapies were applied in a single patient with a single pathology and similar lesions provides evidence supportive of preoperative SRS.

Synchronization of kinetic and kinematic hand tasks with electrocorticography and cortical stimulation during awake craniotomies.

Awake craniotomies provide unique and invaluable scientific opportunities for neurophysiological experimentation in consenting human subjects. While such experimentation carries a long history, rigorous reporting of methodologies focusing on synchronizing data across multiple platforms is not universally reported and often not translatable to across operating rooms, facilities, or behavioral tasks. Therefore, here we detail an intraoperative data synchronization methodology designed to work across multiple commercially available platforms to collect behavioral and surgical field videos, electrocorticography, brain stimulation timing, continuous finger joint angles, and continuous finger force production. Our technique was developed to be nonobstructive to operating room (OR) staff and generalizable to a variety of hand-based tasks. We hope that the detailed reporting of our methods will support the scientific rigor and reproducibility of future studies, as well as aid other groups interested in performing related experiments.