Kerezoudis, Panagiotis

ABSTRACT Introduction The insula is an increasingly important target for functional neurosurgery given its involvement in a range of neurological and neuropsychiatric disorders, including epilepsy and chronic pain. As this practice evolves, optimal targeting will require standardized outcome measures that relate electrode or laser trajectory to postprocedural outcome. Traditional whole- brain registration approaches fail to capture the substantial person-to-person variability in insular gyral configuration, including the relative internal rotation of the insular gyri with respect to standard stereotactic space. Objective We propose and validate a stereotactic coordinate system based on local anatomical landmarks to facilitate surgical planning and standardized outcome assessment within the insular cortex. Methods Our approach transforms brain MRI first into standard AC-PC space, and then into an insular-specific space defined by five anatomical landmarks: four points along the central sulcus of the insula and one point at the middle cerebral artery (MCA) bifurcation (at the limen insulae). The system calculates two angles - θ (axial) and φ (sagittal) - between the AC-PC line and the insular axis, and the brain volume undergoes sequential rotation through these angles followed by translation to place the coordinate system’s origin along the insular axis. Results In a sample of 32 patients, the angle between the AC-PC line and the insular axis ranged from -17° to 17° in the axial plane (θ) and 31° to 69° in the sagittal plane (φ). In the resulting coordinate system, the insular axis defines z = 0 and the MCA turning point defines y = 0. We developed a custom, open-access MATLAB graphical interface that allows intuitive implementation of this system for both surgical planning and postoperative analysis; implanted electrodes, laser fiber position, and ablation geometry can each be localized within this common space. As a demonstration of its utility for pooling data across subjects, we applied the transformation to a previously acquired intracranial electrophysiology dataset and found that anatomically consistent, effector-specific motor representations emerged across 18 subjects once electrode positions were expressed in insular-specific coordinates. Conclusion As stereotactic surgery for insular targets becomes more common with expanding scientific inquiry, an insular-specific coordinate system may facilitate operative planning and functional mapping, and may help standardize outcome assessment across patients and institutions. SIGNIFICANCE STATEMENT The insular cortex represents an increasingly important surgical target for therapeutic interventions, yet substantial person-to-person anatomical variability hampers standardized targeting and outcome comparison. The insula is simultaneously the subject of expanding scientific inquiry — into interoception, pain, autonomic regulation, salience processing, and sensorimotor representation — much of it now pursued through intracranial recording and stimulation in humans, where cohorts are small, electrode sampling is idiosyncratic, and progress therefore depends on pooling data across patients in a frame that respects insular gyral architecture. We present “ Insulotaxy ,” a stereotactic coordinate system built from consistent, easily identifiable local anatomical landmarks that accounts for the insula’s unique rotational relationship to standard brain coordinates. An open-source MATLAB tool transforms imaging into insular-specific coordinates, facilitating surgical planning for ablation and electrode placement while enabling standardized outcome reporting across institutions. By providing locally anchored, anatomically aligned coordinates rather than relying on whole-brain registration, this framework addresses a practical gap in functional neurosurgery and lays a foundation for pooling clinical and electrophysiological data as insular interventions become more prevalent.

Background: Major depressive disorder remains a leading cause of disability. While subgenual cingulate cortex (sgCC) deep brain stimulation (DBS) shows promise for medically refractory depression, clinical outcomes have been heterogeneous, suggesting that individual differences in neural circuitry engagement may critically influence therapeutic efficacy. We aimed to define the electrophysiological signatures of sgCC efferent connectivity using single-pulse electrical stimulation (SPES) with intracranial stereo-EEG (sEEG) to inform rational targeting and physiological biomarkers for sgCC-DBS. Methods: In four patients undergoing clinically indicated sEEG for seizure mapping, SPES was delivered through sgCC pairs, while distributed brain stimulation-evoked potentials (BSEPs) were recorded across cortical and subcortical sites. Responses were characterized using Canonical Response Parameterization to extract reproducible waveforms and per-trial reliability. Results: sgCC stimulation elicited reproducible, spatially organized BSEPs across frontal, limbic, and paralimbic networks, aligning with known anatomical pathways. Frontal recruitment featured robust, lateralized orbitofrontal activation favoring the ipsilateral central, medial OFC and bilateral ventromedial prefrontal responses. Limbic effects demonstrated bilateral cingulate activation with stronger ipsilateral recruitment and lateralized amygdala and hippocampal responses. Paralimbic engagement included insular responses with subject-specific anterior predominance and bi-hemispheric temporal-polar slow-wave deflections. Conclusion: These findings provide direct electrophysiological evidence of distributed, lateralized sgCC divergent network connectivity in the human brain, offering physiologic confirmation of its role in affective circuitry. The observed topography and laterality have direct applications for sgCC-DBS targeting and implicate BSEP signatures as candidate biomarkers to guide patient-specific therapy.

OBJECTIVE Craniopharyngiomas are challenging lesions, and aggressive resections may cause significant postoperative morbidity and mortality. To mitigate morbidity, a potential strategy of subtotal resection (STR) and adjuvant radiation therapy (RT) has been used, but its impact on survival when compared to gross-total resection (GTR) has been under-investigated. Thus, the objective of this study was to analyze short-term mortality between patients undergoing STR ± RT and GTR, and differences in overall survival (OS) between patients undergoing STR, STR + RT, and GTR in a large, nationally representative database. METHODS The authors queried the National Cancer Database for patients diagnosed with craniopharyngioma between 2004 and 2017. Tumor characteristics, treatment strategies, and extent of resection were analyzed. Endpoints were 3-month mortality rate and OS, which were compared between treatment modalities. Firth’s logistic regression was used to analyze 3-month mortality and was adjusted for age, sex, Charlson Comorbidity Index score, histopathological diagnosis, income quartile, insurance payor, and maximal tumor diameter. Differences in survival between treatment modalities were compared with log time-to-event analyses after excluding deaths occurring within 3 months to control for immortal time bias. RESULTS A total of 1460 adult and 390 pediatric patients were included. Adults undergoing STR ± RT had a lower rate of 3-month mortality compared to those undergoing GTR in adjusted analysis (2.8% vs 4.6%, odds ratio 0.42; p = 0.03). Survival curves for the STR + RT and GTR cohorts did not significantly differ (p = 0.198). A strategy of STR alone showed worse OS compared with GTR and STR + RT (p < 0.01). The average follow-up length for adults was 65.5 months. For pediatric patients, 3-month mortality for those undergoing GTR and STR ± RT was similar (0% vs 1%, respectively; p = 0.33). Additionally, compared to GTR, there were no significant differences in OS between STR + RT (p = 0.41) and STR alone (p = 0.44). The average follow-up length for the pediatric cohort was 79 months. CONCLUSIONS STR + RT was associated with a favorable perioperative mortality profile when compared with GTR and provided similar long-term survival outcomes. Therefore, STR + RT may be considered when GTR carries significant risks.

Understanding motor representation in the human brain requires mapping beyond the primary motor cortex, into the distributed networks that coordinate complex movements. The insular cortex, a multifunctional hub buried within the Sylvian fissure, has been implicated in motor control through clinical observations and neuroimaging. Yet its precise relation to primary sensorimotor processing remains one of the least understood aspects of motor neurophysiology. To address this gap, we quantified electrophysiological changes from implanted depth electrodes in patients performing simple movement tasks combined with single-pulse electrical stimulation (SPES) to map effective connectivity. The movement data reveal somatotopically specific representation bilaterally, as well as intereffector regions that are active for different movement types. Hand representation is centered along the contralateral ventral aspect of the middle and posterior short gyri bilaterally, while tongue/mouth tuned sites cluster in the dorsal posterior short gyrus and the dorsal long gyri. Insular activity temporally follows the primary motor cortex (M1) and precedes movement onset. SPES revealed somatotopically specific connectivity between corresponding sites in M1 and insula (hand-to-hand, tongue-to-tongue) and between bilateral insulae. These observations establish that somatotopy is a conserved property of distributed motor control incorporating the insular representations and connectivity.

AbstractObjectiveNeuromodulation for pediatric refractory epilepsy (PRE) is preferred when the seizure onset zone is not amenable to surgical resection, due to multifocal onset or involvement of eloquent cortex. Given its rapidly evolving landscape, we describe our institutional experience with neurostimulation therapies including deep brain stimulation (DBS) of the anterior nucleus (DBS‐ANT), the centromedian nucleus (DBS‐CM), responsive neurostimulation (RNS), and chronic subthreshold stimulation (CSS) to treat PRE.MethodsA retrospective chart review was conducted to identify pediatric patients (≤18 years of age) who presented to our institution with PRE. Patients were included who had at least 1 year of follow‐up after neurostimulation was started. Patients with ≥50% seizure frequency reduction at last follow‐up compared to baseline were classified as responders.ResultsA total of 35 patients (21 females) were included in the series. Nine patients underwent DBS‐ANT, 9 underwent DBS‐CM (+ ANT in 7 patients), 5 underwent RNS, and 12 underwent CSS. The median age at seizure onset and surgery was 8 and 16 years, respectively. Structural lesions were the most common etiology of epilepsy (54%). Eighteen patients had prior interventions and 13 received invasive EEG. Post‐operative complications following neurostimulation implantation were noted in three patients (9%). However, no permanent deficits were noted. Median follow‐up time was 46 months (range 13–162 months). Twenty‐three patients (59%) were responders (3/9 DBS‐ANT; 7/9 DBS‐CM; 4/5 RNS; 9/12 CSS). Further, median seizure reduction was 25% (DBS‐ANT), 89% (DBS‐CM), 87% (RNS), and 88% (CSS) across the cohort. Six patients (17%) had improved subjective neurocognitive outcomes while the other 29 had stable neurocognitive outcomes.SignificanceDBS, RNS, and CSS are safe and effective options for PRE. An understanding of treatment approaches can optimize results by tailoring therapy to individual patients.Plain Language SummaryThis study investigates the use of various neurostimulation therapies for treating pediatric refractory epilepsy (PRE) including deep brain stimulation (DBS), responsive neurostimulation (RNS), and chronic subthreshold stimulation (CSS). Overall, neuromodulation was found to be effective in reducing seizures in most patients, with 59% of patients showing at least a 50% reduction in seizure frequency. Additionally, the treatments were generally safe, with few complications and no instances of permanent deficits.

BACKGROUND AND OBJECTIVES: Stereotactic procedures are used to manage a diverse set of patients across a variety of clinical contexts. The stereotactic devices and software used in these procedures vary between surgeons, but the fundamental principles that constitute safe and accurate execution do not. The aim of this work is to describe these principles to equip readers with a generalizable knowledge base to execute and understand stereotactic procedures. METHODS: A combination of a review of the literature and empirical experience from several experienced surgeons led to the creation of this work. Thus, this work is descriptive and qualitative by nature, and the literature is used to support instead of generate the ideas of this framework. RESULTS: The principles detailed in this work are categorized based on 5 clinical domains: imaging, registration, mechanical accuracy, target planning and adjustment, and trajectory planning and adjustment. Illustrations and tables are used throughout to convey the concepts in an efficient manner. CONCLUSION: Stereotactic procedures are complex, requiring a thorough understanding of each step of the workflow. The concepts described in this work enable functional neurosurgeons with the fundamental knowledge necessary to provide optimal patient care.

BACKGROUND AND OBJECTIVES: Identifying and characterizing sources of targeting error in stereotactic procedures is essential to maximizing accuracy, potentially improving surgical outcomes. We aim to describe a generic framework which characterizes sources of stereotactic inaccuracy. METHODS: We assembled a list of stereotactic systems: ROSA, Neuromate, Mazor Renaissance, ExcelsiusGPS, Cirq, STarFix (FHC), Nexframe, ClearPoint, CRW, and Leksell. We searched the literature for qualitative and quantitative work identifying and quantifying potential sources of inaccuracy and describing each system's implementation using Standards for Reporting Qualitative Research guidelines. Our literature search spanned 1969 to 2024, and various studies were included, with formats ranging from phantom studies to systematic reviews. Keyword searches were conducted, and the details about each system were used to create a framework for identifying and describing the unique targeting error profile of each system. RESULTS: We describe and illustrate the details of various sources of stereotactic inaccuracies and generate a framework to unify these sources into a single framework. This framework entails 5 domains: imaging, registration, mechanical accuracy, target planning and adjustment, and trajectory planning and adjustment. This framework was applied to 10 stereotactic systems. CONCLUSION: This framework provides a rubric to analyze the sources of error for any stereotactic system. Illustrations allow the reader to understand sources of error conceptually so that they may apply them to their practice.

OBJECTIVE Stereoelectroencephalography (SEEG) has become the predominant method for intracranial seizure localization. When imaging, semiology, and scalp EEG findings are not in full agreement or definitively localizing, implanted SEEG recordings are used to test candidate seizure onset zones (SOZs). Discovered SOZs may then be targeted for resection, laser ablation, or neurostimulation. If an SOZ is eloquent, resection and ablation are both contraindicated, so identifying functional representation is crucial for therapeutic decision-making. The authors present a novel functional brain mapping technique that utilizes task-based electrophysiological changes in SEEG during behavioral tasks and test this in pediatric and adult patients. METHODS SEEG was recorded in 20 patients with epilepsy who ranged in age from 6 to 39 years (12 female, 18 of 20 patients < 21 years of age) and underwent implanted monitoring to identify seizure onset. Each performed 1) visually cued simple repetitive movements of the hand, foot, or tongue while electromyography was recorded; and 2) simple picture-naming or verb-generation speech tasks while audio was recorded. Broadband changes in the power spectrum of the SEEG recording were compared between behavior and rest. RESULTS Electrophysiological functional mapping of movement and/or speech areas was completed in all 20 patients. Eloquent representation was identified in both cortex and white matter and generally corresponded to classically described functional anatomical organization as well as other clinical mapping results. Robust maps of brain activity were identified in healthy brain, regions of developmental or acquired structural abnormality, and SOZs. CONCLUSIONS Task-based electrophysiological mapping using broadband changes in the SEEG signal reliably identifies movement and speech representation in pediatric and adult epilepsy patients.

OBJECTIVE Unplanned returns to the operating room (RORs) constitute an important quality metric in surgical practice. In this study, the authors present a methodology to compare a department’s unplanned ROR rates with national benchmarks in the context of large-scale quality of care surveillance. METHODS The authors identified unplanned RORs within 30 days from the initial surgery at their institution during the period 2014–2018 using an institutional documentation platform that facilitates the collection of reoperation information by providers in the clinical setting. They divided the procedures into 28 groups by Current Procedural Terminology and International Classification of Diseases, 9th and 10th Revision codes. They estimated national benchmarks of unplanned RORs for these procedure groups via querying the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) registry during the period 2014–2018. Finally, they numerically assessed the unplanned ROR rates at their institution compared with those calculated from the ACS NSQIP registry. RESULTS Using the above methodology, the authors were able to classify 12,575 of the cases performed in their department during the period of interest, including 6037 (48%) cranial cases and 6538 (52%) spinal or peripheral nerve cases. Among those, 161 (1.3%) presented with complications that required an unplanned ROR within 30 days from the initial surgery. The respective cumulative unplanned ROR rate in the ACS NSQIP registry during the same timeframe was 3.6%. Among 15 categories of cranial procedures, the cumulative unplanned ROR rate was 1.3% in the authors’ department and 5.6% in the ACS NSQIP registry. Among 13 categories of spinal and peripheral nerve procedures, the cumulative unplanned ROR rate was 1.3% in the authors’ department and 2.8% in the ACS NSQIP registry. Unplanned ROR rates at the authors’ institution were lower than the national average for each of the 28 procedure groups of interest. Yearly analysis of institutional ROR rates for the five most commonly performed procedures showed lower reoperation rates compared with the national benchmarks. CONCLUSIONS Using an institutional documentation tool and a widely available national database, the authors developed a reproducible and standardized method of comparing their department’s outcomes with national benchmarks per procedure subgroup. This methodology accommodates longitudinal quality surveillance across the different subspecialties in a neurosurgical department and may illuminate potential shortcomings of care delivery in the future.